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5. A 65-year-old kidney transplant recipient developed this lesion 7 years after his cadaveric transplantation. Currently, he is on Tacrolimus (trough level 7.4 ng/ml) and MMF 750 mg bd. He has poor kidney function (eGFR is 15 ml/min) due to cAMR.
- What is your differential diagnosis?
- How do you manage this case?
- Substantiate your answer.
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Differential diagnosis
Kaposi sarcoma associated with fungal infection in nails
Management
Detailed history and examination
Skin biopsy
Imagine for diagnosis of metastasis (CT chest and CT abdomen and pelvis )
HHV8 PCR
stop Tac and initiation of mTor inhibitors
DIFFERENTIAL DIAGNOSIS
kaposi sarcoma.
SCC
BCC
Melanoma
the management
skin biopsy
Chest and abdominal CT to rule out visceral involvements
According to the note of professor Halawa, yes the eGFR oc this patient is only 15ml/min therefore we should stop immunosuppression and start treatment with mTOR.
DD:
Kaposi sarcoma
BCC
SCC
nail fungal infection
A case of failing graft so better to stop all immunosuppressive medications
also we should exclude affection of any other part of the body and to exclude visceral kaposi
Knowing sarcoma
Fungal infection
BCC
Differential diagnosis include Kaposi sarcoma with obvious fungal infection of the nails indicating over immunosuppression, other diagnoses may vary from basal cell carcinoma or squamous cell carcinomas.
Management of such case mainly starts by biopsy from the lesion, viral serology for EBV, exclusion of visceral involvement is a must, and reduction of immunosuppression with better switching to mTORi agent is advisable.
Multidisciplinary team including dermatologist, oncologist and transplant specialist is recommended. Treatment of concurrent fungal infection should be performed.
What is your differential diagnosis?
The present figure most likely showing kaposi sarcoma with associated fungal infections of nails.
Other possible diagnosis-
Basal cell carcinoma
SCC
How do you manage this case?
Biopsy of the lesion is must for diagnosis of kaposi sarcoma.In addition Visceral involvement should be ruled out if symptoms of viscreal involvement is present, by ct scan of abdomen,Ct of chest,endoscopy or bronchopscopy.If it is local KS,we should reduce his immunosuppression and change the tacrolimus to mTOR inhibitor.But this is also case of failing graft,so we can completly stop other immunosuppression and mTOR inhibitors should continue.If there is visceral involvement,in addditon to mTOR we should give liposomal anthacyclines.Cardiomyopathy should be ruled out before giving Liposomal anthacyclines.
What is your differential diagnosis?
· Kaposi sarcoma is on the top of the list
· Other DD:
· SCC
· BCC
· Fungal infection (patient has fungal infection in the nails)
How do you manage this case?
· Biopsy and histopathology to confirm the nature of the lesion
· Examine other parts of the body for other skin lesions
· Exclude visceral involvement and ask for symptoms (carry a poor prognosis) and do OGD, colonoscopy and bronchoscopy
· Screening for HHV-8 viral load(mostly associated with Kaposi sarcoma)
· Decrease Tacrolimus (keep trough 3-5 ng/ml) OR stop all immunosuppression and keep only on steroids
· Switching to mTOR inhibitors(has anti-proliferative actions). However, with such low eGFR, this cannot be done.
· In patients without good response, chemotherapy or radiotherapy are additional options.
· Proper education and prepare the patient for RRT.
Substantiate your answer.
· Kaposi’s sarcoma is a skin cancer is higher in kidney transplanted patients.
· The disease involves mainly the skin . However, visceral involvement can occur and carries a poor prognosis.
· The recurrence is frequent, and it associated with over immunosuppression.
· risk factors includes infections with oncogenic viruses as HHV- 8 .
and black skin.
· Diagnoses is made by skin biopsy and immunohistochemistry.
· CT scan and endoscopies is mandated to exclude visceral involvement .
· Reduction in immunosuppression is the cornerstone of management However, this must be balanced with increased risk of acute rejection.
· Switching from CNIs to mTORi has become a commonly accepted management strategy(anti-proliferative effect).
· There are no guidelines about chemotherapeutics used in disseminated transplant-associated KS.
References:
1. Al-Adra D, Al-Qaoud T, Fowler K, Wong G. De Novo Malignancies after Kidney Transplantation. Clinical journal of the American Society of Nephrology : CJASN. 2022 Mar;17(3):434-43.
2. Raeisi D, Payandeh M, Madani SH, Zare ME, Kansestani AN, Hashemian AH. Kaposi’s Sarcoma after Kidney Transplantation: a 21-Years’ Experience. International journal of hematology-oncology and stem cell research. 2013;7(4):29-33.
3. Stallone G, Schena A, Infante B, Di Paolo S, Loverre A, Maggio G, et al. Sirolimus for Kaposi’s sarcoma in renal-transplant recipients. The New England journal of medicine. 2005 Mar 31;352(13):1317-23.
A 65-year-old kidney transplant recipient developed this lesion 7 years after his cadaveric transplantation. Currently, he is on Tacrolimus (trough level 7.4 ng/ml) and MMF 750 mg bd. He has poor kidney function (eGFR is 15 ml/min) due to cAMR.
● What is your differential diagnosis?
A purple, red and brown skin lesions that is flat and in some lesions is raised on the hand with fungal infection in the nails which consists with kaposi sarcoma.
Others have to be excluded :
BCC
SCC
Melanoma
Angiosarcomas
● How do you manage this case?
Biopsy with immunohistochemical staining
Viral serology for HHV8
Radiology evaluation
As GFR 15 ml/min so I will stopping all immunosuppressants drugs and starting m-TORi
● Substantiate your answer.
Elizabeth K. Cahoon, Martha S. Linet, Christina A. Clarke, Karen S. Pawlish, Eric A. Engels, Ruth M. Pfeiffer
Risk of Kaposi sarcoma after solid organ transplantation in the United States. International Journal of Cancer .Volume 143, Issue 11 p. 2741-2748.
65-year-old kidney transplant recipient developed purple-red-bluish macules, papules, and nodules 7 years after his cadaveric transplantation.
Currently, he is on Tacrolimus (trough level 7.4 ng/ml) which is high for his current failing graft
and MMF 750 mg bd. He has poor kidney function (eGFR is 15 ml/min) due to cAMR.
differential diagnosis of skin lesions
Kaposi sarcoma
basal cell carcinoma
with fungal nail infection
The incidence of KS is higher in transplant patients than in non-immunosuppressed populations.
In kidney transplant recipients, the intensity and duration of immunosuppression, and the presence of HHV8 serology pre-transplantation, older age and male gender increase the risk of developing KS,
– Biopsy and histopathology to confirm the nature of the lesion.
In case of confirmed diagnosis of Kaposi sarcoma
– PCR for HHV-8 as it is mostly associated with Kaposi sarcoma .
– upper GIT & biopsy
– CT scan of chest
– ask for symptoms of dissemination to visceral mucosa of the trachea, lungs and gastrointestinal tract which is common in immunosuppressed patients
Treatment:
Reduction of immunosuppressive therapy, as well as a switch of calcineurin inhibitor to mammalian target of rapamycin may obtain resolution of disease in the early stages of the disease.
For extensive involvement, liposomal anthracyclines is proposed as a first-line therapy.
Mucosal dissemination or visceral involvement has usually a poor prognosis.
In case of poor graft function, we may go for complete stopping of all immunosuppressive and start RRT and follow up for regression of the lesion.
References
Kaposi sarcoma after kidney transplantation Juliette Raedemaeker, Liliane Marot, Alessandra Camboni, Nada Kanaan
This most likely kaposi sarcoma
minimization of immunosuppression, stopping MMF, tacrolimus and adding mTORi
What is your differential diagnosis?
The differential diagnosis is of Kaposi sarcoma as purple lesions are present a fungal infection on the nails.
How do you manage this case?
Switching Tacrolimus to Sirolimus or mTOR inhibitors.
Substantiate your answer.
Campistol JM, Schena FP. Kaposi’s sarcoma in renal transplant recipients–the impact of proliferation signal inhibitors. Nephrol Dial Transplant. 2007;22 Suppl1:i17-22.
The lesions are very suggestive of Kaposi, but differential diagnosis with other skin cancers and also with fungal infection (mainly fusariosis) is necessary.
Decreased immunosuppression
Biopsy for histopathological diagnosis of the lesion.
I would only initiate empirical treatment for the fungus if there was a delay in performing the biopsy.
Q1: purple lesions of hands and nail changes. The most probable diagnosis is Kaposi sarcoma with nail fungal infection that indicates a high dose of immunosuppression. Other ΔΔ are: non-Melanotis skin cancer or angiosarcoma, SCC, bacillary angiomatosis.
Q2:
· An MDT team is needed.
· Biopsy and histopathologic evaluation
· If Kaposi sarcoma is the diagnosis:
Screening for HHV-8 viral load
Chest, abdomen, pelvic CT scan or PET-scan
Endoscopy, colonoscopy, bronchoscopy
· Considering CFR:
Discontinue all immunosuppressives and initiate dialysis to mTOR
Local and systemic therapies may be used for management, too. Initial therapy with pegylated liposomal doxorubicin is approved for AIDS-related KS.
· For Onychomycosis:
A sampling of nails with KOH staining.
Treatment with oral antifungal drug with renal adjustment.
· What is your differential diagnosis?
Picture shows brownish red lesions on the dorsum of hand plus nail changes that could be fungal infection all raise the suspicion for Kaposi sarcoma.
other DD which are less likely: bacillary angiomatosis, pyogenic granuloma.
· How do you manage this case?
1- Full general examination and history taking looking for other lesions or other organ affection symptoms and signs.
2- Skin biopsy
3- MDT including dermatologist, oncologist, nephrologist and other specialties if there is extra-cutaneous affection.
4- Routine bloods.
5- CT-Chest, abdomen and pelvis looking for distant metastasis or another organ involvement, OGD if GIT affection is suspected.
6- Reduction of immunosuppression. This graft is failing now so minimal IS is required.
7- Prepare for Renal replacement therapy
Kaposi sarcoma with nails fungal infection
HHS-8PCR
oncology and dermatology consultation
RI by stoping antimetabolites
gradual reduction of Tac
prepare him for RRT
we cannot use mTORi as his GFR is 15
looking for visceral involvement by endoscopic examination
sun exposure avoidance
use of sunscreen
Reference
Dr.Ahmed Halawa lecture
65 years 7 years post cadaveric transplant with eGFR = 15 ml/min sec cAMR now having Multiple erythematous to violaceous plaques of varying sizes on dorsum of hand. Single violaceous well circumscribed nodule on dorsum of middle finger along with onychomycosis.
What is your differential diagnosis?
· Kaposi sarcoma
· Non-melanotic skin cancer
· Infection (fungal vs bacillary angiomatosis)
How do you manage this case?
1. History and examination
o Detailed history and examination for systemic involvement. Special emphasis on mucocutaneous surfaces and lymphadenopathy.
2. Confirm the diagnosis
o Deep skin biopsy for histopathology and immunohistochemistry for LANA-1
o HHV 8 PCR
o HIV
o Stool for occult blood (if positive then endoscopic imaging)
o Imaging for metastatic disease (non-contrast CT vs PET Scan)
3. Counseling:
o Breaking the news gently
o Reassure the patient
o Inform in detail regarding current status and management plan
4. Multidisciplinary care
o Oncology (radiation and medical)
o Dermatology
o Nephrology
o Gastroenterology (in case of GI involvement)
5. Treatment:
o Switch from CNI to mTOR therapy (graft has already failed)
o Prepare for re-initiation of dialysis
o No proven role for stopping or switching antimetabolite for KS unlike other post-transplant malignancies
o Radiotherapy +/- chemotherapy if indicated for systemic disease after MDT
o Close follow up for assessing resolution of lesions
Substantiate your answer.
REFERENCES:
1. Raeisi D, Payandeh M, Madani SH, Zare ME, Kansestani AN, Hashemian AH. Kaposi’s Sarcoma after Kidney Transplantation: a 21-Years Experience. Int J Hematol Oncol Stem Cell Res. 2013;7(4):29-33. PMID: 24505540; PMCID: PMC3915423.
2. Bishop BN, Lynch DT. Kaposi Sarcoma. [Updated 2022 Jun 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK534839/
3. Schneider JW, Dittmer DP. Diagnosis and Treatment of Kaposi Sarcoma. Am J Clin Dermatol. 2017 Aug;18(4):529-539. doi: 10.1007/s40257-017-0270-4. PMID: 28324233; PMCID: PMC5509489.
DD:
-Kaposi Sarcoma with fungal infection ;most likely.
-Squamous cell carcinoma
-Basal cell carcinoma
Management :
Checking of possible visceral involvement of GIT and other pars using endoscopy ,ct …
Immunosuppression reduction , holding MMF, switching of CNI to MTOR inhibitor.
· Oncology and dermatology for other options if no improvement.
· Antifungal treatment for infected nails.
· For prevention: avoidance of sun exposure and use of sunscreen.
References:
Kaposi sarcoma after kidney transplantation Juliette Raedemaeker, Liliane Marot, Alessandra Camboni, Nada Kanaan
Post renal-transplant malignancy surveillance, Clinical Medicine 2020 Vol 20, No 2: 142–5
Differential diagnosis:
Management of this case:
· Reduction of Immunosuppression, holding the anti inflammatory MMF, switching CNI to the MTOR inhibitor sirolimus or reducing tacrolimus dose to trough level of 3-5, as there is contra indication to sirolimus with e GFR 15ml/min.
· Evaluate for visceral involvement of GIT tract and other part of body.
· Oncology consultation for second line options if no improvement.
· Dermatology consultation.
· Antifungal treatment for infected nails.
· To prevent recurrence or development of new lesion, avoidance of sun exposure and the use of sunscreen may help.
References:
1- Kaposi sarcoma after kidney transplantation Juliette Raedemaeker, Liliane Marot, Alessandra Camboni, Nada Kanaan
2- Post renal-transplant malignancy surveillance, Clinical Medicine 2020 Vol 20, No 2: 142–5
3- KDIGO Guidelines 2020
Differential diagnosis:
Management of this case:
· Reduction of Immunosuppression, holding the anti inflammatory MMF, switching CNI to the MTOR inhibitor sirolimus or reducing tacrolimus dose to trough level of 3-5, as there is contra indication to sirolimus with e GFR 15ml/min.
· Evaluate for visceral involvement of GIT tract and other part of body.
· Oncology consultation for second line options if no improvement.
· Dermatology consultation.
· Antifungal treatment for infected nails.
· To prevent recurrence or development of new lesion, avoidance of sun exposure and the use of sunscreen may help.
References:
1- Kaposi sarcoma after kidney transplantation Juliette Raedemaeker, Liliane Marot, Alessandra Camboni, Nada Kanaan
2- Post renal-transplant malignancy surveillance, Clinical Medicine 2020 Vol 20, No 2: 142–5
3- KDIGO Guidelines 2020
The first thing coming to mind with this purpule brown lesion is kaposi sarcoma. nails can be as menisoned tinea unginum. Bad renal function and therse lesions suggest minimization of immunosuppression. Shifting treatment to mTOR inhibitors. examination of the rest of the body fr any suspected lesion.
——————–
Zmonarski SC, Boratyńska M, Puziewicz-Zmonarska A, Kazimierczak K, Klinger M. Kaposi’s sarcoma in renal transplant recipients. Ann Transplant. 2005;10(2):59-65. PMID: 16218035.
There are multiple purplish brown maculopapular lesion over dorsum of hand & onycholysis of nalis. My differential diagnosis of skin lesions are-
a) Kaposi sarcoma
b) Bacillary angiomatosis
c) Angiosarcoma
History- other symptom related to visceral involvement of kaposi sarcoma-
-GIT- abdominal pain, vomiting, bloody diarrhoea, obstructive symptom.
– Pulmonary- Dry cough, haemoptysis, dyspnoea
– Fever
– Weight loss
Investigation:
– Biopsy of lesion & histopathological examination ( angioproliferative histologic features)
– Immunohistochemistry of the biopsy slide to detect HHV-8.
– PCR for HHV-8.
– Endoscopy of upper GIT & biopsy
– CT scan of chest
– Bronchoscopy & biopsy
– FNAC from lymphnode if any
– USG of whole abdomen (any organomegaly)
Treatment:
– Dissemination is common if not treated rapidly & adequately
– Poor prognosis in case of visceral involvement
– Conversion to sirolimus based, CNI free therapy has been shown to produce remission of kaposi’s syndrome in renal transplant recipient.
– But in this case as poor renal function
( eGFR 15), sirolimus can’t be given.
– Gradual withdrawl of all immunosuppressive and plan for renal replacement therapy is needed
– After 3 month of withdrawl of CNI, skin lesion usually disappear & after 6 month, biopsy become negative for kaposi sarcoma.
1. NCCN Clinical Practice Guidelines in Oncology ( NCCN Guidelines Kaposi Sarcoma Version 1. 2023- December 20, 2022)
2. Duma S, Toz H, Asci G, Alper S, Ozkahya M, Unal I et al. Successful treatment of post- transplant kaposi’s sarcoma by reduction of immunosuppression. Nephrol Dial Transplant (2002) 17: 892- 896
3. Rosai J. A riddle within a puzzle. In: Gott lieb G, Acuerman AB, eds, Kaposi’s Sarcoma: a Text and Atlas, Lea and Febiger, philadelphia, 1988; 255- 269
◇ What is your differential diagnosis?
In this 65-year-old kidney transplant recipient who developed this lesion 7 years after his cadaveric transplantation. and he is currently, he is on Tacrolimus and MMF with cAMR.
The lesion is reddish-brown plaques with nodules on the dorsum of the left hand, there is fungal infection of the nail beds.
Differential diagnosis:
How do you manage this case?
1. Proper history and examination:
To look for other skin lesions on the other parts of the body ( eg: look for lymphadenopathy).
2. Consult a dermatologist
3. Biopsy of the lesion, and if there is a lymph node – consider a lymph node biopsy – we can confirm the diagnosis of Kaposi sarcoma by the presence of spindle cells consistently stained for CD31 and CD34, and detection of HHV-8 latent antigen within those cells by immunohistochemical staining of biopsy specimen [1].
4. Investigate for GIT and other visceral involvements by:
▪︎CT chest and abdomen.
▪︎Upper and lower GIT endoscopy
5. Treatment:
– Refer him to an oncologist, to consider
the patient’s need for chemotherapy
regimen that consist of combination of
vinblastine and bleomycine.
– Concerning Immunosuppression:
Stop MMF and Switch Tacrolimus
to Sirolimus to prevent further rejection
episodes, and try to preserve the renal
function and decrease sensitization.
___________________________________
References:
[1] Zafer Ercana, Mehmet E. Demirb, Ozgur Merhametsiza, et al. Kaposi’s sarcoma in the early post-transplant period in a kidney transplant recipient. November 2013; 751-868.
[2] up to date
Kaposi sarcoma with fungal infection affecting the nails
1) Test for HSV-8 infection
2) Reduce or even stopping MMF
3) Change CNI to mTOR inhibitor
4) Looking for visceral involvement ( CT scan , endoscopes )
Referance :
1) Up to date
2) Prof Ahmad Hallawah Lecture
A 65-year-old kidney transplant recipient developed this lesion 7 years after his cadaveric transplantation. Currently, he is on Tacrolimus (trough level 7.4 ng/ml) and MMF 750 mg bd. He has poor kidney function (eGFR is 15 ml/min) due to cAMR
The above scenario shows features of a post renal transplant recipient with a skin lesion which papular lesion with violaceous color associated with macular skin changes near by in the hand….
Differential diagnosis include Kaposi’s sarcoma, bacillary angiomatosis, Malignant Melanoma
He also has onychomycosis of the nails…
He needs a detailed evaluation including CBC, LDH, Liver function test, skin biopsy of the lesion.. He also needs to be evaluated for the distant spread by a PET CT scan…skin biopsy sample can be stained by immunohistochemistry against HHV 8 or to locate HHV 8 antigen in the spindle cells of the tumour
Management involves the reduction of immunosuppression.. This patient already has chronic allograft nephropathy due to Chronic antibody mediated rejection with eGFR being 15ml/min…. Reduction of the immunosuppression will not matter a difference to the overall graft survival…WE need to get ready for AVF creation for dialysis, oral sodium bicarbonate supplementation and EPO use…We should counsel the patient for the next transplant.. The management of the skin lesion depends on the diagnosis…If there is multifocal Kaposi’s sarcoma patient needs chemotherapy with agents etoposide, bleomycin and Vincristine…. Needs local skin excision and local radiotherapy to control the disease…There is no specific therapy for HHV 8…
Immunosuppression can be changed to mTOR inhibitors but in the situation of pre existing Chronic allograft nephropathy it may not be advisable…We also need to know the degree of proteinuria in this patient…In general mTOR inhibitors will be useful for eGFR>30ml/min and proteinuria <500mg/24 hours
What is your differential diagnosis?
D/D
· BCC
· SCC
· Bacillary angiomatosis,
Fungal infection of nail
How do you manage this case?
Diagnosis: detail history, through clinical examination to look for other skin lesions
Dermatologist consultation
Biopsy – test for HHV-8 PCR in the tissue sample
Look for visceral involvement – CeCT chest and abdomen
Upper GI endoscopy and colonoscopy
Multi disciplinary meeting with oncologist, dermatologist – discussion with patient party for reduction of immunosuppression, its pros and cons; make him free of cancer and imnfection to prepare for next transplant.
Reduce Immunosuppression:
In view of diagnosis Kaposi sarcoma, failing kidney and fungal infection of nail –
Stopping MMF and Switching Tacrolimus to Sirolimus – prevent further rejection, preserve residual renal function and decrease sensitization for next transplant.
For prevention of recurrence of new lesion – avoidance of sun exposure and the use of broad spectrum sunscreen with SPF 50+ / sun protective clothing, googles.
Substantiate your answer.
KDIGO guidelines 2020
Marco F, Pasquale G, Marica G, et al. Management of patients with a failed kidney transplant: what should we do?, Clinical Kidney Journal 2021 Jan: 14 – 1, 98–106,
Post renal-transplant malignancy surveillance, Clinical Medicine 2020; (20) 2: 142–145
Stoff B, Salisbury C, Parker D, O’Reilly Zwald F.Dermatopathology of skin cancer in solid organ transplant recipients. Transplant Rev 2010;24(4):172–189.
Euvrard S, Morelon E, Rostaing L, et al. Sirolimus and secondary skin-cancer prevention in kidney transplantation. N Engl J Med 2012; 367:329
What is your differential diagnosis?
D/D
· BCC
· SCC
· Bacillary angiomatosis,
Fungal infection of nail
How do you manage this case?
Diagnosis: detail history, through clinical examination to look for other skin lesions
Dermatologist consultation
Biopsy – test for HHV-8 PCR in the tissue sample
Look for visceral involvement – CeCT chest and abdomen
Upper GI endoscopy and colonoscopy
Multi disciplinary meeting with oncologist, dermatologist – discussion with patient party for reduction of immunosuppression, its pros and cons; make him free of cancer and imnfection to prepare for next transplant.
Reduce Immunosuppression:
In view of diagnosis Kaposi sarcoma, failing kidney and fungal infection of nail –
Stopping MMF and Switching Tacrolimus to Sirolimus – prevent further rejection, preserve residual renal function and decrease sensitization for next transplant.
For prevention of recurrence of new lesion – avoidance of sun exposure and the use of broad spectrum sunscreen with SPF 50+ / sun protective clothing, googles.
Substantiate your answer.
KDIGO guidelines 2020
Marco F, Pasquale G, Marica G, et al. Management of patients with a failed kidney transplant: what should we do?, Clinical Kidney Journal 2021 Jan: 14 – 1, 98–106,
Post renal-transplant malignancy surveillance, Clinical Medicine 2020; (20) 2: 142–145
Stoff B, Salisbury C, Parker D, O’Reilly Zwald F.Dermatopathology of skin cancer in solid organ transplant recipients. Transplant Rev 2010;24(4):172–189.
Euvrard S, Morelon E, Rostaing L, et al. Sirolimus and secondary skin-cancer prevention in kidney transplantation. N Engl J Med 2012; 367:329
What is your differential diagnosis?
How do you manage this case?
Complete history and through examination(look for other lesions)
In view of diagnosis Kaposi sarcoma, failing kidney and fungal infection of nail
Immunosuppression reduction,
Stopping MMF
Switching CNI to the MTOR inhibitor( sirolimus) in low level to prevent ongoing rejection in graft and decrease immunogenicity for next transplant, preserve residual renal function
Evaluate for visceral involvement of GIT tract and other part of body.(Non contrast MRI/endoscopy/ultrasonography)
Multi disciplinary meeting with oncologist, dermatologist.(skin and nail lesions)
For prevention of recurrence of new lesion- avoidance of sun exposure and the use of sunscreen/ protective clothing.
Substantiate your answer.
Kaposi sarcoma after kidney transplantation Juliette Raedemaeker, Liliane Marot, Alessandra Camboni, Nada Kanaan
Marco Fiorentino, Pasquale Gallo, Marica Giliberti, Vincenza Colucci, Antonio Schena, Giovanni Stallone, Loreto Gesualdo, Giuseppe Castellano, Management of patients with a failed kidney transplant: what should we do?, Clinical Kidney Journal, Volume 14, Issue 1, January 2021, Pages 98–106, https://doi.org/10.1093/ckj/sfaa094
PICTURE SHOWES SKIN LESION LILEY TO BE KAPOSI SARCOMA
AND NAILS HAS CHRONIC FUNGAL LESIONS
SKIN LESION CAN BE
SCC
BCC
OTHE KS LESION AND SOLID ORGAN INVOLVEMENT NEED TO BE RULED OUT WITH INVESTIGATION( CT SCAN ) AND PHYSICAL EXAMINATION
AS HIS GRAFT IS FAILING , TAC CAN BE REDUCED AT FIRSTA OR SUBSEQUENTLY STOPPED AND SIROLIMUS CAN BE STARTED
MOST KS LESION WILL RESOLEV WITH THIS
THIS IS NOT A CONTRA INDICATION FOR FUTURE RE-TRANSPLANTATION IF THIS GRAFT FAILURE LEADS HIM TO ESRD
Kaposi Sarcoma, Fungal infection, Squamous cell carcinoma, Basal cell carcinoma.
history, physical examination dermatological consultation for skin biopsy
Reducing of immunosuppression or switching immunosuppressants to mTOR inhibitors, such as sirolimus or everolimus, are cornerstones of treatment.
Surgery, radiotherapy, chemotherapy.
https://pubmed.ncbi.nlm.nih.gov/36334939/.
UpToDate
Kaposi Sarcoma
Fungal infection
Squamous cell carcinoma
Basal cell cardcinoma
· Immunosuppression reduction, holding the anti inflammatory MMF, switching CNI to the MTOR inhibitor sirolimus or reducing tacrolimus dose to trough level of 3-5, as there is contra indication to sirolimus with e GFR 15ml/min.
· Evaluate for visceral involvement of GIT tract and other part of body.
· Oncology consultation for second line options if no improvement.
· Dermatology consultation.
· Antifungal treatment for infected nails.
· To prevent recurrence or development of new lesion, avoidance of sun exposure and the use of sunscreen may help.
References:
1- KDIGO guidelines 2020
2- Post renal-transplant malignancy surveillance, Clinical Medicine 2020 Vol 20, No 2: 142–5
3- Kaposi sarcoma after kidney transplantation Juliette Raedemaeker, Liliane Marot, Alessandra Camboni, Nada Kanaan
This man has two lesions on his hand, Kaposi sarcoma and fungal infection affected all his nails of the hand.
Kaposi sarcoma (KS) is an angioproliferative disorder that requires infection with human herpes virus 8 (HHV-8)
KS is classified into four types:
1) classic (the type originally described by Kaposi, which typically presents in middle or old age)
2) endemic (several forms described in individuals from sub-Saharan Africa prior to the [AIDS] epidemic)
3) iatrogenic (a type associated with immunosuppressive drug therapy, typically seen in renal allograft recipients)
4) AIDS associated (epidemic KS)
Skin lesions
· Classic KS is characterized by the appearance of purplish, reddish blue, or dark brown/black macules, plaques, and nodules on the skin
· There may be accompanying lymphedema of the affected extremity.
Extracutaneous involvement
· mucous membranes of the mouth and gastrointestinal tract, and regional lymph nodes may be affected.
· Gastrointestinal tract involvement is usually asymptomatic, but bleeding, diarrhea, protein-losing enteropathy, intussusception, and perforation have been reported
· Regional nodal involvement is relatively uncommon, and it is rarely bulky.
· Involvement of visceral organs other than the lining of the alimentary tract (eg, lung, liver, bone, bone marrow) is extremely rare
Biopsy — is required for definitive diagnosis.
In addition PCR can be performed on the skin lesions to detect amplified (HHV-8) DNA sequences, and immunohistochemical staining of biopsy specimens can also be performed to detect the presence of HHV-8 latency-associated nuclear antigen (LANA-1) within the spindle cells, thus confirming the diagnosis
· The type and degree of immunosuppression play an important role in the development of posttransplant KS.
· Patients treated with calcineurin inhibitor-based immunosuppressive therapies are at particularly high risk of developing aggressive KS.
Management
· Reducing the intensity of immunosuppression or switching immunosuppressants to mTOR inhibitors, such as sirolimus or everolimus, are cornerstones of treatment.
· Many articles approved that sirolimus-based immunosuppression proffers the possibility of KS regression with concomitant renal function preservation among renal graft recipients.
· Regression of KS has been reported after switching from calcineurin inhibitors to sirolimus by restoring effector and memory T-cell immune activity against HHV-8
· If no response to a change in immunosuppression, KS is treated similarly to classic KS.
· We should exclude visceral involvement, extensive lymph node involvement, or progressive mucocutaneous involvement, as this indicates systemic chemotherapy such as Doxorubicine
· Radiation therapy — All forms of KS, including classic KS, are very sensitive to RT.
· The use of interferon alfa is not recommended because its use is associated with a higher risk of rejection
1) https://www.uptodate.com/contents/classic-kaposi-sarcoma-clinical-features-staging-diagnosis-and-treatment?search=kaposi%20sarcoma%20post%20transplant&topicRef=16332&source=see_link#:~:text=Classic%20Kaposi%20sarcoma%3A%20Clinical%20features%2C%20staging%2C%20diagnosis%2C%20and%20treatment
2) https://onlinelibrary.wiley.com/doi/full/10.1111/ddg.14788#:~:text=Guidelines%20for%20the,03%20June%202022
3) https://www.sciencedirect.com/science/article/abs/pii/S0041134504016306?via%3Dihub#:~:text=Regression%20of%20Kaposi%27s%20Sarcoma%20in%20Renal%20Graft%20Recipients%20After%20Conversion%20to%20Sirolimus%20Treatment
What is your differential diagnosis?
Patient also has onychomycoses of fingers.
How do you manage this case?
References:
Prof. Ahmed Halawa lecture, Post-transplantation lymphoproliferative disorders: Current concepts and future therapeutic approaches
Schwartz RA. Kaposi’s sarcoma: an update. J Surg Oncol. 2004 Sep 1;87(3):146-51. doi: 10.1002/jso.20090. PMID: 15334644
references – Moloney et al. Population based study of skin cancer incidence and prevalence in renal transplant recipients Br J Dermatol 2006
The image is consistent with Kaposi’s sarcoma. Other skin diseases (BCC, SCC, melanoma) should be investigated and biopsy with free margins and immunohistochemical study will help in the diagnosis. Severe and bilateral onychomycosis suggests important immunosuppression and potential future complications.
CNI suspension and switching to mTOR inhibitors will minimize tumor progression and have a direct antitumor effect. Less interaction with azoles (evaluate itraconazole with TDM for adequate adjuvant treatment).
Investigation of other foci (oral evaluation, upper digestive endoscopy, colonoscopy), visceromegaly, and other cutaneous and mucosal lesions.
Finally, biopsy the kidney and assess the risk of graft rejection to define further therapy. Aggressive evaluation of renal function and investigation of possible opportunistic infections.
What is your differential diagnosis?
Mostly a case of Kaposi sarcoma with onychomycosis of the nails
DD:
– SCC
– BSC
– Haemangioma
– Merkel cell carcinoma
How do you manage this case?
– Dermatology opinion for biopsy, staging, and management options (surgical excision, radiotherapy & chemotherapy)
– Staging of the disease by pan CTs, PET CT & endoscopes
– Baseline investigations: CBC, LFTs, CXR, ECHO
– Reduction of immunosuppression:
Ø Hold MMF, shift to sirolimus
Ø Here with a failing graft & low GFR & if there is no plan for retransplantation within one year, hold all immunosuppression could be considered .
· What is your differential diagnosis?
Kaposi sarcoma,
Cutaneous squamous carcinoma,
Angiosarcoma,
Bacillary angiomatosis, (caused by Bartonella species associated with sign /symptoms of fever, chills, malaise, headache, and anorexia).
Merkel cell carcinoma.
Benign vascular lesions.
Heamangioma.
· How do you manage this case?
Thorough history,
Thorough examination for extent and lymphadenopathy,
Dermatologist, oncologist, surgeon opinion,
Baseline investigation,
KoH from nail to confirm the fungal infection,
HHV-8 PCR for DNA sequencing,
For definitive diagnosis excisional biopsy for histological diagnosis,
Thorough radiological examination, if gut involvement need scopy.
Need antifungal tropical and systemic.
Staging the latest staging by AJCC for staging system for nodal involvement, metastasis (TNM).
Four stages 1, maculonodular stage, 2. Infiltrative stage, 3. Florid stage, 4. Disseminated stage.
Stage I & II are slow progression, fewer complication, while stage II and IV are aggressive disease with more dissemination and complications so would be needed more aggressive treatment accordingly.
No such eradicating treatment for human herpes virus infection.
The aim of treatment is achieving palliative care, improving function, preventing disease progression.
No consensus on systemic therapy.
However, there is no such cytotoxic chemotherapeutic agents have been approved for Kaposi sarcoma.
In addition, there are few drugs like PLD (paclitaxel, vinblastine, bleomycin. Chemotherapy with pegylated liposomal doxorubicin if no contraindication for cardiac.
Radiotherapy for extensive disease.
And for localized disease topical, cryotherapy, intralesional therapy, and excision.
· Substantiate your answer.
There is risk of denovo Kaposi sarcoma post-transplantation, however the skin involvement is more common. Visceral involvement has poor prognosis. Risk factors no eradication of HHV-8.
1. https://pubmed.ncbi.nlm.nih.gov/36334939/.
2. https://www.uptodate.com/contents/classic-kaposi-sarcoma-clinical-features-staging-diagnosis-and-treatment?search=kaposi%20sarcoma&source=search_result&selectedTitle=3~132&usage_type=default&display_rank=3.
3. https://www.uptodate.com/contents/aids-related-kaposi-sarcoma-staging-and-treatment/abstract/1.
4. https://pubmed.ncbi.nlm.nih.gov/24319170/.
What is your differential diagnosis?
1- Kaposi sarcoma is my main diagnosis, I will perform a biopsy for differential diagnosis of other cutaneous and lymphoproliferative neoplasms
In the setting of kidney transplantation and long-term exposure to immunosuppressive therapy 7 years, high level of Tac ) skin cancer should be suspected.
2- Melanoma
3- Angiosarcoma
4- Hemangioma
5- Pyogenic granuloma
6- Dermatofibroma
7- Nail fungal infection (onchomycosis)
How do you manage this case?
KS is an angio-proliferative cutaneous cancer caused by HHV 8
-The incidence is higher in transplant patients, the SIR is 17 in transplant population
-Generally, occurred 13 months after transplantation (range few weeks to 18 years)
-Dissemination to visceral mucosa of the trachea, lungs and gastrointestinal tract is common in immunosuppressed patient, develops in 25 to 30 percent of renal transplant recipients and 50 percent of heart or liver transplant recipients
-Mucosal dissemination or visceral involvement has usually a poor prognosis
Searching for visceral affection is important,
The majority of cases presents by skin and mucosal lesion and only 10 % presents with isolated visceral lesions
Around ¼ the cases have visceral involvement in the setting of renal transplantation; in contrary half of the patients have visceral involvement in liver and heart transplantation .
So, pan CT with contrast is indicated in all cases of KS
-The patient should be evaluated by a dermatologist and biopsy from the lesion is mandatory for confirmation of the diagnosis
-Complete clinical examination, including mucosal examination and ultrasound abdomen should be done (to assess the extent of lesions – for visceral involvement).
-The management includes confirmation of diagnosis by a biopsy from the lesion .
-The biopsy will reveal endothelial fusiform cells and neovessel formation.
-Immunohistochemical staining may show HHV-8 on endothelial cells.
The treatment includes Re-enforcement of behavioural interventions for sun-protection.
-Reduction of immunosuppression: The tacrolimus trough level in the patient is 8.3 ng/ml, which is high and should be reduced to 4-5 ng/ml.
-Switching of immunosuppression from Tacrolimus to mTOR inhibitors (Sirolimus)
Changing Tacrolimus to sirolimus
Checking PCR for HHV-8
Oncologist opinion for possible chemo and/or radiotherapy
Substantiate your answer?
The cornerstone to manage such patient is diagnosing the lesion by a biopsy, and then treatment by switching the immunosuppression from Tacrolimus to Sirolimus. Multidisciplinary approach with involvement of dermatologist and oncologist is essential.
•Alteration in immunosuppression has been shown to be associated with regression of the lesions.
Ithe lesions do not respond, then treatment would involve use of chemotherapeutic agents like liposomal pegylated doxorubicin, immune response modifier imiquimod, or radiotherapy, in case chemotherapeutic agents are contraindicated .
References:
Prof. Ahmed Halawa lecture, Post-transplantation lymphoproliferative disorders: Current concepts and future therapeutic approaches
Schwartz RA. Kaposi’s sarcoma: an update. J Surg Oncol. 2004 Sep 1;87(3):146-51. doi: 10.1002/jso.20090. PMID: 15334644.
Al-Adra D, Al-Qaoud T, Fowler K, Wong G. De Novo Malignancies after Kidney Transplantation. Clin J Am Soc Nephrol. 2022 Mar;17(3):434-443. doi: 10.2215/CJN.14570920. Epub 2021 Mar 29.PMID: 33782034; PMCID: PMC8975024.
Berman H, Shimshak S, Reimer D, Brigham T, Hedges MS, Degesys C, Tolaymat L. Skin Cancer in Solid Organ Transplant Recipients: A Review for the Nondermatologist. Mayo Clin Proc. 2022 Dec;97(12):235 -2368. doi: 10.1016/j.mayocp.2022.07.004. Epub 2022 Nov 3. PMID: 36334939.
Raedemaeker J, Marot L, Camboni A, Kanaan N. Kaposi sarcoma after kidney transplantation. BMJ Case Rep. 2019 May 5;12(5):e229681. doi: 10.1136/bcr-2019-229681. PMID: 31061183; PMCID: PMC6506100.
Sunil M, Reid E, Lechowicz MJ. Update on HHV-8-Associated Malignancies. Curr Infect Dis Rep. 2010 Mar;12(2):147-54. doi: 10.1007/s11908-010-0092-5. Epub 2010 Mar 26. PMID: 20461118; PMCID: PMC2860558.
Delyon J, Rabate C, Euvrard S, Harwood CA, Proby C, Güleç AT, Seçkin D, Del Marmol V, Bouwes-Bavinck JN,Ferrándiz-Pulido C, Ocampo MA, Barete S, Legendre C, Francès C, Porcher R, Lebbe C; Skin Care in OrganTransplant Patients Europe (SCOPE) group. Management of Kaposi sarcoma after solid organ transplantation: A Europea retrospective study. J Am Acad Dermatol. 2019 Aug;81(2):448-455. doi: 10.1016/j.jaad.2019.03.028. Epub 2019 Mar 19. PMID: 30902727.
Di Lorenzo G. Update on classic Kaposi sarcoma therapy: new look at an old disease. Crit Rev Oncol Hematol. 2008 Dec;68(3):242-9. doi: 10.1016/j.critrevonc.2008.06.007. Epub 2008 Jul 25. PMID: 18657433.
UpToDate
Differential Diagnosis
Kaposi sarcoma
Kaposi sarcoma (KS) is a tumor of endothelial cell origin associated with herpes human virus-8 (HHV-8) infection that occurs with increased frequency in the setting of immunosuppression.
Visceral involvement develops in 25 to 30 percent of renal transplant recipients and 50 percent of heart or liver transplant recipients
Merkel cell carcinoma (MCC) is a rare tumor of neuroendocrine origin that usually presents as a red or red-blue papule or nodule in a sun-exposed area
Cutaneous Squamous Cell Carcinoma
cSCC typically presents as a scaly, erythematous papule, nodule, or plaque within an area of actinic damage
Other lesions that may mimic the appearance of classic KS include bacillary angiomatosis and other infections, angiosarcoma, and benign vascular lesions, such as hemangiomas.
Management
Skin biopsy to confirm the diagnosis.In addition to observing typical histologic features on standard microscopy, polymerase chain reaction can be performed on the skin lesions to detect amplified human herpes virus 8 (HHV-8) DNA sequences, and immunohistochemical staining of biopsy specimens can also be performed to detect the presence of HHV-8 latency-associated nuclear antigen (LANA-1) within the spindle cells, thus confirming the diagnosis.
If confirmed Kaposi then search for visceral involvement in symptomatic patients should include GI endoscopy.
Staging — In contrast to acquired immunodeficiency syndrome (AIDS)-related KS, there is no commonly used or universally agreed upon staging system for classic KS.
A multidisciplinary approach is again needed
In view of already failing graft immunosupression can be with held
Treatment should revolve around local treatmet
Surgical and radiotherapy.
This picture showing multiple purplish brown maculopapular lesions of varying size.
The differential diagnosis with such skin lesions would include
1. non melanoma skin cancer (NMSC) – Kaposi Sarcoma.
2. infections like bacillary angiomatosis.
3. Melanoma.
The most probable diagnosis is non melanoma skin cancer (NMSC) – Kaposi Sarcoma.
The patient should be evaluated by a dermatologist with tissue biopsy for confiramtion.
Screening by examination and radiology (pan CT with contrast or PETCT) looking for metastasis.
The management should be done by Multidisciplinary approach with involvement of dermatologist and oncologist.
Reduction of immunosuppression or even stopping all immunosuppression in such advanced kidney disease (NB mTOR switching in such advanced kidney disease is not preferred) after proper counselling of the patient about he may develop AKI and ESRD he may need dialysis after stopping and he should be prepared.
If no response, then treatment would involve use of chemotherapeutic agents including doxorubicin, immune response modifier imiquimod.
References:
1. Schwartz RA. Kaposi’s sarcoma: an update. J Surg Oncol. 2004 Sep 1;87(3):146-51. doi: 10.1002/jso.20090. PMID: 15334644.
2. Al-Adra D, Al-Qaoud T, Fowler K, Wong G. De Novo Malignancies after Kidney Transplantation. Clin J Am Soc Nephrol. 2022 Mar;17(3):434-443. doi: 10.2215/CJN.14570920. Epub 2021 Mar 29. PMID: 33782034; PMCID: PMC8975024.
3. Berman H, Shimshak S, Reimer D, Brigham T, Hedges MS, Degesys C, Tolaymat L. Skin Cancer in Solid Organ Transplant Recipients: A Review for the Nondermatologist. Mayo Clin Proc. 2022 Dec;97(12):2355-2368. doi: 10.1016/j.mayocp.2022.07.004. Epub 2022 Nov 3. PMID: 36334939.
4. Raedemaeker J, Marot L, Camboni A, Kanaan N. Kaposi sarcoma after kidney transplantation. BMJ Case Rep. 2019 May 5;12(5):e229681. doi: 10.1136/bcr-2019-229681. PMID: 31061183; PMCID: PMC6506100.
5. Sunil M, Reid E, Lechowicz MJ. Update on HHV-8-Associated Malignancies. Curr Infect Dis Rep. 2010 Mar;12(2):147-54. doi: 10.1007/s11908-010-0092-5. Epub 2010 Mar 26. PMID: 20461118; PMCID: PMC2860558.
6. Delyon J, Rabate C, Euvrard S, Harwood CA, Proby C, Güleç AT, Seçkin D, Del Marmol V, Bouwes-Bavinck JN, Ferrándiz-Pulido C, Ocampo MA, Barete S, Legendre C, Francès C, Porcher R, Lebbe C; Skin Care in Organ Transplant Patients Europe (SCOPE) group. Management of Kaposi sarcoma after solid organ transplantation: A European retrospective study. J Am Acad Dermatol. 2019 Aug;81(2):448-455. doi: 10.1016/j.jaad.2019.03.028. Epub 2019 Mar 19. PMID: 30902727.
7. Di Lorenzo G. Update on classic Kaposi sarcoma therapy: new look at an old disease. Crit Rev Oncol Hematol. 2008 Dec;68(3):242-9. doi: 10.1016/j.critrevonc.2008.06.007. Epub 2008 Jul 25. PMID: 18657433.
Differential Diagnosis
· Kaposi sarcoma
· NMSC
· Fungal infection
· Hemangiomas
Management
Diagnostic work up including but not limited to infectious etiology, scans for malignancy(internal organs) and tissue biopsy.
· Stopped immunosuppressant’s MMF, reduce TAC and steroids if good residual urine output along with initiation of RRT if uremic feature.
· Stopped all Immunosuppressants if no residual urine output along with option of nephrectomy.
· Treatment according to labs Bx reports like anti-fungal agents, closed observation with reducing IS and surgical option.
Reference UpToDate.
This 65 year old patient with failing graft and GFR 15 on immunosuppressive drugs presented with skin lesion most probably skin cancer ( kaposi sarcoma )
Non melanoma skin carcinoma
Kaposi sarcoma
Infection including bacillary angiomatosis and fungal infection
Melanoma
Cavernous hemangioma
Purpic rash
Drug induced rash
Pyogenic granuloma
MDT including nephrologist,dermatologist,oncologist and surgeon
History and proper physical examination to exclude any other lesions or organomegaly….
This patient must be educated about the hazards of sun exposure and the of self examination
Labs including routine one must be done
Biopsy is required for definitive diagnosis.
To exclude Extracutaneous involvement neck ,chest ,abdomen and pelvis CT with upper and lower GIT endoscopy should be done
Decreasing the dose of tacrolimus to decrease it’s level on serum.Reduction of immunosuppression allows for the immune system to reduce viral replication producing clinical remission of disease. New antiviral agents have recently been introduced as a promising therapeutic option in patients with KS.
We also can stop all medication and keep this patient on prednisone 5 mg daily
Here the patient od GFR 15 so sirolimus is not indicated but generally Cutaneous KS lesions disappeared in all patients three months from the initiation of sirolimus therapy.Sirolimus may become the first choice immunosuppressant in renal transplant recipients with KS for pro-viding optimal immunosuppression and inhibiting the progression of malignancy.
radiation and chemotherapy may be considered in treatment.
This patient should be prepared for dialysis.
Kaposi’s Sarcoma after Kidney Transplantation: a 21-Years Experience
Dariyush Raeisi, Mehrdad Payandeh, […], and Amir Hossein Hashemian
Uptodate Classic Kaposi sarcoma: Clinical features, staging, diagnosis, and treatment
Kaposi sarcoma
Basal cell cancer
squamous cell carcinoma
Melanoma
Fungal infection involves the nails
MDT as to be evaluated by dermatologist and transplant physician and oncologist
Its need biopsy and histopathology
Shift calcinurine inhibitors to sirolimus
Continuous steroid dose
Tropical cream
Chemotherapy and radiotherapy after staging
Kaposi sarcoma is common after transplant and associated with HHV8.
Mainly occur in male and it’s management by reducing or cessation of immunosuppressive therapy and start mTOR inhibitors and avoid ultraviolet ray from sun exposure
Differential diagnosis:
Managment of the case:
References:
Skin cancer in organ transplant recipientsWerner Kempf 1, Kirsten D Mertz, Günther F L Hofbauer, Marianne Tinguely
Hassan NA, Abudayyeh A, Shah M, et al. The outcome of checkpoint inhibitor therapy in patients with cancer and solid organ transplant: a systematic review of the literature. J Clin Oncol 2018. 11 Au EH, Chapman JR, Craig JC, et al. Overall and site-specific cancer mortality in patients on dialysis and after kidney transplant. J Am Soc Nephrol 2019;30:471–80. 12 Martinez J-C, Otley CC, Stasko T, et al. Defining the clinical course of metastatic skin cancer in organ transplant recipients: a multicenter collaborative study. Arch Dermatol 2003;139:301–6. 13 Registry A. 38Th report, chapter 10: cancer. Adelaide, Australia.: Australia and New Zealand Dialysis and Transplant Registry, 20
1.What is your differential diagnosis?
This clinical picture is more likely of Kaposi Sarcoma.
Other differential diagnosis are:
Bacillary Angiomatosis
Hematoma
Hemangioma
Pyogenic granuloma
Purpura
How do you manage this case?
-Detail medical history, a complete inspection including the visible mucous membranes as well as palpation of the lymph nodes and the abdomen with recording of all lesions and symptoms are part of the (initial) examination.
-Dermatological consultation and lesion biopsy.
-All KS patients without known HIV infection should be offered HIV testing at initial KS diagnosis.
– Further investigation should be individualized based on disease dissemination, symptoms, course, and KS subtype.
– In the case of (suspected) visceral KS involvement, a whole-body computed tomography (CT: thorax, abdomen/pelvis) should be performed. If necessary, esophagogastro-duodenoscopy, colonoscopy, and bronchoscopy may also be performed.
-Post-transplantation Kaposi sarcoma commonly responds to reduction or discontinuation of immunosuppression. However, this approach may not always be feasible and can place patients at risk for graft rejection.
-Switching from calcineurin inhibitors ( tacrolimus) to a mammalian target of rapamycin (mTOR) inhibitor, specifically sirolimus.
– Chemotherapy is commonly reserved for limited disease refractory to local therapy or in patients with disseminated disease.
-Monitor graft function.
References:
1.Barete S, Calvez V, Mouquet C, Barrou B, Kreis H, Dantal J, et al. Clinical features and contribution of virological findings to the management of Kaposi sarcoma in organ-allograft recipients. Arch Dermatol. 2000 Dec. 136 (12):1452-8. [QxMD MEDLINE Link].
2.Stefan Esser, Helmut Schöfer et al. S1 Guidelines for the Kaposi Sarcoma.JDDG. 03 June 2022 https://doi.org/10.1111/ddg.14788
The differential diagnosis ;
——————————————————–
1-Kaposi sarcoma (KS)
2-SCC
3-BCC
4-melanoma
How do you manage this case?
———————————————–
1-Multidisciplinary approach to care;
A multidisciplinary approach, with nephrologists, dermatologists and oncologists, is required for the treatment of this case .
2-Diagnosis and staging ;
1-Obtain a complete history and perform a physical examination, paying specific attention to sites of prior skin cancers and palpating the regional nodal basin for high-risk skin cancers.
2-Obtain skin biopsy plus immunohistochemistry to confirm the diagnosis of KS.
3-CT scan to exclude visceral involvement ( in this case consider the risk for contrast nephropathy is high ) +endoscopy .
3-Graft unction ;
Should be assessed by the transplant physician .The decreased GFR in this patient plays an important role in treatment plan .
4-Treatment of Kaposi’s sarcoma in kidney transplant patients includes ;
1-immunosuppression reduction as a first step.
2-Switching immunosuppressive therapy to sirolimus or other mTOR inhibitors is another option.
3- In patients without good response,chemotherapy or radiotherapy are additional options.
Substantiate your answer.
—————————————————————
The incidence of Kaposi’s sarcoma in kidney transplanted patients is increased, but in the majority of patients, the disease involves only the skin . The visceral involvement carries a poor prognosis. Recurrence is frequent and associated with the increase of immunosuppression.
The risk factors for development of Kaposi’s sarcoma in kidney transplanted patients includes ;
1-Patients with persistent infections with oncogenic viruses, such as human herpes virus 8 .
2- Patients with black skin, even in European series .
Kaposi’s sarcoma is diagnosed with skin biopsy and immunohistochemistry. CT scan and endoscopy to rule out visceral involvement .
Reduction in immunosuppression is the cornerstone of management in transplant-associated KS and is often adequate in treating cutaneous-limited disease. However, any reduction in immunosuppression must be balanced with the risk of allograft loss from rejection.
Switching the more oncogenic immunosuppressants (particularly calcineuirin inhibitors) for an mTORi has become a commonly accepted management strategy.
There are no guidelines recommending which chemotherapeutic agent to use in disseminated transplant-associated KS. Treatment decisions are typically based off safety and efficacy data extrapolated from AIDS-related and classic KS cohorts with disseminated disease.
Reference ;
——————————–
!- MA Anderson · 2021 · Kaposi’s sarcoma is an uncommon complication in renal transplant patients, and typically presents with cutaneous lesions on the lower …
2-EK Cahoon · 2018 Due to treatment with immunosuppressive medications, solid organ transplant recipients have elevated risk for Kaposi sarcoma (KS), …
3-R Torres-Serrano · 2022 — Introduction: Kaposi sarcoma in post–renal transplantation patients is a rare entity, usually associated with herpes 8 infection
5. A 65-year-old kidney transplant recipient developed this lesion 7 years after his cadaveric transplantation. Currently, he is on Tacrolimus (trough level 7.4 ng/ml) and MMF 750 mg bd. He has poor kidney function (eGFR is 15 ml/min) due to cAMR.
What is your differential diagnosis?
– Most probable diagnosis – Kaposi sarcoma (KS) with onychomycosis
– Other differential diagnosis include: –
o Bacillary angiomatosis
o Melanoma
o Hemangioma
o Pyogenic granuloma
o Dermatofibroma
How do you manage this case?
– Detailed history and thorough physical examination
– Baseline investigations: – CBC, kidney function test, liver function test, HIV test
– Perform a skin biopsy plus immunohistochemistry to confirm the diagnosis of KS.
– Examine for mucosal involvement and screen for visceral involvement – abdominopelvic and chest CT scans, endoscopy, colonoscopy, bronchoscopy
– Sun-protection i.e., wear sunscreen SPF30+, avoid sun exposure between 11am and 4pm, wear sun protective clothing, hat, sunglasses
– Encourage patient to perform the regular skin checks i.e., monthly skin self-examination and report any new lesions to the doctor.
– Multidisciplinary approach – oncologist, dermatologist, nutritionist (renal dietitian), counsellor among others
– Consider reduction of immunosuppressive therapy aiming for a tacrolimus trough level of 3-5ng/mL (since he is 7years post kidney transplant), further reduce MMF to 500mg BD and maintain low-dose steroid. Patient should be informed/ counseled about the poor graft function.
– mTORi is not a favourable option given the current eGFR
– The patient requires kidney replacement therapy since his graft is failing. So, he should be counseled and prepared for possible hemodialysis by fashioning an AV-fistula as well as advised on getting another kidney donor.
– The other complications associated with end stage kidney disease should be addressed i.e., anaemia, mineral bone disorder, metabolic acidosis
– In extensive disease – liposomal anthracyclines are considered as 1st line therapy.
– Chemotherapy (vincristine, vinblastine, doxorubicin, bleomycin) and local radiotherapy – helps improve the lesions
– Remission can be confirmed histologically by doing a repeat biopsy
– Ganciclovir, foscarnet and cidofovir – if HHV seropositive
Substantiate your answer (1-4)
1. Campistol JM, Schena FP. Kaposi’s sarcoma in renal transplant recipients–the impact of proliferation signal inhibitors. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association – European Renal Association. 2007 May;22 Suppl 1:i17-22. PubMed PMID: 17456614. Epub 2007/04/26. eng.
2. Raeisi D, Payandeh M, Madani SH, Zare ME, Kansestani AN, Hashemian AH. Kaposi’s Sarcoma after Kidney Transplantation: a 21-Years Experience. International journal of hematology-oncology and stem cell research. 2013;7(4):29-33. PubMed PMID: 24505540. Pubmed Central PMCID: PMC3915423. Epub 2014/02/08. eng.
3. Stallone G, Schena A, Infante B, Di Paolo S, Loverre A, Maggio G, et al. Sirolimus for Kaposi’s sarcoma in renal-transplant recipients. The New England journal of medicine. 2005 Mar 31;352(13):1317-23. PubMed PMID: 15800227. Epub 2005/04/01. eng.
4. Al-Adra D, Al-Qaoud T, Fowler K, Wong G. De Novo Malignancies after Kidney Transplantation. Clinical journal of the American Society of Nephrology : CJASN. 2022 Mar;17(3):434-43. PubMed PMID: 33782034. Pubmed Central PMCID: PMC8975024. Epub 2021/03/31. eng.
Dear All
Thanks for the guidance Dr Ahmed Halawa especially about failing kidney and liberty to start mtor
1-What is your differential diagnosis?
Kaposi sarcoma (KS) is an angioproliferative disorder
iatrogenic (a type associated with immunosuppressive drug therapy, typically seen in renal allograft recipients)
Other lesions that may mimic the appearance of classic KS include
bacillary angiomatosis and other infections,
angiosarcoma, and benign vascular lesions, such as hemangiomas.
Bacillary angiomatosis is caused by the Bartonella species, a slow-growing, fastidious, gram-negative bacillus, and is readily treated with antibiotic therapy. The skin lesions of bacillary angiomatosis usually appear as numerous, small, red to purple papules that may gradually expand into large pedunculated lesions or nodules that may become friable. The rash may be associated with symptoms such as fever, chills, malaise, headache, and anorexia.
Sporothrix schenckii (sporotrichosis) and Mycobacterium marinum skin infections could also be confused with the nodular form of KS.
2-How do you manage this case?
Biopsy on standard microscopy, polymerase chain reaction can be performed on the skin lesions to detect amplified human herpes virus 8 (HHV-8) DNA sequences, and immunohistochemical staining of biopsy specimens can also be performed to detect the presence of HHV-8 latency-associated nuclear antigen (LANA-1) within the spindle cells, thus confirming the diagnosis.
Radiographic evaluation
.
TREATMENT
Rapamycin – A single case report described KS regression after 16 weeks of topical treatment with rapamycin (sirolimus)
mTOR inhibitors – Case reports describing regression of classic KS in patients treated with the mTOR inhibitor rapamycin (sirolimus) suggest that this approach, which has proven effective in some cases of transplant-associated KS, may be more generally applicable. Another member of this class of drugs, everolimus, has been used successfully to treat KS in transplant recipients; the reported experience with this agent in classic KS has been scant and mixed.
3-Substantiate your answer.
Elimination tacrolimus are excreted in the bile. . Liver dysfunction prolongs the half-life of both cyclosporine and tacrolimus
The side effects of tacrolimus
Nephrotoxicity which is largely reversible after reducing the dose, or as chronic occasionally progressive kidney disease, which is usually irreversible.
Hypertension
Neurotoxicity
Glucose intolerance and diabetes mellitus
Hyperlipidemia
Hyperuricemia and gout
Hyperkalemia
Hypomagnesemia
Risk of malignancy — Both cyclosporine and tacrolimus are associated with an increased risk of squamous cell skin cancer and benign or malignant lymphoproliferative disorders. Spontaneous regression of lymphoma may occur if the drug is discontinued early.
CONTRAINDICATIONS
Concurrent malignancy (except for nonmelanoma skin carcinoma)
Uncontrolled hypertension
Uncontrolled infections
TREATMENT OF CHRONIC ANTIBODY-MEDIATED REJECTION
Chronic ABMR, the most common cause of graft failure, is more difficult to treat than active ABMR since irreversible tissue damage has already occurred to the kidney allograft
For patients with chronic ABMR, we suggest initial therapy with glucocorticoids and intravenous immune globulin (IVIG) rather than other therapies. In addition, some experts administer rituximab if the patient is younger (eg, age <70 years), has better allograft function (eg, estimate glomerular filtration rate [eGFR] ≥20 mL/min/1.73 m2 and lower chronicity scores on biopsy [ie, interstitial fibrosis + tubular atrophy + fibrous intimal thickening + allograft glomerulopathy <8]), and has evidence of severe disease (eg, higher donor-specific antibodies (DSA), diffuse C4d staining, or more extensive microvascular inflammation [ie, glomerulitis score + peritubular capillary score ≥4] on biopsy)
PTLD is suggested by a diffuse lymphocytic infiltrate of such severity that it is difficult to visualize tubular architecture, which can occasionally be observed in patients with severe T cell-mediated rejection (TCMR) (frequently secondary to noncompliance with immunosuppression).
Since the treatment options for rejection and PTLD are markedly different, additional studies must be performed to differentiate the two possibilities. Studies include special stains for T and B cell populations, Epstein-Barr virus (EBV) antigens, and monoclonal light chains, as well as quantitative EBV polymerase chain reaction (PCR) and serum and urine protein electrophoresis.
Imaging of the graft should also include the abdomen, pelvis, and any other clinically relevant areas
Detection of specific cell markers for T cells, B cells, plasma cells, and monocytes may also be useful to guide rejection therapy in the setting of a significant cellular infiltrate with graft dysfunction.
REFERENCES uptodate
Thank you
1-DD:
Kaposi sarcoma: most likely with this pigmented skin lesions in high immunosuppression and 7-years post renal tx.
other DD:
SCC
BCC
melanoma
in addition : nail fungal infection (onchomycosis)
II- Management:
avoid sun exposure, skin protective measures and self examination.
Differential diagnosis:
· Kaposi sarcoma is the most possible diagnosis
· Squamous cell carcinoma
· Basal cell carcinoma
· Melanoma
-With onychomycosis
Management:
· Diagnosis should be confirmed by biopsy and histopathology.
· Multi disciplinary approach needed.
· Reduction of immunosuppression, discontinuation of antimetabolite, switching from CNI to mTOR inhibitor.
· Preventive measure by avoiding excess immunosuppression, repeated exposure to antilymphocyte drugs and regular careful screening.
· Diagnosis of onychomycosis by nail scraping and treat accordingly with systemic and topical antifungals, laser, PDT, and surgery.
This patient’s GFR is 15ml/min; so main stay of treatment is reduction of immunosuppression and plan for dialysis treatment.
Reference:
UpToDate
DEAR ALL ,DO YOU THINK MENTIONING THE POOR GRAFT FUNCTION WITH A GFR OF 15 DUE TO cAMR HAS A SIGNIFICANCE IN MANAGEMENT PLAN.
Imapired graft function will support the decision of immunosuppression reduction and the possibilities of resuming dialysis
Yes prof: 2 plans
Dialysis and no option for re-transplantation:
Re-transplantation:
Yes, plan for renal replacement therapy in the form of hemodialysis.
Yes, it has a significance in the patient’s management plan.
It helps decide on the goals of treatment i.e.,
– need to reduce the immunosuppressive therapy
– discuss with the patient the kidney replacement therapy (KRT) options i.e., hemodialysis, possible re-transplantation after a prespecified waiting period
– prepare and counsel the patient for HD i.e., place an AV fistula to allow for maturation
– management of complications related to chronic graft dysfunction i.e., hyperkalemia, metabolic acidosis, anaemia, CKD-MBD
– offer dietary advise (renal diet)
– ensure the patient understands that graft loss at this stage is inevitable
What is your differential diagnosis?
These are pigmented skin lesions with raised edge and a form of coalescent patches. Kaposi sarcomais the most likely diagnosis considering 7years post-transplant and high level of immunosuppression beside characteristic of the skin lesion.
Other differentials are:
· SCC.
· BCC.
· Bacillary angiomatosis.
· Melanoma
· Haemangioma.
How do you manage this case?
· MDT; including transplant nephrologist, pathologist, plastic surgeon, dermatologist and oncologist.
· Detailed history and relevant clinical examination.
· CBC, LFT, RFT, blood sugar, LDH, virology screening for HHV-8 and HIV.
· Skin biopsy; For a definitive diagnosis of Kaposi sarcoma, biopsy or excision of the suspicious areas must be performed. A pathologist examines the tissue under the microscope and looks for the characteristic features: a spindle cell vascular proliferation in the dermis.
· Immunohistochemistry positivity for LANA1 (a surrogate marker for HHV-8) helps to differentiate Kaposi sarcoma from similar lesions(1).
· Management options:
a. Decreasing the intensity or switching immunosuppressive agents to an mTOR inhibitor is the cornerstone of treatment.
b. Skin involvement of Kaposi sarcoma is treated by local excision, liquid nitrogen, and injection of vincristine(2).
c. Chemotherapy is a mainstay of treatment for endemic and systemic forms, in particular in children(3).
d. Other therapeutic strategies could rely in targeting signaling pathways important for HHV8 de novo infection, reaction, cell persistence or cellular pathways activated by viral pirated genes such as the mitogen-activated protein kinase or the PI3 kinase pathway. Rapamycin, a mammalian target of rapamycin inhibitor located downstream the PI3 kinase, has already proven of benefit and should be discussed in all post-transplant KS(4).
· Advice regarding post-transplant behavioral intervention to minimize the risk of recurrence and other skin cancers:
a) Protective sunscreen and clothes.
b) Avoiding direct sunlight at the peak hours.
c) Doing routine self-examination of the skin for early detection of skin lesions or recurrence.
References
1. NIH;National Library of Medicine Kaposi Sarcoma Bradie N. Bishop; David T. Lynch. Last Update: June 11, 2022.
2. Kaplan LD. Human herpesvirus-8: Kaposi sarcoma, multicentric Castleman disease, and primary effusion lymphoma. Hematology Am Soc Hematol Educ Program. 2013;2013:103-8.[PubMed] [Reference list]
3. Fatahzadeh M. Kaposi sarcoma: review and medical management update. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012 Jan;113(1):2-16. [PubMed] [Reference list]
4. Lebbé C, Legendre C, Francès C. Kaposi sarcoma in transplantation. Transplant Rev (Orlando). 2008 Oct;22(4):252-61. doi: 10.1016/j.trre.2008.05.004. Epub 2008 Jul 24. PMID: 18656341.
Thankyou Assafi but protective measures are for OTHER skin cancers.!
DIFFERENTIAL DIAGNOSIS.
KS
Onychomycosis
Bacillary angiomatosis.
Dermatofibroma.
Hemangioma.
Purpura
RISK FACTORS FOR KS IN OUR CASE;
7 YRS Post transplant.
65 yrs old patient.
High Immunosuppressive doses 7 yrs post transplant.
White pt ,possibly Mediterranean origin.
Unknown sero-status.
MANAGEMENT;
-MDT approach – An Oncologist, Nephrologist and Dermatologist to be involved from the very onset in evaluating this patient.
INVESTIGATIONS.
-Do baseline investigations – FHG, RBS, Lipids profile, UECS,LFTS,URIC ACIDand LDH to assess other organ involvement, long term side effects of immunosuppressive medications and establish the general state of the patient before we start treatment. An occult blood will be important in this case to screen for any GI involvement.
-Assess other risk factors or diseases emanating post transplant from over immunosuppression that could impact negatively on the graft -HIV status,HHV8 PCR/VIRAL load, CMV PCR,EBV Status.
-Do other tests to check out for mets- CXR – Non specific and could show non specific interstitial infiltrates, effusions or even pulmonary nodules, Thoraco abd CT scan, Endoscopy and Bronchoscopy where needed to look out for and biopsy for histological diagnosis any suspicious lesions.
-A skin biopsy of the lesion will be important for a definitive diagnosis, we expect spindle shaped cells with prominent slit like vascular spaces.
-Assess complications of ESRD- serum Ca,Pho,PTH,bicarbonate levels, and iron studies.
SUPPORTIVE MGT;
-Nutritional review.
-Counselling on graft dysfunction, malignancies post transplant and future renal replacement options including going back to hemodialysis from graft dysfunction.
-Use of sunscreen and minimize sun exposure, use of sunscreen, SPF 50+ to get protection from UVB and UVA rays. T o use appropriate clothing including hats when exposed to the sun,.
DEFINITIVE MGT.
-Reduction of immunosuppressive medication will decrease the aggressiveness of the malignancy. We would decrease CNI to 3-5 ng/ml considering we are 7 years post transplant, decrease antimetabolite and maintain steroid. There has to be a balance to avoid loss of graft from rejection due to under dosing of the immunosuppressive medication.. MTOR inhibitors will be preferred to tacrolimus but with the low EGFR, it would not be appropriate in our set up.
-For KS depending on staging, we could use chemotherapy (Vincristine or vinblastine, bleomycin and doxorubicin singly or in combination in those with systemic disease),Other chemo drugs; Etoposide and Cisplatin. Topical Imiquimod and retinoids could be used for localized lesions. SX excision with wide margins could be used for solitary lesions. Antivirals esp Ganciclovir could be applied if HHV 8 turns out positive.
-Considering Graft dysfunction, we could fashion an AVF in preparation for dialysis. Other elements of ESRD should also be addresses, e.g Sodium bicarbonate supplementation, diuretics use, EPO + Iron supplementation and an appropriate diet.
-Once we initiate dialysis, pt will be maintained on low dose immunosuppression possibly steroids to minimize sensitization in preparation of future transplantation,pt will equally be advised to wait 2-5 yrs post treatment depending on disease stage before evaluation for the next transplant is made.
SUBSTANTIATE ANSWERS.
1.Prof Halawa lecture on Post transplant Malignancies.
2.Schwartz RA et al. Kaposi Sarcoma- An update.J Surg Oncol.2004.Sep 1;87(3);146-51
3.Francesco P et al – Conversion from CNI to sirolimus maintenance therapy on renal allograft recipient;24 months safety and efficacy resulting from CONVERT Trial.Transplantation.2009 Jan 27;87(2);233-42
4.UPtodate – Epidemiology, presentation, diagnosis and management of Kaposi Sarcoma.
Well done.
Skin lesions such as this in an immune-compromised patients can be Kaposi sarcoma, basal cell carcinoma or Sq cell Ca (SCCs).
Excision biopsy is essential and accordingly, therapy can be decided.
Treatment of SCCs
Surgical procedures that provide pathologic confirmation of complete tumour removals, such as Mohs surgery or conventional surgical excision with margin control, are the preferred treatments for invasive SCCs in these patients to prevent local recurrence and disease spread.
Basal cell carcinoma The management of BCC in this population resembles management in immunocompetent patients.
Imiquimod is a topical immunostimulatory agent that is sometimes used for the treatment of superficial BCC. The use of imiquimod for limited periods on small areas (60 to 100 cm2) appears to be safe in organ transplant recipients.
Kaposi sarcoma — Reducing the level of immunosuppression is the primary therapy for Kaposi sarcoma in organ transplant recipients. In addition, regression of Kaposi sarcoma has been reported in renal transplant patients after a change in immunosuppressive medication from cyclosporine to sirolimus. Local and systemic therapies may also be used in the management of these patients.
This particular patient has stage 5 CKD. I will reduce his immune suppressants. I will aim tacrolimus at a minimum level, and I will switch MMF to mTOR I and watch the skin lesions after confirming the type of malignancy.
Reference:
Prevention and management of skin cancer in solid organ transplant recipients. UpToDate
Well done.
In the current scenario of immunocompromised patient on longstanding CNI based immunosuppression, Differential diagnosis: Kaposi sarcoma and diagnosis can be proved easily with skin biopsy.
The incidence of Kaposi sarcoma in recipients of transplants exceeds 100 times that of the general population.
How do you manage this case?
Patients treated with CNIs are at high risk for Kaposi sarcoma. Decreasing the intensity or switching immunosuppressive agents to an mTOR inhibitor is the cornerstone of treatment. In the current scenario with poor renal graft function we can switch to mTOR inhibitors provided that ,there is no significant proteinuria. Regression of Kaposi sarcoma has been reported after switching from calcineurin inhibitors to sirolimus by restoring effector and memory T-cell immune activity against human herpesvirus 8
References:
Sunil M, Reid E, Lechowicz MJ: Update on HHV-8-associated malignancies. Curr Infect Dis Rep 12: 147–154, 2010
Remember mTOR is not given if GFR is below 30 which is a problem in this case.
What is your differential diagnosis?
The above image showing dorsum of hand with brownish violet raised circumscribed nodules and plaques of various sizes in an immunocompromised renal transplant patient-likely Kaposi sarcoma.Other differentials which need to be considered include :.
Angiosarcomas
Haemangiomas
Pyogenic granuloma
fungal nail infection
How do you manage this case?
MDT should be involved including dermatologist,transplant physician ,psychologist and oncologist.Detailed examination from head to toe including general physical examination [mucous membranes ,lymph nodes also]abdominal examination for organomegaly,chest and neurological examination.Laboratory investigations include complete blood picture ,inflammatory markers ,LDH,HIV and HHV-8 serology,CT scan abdomen pelvis,brain and chest followed by upper and lower GI endoscopy if needed.Skin biopsy with IHC of the lesion.
First strategy in the treatment is reduction if immunosuppression followed by switch of CNI to mTOR-if there is no response then specific treatment for kaposi sarcome like radiotherapy ,Intralesional chemotherapy, cryotherapy ,laser therapy may be needed.Supportive treatment include counseling for need of hemodialysis later or retransplantation ,avoidance of sun exposure and applying sunscreens.
Substantiate your answer.
1-Al-Adra D, Al-Qaoud T, Fowler K, Wong G. De Novo Malignancies after Kidney Transplantation. Clin J Am Soc Nephrol. 2022 Mar;17(3):434-443. doi: 10.2215/CJN.14570920. Epub 2021 Mar 29. PMID: 33782034; PMCID: PMC8975024.
2-Lecture of Prof. Ahmed Halawa, 2023.
3- Euvrard S, Kanitakis J, Bosshard S, et al.. No recurrence of posttransplantation Kaposi’s sarcoma three years after renal retransplantation. Transplantation. 2002 Jan 27;73(2):297-9
Are there limitations for mTOR inhibitors in this case.
Differential diagnosis:
In the setting of immunosuppressed transplant patient, the likely diagnosis is Kaposi sarcoma, differential include haemangioma.
Management:
History and physical examination to look for similar lesions, mucosal, lymph node and visceral involvement
Dermatology consultation and biopsy of the lesion. (IHC, HHV8 PCR)
CT TAB +/- OGD, colonoscopy, bronchoscopy to look for visceral involvement
Laboratory investigation
If lesion confirmed to be KS, then reduction of immunosuppression, aim for Tac level of 3-5, switch CNI to mTORI, if no response consider chemotherapy
Monitor graft function, counselling about risk of graft loss with RIS, close monitoring of renal function and early referral to low clearance clinic.
MDT
Thankyou
What is your differential diagnosis?
Kaposi sarcoma of the skin which is angioproliferative cutaneous cancer which caused by HHV8 appeared as red-purple skin lesion in the form of papule or nodular shape.
The mean interval to diagnosis is 13 months.
Visceral involvement develops in 25 to 30 percent of renal transplant recipients.
How do you manage this case?
1-Multidisciplinary team care should be applied (dermatologist , transplant nephrologist, oncologist, social worker, dietitian, clinical psychologist, and others).
2-HIV and HHV8 screening.
3-Biopsy is required for definitive diagnosis.
4-Reduction of immunosuppression specially with low GFR, with high GFR >30 we could shift CNI to mTORis.
4-Local therapy such as (Surgery, Radiation therapy, Cryotherapy and laser therapy, and Intralesional therapy ).
5- Chemotherapy.
Substantiate your answer.
1- Classic Kaposi sarcoma: Clinical features, staging, diagnosis, and treatment, UP TO DATE 2022.
2- Brenner B, Rakowsky E, Katz A, et al. Tailoring treatment for classical Kaposi’s sarcoma: comprehensive clinical guidelines. Int J Oncol. 1999;14(6):1097-1102. doi:10.3892/ijo.14.6.1097.
3- Tombolini V, Osti MF, Bonanni A, et al. Radiotherapy in classic Kaposi’s sarcoma (CKS): experience of the Institute of Radiology of University “La Sapienza” of Rome. Anticancer Res. 1999;19(5C):4539-4544.
4- Tappero JW, Berger TG, Kaplan LD, Volberding PA, Kahn JO. Cryotherapy for cutaneous Kaposi’s sarcoma (KS) associated with acquired immune deficiency syndrome (AIDS): a phase II trial. J Acquir Immune Defic Syndr (1988). 1991;4(9):839-846.
5- Guenova E, Metzler G, Hoetzenecker W, Berneburg M, Rocken M. Classic Mediterranean Kaposi’s sarcoma regression with sirolimus treatment. Arch Dermatol. 2008;144(5):692-693. doi:10.1001/archderm.144.5.692.
Thankyou
post transplant Kaposi sarcoma purple-red-bluish maculopapular plaques .
Bacillary angiomatosis
Squamous cell carcinoma
Melanoma
Hemangioma
Dermatofibroma
Pyogenic granuloma
Management:
need full and MTD assessment
need to do all the rutine investigations first thn he will need to do punch biospy and histological classifications .
he will need Pan CT to see if he has any VISERAL involvement as well .
Post-transplantation Kaposi sarcoma commonly responds to discontinuation of immunosuppression, and shifting the patient to M-TOR.
This patient also has ONychomicosis which need further work up including scraping and further managment .
This patient eGFR IS 15ml/mint and we need to discusse with him that reducing IS theraby may subject him to acute on top of CAMR and he may need to go for dialysis.
references
uptodate
–Differential diagnosis
Post transplant Kaposi sarcoma purple-red-bluish maculopapular plaques .
Bacillary angiomatosis
Squamous cell carcinoma
Melanoma
Hemangioma
Dermatofibroma
Pyogenic granuloma
Purpura
Management
Kaposi sarcoma
· An MDT has to be involved ,including dermatologist and an oncologist besides the transplantation team
· The general condition of the patient has to be fully assessed and punch biopsy is needed from the lesions and then for histopathological evaluation and Kaposi detection and staging which will decide for the treatment
· HHV 8 viral load assessment
· CT scans of the chest, abdomen, pelvis; or PET/CT to detect lymphadenopathy, visceral masses, splenomegaly, effusions, or bone lesions
· Upper GIT endoscopy ,colonoscopy and bronchoscopy
· post-transplantation Kaposi sarcoma commonly responds to discontinuation of immunosuppression (Tac and MMF) which has to be stopped and prepare the patient with an AV Fistula for dialysis as it seems that the graft failed due to CAMR with GFR 15 ml/min .
· Dissemination to visceral mucosa of the trachea, lungs and GIT is common in immunosuppressed patients.
· Mucosal dissemination or visceral involvement has usually a poor prognosis
• Local therapy include radiotherapy ,Intralesional chemotherapy, cryotherapy ,laser therapy.
· Chemotherapy is reserved for limited disease refractory to local therapy or for disseminated disease.
Onychomycosis
· KOH examination is needed to be done from an incisonal biopsy of the affected nail for confirmation of onychomycosis.
· For onychomycosis therapy a combination of systemic treatment in the forum of oral antifungal agents with renal adjusted doses and topical treatment along with laser therapy increases the cure rate.
· Surgical approaches to onychomycosis treatment include mechanical, chemical, or surgical nail avulsion.
Reference
– Raedemaeker J et al. Kaposi sarcoma after kidney transplantation.BMJ Case reports 2019;12:e229681
-Katz J .Kaposi sarcoma treatment and management .Medscape 2022
-Lee K. J .et al. Proximal Subungual Onychomycosis in a Patient with Classic Kaposi Sarcoma Caused by Trichophyton rubrum.Ann Dermatol2011, 23(S1) S11∼S15.
-Tosti A.Onychomycosis Guidelines.Medscape 2020
Well done.
1-What is your differential diagnosis?
-Kaposi sarcoma (most likely)
-Haemangioma with bruises
-Angiosarcoma
-Fungal nail infection
-Calciphylaxis
Risk factors for Kaposi Sarcoma:.
-The intensity and duration of immunosuppression
-The presence of HHV8 -HIV
-Male gender -Non-White patients
-Mediterranean origin Jewish, Arabic, Caribbean, or African descent parallels HHV-8 seroprevalence
-Lung transplant recipients were at increased risk of KS.
2-How do you manage this case?
A-Work up for this lesion required;
-CBC, Virology, Serology of HHV-8-PCR, HIV,CMV,EBV,
-Skin Biopsy of skin lesion.
B-Searching for visceral affection;
-So pan CT with contrast is indicated in all cases of KS (will be a problem in the current case due to renal impairment)
-Upper and Lower GIT Endoscopy
-Bronchoscopy
C- Dermatology consultation; and biopsy from the lesion is mandatory for confirmation of the diagnosis.
D- Treatment;
-Reduction of immunosuppression is associated with regression IN 17% of cases of KS,
-FK level in the current patient is (7.4) which is above the target in a patient with renal transplant for 7 years, so tacrolimus dose can be reduced maintain trough between 3-5 ng/l.
-The ideal treatment is to shift from CNI to sirolimus if not contraindicated with is associated with complete resolution within 3-6 months of conversion,
-But in the current case sirolimus cannot be used due to severe renal impairment (eGFR 15 ml/min)
-So in the current case if the biopsy confirmed Kaposi sarcoma, to stop antimetabolite and reduce tacrolimus dose to keep a target between 3-5ng/ml.
-If no resolution after reduction of immunosuppression, Chemotherapy may be offered to patients with diffuse and symptomatic disease .
-In this patient with chronic ABMR and for possible PAN CT Scan with IV contrast pt most probably he will lose his graft up on reduction of immunosuppression so, he may require initiation of RRT if indicated.
3-Substantiate your answer.
1-Schwartz RA. Kaposi’s sarcoma: an update. J Surg Oncol. 2004 Sep 1;87(3):146-51. doi: 10.1002/jso.20090. PMID: 15334644.
2-American cancer society cancer.org | 1.800.227.2345.
3-Aseni P, Vertemati M, Minola E, et al. Kaposi’s sarcoma in liver transplant recipients: morphological and c Francès C. Kaposi’s sarcoma after renal transplantation. Nephrol Dial Transplant 1998; 13:2768
Exellent.
What is your differential diagnosis?
Squamous cell carcinoma
Basal cell carcinoma
Kaposi sarcoma
Merkel cell carcinoma
Melanoma
How do you manage this case?:
· Detailed history and examination
· laboratory investigation:
· CBC ,CRP.
· Viral screen : EBV.CMV .BK virus ,liver function test
· Urine analysis . and imaging to detect any metastases
· skin biopsy
Kaposi sarcoma is a disease of the endothelial cell of blood vessels and lymphatic system .
KS is a common long term complication post kidney transplant .
Treatment :
Ø MODIFIED IMMUNOSUPRSSANT MEDICATION
1.Start PSI (Proliferation Signal Inhibitor ) sirolimus
2-Stop CNI (Calcinuerin inhibitor )
3- Minimized AZAl MMF Maintain steroid
4-Monitor disease if no response high dose of PSI
Ø Radiotherapy
Ø Chemotherapy .
Ø Ganciclovir in case of HHV seropositive .
References :
handbook of kidney transplant 6th edition
GFR !?
The lesion on the dorsal surface of the patient shows multiple purplish, reddish blue macules and a plaque that is fleshy looking in appearance. The nails are hyper keratinized
What is my differential diagnosis?
How do we manage this condition – Kaposi sarcoma
A multidisciplinary team of dermatologists, surgeons, oncologists, and transplant nephrologists will be consulted
a) Investigations
b) Treatment
The aim of therapy is to alleviate symptoms and slow disease progress as no treatment is available to eradicate HHV-8 infection.
Substantiate your answer
GFR 15!!
Thank you, prof Dawlat for the response.
I will like to withdraw the use of treatments like radiation therapy, and a combination like vincristine, doxorubicin, bleomycin, and actinomycin in view of stage 5 CKD as these medications will worsen renal function.
Thank you.
excisional biopsy to confirm the diagnosis, histology revealed the fusiform cells of endothelial organs and neovessels.
immunohistochemical showed positive.
CXR, CT scan for chest abdomen, and pelvis
others such as Upper GIT endoscopy, colonoscopy, and bronchoscopy
labeling of erythroblast transformation-specific related gene ERG and HHV-8.
chemotherapy based on doxorubicin, cessation of MMF, and switching TAC to sirolimus.
References
O. Michielin, A.C.J. van Akkooi, P.A. Ascierto, R. Dummer, U. Keilholz.
Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.
Annals of Oncology, 30 (2019), pp. 1884-1901
GFR15!!!
Differential diagnosis
Probable diagnosis is kaposi sarcoma with differentials of bacillary angiomatosis, pyogenic granuloma, hepatoma.
Management
Should be in consultation with the oncology team.
Begins with history interested in any GIT/ respiratory symptoms.
A physical exam looking for other lesions and close inspection of the bucal mucosa.
Baseline investigations including a complete blood count, LFTS, UECS, HIV and HHV8 viral load.
Excisional biopsy to confirm the diagnosis, Kaposi sarcoma will find spindle cells proliferation.
Imaging to rule out visceral organs involvement- should include CT chest, abdomen, endoscopy if there any GIT symptoms.
First line should be reduction of the immunosuppression- the MMF should be reduced or removed. The tacrolimus should be switched to sirolimus.
However this patients graft is already failing and reduced immunosuppression may also worsen the rejection, it would be wise to also start preparing for dialysis by fixing an AVF.
Well done.
What is your differential diagnosis?
These will include-
Kaposi Sarcoma
Fungal infections
Lichen Planus
How do you manage this case?
This patient will need detailed history and examination for lymphadenopathy and visceromegaly.
Blood tests like Blood CP /ESR. renal and liver functions, viral serology
CT scan to assess and visceral involvement by disease.
The case needs assessment by Dermatology team and MDT.
This lesion will requires a biopsy. Kaposi sarcoma can be confirmed by a biopsy and presence of HHV 8 DNA.
Modification of immune suppression regimen
Final treatment will depend on the histology results.
Substantiate your answer.
Bieryło A, Brzósko S, Laudańska E, Naumnik B. Skin cancers in kidney transplant recipients. Wiad Lek. 2017;70(1):68-73. Polish.
How will you deal with the failing graft.
It may be sensible to coommunicate to patient and family about risk of graft failure. Creation of vasculat access will be required.
Differential diagnosis:
1)Kaposi Sarcoma
2)Dermatofibroma
3)Angiomatoid fibrous Histiocytoma.
4)Spindle cell sarcoma.
5)Bacillary angiomatosis.
6)Ecchymosis
The other lesion shown in this patient is generalized nail dystrophy
Diagnosis:
Excisional biopsy is essential for diagnosing the underlying lesion.
In Kaposi Sarcoma characteristically features increased clusters of spindle cells with vascular structure predominated by endothelial cells.
Kaposi Sarcoma:
Its vascular tumor originated from lymphatic vascular endothelial cells infected by human herpesvirus 8(HH8). 4 types of KS are identified.endemic, pandemic,classic and iatrogenic. It might be multiple , spreading widly. or solitary.
Its slowly growing but visceral involvement is reported and herald adverse outcome.
Management:
Cornerstone in management of KS revolve around 3 axis’s
1] Gradual reduction of immunosuppression status might alleviate immune system potency.
2] Switching to mTORi with its propensity of being anti-proliferative agent, curtailing uncontrolled growth of tumor cells.
3] Chemotherapeutic agent
4] Combination of all.
References:
1]Julie Deylon et al . Management of Kaposi sarcoma after solid organ transplantation: A European retrospective study.JAAD VOLUME 81, ISSUE 2, P448-455, AUGUST 2019.ulihttps://crossmark-cdn.crossref.org/widget/v2.0/logos/
GFR 15 and SIROLIMUS!
Considering that the patient is a kidney transplant patient with long standing exposure to potent immunosuppression, skin cancer should be strongly suspected. These skin lesions are typical of Kaposi’s sarcoma.
The patient should be assessed by an experienced dermatologist Complete clinical examination should be performed, including mucosal examination and abdominal imaging using US or CT.
The approach includes histological evaluation of the lesion to confirm the diagnosis . In the settings of Karpoci Sarcoma,the biopsy will reveal endothelial fusiform cells and the creation of new blood vessels . Immunohistochemical staining of endothelial cells may reveal HHV-8.
The treatment consists of preventive and therapeutic masures including:
Sunlight protective behavioral approaches.
Immunosuppression reduction: MMF should be stopped or decreased. The patient’s tacrolimus trough level is 7.4 ng/ml, which is considered high, hence, should be lowered to a trough level of 3-5 ng/ml.
Substitution of mTOR inhibitors for Tacrolimus in immunosuppression. However knowing that pt has cAMP, switching to less potent immunosuppression may cause a rapid decline in kidney function.
As the patient has advanced CKD, with expected decline in kidney function due to the reduction in immunosuppression, it is wise to prepare the patient with vascular access/AV fistula for future use.
Well done.
The index patient is a 65-year-old male kidney transplant recipient (cadaveric donor – 7 years back), with chronic AMR and poor graft function (eGFR 15 ml/min), and is on Tacrolimus and MMF.
He presents with multiple purplish brown maculopapular lesions of varying size over his hand.
The differential diagnosis with such skin lesions would include non melanoma skin cancer (NMSC) – Kaposi Sarcoma, infections like bacillary angiomatosis, blue rubber bleb nevus syndrome, pyogenic granuloma (lobular capillary hemangioma), tufted angioma, melanocytic nevi, melanoma, cavernous hemangioma, angiokeratoma, Stewart–Treves syndrome, spindle cell hemangioendothelioma, and severe statis dermatitis (1).
The most probable diagnosis in view of the clinical picture (7 year of kidney transplant, failing graft, male patient, on MMF 750 mg BD, Tacrolimus with trough levels of 7.4, and typical skin lesions) is non melanoma skin cancer (NMSC) – Kaposi Sarcoma (2,3).
Kaposi Sarcoma, a vascular tumor, caused by human herpes vius-8 (HHV-8) is 100 times more common in transplant recipients than in the general population, with increased risk in those on calcineurin inhibitors (2). The lesions are usually seen on distal extremities, especially lower limbs, but can be extensively spread over whole body.
The patient should be evaluated by a dermatologist. Complete clinical examination, including mucosal examination and ultrasound abdomen should be done (to assess the extent of lesions – for visceral involvement). The patient may need CT abdomen for further evaluation for visceral involvement.
The management includes confirmation of diagnosis by a biopsy from the lesion (1). The biopsy will reveal endothelial fusiform cells and neovessel formation (4). Immunohistochemical staining may show HHV-8 on endothelial cells (4).
The treatment includes (1,5):
1) Re-enforcement of behavioural interventions for sun-protection.
2) Reduction of immunosuppression: The tacrolimus trough level in the patient is 7.4 ng/ml, which is high and should be reduced to 4-5 ng/ml. MMF should be stopped.
3) Switching of immunosuppression from Tacrolimus to mTOR inhibitors (Sirolimus). But as the eGFR is low, switching to mTOR inhibitors can not be done in the index patient.
4) Preparation for further need of RTT: Vascular access creation, and search for another living donor in family in anticipation of further graft dysfunction and graft loss.
The cornerstone to manage such patient is diagnosing the lesion by a biopsy, and then treatment by switching the immunosuppression from Tacrolimus to Sirolimus (not possible in this patient, hence tacrolimus dose reduction should be done). Multidisciplinary approach with involvement of dermatologist and oncologist is essential.
Alteration in immunosuppression has been shown to be associated with regression of the lesions (6). If the lesions do not respond, then treatment would involve use of chemotherapeutic agents like liposomal pegylated doxorubicin, immune response modifier imiquimod, or radiotherapy, in case chemotherapeutic agents are contraindicated (3,7).
References:
1. Schwartz RA. Kaposi’s sarcoma: an update. J Surg Oncol. 2004 Sep 1;87(3):146-51. doi: 10.1002/jso.20090. PMID: 15334644.
2. Al-Adra D, Al-Qaoud T, Fowler K, Wong G. De Novo Malignancies after Kidney Transplantation. Clin J Am Soc Nephrol. 2022 Mar;17(3):434-443. doi: 10.2215/CJN.14570920. Epub 2021 Mar 29. PMID: 33782034; PMCID: PMC8975024.
3. Berman H, Shimshak S, Reimer D, Brigham T, Hedges MS, Degesys C, Tolaymat L. Skin Cancer in Solid Organ Transplant Recipients: A Review for the Nondermatologist. Mayo Clin Proc. 2022 Dec;97(12):2355-2368. doi: 10.1016/j.mayocp.2022.07.004. Epub 2022 Nov 3. PMID: 36334939.
4. Raedemaeker J, Marot L, Camboni A, Kanaan N. Kaposi sarcoma after kidney transplantation. BMJ Case Rep. 2019 May 5;12(5):e229681. doi: 10.1136/bcr-2019-229681. PMID: 31061183; PMCID: PMC6506100.
5. Sunil M, Reid E, Lechowicz MJ. Update on HHV-8-Associated Malignancies. Curr Infect Dis Rep. 2010 Mar;12(2):147-54. doi: 10.1007/s11908-010-0092-5. Epub 2010 Mar 26. PMID: 20461118; PMCID: PMC2860558.
6. Delyon J, Rabate C, Euvrard S, Harwood CA, Proby C, Güleç AT, Seçkin D, Del Marmol V, Bouwes-Bavinck JN, Ferrándiz-Pulido C, Ocampo MA, Barete S, Legendre C, Francès C, Porcher R, Lebbe C; Skin Care in Organ Transplant Patients Europe (SCOPE) group. Management of Kaposi sarcoma after solid organ transplantation: A European retrospective study. J Am Acad Dermatol. 2019 Aug;81(2):448-455. doi: 10.1016/j.jaad.2019.03.028. Epub 2019 Mar 19. PMID: 30902727.
7. Di Lorenzo G. Update on classic Kaposi sarcoma therapy: new look at an old disease. Crit Rev Oncol Hematol. 2008 Dec;68(3):242-9. doi: 10.1016/j.critrevonc.2008.06.007. Epub 2008 Jul 25. PMID: 18657433.
Exellent.
-The picture showed multiple skin lesions over the dorsum; the lesions looked purplish, dark brown macules and nodule.
–The lesions are typical for cutaneous Kaposi Sarcoma considering the index is KTR and who has long term exposure to IS (7 years, high level of Tac ) skin cancer should be highly suspected.
Differential diagnosis:
-KS is an angio-proliferative cutaneous cancer caused by HHV 8
-The incidence is higher in transplant patients, the SIR is 17 in transplant population
-Generally, occurred 13 months after transplantation (range few weeks to 18 years)
-Dissemination to visceral mucosa of the trachea, lungs and gastrointestinal tract is common in immunosuppressed patient, develops in 25-30 % of renal transplant recipients and 50 % of heart or liver transplant recipients
-Mucosal dissemination or visceral involvement has usually a poor prognosis
Risk factors for Kaposi Sarcoma:
Work up:
-Skin biopsy to confirm the diagnosis.
-Send for HHV8 and HIV viral load
-CBC
-KFT and LFT
-Serum protein electrophoresis
-Screen for dissemination and visceral involvement CT without contrast ( as GFR is low) endoscopy, bronchoscopy.
How do you manage this case?
-Dermatology opinion
–Oncologist opinion in case of persistent lesion or life threatening disease for chemotherapy (vincristine or vinblastine, bleomycin, and doxorubicin (singly or in various combinations)
-Radiation oncologist involvement; for radiotherapy
-Isolated lesions can be excised surgically or treated with cryotherapy.
-The clinical usefulness of antiviral drugs (foscarnet, ganciclovir, cidofovir, and adefovir) that have in vitro activity against HHV-8 has not yet been adequately documented.
Immunosuppression management:
-Reduce immunosuppression level likely result in partial or complete regression of the lesions.
-Generally, If no response switch from Tacrolimus to Sirolimus based IS lead to complete remission as described in CONVERT trial.
-This patient has failing allograft, complete withdrawal may be more appropriate, however; in the setting of cAMR, keeping low level of IS another option.
-Prolog the life of allograft and decrease graft-intolerance syndrome the benefits of continued IS must be weighed against the risk of complications from their ongoing exposure, such as infection, malignancy, secondary adrenal insufficiency, and cost. the priority is patient life.
-Complete withdrawal of antimetabolite.
-Reduce Tacrolimus and keep the level 3-5.
-Conversion to mTORi is not preferred (GFR)
-To continue on Prednisolone
CKD Management and Dialysis Modality.
Adequately prepare for transition to dialysis, modality, access.
Usual CKD management; anemia, MBD.
Psychological support.
Pre-emptive listing on transplant list ( not applicable patient with active malignancy)
Others:
– Frequent skin examination and surveillance for development of any skin lesion.
– Sun protective methods. Avoid mid-day sun exposure, avoid bed tanning, apply broad spectrum sunscreen, Patients should cover up with long sleeved shirts and pants, wear a hat and sunglasses when outdoors.
Substantiate your answer.
· Collet et al AJT 2010; 10: 1889–1896
· Euvrard S, Kanitakis J, Claudy A. Skin cancers after organ transplantation. N Engl J Med. 2003 Apr 24;348(17):1681-91. doi: 10.1056/NEJMra022137. PMID: 12711744.
· Raedemaeker J, Marot L, Camboni A, et al Kaposi sarcoma after kidney transplantation BMJ Case Reports CP 2019;12:e229681
· Zmonarski SC, Boratyńska M, Rabczyński J, Kazimierczak K, Klinger M. Regression of Kaposi’s sarcoma in renal graft recipients after conversion to sirolimus treatment. Transplant Proc. 2005 Mar;37(2):964-6. doi: 10.1016/j.transproceed.2004.12.172. PMID: 15848592.
· Schena FP, Pascoe MD, Alberu J, del Carmen Rial M, Oberbauer R, Brennan DC, Campistol JM, Racusen L, Polinsky MS, Goldberg-Alberts R, Li H, Scarola J, Neylan JF; Sirolimus CONVERT Trial Study Group. Conversion from calcineurin inhibitors to sirolimus maintenance therapy in renal allograft recipients: 24-month efficacy and safety results from the CONVERT trial. Transplantation. 2009 Jan 27;87(2):233-42. doi: 10.1097/TP.0b013e3181927a41. PMID: 19155978.
· Davis, Scott1,2,3; Mohan, Sumit1,2,3. Managing Patients with Failing Kidney Allograft: Many Questions Remain. CJASN 17(3):p 444-451, March 2022. | DOI: 10.2215/CJN.14620920
Thankyou well done
Sirolimus in a failing graft.!
With this eGFR is not recommended to start Sirolimus
Kaposi sarcoma.
Dermatofibroma
Bacillary angiomatosis .
Pyogenic granuloma..
Cutaneous angiosarcoma.
Hematoma.
post-transplantation Kaposi sarcoma commonly responds to reduction or discontinuation of immunosuppression.
this patient with chronic allograft nephropathy GFR of 15 withdrawn of of immunosuppression both TAC and MMF and treatment of KS is best option after counseling with patient and dermatologist and oncologist ,to confirm diagnosis with skin biopsy and choice of modalities of treatment either with radiotherapy or local Imiquimod.
👉 The present case, old aged male, transplanted 7 years ago and has been on long term immunosupression, with higher tacrolimus trough level than needed 7 years post transplant (idea traget is 4-5) presented with dark red or brown papules so the most probable diagnosis is Kaposi sarcoma.
👉 Differential diagnosis:
_ hematoma.
_pyogenic granuloma.
👉 Management requires skin biopsy to confirm the diagnosis and draw the plan of management.
_ Reduction of immunosupression (stop MMf or decrease it to 360 BID, decrease CNI especially in this affected GFR as the ideal target trough is around 3_5), restart steroids to compensate for decreasing CNI and MMF.
_shift to sirolimus would be another option.However, the affected GFR may not favor mTORi.
_ Evaluation of metastasis by CT chest , abdomen and pelvis is required.
_ Visceral involvement is common in 20 _30 % of cases (so upper endoscopy to evaluate GIT , and bronchoscopy to evaluate mucosal involvement ) .
_ Lab investigations as CBC, liver function and electrolytes.
_ Systemic chemotherapy in advanced and visceral involvement.
_ General management of CKD patients as we are dealing with failing graft (manage anemia, CKD_BMD) , close monitoring of GFR and protinuria plus counseling regarding Retransplantation (we need to wait for 2_5 years after complete cure), so return to dialysis is inevitable (we need to prepare AVF as vascular access).
_ Adjuvant therapy as ACEi if protinuriais present, control blood pressure and dyslipidemia if present.
_Avoid sun exposure around the midday.
_ use of broad spectrum sunscreen and sun protective clothes.
Well done.
This is a patient with a failing allograft 7 years post transplant and he is on tacrolimus and MMF
He has a violaceous nodule on the dorsal surface of the metacarpophalangeal joint with several erythematous plaques
The differential diagnosis includes:
The diagnosis would require a biopsy.
Based on the characteristic of the lesion, the diagnosis most likely is Kaposi Sarcoma (KS). KS is a tumor of endothelial origin and is associated with Human Herpes Virus 8 (HHV 8). It occurs most commonly in individuals of African, Arab, Jewish or Mediterranean descent. Majority (approximately 90%) develop cutaneous lesions and more commonly involving the lower limbs. 25-30% of renal transplant patients develop visceral KS
Investigations
A PET CT scan is recommended to assess for any visceral involvement as the management would be different for visceral KS and cutaneous KS
A CT scan of chest and abdomen is important to assess for visceral involvement and to detect lymphadenopathy
If the patient has symptoms of dyspepsia or lower GI bleeding, an upper GI endoscopy and colonoscopy is warranted
Management
Since this patient has cAMR and a failing allograft, it would be reasonable to reduce his immunosuppression. I would stop his MMF and change his tacrolimus to sirolimus. In retrospective case series, reduction of immunosuppression alone would induce remission in 30-50% of cases. Conversion of CNIs to mTOR inhibitors for cutaneous KS induced remission in more than 70% of cases.
The oncology team would also need to be involved
Chemotherapy is usually required for severe KS with visceral involvement
Radiotherapy is also used for severe cutaneous KS with heavy tumor burden causing intractable pain
Generally, it is important to counsel patients with a good functioning graft that there is a risk of rejection after reducing immunosuppression
Thankyou
What is your differential diagnosis?
The lesion has a brown, pink, red colour, with a nodule and plaque-like appearance. The most likely diagnosis is Kaposi’s sarcoma because of immunosuppression and HHV-8 reactivation
Other differential diagnoses:
1. Haematoma
2. Purpura
3. Haemangioma
4. Dermatofibroma
5. Pyogenic granuloma
Kaposi’s sarcoma usually appears early after transplantation (a mean of 13 months after) but may be as late as 18 years
The incidence is much higher in transplant recipients than in nonimmunosuppressed (84-500 folds)
Most cases occur in transplant recipients of Mediterranean, Jewish, Arabic, Caribbean, or African descent
The incidence ranges from 0.5- 5.3 %
Male to female ratio is 3.3:1.0 (the mean age at the time of diagnosis is 43 years)
90% have cutaneous or mucosal lesions or both
A grading system (grades I through IV) reflects the extent of the disease
The oropharyngeal and conjunctival mucosa may be affected
Visceral disease:
· Predominantly affects the lymph nodes, GIT, and lungs
· Purely visceral in 10 %
· Occurs in 25-30 % of kidney transplant patients (50 % of those with heart or liver transplants)
· Poor prognosis
How do you manage this case?
MD approach and dermatology referral
Full history and clinical examination including mucous membrane (palate, gigiva, and conjuctiva)] and lymphnodes
Laboratory tests include CRP, HHV-viral load, and serum protein electrophoresis
Imaging: chest radiographs for pulmonary involvement. CT chest, abdomen, pelvis (visceral K sarcoma), MRI of spine (bone), and PET/CT (lymphadenopathy, visceral masses, splenomegaly, effusions, or bone lesions)
The definitive diagnosis can be obtained with tissue biopsy and histopathology
Immunosuppressions in failed kidney transplant with Kaposi’s sarcoma:
o Reduction of immunosuppression results in partial or complete regression of the lesions. In cases of progressive disease, discontinuation of immunosuppressive treatment
o Evaluate and prepare for dialysis
o Stop anti-proliferative agents immediately (azathioprine and mycophenolate)
o Keep steroid at a dose of 5mg/day (in case of residual renal function or with a plan to retransplant)
o Keep low dose of mTORi (late graft failure and Kaposi sarcoma), and discontinue at initiation of dialysis/Kaposi sarcoma remission (tapper over 4-6 weeks)
Patient education and counseling:
· Proper counselling before and after transplantation
· Regular use of high factor sun blocks -SPF 50+, regardless of the weather with some combination of UVA screening ingredients or broad spectrum or UVA/UVB sunscreen
· Sun-protective clothing
· Avoid intense sun exposure
· Avoid the mid-day sun and one to 2 hours around the mid-day
· Self-examination
· supplementation of vitamin D
Other options of treatment:
1. chemotherapy with vincristine or vinblastine, bleomycin, and doxorubicin (singly or in various combinations)
2. Liposomal daunorubicin; paclitaxel; etoposide; dactinomycin; and cisplatin
3. Radiotherapy and interferon alfa
4. Surgical excision or cryotherapy for isolated lesions
References
1. Sylvie Euvrard, Jean Kanitakis, Alain Claudy. Skin Cancers after Organ Transplantation. N Engl J Med 2003; 348:1681-1691. DOI: 10.1056/NEJMra022137
2. Prof. Ahmed Halawa, Consultant Transplant Surgeon Sheffield Teaching Hospitals – UK. Post-transplant Malignancy lecture, 2023.
3. Marco Fiorentino et al, Management of patients with a failed kidney transplant: what should we do?, Clinical Kidney Journal, Volume 14, Issue 1, January 2021, pages 98-106.
4. Medscape
Well done.
Kidney transplantation increases the risk for malignancy that is the second leading cause of death after cardiovascular complications among transplant patients . athis patient suffers from pigmented papule and macules on dorsum of the hand ,mostly kaposi sarcoma.
Differntial diagnosis
1- Infectoius causes :
-Viral :HIV , disseminated herpes
-Bacterial :Bacillary angiomatosis opportunistic infection very close to KS , caused by bortonella species can can produce cutinous and systemic lesions.
2- Hemangiomas : hemosiderotic hemangioma
3- Fibrous histiocytoma
4- Interstitial granuloma annular
5- Benign lesions : pyogenic granuloma, dermatofibroma
-Good physical examination to detect other organ involvement by KS especially mucosal cavity and GIT
-Skin biopsy: with staining for CD31 and CD34 and immunehistochestery for HHV-8 latent antigen detection
– CBC with differnial
– KFT and LFT
-CRP
-KSHV/HHV-8 viral load
-Serum protein electrophoresis
Radiological evaluation
-C T scan for chest , abdomen and pelvis
-MRI on spine
-PET/CT for lymphadenopathy , spleenomegaly and other visceral involvement (KS can affect internal organs in upto 40% of cases).
Management
1- IS modification : this patient has high FK level that need to lowered to around 5 and decrease the dose of MMF .
2- Close monitoring of graft function as the patient already have c AMR.
3- Chemotherapy for rapidly growing cutinous lesions and internal organ involvement
Ref
1- Ngan V Bacillary angiomatosis. DermNet NZ Update August 2021
2- Katz J and Choy E, Kaposi Sarcoma Clinical Presentation Medscape , Updated: Feb 15, 2022
3- Arora M, Goldberg EM. Kaposi sarcoma involving the gastrointestinal tract. Gastroenterol Hepatol (N Y). 2010 Jul;6(7):459-62. PMID: 20827371; PMCID: PMC2933764.
Well done.
-What is your differential diagnosis?
-The patient had hyperpigmented (pink colored) nodular,papular,and macular lesions of his left hand. Given the history of kidney trasplanation one would think about kaposi sarcoma (KS). We need to exam his oral cavity, lymph nodes, chest , and abdomen to rule out systemic involvments. History of cough, sob, GIT bleeding and lower limb swelling may be important. skin biopsy is mandatory to rule out other diagnosis.
-The differential diagnosis of KS are:
-How do you manage this case?
-Managment is multi-displinary: transplant nephrologist, dermatologist, nutritionist ,pathologist, social worker / psychologist and surgeon
-General management of skin conditons
-KS:
-Management of failing allograft or CKD-5GTx:
-Re-transplantation:
Source; ITSCC, handbook of kidney transplantaion 6th edition by Gabriel Danovitch, Oxford hand book of nephrology and hypertension 2th edition
Thank you all for your answer, BUT the investigations required if this lesion is KS are deficient.
Thanka verey much Prof.Halawa
diagnosis KS
Symptoms of Kaposi Sarcoma
Medical History and Physical Exam
A skin biopsy
Chest X-rays or CT Scans
Bronchoscopy
Upper Endoscopy
Colonoscopy
Thanks prof:
History :
====================================================================
What is your differential diagnosis?
Differential diagnosis
1- Topic 5 FU
2- Reduction of immunosuppression
3- Consider Sirolimus.(monitoring for protein in urine )
4- avoid sun.
====================================================================
Substantiate your answer
Reference:-
1. Einollahi B, Noorbala MM, Lessan Pezeshki M, et al. Incidence of post renal transplantation malignancies: a report of two centers in Tehran, Iran. Transplant Proc. 2001;33:2812
2.Tan HH, Goh CL. Viral infections affecting the skin in organ transplant recipients: epidemiology and current management strategies. Am J Clin Dermatol. 2006;7:13–29
3-Management of Kaposi sarcoma after solid organ
transplantation: A European retrospective study 2021
4- Chang Y, Cesarman E, Pessin MS, Lee F, Culpeper J, Knowles DM. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma. Science 1994;266:1865-9
Thank you Dr. Mahmoud
How frequently does KS affect the internal organs?
Thanks alot for you Prof.Halawa
In the context of cutaneous disease, extracutaneous Kaposi’s sarcoma (KS), especially visceral KS, has been well documented.
The esophagus, stomach, small and large bowels, liver, spleen, pancreas, mesentery, and biliary tree are among the visceral organs that have reportedly been affected.
Although KS can manifest anywhere throughout the gastrointestinal (GI) tract, it typically affects the stomach and proximal small bowel.
In rarer cases, KS may affect the digestive system in the absence of cutaneous disease.
Gastrointestinal KS was once thought to affect up to 40% of AIDS patients, but more recently, its prevalence has decreased.
Sorry
Arora M, Goldberg EM. Kaposi sarcoma involving the gastrointestinal tract. Gastroenterol Hepatol (N Y). 2010 Jul;6(7):459–62.
What is your differential diagnosis?
Brown/dark red raised lesions in the dorsum of the hand of variable sizes and irregular shapes, 7 years post cadaveric kidney transplantation.
The DDx :
Infectious causes- HIV , disseminated herpes, bacillary angiomatosis.
Malignancies- Lymphoma, Kaposi sarcoma, melanoma, unlikely basal cell, or squamous cell carcinoma, Lymphoproliferative disorders.
Most probable diagnosis is Kaposi sarcoma.
How do you manage this case?
First I would ask for CBC, ESR, LDH , full chemistry and a blood film, then consult both dermatologist and oncologist and will review his viral serology in the medical chart, and do a thorough clinical examination including mucous membranes, and organomegaly.
Then will do a skin biopsy-
Lymphoma can present with such an angioprolifreative skin lesions (T-cell lymphoma-sezary syndrome) can be caused by EBV.( the most likely diagnosis >36 months post transplant).
Melanoma
Kaposi sarcoma as it is cutaneous angioproliferative lesions caused by HSV-8,and HIV rarely disseminated usually occurs in the first two years post transplant.
Will discuss the screening for metastatic disease by oncologist, and insist the patient to follow the oncologist treatment plan.
After getting the diagnosis the first thing to do is to stop CNI and MMF, consider starting on m-TOR inhibitors to control the disease.
medical treatment either local or systemic, radiotherapy , cryotherapy, intralesional chemotherapy, laser therapy, and/or surgical excision.
Given that he had c-AMR with CKD – impaired graft function then I’ll do monitor his urine protein before and after the m-TOR inhibitors, and council him about the risk of being back to hemodialysis.
However; no consensus whether re-transplant such patients, there have been some case series with successful re-transplantation after 3 years disease free period with low risk of recurrence with modified m-TORi based immunosuppressive medications.
Substantiate your answer.
References:
(1) Berman H, Shimshak S, Reimer D, Brigham T, Hedges MS, Degesys C, Tolaymat L. Skin Cancer in Solid Organ Transplant Recipients: A Review for the Nondermatologist. Mayo Clin Proc. 2022 Dec;97(12):2355-2368. doi: 10.1016/j.mayocp.2022.07.004. Epub 2022 Nov 3. PMID: 36334939.
(2) Stenz NA, Stampf S, Arnold AW, Cozzio A, Dickenmann M, Gaide O, Harms M, Hunger RE, Laffitte E, Mühlstädt M, Nägeli M, Hofbauer GFL; and the Swiss Transplant Cohort Study. Skin Cancer Development in Solid Organ Transplant Recipients in Switzerland (Swiss Transplant Cohort Study). Dermatology. 2021;237(6):970-980. doi: 10.1159/000510685. Epub 2020 Nov 23. PMID: 33227788; PMCID: PMC8619732.
(3) Bécuwe C, Euvrard S, Bosshard S, Pouteil-Noble C, Garnier JL, Lefrançois N, Boillot O, Kanitakis J, Touraine JL, Claudy A. Maladie de Kaposi et transplantation d’organes: 22 cas [Kaposi’s sarcoma and organ transplantation: 22 cases]. Ann Dermatol Venereol. 2005 Nov;132(11 Pt 1):839-43. French. doi: 10.1016/s0151-9638(05)79501-6. PMID: 16327712.
(4) Euvrard S, Kanitakis J, Bosshard S, Lebbé C, Garnier JL, Touraine JL, Claudy A. No recurrence of posttransplantation Kaposi’s sarcoma three years after renal retransplantation. Transplantation. 2002 Jan 27;73(2):297-9. doi: 10.1097/00007890-200201270-00025. PMID: 11821747.
Thank you Dr. Mohamed
How frequently does KS affect the internal organs?
Extracutaneous involvement — During the course of the disease mucous membranes of the mouth and gastrointestinal tract, and regional lymph nodes may be affected. Gastrointestinal tract involvement is usually asymptomatic, but bleeding, diarrhea, protein-losing enteropathy, intussusception, and perforation have been reported.
In general, gastrointestinal tract/oral mucosal involvement is less common than with acquired immunodeficiency syndrome (AIDS)-related KS, affecting ≤10 percent of patients.
However, in one report, an extraordinary 82 percent of Greek patients (71 of 87) with biopsy-proven classic KS who were investigated with upper gastrointestinal endoscopy had gastrointestinal lesions; all 71 had stomach lesions, 19 had esophageal lesions, 8 had lesions of the proximal duodenum, and 2 had both esophageal and duodenal lesions. Although this finding could be interpreted as suggesting the need for screening endoscopy in patients with newly diagnosed classic KS, it also supports the view that the presence of asymptomatic gastrointestinal involvement probably has little effect on prognosis. In practice, routine endoscopy is not performed in people diagnosed with classic KS who do not have symptoms referable to the gastrointestinal tract.
Regional nodal involvement is relatively uncommon, and it is rarely bulky. Nodal involvement was reported in 15 percent of 66 Greek patients with classic KS in one study.
The presence of nodal disease probably does not worsen overall prognosis, although this has been demonstrated in AIDS-related KS, not classic KS. Rare cases of isolated lymph node involvement with classic KS have been described.
Involvement of visceral organs other than the lining of the alimentary tract (eg, lung, liver, bone, bone marrow) is extremely rare.
Reference:
UpToDate- Classic Kaposi sarcoma: Clinical features, staging, diagnosis, and treatment
What is your differential diagnosis?
Paraneoplastic dermatoses:
Sweet syndrome:
-characterized by multiple painful, sharply circumscribed dark red edematous nodules
-usually associated with myeloproliferative and lympho-proliferative disorders.
Acanthosis nigricans maligna
Necrolytic migratory erythema:
-associated with glucagonoma
-Vesicles, erosions, crusts, and pustules arise at the periphery
-The lesions enlarge in annular pattern, leaving pigmentation in the central area.
Gottron’s papules
Severe onycholysis and nail bed infection of fingernails.
Kaposi sarcoma
/////////////////////////////
How do you manage this case?
History, examination, and laboratory tests should focus on search for internal malignancy.
Skin biopsy to delineate the nature of the disease.
A broad cancer screening should be performed: chest, abdomen, and pelvic CT scan.
Excisional biopsy of the skin lesions.
Immunosuppression manipulation
/////////////////////////////
Substantiate your answer.
References
Dario Didona, Luca Fania, Biagio Didona, Rüdiger Eming, Michael Hertl, and Giovanni Di Zenzo, Paraneoplastic Dermatoses: A Brief General Review and an Extensive Analysis of Paraneoplastic Pemphigus and Paraneoplastic Dermatomyositis, Int. J. Mol. Sci. 2020, 21(6), 2178; https: //doi.org/10.3390/ijms21062178
Thank you Dr Mohamed
Do you think it is Kaposi Sarcoma?
The violaceous macules and nodules would suggest Kaposi Sarcoma, Histopathology is needed to confirm the diagnosis.
Multiple skin lesions are distributed over the dorsum of the hand, brownish-violet, raised, and irregular pattern. The lesion looks like skin cancer due to the cumulative effects of immunosuppressants.
most likely Kaposi sarcoma (confirmation requires a biopsy and the presence of HHV-8 DNA in the involved tissue). Kaposi sarcoma is linked to HHV-8 and usually shows up 30 months after a transplant.
Bacillary angiomatosis, hemosiderotic hemangioma, fibrous histiocytoma, lymphangioma, interstitial granuloma annulare, and pyogenic granuloma are some of the possible diagnoses.
The patient has CKD stage 5, so these high doses of immunosuppressive medication are unnecessary. I will discontinue the MMF and decrease the dose of tacrolimus to levels 3–4. then I will discontinue. During this time, I will prepare the patient for dialysis.
I will search for internal organ involvement.
Shifting CNI to sirolimus at this stage, when GFR is 40 ml/min, is not recommended.
The treatment of KS depends on the extent and localization of the lesions, as well as on the clinical type of the disease. Localized skin lesions have been treated with cryotherapy, ionizing radiation, surgical excision, and photodynamic therapy. for more aggressive diseases. Radiation and chemotherapy in resistant cases
Ponticelli C. Faculty opinions recommendation of conversion from calcineurin inhibitors to sirolimus maintenance therapy in renal allograft recipients: 24-month efficacy and safety results from the convert trial. Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature. 2009;
Thank you
DDx of skin bruises with one hemorrhagic blister associated yellow nail destruction with arrested growth
– Kaposi sarcoma
– Nail fungal infection
– Drug induced ( tac skin rash )
– Internal malignancies
– PTLD
– Chronic bronchiectasis
– CKD related platelet dysfunction
Management
History and clinical exam focusing on respiratory system symptoms and signs and immunosuppressive regimen associated with regional lymph node exam with other system affection review
Dermatological evaluation ” MDT involvement
Lab : ESR CRP, LDH, Ca, uric acid, serology for HIV HBV HCV EBV
Radiology : CT scan of neck chest abdomen and pelvis
MDT evaluation
Excision biopsy
Patient education
immunosuppressive modulation: reduction of the TAC to achieve drug trough level between 3-5 ng/dl even starting RRT if there is no improvement
subsequent management will be according to the diagnosis
Thank you
Diagnosis and Differential diagnosis:
Kaposi Sarcoma
Angiosarcomas
Haemangiomas
Management:
1. Detailed physical examination, examining the whole skin for similar lesions, mucosal surfaces, and lymph nodes.
2. Biopsy of skin lesion.
3. HHV-8 DNA PCR
4. Extracutaneous manifestations:
CBC.
If respiratory symptoms such as cough, dyspnea, hemoptysis, fever then Chest X-ray, CT chest, bronchoscopy.
GIT evaluation: Stool for occult blood, Ultrasound abdomen, Endoscopy.
FNAC for lymph node biopsy in case of lymphadenopathy.
5. Reduction of immunosuppression and monitoring for rejection.
Withdrawal of MMF/AZA, reduction in dose of TAC.
Switch to mTOR inhibitors
Oncology consult.
Chemotherapy
Thank you
What is your differential diagnosis?
How do you manage this case? Substantiate your answer.
A- Dermatology consultation, and biopsy from the lesion is mandatory for confirmation of the diagnosis
B- Searching for visceral affection is important
C- Treatment
REFERANCES
Thank You Dr Sherif for this wonderful answer. I will quote this from your answer as it was missing from many answers I have read so far
Searching for visceral affection is important
Differential diagnoses are;
Kaposi sarcoma
Haemangioma with bruises
Angiosarcoma
Fungal nail infection
Calciphylaxis
Work up for this lesion required;
CBC, VIRAL SEROLIGY OF HHV-8, HIV;
Skin biopsy of the lesion for definite diagnoses;
Treatment;
For treatment purpose we need multispecialty team including
Oncologist, dermatologist and surgeon opinion for definite treatment.
Reduce immunosuppression and switch to MTOR inhibitors.
Radiation, chemotherapy and treatment of infection
American cancer society cancer.org | 1.800.227.2345
Thank you
What is your differential diagnosis?
How do you manage this case?
Thank you
DD:
1- kaposi sarcoma
2-skin cancer
3-calciphylaxis
management include skin biopsy to confirm diagnosis of and shift tacrolimus to sirolimus
Thank you for this answer. Can you expand more, please?