2. A 71-year-old male with hypertensive nephropathy received a kidney graft in February 2016. He had a history of colon adenocarcinoma in June 2019. His baseline Cr was 240–260 μmol/L. His immunosuppressive regimen included prednisolone 5 mg OD, tacrolimus (trough level was 6.4 ng/mL), and MMF 250 mg BD. He was also on calcium channel blockers and proton pump inhibitors. He presented in April 2020 with a dry cough with no other symptoms but stable vital signs. However, a chest X-ray revealed an infra-hilar consolidation on the right side.
Lung consolidation with dry cough in post TX kidney patients had many differential diagnosis starting by viral pneumonia like CMV,Atypical pneumonia,fungal pneumonia,pulmonary TB and Carcinoma of the lung one of the most important differential butting in mind the Hx of the CA colon
so we need to screen for viral,fungal and bacterial causes plus broncoscopy with tissue biopsy
With the given scenerion i have following differentials:
1. Community acquired pneumonia
2. Covid-19 pnrumonia
3. CMV pneumonia
4. Pulmonary aspergillosis
5. Pulmonar TB
6. PJP
7. Metastatic adenocarcinoma of colon
8. PTLD
Management
A. Hospitalization & isolation
B. Detail history
C. Physical examination
D. Monitoting vitals: HR, RR, BP, SpO2, urine output
E. Investigation:
– CBC, CRP
– RFT, LFT
– Nasopharyngeal swab for Covid-19 RT PCR
– CMV PCR
– Blood & urine C/S
– Sputum for gram staining, C/S, gene X-pert and malignant cell
– BAL for microscopy & PCR
– IL-6 in case of covid -19 pneumonia
– CEA, CA19-9
– HRCT of chest, CT/MRI of abdomen
– Broncoscopy with biopsy
F. Treatment
– Supportive i.e respiratory support as required, adequate hydration, renal support (CVVH)
– Modification of immunosuppression ( Stop MMF, tacrolimus trough level 4-6 ng/dl, increase dose of prednisolone)
– In case of covid -19 pneumonia dexamethasone, remdicivir.
What are differentials? We divide the transplant related infection according to the most common and less common with duration of transplantation. 1. In first six months the most common infections are and differentials will be, A. Bacterial infections, B. Viral infections, like CMV, BKVAP, COVID-19, dengue. C. Fungal infection, D. Malaria, E. Tuberculosis. 2. After one year of transplantation the DDs would be, EBV related PTLD, Fungal infections, Secondary metastatic disease, But could BACTERIAL infection as the scan shows consolidation, need further confirmation. How would you manage this case? A detailed history, Detailed examination, Baseline investigation, Radiological examination, Viral serology, CRP, procalcitonine, May need BAL, may need biopsy of the lesion. Sputum for GS, C/S, and AFB, Gene Xpert. Management; Will proceed according to the final BAL, biopsy and culture report, till then will treat as bacterial pneumonia/ PCP.
DIFERENCIAL DIAGNÓSIS: One year after transplantation – risk of opportunistic infections is less; community infection more likely. Etiology depends on exposure to community infection Common causes: Covid-19, parainfluenza, respiratory syncytial, influenza Community Acquired Pneumonia M-TB and Community acquired pneumonia Fungal infection – Aspergillus Less likely causes: – CMV pneumonia – Fungal pneumonia: Aspergillosis, Cryptococcosis, PCP – Cancer: Lung Mets from Colon Cancer; PTLD MANAGMENT Monitoring Respiratory rate and SPO2; keep under observation for respiratory distress and hypoxia Lab tests – – Covid-RTPCR, CMV-PCR, EBV serology CBC, ESR, Montoux, IgRA Sputum (induced) – Gram stain, Culture (Bacterial & Fungal); look for CMV, PCP If scanty / no sputum – BAL – PCP, CMV CECT Chest and Abdomen / PET-CT scan whole body Treatment: Due to Covid Pandemic wave in community home-isolation, steam inhalation, cough syrup, multivitamin, good hydration advised. IS reduction: withhold or reduce MMF, minimize Tac to target C0 of 5-6, Prednisone to continue same or increase (if Covid). Infra-hilar consolidation with Cough indicates towards possibility of Community Pneumonia (CAP) – – Broad Spectrum IV antibiotics (Piperacillin-Tazobactam + respiratory macrolide or quinolone) should be started.
depending CT image features and clinical improvement – – bronchoscopy with BAL or Biopsy – look for TB / CMV / PCP / Fungus Further treatment as per the etiology TB – ATT (preferably Rifa-sparing regimen) x 1yr Fungal – Liposomal-Amphotericin à voriconazole, itraconazole Colonic cancer Mets – Chemotherapy +/- RT
presence of a solitary pulmonary lesion on chest Xray in an immune compromised patient would be approached in a particular way.
essentially, its either infective or neoplastic. CAT scan without contrast might delineate the extent of the lesion, presence of satellite lesion and give a clue on its nature, however, being without contrast would compromise its utility. Induced sputum and BAL secretion exam: with gram stain and culture, immunofluorescent and PCR for PCP and TB and examination for malignant cells are the baseline investigation.
Blood tests :
QuantiFERON gold TB and PCR for EBV.
Blood film for abnormal white blood cells.
Second step in management:
1] Endobronchial ultrasound and transbronchial biopsy
Differential diagnosis is
1] EBV related lymphoma.
2] Tuberculoma.
3] Other malignancies
4] Fungal infection, such as aspegillosis.
Reference:
1]Nikita Leiter. June Kim. Lung Nodules in an Immunosuppressed Patient. PULMONARY MANIFESTATIONS OF SYSTEMIC DISEASE| VOLUME 152, ISSUE 4, SUPPLEMENT , A920, OCTOBER 2017
The differential diagnosis is: 1. Covid-19 infection 2. Other respiratory viral infections like influenza. 3. Tuberculosis 4. Pneumocystis Jirovani pneumonitis 5. CMV, EBV, HSV infection 6. CDPD or malignancy like PTLD 7. Metastasis of colon adenolar cinomal
To manage this case comprehensive lab tests are necessary. (CBC.diff, PLT, ESR, CRP, LDH, PT, PTT, INR, LFT, RFT and biochemistry, procalcitonin, d-dimer, and fibrinogen, viral PCR for covid-19, CMV, influenza and other respiratory viruses.) PerformingIGRA PPD MMF or even reduction of CNIs if necessary with measurement of their levels. Close monitoring for O2 saturation and if below 93%, hospitalization is necessary. Paxlovid can be considered in the outpatient setting.
kidney transplant patient presented with dry cough , no other symptoms but stable vital signs.a chest X-ray revealed an infra-hilar consolidation on the right side. The differential diagnoses include: -dry cough with infra hilar consolidation are non-specific symptoms in time of COVID 19 pandemic it would be the most likely DD without any other clear sing or symptoms of other infection. -Other upper respiratory tract common infection either Viral Infections as influenza , respiratory syncytial CMV, EBV,HSV), bacterial or fungal. -PCP infection. -Asthma Exacerbation -malignancy with metastasis to lung -Sinusitis, post nasal discharge. -allergic cough How would you manage this case? -full history with history of recent contact to a case of covid 19, allergy, and full clinical examination. -Measurement of Oxygen saturation. -investigations: CBC, CRP.LDH, FERRITIN, D dimer, procalcitonin. High resolution CT scan. Kidney function tests. CNIs level. Nasopharyngeal swab induced sputum or BAL for PCP CMV viral load. ABG. management according to the results of investigation If COVID-19 was confirmed: Supportive therapy. good hydration antipyretic in case of fever. Oxygen supply if indicated Discontinued MMF for few days with close graft monitoring. in case of severe infection reduce CNI through level with increasing steroids does. Anti viral Remdesivir; for COVID-19 treatment, References Bitterman R, Kumar D. Respiratory Viruses in Solid Organ Transplant Recipients. Viruses. 2021 Oct 25;13(11):2146. doi: 10.3390/v13112146. PMID: 34834953; PMCID: PMC8622983.
One year after transplantation, there is a significant decrease in the risk of opportunistic infections, making community infection more likely. Logically, etiologies that may have some connection with important environmental exposure should also be investigated.
But among the main causes I would point out:
– Viral infections by: parainfluenza, respiratory syncytial, influenza, COVID
– Bacterial: Community pneumonia and tuberculosis (high prevalence in Brazil)
– Cancer: metastasis from a recurrence of colon adenocarcinoma
I would point out as less likely causes:
– CMV pneumonia
– Fungal pneumonia: Aspergillosis, Cryptococcosis, PCP
– Cancer: PTLD
MANAGMENT
As a patient with only the possibility of Community Pneumonia (CAP), I would start coverage with third-generation cephalosporin + respiratory macrolide or quinolone. And meanwhile I would run more tests:
1 – Image:
– I would perform a CT scan of the chest in the expectation of better characterizing the consolidation and perhaps motivating the performance of bronchoscopy with BAL or even a biopsy;
2 – Blood:
Associated with serological tests or molecular markers and biomarkers in the blood:
– Galactomannan and B-Glucan
– CMV PCR, COVID19
– Blood culture and urine culture
– IGRA
– Serology for EBV
The patient is an elderly kidney transplant recipient who has Ca colon from post transplant ..He is on triple immunosuppression…with tacrolimus, MMF,steroids..He is on Calcium channel blockers for hypertension….He has chronic graft dysfunction with elevated creatinine….
He has presented with non productive cough and has stable vital signs..CXR shows right hilar consolidation…
the patient has a consolidation after 5 years of transplant…
The differential diagnosis for such a case scenario is Viral – RSV, COVID, Influenza, CMV; Fungal – PCP, histoplasma and CMV; Bacterial – Streptococci, pneumococci; Parasitic; like strongyloides or toxoplasma etc
But bacterial etiology is unlikely as there is no fever…
Patient also needs to be evaluated for lung metastasis as there is a history of carcinoma colon….
I would get a basic lab workup done and a CT chest and then decide on further management…
Differential diagnosis: · Viral- Covid 19, CMV, influenza, adenovirus, parainfluenza · Bacterial (Atypical)- Tuberculosis · Deep fungal infection · Malignancy: primary or secondary Management: · Detailed history and clinical examination. · Multi-disciplinary approach is needed. · Workups will includes: CBC, PCR for Covid 19, CMV, influenza, parainfluenza and adenovirus, CRP, procalcitonin levels, D dimer levels, UECS, blood slide for malaria, LDH, ESR. · Supportive treatment: Anti-pyretics for fever, adequate hydration, oxygen if SPO2<92%. · Reduction/ modification of IS: Stop MMF, Reduce CNI by 50% in severe disease., Oral steroids switched to IV dexamethasone in those requiring oxygen supplementation or mechanical ventilation. · Specific treatment according to confirm diagnosis.
Differential diagnosis
1) Viral infection (COVID-19, Influenza, Para-influenza, CMV)
2) PCP
3) Other bacterial causes of Community-acquired pneumonia
4) Tuberculosis
Investigations
1) Inflammatory marker
2) BAL – sputum for culture, AFB and mycobacterium culture
3) COVID PCR, Swab for viral panel
4) CMV PCR
5) CT Thorax
6) Blood culture
Management
1) Monitor oksigen saturation
2) Vital sign monitoring- may need to withhold anti-HPT
3) Reduction of immunosuppression, may need to withhold MMF
4) Empirical antibiotic to cover for community-acquired pneumonia
5) Steroid in the setting of COVID-19
Viral infection
– Covid-19
– PCP
– CMV
– Influenza and parainfluenza virus and others
Bacterial pneumonia including typical and atypical bacteria
Recurrence of Adenocarcinoma or metastatic carcinoma
PTLD Workup includes laboratory and imaging studies CBC Procalcitonin Renal function test Liver function test PCR COVID-19, EBV, CMV Sputum analysis and culture ABG BAL for PCP, TB culture, PCR of viruses
CT chest to check for characteristic findings which could be suggestive of fungal/malignancy. Treatment Initial step is temporary isolation to prevent the transmission of infection to health care personnel and the general public. Supportive care, adequate hydration, intravenous fluids, and antipyretics-symptomatic treatment Reduction of IS as cessation of MMF and use of reduced CNI levels to target lower trough levels Oxygen therapy or assisted ventilation may be necessary if a patient has hypoxemia. Empirical antibiotics using broad spectrum antibiotics to cover gram positive and negative bacteria as well as atypical bacterial infection. High-dose steroids can be helpful in complicated infections or COVID-19 Treatment of specific viruses is virus oriented
Differential diagnosis 1-Pneumonia a- Viral : influenza , RSV b- bacterial pneumonia c- tuberculosis d- fungal pneumonia – PCP, aspergillosis 2- Neoplastic causes -PTLD – metastasis from adenocarcinoma . 3-cardiac causes of dry cough as pulmonary hypertension , pulmonary congestion. 4- Pulmonary atelectasis. Investigations – CBC , ESR , CRP,procalcitonin – Quanteferon TB gold. – Multi slice CT chest – Echo Management : As the patient is generally stable , only symptomatic treatment with antitussive and monitoring of the patient is needed , changing the regimen of immunesuppression is required in contex of adenocarcinoma , its better to switch MMF to sirolimus.
Acute respiratory infection is very likely
COVID-19 pneumonia
viral pneumonia
bacterial pneumonia
opportunistic pneumonia
MULTIDSIPLINARY TEAM involving ICU , respiratory and infectious specialist
labs- routine blood labs and sputum test CBC, ESR, CRP, procalcitonin, ferritin levels, nasopharyngeal swabs for SARS-CoV-2 RT-PCR and influenza, coagulation profile, D-dimers, BGA, IGRA, sputum gene xpert, sputum m/c/s, urine LAM, BAL for PCP and aspergillosis, CMV quantitative PCR, BKV quantitative PCR, EBV quantitative PCR, serum LDH, fungal markers (BDG, galactomannan),
covid is more likely and can be confirmed with nasal RT=PCR test , HRCT of chest
management
supportive therapy like nasal o2, hydration , physiotherapy
NO change in IS is advised for covid pneumonia in this case
in general covid pneumonia is not very aggressive in the presence of IS in transplant patients
A 71-year-old male with hypertensive nephropathy received a kidney graft in February 2016. He had a history of colon adenocarcinoma in June 2019. His baseline Cr was 240–260 μmol/L. His immunosuppressive regimen included prednisolone 5 mg OD, tacrolimus (trough level was 6.4 ng/mL), and MMF 250 mg BD. He was also on calcium channel blockers and proton pump inhibitors. He presented in April 2020 with a dry cough with no other symptoms but stable vital signs. However, a chest X-ray revealed an infra-hilar consolidation on the right side.
DDx
Respiratory tract infection is the most likely diagnosis in our immunocompromised patient with dry cough cxr findings
The most common pathogens, in order of greatest incidence, include bacteria (eg, Staphylococcus aureus, Pseudomonas species, Enterobacteriaceae, enterococci, Haemophilus influenzae, mycobacteria), viruses (eg, cytomegalovirus, Epstein-Barr virus, herpes simplex virus, influenza, respiratory syncytial virus, adenovirus, parainfluenza virus, coronavirus), and fungi (eg, Pneumocystis jirovecii, Aspergillus)
As the period mentioned above April 2020 make COVID-19 on the top of the list .
How to manage
History including history of recent contact with COVID positive within 14 days ,visiting pandemic area within the last 14 days ….
Physical examination
Routine labs CBC ,Creatinine and BUN, AST ,ALT ,LDH, CRP
Coagulation profile ,RBS ,serum electrolytes, ferritin ,IL6
COVID RT PCR and antigen
CXR
HR Chest CT
Management included supportive treatment (intravenous fluid therapy, monitoring renal function, and symptomatic treatment with or without ward-based oxygen therapy depending on oxygen saturation) and discontinuation of the antiproliferative immunosuppressive drugs.
Since remdisivir was approved for the treatment of COVID-19 and its interaction with CNI is yet unknown, we recommend treatment with remdisivir in a hospital setting where CNI drug level monitoring is available.
2. A 71-year-old male with hypertensive nephropathy received a kidney graft in February 2016. He had a history of colon adenocarcinoma in June 2019. His baseline Cr was 240–260 μmol/L. His immunosuppressive regimen included prednisolone 5 mg OD, tacrolimus (trough level was 6.4 ng/mL), and MMF 250 mg BD. He was also on calcium channel blockers and proton pump inhibitors. He presented in April 2020 with a dry cough with no other symptoms but stable vital signs. However, a chest X-ray revealed an infra-hilar consolidation on the right side.
Issues/ concerns:
– 71yo male, hypertensive nephropathy, KTx Feb 2016
– June 2019 hx of colon adenocarcinoma, baseline sCr 240-260
– detailed history and physical examination: vaccination history (pneumococcal, influenza, SARS-CoV-2), rejection treatment, history of contact (SARS-CoV-2, TB), lymphadenopathy
– imaging: graft ultrasound, HRCT (Chest) to rule out malignancy as well as assess parenchymal involvement
– modification of immunosuppressive regimen: hold MMF since he is already on a small dose at 250mg BD, maintain tacrolimus and prednisone
– specific treatment depending on the results obtained from the investigations done:
SARS-CoV-2 – mainly supportive treatment, isolation, oxygen as required, in case of severe disease consider increasing steroid dose, adding remdesivir
TB – antituberculous drugs for at least 6-9 months but may be extended depending on the site of the infection
community acquired pneumonia – amoxicillin-clavulanic acid plus a macrolide
PCP – high dose TMP-SMX, steroids as indicated
References
1. Nair V, Jandovitz N, Hirsch JS, Nair G, Abate M, Bhaskaran M, et al. COVID-19 in kidney transplant recipients. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2020 Jul;20(7):1819-25. PubMed PMID: 32351040. Pubmed Central PMCID: PMC7267603. Epub 2020/05/01. eng.
2. Sundaram M, Adhikary SD, John GT, Kekre NS. Tuberculosis in renal transplant recipients. Indian journal of urology : IJU : journal of the Urological Society of India. 2008 Jul;24(3):396-400. PubMed PMID: 19468476. Pubmed Central PMCID: PMC2684355. Epub 2009/05/27. eng.
3. Kim JE, Han A, Lee H, Ha J, Kim YS, Han SS. Impact of Pneumocystis jirovecii pneumonia on kidney transplant outcome. BMC Nephrology. 2019 2019/06/10;20(1):212.
Differential diagnosis: · Viral- Covid 19, CMV, influenza, adenovirus, parainfluenza · Bacterial (Atypical)- Tuberculosis · Deep fungal infection · Malignancy: primary or secondary Management: · Detailed history and clinical examination. · Multi-disciplinary approach is needed. · Workups will includes: CBC, PCR for Covid 19, CMV, influenza, parainfluenza and adenovirus, CRP, procalcitonin levels, D dimer levels, UECS, blood slide for malaria, LDH, ESR. · Supportive treatment: Anti-pyretics for fever, adequate hydration, oxygen if SPO2<92%. · Reduction/ modification of IS: Stop MMF, Reduce CNI by 50% in severe disease., Oral steroids switched to IV dexamethasone in those requiring oxygen supplementation or mechanical ventilation. · Specific treatment according to confirm diagnosis.
PCP infection
CMV infection
COVID-19
Herpes virus infection
Respiratory virial infection like Influenzas para influenzas etc
Ca lung/Lung metastases
Community acquired pneumonia – Bacterial
Management
COVID RT PCR prior to admission
Full blood count, LDH, Ferritin, CRP and procalcitonin(PCT)
CT Thorax with HRCT
CMV PCR
BAL for culture and Respiratory Panels
Management
Vital monitoring, observe for exertional desaturation.
Stopped MMF
Continue CNI and Steroids
IV hydration
To treat the cause if any results available
Investigations:
·Full blood count, ESR, LFT, RFTs, RBG, CRP and LDH.
· Further Laboratory work-up is needed to screen for viral infection; COVID-19, PJP, CMV and bacterial infection.
· To screen for Mycobacterial tuberculosis( induced sputum for AAFB and PCR for TB). Plan of management :
Full supportive measures.
To treat in isolation in the hospital.
Management of COVID-19 infection:
A. Mild infections: the usual practice is to continue or reduce the dose of immuno-sup pressive drugs. Discontinuation of the antiproliferative drugs is strongly suggested.
B. Severe infection with requirement to mechanical ventilation: to maintain corticosteroids, hold antiproliferative and to argue about ceasing CNIs.
C. Remdesivir-treated patients had 31% faster time to recovery when compared to control.
D. CRRT may play a role in the management of AKI in COVID-19 patients. It was assumed that high-volume hemofiltration could remove inflammatory cytokines (tumour necrosis factor, IL-6, and IL-1β) involved in the pathogenesis of renal injury. References 1. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current EvidenceMuhammed Ahmed Elhadedy, Yazin Marie, Ahmed HalawaNephron 2021;145:192–198 DOI: 10.1159/000512329
Differential diagnosis
Dry cough with stable vital signs CXR showed a infrahilar consolidation on the right side in a kidney transplant recipient.
Differential will include:
Bacterial pneumonia
Viral- influenza, parainfluenza, adenovirus
TB
Covid 19
Metastasis- had prior history of colon adenocarcinoma.
Management
Detailed history and through physical examination.
Management in a hospital setting this is an elderly patient with prior history of colon cancer and a kidney transplant recipient.
Management should be in consultation with infectious disease specialist.
Workups include: CBC, UECS, LFT, LDH,CRP, procalcitonin, D dimers, Covid 19 PCR, influenza, parainfluenza and adenovirus PRC, blood cultures, HRCT, tacrolimus trough levels.
Supportive management- rehydration and oxygen supplementation if desaturates.
Stop the MMF.
May require to reduce the CNI dose in severe disease.
The oral steroids switched to dexamethasone in severe Covid 19 disease requiring oxygenation or mechanical ventilation.
There is a role of antivirals -remdesvir in patients requiring oxygenation and not on mechanical ventilation.
Other- Baricitinib, Tocilizumab, IVIG.
For influenza- Treatment includes oseltamivir (oral), zanamivir (inhaled and intravenous), peramivir
For adenovirus treatment includes- cidofovir, brincidofovir (investigational), IVIG References
Respiratory Viruses in Solid Organ Transplant Recipients Roni Bitterman
and Deepali Kumar
Horby P et al. Recovery collaborative group; Dexamathasone in hospitalized pts with covid 19.N Eng j med.2021 feb 25;384(8)693-704
Halawa A et al; Covid 19 in KTR; Case series and brief review of current evidence.Nephron2021;142(2);192-198
A 71-year-old male with hypertensive nephropathy received a kidney graft in February 2016. He had a history of colon adenocarcinoma in June 2019. His baseline Cr was 240–260 μmol/L. His immunosuppressive regimen included prednisolone 5 mg OD, tacrolimus (trough level was 6.4 ng/mL), and MMF 250 mg BD. He was also on calcium channel blockers and proton pump inhibitors. He presented in April 2020 with a dry cough with no other symptoms but stable vital signs. However, a chest X-ray revealed an infra-hilar consolidation on the right side DDX;
Considering age and comorbidities, monitor in a hospital set up and initiate IV dexamethasone if we end up desaturating or requiring any resp support.
In severe cases, decrease CNI ,monitor graft function and increase steroids to stress doses.
Antivirals to be considered to either decrease inflammation or hasten recovery ;Remdesivir/Cidofovir for covid infection.Osetalmivir to be used in parainfluenza infection.
Other therapies ; Tocilizumab/IVIG
Modify tx depending on outcome of results requested.
Pt to be vaccinated according to transplant protocol.
Revert to pre infection immunosuppressive medications once infection is cleared with keen interest in graft function and drug interactions.
REF;
Horby P et al. Recovery collaborative group; Dexamathasone in hospitalized pts with covid 19.N Eng j med.2021 feb 25;384(8)693-704
Halawa A et al; Covid 19 in KTR; Case series and brief review of current evidence.Nephron2021;142(2);192-198
DD
Viral ,fungal, bacterial, reactivation of latent TB,COVID 19
Investigations :Routine labs and fluid cultures, Covid PCR, sputum for AFB,HRCT of chest.
Management: supportive treatment ,hydration ,broad spectrum antibiotics.
Specific treatment based on underlying cause.
Immunosuppression modification ;MMF reduction.
Infrahilar consolidation in a 71 year old post transplant patient has wide differential
It could be
Bacterial
Viral
Fungal
Tuberculous
In prevailing circumstances Covid pneumonia should be considered however this is not usual involvement.
To narrow down the diferential and reach a final diagnosis we need to work him up
Blood CP
ESR
CRP
LDH
Electrolytes
Lfts
Covid PCR
sputum for gram stain , culture and AFB
HRCT chest
Definitive treatment should be according to the final diagnosis
We in our setup start broad spectrum Iv antibiotics
to cover community acquired pneumonia along with coverage for opportunistic infections
Maintain adequate hydration
Modification of immunosupression, mainly reduction of MMF if needed
⭐ Differential diagnosis:
_COVID 19 infection.
_Other viral infections as influenza , parainfluenza or RSV.
_CMV infection.
_Bacterial infection especially mycoplasma infection in extreme of ages.
_PJP can be considered in such elderly transplant recipient with prior hx of malignancy and chemotherapy.
_TB also must be in mind.
_pumonary aspergillosis.
_Metastasis or lung cancer.
⭐ Investigations required:
_COVID PCR from nasal /throat swab.
_Swab for culture for bacterial infection.
_CT chest with contrast to exclude lung tumors whether primary or secondaries (as he has hx of adenocarcinoma, then biopsy if suspicious lesions in CT).
⭐ Management plan:
_parient isolation to prevent spread of infection to health care workers and to the community.
_supportive therapy , good hydration , IV fluids and antipyretics (paracetamol).
⭐ Reduction of IS as stoppage of MMF and use lower levels of CNI.
👉 if patient has hypoxemia, oxygen therapy or assisted ventilation may be required.
_i will start empirical combined antibiotics in such old patient as (3 rd or 4th generation cephalosporin and macrolides) .
_use of high dose dexa on severe cases to shorten hospital stay.
_use of remdisivir in COVID 19 infection and oseltamivir in influenza infection.
_use of IVIG in severe cases or CVVHF in case of AkI and cytokine storm.
_PJP is diagnosed through BAL and PCR and treatment is by oxygen, SMX-TMP with steroids only in hypoxemic cases.
_CMV infection if high risk (D+/R-) with diagnosis by PCR and ttt by oral valganciclovir or IV ganciclovir (if bad general condition and can not take oral medications).
_Aspergillosis is diagnosed by BAL and serum galactomanan (treatment by voriconazole ).
Elderly with dry cough and infra hilar consolidation at time of COVID 19 outbreak.
After detailed history of symptoms, infectious disease histoty, including COVID 19, respiratory infections and immunosuppression history.
Differential diagnoses:
COVID 19 pneumonia
Bacterial pneumonia,including aspiration pneumonia
Metastasis from his previous cancer
Fungal infection, like aspergillus.
To manage this case:
After the routine lab, CRP, Ferritin, LDH, COVID-19 swab, if negative will consider other differentials including fungal and PCP.
If confirmed COVID 19 positive, then will follow local protocol for that with involvement of ID team, reduction of immunosuppression, holding MMF, reducing FK level to lower end of target, around 4, dexamethasone, anti-viral drugs etc.
References:
1-COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence Muhammed Ahmed Elhadedya, Yazin Mariea Ahmed Halawaa,
Nephron, Published online: December 8, 2020
4 year post transplant and hx Adenocarcinoma presented with dry cough and chest X-ray revealed an infra-hilar consolidation on the right side with stable vitals DD:
Cancer Metastasis (need a contract study and accepting risk of CI-AKI if other DD excluded.infection (need infection parameters and more blood tests) FBC, CRP, procalcitonin, LFT, U&E, blood culture for bacterial infection, urine legionella and pneumococcal Ag, viral swabs for PCP , COVID and resp viral infection PCR. Keep TB in the back of your mind if had prev hx of TB or high risk populationOthers like sarcoid or Wagner, PE
Manage: untill we get the full pic, I would treat what I see (consolidation) with Abx for CAP as per local guidlines in the first instance. If the patient well enough, no need to alter his immunosupression meds.
KTR presented with dry cough and right-side infra-hilar consolidation at CXR may have the following diseases as differential diagnosis:
a) COVID-19 infection.
b) Pneumocystis Jerovecii Pneumonia.
c) Respiratory viral infection e.g.; RSV, Influenza virus, para-influenza virus, corona-viruses and rhinoviruses.
d) CMV pneumonitis.
e) Atypical bacterial infection.
f) Allergic pneumonitis.
Investigations:
· Full blood count, LFT, RBG, CRP and LDH.
· Laboratory work-up is needed to screen for viral infection; COVID-19, PJP, CMV and bacterial infection.
· To screen for Mycobacterial tuberculosis( induced sputum for AAFB and PCR for TB).
Plan of management :
· Full supportive measures.
· To treat as isolated patient in the hospital.
· Management of COVID-19 infection(1):
A. Mild infections: the usual practice is to continue or reduce the dose of immunosup- pressive drugs. Discontinuation of the antiproliferative drugs is suggested.
B. Severe infection with requirement to mechanical ventilation: to maintain corticosteroids, hold antiproliferative and to argue about ceasing CNIs.
C. Remdesivir-treated patients had 31% faster time to recovery when compared to control.
D. CRRT may play a role in the management of AKI in COVID-19 patients. It was assumed that high-volume hemofiltration could remove inflammatory cytokines (tumour necrosis factor, IL-6, and IL-1β) involved in the pathogenesis of renal injury.
References 1. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current EvidenceMuhammed Ahmed Elhadedy, Yazin Marie, Ahmed HalawaNephron 2021;145:192–198 DOI: 10.1159/000512329
71 years- old male, presents with chest infiltrates +dry cough in kidney transplant recipient (2016), a year after diagnosis of colon adenocarcinoma (2019). Differential diagnosis: Infectious: Most probable community acquired pneumonia: Bacterial (streptococcus, hemophilus influenza, Moraxella catarrhalis, legionella pneumophila, chlamydia, mycoplasma….etc), respiratory viruses(RNA viruses[ influenza viruses, parainfluenza virus, respiratory syncytial virus, human metapneumovirus, rhinovirus, coronavirus],DNA viruses [adenovirus, bocavirus, KI and WU polyomaviruses, CMV]) Fungal is unlikely however the patient had a colon cancer and he might receive chemotherapy with the combination immunosuppressive medications (tac+MMF+prednisolone): Aspergillus spp., Pneumocystis jirovecii. Non-infectious: o Metastatic adenocarcinoma.o Pulmonary embolism.o Bronchiolitis obliterans organizing pneumonia.o Drug induced pneumonitis: CAR-T cell therapies, checkpoint inhibitors and others.o PTLD. This patient with old age and suboptimal graft function and malignancy, there is a high risk for opportunistic infections. Management plan: o Full history, contact with sick people, history of recent travel, occupational history.
Full clinical examination: head and neck , lymphnodes exam, chest exam, abdomen and lower limbs exam, respiratory rate , O2 saturation, and spirometry. o Identify Risk factors: HLA miss match, use of ATG, History of rejection.
Evaluate the hemodynamic status, volume status of the patient, age of the patient, and comorbidities(ca colon). o Laboratory: Full blood count(CBC), urinalysis, CRP, ESR, Kidney function test- creatinine, BUN, Na,k, Liver function test-AST, ALT, bilirubins, albumin, INR, LDH, ferritin, and D-dimer. o Microbiology: Blood, urine and throat swab culture.
NAT-PCR for all the above mentioned viruses, PCR and viral load of CMV, EBV, PJP., Serum galactomannan and 1,3-beta-D-glucan levels for aspergillosis
Identify Risk factors: HLA miss match, use of ATG, History of rejection.
Evaluate the hemodynamic status, volume status of the patient.
o BAL for culture, cytology and PCR.
o Further imaging: chest CT scan: high resolution or with contrast if needed.
o Trail of stopping the calcium channel blocker that might worsen his GERD and produce an aspiration pneumonia or pneumonitis. o Medications:
IV hydration, nebulizers, anti-cough. I would decrease tacrolimus dose to (4 ng/dl), and will evaluate for stopping MMF when needed, with stress dose prednisolone /dexamethasone. I would start him on empirical antibiotics for CAP (ie IV ceftriaxone + macrolide /res. quinolones) Remdisivir for COVID-19 Ribavirin for influenza and other respiratory viruses IVIG may be an option.
References: (1) Ahmad Z, Bagchi S, Naranje P, Agarwal SK, Das CJ. Imaging spectrum of pulmonary infections in renal transplant patients. Indian J Radiol Imaging. 2020 Jul-Sep;30(3):273-279. doi: 10.4103/ijri.IJRI_357_19. Epub 2020 Oct 15. PMID: 33273760; PMCID: PMC7694710. (2) Samavat S, Nafar M, Firozan A, Pourrezagholi F, Ahmadpoor P, Samadian F, Ziaei S, Fatemizadeh S, Dalili N. COVID-19 Rapid Guideline in Kidney Transplant Recipients. Iran J Kidney Dis. 2020 May;14(3):231-234. PMID: 32361701. (3) Namazee N, Mahmoudi H, Afzal P, Ghaffari S. Novel coronavirus 2019 pneumonia in a kidney transplant recipient. Am J Transplant. 2020 Sep;20(9):2599-2601. doi: 10.1111/ajt.15999. Epub 2020 Jun 12. PMID: 32400099; PMCID: PMC7272986. (4) Manuel O, Estabrook M; American Society of Transplantation Infectious Diseases Community of Practice. RNA respiratory viral infections in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13511. doi: 10.1111/ctr.13511. Epub 2019 Mar 22. PMID: 30817023; PMCID: PMC7162209.
a) Covid-19. b) PCP. c) PCP/CMV. d) CMV. e) Influenza and parainfluenza virus. f) BK virus infection. g) Other viral infections.
Bacterial pneumonia.
Metastetic carcinoma from adenocarcinoma.
PTLD.
Workup
Viral screening;
a) Swab for covid-19. b) Pan cultures. c) Viral loads and PCR. d) Urien microscopic examination.
CTHR lung.
Treatment
Supportive management (IV fluid and O2 therapy if desaturated).
Stop MMF.
Reduce TAC to 25-50% with drug monitoring level (Target level 3-6).
As the patient at graft impairment, return back to immunosuppressant as early as the infection is controlled to avoid allograft rejection and graft loss.
Remdisivir.
Dexamethasone.
Cidofovir (covid-19, BK)
Tocilizumab, (in covid-19)
Leflunomide (in BKV infection).
Rituximab (PTLD, BKVN)
IVIG in severe condition.
Monitor drug level, kidney function, and viral loads.
vaccination after curing the condition.
References
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054–62. 5 Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020 April 30;382(18):1708–20. 6 Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497–506.
López-Medrano, F.; Aguado, J.M.; Lizasoain, M.; Folgueira, D.; Juan, R.S.; Díaz-Pedroche, C.; Lumbreras, C.; Morales, J.M.; Delgado, J.F.; Moreno-González, E. Clinical implications of respiratory virus infections in solid organ transplant recipients: A prospective study. Transplantation 2007, 84, 851–856. [CrossRef] 4. Law, N.; Kumar, D. Post-transplant Viral Respiratory Infections in the Older Patient: Epidemiology, Diagnosis, and Management. Drugs Aging 2017, 34, 743–754. [CrossRef] 5. Ruuskanen, O.; Lahti, E.; Jennings, L.C.; Murdoch, D.R. Viral pneumonia. Lancet 2011, 377, 1264–1275. [CrossRef] 6. Kumar, D.; Husain, S.; Chen, M.H.; Moussa, G.; Himsworth, D.; Manuel, O.; Studer, S.; Pakstis, D.; McCurry, K.; Doucette, K.; et al. A prospective molecular surveillance study evaluating the clinical impact of community-acquired respiratory viruses in lung transplant recipients. Transplantation 2010, 89, 1028–1033. [CrossRe
Thank you Prof
BK virus can directly be a cause of respiratory symptoms (BKviralpneumonia), and many cases are reported as BK pneumonia, with viral inclusion found in the bladder and the lung. Indirectly, although conflicting, but there is a great developing era of association between BK virus and malignancy (BK virus has an oncogenic properties), BK virus isolated from urothelial , bladder, prostate and it can cause adenocarcinoma References
BK Polyoma Virus and Malignancy: Cause or Co-Incidence?R. Prashar, A. Shah, D. Stewart, S. Williamson, A. Patel.
Henry Ford Transplant Institute, Detroit, MI
In this patient with a new history of cancer after transplantation, MMF could be replaced by mTOR. Symptom of dry cough with infra hilar consolidation can be related to malignancy or viral infection. PCP is a probable cause but usually presents as bilateral infiltration. CMV can present with unilateral pneumonitis; Fever can be absent. For better differential diagnosis, we may need CT scan. Evaluation with CBC, CRP, and Biochemistry profile is needed. In case of suspicion of viral infection, respiratory panels can be ordered. In the era of COVID (at that time), sars-cov2 PCR should be ordered.
Antiproliferative drugs like MMF should be reduced or stopped (here, 500 mg/day is given: can be stopped). Steroids can be increased both to relieve the symptoms and oxygenation (if low)
Workup:
CBC
CRP
Procalcitonin
CXR follow-up (repeated on eed according to daily physical examination and clinical need)
Monitoring of vital signs and SPO2
DDX:
Viral infections (ALL can be ) specific evaluation for CMV is needed to start specific therapy. Superimposed bacterial infections can complicate the scenario and may entail antibiotics.
Treatment:
Supportive (Oxygen, nebul/inhaler)
specific treatment (according to the causative agent)
Thank you, Prof. Dr Ahmed. Regarding My suggestion/intention of shifting MMF to mTOR inhibitors here, relying on the probability of covid and viral infections in addition to previous history of cancer with the probability of malignant lesion (either primer or metastatic in the lung). Just as we may do when we face BK and CMV, which is in our list of ddx in this case, although not well justified, there was a trend to stop antiproliferative drugs at the time of the COVID-19 peak.
One of the papers that talked about the immunity against COVID-19 (Kantauskaite M, Müller L, Kolb T, Fischer S, Hillebrandt J, Ivens K, Andree M, Luedde T, Orth HM, Adams O, Schaal H, Schmidt C, Königshausen E, Rump LC, Timm J, Stegbauer J. Intensity of mycophenolate mofetil treatment is associated with an impaired immune response to SARS-CoV-2 vaccination in kidney transplant recipients. Am J Transplant. 2022 Feb;22(2):634-639. doi: 10.1111/ajt.16851. Epub 2021 Nov 1. PMID: 34551181; PMCID: PMC8653081.)
The differentials will include 1. Viral infections 2. Upper respiratory infections 3. COVID 19 infection 4. Ashthma/ COPD 5. Bacterial infections 6. Fungal infections- PCP, Aspergillosis
Management This patient will require hospitalization, hydration and supportive care. Investigations will include- Blood tests like Blood CO. CRP, Renal and liver functions, ProCal Nasal and pharyngeal swabs for COVID 19 and influenza CMV and PCP PCR Urine and blood cultures Imaging like HRCT chest If needed then Bronchoscopy and BAL
Mild cases can be managed at home with home quarantine As regards Immune suppression, MMF should be stopped and CNI can continue Monitoring of graft functions
If concern about rejection , then graft biopsy and management accordingly Treatment with IVIG Antiviral therapy according to results and local protocols.
Singh N, Limaye AP. Infections in Solid-Organ Transplant Recipients. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 2015:3440–52.
Your reply is rather limited. It does not address all the concerns.
I agree that investigating for viral infections including COVID19 as the first step.
I appreciate your clinical approach that includes commencing anti-virals and stopping MMF for few days.
Please use headings and sub-headings to make easier to read your write-up. Please use bold or underline to highlight headings and sub-headings.
Likely differentials in the above scenario includes :
Viral pneumonias : Covid-19 being at the top (because of current pandemic),CMV ,EBV, HSV
Community acquired pneumonia
Tuberculosis
PCP and Fungal infection like Aspergillosis
Mets from the colon adenocarcinoma .How do you manage this case?
Patient should be admitted first, then thorough history taking and examination should be done ,detailed investigations like Chest X-ray PA view followed by HRCT chest ,Complete blood picture ,inflammatory marker like CRP, ferritin, ldh,beta D glucan and Aspergillus precipitans ,IGRA test for TB,Viral studies including PCR for COVID,CMV DNA CR,HSV and EBV PCR, sputum induction with hypertonic saline and staining with special stains of sample for PCP(methenamine silver for PCP)and TB, – all should be carried out and Brochoscopy with BAL if needed.
Treatment includes: hydration with I/V fluids ,Paracetamol for fever, broad spectrum antibiotics to be started anti-metabolite i.e., Mycophenolate moefitil should be stopped and patient should be monitored closely for graft function with serum creatinine and TAC level should be maintained around 5-7ng/ml. Steroids may need to be titrated to high dose in COVID case as it shortens 28 day mortality. Other treatment for COVID -19 remains controversial but can be tried like Remedesivir, Paxlovid but with cautious use due to drug-drug interaction.
REFERENCES:
1-Demir E, Ucar ZA, Dheir H,et al.COVID-19 in Kidney Transplant Recipients: A Multicenter Experience from the First Two Waves of Pandemic. BMC Nephrol. 2022 May 12;23(1):183.
2- Elhadedy MA, Marie Y, Halawa A. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence. Nephron. 2021;145(2):192-198.
I agree that investigating for COVID19 as the first step.
I appreciate your clinical approach that includes commencing anti-virals and stopping MMF for few days.
Please use headings and sub-headings to make easier to read your write-up. Please use bold or underline to highlight headings and sub-headings.
A 71-year-old male with hypertensive nephropathy received a kidney graft in February 2016. He had a history of colon adenocarcinoma in June 2019. His baseline Cr was 240–260 μmol/L. His immunosuppressive regimen included prednisolone 5 mg OD, tacrolimus (trough level was 6.4 ng/mL), and MMF 250 mg BD. He was also on calcium channel blockers and proton pump inhibitors. He presented in April 2020 with a dry cough with no other symptoms but stable vital signs. However, a chest X-ray revealed an infra-hilar consolidation on the right side. What is the differential diagnosis? The differential diagnoses of dry cough in post-kidney transplant patient during COVID19 pandemic era include: COVID 19 infection it’s my 1st DD in the COVID era in immunocompromised patients. Upper respiratory infection, Respiratory Virus Infections with other viral infection such as influenza or bronchitis. Viral pneumonia (CMV, EBV, VZV, and HSV) Fungal infection (PJP) infection. Asthma, COPD Exacerbation Bacterial infection (TB). Herpesvirus infection (EBV, HSV and VZV). Lung cancer (primary or secondary). Chronic GERD, Post nasal drip, smoking ….. This transplant patient is at a high risk of infection due to:
Immunosuppression
Underlying CKD
Hypertension
COVID-19 is suspected in any of the following scenarios: History of dry cough, chills, sore throat, and SOB +/- fever. Patients with upper/lower respiratory symptoms with radiological findings History of close contact with a COVID-19 case within the last 14 days. History of presence in COVID-19 epidemic regions within the last 14 days Pneumonia that deteriorates or fails to improve despite proper treatment. How would you manage this case? Detailed history and comprehensive clinical examination ABCD Any history of contact with SARS2-CoV positive patients. CT thorax without iv contrast (To confirm if there is any chest findings) CBC, (lymphopenia may be seen) Kidney function tests. Urine Analysis, Urine and Blood C/S CNIs level TB (Mantoux, IGRA, and sputum culture) Screening
Fungal (PJP) (induced sputum or bronchoscopy for BAL) screening Nasal and throat swab for COVID-19/PCR. Sr. Ferritin, IL-6. CMV viral load. LDH, Ferritin, CRP and procalcitonin If confirmed to be COVID-19 (mild infection):
Admission in isolation room, under observation
Supportive medical therapy,good hydration (IV fluids and acetaminophen as needed). Reduction of immunosuppressive medications or even discontinued. Discontinued MMFor decrease 50% and continue CNIswith close graft monitoring the patient (immunosuppression treatment should be individualized based on the careful assessment of each patient) Drugs targeting immune response regulation: Interferons And Dexamethasone. Dexamethasone in those receiving respiratory support (invasive mechanical ventilation or oxygen alone): resulted in lower 28-day mortality (3) Drugs that preventing viral replicatation: Paxlovid, remdesivir, molnupiravir, favipiravir, ribavirin, & Kaletra. Remdesivir:The Adaptive COVID-19 Treatment Trial proved that remdesivir-treated patients had 31% faster time to recovery when compared to control (1) Case series and a small RCT suggested better outcomes with interferon and high-dose steroids in conjunction with supportive care (2) References Elhadedy MA, Marie Y, Halawa A. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence. Nephron. 2021;145(2):192-198. doi: 10.1159/000512329. Epub 2020 Dec 8. PMID: 33291120; PMCID: PMC7801980.
Bitterman R, Kumar D. Respiratory Viruses in Solid Organ Transplant Recipients. Viruses. 2021 Oct 25;13(11):2146. doi: 10.3390/v13112146. PMID: 34834953; PMCID: PMC8622983.
RECOVERY Collaborative Group; Horby P, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17. PMID: 32678530; PMCID: PMC7383595. Samavat et al. COVID-19 in Kidney Transplantation Recipients, Iranian Journal of Kidney Diseases | Volume 14 | Number 3 | May 2020
Yes, as you suggest, I would have looked for COVID19 as the first step. I like your comprehensive reply. I agree that you would consider stopping MMF for few days. I appreciate your very well-referenced clinical approach that includes commencing anti-virals and stopping MMF for few days.
Typing whole sentence in bold or typing in capitals amounts to shouting.
-This is post kidney transplant patient with a history of Ca colon and chronic allograft nephropathy present with cough without any other symptoms the differential diagnosis most likely
Covid 19 infection
Metastatic lesion from colon cancer
primary lung cancer
CMV pneumonia
PCP
Pulmonary tuberculosis
Management :
Admit to isolation ward ,check the vitals and assess for the need of oxygen, iv fluids ,antipyretics ,take swab for COVID -19 virus ,full blood counts, renal function test ,inflammatory markers, CMV PCR,TB rapid test , and induced sputum for PCP if other differential is excluded
-HRCT – BAL and bronchoscopy
-Follow the patient’s vitals and if confirmed COVID 19 then management is minimizing immunosuppression ,stopping MMF continue CNI and Steroids along with good supportive care, with antivirals as recommended . -If proved malignancy referral to an oncologist with a multidisciplinary team including a thoracic surgeon .
Your reply is rather short.
Yes, as you suggest, I would have looked for COVID19 as the first step. I agree that you would consider stopping MMF for few days.
The index patient is an elderly kidney transplant recipient, who had a history of adenocarcinoma colon 3 years post-transplant. He is on tacrolimus based triple drug immunosuppression with calcium channel blockers (for hypertension presumably). The patient has an elevated baseline serum creatinine, suggesting chronic graft dysfunction. 4 years post-transplant, he has presented with non-productive cough, and stable vital signs. The chest x ray shows right infra-hilar consolidation. The clinical symptoms are suggestive of pneumonia.
The differential diagnosis in such a scenario would be (1):
a) Viral: Respiratory viruses (like influenza, parainfluenza, SARS-COV2, in view of the timeline of April 2020), Herpesviruses (cytomegalovirus, CMV etc)
b) Fungal: Pneumocystis jirovecii, histoplasma, Cryptococcus
c) Bacterial: community acquired like streptococcus, tuberculosis etc.
d) Parasitic: Toxoplasma, Strongyloides etc.
e) Non-infectious: Lung tumor (primary or metastases), PTLD.
In view of non-productive cough in April 2020, probability of COVID-19 is high. Absence of fever also points towards SARS-COV2 infection as fever is less common and COVID-19 is more commonly seen in hypertensive patients (2).
In view of immunosuppressed status (transplant recipient with chronic graft dysfunction), Pneumocystis pneumonia, PCP (presenting symptom of dry cough) or CMV pneumonia is also a strong possibility in this scenario (3,4).
Bacterial etiology of the clinical picture is unlikely (no expectoration and fever).
How would you manage this case?
The management of the index case involves:
1) A detailed history and clinical examination: Emphasis on travel history and history of exposure to someone affected with COVID-19 should be elicited. SpO2 should be checked to assess hypoxia.
2) Laboratory testing including complete blood count (especially look for lymphopenia), renal function tests, liver function tests, C reactive protein, blood culture, chest X ray, influenza testing (if in season) and other respiratory viral testing (biofire), Tacrolimus trough levels, LDH, ferritin and Interleukin-6 (IL-6).
3) Nasopharyngeal swab test for SARS-COV2 RT-PCR/ Antigen.
4) Induced sputum examination for cytology, gram stain and acid-fast bacilli stain, and culture.
5) High resolution computed tomogram (HRCT) of chest in view of the chest x ray finding.
6) CMV PCR testing
7) Empiric initial treatment:
a) Isolation of the patient.
b) In case there is no hypoxia and only cough without any tachypnea, patient can be isolated at home.
c) If there is hypoxia, empirical anti PCP treatment in form of co-trimoxazole and steroids (if hypoxemia with oxygen saturation <70% on room air) should be started pending the investigation results. Anti-PCP treatment can be stopped once investigations for pneumocystis are negative.
8) Supportive care: Hydration and nutrition.
9) Further management as per the etiology:
a) If SARS-COV2 infection:
Mild to moderate illness (SpO2 >94% without requiring any supplemental oxygen) does not require anything other than symptomatic treatment (5). Those with high risk of progression may be given high-titre COVID-19 convalescent plasma if within 8 days of onset of disease. Other options include 3 days of remdesivir (within 7 days of symptom onset), nirmatrelvir/ritonavir or molnupiravir (within 5 days of onset), or neutralizing monoclonal antibodies (within 7 days of onset). No role of hydroxychloroquine, azithromycin, lopinavir/ritonavir, dexamethasone, inhaled steroids, dexamethasone ivermectin, colchicine, and famotidine in such patients.
In severe (SpO2 <94% on room air) or critical (end-organ dysfunction, requiring ventilatory support) illness,Dexamethasone 6 mg daily for 10 days should be given. 5 days of remdesivir treatment can be given to patients on supplemental oxygen (but not to patients on mechanical ventilation). Those who cannot be given steroids due to contraindication, should be given Baricitinib with remdesivir. In presence of elevated markers of systemic inflammation, use of Tocilizumab (or Sarilumab) is recommended (5).
Immunosuppression: Antimetabolites to be stopped, Tacrolimus doses to be adjusted as per trough (target 4-6) levels in case of severe or critical illness (5).
b) If PCP: Continue PCP treatment.
c) If CMV: Treatment with oral valganciclovir 900 mg twice a day or intravenous ganciclovir (5mg/kg IV 12 hourly, to be adjusted according to creatinine clearance). It should be continued for minimum 2 weeks (gancyclovir can be changed to oral valganciclovir, if patient improves earlier), and until resolution of clinical symptoms and radiological findings with clearance of CMV in blood, if present (6). Complete blood count and serum creatinine should be monitored weekly during the treatment. If no response in 2 weeks, assess for ganciclovir resistance and shift to Foscarnet and additional CMV immunoglobulin or intravenous immunoglobulin (IVIG) (6). Secondary prophylaxis with oral valganciclovir post-treatment can be given for 1-2 months in patients with high-risk of relapse.
d) If influenza: Antiviral against influenza (Oseltamivir) when the results for respiratory virus panel is available.
e) If malignancy: Will require tissue biopsy and further management as per the histological diagnosis.
References:
Dulek DE, Mueller NJ; AST Infectious Diseases Community of Practice. Pneumonia in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13545. doi: 10.1111/ctr.13545. Epub 2019 Apr 23. PMID: 30900275; PMCID: PMC7162188.
Elhadedy MA, Marie Y, Halawa A. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence. Nephron. 2021;145(2):192-198. doi: 10.1159/000512329. Epub 2020 Dec 8. PMID: 33291120; PMCID: PMC7801980.
Fishman JA, Gans H; AST Infectious Diseases Community of Practice. Pneumocystis jiroveci in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13587. doi: 10.1111/ctr.13587. Epub 2019 Jul 1. PMID: 31077616.
Kang EY, Patz EF Jr, Müller NL. Cytomegalovirus pneumonia in transplant patients: CT findings. J Comput Assist Tomogr. 1996 Mar-Apr;20(2):295-9. doi: 10.1097/00004728-199603000-00024. PMID: 8606241.
Bhimraj A, Morgan RL, Shumaker AH, Baden L, Cheng VCC, Edwards KM, Gallagher JC, Gandhi RT, Muller WJ, Nakamura MM, O’Horo JC, Shafer RW, Shoham S, Murad MH, Mustafa RA, Sultan S, Falck-Ytter Y. Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19. Clin Infect Dis. 2022 Sep 5:ciac724. doi: 10.1093/cid/ciac724. Epub ahead of print. PMID: 36063397; PMCID: PMC9494372.
Razonable RR, Humar A. Cytomegalovirus in solid organ transplant recipients-Guidelines of the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13512. doi: 10.1111/ctr.13512. Epub 2019 Mar 28. PMID: 30817026.
That is a fantastic reply that includes investigating for COVID19 and other viruses as the first step, and then looking for DD. I appreciate your very well-referenced clinical approach that includes commencing anti-virals and stopping MMF for few days.
– The current case underwent renal transplant 2016 and diagnosed with colonic adenocarcinoma 2019 and in 2020 had lower lobar pneumonia in chest xray
The patient is hypertensive with basal creatinine level240–260 μmol/L on maintenance triple therapy presented with dry cough
Differential diagnosis
Infection >6 months post transplant
· Community acquired pneumonia Streptoccocus pneumonia, Haemphilus influenzae, Moraxella cattarhalis, Staphylococcus aureus
· Viral as Late CMV infection ,Herpes simplex (HSV),Varicella zoster virus (VZV),Epstein Barr virus (EBV),RSV, Influenza and parainfluenza viruses,Human metapneumovirus, Rhinovirus and Adinovirus as well as Community acquired SARS , COVID 19 pneumonia
· Mycobacterium TB ,Mycobacterium avium
· Atypical: Mycoplasma pneumoniae, Ureaplasma urealyticum, Chlamydia trachomatis, Legionella spp
· Aspergillosis ,atypical molds ,mucor species
· Underlying metastasis or malignancy recurrence have to be evaluated
· Pulmonary PTLD can resemble pneumonia findings in Chest Xray Management
Preliminary the diagnosis depend on local epidemiology, available tests, and practice parameters,patient‐specific risk factors, exposures, and medical history.
No studies of pneumonia severity scoring systems have been applied in SOT recipients inspite that the PSI and CURB‐65 scores had poor performance in cancer patients presenting with pneumonia. -Initial evaluation
involves history taking particularly for recent illnesses ,social exposure , vaccination history , immunosuppression degree ,comorbidities ,rejection episodes .
Thorough clinical examination
The need for isolation have to be considered particularly in such case -Investigations include initially complete blood count with differential, electrolyte chemistries, renal function tests ,urine analysis and liver function testing.
Blood and induced sputum culture since he has dry cough before empirical antibiotic therapy
Specific tests can be performed as CMV PCR, urine antigen testing for legionella , Quantiferon for TB, nasopharyngeal testing for influenza virus by PCR, Multiplex molecular respiratory virus testing,COVID19 nasal swab.
HR CT chest
IF patient deteriorated and did not respond to empirical therapy more invasive investigations can be done as bronchoscopy with bronchoalveolar lavage (BAL), transbronchial biopsy, CT‐guided biopsy, video‐assisted thoracotomy (VATS) with lung biopsy, and open lung biopsy particularly for diagnosis of fungal infection or underlying malignancy . Empirical therapy
Choice depend on patient’s history of antimicrobial drug resistance , drug interactions , influenza season antininfluenza therpy has to be added,
Empirical therapy for community‐acquired pneumonia have to follow national/international guidelines .
Beta‐lactams or fluoroquinolones can be considered paying attention to drug interactions, adverse reactions, and antimicrobial resistance.
Empirical coverage of intracellular pathogens as Mycoplasma pneumoniae, Chlamydia pneumonia, and Legionella is mandatory.
Adding antibiotic against methicillin‐resistant Staphylococcus aureus (MRSA) or Pseudomonas is according to local resistance patterns, prevalence, the patient’s infection, and bacterial colonization history.
If hospitalization for pneumonia is required then a combination therapy with a beta‐lactam agent (±MRSA and ±antipseudomonal activity) and an agent active against intracellular organisms will be needed.
Empirical therapy have to be monitored to assess the patient response as well as investigations results and act according to progression or resolution of the case.
Also reduction of immunosuppression can be needed with monitoring of graft function
Reference
-Jani A A. Infections After Solid Organ Transplantation.Medscape 2022
-Dulek DE, Mueller NJ; AST Infectious Diseases Community of Practice. Pneumonia in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13545. doi:10.1111/ctr.13545
Your reply does address all the concerns and DD. I appreciate your approach that would enable you to diagnose a specific underlying viral infection that may have an effective antiviral treatment. When mentioning modification of immunosuppression, I would consider stopping MMF for few days.
-Infection:
– Viral illness:
– Respiratory viruses (infuenza , PIV, RSV, HMNV, adenovirus and COVID-19)
– CMV, EBV, HSV, VZV
– Bacterial infection: TB, bacterial pneumonia.
– Fungal infection: candida, aspergillus.
– Protozoal : PCP.
– Malignancy;1ry or 2ry; he had history of colon cancer , metastasis should be considered.
– Elderly patient with HTN, should rule out cardiac causes CCF.
– COPD, BA.
– Smoking.
– GERD.
Management:
– Detailed history about: exposure history: COVID, TB and travelling, Smoking history
Work up:
– CBC; VBG
– Inflammatory markers; CRP, ESR, ferritin
– Respiratory multiples; test wide range of respiratory viruses.
– COVID-19 Rapid antigen test, fast result with hour and COVID-19 PCR.
– BAL or induced sputum for; stain ,culture, PCP,T B.
– IGRA and Mantoux test.
– LFT, KFT, LDH
– Viral load PCR: CMV, EBV, BKv and other if history was suggestive.
– Beta-D glucan
– Tacrolimus level.
– Chest CT if malignancy.
The management will be guided by the result of the tests. If confirmed to be COVID-19:
– The clinical manifestations of SARS-CoV-2 infection in SOTR are highly variable.
– Isolation precautions.
– In mild infection: supportive management; ensure good hydration.
– Management of immunosuppressive is challenge need to balance with rejection risk.
– Hold antimetabolite, especially in lymphopenic patients.
– CNI inhibit IL-1 and IL-6 which contribute to the severity of covid infection.
– If infection is sever and progressive we can reduce CNI through level or complete stopping while increasing steroids does.
– Monitor graft function closely.
– Dexamethasone if patient require respiratory support, reduce mortality.
– All antiviral therapy are investigational.
– Consider drug-drud interaction if any new treatment used.
– Remdesivir; the first drug approved by the FDA for COVID-19 treatment,
On 21 January 2022, its use was expanded to include COVID-19 treatment in non-hospitalized patients with positive results of direct viral testing who are at high risk for progression to severe COVID-19 RCT showed 87% reduction in risk of hospitalization or death among high-risk, non-hospitalized patients who received a 3-day course of remdesivir compared to those who received the placebo.
References
Elhadedy MA, Marie Y, Halawa A. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence. Nephron. 2021;145(2):192-198. doi: 10.1159/000512329. Epub 2020 Dec 8. PMID: 33291120; PMCID: PMC7801980.
Bitterman R, Kumar D. Respiratory Viruses in Solid Organ Transplant Recipients. Viruses. 2021 Oct 25;13(11):2146. doi: 10.3390/v13112146. PMID: 34834953; PMCID: PMC8622983.
RECOVERY Collaborative Group; Horby P, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17. PMID: 32678530; PMCID: PMC7383595.
Brady, D.K., Gurijala, A.R., Huang, L., Hussain, A.A., Lingan, A.L., Pembridge, O.G., Ratangee, B.A., Sealy, T.T., Vallone, K.T. and Clements, T.P. (2022), A guide to COVID-19 antiviral therapeutics: a summary and perspective of the antiviral weapons against SARS-CoV-2 infection. FEBS J. https://doi.org/10.1111/febs.16662
I agree that investigating for COVID19 and other viruses as the first step. I appreciate your well-referenced clinical approach that includes commencing anti-virals and stopping MMF for few days.
elderly 71 years post-transplant 4 years now, multiple comorbid including hypertension with a previous history of malignancy( ca colon ), chronic allograft dysfunction with creatinine > 240 indicate chronic allograft dysfunction or AKI on top of CKD on triple immunosuppression presented with dry cough and chest xr shows infra hilar infiltration
this patient needs admission and further work in an isolation room, DDX wide & should include viral pneumonia including covid 19, other atypical viral infections like CMV,adeno, influenza and parainfluenza virus, CAP like mycoplasma, legionella, staph, and other bacterial pneumonia, also PJP especially if there is a dry cough with sob and hypoxemia, fungal infection, TB and finally secondary mets from the primary tumor.
The patient should be tested for covid with nasal and throat swab SARs rapid PCR test, RSV screen, mycoplasma, and legionella, induced sputum for TB staining and genexeprt
CT chest is needed to assess further the extension as he is at high risk for ARDS if confirmed covid with his multiple risk factors and comorbid, CRP, blood culture, ferritin, and LDH, and assess the need for O2 therapy and steroid, MMF will be stopped and if confirmed covid pneumonia with high inflammatory markers this patient need to be treated as in patients in an isolation room with good hydration, and dexamethasone and continue on CNI Based IS plus steroid and hold MMF till he recovers. he is at risk of complications including ARDS and AKI on top of chronic allograft dysfunction and underlying multiple comorbid
References 1.Elhadedy MA, Marie Y, Halawa A. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence. Nephron. 2021;145(2):192-198.
I agree that investigating for COVID19 as the first step.
I appreciate your clinical approach that includes and stopping MMF for few days. I wish you could discuss commencing a very specific anti-virals depending upon the results of urgent testing.
Please use bold or underline to highlight headings and sub-headings.
In the current index case of old renal transplant recipient with chronic allograft dysfunction on triple immunosuppression (CNI based protocol) with recent history of colon adenocarcinoma (?managed surgically or conservative management) presented with only dry cough without other respiratory symptoms.
Most probably it is metastatic malignancy from colon cancer
Other probabilities are PCP pneumonia which presented with dry cough with few symptoms but patient is clinically doing well.
-COVID 19 infection is a strong possibility initially presented with dry cough.
-Other respiratory viral infections.
Management:
-CT chest without IV contrast to establish diagnosis behind the chest x ray findings.
-Inflammatory markers
-COVID nasal swab or PCR
-Respiratory viral panel
-Investigations to rule out PCP and other sources of chest infections
-Investigations to rule out colon cancer recurrence.
Since the patient is clinically doing well management will be based on the patient condition overall:
-Regarding immunosuppression :If there is prove of infections with high inflammatory markers and signs of SIRS to hold antimetabolites initially.
-In case of COVID positive :Isolation, assure of good hydration if clinically permissible, anti viral medications plus steroids.
Your reply is too limited. It does not address all the concerns. I agree that investigating for COVID19 as the first step. I appreciate your clinical approach that includes commencing anti-virals and stopping MMF for few days.
Please use headings and sub-headings to make easier to read your write-up. Please use bold or underline to highlight headings and sub-headings.
He had dry cough, high baseline creatinine, and infra-hilar consolidation on chest x-ray from prior kidney transplant with cancer.
Respiratory infection including viral, bacterial, fungal ( most probably
COVID-19 pneumonia)
Mets of primary malignancy
Management
Admitted to the COVID-19 isolation ward, excellent fluid.
Dexamethasone should be taken by those receiving respiratory support.
CT. Chest And BAL to r/o others causes
Antiviral as nirmatrelvir-ritinovir, remdesivir. But keep monitoring the level of CNI,s
Supportive care includes;
Hydration
Oxygen therapy if satuatrtion is droping
Anti metabolite dosage should be reduced or stoped while monitoring the graft function
Your reply is too limited. It does not address all the concerns. I agree that investigating for COVID19 as the first step. I appreciate your clinical approach that includes that includes commencing anti-virals and stopping MMF for few days.
. A 71-year-old male with hypertensive nephropathy received a kidney graft in February 2016. He had a history of colon adenocarcinoma in June 2019. His baseline Cr was 240–260 μmol/L. His immunosuppressive regimen included prednisolone 5 mg OD, tacrolimus (trough level was 6.4 ng/mL), and MMF 250 mg BD. He was also on calcium channel blockers and proton pump inhibitors. He presented in April 2020 with a dry cough with no other symptoms but stable vital signs. However, a chest X-ray revealed an infra-hilar consolidation on the right side.
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In April 2020 presented with complane of dry cough .
Chest Xray :infrahailr consolidation on the the right side.
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The patient is at a high risk of any infection .
Compared to the general Chinese population, COVID-19 patients exhibited a higher rate of malignancy, with lung cancer being the most common tumor.
The most common site of metastases for colorectal cancer, which includes colon cancer or rectal cancer is the liver.
Colorectal cancer cells may also spread to the lungs, bones, brain or spinal cord.
Other viral or bacterial respiratory infections(Adenovirus and Mycoplasma should be considered in clusters of pneumonia patients, especially in closed settings such as military camps and schools.).
Aspiration pneumonia
Pneumocystis jirovecii pneumonia
Middle East respiratory syndrome (MERS)
Avian influenza A (H7N9) virus infection
Avian influenza A (H5N1) virus infection
Pulmonary tuberculosis
Febrile neutropenia
Other
COVID-19 should be considered a differential diagnosis for many conditions.
The differential is very broad and includes many common respiratory, infectious, cardiovascular, oncological, and gastrointestinal diseases
==================================================================== I will do and ask
Take a detailed history to assess risk of COVID-19.
Suspect the diagnosis of COVID-19 in people who have had contact with a probable or confirmed case, such as face-to-face contact, direct physical contact, direct care, and other situations as determined by local health authorities including a travel history .
Physical exam
Auscultation of the chest may reveal inspiratory crackles, rales, and/or bronchial breathing in patients with pneumonia or respiratory distress.
• Inflammatory markers (e.g., serum C-reactive protein, erythrocyte sedimentation rate, interleukins, lactate dehydrogenase, procalcitonin, amyloid A, and ferritin)
• Cardiac biomarkers
• Serum creatine kinase and myoglobin.
Swap of the nasal and pharynx for COVID-19 PCR.
Molecular tests are expensive and require specialized skills and instruments, while rapid antigen tests are faster, easier, and cheaper.
Serologic tests may be used to establish a late or retrospective diagnosis or inform public policy.
The WHO recommends chest imaging (chest x-ray, chest CT, or lung ultrasound) in the following scenarios:
Symptomatic patients with suspected COVID-19 when RT-PCR is not available, RT-PCR test results are delayed, or initial RT-PCR testing is negative but there is a high clinical suspicion for COVID-19 (for diagnosis)
•Patients with suspected or confirmed COVID-19 who are not currently hospitalized and have mild symptoms (to decide on hospital admission versus home discharge).
•Patients with suspected or confirmed COVID-19 who are not currently hospitalized and have moderate to severe symptoms (to help decide on regular ward admission versus intensive care unit admission).
•Patients with suspected or confirmed COVID-19 who are currently hospitalized and have moderate to severe symptoms (to inform therapeutic management).
Marbun, Maruhum Bonar H et al. “Management of COVID-19 in Kidney Transplant Recipients: A Single-Center Case Series.” International journal of nephrology vol. 2022 9636624. 18 Aug. 2022, doi:10.1155/2022/9636624
Guarnera A, Podda P, Santini E, Paolantonio P, Laghi A. Differential diagnoses of COVID-19 pneumonia: the current challenge for the radiologist-a pictorial essay. Insights Imaging. 2021;12(1):34. Published 2021 Mar 11. doi:10.1186/s13244-021-00967-x
Abolghasemi S, Mardani M, Sali S, Honarvar N, Baziboroun M. COVID-19 and kidney transplant recipients. Transpl Infect Dis. 2020;22(6):e13413. doi:10.1111/tid.13413
Yes, as you suggest, I would have looked for COVID19 as the first step. I like your comprehensive reply. I agree that you would consider stopping MMF for few days. However, I do NOT agree with your suggestion: hydroxychloroquine/chloroquine, azithromycin.
Please read my comment in the thread of second article of journal club in week 9 ridiculing a number of unproven treatments that have been suggested, when I wrote a short story of a dog believing its barking would trigger train to leave the station!
Typing whole sentence in bold or typing in capitals amounts to shouting.
I would have looked for COVID19 as the first step. Your reply is too limited. It does not address all the concerns. How would you diagnose a specific underlying viral infection that may have an effective antiviral treatment? I would consider stopping MMF for few days.
Your reply is too limited. It does not address all the concerns. I would have looked for COVID19 as the first step. How would you diagnose a specific underlying viral infection that may have an effective antiviral treatment? I appreciate your clinical approach that includes stopping MMF for few days.
The differential diagnosis for the patient’s dry cough with a chest X-ray showing an infra-hilar consolidation on the right side include
1 -pneumonia,
2-bronchiectasis
3- lung cancer.
Depending on the diagnosis, the management plan will vary. Some possible management plans include antibiotics and/or changes to immunosuppressive medications, imaging tests to evaluate for pulmonary embolism or lung cancer, or a biopsy to test for the presence of cancer. The patient should be closely monitored via regular monitoring of his vital signs and imaging tests, as well as regular laboratory tests to monitor his kidney graft function.
Your reply is too limited. It does not address all the concerns. How would you diagnose a specific underlying viral infection that may have an effective antiviral treatment? I appreciate your clinical approach that includes reviewing immunosuppresion, that should include stopping MMF for few days (not mentioned by you).
This is a 71 yr old male kidney transplant 4 years ago and a h/o colon adenocarcinoma 10 months ago on triple immunosuppression who has presented with a cough and a consolidation is picked up on CXR
The differential diagnosis include:
PCP – His vital signs are stable so it would be unlikely unless if its early PCP
Metastasis from the colon adenocarcinoma
Management:
He will require further evaluation:
Complete blood count – to assess for leucopenia or leucocytosis
ESR
C reactive protein
Lactate dehydrogenase: Will be elevated in TB and PCP
COVID 19 RT PCR
CMV PCR
Adenovirus PCR
Influenza virus PCR
Parainfluenza virus PCR
1,3 Beta D glucan – a negative test will reduce the likelihood of PCP and fungal pneumonia
HRCT – will help to assess for thoracic lymphadenopathy, if there are any other lesions, any ground glass opacities
May require BAL – to send for MCS, gen xpert for TB, silver methenamine stain, PCP PCR
CEA levels – to rule out recurrence and
The definitive treatment would depend on the diagnosis.
If it is a viral infection: Reduction of immunosuppression and reducing or stopping the antimetabolite.
For the influenza, paramyxo and adenoviruses, treatment is mainly supportive
For COVID 19, the treatment is supportive as the patient has stable vital signs
For CMV, he will require IV ganciclovir then oral valganciclovir
He may also require a lung biopsy if there is a mass detected on the HRCT
MMF should be discontinued with close monitoring of renal function.
Supportive care.
According severity of infection, the patient may need low dose dexamethasone (moderate-severe disease,O2 desaturation).
Antiviral as nirmatrelvir-ritinovir, remdesivir.
References:
Elhadedy M., Marie Y. and Halawa A. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence. Nephron, 2021;145:192-198.
Nair V., Jandovitz N., Hirsch J., Nair G., Abate M., et al. COVID-10 in kidney ransplant recipients. Am J Transplant,2020;20(7):1819-1825.
Thank you
Why you want to admit the patient whilst his vital signs are stable and did not require oxygen.
What do you think the role of antivirals in this case?
A.Differential diagnosis
-This guy unfortunately had Ca colon & now presented with cough 4 years post transplant
-He can be categorized under the differential diagnosis of infections > 6 months posttransplant. However, this presented occurs at the time of COVID-19 pandemic and therefore, the first differential is COVID-19 pneumonia. Other differential are:
Community acquired pneumonia
CMV pneumonia
Pulmonary aspergilosis
Pulmonary TB
PCP
Metastatic adenocarcinoma of the colon
B.How do you manage this case
Admit to isolation ward
Ask for COVID-19 swab
Organized HRCT
Ask for WCC & differenetial, inflammatory marker e.g serum ferritin, and UECs
Differential Diagnosis;
-COVID-19 infection (Most likely),
-Respiratory Virus Infections (influenza virus, respiratory syncytial virus (RSV), human metapneumovirus (HMPV), parainfluenza virus (PIV), rhinovirus, coronavirus (CoV), adenovirus, bocavirus and KI and WU polyomaviruses,
-CMV infection,
-Herpesvirus infection (EBV,HSV and VZV),
-TB infection,
-PJP infection,
-Lung cancer (primary or secondary to Colon adenocarcinoma),
-Less likely PTLD. How would you manage this case? Approach to patient with no oxygen requirement;
-If he has clinical or laboratory risk factors for severe disease and was hospitalized for COVID-19 ; Remdesivir is suggested.
-For patient without any risk factors, care is primarily supportive. All patients warrant close monitoring for disease progression. Approach to patient with oxygen requirement/severe disease; –For patients who require oxygen supplementation because of COVID-19, the approach to COVID-19-specific therapy depends on the level of support;
-If patient receiving low-flow supplemental oxygen, low-dose dexamethasone and remdesivir are suggested.
-It is reasonable to defer dexamethasone for those who are stable on minimal oxygen supplementation (eg, 1 to 2 L/min), particularly if they are immunocompromised and within 10 days of symptom onset.
-For patients who have escalating oxygen requirements despite dexamethasone, have elevated inflammatory markers, and are within 96 hours of hospitalization, adding either tocilizumab or baricitinib are suggested, and prioritize them for more severely ill patients on higher levels of oxygen support.
-For patients receiving high-flow supplemental oxygen or non-invasive ventilation, low-dose dexamethasone is recommended.
-If they are within 24 to 48 hours of admission to an intensive care unit (ICU) or receipt of ICU-level care (and within 96 hours of hospitalization), either baricitinib or tocilizumab in addition to dexamethasone are suggested. and also adding remdesivir is suggested.
-For patients who require mechanical ventilation or extracorporeal membrane oxygenation, low-dose dexamethasone is recommended .
-For those who are within 24 to 48 hours of admission to an ICU (and within 96 hours of hospitalization), adding baricitinib or tocilizumab to dexamethasone are suggested.
-If dexamethasone is not available, other glucocorticoids at equivalent doses are reasonable alternatives.
Limited role for other therapies;
-Generally not using other agents off label for treatment of COVID-19.
-In particular, not using ivermectin, not routinely using convalescent plasma for COVID-19 therapy in hospitalized patients.
Management of hypoxemia;
Patients with severe disease often need respiratory support.
Infection control;
Infection control is an essential component of management of patients with suspected or documented COVID-19.
Supportive treatment and good hydration.
Stop Mycophenolate mofetil and continue CNI and stress dose of steroid (or shifting to IV hydrocortisone , dexamethasone)
-Adjustment of tacrolimustrough level as 4–6 ng/dL.
COVID-19 treatment; (with Pulmonology & ID review);
-In current case remdesivir is not recommended because an estimated glomerular filtration rate (eGFR) <30 mL/min per 1.73 m2 unless the potential benefit outweighs the potential risk.
-Discharged from the hospital on anticoagulation as this patient with H/o of malignancy is high risk for VTE. References;
-UK Government press release. World first coronavirus treatment approved for NHS use by government (Accessed on June 16, 2020).
-Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19 (Accessed on February 21, 2021).
What is the differential diagnosis?This transplant recipient patient presented with dry cough 4 years after transplantation (2020), with high baseline creatinine and infra-hilar consolidation on chest x-ray
In the era of COVID-19, in a patient with dry cough, COVID-19 is a high possibility especially with this high risk patient. Cough (44-65.7%) is the second most presenting symptom after fever (82–87%) according to two large studies
This transplant patient is at a high risk of infection due to:
1. Immunosuppression
2. Underlying CKD
3. Hypertension
4. Post-transplant malignancy (adenocarcinoma of the colon): 1% of COVID-19 patients had a history of malignancy
Other differential diagnoses of post transplant cough include:
1. Other upper respiratort tract infections
2. Viral pneumonia (CMV, EBV, VZV, and HSV)
3. Bacterial infection including TB
4. Fungal infection (PJP)
5. Malignancy
6. GERD
7. Bronchial asthma/COPD/smoking
How would you manage this case?v Detailed history and comprehensive clinical examination
v O2 saturation/ABG
v CBC, RFT & electrolytes, ESR, CRP, LFT, RBS, urine analysis, urine and blood C/S
v CMV serology/PCR
v Screen for TB (Mantoux, IGRA, and sputum culture)
v Screen for PJP (induced sputum or bronchoscopy for BAL)
v Nasal and throat swab for COVID-19/PCR, s.ferritin, IL-6, lymphopenia
v CT chest to exclude malignancy
Management of COVID-19:
o Admission
o Supportive medical therapy (IV fluids and paracetamol)
o Discontinued MMF with close monitoring the patient (immunosuppression treatment should be individualized based on the careful assessment of each patient)
o Remdesivir: the Adaptive COVID-19 Treatment Trial proved that remdesivir-treated patients had 31% faster time to recovery when compared to control
o Case series and a small RCT suggested better outcomes with interferon and high-dose steroids in conjunction with supportive care
o Dexamethasone in those receiving respiratory support (invasive mechanical ventilation or oxygen alone): resulted in lower 28-day mortality
References
1. Elhadedy MA, Marie Y, Halawa A. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence. Nephron. 2021;145(2):192-198. doi: 10.1159/000512329. Epub 2020 Dec 8. PMID: 33291120; PMCID: PMC7801980.
2. Bitterman R, Kumar D. Respiratory Viruses in Solid Organ Transplant Recipients. Viruses. 2021 Oct 25;13(11):2146. doi: 10.3390/v13112146. PMID: 34834953; PMCID: PMC8622983.
3. RECOVERY Collaborative Group; Horby P, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17. PMID: 32678530; PMCID: PMC7383595.
Management:
Oxygen saturation
CBC to role out infection/ LFT / RFT ESR CRP serology for HIV , COVID-19, CMV, EBV,
ABG
High resolution CT chest
BAL and bronchoscopy
PFT
good hydration and increase dose of steroid
drug level and DSA level
Antibiotic and antiviral
CA lung based on past history of adenocarcinoma of the colon
Pulmonary TB
Based on the timing of the occurrence, background disease, and clinical symptom; COVID-19 pneumonia is the most likely diagnosis
Further investigations
COVID-19 nasal and oropharyngeal swap for RT PCR
FBC + differentials
CRP, Ferritin, D- dimers, and procalcitonin
LFT
Urinalysis
CMV DNA PCR
IGRA, TB culture
Beta-D Glucan, LDH, sputum for PJP PCR
Treatment
If the oxygen saturation is also stable (>93%) like the vital signs were, we manage as an outpatient
Ask the patient to self-isolate at home
Discontinue the use of MMF
Continue CNIs but maintain trough level at 4-6ng/ml
Continue the dose of the prednisolone
Close kidney function test
Close tacrolimus trough level monitoring
Self-home oxygen saturation and temperature changes
Presentation to the hospital if clinical signs like fever, cough, and SOB is getting worse
Vaccination can be advised after recovery from acute illness, 2 to 3 doses will be encouraged
References
Muhammed Ahmed Elhadedya, b Yazin Mariea Ahmed Halawa. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence. Nephron. 2021; 145: 192-198
Patient who had kidney transplant with adenocarcinoma in past presented with dry cough in April 2020 Differential diagnosis would be;
COVID-19
PCP infection
CMV infection
TB
Herpes virus infection
Respiratory virial infection like Influenzas para influenzas etc
Ca lung
Management
Confirm diagnosis with
COVID RT PCR
Complete blood count with differentials
HRCT chest
LDH, Ferritin, CRP and procalcitonin
FDPs D- Dimers
IGRA,TST
CMV PCR
RFTS
Management
Isolation and hygiene promotion
vital monitoring like O2 sat RR and labs work if suggestive of sever disease then would have need hospitalization other wise outdoor patient care( in endemic era healthcare facilities overburden should be considered).
Stopped MMF continue CNI and Steroids along with good hydration and supportive care.
May need COVID specific treatment (There were limited option available that time and durg-drug interaction were not known) .
Paxlovid(nirmatrelvir/ritonavir) can be considered in outpatients with using drug interaction tools.
The patient who has respiratory illness after transplantation and whose condition is progressing with perihilar infiltration might consider the following:
the character of the consolidated area? may give the suspicion of cancer (adenocarcinoma with Mets).
Send in the PCR for CMV and EBV
The respiratory panel, Send COVID-19-PCR, IGRA, TB culture, and CT scan of the chest are all necessary to rule out cancer.
According to the diagnosis, the plan for treatment.
General roles:
In all cases, the decision to reduce immunosuppression must be carefully weighed against the risk of acute rejection, particularly in transplant recipients who generally require high levels of maintenance immunosuppression.
We lower or hold the antimetabolite (e.g., mycophenolate mofetil/sodium) initially, especially for patients with lymphopenia (absolute lymphocyte count <700 cells/mL).
We maintain the calcineurin inhibitor (CNI) because it inhibits interleukin (IL) 6 and IL-1 pathways, which may lead to severe, dysregulated immune responses in certain severe COVID-19 patients.
close monitoring of vital signs
keep saturation > 94%
Fishman, Jay A. “Infection in solid-organ transplant recipients.” New England Journal of Medicine 357.25 (2007): 2601-2614.
Post kidney transplant recipient with Dry cough during COVID19 pandemic era.
D.D:
1-COVID 19 infection(Most people who get sick with COVID-19 have dry coughs ).
2- Respiratory Virus Infections with other viral infection such as influenza, etc.
3-TB .
4-PJP infection.
5-CMV infection.
6-Herpesvirus infection(EBV,HSV and VZV).
7-COPD,B.A.
8-Lung cancer (primary or secondary).
9-Others such as PTLD, GERD. How would you manage this case?
1-Send COVID-19 RT-PCR. (if came positive )
Send Laboratory investigations included :
=A complete blood count and serum C-reactive protein, interleukin-6, markers of myocardial damage (creatine kinase, troponin I, lactate dehydrogenase).
=Tests of secondary hemostasis profile (prothrombin time, activated partial thromboplastin time), =Serum biochemical tests (including renal and liver function, and electrolytes).
=Procalcitonin, fibrinogen, d-dimer.
2-Send CMV, and EBV PCR. 3-Respiratory panel . 4-IGRA, Manteaux, and TB culture. 5-CT chest to exclude cancer or COPD changes . =Isolation if COVID 19 came positive and planning for vaccination later on. =We should classify our patient according to his clinical manifestation:
1-Asymptomatic patients and patients with mild disease (oxygen saturation above 93%, no lung involvement on chest computed tomography) were followed up in the outpatient clinic weekly.
2-Patients with moderate disease (oxygen saturation above 90%, respiratory rate under 30 breaths/min) were hospitalized in the first wave of the pandemic and followed up in the outpatient clinic in the later period because of hospital overcrowding.
3-If sever case should be admitted in IUC. =Supportive treatment and good hydration.
=Stop Mycophenolate mofetil and continue CNI and shift steroid to IV, if worsening and our patient being in sever condition , will stop CNI and increase the steroid dose.
=Trough levels were adjusted as 4–6 ng/dL for tacrolimus
=COVID 19 treatment by chest physician using medications such as (hydroxychloroquine, azithromycin Tocilizumab and others) should bear in mind drug-drug interaction.
=Anti-tuberculous medications if TB test came positive. References:
1-2-Demir, E., Ucar, Z.A., Dheir, H. et al. COVID-19 in Kidney Transplant Recipients: A Multicenter Experience from the First Two Waves of Pandemic. BMC Nephrol 23, 183 (2022). https://doi.org/10.1186/s12882-022-02784-w.
2-Study of Scientific Board Republic of Turkey, Ministry of Health. COVID-19 (SARS-CoV-2 INFECTION) GUIDE. April 14th, 2020, Ankara, Turkey.
A patient with a late respiratory condition after transplantation in April 2020 evolving with perihilar infiltrate should consider:
– Viral infection (including COVID-19 and Influenza)
– Bacterial pneumonia
– Mycobacteria
– sarcoidosis
– Pneumoconiosis
– alveolar carcinoma
– bronchiolitis obliterans
– fungal infections
– Actinomycete
– Nocardiosis
– PTLD
– Cytomegalovirus
It is important to perform a viral panel, decrease immunosuppression (consider changing immunosuppression to mTOR in some cases), blood count (consider neutropenia, lymphopenia, drug-induced), hypogammaglobulinemia and other alterations.
Proceed with chest tomography for a better assessment of pulmonary involvement and Arterial blood gases.
If there is no initial diagnosis, proceed with bronchoscopy and bronchoalveolar lavage (well-equipped team for aerosols) for molecular tests (galactomannan, RT-PCR, GeneXpert) and cultures.
In the context of the COVID-19 pandemic and the risk of cyclical pulmonary viral diseases of the period, bacterial pneumonia as a complication of viral pneumonitis should be considered.
Other possibilities like gastroesophageal reflux disease and allergic asthma may be considered.
Tomography can assess complications associated with the condition.
It is a viral lung disease that may be complicated with bacterial infection, and pulmonary aspergillosis and we cannot forget the possibility of pneumocystosis (interstitial disease) given the time of transplantation and the evolution of the lung disease.
DD:
1- acute rejection with infection
2- viral infection like community-acquired respiratory viruses (influenza, respiratory syncytial virus, severe acute respiratory syndrome coronavirus 2), or Legionella spp, CMV.
3- bacterial infection
4-fungal infection aspergillus, PCP
management
1- hospitalization
2-good hydration
3-nasopharyngeal swab for influnza virus and COVID 19
4- CMV PCR
5-induced sputum for PCP
6- CT chest
7-stop MMF
8-continue CNI and steroid and manage according to the clinical course
9-monitor graft function, CBC for lymphopenia
Jay A Fishman. Infection in the solid organ transplant recipient. uptodate. 2022 N. Sarabu, C. Michael, D. E. Hricik, J. J. Augustine. Fever of Unknown Origin in a Kidney Transplant Recipient. American Journal of Transplantation.2015; 15: 2006–2008
Lung consolidation with dry cough in post TX kidney patients had many differential diagnosis starting by viral pneumonia like CMV,Atypical pneumonia,fungal pneumonia,pulmonary TB and Carcinoma of the lung one of the most important differential butting in mind the Hx of the CA colon
so we need to screen for viral,fungal and bacterial causes plus broncoscopy with tissue biopsy
Bacterial ,viral or fungal pneumonia and can be PTLD
With the given scenerion i have following differentials:
1. Community acquired pneumonia
2. Covid-19 pnrumonia
3. CMV pneumonia
4. Pulmonary aspergillosis
5. Pulmonar TB
6. PJP
7. Metastatic adenocarcinoma of colon
8. PTLD
Management
A. Hospitalization & isolation
B. Detail history
C. Physical examination
D. Monitoting vitals: HR, RR, BP, SpO2, urine output
E. Investigation:
– CBC, CRP
– RFT, LFT
– Nasopharyngeal swab for Covid-19 RT PCR
– CMV PCR
– Blood & urine C/S
– Sputum for gram staining, C/S, gene X-pert and malignant cell
– BAL for microscopy & PCR
– IL-6 in case of covid -19 pneumonia
– CEA, CA19-9
– HRCT of chest, CT/MRI of abdomen
– Broncoscopy with biopsy
F. Treatment
– Supportive i.e respiratory support as required, adequate hydration, renal support (CVVH)
– Modification of immunosuppression ( Stop MMF, tacrolimus trough level 4-6 ng/dl, increase dose of prednisolone)
– In case of covid -19 pneumonia dexamethasone, remdicivir.
What are differentials?
We divide the transplant related infection according to the most common and less common with duration of transplantation.
1. In first six months the most common infections are and differentials will be,
A. Bacterial infections,
B. Viral infections, like CMV, BKVAP, COVID-19, dengue.
C. Fungal infection,
D. Malaria,
E. Tuberculosis.
2. After one year of transplantation the DDs would be,
EBV related PTLD,
Fungal infections,
Secondary metastatic disease,
But could BACTERIAL infection as the scan shows consolidation, need further confirmation.
How would you manage this case?
A detailed history,
Detailed examination,
Baseline investigation,
Radiological examination,
Viral serology,
CRP, procalcitonine,
May need BAL, may need biopsy of the lesion.
Sputum for GS, C/S, and AFB,
Gene Xpert.
Management;
Will proceed according to the final BAL, biopsy and culture report, till then will treat as bacterial pneumonia/ PCP.
DIFERENCIAL DIAGNÓSIS:
One year after transplantation – risk of opportunistic infections is less; community infection more likely.
Etiology depends on exposure to community infection
Common causes:
Covid-19, parainfluenza, respiratory syncytial, influenza
Community Acquired Pneumonia
M-TB and Community acquired pneumonia
Fungal infection – Aspergillus
Less likely causes:
– CMV pneumonia
– Fungal pneumonia: Aspergillosis, Cryptococcosis, PCP
– Cancer: Lung Mets from Colon Cancer; PTLD
MANAGMENT
Monitoring Respiratory rate and SPO2; keep under observation for respiratory distress and hypoxia
Lab tests –
– Covid-RTPCR, CMV-PCR, EBV serology
CBC, ESR, Montoux, IgRA
Sputum (induced) – Gram stain, Culture (Bacterial & Fungal); look for CMV, PCP
If scanty / no sputum – BAL – PCP, CMV
CECT Chest and Abdomen / PET-CT scan whole body
Treatment:
Due to Covid Pandemic wave in community home-isolation, steam inhalation, cough syrup, multivitamin, good hydration advised.
IS reduction: withhold or reduce MMF, minimize Tac to target C0 of 5-6, Prednisone to continue same or increase (if Covid).
Infra-hilar consolidation with Cough indicates towards possibility of Community Pneumonia (CAP) –
– Broad Spectrum IV antibiotics (Piperacillin-Tazobactam + respiratory macrolide or quinolone) should be started.
depending CT image features and clinical improvement –
– bronchoscopy with BAL or Biopsy – look for TB / CMV / PCP / Fungus
Further treatment as per the etiology
TB – ATT (preferably Rifa-sparing regimen) x 1yr
Fungal – Liposomal-Amphotericin à voriconazole, itraconazole
Colonic cancer Mets – Chemotherapy +/- RT
Difrential diagnosis
Infection like Covid 19, viral infection, tb, PJP,CMV
Non infectious, malignancy or metastatic
presence of a solitary pulmonary lesion on chest Xray in an immune compromised patient would be approached in a particular way.
essentially, its either infective or neoplastic.
CAT scan without contrast might delineate the extent of the lesion, presence of satellite lesion and give a clue on its nature, however, being without contrast would compromise its utility.
Induced sputum and BAL secretion exam: with gram stain and culture, immunofluorescent and PCR for PCP and TB and examination for malignant cells are the baseline investigation.
Blood tests :
QuantiFERON gold TB and PCR for EBV.
Blood film for abnormal white blood cells.
Second step in management:
1] Endobronchial ultrasound and transbronchial biopsy
Differential diagnosis is
1] EBV related lymphoma.
2] Tuberculoma.
3] Other malignancies
4] Fungal infection, such as aspegillosis.
Reference:
1]Nikita Leiter. June Kim. Lung Nodules in an Immunosuppressed Patient. PULMONARY MANIFESTATIONS OF SYSTEMIC DISEASE| VOLUME 152, ISSUE 4, SUPPLEMENT , A920, OCTOBER 2017
The differential diagnosis is:
1. Covid-19 infection
2. Other respiratory viral infections like influenza.
3. Tuberculosis
4. Pneumocystis Jirovani pneumonitis
5. CMV, EBV, HSV infection
6. CDPD or malignancy like PTLD
7. Metastasis of colon adenolar cinomal
To manage this case comprehensive lab tests are necessary.
(CBC.diff, PLT, ESR, CRP, LDH, PT, PTT, INR, LFT, RFT and biochemistry, procalcitonin, d-dimer, and fibrinogen, viral PCR for covid-19, CMV, influenza and other respiratory viruses.) PerformingIGRA PPD MMF or even reduction of CNIs if necessary with measurement of their levels. Close monitoring for O2 saturation and if below 93%, hospitalization is necessary. Paxlovid can be considered in the outpatient setting.
Differential diagnosis
Management
kidney transplant patient presented with dry cough , no other symptoms but stable vital signs.a chest X-ray revealed an infra-hilar consolidation on the right side. The differential diagnoses include:
-dry cough with infra hilar consolidation are non-specific symptoms
in time of COVID 19 pandemic it would be the most likely DD without any other clear sing or symptoms of other infection.
-Other upper respiratory tract common infection either Viral Infections as influenza , respiratory syncytial CMV, EBV,HSV), bacterial or fungal.
-PCP infection.
-Asthma Exacerbation
-malignancy with metastasis to lung
-Sinusitis, post nasal discharge.
-allergic cough
How would you manage this case?
-full history with history of recent contact to a case of covid 19, allergy, and full clinical examination.
-Measurement of Oxygen saturation.
-investigations:
CBC, CRP.LDH, FERRITIN, D dimer, procalcitonin.
High resolution CT scan.
Kidney function tests.
CNIs level.
Nasopharyngeal swab
induced sputum or BAL for PCP
CMV viral load.
ABG.
management according to the results of investigation
If COVID-19 was confirmed:
Supportive therapy.
good hydration
antipyretic in case of fever.
Oxygen supply if indicated
Discontinued MMF for few days with close graft monitoring.
in case of severe infection reduce CNI through level with increasing steroids does.
Anti viral Remdesivir; for COVID-19 treatment,
References
Bitterman R, Kumar D. Respiratory Viruses in Solid Organ Transplant Recipients. Viruses. 2021 Oct 25;13(11):2146. doi: 10.3390/v13112146. PMID: 34834953; PMCID: PMC8622983.
DIFERENCIAL DIAGNÓSTIC:
One year after transplantation, there is a significant decrease in the risk of opportunistic infections, making community infection more likely. Logically, etiologies that may have some connection with important environmental exposure should also be investigated.
But among the main causes I would point out:
– Viral infections by: parainfluenza, respiratory syncytial, influenza, COVID
– Bacterial: Community pneumonia and tuberculosis (high prevalence in Brazil)
– Cancer: metastasis from a recurrence of colon adenocarcinoma
I would point out as less likely causes:
– CMV pneumonia
– Fungal pneumonia: Aspergillosis, Cryptococcosis, PCP
– Cancer: PTLD
MANAGMENT
As a patient with only the possibility of Community Pneumonia (CAP), I would start coverage with third-generation cephalosporin + respiratory macrolide or quinolone. And meanwhile I would run more tests:
1 – Image:
– I would perform a CT scan of the chest in the expectation of better characterizing the consolidation and perhaps motivating the performance of bronchoscopy with BAL or even a biopsy;
2 – Blood:
Associated with serological tests or molecular markers and biomarkers in the blood:
– Galactomannan and B-Glucan
– CMV PCR, COVID19
– Blood culture and urine culture
– IGRA
– Serology for EBV
The patient is an elderly kidney transplant recipient who has Ca colon from post transplant ..He is on triple immunosuppression…with tacrolimus, MMF,steroids..He is on Calcium channel blockers for hypertension….He has chronic graft dysfunction with elevated creatinine….
He has presented with non productive cough and has stable vital signs..CXR shows right hilar consolidation…
the patient has a consolidation after 5 years of transplant…
The differential diagnosis for such a case scenario is Viral – RSV, COVID, Influenza, CMV; Fungal – PCP, histoplasma and CMV; Bacterial – Streptococci, pneumococci; Parasitic; like strongyloides or toxoplasma etc
But bacterial etiology is unlikely as there is no fever…
Patient also needs to be evaluated for lung metastasis as there is a history of carcinoma colon….
I would get a basic lab workup done and a CT chest and then decide on further management…
Differential diagnosis:
· Viral- Covid 19, CMV, influenza, adenovirus, parainfluenza
· Bacterial (Atypical)- Tuberculosis
· Deep fungal infection
· Malignancy: primary or secondary
Management:
· Detailed history and clinical examination.
· Multi-disciplinary approach is needed.
· Workups will includes: CBC, PCR for Covid 19, CMV, influenza, parainfluenza and adenovirus, CRP, procalcitonin levels, D dimer levels, UECS, blood slide for malaria, LDH, ESR.
· Supportive treatment: Anti-pyretics for fever, adequate hydration, oxygen if SPO2<92%.
· Reduction/ modification of IS: Stop MMF, Reduce CNI by 50% in severe disease., Oral steroids switched to IV dexamethasone in those requiring oxygen supplementation or mechanical ventilation.
· Specific treatment according to confirm diagnosis.
Differential diagnosis
1) Viral infection (COVID-19, Influenza, Para-influenza, CMV)
2) PCP
3) Other bacterial causes of Community-acquired pneumonia
4) Tuberculosis
Investigations
1) Inflammatory marker
2) BAL – sputum for culture, AFB and mycobacterium culture
3) COVID PCR, Swab for viral panel
4) CMV PCR
5) CT Thorax
6) Blood culture
Management
1) Monitor oksigen saturation
2) Vital sign monitoring- may need to withhold anti-HPT
3) Reduction of immunosuppression, may need to withhold MMF
4) Empirical antibiotic to cover for community-acquired pneumonia
5) Steroid in the setting of COVID-19
Differential diagnosis
Viral infection
– Covid-19
– PCP
– CMV
– Influenza and parainfluenza virus and others
Bacterial pneumonia including typical and atypical bacteria
Recurrence of Adenocarcinoma or metastatic carcinoma
PTLD
Workup includes laboratory and imaging studies
CBC
Procalcitonin
Renal function test
Liver function test
PCR COVID-19, EBV, CMV
Sputum analysis and culture
ABG
BAL for PCP, TB culture, PCR of viruses
CT chest to check for characteristic findings which could be suggestive of fungal/malignancy.
Treatment
Initial step is temporary isolation to prevent the transmission of infection to health care personnel and the general public.
Supportive care, adequate hydration, intravenous fluids, and antipyretics-symptomatic treatment
Reduction of IS as cessation of MMF and use of reduced CNI levels to target lower trough levels
Oxygen therapy or assisted ventilation may be necessary if a patient has hypoxemia.
Empirical antibiotics using broad spectrum antibiotics to cover gram positive and negative bacteria as well as atypical bacterial infection.
High-dose steroids can be helpful in complicated infections or COVID-19
Treatment of specific viruses is virus oriented
Differential diagnosis
1-Pneumonia
a- Viral : influenza , RSV
b- bacterial pneumonia
c- tuberculosis
d- fungal pneumonia – PCP, aspergillosis
2- Neoplastic causes
-PTLD
– metastasis from adenocarcinoma .
3-cardiac causes of dry cough as pulmonary hypertension , pulmonary congestion.
4- Pulmonary atelectasis.
Investigations
– CBC , ESR , CRP,procalcitonin
– Quanteferon TB gold.
– Multi slice CT chest
– Echo
Management :
As the patient is generally stable , only symptomatic treatment with antitussive and monitoring of the patient is needed , changing the regimen of immunesuppression is required in contex of adenocarcinoma , its better to switch MMF to sirolimus.
Acute respiratory infection is very likely
COVID-19 pneumonia
viral pneumonia
bacterial pneumonia
opportunistic pneumonia
MULTIDSIPLINARY TEAM involving ICU , respiratory and infectious specialist
labs- routine blood labs and sputum test
CBC, ESR, CRP, procalcitonin, ferritin levels, nasopharyngeal swabs for SARS-CoV-2 RT-PCR and influenza, coagulation profile, D-dimers, BGA, IGRA, sputum gene xpert, sputum m/c/s, urine LAM, BAL for PCP and aspergillosis, CMV quantitative PCR, BKV quantitative PCR, EBV quantitative PCR, serum LDH, fungal markers (BDG, galactomannan),
covid is more likely and can be confirmed with nasal RT=PCR test , HRCT of chest
management
supportive therapy like nasal o2, hydration , physiotherapy
NO change in IS is advised for covid pneumonia in this case
in general covid pneumonia is not very aggressive in the presence of IS in transplant patients
A 71-year-old male with hypertensive nephropathy received a kidney graft in February 2016. He had a history of colon adenocarcinoma in June 2019. His baseline Cr was 240–260 μmol/L. His immunosuppressive regimen included prednisolone 5 mg OD, tacrolimus (trough level was 6.4 ng/mL), and MMF 250 mg BD. He was also on calcium channel blockers and proton pump inhibitors. He presented in April 2020 with a dry cough with no other symptoms but stable vital signs. However, a chest X-ray revealed an infra-hilar consolidation on the right side.
DDx
Respiratory tract infection is the most likely diagnosis in our immunocompromised patient with dry cough cxr findings
The most common pathogens, in order of greatest incidence, include bacteria (eg, Staphylococcus aureus, Pseudomonas species, Enterobacteriaceae, enterococci, Haemophilus influenzae, mycobacteria), viruses (eg, cytomegalovirus, Epstein-Barr virus, herpes simplex virus, influenza, respiratory syncytial virus, adenovirus, parainfluenza virus, coronavirus), and fungi (eg, Pneumocystis jirovecii, Aspergillus)
As the period mentioned above April 2020 make COVID-19 on the top of the list .
How to manage
History including history of recent contact with COVID positive within 14 days ,visiting pandemic area within the last 14 days ….
Physical examination
Routine labs CBC ,Creatinine and BUN, AST ,ALT ,LDH, CRP
Coagulation profile ,RBS ,serum electrolytes, ferritin ,IL6
COVID RT PCR and antigen
CXR
HR Chest CT
Management included supportive treatment (intravenous fluid therapy, monitoring renal function, and symptomatic treatment with or without ward-based oxygen therapy depending on oxygen saturation) and discontinuation of the antiproliferative immunosuppressive drugs.
Since remdisivir was approved for the treatment of COVID-19 and its interaction with CNI is yet unknown, we recommend treatment with remdisivir in a hospital setting where CNI drug level monitoring is available.
2. A 71-year-old male with hypertensive nephropathy received a kidney graft in February 2016. He had a history of colon adenocarcinoma in June 2019. His baseline Cr was 240–260 μmol/L. His immunosuppressive regimen included prednisolone 5 mg OD, tacrolimus (trough level was 6.4 ng/mL), and MMF 250 mg BD. He was also on calcium channel blockers and proton pump inhibitors. He presented in April 2020 with a dry cough with no other symptoms but stable vital signs. However, a chest X-ray revealed an infra-hilar consolidation on the right side.
Issues/ concerns:
– 71yo male, hypertensive nephropathy, KTx Feb 2016
– June 2019 hx of colon adenocarcinoma, baseline sCr 240-260
– Tacrolimus trough level 6.4ng/ml, MMF 250mg BD, CCBs, PPIs
– April 2020 dry cough, no other symptoms, stable vital signs
– CXR revealed infra-hilar consolidation on the right side
Differential diagnosis
– SARS-CoV-2 pneumonia
– bacterial pneumonia i.e., community acquired pneumonia
– tuberculosis
– other viral pneumonia i.e., influenza, RSV
– fungal pneumonia – PCP, aspergillosis
– PTLD
– metastatic disease
Management (1-3)
– multidisciplinary approach: infectious disease team, chest physician
– detailed history and physical examination: vaccination history (pneumococcal, influenza, SARS-CoV-2), rejection treatment, history of contact (SARS-CoV-2, TB), lymphadenopathy
– baseline investigations: CBC, ESR, CRP, procalcitonin, ferritin levels, nasopharyngeal swabs for SARS-CoV-2 RT-PCR and influenza, coagulation profile, D-dimers, BGA, IGRA, sputum gene xpert, sputum m/c/s, urine LAM, BAL for PCP and aspergillosis, CMV quantitative PCR, BKV quantitative PCR, EBV quantitative PCR, serum LDH, fungal markers (BDG, galactomannan), UECs, LFTs, graft biopsy
– imaging: graft ultrasound, HRCT (Chest) to rule out malignancy as well as assess parenchymal involvement
– modification of immunosuppressive regimen: hold MMF since he is already on a small dose at 250mg BD, maintain tacrolimus and prednisone
– specific treatment depending on the results obtained from the investigations done:
References
1. Nair V, Jandovitz N, Hirsch JS, Nair G, Abate M, Bhaskaran M, et al. COVID-19 in kidney transplant recipients. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2020 Jul;20(7):1819-25. PubMed PMID: 32351040. Pubmed Central PMCID: PMC7267603. Epub 2020/05/01. eng.
2. Sundaram M, Adhikary SD, John GT, Kekre NS. Tuberculosis in renal transplant recipients. Indian journal of urology : IJU : journal of the Urological Society of India. 2008 Jul;24(3):396-400. PubMed PMID: 19468476. Pubmed Central PMCID: PMC2684355. Epub 2009/05/27. eng.
3. Kim JE, Han A, Lee H, Ha J, Kim YS, Han SS. Impact of Pneumocystis jirovecii pneumonia on kidney transplant outcome. BMC Nephrology. 2019 2019/06/10;20(1):212.
Differential diagnosis:
Viral as CMV, COVID, influenza
bacterial pneumonia
Workup :
sepsis work up as CRP, procalcitonin, Pan cultures
RFT
LFT
CMV PCR, EBV PCR, COVID
Radiology : ct chest
Treatment
isolation
supportive measures and antipyretics and good hydration
modification of IS
specific treatment according to the cause
Differential diagnosis:
· Viral- Covid 19, CMV, influenza, adenovirus, parainfluenza
· Bacterial (Atypical)- Tuberculosis
· Deep fungal infection
· Malignancy: primary or secondary
Management:
· Detailed history and clinical examination.
· Multi-disciplinary approach is needed.
· Workups will includes: CBC, PCR for Covid 19, CMV, influenza, parainfluenza and adenovirus, CRP, procalcitonin levels, D dimer levels, UECS, blood slide for malaria, LDH, ESR.
· Supportive treatment: Anti-pyretics for fever, adequate hydration, oxygen if SPO2<92%.
· Reduction/ modification of IS: Stop MMF, Reduce CNI by 50% in severe disease., Oral steroids switched to IV dexamethasone in those requiring oxygen supplementation or mechanical ventilation.
· Specific treatment according to confirm diagnosis.
My Differential diagnosis would be:
PCP infection
CMV infection
COVID-19
Herpes virus infection
Respiratory virial infection like Influenzas para influenzas etc
Ca lung/Lung metastases
Community acquired pneumonia – Bacterial
Management
COVID RT PCR prior to admission
Full blood count, LDH, Ferritin, CRP and procalcitonin(PCT)
CT Thorax with HRCT
CMV PCR
BAL for culture and Respiratory Panels
Management
Vital monitoring, observe for exertional desaturation.
Stopped MMF
Continue CNI and Steroids
IV hydration
To treat the cause if any results available
KTR with dry cough and right-side infra-hilar consolidation at CXR.
differential diagnosis:
coronaviruses and rhinoviruses.
Investigations:
·Full blood count, ESR, LFT, RFTs, RBG, CRP and LDH.
· Further Laboratory work-up is needed to screen for viral infection; COVID-19, PJP, CMV and bacterial infection.
· To screen for Mycobacterial tuberculosis( induced sputum for AAFB and PCR for TB).
Plan of management :
Management of COVID-19 infection:
A. Mild infections: the usual practice is to continue or reduce the dose of immuno-sup pressive drugs. Discontinuation of the antiproliferative drugs is strongly suggested.
B. Severe infection with requirement to mechanical ventilation: to maintain corticosteroids, hold antiproliferative and to argue about ceasing CNIs.
C. Remdesivir-treated patients had 31% faster time to recovery when compared to control.
D. CRRT may play a role in the management of AKI in COVID-19 patients. It was assumed that high-volume hemofiltration could remove inflammatory cytokines (tumour necrosis factor, IL-6, and IL-1β) involved in the pathogenesis of renal injury.
References
1. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current EvidenceMuhammed Ahmed Elhadedy, Yazin Marie, Ahmed Halawa Nephron 2021;145:192–198 DOI: 10.1159/000512329
Differential diagnosis
Dry cough with stable vital signs CXR showed a infrahilar consolidation on the right side in a kidney transplant recipient.
Differential will include:
Bacterial pneumonia
Viral- influenza, parainfluenza, adenovirus
TB
Covid 19
Metastasis- had prior history of colon adenocarcinoma.
Management
Detailed history and through physical examination.
Management in a hospital setting this is an elderly patient with prior history of colon cancer and a kidney transplant recipient.
Management should be in consultation with infectious disease specialist.
Workups include: CBC, UECS, LFT, LDH,CRP, procalcitonin, D dimers, Covid 19 PCR, influenza, parainfluenza and adenovirus PRC, blood cultures, HRCT, tacrolimus trough levels.
Supportive management- rehydration and oxygen supplementation if desaturates.
Stop the MMF.
May require to reduce the CNI dose in severe disease.
The oral steroids switched to dexamethasone in severe Covid 19 disease requiring oxygenation or mechanical ventilation.
There is a role of antivirals -remdesvir in patients requiring oxygenation and not on mechanical ventilation.
Other- Baricitinib, Tocilizumab, IVIG.
For influenza- Treatment includes oseltamivir (oral), zanamivir (inhaled and intravenous), peramivir
For adenovirus treatment includes- cidofovir, brincidofovir (investigational), IVIG
References
Respiratory Viruses in Solid Organ Transplant Recipients Roni Bitterman
and Deepali Kumar
Horby P et al. Recovery collaborative group; Dexamathasone in hospitalized pts with covid 19.N Eng j med.2021 feb 25;384(8)693-704
Halawa A et al; Covid 19 in KTR; Case series and brief review of current evidence.Nephron2021;142(2);192-198
A 71-year-old male with hypertensive nephropathy received a kidney graft in February 2016. He had a history of colon adenocarcinoma in June 2019. His baseline Cr was 240–260 μmol/L. His immunosuppressive regimen included prednisolone 5 mg OD, tacrolimus (trough level was 6.4 ng/mL), and MMF 250 mg BD. He was also on calcium channel blockers and proton pump inhibitors. He presented in April 2020 with a dry cough with no other symptoms but stable vital signs. However, a chest X-ray revealed an infra-hilar consolidation on the right side
DDX;
MGT;
REF;
DD
Viral ,fungal, bacterial, reactivation of latent TB,COVID 19
Investigations :Routine labs and fluid cultures, Covid PCR, sputum for AFB,HRCT of chest.
Management: supportive treatment ,hydration ,broad spectrum antibiotics.
Specific treatment based on underlying cause.
Immunosuppression modification ;MMF reduction.
Infrahilar consolidation in a 71 year old post transplant patient has wide differential
It could be
Bacterial
Viral
Fungal
Tuberculous
In prevailing circumstances Covid pneumonia should be considered however this is not usual involvement.
To narrow down the diferential and reach a final diagnosis we need to work him up
Blood CP
ESR
CRP
LDH
Electrolytes
Lfts
Covid PCR
sputum for gram stain , culture and AFB
HRCT chest
Definitive treatment should be according to the final diagnosis
We in our setup start broad spectrum Iv antibiotics
to cover community acquired pneumonia along with coverage for opportunistic infections
Maintain adequate hydration
Modification of immunosupression, mainly reduction of MMF if needed
⭐ Differential diagnosis:
_COVID 19 infection.
_Other viral infections as influenza , parainfluenza or RSV.
_CMV infection.
_Bacterial infection especially mycoplasma infection in extreme of ages.
_PJP can be considered in such elderly transplant recipient with prior hx of malignancy and chemotherapy.
_TB also must be in mind.
_pumonary aspergillosis.
_Metastasis or lung cancer.
⭐ Investigations required:
_COVID PCR from nasal /throat swab.
_Swab for culture for bacterial infection.
_CT chest with contrast to exclude lung tumors whether primary or secondaries (as he has hx of adenocarcinoma, then biopsy if suspicious lesions in CT).
⭐ Management plan:
_parient isolation to prevent spread of infection to health care workers and to the community.
_supportive therapy , good hydration , IV fluids and antipyretics (paracetamol).
⭐ Reduction of IS as stoppage of MMF and use lower levels of CNI.
👉 if patient has hypoxemia, oxygen therapy or assisted ventilation may be required.
_i will start empirical combined antibiotics in such old patient as (3 rd or 4th generation cephalosporin and macrolides) .
_use of high dose dexa on severe cases to shorten hospital stay.
_use of remdisivir in COVID 19 infection and oseltamivir in influenza infection.
_use of IVIG in severe cases or CVVHF in case of AkI and cytokine storm.
_PJP is diagnosed through BAL and PCR and treatment is by oxygen, SMX-TMP with steroids only in hypoxemic cases.
_CMV infection if high risk (D+/R-) with diagnosis by PCR and ttt by oral valganciclovir or IV ganciclovir (if bad general condition and can not take oral medications).
_Aspergillosis is diagnosed by BAL and serum galactomanan (treatment by voriconazole ).
Elderly with dry cough and infra hilar consolidation at time of COVID 19 outbreak.
After detailed history of symptoms, infectious disease histoty, including COVID 19, respiratory infections and immunosuppression history.
Differential diagnoses:
COVID 19 pneumonia
Bacterial pneumonia,including aspiration pneumonia
Metastasis from his previous cancer
Fungal infection, like aspergillus.
To manage this case:
After the routine lab, CRP, Ferritin, LDH, COVID-19 swab, if negative will consider other differentials including fungal and PCP.
If confirmed COVID 19 positive, then will follow local protocol for that with involvement of ID team, reduction of immunosuppression, holding MMF, reducing FK level to lower end of target, around 4, dexamethasone, anti-viral drugs etc.
References:
1-COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence Muhammed Ahmed Elhadedya, Yazin Mariea Ahmed Halawaa,
Nephron, Published online: December 8, 2020
4 year post transplant and hx Adenocarcinoma presented with dry cough and chest X-ray revealed an infra-hilar consolidation on the right side with stable vitals
DD:
Cancer Metastasis (need a contract study and accepting risk of CI-AKI if other DD excluded.infection (need infection parameters and more blood tests) FBC, CRP, procalcitonin, LFT, U&E, blood culture for bacterial infection, urine legionella and pneumococcal Ag, viral swabs for PCP , COVID and resp viral infection PCR. Keep TB in the back of your mind if had prev hx of TB or high risk populationOthers like sarcoid or Wagner, PE
Manage: untill we get the full pic, I would treat what I see (consolidation) with Abx for CAP as per local guidlines in the first instance. If the patient well enough, no need to alter his immunosupression meds.
KTR presented with dry cough and right-side infra-hilar consolidation at CXR may have the following diseases as differential diagnosis:
a) COVID-19 infection.
b) Pneumocystis Jerovecii Pneumonia.
c) Respiratory viral infection e.g.; RSV, Influenza virus, para-influenza virus, corona-viruses and rhinoviruses.
d) CMV pneumonitis.
e) Atypical bacterial infection.
f) Allergic pneumonitis.
Investigations:
· Full blood count, LFT, RBG, CRP and LDH.
· Laboratory work-up is needed to screen for viral infection; COVID-19, PJP, CMV and bacterial infection.
· To screen for Mycobacterial tuberculosis( induced sputum for AAFB and PCR for TB).
Plan of management :
· Full supportive measures.
· To treat as isolated patient in the hospital.
· Management of COVID-19 infection(1):
A. Mild infections: the usual practice is to continue or reduce the dose of immunosup- pressive drugs. Discontinuation of the antiproliferative drugs is suggested.
B. Severe infection with requirement to mechanical ventilation: to maintain corticosteroids, hold antiproliferative and to argue about ceasing CNIs.
C. Remdesivir-treated patients had 31% faster time to recovery when compared to control.
D. CRRT may play a role in the management of AKI in COVID-19 patients. It was assumed that high-volume hemofiltration could remove inflammatory cytokines (tumour necrosis factor, IL-6, and IL-1β) involved in the pathogenesis of renal injury.
References
1. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current EvidenceMuhammed Ahmed Elhadedy, Yazin Marie, Ahmed Halawa Nephron 2021;145:192–198 DOI: 10.1159/000512329
71 years- old male, presents with chest infiltrates +dry cough in kidney transplant recipient (2016), a year after diagnosis of colon adenocarcinoma (2019).
Differential diagnosis:
Infectious:
Most probable community acquired pneumonia: Bacterial (streptococcus, hemophilus influenza, Moraxella catarrhalis, legionella pneumophila, chlamydia, mycoplasma….etc), respiratory viruses (RNA viruses[ influenza viruses, parainfluenza virus, respiratory syncytial virus, human metapneumovirus, rhinovirus, coronavirus],DNA viruses [adenovirus, bocavirus, KI and WU polyomaviruses, CMV])
Fungal is unlikely however the patient had a colon cancer and he might receive chemotherapy with the combination immunosuppressive medications (tac+MMF+prednisolone): Aspergillus spp., Pneumocystis jirovecii.
Non-infectious:
o Metastatic adenocarcinoma.o Pulmonary embolism.o Bronchiolitis obliterans organizing pneumonia.o Drug induced pneumonitis: CAR-T cell therapies, checkpoint inhibitors and others.o PTLD.
This patient with old age and suboptimal graft function and malignancy, there is a high risk for opportunistic infections.
Management plan:
o Full history, contact with sick people, history of recent travel, occupational history.
Full clinical examination: head and neck , lymphnodes exam, chest exam, abdomen and lower limbs exam, respiratory rate , O2 saturation, and spirometry.
o Identify Risk factors: HLA miss match, use of ATG, History of rejection.
Evaluate the hemodynamic status, volume status of the patient, age of the patient, and comorbidities(ca colon).
o Laboratory: Full blood count(CBC), urinalysis, CRP, ESR, Kidney function test- creatinine, BUN, Na,k, Liver function test-AST, ALT, bilirubins, albumin, INR, LDH, ferritin, and D-dimer.
o Microbiology: Blood, urine and throat swab culture.
NAT-PCR for all the above mentioned viruses, PCR and viral load of CMV, EBV, PJP., Serum galactomannan and 1,3-beta-D-glucan levels for aspergillosis
Identify Risk factors: HLA miss match, use of ATG, History of rejection.
Evaluate the hemodynamic status, volume status of the patient.
o BAL for culture, cytology and PCR.
o Further imaging: chest CT scan: high resolution or with contrast if needed.
o Trail of stopping the calcium channel blocker that might worsen his GERD and produce an aspiration pneumonia or pneumonitis.
o Medications:
IV hydration, nebulizers, anti-cough.
I would decrease tacrolimus dose to (4 ng/dl), and will evaluate for stopping MMF when needed, with stress dose prednisolone /dexamethasone.
I would start him on empirical antibiotics for CAP (ie IV ceftriaxone + macrolide /res. quinolones)
Remdisivir for COVID-19
Ribavirin for influenza and other respiratory viruses
IVIG may be an option.
References:
(1) Ahmad Z, Bagchi S, Naranje P, Agarwal SK, Das CJ. Imaging spectrum of pulmonary infections in renal transplant patients. Indian J Radiol Imaging. 2020 Jul-Sep;30(3):273-279. doi: 10.4103/ijri.IJRI_357_19. Epub 2020 Oct 15. PMID: 33273760; PMCID: PMC7694710.
(2) Samavat S, Nafar M, Firozan A, Pourrezagholi F, Ahmadpoor P, Samadian F, Ziaei S, Fatemizadeh S, Dalili N. COVID-19 Rapid Guideline in Kidney Transplant Recipients. Iran J Kidney Dis. 2020 May;14(3):231-234. PMID: 32361701.
(3) Namazee N, Mahmoudi H, Afzal P, Ghaffari S. Novel coronavirus 2019 pneumonia in a kidney transplant recipient. Am J Transplant. 2020 Sep;20(9):2599-2601. doi: 10.1111/ajt.15999. Epub 2020 Jun 12. PMID: 32400099; PMCID: PMC7272986.
(4) Manuel O, Estabrook M; American Society of Transplantation Infectious Diseases Community of Practice. RNA respiratory viral infections in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13511. doi: 10.1111/ctr.13511. Epub 2019 Mar 22. PMID: 30817023; PMCID: PMC7162209.
Approach to cough in a kidney transplant
Dear Mohamed
Could it be another presentation of COVID-19?
Thank you Prof. yes it could be
it could be a PJP also so investigation will help in diagnosis and management in this patient with dry cough and a normal CXR finding,
Differential diagnosis
a) Covid-19.
b) PCP.
c) PCP/CMV.
d) CMV.
e) Influenza and parainfluenza virus.
f) BK virus infection.
g) Other viral infections.
Workup
a) Swab for covid-19.
b) Pan cultures.
c) Viral loads and PCR.
d) Urien microscopic examination.
Treatment
References
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054–62. 5 Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020 April 30;382(18):1708–20. 6 Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497–506.
López-Medrano, F.; Aguado, J.M.; Lizasoain, M.; Folgueira, D.; Juan, R.S.; Díaz-Pedroche, C.; Lumbreras, C.; Morales, J.M.; Delgado, J.F.; Moreno-González, E. Clinical implications of respiratory virus infections in solid organ transplant recipients: A prospective study. Transplantation 2007, 84, 851–856. [CrossRef] 4. Law, N.; Kumar, D. Post-transplant Viral Respiratory Infections in the Older Patient: Epidemiology, Diagnosis, and Management. Drugs Aging 2017, 34, 743–754. [CrossRef] 5. Ruuskanen, O.; Lahti, E.; Jennings, L.C.; Murdoch, D.R. Viral pneumonia. Lancet 2011, 377, 1264–1275. [CrossRef] 6. Kumar, D.; Husain, S.; Chen, M.H.; Moussa, G.; Himsworth, D.; Manuel, O.; Studer, S.; Pakstis, D.; McCurry, K.; Doucette, K.; et al. A prospective molecular surveillance study evaluating the clinical impact of community-acquired respiratory viruses in lung transplant recipients. Transplantation 2010, 89, 1028–1033. [CrossRe
Dear Kamal
You mentioned BKV infection in your differential diagnosis. Please justify it for us
Thank you Prof
BK virus can directly be a cause of respiratory symptoms (BK viral pneumonia), and many cases are reported as BK pneumonia, with viral inclusion found in the bladder and the lung.
Indirectly, although conflicting, but there is a great developing era of association between BK virus and malignancy (BK virus has an oncogenic properties), BK virus isolated from urothelial , bladder, prostate and it can cause adenocarcinoma
References
BK Polyoma Virus and Malignancy: Cause or Co-Incidence?R. Prashar, A. Shah, D. Stewart, S. Williamson, A. Patel.
Henry Ford Transplant Institute, Detroit, MI
In this patient with a new history of cancer after transplantation, MMF could be replaced by mTOR. Symptom of dry cough with infra hilar consolidation can be related to malignancy or viral infection. PCP is a probable cause but usually presents as bilateral infiltration. CMV can present with unilateral pneumonitis; Fever can be absent. For better differential diagnosis, we may need CT scan. Evaluation with CBC, CRP, and Biochemistry profile is needed. In case of suspicion of viral infection, respiratory panels can be ordered. In the era of COVID (at that time), sars-cov2 PCR should be ordered.
Antiproliferative drugs like MMF should be reduced or stopped (here, 500 mg/day is given: can be stopped). Steroids can be increased both to relieve the symptoms and oxygenation (if low)
Workup:
CBC
CRP
Procalcitonin
CXR follow-up (repeated on eed according to daily physical examination and clinical need)
Monitoring of vital signs and SPO2
DDX:
Viral infections (ALL can be ) specific evaluation for CMV is needed to start specific therapy. Superimposed bacterial infections can complicate the scenario and may entail antibiotics.
Treatment:
Supportive (Oxygen, nebul/inhaler)
specific treatment (according to the causative agent)
Thanks, Mahmud
You mentioned switching to mTORi. Will you justify it to us?
Thank you, Prof. Dr Ahmed. Regarding My suggestion/intention of shifting MMF to mTOR inhibitors here, relying on the probability of covid and viral infections in addition to previous history of cancer with the probability of malignant lesion (either primer or metastatic in the lung). Just as we may do when we face BK and CMV, which is in our list of ddx in this case, although not well justified, there was a trend to stop antiproliferative drugs at the time of the COVID-19 peak.
One of the papers that talked about the immunity against COVID-19 (Kantauskaite M, Müller L, Kolb T, Fischer S, Hillebrandt J, Ivens K, Andree M, Luedde T, Orth HM, Adams O, Schaal H, Schmidt C, Königshausen E, Rump LC, Timm J, Stegbauer J. Intensity of mycophenolate mofetil treatment is associated with an impaired immune response to SARS-CoV-2 vaccination in kidney transplant recipients. Am J Transplant. 2022 Feb;22(2):634-639. doi: 10.1111/ajt.16851. Epub 2021 Nov 1. PMID: 34551181; PMCID: PMC8653081.)
The differentials will include
1. Viral infections
2. Upper respiratory infections
3. COVID 19 infection
4. Ashthma/ COPD
5. Bacterial infections
6. Fungal infections- PCP, Aspergillosis
Management
This patient will require hospitalization, hydration and supportive care.
Investigations will include-
Blood tests like Blood CO. CRP, Renal and liver functions, ProCal
Nasal and pharyngeal swabs for COVID 19 and influenza
CMV and PCP PCR
Urine and blood cultures
Imaging like HRCT chest
If needed then Bronchoscopy and BAL
Mild cases can be managed at home with home quarantine
As regards Immune suppression, MMF should be stopped and CNI can continue
Monitoring of graft functions
If concern about rejection , then graft biopsy and management accordingly
Treatment with IVIG
Antiviral therapy according to results and local protocols.
Singh N, Limaye AP. Infections in Solid-Organ Transplant Recipients. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 2015:3440–52.
Your reply is rather limited. It does not address all the concerns.
I agree that investigating for viral infections including COVID19 as the first step.
I appreciate your clinical approach that includes commencing anti-virals and stopping MMF for few days.
Please use headings and sub-headings to make easier to read your write-up. Please use bold or underline to highlight headings and sub-headings.
Likely differentials in the above scenario includes :
Viral pneumonias : Covid-19 being at the top (because of current pandemic),CMV ,EBV, HSV
Community acquired pneumonia
Tuberculosis
PCP and Fungal infection like Aspergillosis
Mets from the colon adenocarcinoma
.How do you manage this case?
Patient should be admitted first, then thorough history taking and examination should be done ,detailed investigations like Chest X-ray PA view followed by HRCT chest ,Complete blood picture ,inflammatory marker like CRP, ferritin, ldh,beta D glucan and Aspergillus precipitans ,IGRA test for TB,Viral studies including PCR for COVID,CMV DNA CR,HSV and EBV PCR, sputum induction with hypertonic saline and staining with special stains of sample for PCP(methenamine silver for PCP)and TB, – all should be carried out and Brochoscopy with BAL if needed.
Treatment includes: hydration with I/V fluids ,Paracetamol for fever, broad spectrum antibiotics to be started anti-metabolite i.e., Mycophenolate moefitil should be stopped and patient should be monitored closely for graft function with serum creatinine and TAC level should be maintained around 5-7ng/ml. Steroids may need to be titrated to high dose in COVID case as it shortens 28 day mortality. Other treatment for COVID -19 remains controversial but can be tried like Remedesivir, Paxlovid but with cautious use due to drug-drug interaction.
REFERENCES:
1-Demir E, Ucar ZA, Dheir H,et al.COVID-19 in Kidney Transplant Recipients: A Multicenter Experience from the First Two Waves of Pandemic. BMC Nephrol. 2022 May 12;23(1):183.
2- Elhadedy MA, Marie Y, Halawa A. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence. Nephron. 2021;145(2):192-198.
I agree that investigating for COVID19 as the first step.
I appreciate your clinical approach that includes commencing anti-virals and stopping MMF for few days.
Please use headings and sub-headings to make easier to read your write-up. Please use bold or underline to highlight headings and sub-headings.
A 71-year-old male with hypertensive nephropathy received a kidney graft in February 2016. He had a history of colon adenocarcinoma in June 2019. His baseline Cr was 240–260 μmol/L. His immunosuppressive regimen included prednisolone 5 mg OD, tacrolimus (trough level was 6.4 ng/mL), and MMF 250 mg BD. He was also on calcium channel blockers and proton pump inhibitors. He presented in April 2020 with a dry cough with no other symptoms but stable vital signs. However, a chest X-ray revealed an infra-hilar consolidation on the right side.
What is the differential diagnosis?
The differential diagnoses of dry cough in post-kidney transplant patient during COVID19 pandemic era include:
COVID 19 infection it’s my 1st DD in the COVID era in immunocompromised patients.
Upper respiratory infection, Respiratory Virus Infections with other viral infection such as influenza or bronchitis.
Viral pneumonia (CMV, EBV, VZV, and HSV)
Fungal infection (PJP) infection.
Asthma, COPD Exacerbation
Bacterial infection (TB).
Herpesvirus infection (EBV, HSV and VZV).
Lung cancer (primary or secondary).
Chronic GERD, Post nasal drip, smoking …..
This transplant patient is at a high risk of infection due to:
Immunosuppression
Underlying CKD
Hypertension
COVID-19 is suspected in any of the following scenarios:
History of dry cough, chills, sore throat, and SOB +/- fever.
Patients with upper/lower respiratory symptoms with radiological findings
History of close contact with a COVID-19 case within the last 14 days.
History of presence in COVID-19 epidemic regions within the last 14 days
Pneumonia that deteriorates or fails to improve despite proper treatment.
How would you manage this case?
Detailed history and comprehensive clinical examination
ABCD
Any history of contact with SARS2-CoV positive patients.
CT thorax without iv contrast (To confirm if there is any chest findings)
CBC, (lymphopenia may be seen)
Kidney function tests.
Urine Analysis, Urine and Blood C/S
CNIs level
TB (Mantoux, IGRA, and sputum culture) Screening
Fungal (PJP) (induced sputum or bronchoscopy for BAL) screening
Nasal and throat swab for COVID-19/PCR.
Sr. Ferritin, IL-6.
CMV viral load.
LDH, Ferritin, CRP and procalcitonin
If confirmed to be COVID-19 (mild infection):
Admission in isolation room, under observation
Supportive medical therapy, good hydration (IV fluids and acetaminophen as needed).
Reduction of immunosuppressive medications or even discontinued.
Discontinued MMF or decrease 50% and continue CNIs with close graft monitoring the patient (immunosuppression treatment should be individualized based on the careful assessment of each patient)
Drugs targeting immune response regulation:
Interferons And Dexamethasone.
Dexamethasone in those receiving respiratory support (invasive mechanical ventilation or oxygen alone): resulted in lower 28-day mortality (3)
Drugs that preventing viral replicatation:
Paxlovid, remdesivir, molnupiravir, favipiravir, ribavirin, & Kaletra.
Remdesivir: The Adaptive COVID-19 Treatment Trial proved that remdesivir-treated patients had 31% faster time to recovery when compared to control (1)
Case series and a small RCT suggested better outcomes with interferon and high-dose steroids in conjunction with supportive care (2)
References
Elhadedy MA, Marie Y, Halawa A. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence. Nephron. 2021;145(2):192-198. doi: 10.1159/000512329. Epub 2020 Dec 8. PMID: 33291120; PMCID: PMC7801980.
Bitterman R, Kumar D. Respiratory Viruses in Solid Organ Transplant Recipients. Viruses. 2021 Oct 25;13(11):2146. doi: 10.3390/v13112146. PMID: 34834953; PMCID: PMC8622983.
RECOVERY Collaborative Group; Horby P, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17. PMID: 32678530; PMCID: PMC7383595.
Samavat et al. COVID-19 in Kidney Transplantation Recipients, Iranian Journal of Kidney Diseases | Volume 14 | Number 3 | May 2020
Yes, as you suggest, I would have looked for COVID19 as the first step. I like your comprehensive reply. I agree that you would consider stopping MMF for few days.
I appreciate your very well-referenced clinical approach that includes commencing anti-virals and stopping MMF for few days.
Typing whole sentence in bold or typing in capitals amounts to shouting.
: .Differential diagnosis
-This is post kidney transplant patient with a history of Ca colon and chronic allograft nephropathy present with cough without any other symptoms the differential diagnosis most likely
Management :
Admit to isolation ward ,check the vitals and assess for the need of oxygen, iv fluids ,antipyretics ,take swab for COVID -19 virus ,full blood counts, renal function test ,inflammatory markers, CMV PCR,TB rapid test , and induced sputum for PCP if other differential is excluded
-HRCT
– BAL and bronchoscopy
-Follow the patient’s vitals and if confirmed COVID 19 then management is minimizing immunosuppression ,stopping MMF continue CNI and Steroids along with good supportive care, with antivirals as recommended .
-If proved malignancy referral to an oncologist with a multidisciplinary team including a thoracic surgeon .
: References
Nephron Clin Pract. 2020 Dec 8 : 1–7.–
Published online 2020 Dec 8. doi: 10.1159/000512329
Nephron 2021;145:192–198-
https://doi.org/10.1159/000512329
Your reply is rather short.
Yes, as you suggest, I would have looked for COVID19 as the first step. I agree that you would consider stopping MMF for few days.
The index patient is an elderly kidney transplant recipient, who had a history of adenocarcinoma colon 3 years post-transplant. He is on tacrolimus based triple drug immunosuppression with calcium channel blockers (for hypertension presumably). The patient has an elevated baseline serum creatinine, suggesting chronic graft dysfunction. 4 years post-transplant, he has presented with non-productive cough, and stable vital signs. The chest x ray shows right infra-hilar consolidation. The clinical symptoms are suggestive of pneumonia.
The differential diagnosis in such a scenario would be (1):
a) Viral: Respiratory viruses (like influenza, parainfluenza, SARS-COV2, in view of the timeline of April 2020), Herpesviruses (cytomegalovirus, CMV etc)
b) Fungal: Pneumocystis jirovecii, histoplasma, Cryptococcus
c) Bacterial: community acquired like streptococcus, tuberculosis etc.
d) Parasitic: Toxoplasma, Strongyloides etc.
e) Non-infectious: Lung tumor (primary or metastases), PTLD.
In view of non-productive cough in April 2020, probability of COVID-19 is high. Absence of fever also points towards SARS-COV2 infection as fever is less common and COVID-19 is more commonly seen in hypertensive patients (2).
In view of immunosuppressed status (transplant recipient with chronic graft dysfunction), Pneumocystis pneumonia, PCP (presenting symptom of dry cough) or CMV pneumonia is also a strong possibility in this scenario (3,4).
Bacterial etiology of the clinical picture is unlikely (no expectoration and fever).
The management of the index case involves:
1) A detailed history and clinical examination: Emphasis on travel history and history of exposure to someone affected with COVID-19 should be elicited. SpO2 should be checked to assess hypoxia.
2) Laboratory testing including complete blood count (especially look for lymphopenia), renal function tests, liver function tests, C reactive protein, blood culture, chest X ray, influenza testing (if in season) and other respiratory viral testing (biofire), Tacrolimus trough levels, LDH, ferritin and Interleukin-6 (IL-6).
3) Nasopharyngeal swab test for SARS-COV2 RT-PCR/ Antigen.
4) Induced sputum examination for cytology, gram stain and acid-fast bacilli stain, and culture.
5) High resolution computed tomogram (HRCT) of chest in view of the chest x ray finding.
6) CMV PCR testing
7) Empiric initial treatment:
a) Isolation of the patient.
b) In case there is no hypoxia and only cough without any tachypnea, patient can be isolated at home.
c) If there is hypoxia, empirical anti PCP treatment in form of co-trimoxazole and steroids (if hypoxemia with oxygen saturation <70% on room air) should be started pending the investigation results. Anti-PCP treatment can be stopped once investigations for pneumocystis are negative.
8) Supportive care: Hydration and nutrition.
9) Further management as per the etiology:
a) If SARS-COV2 infection:
b) If PCP: Continue PCP treatment.
c) If CMV: Treatment with oral valganciclovir 900 mg twice a day or intravenous ganciclovir (5mg/kg IV 12 hourly, to be adjusted according to creatinine clearance). It should be continued for minimum 2 weeks (gancyclovir can be changed to oral valganciclovir, if patient improves earlier), and until resolution of clinical symptoms and radiological findings with clearance of CMV in blood, if present (6). Complete blood count and serum creatinine should be monitored weekly during the treatment. If no response in 2 weeks, assess for ganciclovir resistance and shift to Foscarnet and additional CMV immunoglobulin or intravenous immunoglobulin (IVIG) (6). Secondary prophylaxis with oral valganciclovir post-treatment can be given for 1-2 months in patients with high-risk of relapse.
d) If influenza: Antiviral against influenza (Oseltamivir) when the results for respiratory virus panel is available.
e) If malignancy: Will require tissue biopsy and further management as per the histological diagnosis.
References:
That is a fantastic reply that includes investigating for COVID19 and other viruses as the first step, and then looking for DD.
I appreciate your very well-referenced clinical approach that includes commencing anti-virals and stopping MMF for few days.
– The current case underwent renal transplant 2016 and diagnosed with colonic adenocarcinoma 2019 and in 2020 had lower lobar pneumonia in chest xray
The patient is hypertensive with basal creatinine level240–260 μmol/L on maintenance triple therapy presented with dry cough
Differential diagnosis
Infection >6 months post transplant
· Community acquired pneumonia Streptoccocus pneumonia, Haemphilus influenzae, Moraxella cattarhalis, Staphylococcus aureus
· Viral as Late CMV infection ,Herpes simplex (HSV),Varicella zoster virus (VZV),Epstein Barr virus (EBV),RSV, Influenza and parainfluenza viruses,Human metapneumovirus, Rhinovirus and Adinovirus as well as Community acquired SARS , COVID 19 pneumonia
· Mycobacterium TB ,Mycobacterium avium
· Atypical: Mycoplasma pneumoniae, Ureaplasma urealyticum, Chlamydia trachomatis, Legionella spp
· Aspergillosis ,atypical molds ,mucor species
· Underlying metastasis or malignancy recurrence have to be evaluated
· Pulmonary PTLD can resemble pneumonia findings in Chest Xray
Management
Preliminary the diagnosis depend on local epidemiology, available tests, and practice parameters,patient‐specific risk factors, exposures, and medical history.
No studies of pneumonia severity scoring systems have been applied in SOT recipients inspite that the PSI and CURB‐65 scores had poor performance in cancer patients presenting with pneumonia.
-Initial evaluation
involves history taking particularly for recent illnesses ,social exposure , vaccination history , immunosuppression degree ,comorbidities ,rejection episodes .
Thorough clinical examination
The need for isolation have to be considered particularly in such case
-Investigations
include initially complete blood count with differential, electrolyte chemistries, renal function tests ,urine analysis and liver function testing.
Blood and induced sputum culture since he has dry cough before empirical antibiotic therapy
Specific tests can be performed as CMV PCR, urine antigen testing for legionella , Quantiferon for TB, nasopharyngeal testing for influenza virus by PCR, Multiplex molecular respiratory virus testing,COVID19 nasal swab.
HR CT chest
IF patient deteriorated and did not respond to empirical therapy more invasive investigations can be done as bronchoscopy with bronchoalveolar lavage (BAL), transbronchial biopsy, CT‐guided biopsy, video‐assisted thoracotomy (VATS) with lung biopsy, and open lung biopsy particularly for diagnosis of fungal infection or underlying malignancy .
Empirical therapy
Choice depend on patient’s history of antimicrobial drug resistance , drug interactions , influenza season antininfluenza therpy has to be added,
Empirical therapy for community‐acquired pneumonia have to follow national/international guidelines .
Beta‐lactams or fluoroquinolones can be considered paying attention to drug interactions, adverse reactions, and antimicrobial resistance.
Empirical coverage of intracellular pathogens as Mycoplasma pneumoniae, Chlamydia pneumonia, and Legionella is mandatory.
Adding antibiotic against methicillin‐resistant Staphylococcus aureus (MRSA) or Pseudomonas is according to local resistance patterns, prevalence, the patient’s infection, and bacterial colonization history.
If hospitalization for pneumonia is required then a combination therapy with a beta‐lactam agent (±MRSA and ±antipseudomonal activity) and an agent active against intracellular organisms will be needed.
Empirical therapy have to be monitored to assess the patient response as well as investigations results and act according to progression or resolution of the case.
Also reduction of immunosuppression can be needed with monitoring of graft function
Reference
-Jani A A. Infections After Solid Organ Transplantation.Medscape 2022
-Dulek DE, Mueller NJ; AST Infectious Diseases Community of Practice. Pneumonia in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13545. doi:10.1111/ctr.13545
Your reply does address all the concerns and DD. I appreciate your approach that would enable you to diagnose a specific underlying viral infection that may have an effective antiviral treatment.
When mentioning modification of immunosuppression, I would consider stopping MMF for few days.
Cough in KTR have wide differential:
-Infection:
– Viral illness:
– Respiratory viruses (infuenza , PIV, RSV, HMNV, adenovirus and COVID-19)
– CMV, EBV, HSV, VZV
– Bacterial infection: TB, bacterial pneumonia.
– Fungal infection: candida, aspergillus.
– Protozoal : PCP.
– Malignancy;1ry or 2ry; he had history of colon cancer , metastasis should be considered.
– Elderly patient with HTN, should rule out cardiac causes CCF.
– COPD, BA.
– Smoking.
– GERD.
Management:
– Detailed history about: exposure history: COVID, TB and travelling, Smoking history
Work up:
– CBC; VBG
– Inflammatory markers; CRP, ESR, ferritin
– Respiratory multiples; test wide range of respiratory viruses.
– COVID-19 Rapid antigen test, fast result with hour and COVID-19 PCR.
– BAL or induced sputum for; stain ,culture, PCP,T B.
– IGRA and Mantoux test.
– LFT, KFT, LDH
– Viral load PCR: CMV, EBV, BKv and other if history was suggestive.
– Beta-D glucan
– Tacrolimus level.
– Chest CT if malignancy.
The management will be guided by the result of the tests.
If confirmed to be COVID-19:
– The clinical manifestations of SARS-CoV-2 infection in SOTR are highly variable.
– Isolation precautions.
– In mild infection: supportive management; ensure good hydration.
– Management of immunosuppressive is challenge need to balance with rejection risk.
– Hold antimetabolite, especially in lymphopenic patients.
– CNI inhibit IL-1 and IL-6 which contribute to the severity of covid infection.
– If infection is sever and progressive we can reduce CNI through level or complete stopping while increasing steroids does.
– Monitor graft function closely.
– Dexamethasone if patient require respiratory support, reduce mortality.
– All antiviral therapy are investigational.
– Consider drug-drud interaction if any new treatment used.
– Remdesivir; the first drug approved by the FDA for COVID-19 treatment,
On 21 January 2022, its use was expanded to include COVID-19 treatment in non-hospitalized patients with positive results of direct viral testing who are at high risk for progression to severe COVID-19
RCT showed 87% reduction in risk of hospitalization or death among high-risk, non-hospitalized patients who received a 3-day course of remdesivir compared to those who received the placebo.
References
Elhadedy MA, Marie Y, Halawa A. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence. Nephron. 2021;145(2):192-198. doi: 10.1159/000512329. Epub 2020 Dec 8. PMID: 33291120; PMCID: PMC7801980.
Bitterman R, Kumar D. Respiratory Viruses in Solid Organ Transplant Recipients. Viruses. 2021 Oct 25;13(11):2146. doi: 10.3390/v13112146. PMID: 34834953; PMCID: PMC8622983.
RECOVERY Collaborative Group; Horby P, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17. PMID: 32678530; PMCID: PMC7383595.
Brady, D.K., Gurijala, A.R., Huang, L., Hussain, A.A., Lingan, A.L., Pembridge, O.G., Ratangee, B.A., Sealy, T.T., Vallone, K.T. and Clements, T.P. (2022), A guide to COVID-19 antiviral therapeutics: a summary and perspective of the antiviral weapons against SARS-CoV-2 infection. FEBS J. https://doi.org/10.1111/febs.16662
I agree that investigating for COVID19 and other viruses as the first step.
I appreciate your well-referenced clinical approach that includes commencing anti-virals and stopping MMF for few days.
elderly 71 years post-transplant 4 years now, multiple comorbid including hypertension with a previous history of malignancy( ca colon ), chronic allograft dysfunction with creatinine > 240 indicate chronic allograft dysfunction or AKI on top of CKD on triple immunosuppression presented with dry cough and chest xr shows infra hilar infiltration
this patient needs admission and further work in an isolation room, DDX wide & should include viral pneumonia including covid 19, other atypical viral infections like CMV,adeno, influenza and parainfluenza virus, CAP like mycoplasma, legionella, staph, and other bacterial pneumonia, also PJP especially if there is a dry cough with sob and hypoxemia, fungal infection, TB and finally secondary mets from the primary tumor.
The patient should be tested for covid with nasal and throat swab SARs rapid PCR test, RSV screen, mycoplasma, and legionella, induced sputum for TB staining and genexeprt
CT chest is needed to assess further the extension as he is at high risk for ARDS if confirmed covid with his multiple risk factors and comorbid, CRP, blood culture, ferritin, and LDH, and assess the need for O2 therapy and steroid, MMF will be stopped and if confirmed covid pneumonia with high inflammatory markers this patient need to be treated as in patients in an isolation room with good hydration, and dexamethasone and continue on CNI Based IS plus steroid and hold MMF till he recovers. he is at risk of complications including ARDS and AKI on top of chronic allograft dysfunction and underlying multiple comorbid
References
1.Elhadedy MA, Marie Y, Halawa A. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence. Nephron. 2021;145(2):192-198.
I agree that investigating for COVID19 as the first step.
I appreciate your clinical approach that includes and stopping MMF for few days. I wish you could discuss commencing a very specific anti-virals depending upon the results of urgent testing.
Please use bold or underline to highlight headings and sub-headings.
In the current index case of old renal transplant recipient with chronic allograft dysfunction on triple immunosuppression (CNI based protocol) with recent history of colon adenocarcinoma (?managed surgically or conservative management) presented with only dry cough without other respiratory symptoms.
Most probably it is metastatic malignancy from colon cancer
Other probabilities are PCP pneumonia which presented with dry cough with few symptoms but patient is clinically doing well.
-COVID 19 infection is a strong possibility initially presented with dry cough.
-Other respiratory viral infections.
Management:
-CT chest without IV contrast to establish diagnosis behind the chest x ray findings.
-Inflammatory markers
-COVID nasal swab or PCR
-Respiratory viral panel
-Investigations to rule out PCP and other sources of chest infections
-Investigations to rule out colon cancer recurrence.
Since the patient is clinically doing well management will be based on the patient condition overall:
-Regarding immunosuppression :If there is prove of infections with high inflammatory markers and signs of SIRS to hold antimetabolites initially.
-In case of COVID positive :Isolation, assure of good hydration if clinically permissible, anti viral medications plus steroids.
Your reply is too limited. It does not address all the concerns.
I agree that investigating for COVID19 as the first step.
I appreciate your clinical approach that includes commencing anti-virals and stopping MMF for few days.
Please use headings and sub-headings to make easier to read your write-up. Please use bold or underline to highlight headings and sub-headings.
He had dry cough, high baseline creatinine, and infra-hilar consolidation on chest x-ray from prior kidney transplant with cancer.
Respiratory infection including viral, bacterial, fungal ( most probably
COVID-19 pneumonia)
Mets of primary malignancy
Management
Admitted to the COVID-19 isolation ward, excellent fluid.
Dexamethasone should be taken by those receiving respiratory support.
CT. Chest And BAL to r/o others causes
Antiviral as nirmatrelvir-ritinovir, remdesivir. But keep monitoring the level of CNI,s
Supportive care includes;
Hydration
Oxygen therapy if satuatrtion is droping
Anti metabolite dosage should be reduced or stoped while monitoring the graft function
COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence
Muhammed Ahmed Elhadedy , Yazin Marie, Ahmed Halawa
Infectious Diseases Society of America Guidelines on the
Your reply is too limited. It does not address all the concerns.
I agree that investigating for COVID19 as the first step.
I appreciate your clinical approach that includes that includes commencing anti-virals and stopping MMF for few days.
. A 71-year-old male with hypertensive nephropathy received a kidney graft in February 2016. He had a history of colon adenocarcinoma in June 2019. His baseline Cr was 240–260 μmol/L. His immunosuppressive regimen included prednisolone 5 mg OD, tacrolimus (trough level was 6.4 ng/mL), and MMF 250 mg BD. He was also on calcium channel blockers and proton pump inhibitors. He presented in April 2020 with a dry cough with no other symptoms but stable vital signs. However, a chest X-ray revealed an infra-hilar consolidation on the right side.
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History
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In April 2020 presented with complane of dry cough .
Chest Xray :infrahailr consolidation on the the right side.
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DD
Other
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I will do and ask
Take a detailed history to assess risk of COVID-19.
Physical exam
Laboratory investigations
The WHO recommends chest imaging (chest x-ray, chest CT, or lung ultrasound) in the following scenarios:
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Plane
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Reference
Yes, as you suggest, I would have looked for COVID19 as the first step. I like your comprehensive reply. I agree that you would consider stopping MMF for few days. However, I do NOT agree with your suggestion: hydroxychloroquine/chloroquine, azithromycin.
Please read my comment in the thread of second article of journal club in week 9 ridiculing a number of unproven treatments that have been suggested, when I wrote a short story of a dog believing its barking would trigger train to leave the station!
Typing whole sentence in bold or typing in capitals amounts to shouting.
This case scenario require a work up for
after comprehensive history and physical examination and discussion in an MDT
Investigations:
Treatment:
supportive and then accordingly
I would have looked for COVID19 as the first step. Your reply is too limited. It does not address all the concerns. How would you diagnose a specific underlying viral infection that may have an effective antiviral treatment?
I would consider stopping MMF for few days.
So …
Your reply is too limited. It does not address all the concerns.
I would have looked for COVID19 as the first step. How would you diagnose a specific underlying viral infection that may have an effective antiviral treatment?
I appreciate your clinical approach that includes stopping MMF for few days.
Your reply is too limited. It does not address all the concerns. How would you diagnose a specific underlying viral infection that may have an effective antiviral treatment?
I appreciate your clinical approach that includes reviewing immunosuppresion, that should include stopping MMF for few days (not mentioned by you).
This is a 71 yr old male kidney transplant 4 years ago and a h/o colon adenocarcinoma 10 months ago on triple immunosuppression who has presented with a cough and a consolidation is picked up on CXR
The differential diagnosis include:
Management:
He will require further evaluation:
The definitive treatment would depend on the diagnosis.
If it is a viral infection: Reduction of immunosuppression and reducing or stopping the antimetabolite.
For the influenza, paramyxo and adenoviruses, treatment is mainly supportive
For COVID 19, the treatment is supportive as the patient has stable vital signs
For CMV, he will require IV ganciclovir then oral valganciclovir
He may also require a lung biopsy if there is a mass detected on the HRCT
Thank you. You referred to COVID 19 as a differential. Do you think is there any role for procalcitonin assays in these cases?
Thank you Professor Mohsen
PCT will help to differentiate a bacterial infection from a viral infection
Differential diagnosis:
Management:
References:
Thank you
Why you want to admit the patient whilst his vital signs are stable and did not require oxygen.
What do you think the role of antivirals in this case?
A.Differential diagnosis
-This guy unfortunately had Ca colon & now presented with cough 4 years post transplant
-He can be categorized under the differential diagnosis of infections > 6 months posttransplant. However, this presented occurs at the time of COVID-19 pandemic and therefore, the first differential is COVID-19 pneumonia. Other differential are:
B.How do you manage this case
References
Thankyou for addressing possibility of metastatic lung lesion as well.
Wlcm prof
Differential Diagnosis;
-COVID-19 infection (Most likely),
-Respiratory Virus Infections (influenza virus, respiratory syncytial virus (RSV), human metapneumovirus (HMPV), parainfluenza virus (PIV), rhinovirus, coronavirus (CoV), adenovirus, bocavirus and KI and WU polyomaviruses,
-CMV infection,
-Herpesvirus infection (EBV,HSV and VZV),
-TB infection,
-PJP infection,
-Lung cancer (primary or secondary to Colon adenocarcinoma),
-Less likely PTLD.
How would you manage this case?
Approach to patient with no oxygen requirement;
-If he has clinical or laboratory risk factors for severe disease and was hospitalized for COVID-19 ; Remdesivir is suggested.
-For patient without any risk factors, care is primarily supportive. All patients warrant close monitoring for disease progression.
Approach to patient with oxygen requirement/severe disease;
–For patients who require oxygen supplementation because of COVID-19, the approach to COVID-19-specific therapy depends on the level of support;
-If patient receiving low-flow supplemental oxygen, low-dose dexamethasone and remdesivir are suggested.
-It is reasonable to defer dexamethasone for those who are stable on minimal oxygen supplementation (eg, 1 to 2 L/min), particularly if they are immunocompromised and within 10 days of symptom onset.
-For patients who have escalating oxygen requirements despite dexamethasone, have elevated inflammatory markers, and are within 96 hours of hospitalization, adding either tocilizumab or baricitinib are suggested, and prioritize them for more severely ill patients on higher levels of oxygen support.
-For patients receiving high-flow supplemental oxygen or non-invasive ventilation, low-dose dexamethasone is recommended.
-If they are within 24 to 48 hours of admission to an intensive care unit (ICU) or receipt of ICU-level care (and within 96 hours of hospitalization), either baricitinib or tocilizumab in addition to dexamethasone are suggested. and also adding remdesivir is suggested.
-For patients who require mechanical ventilation or extracorporeal membrane oxygenation, low-dose dexamethasone is recommended .
-For those who are within 24 to 48 hours of admission to an ICU (and within 96 hours of hospitalization), adding baricitinib or tocilizumab to dexamethasone are suggested.
-If dexamethasone is not available, other glucocorticoids at equivalent doses are reasonable alternatives.
Limited role for other therapies;
-Generally not using other agents off label for treatment of COVID-19.
-In particular, not using ivermectin, not routinely using convalescent plasma for COVID-19 therapy in hospitalized patients.
Management of hypoxemia;
Patients with severe disease often need respiratory support.
Infection control;
Infection control is an essential component of management of patients with suspected or documented COVID-19.
Supportive treatment and good hydration.
Stop Mycophenolate mofetil and continue CNI and stress dose of steroid (or shifting to IV hydrocortisone , dexamethasone)
-Adjustment of tacrolimus trough level as 4–6 ng/dL.
COVID-19 treatment; (with Pulmonology & ID review);
-In current case remdesivir is not recommended because an estimated glomerular filtration rate (eGFR) <30 mL/min per 1.73 m2 unless the potential benefit outweighs the potential risk.
-Discharged from the hospital on anticoagulation as this patient with H/o of malignancy is high risk for VTE.
References;
-UK Government press release. World first coronavirus treatment approved for NHS use by government (Accessed on June 16, 2020).
-Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19 (Accessed on February 21, 2021).
Thankyou but anti interleukin 6 is not on solid grounds .
What is the differential diagnosis?This transplant recipient patient presented with dry cough 4 years after transplantation (2020), with high baseline creatinine and infra-hilar consolidation on chest x-ray
In the era of COVID-19, in a patient with dry cough, COVID-19 is a high possibility especially with this high risk patient. Cough (44-65.7%) is the second most presenting symptom after fever (82–87%) according to two large studies
This transplant patient is at a high risk of infection due to:
1. Immunosuppression
2. Underlying CKD
3. Hypertension
4. Post-transplant malignancy (adenocarcinoma of the colon): 1% of COVID-19 patients had a history of malignancy
Other differential diagnoses of post transplant cough include:
1. Other upper respiratort tract infections
2. Viral pneumonia (CMV, EBV, VZV, and HSV)
3. Bacterial infection including TB
4. Fungal infection (PJP)
5. Malignancy
6. GERD
7. Bronchial asthma/COPD/smoking
How would you manage this case?v Detailed history and comprehensive clinical examination
v O2 saturation/ABG
v CBC, RFT & electrolytes, ESR, CRP, LFT, RBS, urine analysis, urine and blood C/S
v CMV serology/PCR
v Screen for TB (Mantoux, IGRA, and sputum culture)
v Screen for PJP (induced sputum or bronchoscopy for BAL)
v Nasal and throat swab for COVID-19/PCR, s.ferritin, IL-6, lymphopenia
v CT chest to exclude malignancy
Management of COVID-19:
o Admission
o Supportive medical therapy (IV fluids and paracetamol)
o Discontinued MMF with close monitoring the patient (immunosuppression treatment should be individualized based on the careful assessment of each patient)
o Remdesivir: the Adaptive COVID-19 Treatment Trial proved that remdesivir-treated patients had 31% faster time to recovery when compared to control
o Case series and a small RCT suggested better outcomes with interferon and high-dose steroids in conjunction with supportive care
o Dexamethasone in those receiving respiratory support (invasive mechanical ventilation or oxygen alone): resulted in lower 28-day mortality
References
1. Elhadedy MA, Marie Y, Halawa A. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence. Nephron. 2021;145(2):192-198. doi: 10.1159/000512329. Epub 2020 Dec 8. PMID: 33291120; PMCID: PMC7801980.
2. Bitterman R, Kumar D. Respiratory Viruses in Solid Organ Transplant Recipients. Viruses. 2021 Oct 25;13(11):2146. doi: 10.3390/v13112146. PMID: 34834953; PMCID: PMC8622983.
3. RECOVERY Collaborative Group; Horby P, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17. PMID: 32678530; PMCID: PMC7383595.
Well done.
guarded use of Interferon.
Differential diagnosis//
Pulmonary infection ( Bacterial/ Viral )
Pulmonary metastasis
Lung cancer
Management:
Oxygen saturation
CBC to role out infection/ LFT / RFT ESR CRP serology for HIV , COVID-19, CMV, EBV,
ABG
High resolution CT chest
BAL and bronchoscopy
PFT
good hydration and increase dose of steroid
drug level and DSA level
Antibiotic and antiviral
Would you ask for Covid – PCR?
would you dc. MMF if confirmed.?
Differential diagnoses are :
Based on the timing of the occurrence, background disease, and clinical symptom; COVID-19 pneumonia is the most likely diagnosis
Further investigations
Treatment
If the oxygen saturation is also stable (>93%) like the vital signs were, we manage as an outpatient
References
What about investigating the CXR in this index case since you mentioned in your DD metastatic lung lesion.!
Patient who had kidney transplant with adenocarcinoma in past presented with dry cough in April 2020
Differential diagnosis would be;
Management
Confirm diagnosis with
Management
Isolation and hygiene promotion
vital monitoring like O2 sat RR and labs work if suggestive of sever disease then would have need hospitalization other wise outdoor patient care( in endemic era healthcare facilities overburden should be considered).
Stopped MMF continue CNI and Steroids along with good hydration and supportive care.
May need COVID specific treatment (There were limited option available that time and durg-drug interaction were not known) .
Paxlovid(nirmatrelvir/ritonavir) can be considered in outpatients with using drug interaction tools.
References. UpToDate Topic 127582 Version 42.0
Thankyou well done.
The patient who has respiratory illness after transplantation and whose condition is progressing with perihilar infiltration might consider the following:
the character of the consolidated area? may give the suspicion of cancer (adenocarcinoma with Mets).
Pneumocystis jirovecii, Nocardia asteroids, Aspergillus spp, Cryptococcus neoformans, cytomegalovirus, varicella-zoster virus, community-acquired respiratory viruses (influenza, respiratory syncytial virus, severe acute respiratory syndrome coronavirus 2), or Legionella spp– Bacterial pneumonia – Mycobacteria – Pneumoconiosis – alveolar cancer – bronchiolitis obliterans – fungal infections
Actinomycete infection; Nocardiosis; PTLD; Cytomegalovirus.
Management:
Send in the PCR for CMV and EBV
The respiratory panel, Send COVID-19-PCR, IGRA, TB culture, and CT scan of the chest are all necessary to rule out cancer.
According to the diagnosis, the plan for treatment.
General roles:
Fishman, Jay A. “Infection in solid-organ transplant recipients.” New England Journal of Medicine 357.25 (2007): 2601-2614.
Thankyou for considering ( in this index case with history of cancer colon) the possibility of a metastatic lesion.
Otherwise well done.
Post kidney transplant recipient with Dry cough during COVID19 pandemic era.
D.D:
1-COVID 19 infection(Most people who get sick with COVID-19 have dry coughs ).
2- Respiratory Virus Infections with other viral infection such as influenza, etc.
3-TB .
4-PJP infection.
5-CMV infection.
6-Herpesvirus infection(EBV,HSV and VZV).
7-COPD,B.A.
8-Lung cancer (primary or secondary).
9-Others such as PTLD, GERD.
How would you manage this case?
1-Send COVID-19 RT-PCR. (if came positive )
Send Laboratory investigations included :
=A complete blood count and serum C-reactive protein, interleukin-6, markers of myocardial damage (creatine kinase, troponin I, lactate dehydrogenase).
=Tests of secondary hemostasis profile (prothrombin time, activated partial thromboplastin time), =Serum biochemical tests (including renal and liver function, and electrolytes).
=Procalcitonin, fibrinogen, d-dimer.
2-Send CMV, and EBV PCR.
3-Respiratory panel .
4-IGRA, Manteaux, and TB culture.
5-CT chest to exclude cancer or COPD changes .
=Isolation if COVID 19 came positive and planning for vaccination later on.
=We should classify our patient according to his clinical manifestation:
1-Asymptomatic patients and patients with mild disease (oxygen saturation above 93%, no lung involvement on chest computed tomography) were followed up in the outpatient clinic weekly.
2-Patients with moderate disease (oxygen saturation above 90%, respiratory rate under 30 breaths/min) were hospitalized in the first wave of the pandemic and followed up in the outpatient clinic in the later period because of hospital overcrowding.
3-If sever case should be admitted in IUC.
=Supportive treatment and good hydration.
=Stop Mycophenolate mofetil and continue CNI and shift steroid to IV, if worsening and our patient being in sever condition , will stop CNI and increase the steroid dose.
=Trough levels were adjusted as 4–6 ng/dL for tacrolimus
=COVID 19 treatment by chest physician using medications such as (hydroxychloroquine, azithromycin Tocilizumab and others) should bear in mind drug-drug interaction.
=Anti-tuberculous medications if TB test came positive.
References:
1-2-Demir, E., Ucar, Z.A., Dheir, H. et al. COVID-19 in Kidney Transplant Recipients: A Multicenter Experience from the First Two Waves of Pandemic. BMC Nephrol 23, 183 (2022). https://doi.org/10.1186/s12882-022-02784-w.
2-Study of Scientific Board Republic of Turkey, Ministry of Health. COVID-19 (SARS-CoV-2 INFECTION) GUIDE. April 14th, 2020, Ankara, Turkey.
Perfect
A patient with a late respiratory condition after transplantation in April 2020 evolving with perihilar infiltrate should consider:
– Viral infection (including COVID-19 and Influenza)
– Bacterial pneumonia
– Mycobacteria
– sarcoidosis
– Pneumoconiosis
– alveolar carcinoma
– bronchiolitis obliterans
– fungal infections
– Actinomycete
– Nocardiosis
– PTLD
– Cytomegalovirus
It is important to perform a viral panel, decrease immunosuppression (consider changing immunosuppression to mTOR in some cases), blood count (consider neutropenia, lymphopenia, drug-induced), hypogammaglobulinemia and other alterations.
Proceed with chest tomography for a better assessment of pulmonary involvement and Arterial blood gases.
If there is no initial diagnosis, proceed with bronchoscopy and bronchoalveolar lavage (well-equipped team for aerosols) for molecular tests (galactomannan, RT-PCR, GeneXpert) and cultures.
In the context of the COVID-19 pandemic and the risk of cyclical pulmonary viral diseases of the period, bacterial pneumonia as a complication of viral pneumonitis should be considered.
Other possibilities like gastroesophageal reflux disease and allergic asthma may be considered.
Thanks, Filipe
Why CT? What information will CT add to the CXR findings mentioned above?
Tomography can assess complications associated with the condition.
It is a viral lung disease that may be complicated with bacterial infection, and pulmonary aspergillosis and we cannot forget the possibility of pneumocystosis (interstitial disease) given the time of transplantation and the evolution of the lung disease.
The differential diagnoses of dry cough in post-kidney transplant patient include:
COVID-19 is suspected in any of the following scenarios:
Management
History & physical examination:
Laboratory:
Treatment:
For mild cases:
Other treatment steps in this scenario include:
References
Perfect
DD:
1- acute rejection with infection
2- viral infection like community-acquired respiratory viruses (influenza, respiratory syncytial virus, severe acute respiratory syndrome coronavirus 2), or Legionella spp, CMV.
3- bacterial infection
4-fungal infection aspergillus, PCP
management
1- hospitalization
2-good hydration
3-nasopharyngeal swab for influnza virus and COVID 19
4- CMV PCR
5-induced sputum for PCP
6- CT chest
7-stop MMF
8-continue CNI and steroid and manage according to the clinical course
9-monitor graft function, CBC for lymphopenia
Jay A Fishman. Infection in the solid organ transplant recipient. uptodate. 2022
N. Sarabu, C. Michael, D. E. Hricik, J. J. Augustine. Fever of Unknown Origin in a Kidney Transplant Recipient. American Journal of Transplantation.2015; 15: 2006–2008
Thanks, Riham
Could be a case of COVID-19?