5. An a-61-year-old female patient presented with a 3-month history of multiple sinuses in the right side of the face (see below) without fever 7 months after receiving a kidney transplant from his 32-year-old son. She is on Tacrolimus-based triple immunosuppression with excellent graft function.
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
91 Comments
Rafi Nazrul Islam
What is your differential diagnosis?
Actinomycosis
Non-tuberculous mycobacterial infection
Nocardiosis
Mucormycosis
Is it a common site for this form of infection?
Yes, it may involve the face, mandible, cheek & chin. Other sites are thoracic & abdomino-pelvic.
· Principle of diagnosis
Tissue diagnosis by biopsy & histopathology
Prolonged culture
Treatment of this condition
Actinomycosis: Penicillin for prolonged periods, even up to 6 months.
Tuberculosis: Anti-tubercular chemotherapy for 6 months
Immunosuppression reduction by decreasing the dose of MMF and keeping tacrolimus to low trough levels may be needed.
Reference:
Valour F et al. Actinomycosis: etiology, clinical features, diagnosis, treatment and management. Infect Drug Resist 2014;7:183
Stabrowski T, Chuard C. Actinomycosis. Rev Med Suisse. 2019 Oct 9;15(666):1790-1794. French. PMID: 31599519
Actinomycosis is caused by non spore forming actinomyces israelii which is a common organism found in nose and throat, hence neck and head infection is common presentation. diagnosis is accomplished by identifying the microorganism in the culture of biopsy, secretion or pus . treatment is penicillin g as the drug of choice.
Long term management is reducing the immune suppressant medication as its resulting from over suppression of immune system.
reference:
1] Hall V. Actinomyces–gathering evidence of human colonization and infection. Anaerobe. 2008 Feb. 14(1):1-7.
There are 4 primary subtypes of actinomycosis infection:
Cervical-oral (60 %)
Abdominal (20 %)
Pulmonary (15 %)
Pelvic (5 %)
Actinomycosis is caused by branched, filamentous anaerobic Gram-positive bacteria called Actinomyces.
It is a chronic granulomatous & suppurative infectious disease.
In healthy individuals, actinomycosis is a commensal of the oral cavity, colon, & vagina. Actinomycosis becomes pathological in immunocompromised patients
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
Clinical diagnosis must be confirmed by histopathologic & bacteriologic examinations.
Only few cases of actinomycosis have been reported in renal transplant recipients to date.
Treatment is with prolonged courses of penicillins.
Surgical drainage, debridement, & resection may be required.
Actinomycosis is differentiated from other diseases with acid-fast negative ray-like bacilli & sulphur granules being pathognomonic.
Immunosuppressive medications may need to be adjusted to the minimal possible doses (guided by drug levels) to control infection guard against possible rejection.
What is your differential diagnosis? Most common cervicofacial infection is Actinomycosis. Other D/D are: Nocardiosis Tuberculosis Skin cancer Is it a common site for this form of infection? Actinomycosis can present in this site frequently; Jaw involvement and regional lymph node spread is very common and accounts for the main 50% of the cases of actinomycosis…. Pulmonary and abdomino-pelvic sites are the next areas of involvement…
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients! Post-transplant 7months, from well matched donor. Presented with multiple sinuses in the cervico-facial region for last 3 months without fever past h/o active or latent TB in recipient and TB-endemicity need to be enquired. The most likely diagnosis could be actinomycosis or tuberculosis We need to get CBC, ESR, Mantoux test, IGRA CT scan of the neck and chest is indicated to find out lymph node involvement, pulmonary TB We can send the pus for AFB stain, Gene-Xpert MTB and AFB culture… cervical lymph node biopsy may be diagnostic Actinomycosis – requires microbiological tests – Gram stain reveals non spore gram positive rods – slow growing in culture in anaerobic medium. – HPE of lymph node biopsy – may shows Sulfur granules with filamentous structures resembling fungi on H & E stain, is confirmatory. Treatment of Actinomycosis: high dose IV penicillin G 24 MIU/day x 2-6 wks, followed by oral penicillin for 6 months to prevent relapse. Macrolides, Doxycycline are other alternatives Treatment for TB will be 2 months of HRZE (CNI dose increase to achieve trough level) and 6-9months of HR (extra-pulmonary, transplant recipient) IS: Reduce antimetabolite and maintain low dose Tacrolimus and steroids
REFERENCES: 1) Reichenbach J, Lopatin U, Mahlaoui N, et al. Actinomyces in chronic granulomatous disease: an emerging and unanticipated pathogen. Clin Infect Dis 2009 Dec1; 49(11): 1703-10. doi: 10.1086/647945. PMID: 19874205; PMCID: PMC4100544. 2) Stabrowski T, Chuard C. Actinomycosis. Rev Med Suisse. 2019 Oct 9;15(666):1790-1794. French. PMID: 31599519. Thank you ALL for getting the correct diagnosis. What about immunosuppression? Will you reduce immunosuppression? I would stop MMF, decrease the dose of tacrolimus to trough level of 4-6 ng/dl, but will keep on prednisolone. with frequent monitoring of graft function and for any rejection.as an inhibition of CD4 cells in murine Peyer’s patch stops the production of specific antibodies in the case of infection due to A. viscosus. In transplant patients, immunosuppressive drugs induce lower rates of CD4+. Reference: Sosroseno W, Bird PS, Gemmell E, et al. Role of CD4+ and CD8+ T cells on antibody production by murine Peyer’s patch cells following mucosal presentation of Actinomyces viscosus. Oral Microbiol Immunol. 2006 Dec;21(6):411-4. doi: 10.1111/j.1399-302X.2006.00308. PMID: 17064401.
· What is your differential diagnosis?
1. Actinomycosis
2. TB
3. Lymphoma
· Is it a common site for this form of infection?
Yes, commonly it involves the face. it is facial in 50%. other sites are mandible 35 %, cheek 16 %, chin 13 %, Submaxillary and angle 10 %, Upper jaw 5.7 %, rare sites are central nervous system, thoracic, and abdomen.
· Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
Diagnosis depends on clinical presentation and tissue diagnosis and culture.
Treatment require antibiotics, namely penicillin, long courses up to 6months.
Tissue debridement may be needed
In immunosuppressed patients, reduction of immunosuppression and longer course may be needed plus involvement of ID consultant.
Reference:
1-Valour F et al. Actinomycosis: etiology, clinical features, diagnosis, treatment and management. Infect Drug Resist 2014;7:183
Q2: yes, it is the comment site. Abdominal, pulmonary, and pelvic are the other sites. For this anaerobic, filamentous, grt bacteria. Q3: confirmation of the diagnosis by culture or biopsy is needed. Treatment includes penicillin for a long time from 3 to even 12 months until the resolution of the infection. Surgical drainage may be needed if indicated monitoring of tacrolimus level during treatment.
Yes, cervicofacial region is common site for actinomycosis. Other possible sites for this infection are jaw and regional lymph nodes, lungs, pelvis, abdomen.
Principle of diagnosis and treatment for immunocompromised patients
actinomycosis – gram stain, culture, HPE lymph nodes are done for investigation. Treatment include high dose IV penicillin, doxycycline, macrocodes. Actinomycosis has good prognosis.
for patients with penicillin allergy, tetracycline or cephalosporins can be given.
TB investigations include CBC, IGRA, Mantoux, CT chest, AFB culture of pus, and biopsy of lymph node
renal transplant patient on tacrolimus-based triple IS, have chronic multiple abscess in her face , no fever. differential diagnosis of (1): -Actinomycosis (Gram-positive anaerobic bacteria, which are commensals in the oral cavity and digestive tract) . – Trichosporon. -bacterial infection. – lymphoma. – Cutaneous nocardiosis – Infections with the atypical mycobacteria,( which include Mycobacterium marinum, M fortuitum, M abscessus, M haemophilum and M avium-intracellulare)
Is it a common site for this form of infection?
It is a common site for actinomycosis. Actinomycosis occurs mean age was 55.7 years, and Median time between transplantation and infection was 4- 104 months. Locations of actinomycosis were cervicofacial in most of cases , other sites are, pulmonary , abdominopelvic , or cutaneous Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patient Actinomycosis is a slowly progressing infection Diagnosis was made possible by microbiology (71%) or histopathology (filaments and sulfur granules) (14%) of the infection site. The suspected gate of entry for the infection was dental (57%), abdominal (28.5%) or through the sinuses (14%). microscopic examination non-spore Gram-positive rods. Histopathological examination abscess with purulent, granulomatous inflammation and fibrosis. Treatment of Actinomycosis: patients were treated with amoxicillin- clavulanic acid for 30-200 days (median duration of 115 days). large abscess may require surgical evacuation. Reduction of IS is not indicated unless in most of cases.
References: Rousseau C, Piroth L, Pernin V, Cassuto E, Etienne I, Jeribi A, Kamar N, Pouteil-Noble C, Mousson C. Actinomycosis: An infrequent disease in renal transplant recipients? Transpl Infect Dis. 2018 Dec;20(6):e12970.
· What is your differential diagnosis?The most common cervicofacial infection is Actinomycosis. But other differential diagnoses are:- Nocardiosis- Tuberculosis- Skin câncer · Is it a common site for this form of infection?The skin is the most common site, but it can involve the lung, gastrointestinal tract. · Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
Even in immunosupressed patient the gold standard for diagnosis of actinomycosis is isolation and culture from a usually sterile body site.
The disease should be treated with high doses of antimicrobials for a prolonged period : use intravenous treatment for 2–6 weeks followed by oral therapy for at least 6–12 months. The antibiotic of choice is penicillin. In cases of allergy or nonresponse, alternatives include erythromycin, tetracycline, clindamycin, cephalosporins, meropenem, and chloramphenicol and surgical procedure should be considered.
REFERENCES: – Reichenbach J, Lopatin U, Mahlaoui N, Beovic B, Siler U, Zbinden R, Seger RA, Galmiche L, Brousse N, Kayal S, Güngör T, Blanche S, Holland SM. Actinomyces in chronic granulomatous disease: an emerging and unanticipated pathogen. Clin Infect Dis. 2009 Dec 1;49(11):1703-10. doi: 10.1086/647945. PMID: 19874205; PMCID: PMC4100544. – Stabrowski T, Chuard C. Actinomycose [Actinomycosis]. Rev Med Suisse. 2019 Oct 9;15(666):1790-1794. French. PMID: 31599519.
The patient is a renal transplant recipient on triple immunosuppression…Donor was her son..Renal transplant was done 7 months ago…..The DSA,induction used, any rejection episodes are not mentioned here…. The current problem is multiple sinuses in the cervico-facial region from the last 3 months without any fever…..Past history of TB or latent TB in the recipient and the endemic region for TB is also important…
The following differential diagnosis can be considered here
Cold abscess due to tuberculosis
Actinomycosis
Nocardiosis
Malignant lymph node and sinus
The most likely diagnosis could be actinomycosis or tuberculosis…
Actinomycosis can present in this site frequently…Jaw involvement and regional lymph node spread is very common and accounts for the main 50% of the cases of actinomycosis…. Pulmonary and abdomino pelvic sites are the next areas of involvement…
Tuberculosis can present as non healing sinus….We need to get CBC, IGRA, Mantoux test and baseline investigations for the same.. CT scan of the neck and chest is indicated to find out lymph node involvement…Pulmonary TB could co exist with lymph nodes…. We can send the pus for AFB stain, Gene Xpert MTB and AFB culture… For definitive diagnosis we need to do cervical lymoh node biopsy
Actinomycosis – requires microbiological expertise to diagnose it…Gram stain reveals non spore gram positive rods…slow growing in culture…require anerobic culture….HPE of lymph node shows sulfur granules with filamentous structures resembling fungi in H and E stain.. This confirms the diagnosis….
So in this patient i would do Cervical lymph node excision biopsy to confirm the diagnosis
Treatment of Actimumycosis is prolonged… high dose Intravenous penicillin G 24 MIU/day for 2 to 6 weeks followed by high dose of oral penicillin for 6 months to precent relapse is needed…Macrolides, Doxycycline are other alternatives…
Treatment for TB will be 2 months of HRZE and 4 months of HR as per our national guidelines RNTCP India
I will reduce antimetabolite and maintain low dose Tacrolimus and steroids
Cervical actinomycosis is the most likely diagnosis
. Other defferentilas :
Tuberculosis tuberculosis lymphadenitis may present with multiple discharge sinuses
Nocardiosis
Malignancy – lymphoma
Is it a common site for this form of infection?
Actinomyces are non-spore-forming, filamentous anaerobes. They are one of oral normal flora present in gingival crevices and tonsillar crypts and are particularly prevalent in periodontal pockets, dental plaques, and on carious teeth. Actinomycotic infection affecting the mandible (53.6%), cheek (16.4%), chin (13.3%), submaxillary ramus and angle (10.7%), maxilla (5.7%), and temporomandibular joints (0.3%). Immunosuppression and local trauma are important risk factors of infection .
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients Diagnosis :
– Histopathology or microbiology of the infected site is the confirmatory test for actinomycosis . Direct examination may reveal the presence of non -spore Gram -positive rods.
– These bacteria are slow-growing (5-20 days)and require anaerobic culture (blood agar media at 35–37°C) , this why cultures are positive in only 50% of cases.
– rRNA gene sequencing is sometimes performed when identification of Actinomyces isolates fails by conventional methods Treatment :
-The cornerstone for treatment of actinomycosis is high doses of intravenous penicillin( 2–5 million IU per day ) followed by oral penicillin .
– Antibiotic treatment duration has to be adjusted to the location of infection, the severity of the lesion and patient history. Generally IV penicillin given for two to six weeks followed by high doses of oral penicillin for six to twelve months to prevent relapse.
– Tetracycline or cephalosporins are options of treatment in penicillin allergy .
– Surgery for drainage is more common in renal transplant recipients than in the general population,but , surgery should be avoided, except in cases of hemoptysis or abscess , because it often leads to a large surgery.
– The global outcome of actinomyces infection is good regardless of immunosuppressive status References:
cervicofacial actinomycosis is the most common location
Actinomycosis is usually diagnosed by culturing the organism, although the specimens must be handled properly and cultures held for at least 14 days.
treatment of this condition regarding immunosuppressed patients Reduction of immunosupressants high-dose penicillin as the treatment of choice for actinomycosis. Alternative agents include amoxicillin or amoxicillin-clavulanate or doxycycline. Management of cervicofacial actinomycosis often requires prolonged courses of antibiotics. Surgical intervention may also be necessary in more complicated cases. In severe periapical actinomycosis resistant to conventional therapy, root-end surgery with bone grafting may be required
Management
1) Septic parameter and blood culture
2) To start the patient with an antibiotic (amoxicillin-clavulanic)
3) Surgery and drainage
4) Reduction of immunosuppression ie: withholding MMF
5) Monitor graft function
Reference
1) Rousseau C, Piroth L, Pernin V, Cassuto E, Etienne I, Jeribi A, Kamar N, Pouteil-Noble C, Mousson C. Actinomycosis: An infrequent disease in renal transplant recipients? Transpl Infect Dis. 2018 Dec;20(6):e12970. doi: 10.1111/tid.12970. Epub 2018 Aug 11. PMID: 30055044.
The differential diagnosis included the following: Cervicofacial actinomycosis Mycobacterial cutaneous infection Mucormycosis Bacterial infection Osteomyelitis The most prevalent presentation of cervicofacial actinomycosis is fistula formation in the perimandibular area.
Diagnosis and treatment
The clinical diagnosis must be validated by histopathologic and bacterial tests.
Actinomycosis has been reported in renal transplant recipients infrequently to date.
The treatment consists of protracted penicillin administration.
There may be a need for surgical drainage, debridement, and resection.
Actinomycosis is distinguished from other diseases by the presence of acid-fast negative ray-like bacilli and sulfur granules.
Immunosuppressive medications may need to be adjusted to the lowest effective quantities (guided by trough levels) in order to prevent infection and rejection.
· Is it a common site for this form of infection? 60% of cases of actinomycosis affects cervicofacial area, so , yes this is the commonest site for this infection.
· Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
1-Diagnosis of actinomycesis
-Detailed history and examination .
-Assess risk factors for this infection including : dental cares , extraction or implants , diabetes
2- Investigations
– CBC , ESR, CRP , LFT, KFT
– Tac trouh level
– HbA1c , fasting and postprandial blood suger
– CT /MRI head to exclude any ostelytic focuses
– Gold standard investigation is tissue biopsy and culture , but not swap biopsy that could be false positive. Treatment :
1- A long term course of pencillin is the treatment of choice but as actinomycosis commonly present a polymicrobial infection so combination antibiotic is required . Combination of beta lactamase inhibitor and metronidazole is reasonable . Also macrolids, clindamycin and doxycyclin are effective.Antibiotic should be continued for 6-12 months to prevent relapse or till complete cure of affected site.
2- Eradicate any other focus for actinomycis .
3- Surgical intervention as abcess drain , decompression or excision of abcess track may be required.
4- Actinomycosis isa surrogate marker of immunesuppression , thus the dose and trough level of IS need to be reduced specially MMF with close monitoring of graft function to detect any graft rejection early.
Ref:
Rousseau C, Piroth L, Pernin V, Cassuto E, Etienne I, Jeribi A, Kamar N, Pouteil-Noble C, Mousson C. Actinomycosis: An infrequent disease in renal transplant recipients? Transpl Infect Dis. 2018 Dec;20(6):e12970. doi: 10.1111/tid.12970. Epub 2018 Aug 11. PMID: 30055044
· Is it a common site for this form of infection? 60% of cases of actinomycosis affects cervicofacial area, so , yes this is the commonest site for this infection.
· Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
1-Diagnosis of actinomycesis
-Detailed history and examination .
-Assess risk factors for this infection including : dental cares , extraction or implants , diabetes
2- Investigations
– CBC , ESR, CRP , LFT, KFT
– Tac trouh level
– HbA1c , fasting and postprandial blood suger
– CT /MRI head to exclude any ostelytic focuses
– Gold standard investigation is tissue biopsy and culture , but not swap biopsy that could be false positive. Treatment :
1- A long term course of pencillin is the treatment of choice but as actinomycosis commonly present a polymicrobial infection so combination antibiotic is required . Combination of beta lactamase inhibitor and metronidazole is reasonable . Also macrolids, clindamycin and doxycyclin are effective.Antibiotic should be continued for 6-12 months to prevent relapse or till complete cure of affected site.
2- Eradicate any other focus for actinomycis .
3- Surgical intervention as abcess drain , decompression or excision of abcess track may be required.
4- Actinomycosis isa surrogate marker of immunesuppression , thus the dose and trough level of IS need to be reduced specially MMF with close monitoring of graft function to detect any graft rejection early.
Ref:
Rousseau C, Piroth L, Pernin V, Cassuto E, Etienne I, Jeribi A, Kamar N, Pouteil-Noble C, Mousson C. Actinomycosis: An infrequent disease in renal transplant recipients? Transpl Infect Dis. 2018 Dec;20(6):e12970. doi: 10.1111/tid.12970. Epub 2018 Aug 11. PMID: 30055044
The five infections (32 cases) that were identified, included 18 cases of tuberculosis (56.25%) followed by 9 cases of actinomycosis (28.12%), 3 cases of pheohypomycosis (9.37%), and one case each of Nocardia (3.12%) and eumycetoma (3.12%) which presented as swelling with discharging sinus.
Is it a common site for this form of infection?
Yes, Orocervicofacial actinomycosis is the most common form of the disease, seen in up to 55% of cases.
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
(CT) scan
Histopathological examination of the excised specimen suggested soft-tissue fibroma secondarily infected with actinomycosis. Demonstration of Gram-positive filamentous organisms and sulphur granules on histological examination is strongly supportive of a diagnosis of actinomycosis.
For definitive diagnosis, direct isolation of the organisms from a clinical specimen or from sulphur granules is necessary.
Penicillin or amoxicillin/clavulanic acid are the preferred antibiotic regimens.
The traditional treatment is high-dose penicillin for a prolonged period (6 months to 1 year).The duration of antibiotic therapy with 6–12 million IU penicillins can range from 4 weeks to 1 year based on the severity of the disease. Surgical management without antibiotic therapy is associated with recurrence.
In case of penicillin allergy, clindamycin would be administered.
Fistula formation at peri mandibular area is most common presentation at cervicofacial actinomycosis.
Principle of diagnosis and treatment of this condition regarding immunosuppressed patients:
Diagnosis:
– Culture; FNA/Large biopsy without contamination by other skin organisms with incubation in anaerobic or microaerophilic condition for 14 days. – Histology; Multiple sections of biopsy. – Monoclonal antibody staining. – Molecular techniques -PCR, rRNA
Treatment:
– Penicillin is the treatment of choice. – Alternates areamoxicillin, amoxicillin-clavulanate, doxycycline. – Modification of IS can be needed in extensive disease with stopping of MMF and reducing CNI at lower therapeutic level. Reference:
5. An a-61-year-old female patient presented with a 3-month history of multiple sinuses in the right side of the face (see below) without fever 7 months after receiving a kidney transplant from his 32-year-old son. She is on Tacrolimus-based triple immunosuppression with excellent graft function.
Issues/ concerns
– 61yo female, LDKT, 7 months ago, donor 32yo son
– 3/12 hx of multiple sinuses on the right side of the face, no fevers
cervicofacial (60%) due to an oral procedure or injury
pulmonary due to aspiration of oral and gastrointestinal secretions and chronic lung diseases
genitourinary tract due to use of IUCDs
abdominal due to abdominal surgeries appendix, caecum, colon
skin and soft tissues – rare, occurs secondary to skin injury
hematogenous dissemination – extremely rare
– actinomyces is part of the normal flora in the human oral cavity, GI tract, female urogenital tract
– it is not virulent; it only invades the body when there is tissue injury and subsequent break in the normal mucosal barrier leading to deeper infections and an intense suppurative and granulomatous inflammatory response
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients (1-3)
– actinomycosis is a rare disease, the infection is polymicrobial and is associated with disruption of the mucosal barrier leading to severe infection in immunosuppressed patients, it is a surrogate marker of poor prognosis among these patients
– actinomyces is a gram positive non-acid fast anaerobe, it causes infection by inhibiting host defenses and/ or reducing partial pressures of oxygen
– chronic actinomycosis presents with multiple abscesses which form sinus tracts and are associated with sulphur granules which can be detected on microscopy
– diagnosis: is difficult since isolation of the organism requires prolonged bacterial culture under anaerobic conditions
– baseline investigations: CBC, ESR, CRP, LFTs, tacrolimus trough level blood sugar, HIV Ab, dental radiograph, CT/ MRI to check for osteolysis in the setting of chronic infection
– gold standard test for diagnosis – tissue biopsy culture with anaerobic pus cultures
– avoid swabs from infected sites, cultures can be falsely negative
– serological tests: have no additional diagnostic value
– imaging studies: depends on the site of infection, can mimic other chronic infections like TB, malignancy
Treatment/ management
– for most cases, the mainstay of management is antibiotics, surgery can be adjunctive
– Penicillin G, beta-lactams with long course of oral amoxicillin, cephalosporin
– alternative antibiotics for patients allergic to penicillin: macrolides, clindamycin, doxycycline
– combination of beta-lactamase inhibitor and metronidazole may be used in polymicrobial infections
– duration of treatment is usually 6-12months but if surgical resection of the infected site is done the duration of treatment can be shortened
– surgery usually involves incision and drainage of abscesses, excision of sinus tracts, decompression of closed space
– imaging can be used to monitor response to treatment
Cervicofacial actinomycosisNontuberculous mycobacterium infectionMucormycosisMycetomaCancer (metastatic)Is it a common site for this form of infection?
Yes
There are 4 primary subtypes of actinomycosis infection:
Cervical-oral (60 %)Abdominal (20 %)Pulmonary (15 %)Pelvic (5 %)Actinomycosis is caused by branched, filamentous anaerobic Gram-positive bacteria called Actinomyces.
chronic granulomatous & suppurative infectious disease.
. Actinomycosis becomes pathological in immunocompromised patients.
Management:
must be confirmed by histopathologic & bacteriologic examinations.Treatment is with prolonged courses of penicillinsActinomycosis is differentiated from other diseases with acid-fast negative like bacilli & sulphur granules being pathognomonic.Immunosuppressive medications may need to be adjusted to the minimal possible doses,guided by drug levelsSurgical drainage, debridement, & resection may be required.References:
Wong VK, Turmezei TD, Weston VC. Actinomycosis. BMJ 2011; 343:d6099.Smego RA Jr, Foglia G. Actinomycosis. Clin Infect Dis 1998; 26:1255.Gilbert DN, Moellering RC Jr, Sande MA. The Sanford Guide to Antimicrobial Therapy. Antimicrobial Therapy, Inc 2001; 31:70.
DD _Craniofacial actinomycosis , most probable. _Mycetoma -.Skin cancer. _Non tuberculous mycobacterial infection. _Pyogenic bacterial infection Diagnosis needs microbiological testing (swab and aspirate with gram staining , culture on anaerobic media may reveal filamentous rods. Treatment: .IS reduction (stopping MMF and use CNI with lower trough level) with graft function monitoring. . Penicillin for 4-6 weeks ; erythromycin in allergic patients . .surgical drainage & debridement may be needed.
An a-61-year-old female patient presented with a 3-month history of multiple sinuses in the right side of the face (see below) without fever 7 months after receiving a kidney transplant from his 32-year-old son. She is on Tacrolimus-based triple immunosuppression with excellent graft function. What is your differential diagnosis?
Cervicofacial actinomycosis.
TB.
Bacterial infection.
Granulomatous dx.
Norcadiasis.
Mucomycosis.
Abscess.
Is it a common site for this form of infection?
Fistula formation at peri mandibular area is most common presentation at cervicofacial actinomycosis.
Sites;
Mandible 53.6%
Cheek 16.4%
Chin 13.3%
Sub maxillary ramus and angle 10.7%
Upper jaw 5.7%
Mandibular joint 0.3%
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
Diagnosis;
Culture; FNA/Large biopsy without contamination by other skin organisms with incubation in anaerobic or microaerophilic condition for 14/7.
Histology; Multiple sections recommended.
Monoclonal antibody staining
Molecular techniques -PCR with rRNA- MALDI- TOF ms which is accurate in identifying actinomycosis spp.
Treatment;
SX for complicated cases.
High dose penicillin.
Other alternatives ;Amoxixillin/augmentin /Doxycycline.
Dose ; Severe or extensive actinomycosis- IV pen G (10-20million units daily 4-6 hrly) – 4-6/52,PO Amoxicillin 1.5-3g/day can be used. Mild actinomycosis ;PO Pen V (2-4G/24hrs) divided into 4 daily doses. Alternative; PO Amoxicillin 1.5-3g/24hrs
Allergic to penicillin; Ceftriaxone, doxy, macrolides and carbapenems.
Agents that are not effective ;aminoglycosides,flagyl,aztreonam,septrin, penicillinase resistant penicillin,cephalexin,ceftazidime and antifungal drugs.
Duration ;Maintain tx for 1-2/12 after resolution of manifested infection;2-6/12 for mild dx and 6-12/12 for severe. Duration is extended to 12-18/12 in immunosuppressed pts, HIV, Complicated and invasive cases. Shorter duration of less than 2 months not recommended due to risk of recurrence.
RIS – Reduce the dose of antimetabolite. In mild cases this is not a must. We don’t have clear guidelines on this.
REF;
Uptodate – Tx of actinomycosis.
Piroth V et .Actinomycosis;an infrequent disease in renal transplant recipient;Transp infec dis 2018 dec;20(6);e12970
Valentin MN et al;Cervicofacial actinomycosis int J Dermtol 2020 oct ;59(10)1185-1190
What is your differential diagnosis?skin cancer
chronic bactrial infection nocradia
tuberculosis
actinomycosis ( cervicofascial suppourative actinomycosis with super added bacterial infection
Is it a common site for this form of infection?
the lesion involve typical anatomial site for actinomycosis , need to ask about any recent truama ,surgical intervention ,or orodental surgery, bad oral hygiene
actinomycosis is very infrequent and rare chronic granulomatous bacterial infection evidence is limited to a few case reports, and case series of granulomatous bacterial infection caused by actinomycetes which belong to gram-positive anaerobic bacteria, a very heterogenous and nonspecific presentation that delay the diagnosis, typically involve the cervicofacial sites from oropharyngeal lesions, also in a french cohort of 25 cases have been reported from different sites including soft tissues, orofacial, thoracic and gut involvement, diagnosis based on a high index of clinical suspicion with microbiology and tissue histology, treatment mainly with amoxicillin for long course minimum of 90 days but average between 6-12 months along with surgical drainage
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
high index of clinical suspicion especially in immunosuppressed patients, DM, poor oral hygiene, recent trauma or surgery, ICUD in females with abdominal pelvic actinomycosis
microbiology and histopathology are important for the diagnosis
treatment involve B lactam ABlike amoxicillin for 6-12 months along with surgical drainage ,immunsuppression role is not clear as its have been found in immunocompetent patients as well , however,thereis reported cases of disseminated actinomycosis in immunocompromized patient with associated mortality up to 21% in one case series (3).
References
1. Rousseau C, Piroth L, Pernin V, Cassuto E, Etienne I, Jeribi A, Kamar N, Pouteil-Noble C, Mousson C. Actinomycosis: An infrequent disease in renal transplant recipients? Transpl Infect Dis. 2018 Dec;20(6):e12970. doi: 10.1111/tid.12970. Epub 2018 Aug 11. PMID: 30055044.
2. Bonnefond S, Catroux M, Melenotte C, Karkowski L, Rolland L, Trouillier S, Raffray L. Clinical features of actinomycosis: A retrospective, multicenter study of 28 cases of miscellaneous presentations. Medicine (Baltimore). 2016 Jun;95(24):e3923. doi: 10.1097/MD.0000000000003923. Erratum in: Medicine (Baltimore). 2016 Aug 07;95(31):e5074.
3. Cunha F, Sousa DL, Trindade L, Duque V. Disseminated cutaneous Actinomyces bovis infection in an immunocompromised host: case report and review of the literature. BMC Infect Dis. 2022 Mar 29;22(1):310. doi 10.1186/s12879-022-07282-w. PMID: 35351021; PMCID: PMC8962608.
Is it a common site for this form of infection? Cervicofacial actinomycosis is a chronic disease characterized by abscess formation, draining sinus tracts, fistulae, and tissue fibrosis.
It can mimic a number of other conditions, particularly malignancy and granulomatous disease, and should be included in the differential diagnosis of any soft tissue swelling in the head and neck.
Cervicofacial involvement is the most common manifestation of actinomycosis, accounting for 50 percent of all cases, while central nervous system, thoracic, abdominal, and pelvic actinomycosis occur less frequently
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients! Culture — Confirmation of the diagnosis requires the recovery of Actinomyces species from an appropriately cultured specimen, typically by needle aspiration of an abscess, fistula, or sinus tract or from a large biopsy specimen.
Histology — Multiple sections of a biopsy specimen from different tissue levels are suggested to improve histologic diagnosis Sections of biopsy material typically reveal acute or chronic inflammatory granulation tissue with infiltration by neutrophils, foamy macrophages, plasma cells and lymphocytes, and a surrounding dense fibrosis. Healing lesions tend to demonstrate profound fibrosis, even avascular in nature, often in proximity to areas of acute suppuration. Sulfur granules may comprise no more than 1 percent of total tissue in a given lesion, and hence are easily missed by routine tissue staining.
Monoclonal antibody staining — In contrast, specific staining using fluorescent-conjugated monoclonal antibody (FA) has been shown to improve the identification of various Actinomyces species, even in mixed infections and after fixation in formalin
Molecular techniques — The diagnosis of cervicofacial actinomycosis has been greatly improved with the advent of molecular techniques such as detection by polymerase chain reaction with 16S ribosomal ribonucleic acid (rRNA) gene probes from clinical specimens.
High dose penicillin is the treatment of choice for actinomycosis . Alternative agents include amoxicillin or amoxicillin-clavulanate or doxycycline. Management of cervicofacial actinomycosis often requires prolonged courses of antibiotics. Surgical intervention may also be necessary in more complicated cases. In severe periapical actinomycosis resistant to conventional therapy, root-end surgery with bone grafting may be required . Reduction of immunosupression is usually not required however it can be considered if the response is not appropriate
What is your differential diagnosis?
Skin lesion with indurated area of multiple, small, communicating abscesses surrounded by granulation tissue. There seem to be a sinus with discharge looks like having a tendency to spread contiguous tissues.
Cervico-facial actinomycosis is the most likely differential diagnosis. Actinomyces species are commensal in human open cavities, including the mouth, and the most common pathogenic species encountered is A. israelii(1)
Differential diagnosis to this skin lesion is as follows: · Cervico-facial actinomycosis. · Skin TB and non-tuberculous MB infection of the skin. · Bacterial infection. · Malignant lesion; desmoid tumor, cutaneous tumor and SCC(2).
Is it a common site for this form of infection? 1. Cervicofacial involvement is the most common manifestation of actinomycosis, accounting for 50 percent of all cases, while central nervous system, thoracic, abdominal, and pelvic actinomycosis occur less frequently(3). 2. The cervicofacial form usually begins as a small, flat, hard swelling, with or without pain, under the oral mucosa or the skin of the neck or as a subperiosteal swelling of the jaw. Subsequently, areas of softening appear and develop into sinuses and fistulas that discharge the characteristic sulfur granules. 3. Actinomycosis usually involves multiple small, communicating abscesses with sinus tracts that drain a purulent discharge. 4. Infection typically involves the neck and face, lungs, or abdominal and pelvic organs. The cheek, tongue, pharynx, salivary glands, cranial bones, meninges, or brain may be affected, usually by direct extension. 5. Microscopically, Actinomyces appears as distinctive “sulfur” granules (rounded or spherical particles, usually yellowish, and ≤ 1 mm in diameter) or as tangled masses of branched and unbranched wavy bacterial filaments. 6. High-dose penicillin is usually effective but must be given long-term (8 weeks to 1 year).Surgery to drain abscesses and excise fistulas may be needed.
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients! 1. Diagnosis of actinomycosis(4): Actinomycosis is suspected clinically and confirmed by identification of A. israelii or other Actinomyces species using microscopy and culture of sputumand drained fluid. CT scan of the affected areas may be needed. 2. Prognosis relates directly to early diagnosis and is most favorable in the cervicofacial form. 3. Treatment of actinomycosis: a) Most patients with actinomycosis respond to antibiotics, but response is usually slow because of extensive tissue induration and the relatively avascular nature of the lesions. b) High doses of penicillin G (eg, 3 to 5 million units IV every 6 hours) are usually effective. Penicillin V 1 g orally 4 times a day may be substituted after about 2 to 6 weeks. c) There were reported cases of actinomycosis treated with amoxicillin for 30-200 days (median duration of 115 days), and clavulanic acid was added for 28.5% of cases(5). d) Oral tetracycline 500 mg every 6 hours or doxycycline 100 mg every 12 hours may be given instead of penicillin. e) Minocycline, clindamycin, and erythromycin have also been successful. Erythromycin increase the level of TAC. 4. Adjustment of immunosuppression: actinomycosis is infrequently encountered in immunocompromised patients and in those under immunosuppressants. Although, global and renal outcomes do not seem to be affected by actinomycosis(5), immunosuppressants should be adjusted to the minimally accepted target to minimize the contagious spread of actinomycosis. Anti-metabolite should reduced by 25% to 50%, and CNI to be kept at the lower target.
References 1. Bonnefond S., Catroux M., Melenotte C. Clinical features of actinomycosis: a retrospective, multicenter study of 28 cases of miscellaneous presentations. Medicine (Baltim) 2016;95 [PMC free article] [PubMed] [Google Scholar] 2. Shinpei Matsuda, Hisato Yoshida, and Hitoshi Yoshimura Orofacial soft tissues actinomycosis: A retrospective, 10-year single-institution experience J Dent Sci. 2021 Jan; 16(1): 365–369. https://www.ncbi.nlm.nih.gov/ 3. UpToDate; Cervicofacial actinomycosis. Abdu A Sharkawy, Anthony W Chow.https://www.uptodate.com/contents/search 4. Actinomycosis by Larry M. Bush https://www.merckmanuals.com/professional/infectious-diseases/anaerobic-bacteria/actinomycosis 5. Rousseau C, Piroth L, Pernin V, Cassuto E, Etienne I, Jeribi A, Kamar N, Pouteil-Noble C, Mousson C. Actinomycosis: An infrequent disease in renal transplant recipients? Transpl Infect Dis. 2018 Dec;20(6):e12970. doi: 10.1111/tid.12970. Epub 2018 Aug 11. PMID: 30055044.
👉 Differential diagnosis of multiple skin sinuses:
_Craniofacial actinomycosis (anaerobic gram postive bacilli).
_Mycetoma.
_Non tuberculous mycobacterial infection.
_Pyogenic bacterial infection
_Skin cancer.
👉 yes, it is a common site of infection and skin sinuses.
_otger sites thoracic, abdominal , pelvic and cutaneous . 👉 Diagnosis is based on microbiological identification (swab and aspirate with gram staining and has diagnostic sulfur granules ) or by culture on anaerobic media revealing filamentous rodes.
👉 Treatment involves:
_reduction of IS (stop MMf and use CNI with lower window of trough level).
_use prolonged course of penicillin for 4-6 weeks or erythromycin in allergic patients ).
_surgical drainage and debridement may be used
_ close monitoring of graft function in the context of reduction of IS therapy.
What is your differential diagnosis?
D/D are Actinomycosis Tuberculosis’
Osteomyelitis
Herpes Simplex
Fungal infection
Is it a common site for this form of infection?Orofacial
Cervical and Facial area
Pulmonary actinomycosis
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
Stop anti metabolites drug
Reduce tacrolimus to lower limit
Keep steroid dose
Intravenous penicillin G for long time 6 weeks and then oral penicillin V for 6 months to one year Amoxicillin intravenous
Cervical actinomycosis is the most likely diagnosis
. Other defferentilas :
Tuberculosis tuberculosis lymphadenitis may present with multiple discharge sinuses
Nocardiosis
Malignancy – lymphoma
Is it a common site for this form of infection?
Actinomyces are non-spore-forming, filamentous anaerobes. They are one of oral normal flora present in gingival crevices and tonsillar crypts and are particularly prevalent in periodontal pockets, dental plaques, and on carious teeth. Actinomycotic infection affecting the mandible (53.6%), cheek (16.4%), chin (13.3%), submaxillary ramus and angle (10.7%), maxilla (5.7%), and temporomandibular joints (0.3%). Immunosuppression and local trauma are important risk factors of infection .
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients
Diagnosis :
– Histopathology or microbiology of the infected site is the confirmatory test for actinomycosis . Direct examination may reveal the presence of non -spore Gram -positive rods.
– These bacteria are slow-growing (5-20 days)and require anaerobic culture (blood agar media at 35–37°C) , this why cultures are positive in only 50% of cases.
– rRNA gene sequencing is sometimes performed when identification of Actinomyces isolates fails by conventional methods
Treatment :
-The cornerstone for treatment of actinomycosis is high doses of intravenous penicillin( 2–5 million IU per day ) followed by oral penicillin .
– Antibiotic treatment duration has to be adjusted to the location of infection, the severity of the lesion and patient history. Generally IV penicillin given for two to six weeks followed by high doses of oral penicillin for six to twelve months to prevent relapse.
– Tetracycline or cephalosporins are options of treatment in penicillin allergy .
– Surgery for drainage is more common in renal transplant recipients than in the general population,but , surgery should be avoided, except in cases of hemoptysis or abscess , because it often leads to a large surgery.
– The global outcome of actinomyces infection is good regardless of immunosuppressive status
Cervicofacial discharging sinuses without fever DDx are:
o Cervicofacial Actinomycosis.
o Granulomatous invasive aspergillosis.
o Oral squamous cell carcinoma.
o Tuberculosis.
o Nocardiosis.
o Mucormycosis.
Is it a common site for this form of infection?
Yes, it is the cervico- facial involvement is the most common site in 50%.
other sites are mandible 35 %, cheek 16 %, chin 13 %, Submaxillary ramus and angle 10 %, Upper jaw 5.7 %, rare sites are central nervous system, thoracic, and abdomen.
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patient?
Diagnosis:
The Gold standard is a histopathological after a surgical excision and tissue culture, reveals a central zone of necrosis, multiple lobulated microcolonies, mixed cell infiltrate, microabscesses, and sinus tracts, surrounded by fibrosis and connective tissue, biopsy alone would not give the diagnosis if not taken from the disease focus area, sulfur granules surrounded by brightly eosinophilic areas (Splendore-Hoeppli phenomenon) may be suggestive.Actinomycosis is It is a slow growing anaerobic gram positive rod –need special culture for growth.Risk factors: deceased organ, immunosuppressive medications and induction with ATG, other comorbidities(DM). Treatment:
First line after surgical excision treatment is penicillin/ augmnetin for 4-12 weeks, in penicillin allergyMinocycline for 6- 18 weeks, carbapenems or tegacyclin.Clindamycin and metronidazole should be avoidedwith high resistance rate. Recurrence usually occurs a year after, so biannual follow-up and intervention is required, the patient must have a good dental hygiene. The Nd:YAG laser has potential as a novel treatment for cervicofacial actinomycosisin vitro. However, it has yet to be studied in vivo.The response to treatment should be carefully monitored and imaging with computed tomography or magnetic resonance imaging may be necessary to ensure resolution. The cure rate is high but deformities and death is common.In index case 3 months’ post kidney transplant, I would stop MMF, decrease the dose of tacrolimus to trough level of 4-6 ng/dl, but will keep on prednisolone. with frequent monitoring of graft function and for any rejection.as an inhibition of CD4 cells in murine Peyer’s patch stops the production of specific antibodies in the case of infection due to A. viscosus. In transplant patients, immunosuppressive drugs induce lower rates of CD4+. References:
(1) Karanfilian KM, Valentin MN, Kapila R, Bhate C, Fatahzadeh M, Micali G, Schwartz RA. Cervicofacial actinomycosis. Int J Dermatol. 2020 Oct;59(10):1185-1190. doi: 10.1111/ijd.14833. Epub 2020 Mar 11. PMID: 32162331.
(2) Rousseau C, Piroth L, Pernin V, Cassuto E, Etienne I, Jeribi A, Kamar N, Pouteil-Noble C, Mousson C. Actinomycosis: An infrequent disease in renal transplant recipients? Transpl Infect Dis. 2018 Dec;20(6):e12970. doi: 10.1111/tid.12970. Epub 2018 Aug 11. PMID: 30055044..
(3) Sosroseno W, Bird PS, Gemmell E, Seymour GJ. The role of CD4+ and CD8+ T cells on antibody production by murine Peyer’s patch cells following mucosal presentation of Actinomyces viscosus. Oral Microbiol Immunol. 2006 Dec;21(6):411-4. doi: 10.1111/j.1399-302X.2006.00308.x. PMID: 17064401.
The global outcome of actinomycosis is good regardless of immunosuppressive status. In renal transplant recipients, renal outcomes was not found to be affected and no graft rejection was observed.
Reference :
Actinomycosis: an infrequent disease in renal transplant recipients?. Transplant Infectious Disease, (), e12970–. doi:10.1111/tid.12970
I would stop MMF, decrease the dose of tacrolimus to trough level of 4-6 ng/dl, but will keep on prednisolone. with frequent monitoring of graft function and for any rejection.as an inhibition of CD4 cells in murine Peyer’s patch stops the production of specific antibodies in the case of infection due to A. viscosus. In transplant patients, immunosuppressive drugs induce lower rates of CD4+.
Reference:
Sosroseno W, Bird PS, Gemmell E, Seymour GJ. The role of CD4+ and CD8+ T cells on antibody production by murine Peyer’s patch cells following mucosal presentation of Actinomyces viscosus. Oral Microbiol Immunol. 2006 Dec;21(6):411-4. doi: 10.1111/j.1399-302X.2006.00308.x. PMID: 17064401.
My approach will be to start the antibiotics, wait & wee, if the lesions started to respond to treatment I will not touch the immune suppression. However, in dificult cases I will be tempted to come down a bit with anti-metabolites.
Immunosuppression reduction is usually not required. The outcome of actinomycosis is good regardless of immunosuppressive status and does not affect graft outcome in renal transplant recipients (1). In disseminated/ systemic involvement, immunosuppression might be required to be reduced or stopped temporarily, according to the clinical status of the patient, as in management of any life-threatening sepsis.
Reference:
Rousseau C, Piroth L, Pernin V, Cassuto E, Etienne I, Jeribi A, Kamar N, Pouteil-Noble C, Mousson C. Actinomycosis: An infrequent disease in renal transplant recipients? Transpl Infect Dis. 2018 Dec;20(6):e12970. doi: 10.1111/tid.12970. Epub 2018 Aug 11. PMID: 30055044.
Adjustment of immunosuppression: actinomycosis is infrequently encountered in immunocompromised patients and in those under immunosuppressants. Although, global and renal outcomes do not seem to be affected by actinomycosis(5), immunosuppressants should be adjusted to the minimally accepted target to minimize the contagious spread of actinomycosis. Anti-metabolite should reduced by 25% to 50%, and CNI to be kept at the lower target.
Thanks prof
As we know actinomycosis would required prolong therapy and responsive to antibiotics which could have less potential of drug-drug interactions, so will see the response if not improving with prolong therapy than no need for IS reduction and in case of lack of improvement will have to reduce/stop MMF/AZA with monitoring for allograft functions.
– for most cases, the mainstay of management is antibiotics, with good response to treatment
– unless the patient has life-threatening/ disseminated/ systemic disease in which case I would reduce the immunosuppression
Reference
1. Rousseau C, Piroth L, Pernin V, Cassuto E, Etienne I, Jeribi A, et al. Actinomycosis: An infrequent disease in renal transplant recipients? Transplant infectious disease : an official journal of the Transplantation Society. 2018 Dec;20(6):e12970. PubMed PMID: 30055044. Epub 2018/07/29. eng.
It has a good response to antibiotics and sx where indicated, unless the pt develops a life threatening infection, we maintain the current immunosuppressive meds doses.
– No, I would not modify the immunosuppression
– for most cases, the mainstay of management is antibiotics, with good response to treatment
– unless the patient has life-threatening/ disseminated/ systemic disease in which case I would reduce the immunosuppression Reference
1. Rousseau C, Piroth L, Pernin V, Cassuto E, Etienne I, Jeribi A, et al. Actinomycosis: An infrequent disease in renal transplant recipients? Transplant infectious disease : an official journal of the Transplantation Society. 2018 Dec;20(6):e12970. PubMed PMID: 30055044. Epub 2018/07/29. eng.
according to one study conducted in France, actinomycosis is a rare, progressive disease occurring in kidney transplant recipients, responsive to penicillin course of few months. However, actinomycosis infection does not impact the global and renal outcome.
Hence, I don’t think modulating immune suppressive protocol is warranted.
References:
1] Celia Rousseau et al. Actinomycosis: An infrequent disease in renal transplant recipients?. Transpl Infect Dis. 2018 Dec;20(6):e12970.
This patient has a chronic infection that has resulted in the formation of sinuses in the cervicofacial region
The differential diagnosis includes:
Cervicofacial actinomycosis
Tuberculosis
Nocardiosis
Mucormycosis
Osteomyelitis of the mandible
Skin malignancy
The most common site of actinomycosis infection is the cervicofacial region accounting for 50% of cases followed by the central nervous system, thoracic, abdominal and pelvic sites
Adult males with poor oral hygiene appear to be at greater risk of developing cervicofacial actinomycosis. The predisposing factors include:
Dental caries and extractions
Dental implants
Gingivitis and gingival trauma
Infections in erupting secondary teeth
Patients with DM, malnutrition, immunosuppression are at greater risk
Diagnosis:
Actinomycosis is usually diagnosed by recovery of the organism from an appropriately cultured specimen typically by needle aspiration of the abscess, fistula or sinus tract or from a large biopsy specimen. Care needs to be taken to avoid contaminating the specimen with the normal flora in the oral cavity. The specimen needs to be incubated under strict anaerobic conditions for at least 14 days
Histology: Multiple sections from a biopsy specimen can aid in the histological diagnosis. Sections of biopsy material typically reveal acute or chronic inflammatory granulation tissue with infiltration by neutrophils, foamy macrophages, plasma cells and lymphocytes. It is difficult to differentiate filaments of nocardia and actinomycosis using conventional methods such as Grocott-Gomori-methenamine stain
Monoclonal Antibody Staining:Specific staining using fluorescent-conjugated monoclonal antibody has been shown to improve the identification of the various actinomyces species
Molecular techniques: Molecular techniques have greatly helped in the diagnosis of cervicofacial actinomycosis
Treatment:
High dose penicillin (10-20 million units daily in divided doses) is the treatment of choice for actinomycosis
Alternative agents include ceftriaxone amoxicillin, amoxicillin-clavulanate or doxicycline
The treatment duration is usually 2-6 months for mild disease and 6-12 months for severe disease
Surgical intervention may be necessary in more complicated cases
Olga Eastman et al. Actinomycosis: Diagnosis and Management. Curr Infect Dis Resp. 2005 Valour F et al. Actinomycosis: etiology, clinical features, diagnosis, treatment and management. Infect Drug Resist 2014;7:183
Cervicofacial actinomycosis is an invasive destructive infectious syndrome, caused by Gram-positive, branching filamentous bacteria, Actinomyces. Most of the cases are traced to an odontogenic source with periapical abscess and posttraumatic or surgical complications with poor hygiene and immunosuppression as contributing factors. Cervicofacial involvment happens in 50%- Jumpy Jaw Syndrome. Presenting clinical manifestations is confusing because they often mimic a malignancy or a granulomatous lesion.
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
Diagnosis is based on histology and microbiological assessment. Cultural isolation of Actinomyces species from clinical specimens, or microscopic visualization of gram-positive, non-acid-fast, thin, branching filaments in cytologic aspirates or histopathologic sections are the best methods of diagnosis of cervicofacial actinomycosis.
Such patients requires admission and immune suppression modification. MMF has to be stopped and TAC levels to be kept between 5-7 ng/ml.
Drug of choice is Penicillin G 20 million IU per day for 2-6 weeks. This is followed by oral penicillin for 6-12 months.
Surgical therapy is often indicated for curettage of bone, resection of necrotic tissue, excision of sinus tracts, and drainage of soft tissue abscesses. The prognosis for treated infection is excellent.
Moturi K, Kaila V. Cervicofacial Actinomycosis and its Management. Ann Maxillofac Surg. 2018 Jul-Dec;8(2):361-364. doi: 10.4103/ams.ams_176_18. PMID: 30693266; PMCID: PMC6327805.
Oostman O, Smego RA. Cervicofacial Actinomycosis: Diagnosis and Management. Curr Infect Dis Rep. 2005 May;7(3):170-174. doi: 10.1007/s11908-005-0030-0. PMID: 15847718.
What is your differential diagnosis?
Renal transplant patient with multiple sinuses in the cervicofacial region-likely diagnosis is Cervicofacial Actinomycosis. Other possibilities which can be considered in the above case includes: Tuberculosis and non-mycobacterial skin infection, Nocardiosis,Mucormycosis,osteomyelitis and lymphoma. Is it a common site for this form of infection?
Actinomycosis- a branched, filamentous anaerobic Gram-positive bacteria- involves different sites. However, cervico-facial site (lumpy-jaw syndrome)is the most common presenting in about 50% cases. Other sites include :abdominopelvic and pulmonary sites.
. Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patient?
Gold standard test for diagnosis is made by histopathological and microbiological examination of sample of the involved site of presentation like sputum, pus or tissue. It is a slow growing anaerobic gram positive rod –need special culture for growth. Granulomatous inflammation and fibrosis seen on histopathological examination and staining revealed sulfur granule with branched, gram-positive filamentous rods .Other supportive tests include: CBC, inflammatory markers like CRP,ESR etc. HRCT chest showed pneumonitis or cavitatory lesion, with or without pleural involvement.
Treatment –Firstly ,patient should be admitted and anti-metabolite i.e., MMF to be stopped and Tac level to be maintained around 5-7ng/ml.Drug of choice for actinomycosis is penicillin G –in a dose of 24MIU/day for 2-6 weeks followed by high doses of oral penicillin for 6-12 months .Alternatives include: Clindamycin, Macrolides ,and Doxycycline. Surgical intervention in the form of drainage with or without bone grafting is needed in resistant and complicated cases like enlarging abscess, recalcitrant fibrotic lesion, and osteomyelitis of the bone. Patient should be counseled to maintain dental hygiene
REFERENCES:
Moturi K, Kaila V. Cervicofacial Actinomycosis and its Management. Ann Maxillofac Surg. 2018 Jul-Dec;8(2):361-364.
What is your differential diagnosis? – Cervical actinomycosis (likely diagnosis) – Non-tuberculous mycobacterial infection. – Mucormycosis. . – Nocardiosis.
– Odontogenic Abscess
– Fungal infection (Blastomycosis)
– Malignancy
Is it a common site for this form of infection? Yes, Cervicofacial involvement is the most common site in 50%. -Mandible – 53.6 % -Cheek – 16.4 % -Chin – 13.3 % -Submaxillary ramus and angle – 10.7 % -Upper jaw – 5.7 % -Mandibular joint – 0.3 % while central nervous system, thoracic, abdominal, and pelvic actinomycosis occur less frequently Actinomycosis: – Itis a rare chronic disease caused by Actinomyces spp, gram positive facultative anaerobes – Normal flora colonize the human mouth and digestive and genital tracts.
– Disease occurs almost exclusively by direct invasion and rarely by hematogenous spread.
– It is a chronic disease characterized by abscess formation, draining sinus tracts, fistulae, and tissue fibrosis
-A hallmark is the tendency to spread without regard for anatomical barriers, including fascial planes or lymphatic drainage, and the development of multiple sinus tracts. – Risk factor: poor oral hygiene, and immunocompromised individuals. –It is mainly reported in immunocompetent patients. Diagnosis :
Culture: for definitive diagnosis, should be held for at least 14 days(slow growing)
Gram stain: Direct examination non-spore Gram-positive rods
Histopathology (filaments and sulfur granules)
Monoclonal antibody staining: specific staining using fluorescent-conjugated.
Serology: Serology does not appear to be a practical or reliable diagnostic tool.
Treatment: Antibiotic therapy: Severe / extensive infections: IV penicillin G 10 to 20 million units daily in divided doses),ceftriaxone is an alternative. For mild infection (no significant suppuration or fistulous tracts) or step-down therapy: Oral penicillin, Amoxicillin is an alternative.
-If patient is allergic to penicillin, tetracycline and erythromycin are suitable alternatives
Duration: debatable and has to be adapted to the severity of onset, location of the infection and patient history.
IV therapy for 4-6 weeks then continue oral 2- 6 months for mild disease and 6-12 months for severe disease) to prevent disease recrudescence
Surgery for drainage in severe infection. Prevention: maintenance of good oral hygiene and appropriate dental plaque removal.
Immunosuppression management:
-Balance the risks and benefits when modifying IS.
-Reduce the dose or stopping antimetabolite.
In renal transplantation:
– The global outcome is good and relapse is rare.
– Excellent renal outcome is regardless of immunosuppressive drugs
– It does not seem to increase graft rejection rates, References:
-Rousseau C, Piroth L, Pernin V, Cassuto E, Etienne I, Jeribi A, Kamar N, Pouteil-Noble C, Mousson C. Actinomycosis: An infrequent disease in renal transplant recipients? Transpl Infect Dis. 2018 Dec;20(6):e12970. doi: 10.1111/tid.12970. Epub 2018 Aug 11. PMID: 30055044.
Valour F, Sénéchal A, Dupieux C, Karsenty J, Lustig S, Breton P, Gleizal A, Boussel L, Laurent F, Braun E, Chidiac C, Ader F, Ferry T. Actinomycosis: etiology, clinical features, diagnosis, treatment, and management. Infect Drug Resist. 2014 Jul 5;7:183-97. doi: 10.2147/IDR.S39601. PMID: 25045274; PMCID: PMC4094581.
The index patient is a renal transplant (7 month back) recipient on tacrolimus-based triple immunosuppression, now presenting with multiple sinuses over right mandible for last 3 months, without any fever.The clinical scenario of multiple sinuses in cervicofacial region in an immunosuppressed patient points towards formation of cold abscess, with the differential diagnosis of (1):
Actinomycosis
Tuberculosis
Nocardiosis
Malignancy – lymphoma
Is it a common site for this form of infection?
Yes. It is a common site for actinomycosis. Actinomycosis presents at different sites (2):
Cervicofacial site (“lumpy jaw syndrome”) being most common site (with mandible involved in 50% cases): 50% cases.
Abdominopelvic site: 20% cases.
Pulmonary sites: 15-20% cases.
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patient
Diagnosis of Actinomycosis: Actinomycosis is a slowly progressing infection, lacks virulence, and has high risk of abscess or fistula formation. The diagnosis can be established by histopathology or microbiological analysis of the affected site. Direct microscopic examination reveals non-spore Gram-positive rods (2). These bacteria are clow growing, require anaerobic culture, and are often co-infected, hence cultures are positive in only 50% of cases (due to previous antibiotic exposure).
Histopathological examination of tissue from surgical biopsy or pus reveals abscess with purulent, granulomatous inflammation and fibrosis. Hematoxylin and eosin staining will reveal solid nodules (“sulfur granule”) with filamentous structures visible at the periphery of the abscess.
Treatment of Actinomycosis: Treatment of Actinomycosis is lengthy (due to avascular nature of the infection). It involves high doses of intravenous penicillin G (up to 24MIU/day) for 2-6 weeks followed by high doses of oral penicillin ( or amoxycillin 200 mg/kg/day) for 6-12 months to prevent relapse.
Lower doses and shorter treatment can be given if the diagnosis is made early, there is absence of bone involvement, and satisfactory patient response is observed rapidly (1).
Co-infected bacteria should be treated early. In case of penicillin allergy, clindamycin, doxycycline, or macrolides can be used.
Surgery for drainage should be avoided except in case of large abscess, recalcitrant fibrotic lesion, and osteomyelitis of the bone (1). Dental caries, if present, should be treated.
References:
Valour F, Sénéchal A, Dupieux C, Karsenty J, Lustig S, Breton P, Gleizal A, Boussel L, Laurent F, Braun E, Chidiac C, Ader F, Ferry T. Actinomycosis: etiology, clinical features, diagnosis, treatment, and management. Infect Drug Resist. 2014 Jul 5;7:183-97. doi: 10.2147/IDR.S39601. PMID: 25045274; PMCID: PMC4094581.
Rousseau C, Piroth L, Pernin V, Cassuto E, Etienne I, Jeribi A, Kamar N, Pouteil-Noble C, Mousson C. Actinomycosis: An infrequent disease in renal transplant recipients? Transpl Infect Dis. 2018 Dec;20(6):e12970. doi: 10.1111/tid.12970. Epub 2018 Aug 11. PMID: 30055044.
-What is your differential diagnosis?
Mostly a case of Cervicofacial Actinomycosis
DD include blastomycosis, brain abscess, colon cancer, crohn disease, diverticulitis, liver abscess, lung abscess, lymphoma, nocardiosis, pelvic inflammatory disease, pneumonia, tuberculosis and uterine cancer. -Is it a common site for this form of infection?
Yes cervicofacial ,genitourinary ,respiratory ,digestive tracts ,CNS ,skin and bone and joint
-Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
It is a rare and heterogeneous infection involving Gram-positive anaerobic bacteria, which are commensals in the oral cavity and digestive tract.
Actinomyces israelii and Actinomyces gerencseriae are the bacteria responsible for this condition though other types of Actinomyces bacteria have also been reported .
Diagnosis was made possible by microbiology or histopathology (filaments and sulfur granules) of the infection site, prolonged bacterial culture of an abscess or of a suspected tissue is required to identify the bacteria.
CT or MRI to detect further affection
Treatment with amoxicillin for 2-6 weeks, and clavulanic acid during the initial stages of treatment.
Surgical intervention is required to remove the infected tissues and for draining out of the excessive abscesses. Dental treatment is necessary for dental caries.
There is no recommendation for the management of concomitant immunosuppressive treatment meanwhile reduction of immunosuppression can be needed
Antimetabolite can be suspended , Tac dose reduced to reach minimum trough level and steroids reduction along with graft monitoring
Reference – Rousseau C et al .Actinomycosis: An infrequent disease in renal transplant recipients?Transplant infectious disease 2018 ;20(6) e12970
– Yiğiter M, Kiyici H, Arda IS, Hiçsönmez A (2007). “Actinomycosis: a differential diagnosis for [[appendicitis]]. A case report and review of the literature”. J Pediatr Surg. 42 (6): E23–6.
-Hasper D, Schefold JC, Baumgart DC (2009). “Management of severe abdominal infections”. Recent Pat Antiinfect Drug Discov. 4 (1): 57–65.
-Lederman ER, Crum NF (2004). “A case series and focused review of nocardiosis: clinical and microbiologic aspects”. Medicine (Baltimore). 83 (5): 300–13..
– Hoffman, Barbara (2012). Williams gynecology. New York: McGraw-Hill Medical. ISBN 9780071716727.
-Humes, D J (2006). “Acute appendicitis”. BMJ. 333 (7567): 530–534.
– Saccente M, Woods GL (2010). “Clinical and laboratory update on blastomycosis”. Clin. Microbiol. Rev. 23 (2): 367–81.
Kim, Eun Ran (2014). “Colorectal cancer in inflammatory bowel disease: The risk, pathogenesis, prevention and diagnosis”. World Journal of Gastroenterology. 20 (29): 9872. doi:10.3748/wjg.v20.i29.9872. ISSN 1007-9327.
Hanauer, Stephen B. (1996). “Inflammatory bowel disease”. New England Journal of Medicine. 334 (13): 841–848. PMID 8596552. Retrieved 2006-11-10.
Kuhajda I, Zarogoulidis K, Tsirgogianni K, Tsavlis D, Kioumis I, Kosmidis C, Tsakiridis K, Mpakas A, Zarogoulidis P, Zissimopoulos A, Baloukas D, Kuhajda D (2015). “Lung abscess-etiology, diagnostic and treatment options”. Ann Transl Med. 3 (13): 183. doi:10.3978/j.issn.2305-5839.2015.07.08. PMC 4543327. PMID 26366400.
Soper DE (2010). “Pelvic inflammatory disease”. Obstet Gynecol. 116 (2 Pt 1): 419–28.
– Cunha, F., Sousa, D.L., Trindade, L. et al. Disseminated cutaneous Actinomyces bovis infection in an immunocompromised host: case report and review of the literature. BMC Infect Dis 22, 310 (2022).
An a-61-year-old female patient presented with a 3-month history of multiple sinuses in the right side of the face (see below) without fever 7 months after receiving a kidney transplant from his 32-year-old son. She is on Tacrolimus-based triple immunosuppression with excellent graft function.
A case of oropharyngeal actinomycosis post kidney transplant which is not common infection which is considered a rare and heterogeneous infection involving Gram-positive anaerobic bacteria, which are commensals in the oral cavity and digestive tract. What is your differential diagnosis?
It is characterized by contiguous spread, suppurative and granulomatous inflammation, and the formation of multiple abscesses and sinus tracts that may discharge sulfur granules. The most common clinical forms of actinomycosis are cervicofacial (i.e., lumpy jaw).
There are 4 primary subtypes of actinomycosis infection:
Actinomycosis is caused by branched, filamentous anaerobic Gram-positive bacteria called Actinomyces.
It is a chronic granulomatous and suppurative infectious disease. In healthy individuals, actinomycosis is a commensal of the oral cavity, colon, and vagina. Actinomycosis becomes pathological in immunocompromised patients.
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
Clinical diagnosis must be confirmed by histopathologic and bacteriologic examinations (samples of sputum, pus, or tissue), If the infection is present the pus or tissue will usually contain yellow sulfur granules. Only few cases of actinomycosis have been reported in renal transplant recipients to date.
Surgical drainage, debridement and resection may be required. In some cases, a surgeon may drain an abscess or remove an infected part. After this, the person may need a 3-month course of antibiotics to resolve the problem. Actinomycosis is differentiated from other diseases with acid-fast negative ray-like bacilli and sulphur granules being pathognomonic. Immunosuppressive medications may need to be adjusted to the minimal possible doses (guided by drug levels) to control infection guard against possible rejection. References
Rousseau, C., Piroth, L., Pernin, V., Cassuto, E., Etienne, I., Jeribi, A., … and Mousson, C. (2018). Actinomycosis: an infrequent disease in renal transplant recipients? Transplant Infectious Disease, 20(6), e12970.
Miladipour et al., Mucormycosis After Kidney Transplantation, Iranian Journal of Kidney Diseases | Volume 2 | Number 3 | July 2008 Paolo Bortoluzzi , Gianluca Nazzaro, Serena Giacalone, Stefano Veraldi, Cervicofacial actinomycosis: a report of 14 patients observed at the Dermatology Unit of the University of Milan, Italy, International Journal of Dermatology, First published: 13 May 2020 https://doi.org /10.1111/ijd.14934
5. An a-61-year-old female patient presented with a 3-month history of multiple sinuses in the right side of the face (see below) without fever 7 months after receiving a kidney transplant from his 32-year-old son. She is on Tacrolimus-based triple immunosuppression with excellent graft function.
Actinomyces are part of the normal flora of the human oral cavity, GI tract, and female urogenital tract.
They are mostly polymicrobial, with as many as 5 to 10 other bacterial species present.
Around 60% of infections are cervicofacial and described as “lumpy jaw syndrome.
” Risk factors include infection in erupting teeth, dental caries, gingivitis, and dental extraction, diabetes, alcohol use disorder, malnutrition, and malignancy.
Pulmonary infections are primarily due to the aspiration of oral and GI secretions, as well as any chronic lung disease that lead to tissue destruction and break in normal mucosal defenses.
The second most frequent site for Actinomyces infection is the genitourinary tract, where the primary risk factor is the use of the intrauterine device.
Abdominal surgery is the most significant risk factor.
The maxilla and lower mandible are frequently affected by this infection (nearly 50% of cases), which accounts for about 60% of infections.
The most typical presenting feature is a growing, painless mass that is indurated and may or may not be accompanied by reddish or bluish discoloration of the skin overlying it.
This mass eventually develops into multiple abscesses with sinus tract formation and the discharge of yellow sulfur granules.
The patient can describe an oral procedure or injury in the past.
Infections that are in the chronic phases might cause trismus and difficulty eating food.
The illness process is not connected to lymphadenopathy.
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
Laboratory Studies
CBC
Anemia and mild leukocytosis are common.
Erythrocyte sedimentation rate and C-reactive protein
Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels are often elevatedز
Chemistry results usually are normal
Actinomycosis is difficult to diagnose based on clinical features, so direct identification and/or isolation of the infecting organism from a clinical specimen or from sulfur granules is necessary for definitive diagnosis.
Acceptable specimen material is obtained from draining sinuses, deep needle aspirate, or biopsy specimens; swabs, sputum, and urine specimens are unacceptable or inappropriate.
Gram-stained smear of the specimen may demonstrate the presence of beaded, branched, gram-positive filamentous rods, and sulfur granules should be crushed between 2 slides, stained with 1% methylene-blue solution, and examined microscopically for features characteristic of actinomycetes.
Nucleic acid probes and PCR methods are being developed for more rapid and accurate identification, but antimicrobial susceptibility testing is not indicated.
The prevalence of smears positive for Actinomyces organisms in women who use IUCDs is approximately 7%.
The gold standard test for diagnosis is tissue biopsy culture with anaerobic pus cultures, which can be falsely negative.
Chest radiography and CT scanning can reveal a poorly defined mass or pneumonitis or cavitary lesion, with or without pleural involvement. Hilar adenopathy is uncommon.
Moghimi M, Salentijn E, Debets-Ossenkop Y, Karagozoglu KH, Forouzanfar T. Treatment of cervicofacial actinomycosis: a report of 19 cases and review of literature. Med Oral Patol Oral Cir Bucal. 2013;18(4):e627-e632. Published 2013 Jul 1. doi:10.4317/medoral.19124
Hall V. Actinomyces–gathering evidence of human colonization and infection. Anaerobe. 2008 Feb. 14(1):1-7.
Moturi K, Kaila V. Cervicofacial Actinomycosis and its Management. Ann Maxillofac Surg. 2018;8(2):361-364. doi:10.4103/ams.ams_176_18
1-What is your differential diagnosis? -Cervicofacial actinomycosis (most likely) -Nocardia infection –Mucormycosis -Granulomatous diseases including tuberculosis -Skin malignancy -Odontogenic Abscess -Fungal infection (Blastomycosis) -Suppurative dermatosis 2-Is it a common site for this form of infection? –Cervicofacial involvement is the most common manifestation of actinomycosis, accounting for 50 % of all cases, while central nervous system, thoracic, abdominal, and pelvic actinomycosis occur less frequently. -Cervicofacial actinomycosis may involve almost any tissue or structure surrounding the upper or lower mandible. -However, the mandible itself is consistently the most commonly identified site of infection. -In one study of 317 patients reported from Cologne between 1952 and 1975, the presenting sites were identified as : *Mandible – 53.6 % *Cheek – 16.4 % *Chin – 13.3 % *Submaxillary ramus and angle – 10.7 % *Upper jaw – 5.7 % *Mandibular joint – 0.3 % . 3-Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients! Definitive diagnosis; -Actinomycosis is usually diagnosed by culturing the organism, although the specimens must be handled properly and , cultures held for at least 14 days. Culture; -Confirmation of the diagnosis requires the recovery of Actinomyces species from an appropriately cultured specimen, typically by needle aspiration of an abscess, fistula, or sinus tract or from a large biopsy specimen. Histology; -Multiple sections of a biopsy specimen from different tissue levels are suggested to improve histologic diagnosis. -Sections of biopsy material typically reveal acute or chronic inflammatory granulation tissue with infiltration by neutrophils, foamy macrophages, plasma cells and lymphocytes, and a surrounding dense fibrosis. -Healing lesions tend to demonstrate profound fibrosis, even avascular in nature, often in proximity to areas of acute suppuration. -Sulfur granules may comprise no more than 1% of total tissue in a given lesion, and hence are easily missed by routine tissue staining. -Often, a series of biopsies is required to confirm a pathologic diagnosis. Treatment; -High-dose penicillin is the treatment of choice for actinomycosis. -Alternative agents include (Amoxicillin or Amoxicillin-clavulanate or Doxycycline). -Management of cervicofacial actinomycosis often requires prolonged courses of antibiotics. -Surgical intervention may also be necessary in more complicated cases. -In severe periapical actinomycosis resistant to conventional therapy, root-end surgery with bone grafting may be required. Prevention; -There are no defined measures for preventing cervicofacial actinomycosis. However, maintenance of good oral hygiene and appropriate dental plaque removal can limit the tendency of Actinomyces to establish dense colonization and subclinical periodontal infection, an important precipitating event for more extensive disease. Reduction of I.S.;
-Decrease dose of antimetabolite or holding it temporarily
-keep pt on CNI + steroid (target of Tac. trough 4-6 ng/ml) References;
–Schaal KP, Beaman BL. Clinical significance of actinomycetes. In: The Biology of the Actinomycetes, Goodfellow M, Mordarski M, Williams ST (Eds), Academic Press, New York 1983. Vol 389.
–Kwartler JA, Limaye A. Pathologic quiz case 1. Cervicofacial actinomycosis. Arch Otolaryngol Head Neck Surg 1989; 115:524. –Könönen E, Wade WG. Actinomyces and related organisms in human infections. Clin Microbiol Rev 2015; 28:419. –Lerner PI. The lumpy jaw. Cervicofacial actinomycosis. Infect Dis Clin North Am 1988; 2:203. –Smego RA Jr, Foglia G. Actinomycosis. Clin Infect Dis 1998; 26:1255. –Gilbert DN, Moellering RC Jr, Sande MA. The Sanford Guide to Antimicrobial Therapy. Antimicrobial Therapy, Inc 2001; 31:70. –Asgary S, Roghanizadeh L. Grafting with Bone Substitute Materials in Therapy-Resistant Periapical Actinomycosis. Case Rep Dent 2021; 2021:6619731.
Cervicofacial actinomycosis is the most probable diagnosis
Nocardia infection
Granulomatous diseases including tuberculosis
Malignancy
Is it a common site for this form of infection?
Cervicofacial actinomycosis is most common form of the disease, around half of cases presents with cervicofacial form (1)
Other sites includes abdomen (commonly the appendix and ileocecal region ) in 20% and thorax in 20% of cases (1) and rarely pelvis and CNS.
Important criteria of this disease includes
Actinomycosis is a chronic disease characterized by multiple abscess and sinus and fistula formation
It is uncommon and seen mainly in immunocompromised patients
It does not respect anatomical planes
Not associated with lymphadenopathy
Hematogenous spread is rare (2)
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
Diagnosis
A chronic slowly growing non-tender indurated mass in the cervicofacial region that forms abscess and sinus
Usually occurring in immunosuppressed individual (HIV, SOT, DM)
History of predisposing factor including dental caries and extractions, implants, infections, irradiation, facial malignancy or bisphosphate related osteonecrosis of the jaws
Diagnosis is settled by culturing the organism
Specimen is taken usually by fine needle aspiration of the abcess or sinus
The result may be delayed up to 14 days since the organism is slowly growing
Treatment
A- Reduction of immunosuppression
Benefit should be weighed against risk of rejection
Reduction of immunosuppression is done by reducing the dose or stopping antimetabolite (the kidney can survive without antimetabolite), and reduction of the dose of CNI and keep trough level at lower target.
B- Antibiotics
Either IV (penicillin G 10 to 20 million units daily in divided doses or ceftriaxone as alternative) for severe infection or oral therapy (penicillin 2 to 4 g daily in divided doses or amoxacillin) for mild to moderate infection without significant suppuration or fistula (3-5)
If the patient is allergic to penicillin, doxycycline, macrolides or carbapenems can be given instead
Treatment of actinomycosis needs prolonged treatment of antibiotics for 2-6 months in case of mild disease and for 6-12 months in severe disease with at least 4-6 weeks on IV therapy
C- Surgical debridement may be required in some severe cases
References
Wong VK, Turmezei TD, Weston VC. Actinomycosis. BMJ 2011; 343:d6099.
Cintron JR, Del Pino A, Duarte B, Wood D. Abdominal actinomycosis. Dis Colon Rectum 1996; 39:105.
Smego RA Jr, Foglia G. Actinomycosis. Clin Infect Dis 1998; 26:1255.
Gilbert DN, Moellering RC Jr, Sande MA. The Sanford Guide to Antimicrobial Therapy. Antimicrobial Therapy, Inc 2001; 31:70.
Valour F, Sénéchal A, Dupieux C, et al. Actinomycosis: etiology, clinical features, diagnosis, treatment, and management. Infect Drug Resist 2014; 7:183.
What is your differential diagnosis?Differential diagnoses of angle jaw multiple sinuses 4 months after kidney transplantation include:
1. Cervicofacial ctinomycosis
2. Nocardiosis
3. Odontogenic Abscess
4. Fungal infection (Blastomycosis)
5. Malignancy
6. Tuberculosis
7. Rare: brucellosis, anthrax, toxoplasmosis and infectious mononeucleosis
Is it a common site for this form of infection?o Actinomycosis is a gram positive bacilli, anaerobic or microphilic characterized by purulent granulomatosis disease accompany by sinus tract. The most common species in humans is Actinomyces israelii
o Yes, The classic lesion located at the angle of the jaw is the most frequent location (submandibular)
o In up to 15%-20% of the cases it involves throat and in 10%-20% cases it involves the pelvic area
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!o Detailed history and comprehensive examination including oral cavity and and cervical examination for lymphadenopathy
o ENT consultation
o CBC, CRP, ESR, RFT & electrolytes, PT, PTT
o Soft tissue sonography of the neck/CT scan
o Tuberculin skin test/IGRA
o Draining sinus sample for gram stain and culture (sulfur granulesare characteristic for actinomycosis but grains are seen inmycetoma and butriomycosis)/PCR/tissue histopathology
o Drain sinus AFB stain and culture
o Excisional biopsy and histopathology
o Intravenous Penicillin therapy 4 million units, every 4 hours, for 2-6 weeks, followed by oral therapy with PNC-V 500 mg every 6 hours for 6-12 months (successful in 90% of the cases). Antibiotic treatment in transplant patients produces results similar to those in immunocompetent patients. If patient is allergic to penicillin, tetracycline and erythromycin are suitable alternatives
References
1. Avijgan M et al. A case report of cervicofacial actinomycosis. Asian Pacific Journal of Tropical Medicine (2010)838-840.
2. María Isabel Sáez et al. Actinomyces viscosus infection in a kidney–pancreas trasplanted patient. Nefrolgia. 2017;37(4): 429–449.
A differential diagnosis would include actinomycosis, tuberculosis, osteomyelitis,and nocardiosis. Let us not forget malignancy as well such as squamous cell carcinoma
-Is it a common site for this form of infection?
Yes,sinus is seen commonly in this area
-Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
History e.g., weight loss, night sweats, fever , oral & dental examination
What is your differential diagnosis?actinomycosis nocardiasis blastomycosis TB suppurative dermatosis malignancy
Is it a common site for this infection Yes,
It is characterized by contiguous spread, suppurative and granulomatous inflammation, and the formation of multiple abscesses and sinus tracts that may discharge sulfur granules. The most common clinical forms of actinomycosis are cervicofacial (ie, lumpy jaw).
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients! Diagnosis is made through cytologic or histologic examination, of samples of sputum, pus, or tissue to send for microscopic investigation in a laboratory. Sometimes, the laboratory will make a culture of the bacteria. If the infection is present, the pus or tissue will usually contain yellow sulfur granules.
TreatmentActinomycosis can persist for a long time. Long-term treatment with antibiotics, such as penicillin, is common. It may last from 8 weeks to over 12 months.
In some cases, a surgeon may drain an abscess or remove an infected part. After this, the person may need a 3-month course of antibiotics to resolve the problem.
It may be necessary to reduce the dosage of immunosuppressant drugs to the lowest effective level in order to prevent and treat infections and minimize the risk of organ rejection.
Rousseau, C., Piroth, L., Pernin, V., Cassuto, E., Etienne, I., Jeribi, A., … & Mousson, C. (2018). Actinomycosis: an infrequent disease in renal transplant recipients? Transplant Infectious Disease, 20(6), e12970.
YES, as it has been reported to be of about 53.6% at the mandibular area
Diagnosis
Cervicofacial actinomycosis has been dubbed the “great masqueraded” of the head and neck, hence a high index of suspicion is required
Cytology analysis of the fine needle aspirate
Histopathology examination
Imaging tests like CT/ MRI of the head and neck
Culture with the aid of sheep blood agar in a strict anaerobic state for 14 days
Full blood count and differential
CRP/ESR
Treatment
Penicillin or other beta-lactam antibiotics for a minimum of 3 months or two-week extensions after resolved infection and some may take up to 12 months
For those allergic to penicillin, Erythromycin or third generation antibiotic can be used
Care must be taken for drug-drug interaction of tacrolimus with the antibiotics that are inhibitors of cytochrome P450 the same enzyme that metabolizes CNIs, hence resulting in tacrolimus toxicity.
Regular close monitoring of Tacrolimus trough level since the antibiotic will be used for a long time for the treatment
Surgical procedures like sinus tract drainage of abscess cavities
References
Cervicofacial actinomycosis: important considerations on a mimicking disease.Revista Estomatológica Herediana2020; 30(2): 126-133.
============================ Is it a common site for this form of infection?
Yes
There are 4 primary subtypes of actinomycosis infection:
Cervical-oral (60 %)
Abdominal (20 %)
Pulmonary (15 %)
Pelvic (5 %)
Actinomycosis is caused by branched, filamentous anaerobic Gram-positive bacteria called Actinomyces.
It is a chronic granulomatous & suppurative infectious disease.
In healthy individuals, actinomycosis is a commensal of the oral cavity, colon, & vagina. Actinomycosis becomes pathological in immunocompromised patients.
============================ Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
Clinical diagnosis must be confirmed by histopathologic & bacteriologic examinations.
Only few cases of actinomycosis have been reported in renal transplant recipients to date.
Treatment is with prolonged courses of penicillins.
Surgical drainage, debridement, & resection may be required.
Actinomycosis is differentiated from other diseases with acid-fast negative ray-like bacilli & sulphur granules being pathognomonic.
Immunosuppressive medications may need to be adjusted to the minimal possible doses (guided by drug levels) to control infection guard against possible rejection.
References
Miladipour et al., Mucormycosis After Kidney Transplantation, Iranian Journal of Kidney Diseases | Volume 2 | Number 3 | July 2008
What is your differential diagnosis?A case of oropharyngeal actinomycosis post kidney transplant which is not common infection which is considered a rare and heterogeneous infection involving Gram-positive anaerobic bacteria, which are commensals in the oral cavity and digestive tract.
Is it a common site for this form of infection?In one study done on seven cases post kidney transplant showing 2 cases in this site.
Locations of actinomycosis were cervicofacial (n = 2), pulmonary (n = 2), abdominopelvic (n = 2), or cutaneous (n = 1)
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!Diagnosis was made possible by microbiology or histopathology (filaments and sulfur granules) (of the infection site.
Adjust immunosuppression and decreasing or stopping MMF.
Initial parenteral therapy is typically given for four to six weeks. Switching from intravenous to oral therapy is usually possible after there is significant improvement in the patient’s condition. Patients should be treated with amoxicillin for long time with median duration of 115 days.
Some patient treated with surgical intervention. References: 1- Rousseau C, Piroth L, Pernin V, et al. Actinomycosis: An infrequent disease in renal transplant recipients?. Transpl Infect Dis. 2018;20(6):e12970. doi:10.1111/tid.12970. 2- Treatment of actinomycosis – UpToDate 2023.
What is your differential diagnosis?Varicella Zoster is the main hypothesis associated with this condition.
Other lesions such as streptococci, ecthyma, skin neoplasia, and vasculitis can be considered as a differential diagnosis.
Is it a common site for this form of infection?No, the most common is to occur in thoracic dermatomes, but they can occur in any region, including the face, evolving into complications such as Ramsay Hunt Syndrome
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
Exposure to the Varicella virus in childhood is essential
Recent contact or aerosol exposure
Stress
Malnutrition
Diagnosis is clinical and treatment includes:
Acyclovir 800 mg orally five times daily (omitting the morning dose) or 10 mg/kg/dose three times daily.
In facial infections in immunosuppressed patients, prioritize venous treatment.
Pain control with neuropathic pain medications such as pregabalin depending on the pain status
Treatment should be carried out for at least seven days and all lesions should be healed or crusted over. The presence of vesicles defines disease activity.
What is your differential diagnosis?
Is it a common site for this form of infection?
Yes, it may involve the face, mandible, cheek & chin. Other sites are thoracic & abdomino-pelvic.
·
Principle of diagnosis
Tissue diagnosis by biopsy & histopathology
Prolonged culture
Treatment of this condition
Immunosuppression reduction by decreasing the dose of MMF and keeping tacrolimus to low trough levels may be needed.
Reference:
Valour F et al. Actinomycosis: etiology, clinical features, diagnosis, treatment and management. Infect Drug Resist 2014;7:183
Stabrowski T, Chuard C. Actinomycosis. Rev Med Suisse. 2019 Oct 9;15(666):1790-1794. French. PMID: 31599519
differential diagnosis:
Actinomycosis is caused by non spore forming actinomyces israelii which is a common organism found in nose and throat, hence neck and head infection is common presentation. diagnosis is accomplished by identifying the microorganism in the culture of biopsy, secretion or pus . treatment is penicillin g as the drug of choice.
Long term management is reducing the immune suppressant medication as its resulting from over suppression of immune system.
reference:
1] Hall V. Actinomyces–gathering evidence of human colonization and infection. Anaerobe. 2008 Feb. 14(1):1-7.
What is your differential diagnosis?
Is it a common site for this form of infection?
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
thank you dear Sir,
For this condition usually immunosuppression does not required.
What is your differential diagnosis?
Most common cervicofacial infection is Actinomycosis.
Other D/D are:
Nocardiosis
Tuberculosis
Skin cancer
Is it a common site for this form of infection?
Actinomycosis can present in this site frequently; Jaw involvement and regional lymph node spread is very common and accounts for the main 50% of the cases of actinomycosis…. Pulmonary and abdomino-pelvic sites are the next areas of involvement…
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
Post-transplant 7months, from well matched donor.
Presented with multiple sinuses in the cervico-facial region for last 3 months without fever past h/o active or latent TB in recipient and TB-endemicity need to be enquired.
The most likely diagnosis could be actinomycosis or tuberculosis
We need to get CBC, ESR, Mantoux test, IGRA
CT scan of the neck and chest is indicated to find out lymph node involvement, pulmonary TB
We can send the pus for AFB stain, Gene-Xpert MTB and AFB culture…
cervical lymph node biopsy may be diagnostic
Actinomycosis – requires microbiological tests
– Gram stain reveals non spore gram positive rods
– slow growing in culture in anaerobic medium.
– HPE of lymph node biopsy – may shows Sulfur granules with filamentous structures resembling fungi on H & E stain, is confirmatory.
Treatment of Actinomycosis: high dose IV penicillin G 24 MIU/day x 2-6 wks, followed by oral penicillin for 6 months to prevent relapse.
Macrolides, Doxycycline are other alternatives
Treatment for TB will be 2 months of HRZE (CNI dose increase to achieve trough level) and 6-9months of HR (extra-pulmonary, transplant recipient)
IS: Reduce antimetabolite and maintain low dose Tacrolimus and steroids
REFERENCES:
1) Reichenbach J, Lopatin U, Mahlaoui N, et al. Actinomyces in chronic granulomatous disease: an emerging and unanticipated pathogen. Clin Infect Dis 2009 Dec1; 49(11): 1703-10. doi: 10.1086/647945. PMID: 19874205; PMCID: PMC4100544.
2) Stabrowski T, Chuard C. Actinomycosis. Rev Med Suisse. 2019 Oct 9;15(666):1790-1794. French. PMID: 31599519.
Thank you ALL for getting the correct diagnosis.
What about immunosuppression? Will you reduce immunosuppression?
I would stop MMF, decrease the dose of tacrolimus to trough level of 4-6 ng/dl, but will keep on prednisolone. with frequent monitoring of graft function and for any rejection.as an inhibition of CD4 cells in murine Peyer’s patch stops the production of specific antibodies in the case of infection due to A. viscosus. In transplant patients, immunosuppressive drugs induce lower rates of CD4+.
Reference:
Sosroseno W, Bird PS, Gemmell E, et al. Role of CD4+ and CD8+ T cells on antibody production by murine Peyer’s patch cells following mucosal presentation of Actinomyces viscosus. Oral Microbiol Immunol. 2006 Dec;21(6):411-4. doi: 10.1111/j.1399-302X.2006.00308. PMID: 17064401.
What is your differential diagnosis?TB
Actinomycosis
Lymphoma
Other malignancies
· What is your differential diagnosis?
1. Actinomycosis
2. TB
3. Lymphoma
· Is it a common site for this form of infection?
Yes, commonly it involves the face. it is facial in 50%.
other sites are mandible 35 %, cheek 16 %, chin 13 %, Submaxillary and angle 10 %, Upper jaw 5.7 %, rare sites are central nervous system, thoracic, and abdomen.
· Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
Diagnosis depends on clinical presentation and tissue diagnosis and culture.
Treatment require antibiotics, namely penicillin, long courses up to 6months.
Tissue debridement may be needed
In immunosuppressed patients, reduction of immunosuppression and longer course may be needed plus involvement of ID consultant.
Reference:
1-Valour F et al. Actinomycosis: etiology, clinical features, diagnosis, treatment and management. Infect Drug Resist 2014;7:183
Q1: the differential diagnosis includes:
1. Cervicofacial actinomycosis
2. Mycobacterial skin infection (non TB)
3. Osteomyelitis
4. Mucormycosis
5. malignancies
Q2: yes, it is the comment site. Abdominal, pulmonary, and pelvic are the other sites. For this anaerobic, filamentous, grt bacteria.
Q3: confirmation of the diagnosis by culture or biopsy is needed.
Treatment includes penicillin for a long time from 3 to even 12 months until the resolution of the infection. Surgical drainage may be needed if indicated monitoring of tacrolimus level during treatment.
Differential diagnosis
Common site of infection
Yes, cervicofacial region is common site for actinomycosis. Other possible sites for this infection are jaw and regional lymph nodes, lungs, pelvis, abdomen.
Principle of diagnosis and treatment for immunocompromised patients
renal transplant patient on tacrolimus-based triple IS, have chronic multiple abscess in her face , no fever.
differential diagnosis of (1):
-Actinomycosis (Gram-positive anaerobic bacteria, which are commensals in the oral cavity and digestive tract) .
– Trichosporon.
-bacterial infection.
– lymphoma.
– Cutaneous nocardiosis
– Infections with the atypical mycobacteria,( which include Mycobacterium marinum, M fortuitum, M abscessus, M haemophilum and M avium-intracellulare)
It is a common site for actinomycosis. Actinomycosis occurs mean age was 55.7 years, and Median time between transplantation and infection was 4- 104 months.
Locations of actinomycosis were cervicofacial in most of cases , other sites are, pulmonary , abdominopelvic , or cutaneous
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patient
Actinomycosis is a slowly progressing infection Diagnosis was made possible by microbiology (71%) or histopathology (filaments and sulfur granules) (14%) of the infection site. The suspected gate of entry for the infection was dental (57%), abdominal (28.5%) or through the sinuses (14%).
microscopic examination non-spore Gram-positive rods.
Histopathological examination abscess with purulent, granulomatous inflammation and fibrosis.
Treatment of Actinomycosis:
patients were treated with amoxicillin- clavulanic acid
for 30-200 days (median duration of 115 days).
large abscess may require surgical evacuation.
Reduction of IS is not indicated unless in most of cases.
References:
Rousseau C, Piroth L, Pernin V, Cassuto E, Etienne I, Jeribi A, Kamar N, Pouteil-Noble C, Mousson C. Actinomycosis: An infrequent disease in renal transplant recipients? Transpl Infect Dis. 2018 Dec;20(6):e12970.
· What is your differential diagnosis?The most common cervicofacial infection is Actinomycosis. But other differential diagnoses are:- Nocardiosis- Tuberculosis- Skin câncer
· Is it a common site for this form of infection?The skin is the most common site, but it can involve the lung, gastrointestinal tract.
· Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
Even in immunosupressed patient the gold standard for diagnosis of actinomycosis is isolation and culture from a usually sterile body site.
The disease should be treated with high doses of antimicrobials for a prolonged period : use intravenous treatment for 2–6 weeks followed by oral therapy for at least 6–12 months. The antibiotic of choice is penicillin. In cases of allergy or nonresponse, alternatives include erythromycin, tetracycline, clindamycin, cephalosporins, meropenem, and chloramphenicol and surgical procedure should be considered.
REFERENCES:
– Reichenbach J, Lopatin U, Mahlaoui N, Beovic B, Siler U, Zbinden R, Seger RA, Galmiche L, Brousse N, Kayal S, Güngör T, Blanche S, Holland SM. Actinomyces in chronic granulomatous disease: an emerging and unanticipated pathogen. Clin Infect Dis. 2009 Dec 1;49(11):1703-10. doi: 10.1086/647945. PMID: 19874205; PMCID: PMC4100544.
– Stabrowski T, Chuard C. Actinomycose [Actinomycosis]. Rev Med Suisse. 2019 Oct 9;15(666):1790-1794. French. PMID: 31599519.
The patient is a renal transplant recipient on triple immunosuppression…Donor was her son..Renal transplant was done 7 months ago…..The DSA,induction used, any rejection episodes are not mentioned here…. The current problem is multiple sinuses in the cervico-facial region from the last 3 months without any fever…..Past history of TB or latent TB in the recipient and the endemic region for TB is also important…
The following differential diagnosis can be considered here
The most likely diagnosis could be actinomycosis or tuberculosis…
Actinomycosis can present in this site frequently…Jaw involvement and regional lymph node spread is very common and accounts for the main 50% of the cases of actinomycosis…. Pulmonary and abdomino pelvic sites are the next areas of involvement…
Tuberculosis can present as non healing sinus….We need to get CBC, IGRA, Mantoux test and baseline investigations for the same.. CT scan of the neck and chest is indicated to find out lymph node involvement…Pulmonary TB could co exist with lymph nodes…. We can send the pus for AFB stain, Gene Xpert MTB and AFB culture… For definitive diagnosis we need to do cervical lymoh node biopsy
Actinomycosis – requires microbiological expertise to diagnose it…Gram stain reveals non spore gram positive rods…slow growing in culture…require anerobic culture….HPE of lymph node shows sulfur granules with filamentous structures resembling fungi in H and E stain.. This confirms the diagnosis….
So in this patient i would do Cervical lymph node excision biopsy to confirm the diagnosis
Treatment of Actimumycosis is prolonged… high dose Intravenous penicillin G 24 MIU/day for 2 to 6 weeks followed by high dose of oral penicillin for 6 months to precent relapse is needed…Macrolides, Doxycycline are other alternatives…
Treatment for TB will be 2 months of HRZE and 4 months of HR as per our national guidelines RNTCP India
I will reduce antimetabolite and maintain low dose Tacrolimus and steroids
What is your differential diagnosis?
. Other defferentilas :
Is it a common site for this form of infection?
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients
Diagnosis :
– Histopathology or microbiology of the infected site is the confirmatory test for actinomycosis . Direct examination may reveal the presence of non -spore Gram -positive rods.
– These bacteria are slow-growing (5-20 days)and require anaerobic culture (blood agar media at 35–37°C) , this why cultures are positive in only 50% of cases.
– rRNA gene sequencing is sometimes performed when identification of Actinomyces isolates fails by conventional methods
Treatment :
-The cornerstone for treatment of actinomycosis is high doses of intravenous penicillin( 2–5 million IU per day ) followed by oral penicillin .
– Antibiotic treatment duration has to be adjusted to the location of infection, the severity of the lesion and patient history. Generally IV penicillin given for two to six weeks followed by high doses of oral penicillin for six to twelve months to prevent relapse.
– Tetracycline or cephalosporins are options of treatment in penicillin allergy .
– Surgery for drainage is more common in renal transplant recipients than in the general population,but , surgery should be avoided, except in cases of hemoptysis or abscess , because it often leads to a large surgery.
– The global outcome of actinomyces infection is good regardless of immunosuppressive status
References:
1.Ann Maxillofac Surg. 2018 Jul-Dec; 8(2): 361–364. doi: 10.4103/ams.ams_176_18
2. Actinomycosis: an infrequent disease in renal transplant recipients?. Transplant Infectious Disease, (), e12970–. doi:10.1111/tid.12970
cervicofacial actinomycosis
Tuberculosis’
Osteomyelitis
Herpes Simplex
Fungal infection
cervicofacial actinomycosis is the most common location
Actinomycosis is usually diagnosed by culturing the organism, although the specimens must be handled properly and cultures held for at least 14 days.
treatment of this condition regarding immunosuppressed patients
Reduction of immunosupressants
high-dose penicillin as the treatment of choice for actinomycosis. Alternative agents include amoxicillin or amoxicillin-clavulanate or doxycycline. Management of cervicofacial actinomycosis often requires prolonged courses of antibiotics. Surgical intervention may also be necessary in more complicated cases. In severe periapical actinomycosis resistant to conventional therapy, root-end surgery with bone grafting may be required
Differential diagnosis
1) Cervicofacial actinomycosis
2) Tuberculosis
3) Non-mycobacterium tuberculosis
4) Fungal infection
5) Bacterial infection
Is it a common site of infection?
Yes
Management
1) Septic parameter and blood culture
2) To start the patient with an antibiotic (amoxicillin-clavulanic)
3) Surgery and drainage
4) Reduction of immunosuppression ie: withholding MMF
5) Monitor graft function
Reference
1) Rousseau C, Piroth L, Pernin V, Cassuto E, Etienne I, Jeribi A, Kamar N, Pouteil-Noble C, Mousson C. Actinomycosis: An infrequent disease in renal transplant recipients? Transpl Infect Dis. 2018 Dec;20(6):e12970. doi: 10.1111/tid.12970. Epub 2018 Aug 11. PMID: 30055044.
The differential diagnosis included the following:
Cervicofacial actinomycosis
Mycobacterial cutaneous infection
Mucormycosis
Bacterial infection
Osteomyelitis
The most prevalent presentation of cervicofacial actinomycosis is fistula formation in the perimandibular area.
Diagnosis and treatment
The clinical diagnosis must be validated by histopathologic and bacterial tests.
Actinomycosis has been reported in renal transplant recipients infrequently to date.
The treatment consists of protracted penicillin administration.
There may be a need for surgical drainage, debridement, and resection.
Actinomycosis is distinguished from other diseases by the presence of acid-fast negative ray-like bacilli and sulfur granules.
Immunosuppressive medications may need to be adjusted to the lowest effective quantities (guided by trough levels) in order to prevent infection and rejection.
· What is your differential diagnosis?
· Is it a common site for this form of infection?
60% of cases of actinomycosis affects cervicofacial area, so , yes this is the commonest site for this infection.
· Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
1-Diagnosis of actinomycesis
-Detailed history and examination .
-Assess risk factors for this infection including : dental cares , extraction or implants , diabetes
2- Investigations
– CBC , ESR, CRP , LFT, KFT
– Tac trouh level
– HbA1c , fasting and postprandial blood suger
– CT /MRI head to exclude any ostelytic focuses
– Gold standard investigation is tissue biopsy and culture , but not swap biopsy that could be false positive.
Treatment :
1- A long term course of pencillin is the treatment of choice but as actinomycosis commonly present a polymicrobial infection so combination antibiotic is required . Combination of beta lactamase inhibitor and metronidazole is reasonable . Also macrolids, clindamycin and doxycyclin are effective.Antibiotic should be continued for 6-12 months to prevent relapse or till complete cure of affected site.
2- Eradicate any other focus for actinomycis .
3- Surgical intervention as abcess drain , decompression or excision of abcess track may be required.
4- Actinomycosis isa surrogate marker of immunesuppression , thus the dose and trough level of IS need to be reduced specially MMF with close monitoring of graft function to detect any graft rejection early.
Ref:
Rousseau C, Piroth L, Pernin V, Cassuto E, Etienne I, Jeribi A, Kamar N, Pouteil-Noble C, Mousson C. Actinomycosis: An infrequent disease in renal transplant recipients? Transpl Infect Dis. 2018 Dec;20(6):e12970. doi: 10.1111/tid.12970. Epub 2018 Aug 11. PMID: 30055044
Differential diagnosis
-cervicofacial actinomycosis
-TB
-fungal infection
-Bacterial infection
Is it a common site of infection?
Yes
Management
-reduction of IS
-Septic work up and blood culture
-start antibiotics as amoxicillin clavulinic
-surgery
· What is your differential diagnosis?
· Is it a common site for this form of infection?
60% of cases of actinomycosis affects cervicofacial area, so , yes this is the commonest site for this infection.
· Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
1-Diagnosis of actinomycesis
-Detailed history and examination .
-Assess risk factors for this infection including : dental cares , extraction or implants , diabetes
2- Investigations
– CBC , ESR, CRP , LFT, KFT
– Tac trouh level
– HbA1c , fasting and postprandial blood suger
– CT /MRI head to exclude any ostelytic focuses
– Gold standard investigation is tissue biopsy and culture , but not swap biopsy that could be false positive.
Treatment :
1- A long term course of pencillin is the treatment of choice but as actinomycosis commonly present a polymicrobial infection so combination antibiotic is required . Combination of beta lactamase inhibitor and metronidazole is reasonable . Also macrolids, clindamycin and doxycyclin are effective.Antibiotic should be continued for 6-12 months to prevent relapse or till complete cure of affected site.
2- Eradicate any other focus for actinomycis .
3- Surgical intervention as abcess drain , decompression or excision of abcess track may be required.
4- Actinomycosis isa surrogate marker of immunesuppression , thus the dose and trough level of IS need to be reduced specially MMF with close monitoring of graft function to detect any graft rejection early.
Ref:
Rousseau C, Piroth L, Pernin V, Cassuto E, Etienne I, Jeribi A, Kamar N, Pouteil-Noble C, Mousson C. Actinomycosis: An infrequent disease in renal transplant recipients? Transpl Infect Dis. 2018 Dec;20(6):e12970. doi: 10.1111/tid.12970. Epub 2018 Aug 11. PMID: 30055044
actinomycosis
tuberculosis
pheohypomycosis
Nocardia
eumycetoma
The five infections (32 cases) that were identified, included 18 cases of tuberculosis (56.25%) followed by 9 cases of actinomycosis (28.12%), 3 cases of pheohypomycosis (9.37%), and one case each of Nocardia (3.12%) and eumycetoma (3.12%) which presented as swelling with discharging sinus.
Yes, Orocervicofacial actinomycosis is the most common form of the disease, seen in up to 55% of cases.
(CT) scan
Histopathological examination of the excised specimen suggested soft-tissue fibroma secondarily infected with actinomycosis. Demonstration of Gram-positive filamentous organisms and sulphur granules on histological examination is strongly supportive of a diagnosis of actinomycosis.
For definitive diagnosis, direct isolation of the organisms from a clinical specimen or from sulphur granules is necessary.
Penicillin or amoxicillin/clavulanic acid are the preferred antibiotic regimens.
The traditional treatment is high-dose penicillin for a prolonged period (6 months to 1 year).The duration of antibiotic therapy with 6–12 million IU penicillins can range from 4 weeks to 1 year based on the severity of the disease. Surgical management without antibiotic therapy is associated with recurrence.
In case of penicillin allergy, clindamycin would be administered.
Decreasing tacrolimus level stopping MMF keeping steroids
Monitoring KFT and renal rejection.
ACTINOMYCOSISis likely
cervical TB lymphadenopathy need to be ruled out
microscopy of discharge fluid will establish the diagnosis
penicillins or tetracyclins will heal the lesion
reduction of IS is not commonly advised
Differential diagnosis:
Common site for this form of infection:
Principle of diagnosis and treatment of this condition regarding immunosuppressed patients:
– Culture; FNA/Large biopsy without contamination by other skin organisms with incubation in anaerobic or microaerophilic condition for 14 days.
– Histology; Multiple sections of biopsy.
– Monoclonal antibody staining.
– Molecular techniques -PCR, rRNA
– Penicillin is the treatment of choice.
– Alternates areamoxicillin, amoxicillin-clavulanate, doxycycline.
– Modification of IS can be needed in extensive disease with stopping of MMF and reducing CNI at lower therapeutic level.
Reference:
5. An a-61-year-old female patient presented with a 3-month history of multiple sinuses in the right side of the face (see below) without fever 7 months after receiving a kidney transplant from his 32-year-old son. She is on Tacrolimus-based triple immunosuppression with excellent graft function.
Issues/ concerns
– 61yo female, LDKT, 7 months ago, donor 32yo son
– 3/12 hx of multiple sinuses on the right side of the face, no fevers
– on tacrolimus-based triple immunosuppression
– excellent kidney function
What is your differential diagnosis? (1, 2)
– actinomycosis (cervicofacial)
– tuberculous mycobacterium
– nontuberculous mycobacterium infection
– pyogenic bacterial infection/ abscess
– mycetoma
– nocardiosis
Is it a common site for this form of infection?
– yes, it is
– common sites include:
– actinomyces is part of the normal flora in the human oral cavity, GI tract, female urogenital tract
– it is not virulent; it only invades the body when there is tissue injury and subsequent break in the normal mucosal barrier leading to deeper infections and an intense suppurative and granulomatous inflammatory response
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients (1-3)
– multidisciplinary approach: infectious disease specialist
– detailed history and physical examination
– assess for predisposing factors: dental caries, extractions, implants, gingivitis, gingival trauma, diabetes, immunosuppression, malnutrition, malignancy, irradiation, bisphosphonate (4, 5)
– actinomycosis is a rare disease, the infection is polymicrobial and is associated with disruption of the mucosal barrier leading to severe infection in immunosuppressed patients, it is a surrogate marker of poor prognosis among these patients
– actinomyces is a gram positive non-acid fast anaerobe, it causes infection by inhibiting host defenses and/ or reducing partial pressures of oxygen
– chronic actinomycosis presents with multiple abscesses which form sinus tracts and are associated with sulphur granules which can be detected on microscopy
– diagnosis: is difficult since isolation of the organism requires prolonged bacterial culture under anaerobic conditions
– baseline investigations: CBC, ESR, CRP, LFTs, tacrolimus trough level blood sugar, HIV Ab, dental radiograph, CT/ MRI to check for osteolysis in the setting of chronic infection
– gold standard test for diagnosis – tissue biopsy culture with anaerobic pus cultures
– avoid swabs from infected sites, cultures can be falsely negative
– serological tests: have no additional diagnostic value
– imaging studies: depends on the site of infection, can mimic other chronic infections like TB, malignancy
Treatment/ management
– for most cases, the mainstay of management is antibiotics, surgery can be adjunctive
– Penicillin G, beta-lactams with long course of oral amoxicillin, cephalosporin
– alternative antibiotics for patients allergic to penicillin: macrolides, clindamycin, doxycycline
– combination of beta-lactamase inhibitor and metronidazole may be used in polymicrobial infections
– duration of treatment is usually 6-12months but if surgical resection of the infected site is done the duration of treatment can be shortened
– surgery usually involves incision and drainage of abscesses, excision of sinus tracts, decompression of closed space
– imaging can be used to monitor response to treatment
References
1. Pierre I, Zarrouk V, Noussair L, Molina JM, Fantin B. Invasive actinomycosis: surrogate marker of a poor prognosis in immunocompromised patients. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases. 2014 Dec;29:74-9. PubMed PMID: 25449239. Epub 2014/12/03. eng.
2. Sharma S, Hashmi MF, Valentino ID. Actinomycosis. StatPearls. Treasure Island FL: © 2023, StatPearls Publishing LLC.; 2023.
3. Rousseau C, Piroth L, Pernin V, Cassuto E, Etienne I, Jeribi A, et al. Actinomycosis: An infrequent disease in renal transplant recipients? Transplant infectious disease : an official journal of the Transplantation Society. 2018 Dec;20(6):e12970. PubMed PMID: 30055044. Epub 2018/07/29. eng.
4. Feder HM, Jr. Actinomycosis manifesting as an acute painless lump of the jaw. Pediatrics. 1990 May;85(5):858-64. PubMed PMID: 2109853. Epub 1990/05/01. eng.
5. Khadka P, Koirala S. Primary cutaneous actinomycosis: a diagnosis consideration in people living with HIV/AIDS. AIDS research and therapy. 2019 Jul 30;16(1):16. PubMed PMID: 31362755. Pubmed Central PMCID: PMC6668064. Epub 2019/08/01. eng.
My differential diagnosis will be:
Cervicofacial actinomycosisNontuberculous mycobacterium infectionMucormycosisMycetomaCancer (metastatic)Is it a common site for this form of infection?
Yes
There are 4 primary subtypes of actinomycosis infection:
Cervical-oral (60 %)Abdominal (20 %)Pulmonary (15 %)Pelvic (5 %)Actinomycosis is caused by branched, filamentous anaerobic Gram-positive bacteria called Actinomyces.
chronic granulomatous & suppurative infectious disease.
. Actinomycosis becomes pathological in immunocompromised patients.
Management:
must be confirmed by histopathologic & bacteriologic examinations.Treatment is with prolonged courses of penicillinsActinomycosis is differentiated from other diseases with acid-fast negative like bacilli & sulphur granules being pathognomonic.Immunosuppressive medications may need to be adjusted to the minimal possible doses,guided by drug levelsSurgical drainage, debridement, & resection may be required.References:
Wong VK, Turmezei TD, Weston VC. Actinomycosis. BMJ 2011; 343:d6099.Smego RA Jr, Foglia G. Actinomycosis. Clin Infect Dis 1998; 26:1255.Gilbert DN, Moellering RC Jr, Sande MA. The Sanford Guide to Antimicrobial Therapy. Antimicrobial Therapy, Inc 2001; 31:70.
DD
_Craniofacial actinomycosis , most probable.
_Mycetoma
-.Skin cancer.
_Non tuberculous mycobacterial infection.
_Pyogenic bacterial infection
Diagnosis needs microbiological testing (swab and aspirate with gram staining , culture on anaerobic media may reveal filamentous rods.
Treatment:
.IS reduction (stopping MMF and use CNI with lower trough level) with graft function monitoring.
. Penicillin for 4-6 weeks ; erythromycin in allergic patients .
.surgical drainage & debridement may be needed.
An a-61-year-old female patient presented with a 3-month history of multiple sinuses in the right side of the face (see below) without fever 7 months after receiving a kidney transplant from his 32-year-old son. She is on Tacrolimus-based triple immunosuppression with excellent graft function.
What is your differential diagnosis?
Is it a common site for this form of infection?
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
REF;
.
What is your differential diagnosis?skin cancer
chronic bactrial infection nocradia
tuberculosis
actinomycosis ( cervicofascial suppourative actinomycosis with super added bacterial infection
Is it a common site for this form of infection?
the lesion involve typical anatomial site for actinomycosis , need to ask about any recent truama ,surgical intervention ,or orodental surgery, bad oral hygiene
actinomycosis is very infrequent and rare chronic granulomatous bacterial infection evidence is limited to a few case reports, and case series of granulomatous bacterial infection caused by actinomycetes which belong to gram-positive anaerobic bacteria, a very heterogenous and nonspecific presentation that delay the diagnosis, typically involve the cervicofacial sites from oropharyngeal lesions, also in a french cohort of 25 cases have been reported from different sites including soft tissues, orofacial, thoracic and gut involvement, diagnosis based on a high index of clinical suspicion with microbiology and tissue histology, treatment mainly with amoxicillin for long course minimum of 90 days but average between 6-12 months along with surgical drainage
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
high index of clinical suspicion especially in immunosuppressed patients, DM, poor oral hygiene, recent trauma or surgery, ICUD in females with abdominal pelvic actinomycosis
microbiology and histopathology are important for the diagnosis
treatment involve B lactam ABlike amoxicillin for 6-12 months along with surgical drainage ,immunsuppression role is not clear as its have been found in immunocompetent patients as well , however,thereis reported cases of disseminated actinomycosis in immunocompromized patient with associated mortality up to 21% in one case series (3).
References
1. Rousseau C, Piroth L, Pernin V, Cassuto E, Etienne I, Jeribi A, Kamar N, Pouteil-Noble C, Mousson C. Actinomycosis: An infrequent disease in renal transplant recipients? Transpl Infect Dis. 2018 Dec;20(6):e12970. doi: 10.1111/tid.12970. Epub 2018 Aug 11. PMID: 30055044.
2. Bonnefond S, Catroux M, Melenotte C, Karkowski L, Rolland L, Trouillier S, Raffray L. Clinical features of actinomycosis: A retrospective, multicenter study of 28 cases of miscellaneous presentations. Medicine (Baltimore). 2016 Jun;95(24):e3923. doi: 10.1097/MD.0000000000003923. Erratum in: Medicine (Baltimore). 2016 Aug 07;95(31):e5074.
3. Cunha F, Sousa DL, Trindade L, Duque V. Disseminated cutaneous Actinomyces bovis infection in an immunocompromised host: case report and review of the literature. BMC Infect Dis. 2022 Mar 29;22(1):310. doi 10.1186/s12879-022-07282-w. PMID: 35351021; PMCID: PMC8962608.
What is your differential diagnosis?
Is it a common site for this form of infection?
Cervicofacial actinomycosis is a chronic disease characterized by abscess formation, draining sinus tracts, fistulae, and tissue fibrosis.
It can mimic a number of other conditions, particularly malignancy and granulomatous disease, and should be included in the differential diagnosis of any soft tissue swelling in the head and neck.
Cervicofacial involvement is the most common manifestation of actinomycosis, accounting for 50 percent of all cases, while central nervous system, thoracic, abdominal, and pelvic actinomycosis occur less frequently
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
Culture — Confirmation of the diagnosis requires the recovery of Actinomyces species from an appropriately cultured specimen, typically by needle aspiration of an abscess, fistula, or sinus tract or from a large biopsy specimen.
Histology — Multiple sections of a biopsy specimen from different tissue levels are suggested to improve histologic diagnosis
Sections of biopsy material typically reveal acute or chronic inflammatory granulation tissue with infiltration by neutrophils, foamy macrophages, plasma cells and lymphocytes, and a surrounding dense fibrosis. Healing lesions tend to demonstrate profound fibrosis, even avascular in nature, often in proximity to areas of acute suppuration. Sulfur granules may comprise no more than 1 percent of total tissue in a given lesion, and hence are easily missed by routine tissue staining.
Monoclonal antibody staining — In contrast, specific staining using fluorescent-conjugated monoclonal antibody (FA) has been shown to improve the identification of various Actinomyces species, even in mixed infections and after fixation in formalin
Molecular techniques — The diagnosis of cervicofacial actinomycosis has been greatly improved with the advent of molecular techniques such as detection by polymerase chain reaction with 16S ribosomal ribonucleic acid (rRNA) gene probes from clinical specimens.
High dose penicillin is the treatment of choice for actinomycosis . Alternative agents include amoxicillin or amoxicillin-clavulanate or doxycycline.
Management of cervicofacial actinomycosis often requires prolonged courses of antibiotics. Surgical intervention may also be necessary in more complicated cases. In severe periapical actinomycosis resistant to conventional therapy, root-end surgery with bone grafting may be required .
Reduction of immunosupression is usually not required however it can be considered if the response is not appropriate
What is your differential diagnosis?
Skin lesion with indurated area of multiple, small, communicating abscesses surrounded by granulation tissue. There seem to be a sinus with discharge looks like having a tendency to spread contiguous tissues.
Cervico-facial actinomycosis is the most likely differential diagnosis. Actinomyces species are commensal in human open cavities, including the mouth, and the most common pathogenic species encountered is A. israelii(1)
Differential diagnosis to this skin lesion is as follows:
· Cervico-facial actinomycosis.
· Skin TB and non-tuberculous MB infection of the skin.
· Bacterial infection.
· Malignant lesion; desmoid tumor, cutaneous tumor and SCC(2).
Is it a common site for this form of infection?
1. Cervicofacial involvement is the most common manifestation of actinomycosis, accounting for 50 percent of all cases, while central nervous system, thoracic, abdominal, and pelvic actinomycosis occur less frequently(3).
2. The cervicofacial form usually begins as a small, flat, hard swelling, with or without pain, under the oral mucosa or the skin of the neck or as a subperiosteal swelling of the jaw. Subsequently, areas of softening appear and develop into sinuses and fistulas that discharge the characteristic sulfur granules.
3. Actinomycosis usually involves multiple small, communicating abscesses with sinus tracts that drain a purulent discharge.
4. Infection typically involves the neck and face, lungs, or abdominal and pelvic organs. The cheek, tongue, pharynx, salivary glands, cranial bones, meninges, or brain may be affected, usually by direct extension.
5. Microscopically, Actinomyces appears as distinctive “sulfur” granules (rounded or spherical particles, usually yellowish, and ≤ 1 mm in diameter) or as tangled masses of branched and unbranched wavy bacterial filaments.
6. High-dose penicillin is usually effective but must be given long-term (8 weeks to 1 year).Surgery to drain abscesses and excise fistulas may be needed.
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
1. Diagnosis of actinomycosis(4): Actinomycosis is suspected clinically and confirmed by identification of A. israelii or other Actinomyces species using microscopy and culture of sputumand drained fluid. CT scan of the affected areas may be needed.
2. Prognosis relates directly to early diagnosis and is most favorable in the cervicofacial form.
3. Treatment of actinomycosis:
a) Most patients with actinomycosis respond to antibiotics, but response is usually slow because of extensive tissue induration and the relatively avascular nature of the lesions.
b) High doses of penicillin G (eg, 3 to 5 million units IV every 6 hours) are usually effective. Penicillin V 1 g orally 4 times a day may be substituted after about 2 to 6 weeks.
c) There were reported cases of actinomycosis treated with amoxicillin for 30-200 days (median duration of 115 days), and clavulanic acid was added for 28.5% of cases(5).
d) Oral tetracycline 500 mg every 6 hours or doxycycline 100 mg every 12 hours may be given instead of penicillin.
e) Minocycline, clindamycin, and erythromycin have also been successful. Erythromycin increase the level of TAC.
4. Adjustment of immunosuppression: actinomycosis is infrequently encountered in immunocompromised patients and in those under immunosuppressants. Although, global and renal outcomes do not seem to be affected by actinomycosis(5), immunosuppressants should be adjusted to the minimally accepted target to minimize the contagious spread of actinomycosis. Anti-metabolite should reduced by 25% to 50%, and CNI to be kept at the lower target.
References
1. Bonnefond S., Catroux M., Melenotte C. Clinical features of actinomycosis: a retrospective, multicenter study of 28 cases of miscellaneous presentations. Medicine (Baltim) 2016;95 [PMC free article] [PubMed] [Google Scholar]
2. Shinpei Matsuda, Hisato Yoshida, and Hitoshi Yoshimura Orofacial soft tissues actinomycosis: A retrospective, 10-year single-institution experience J Dent Sci. 2021 Jan; 16(1): 365–369. https://www.ncbi.nlm.nih.gov/
3. UpToDate; Cervicofacial actinomycosis. Abdu A Sharkawy, Anthony W Chow.https://www.uptodate.com/contents/search
4. Actinomycosis by Larry M. Bush https://www.merckmanuals.com/professional/infectious-diseases/anaerobic-bacteria/actinomycosis
5. Rousseau C, Piroth L, Pernin V, Cassuto E, Etienne I, Jeribi A, Kamar N, Pouteil-Noble C, Mousson C. Actinomycosis: An infrequent disease in renal transplant recipients? Transpl Infect Dis. 2018 Dec;20(6):e12970. doi: 10.1111/tid.12970. Epub 2018 Aug 11. PMID: 30055044.
👉 Differential diagnosis of multiple skin sinuses:
_Craniofacial actinomycosis (anaerobic gram postive bacilli).
_Mycetoma.
_Non tuberculous mycobacterial infection.
_Pyogenic bacterial infection
_Skin cancer.
👉 yes, it is a common site of infection and skin sinuses.
_otger sites thoracic, abdominal , pelvic and cutaneous .
👉 Diagnosis is based on microbiological identification (swab and aspirate with gram staining and has diagnostic sulfur granules ) or by culture on anaerobic media revealing filamentous rodes.
👉 Treatment involves:
_reduction of IS (stop MMf and use CNI with lower window of trough level).
_use prolonged course of penicillin for 4-6 weeks or erythromycin in allergic patients ).
_surgical drainage and debridement may be used
_ close monitoring of graft function in the context of reduction of IS therapy.
What is your differential diagnosis?
D/D are Actinomycosis
Tuberculosis’
Osteomyelitis
Herpes Simplex
Fungal infection
Is it a common site for this form of infection?Orofacial
Cervical and Facial area
Pulmonary actinomycosis
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
Stop anti metabolites drug
Reduce tacrolimus to lower limit
Keep steroid dose
Intravenous penicillin G for long time 6 weeks and then oral penicillin V for 6 months to one year
Amoxicillin intravenous
Differential Diagnosis
Sites of infection
Diagnosis
Treatment in transplanted patients;
Actinomyces
References
1.actinomycosis; immunosuppression; kidney transplantation.
© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
2. Smego RA Jr, Foglia G. Actinomycosis. Clin Infect Dis 1998; 26:1255.
3.Gilbert DN, Moellering RC Jr, Sande MA. The Sanford Guide to Antimicrobial Therapy. 4. Antimicrobial Therapy, Inc 2001; 31:70.
5.Valour F, Sénéchal A, Dupieux C, et al. Actinomycosis: etiology, clinical features, 6. diagnosis, treatment, and management. Infect Drug Resist 2014; 7:183.
7. Martin MV. The use of oral amoxicillin for the treatment of actinomycosis. A clinical and in vitro study. Br Dent J 1984; 156:252.
8. Smego RA Jr. Actinomycosis. In: Infectious Diseases, Hoeprich PD, Jordan MC, 9. Ronald AR (Eds), Lippincott, New York 1994. p.493.
10. PEABODY JW Jr, SEABURY JH. Actinomycosis and nocardiosis. A review of basic differences in therapy. Am J Med 1960; 28:99.
What is your differential diagnosis?
. Other defferentilas :
Is it a common site for this form of infection?
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients
Diagnosis :
– Histopathology or microbiology of the infected site is the confirmatory test for actinomycosis . Direct examination may reveal the presence of non -spore Gram -positive rods.
– These bacteria are slow-growing (5-20 days)and require anaerobic culture (blood agar media at 35–37°C) , this why cultures are positive in only 50% of cases.
– rRNA gene sequencing is sometimes performed when identification of Actinomyces isolates fails by conventional methods
Treatment :
-The cornerstone for treatment of actinomycosis is high doses of intravenous penicillin( 2–5 million IU per day ) followed by oral penicillin .
– Antibiotic treatment duration has to be adjusted to the location of infection, the severity of the lesion and patient history. Generally IV penicillin given for two to six weeks followed by high doses of oral penicillin for six to twelve months to prevent relapse.
– Tetracycline or cephalosporins are options of treatment in penicillin allergy .
– Surgery for drainage is more common in renal transplant recipients than in the general population,but , surgery should be avoided, except in cases of hemoptysis or abscess , because it often leads to a large surgery.
– The global outcome of actinomyces infection is good regardless of immunosuppressive status
References:
1.Ann Maxillofac Surg. 2018 Jul-Dec; 8(2): 361–364. doi: 10.4103/ams.ams_176_18
2. Actinomycosis: an infrequent disease in renal transplant recipients?. Transplant Infectious Disease, (), e12970–. doi:10.1111/tid.12970
What is your differential diagnosis?
Cervicofacial discharging sinuses without fever DDx are:
o Cervicofacial Actinomycosis.
o Granulomatous invasive aspergillosis.
o Oral squamous cell carcinoma.
o Tuberculosis.
o Nocardiosis.
o Mucormycosis.
Is it a common site for this form of infection?
Yes, it is the cervico- facial involvement is the most common site in 50%.
other sites are mandible 35 %, cheek 16 %, chin 13 %, Submaxillary ramus and angle 10 %, Upper jaw 5.7 %, rare sites are central nervous system, thoracic, and abdomen.
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patient?
Diagnosis:
The Gold standard is a histopathological after a surgical excision and tissue culture, reveals a central zone of necrosis, multiple lobulated microcolonies, mixed cell infiltrate, microabscesses, and sinus tracts, surrounded by fibrosis and connective tissue, biopsy alone would not give the diagnosis if not taken from the disease focus area, sulfur granules surrounded by brightly eosinophilic areas (Splendore-Hoeppli phenomenon) may be suggestive.Actinomycosis is It is a slow growing anaerobic gram positive rod –need special culture for growth.Risk factors: deceased organ, immunosuppressive medications and induction with ATG, other comorbidities(DM). Treatment:
First line after surgical excision treatment is penicillin/ augmnetin for 4-12 weeks, in penicillin allergy Minocycline for 6- 18 weeks, carbapenems or tegacyclin.Clindamycin and metronidazole should be avoided with high resistance rate. Recurrence usually occurs a year after, so biannual follow-up and intervention is required, the patient must have a good dental hygiene. The Nd:YAG laser has potential as a novel treatment for cervicofacial actinomycosis in vitro. However, it has yet to be studied in vivo.The response to treatment should be carefully monitored and imaging with computed tomography or magnetic resonance imaging may be necessary to ensure resolution. The cure rate is high but deformities and death is common.In index case 3 months’ post kidney transplant, I would stop MMF, decrease the dose of tacrolimus to trough level of 4-6 ng/dl, but will keep on prednisolone. with frequent monitoring of graft function and for any rejection.as an inhibition of CD4 cells in murine Peyer’s patch stops the production of specific antibodies in the case of infection due to A. viscosus. In transplant patients, immunosuppressive drugs induce lower rates of CD4+.
References:
(1) Karanfilian KM, Valentin MN, Kapila R, Bhate C, Fatahzadeh M, Micali G, Schwartz RA. Cervicofacial actinomycosis. Int J Dermatol. 2020 Oct;59(10):1185-1190. doi: 10.1111/ijd.14833. Epub 2020 Mar 11. PMID: 32162331.
(2) Rousseau C, Piroth L, Pernin V, Cassuto E, Etienne I, Jeribi A, Kamar N, Pouteil-Noble C, Mousson C. Actinomycosis: An infrequent disease in renal transplant recipients? Transpl Infect Dis. 2018 Dec;20(6):e12970. doi: 10.1111/tid.12970. Epub 2018 Aug 11. PMID: 30055044..
(3) Sosroseno W, Bird PS, Gemmell E, Seymour GJ. The role of CD4+ and CD8+ T cells on antibody production by murine Peyer’s patch cells following mucosal presentation of Actinomyces viscosus. Oral Microbiol Immunol. 2006 Dec;21(6):411-4. doi: 10.1111/j.1399-302X.2006.00308.x. PMID: 17064401.
Thank you ALL for getting the correct diagnosis.
What about immunosuppression? Will you reduce immunosuppression?
Thank you Prof .Halwa
The global outcome of actinomycosis is good regardless of immunosuppressive status. In renal transplant recipients, renal outcomes was not found to be affected and no graft rejection was observed.
Reference :
Thank you Prof. Ahmad.
I would stop MMF, decrease the dose of tacrolimus to trough level of 4-6 ng/dl, but will keep on prednisolone. with frequent monitoring of graft function and for any rejection.as an inhibition of CD4 cells in murine Peyer’s patch stops the production of specific antibodies in the case of infection due to A. viscosus. In transplant patients, immunosuppressive drugs induce lower rates of CD4+.
Reference:
Thank you prof
Immunosuppression reduction is usually not required. The outcome of actinomycosis is good regardless of immunosuppressive status and does not affect graft outcome in renal transplant recipients (1). In disseminated/ systemic involvement, immunosuppression might be required to be reduced or stopped temporarily, according to the clinical status of the patient, as in management of any life-threatening sepsis.
Reference:
Adjustment of immunosuppression: actinomycosis is infrequently encountered in immunocompromised patients and in those under immunosuppressants. Although, global and renal outcomes do not seem to be affected by actinomycosis(5), immunosuppressants should be adjusted to the minimally accepted target to minimize the contagious spread of actinomycosis. Anti-metabolite should reduced by 25% to 50%, and CNI to be kept at the lower target.
Thanks prof
As we know actinomycosis would required prolong therapy and responsive to antibiotics which could have less potential of drug-drug interactions, so will see the response if not improving with prolong therapy than no need for IS reduction and in case of lack of improvement will have to reduce/stop MMF/AZA with monitoring for allograft functions.
– no, I would not modify the immunosuppression
– for most cases, the mainstay of management is antibiotics, with good response to treatment
– unless the patient has life-threatening/ disseminated/ systemic disease in which case I would reduce the immunosuppression
Reference
1. Rousseau C, Piroth L, Pernin V, Cassuto E, Etienne I, Jeribi A, et al. Actinomycosis: An infrequent disease in renal transplant recipients? Transplant infectious disease : an official journal of the Transplantation Society. 2018 Dec;20(6):e12970. PubMed PMID: 30055044. Epub 2018/07/29. eng.
It has a good response to antibiotics and sx where indicated, unless the pt develops a life threatening infection, we maintain the current immunosuppressive meds doses.
THANKS PROF HALAWA
– No, I would not modify the immunosuppression
– for most cases, the mainstay of management is antibiotics, with good response to treatment
– unless the patient has life-threatening/ disseminated/ systemic disease in which case I would reduce the immunosuppression
Reference
1. Rousseau C, Piroth L, Pernin V, Cassuto E, Etienne I, Jeribi A, et al. Actinomycosis: An infrequent disease in renal transplant recipients? Transplant infectious disease : an official journal of the Transplantation Society. 2018 Dec;20(6):e12970. PubMed PMID: 30055044. Epub 2018/07/29. eng.
Thank you prof
In case of local & responsive actinomycosis no need to reduce immunosuppression.
according to one study conducted in France, actinomycosis is a rare, progressive disease occurring in kidney transplant recipients, responsive to penicillin course of few months. However, actinomycosis infection does not impact the global and renal outcome.
Hence, I don’t think modulating immune suppressive protocol is warranted.
References:
1] Celia Rousseau et al. Actinomycosis: An infrequent disease in renal transplant recipients?. Transpl Infect Dis. 2018 Dec;20(6):e12970.
This patient has a chronic infection that has resulted in the formation of sinuses in the cervicofacial region
The differential diagnosis includes:
The most common site of actinomycosis infection is the cervicofacial region accounting for 50% of cases followed by the central nervous system, thoracic, abdominal and pelvic sites
Adult males with poor oral hygiene appear to be at greater risk of developing cervicofacial actinomycosis. The predisposing factors include:
Patients with DM, malnutrition, immunosuppression are at greater risk
Diagnosis:
Treatment:
High dose penicillin (10-20 million units daily in divided doses) is the treatment of choice for actinomycosis
Alternative agents include ceftriaxone amoxicillin, amoxicillin-clavulanate or doxicycline
The treatment duration is usually 2-6 months for mild disease and 6-12 months for severe disease
Surgical intervention may be necessary in more complicated cases
Olga Eastman et al. Actinomycosis: Diagnosis and Management. Curr Infect Dis Resp. 2005
Valour F et al. Actinomycosis: etiology, clinical features, diagnosis, treatment and management. Infect Drug Resist 2014;7:183
Thank you.
What about immunosuppression? Will you reduce it?
Yes Professor Halawa
I will reduce the ISS
What is your differential diagnosis?
· Cervicofacial Actinomycosis
· Tuberculosis
· Mucoromycosis
· Non mycobacterial skin infection
· Nocardiosis
· Osteomyelitis
· lymphoma
Is it a common site for this form of infection?
Cervicofacial actinomycosis is an invasive destructive infectious syndrome, caused by Gram-positive, branching filamentous bacteria, Actinomyces. Most of the cases are traced to an odontogenic source with periapical abscess and posttraumatic or surgical complications with poor hygiene and immunosuppression as contributing factors. Cervicofacial involvment happens in 50%- Jumpy Jaw Syndrome. Presenting clinical manifestations is confusing because they often mimic a malignancy or a granulomatous lesion.
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
Diagnosis is based on histology and microbiological assessment. Cultural isolation of Actinomyces species from clinical specimens, or microscopic visualization of gram-positive, non-acid-fast, thin, branching filaments in cytologic aspirates or histopathologic sections are the best methods of diagnosis of cervicofacial actinomycosis.
Such patients requires admission and immune suppression modification. MMF has to be stopped and TAC levels to be kept between 5-7 ng/ml.
Drug of choice is Penicillin G 20 million IU per day for 2-6 weeks. This is followed by oral penicillin for 6-12 months.
Surgical therapy is often indicated for curettage of bone, resection of necrotic tissue, excision of sinus tracts, and drainage of soft tissue abscesses. The prognosis for treated infection is excellent.
Moturi K, Kaila V. Cervicofacial Actinomycosis and its Management. Ann Maxillofac Surg. 2018 Jul-Dec;8(2):361-364. doi: 10.4103/ams.ams_176_18. PMID: 30693266; PMCID: PMC6327805.
Oostman O, Smego RA. Cervicofacial Actinomycosis: Diagnosis and Management. Curr Infect Dis Rep. 2005 May;7(3):170-174. doi: 10.1007/s11908-005-0030-0. PMID: 15847718.
What would be a prophylactic measure in a recipient workup that is often forgotten.?
I think dental evaluation and forgotten treatment of dental caries can predispose to this
Thank you
Thank you.
What about immunosuppression? Will you reduce it?
MMF has to be stopped and TAC levels to be kept between 5-7 ng/ml.
What is your differential diagnosis?
Renal transplant patient with multiple sinuses in the cervicofacial region-likely diagnosis is Cervicofacial Actinomycosis. Other possibilities which can be considered in the above case includes: Tuberculosis and non-mycobacterial skin infection, Nocardiosis,Mucormycosis,osteomyelitis and lymphoma.
Is it a common site for this form of infection?
Actinomycosis- a branched, filamentous anaerobic Gram-positive bacteria- involves different sites. However, cervico-facial site (lumpy-jaw syndrome)is the most common presenting in about 50% cases. Other sites include :abdominopelvic and pulmonary sites.
.
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patient?
Gold standard test for diagnosis is made by histopathological and microbiological examination of sample of the involved site of presentation like sputum, pus or tissue. It is a slow growing anaerobic gram positive rod –need special culture for growth. Granulomatous inflammation and fibrosis seen on histopathological examination and staining revealed sulfur granule with branched, gram-positive filamentous rods .Other supportive tests include: CBC, inflammatory markers like CRP,ESR etc. HRCT chest showed pneumonitis or cavitatory lesion, with or without pleural involvement.
Treatment –Firstly ,patient should be admitted and anti-metabolite i.e., MMF to be stopped and Tac level to be maintained around 5-7ng/ml.Drug of choice for actinomycosis is penicillin G –in a dose of 24MIU/day for 2-6 weeks followed by high doses of oral penicillin for 6-12 months .Alternatives include: Clindamycin, Macrolides ,and Doxycycline. Surgical intervention in the form of drainage with or without bone grafting is needed in resistant and complicated cases like enlarging abscess, recalcitrant fibrotic lesion, and osteomyelitis of the bone. Patient should be counseled to maintain dental hygiene
REFERENCES:
Moturi K, Kaila V. Cervicofacial Actinomycosis and its Management. Ann Maxillofac Surg. 2018 Jul-Dec;8(2):361-364.
Well done
What is your differential diagnosis?
– Cervical actinomycosis (likely diagnosis)
– Non-tuberculous mycobacterial infection.
– Mucormycosis. .
– Nocardiosis.
– Odontogenic Abscess
– Fungal infection (Blastomycosis)
– Malignancy
Is it a common site for this form of infection?
Yes, Cervicofacial involvement is the most common site in 50%.
-Mandible – 53.6 %
-Cheek – 16.4 %
-Chin – 13.3 %
-Submaxillary ramus and angle – 10.7 %
-Upper jaw – 5.7 %
-Mandibular joint – 0.3 %
while central nervous system, thoracic, abdominal, and pelvic actinomycosis occur less frequently
Actinomycosis:
– It is a rare chronic disease caused by Actinomyces spp, gram positive facultative anaerobes
– Normal flora colonize the human mouth and digestive and genital tracts.
– Disease occurs almost exclusively by direct invasion and rarely by hematogenous spread.
– It is a chronic disease characterized by abscess formation, draining sinus tracts, fistulae, and tissue fibrosis
-A hallmark is the tendency to spread without regard for anatomical barriers, including fascial planes or lymphatic drainage, and the development of multiple sinus tracts.
– Risk factor: poor oral hygiene, and immunocompromised individuals.
–It is mainly reported in immunocompetent patients.
Diagnosis :
Culture: for definitive diagnosis, should be held for at least 14 days(slow growing)
Gram stain: Direct examination non-spore Gram-positive rods
Histopathology (filaments and sulfur granules)
Monoclonal antibody staining: specific staining using fluorescent-conjugated.
Serology: Serology does not appear to be a practical or reliable diagnostic tool.
Treatment:
Antibiotic therapy:
Severe / extensive infections:
IV penicillin G 10 to 20 million units daily in divided doses),ceftriaxone is an alternative.
For mild infection (no significant suppuration or fistulous tracts) or step-down therapy: Oral penicillin, Amoxicillin is an alternative.
-If patient is allergic to penicillin, tetracycline and erythromycin are suitable alternatives
Duration: debatable and has to be adapted to the severity of onset, location of the infection and patient history.
IV therapy for 4-6 weeks then continue oral 2- 6 months for mild disease and 6-12 months for severe disease) to prevent disease recrudescence
Surgery for drainage in severe infection.
Prevention: maintenance of good oral hygiene and appropriate dental plaque removal.
Immunosuppression management:
-Balance the risks and benefits when modifying IS.
-Reduce the dose or stopping antimetabolite.
In renal transplantation:
– The global outcome is good and relapse is rare.
– Excellent renal outcome is regardless of immunosuppressive drugs
– It does not seem to increase graft rejection rates,
References:
-Rousseau C, Piroth L, Pernin V, Cassuto E, Etienne I, Jeribi A, Kamar N, Pouteil-Noble C, Mousson C. Actinomycosis: An infrequent disease in renal transplant recipients? Transpl Infect Dis. 2018 Dec;20(6):e12970. doi: 10.1111/tid.12970. Epub 2018 Aug 11. PMID: 30055044.
Valour F, Sénéchal A, Dupieux C, Karsenty J, Lustig S, Breton P, Gleizal A, Boussel L, Laurent F, Braun E, Chidiac C, Ader F, Ferry T. Actinomycosis: etiology, clinical features, diagnosis, treatment, and management. Infect Drug Resist. 2014 Jul 5;7:183-97. doi: 10.2147/IDR.S39601. PMID: 25045274; PMCID: PMC4094581.
Your last paragraph is very relevant.
The index patient is a renal transplant (7 month back) recipient on tacrolimus-based triple immunosuppression, now presenting with multiple sinuses over right mandible for last 3 months, without any fever.The clinical scenario of multiple sinuses in cervicofacial region in an immunosuppressed patient points towards formation of cold abscess, with the differential diagnosis of (1):
Yes. It is a common site for actinomycosis. Actinomycosis presents at different sites (2):
Diagnosis of Actinomycosis: Actinomycosis is a slowly progressing infection, lacks virulence, and has high risk of abscess or fistula formation. The diagnosis can be established by histopathology or microbiological analysis of the affected site. Direct microscopic examination reveals non-spore Gram-positive rods (2). These bacteria are clow growing, require anaerobic culture, and are often co-infected, hence cultures are positive in only 50% of cases (due to previous antibiotic exposure).
Histopathological examination of tissue from surgical biopsy or pus reveals abscess with purulent, granulomatous inflammation and fibrosis. Hematoxylin and eosin staining will reveal solid nodules (“sulfur granule”) with filamentous structures visible at the periphery of the abscess.
Treatment of Actinomycosis: Treatment of Actinomycosis is lengthy (due to avascular nature of the infection). It involves high doses of intravenous penicillin G (up to 24MIU/day) for 2-6 weeks followed by high doses of oral penicillin ( or amoxycillin 200 mg/kg/day) for 6-12 months to prevent relapse.
Lower doses and shorter treatment can be given if the diagnosis is made early, there is absence of bone involvement, and satisfactory patient response is observed rapidly (1).
Co-infected bacteria should be treated early. In case of penicillin allergy, clindamycin, doxycycline, or macrolides can be used.
Surgery for drainage should be avoided except in case of large abscess, recalcitrant fibrotic lesion, and osteomyelitis of the bone (1). Dental caries, if present, should be treated.
References:
Well done
-What is your differential diagnosis?
Mostly a case of Cervicofacial Actinomycosis
DD include blastomycosis, brain abscess, colon cancer, crohn disease, diverticulitis, liver abscess, lung abscess, lymphoma, nocardiosis, pelvic inflammatory disease, pneumonia, tuberculosis and uterine cancer.
-Is it a common site for this form of infection?
Yes cervicofacial ,genitourinary ,respiratory ,digestive tracts ,CNS ,skin and bone and joint
-Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
It is a rare and heterogeneous infection involving Gram-positive anaerobic bacteria, which are commensals in the oral cavity and digestive tract.
Actinomyces israelii and Actinomyces gerencseriae are the bacteria responsible for this condition though other types of Actinomyces bacteria have also been reported .
Diagnosis was made possible by microbiology or histopathology (filaments and sulfur granules) of the infection site, prolonged bacterial culture of an abscess or of a suspected tissue is required to identify the bacteria.
CT or MRI to detect further affection
Treatment with amoxicillin for 2-6 weeks, and clavulanic acid during the initial stages of treatment.
Surgical intervention is required to remove the infected tissues and for draining out of the excessive abscesses. Dental treatment is necessary for dental caries.
There is no recommendation for the management of concomitant immunosuppressive treatment meanwhile reduction of immunosuppression can be needed
Antimetabolite can be suspended , Tac dose reduced to reach minimum trough level and steroids reduction along with graft monitoring
Reference
– Rousseau C et al .Actinomycosis: An infrequent disease in renal transplant recipients?Transplant infectious disease 2018 ;20(6) e12970
– Yiğiter M, Kiyici H, Arda IS, Hiçsönmez A (2007). “Actinomycosis: a differential diagnosis for [[appendicitis]]. A case report and review of the literature”. J Pediatr Surg. 42 (6): E23–6.
-Hasper D, Schefold JC, Baumgart DC (2009). “Management of severe abdominal infections”. Recent Pat Antiinfect Drug Discov. 4 (1): 57–65.
-Lederman ER, Crum NF (2004). “A case series and focused review of nocardiosis: clinical and microbiologic aspects”. Medicine (Baltimore). 83 (5): 300–13..
– Hoffman, Barbara (2012). Williams gynecology. New York: McGraw-Hill Medical. ISBN 9780071716727.
-Humes, D J (2006). “Acute appendicitis”. BMJ. 333 (7567): 530–534.
– Saccente M, Woods GL (2010). “Clinical and laboratory update on blastomycosis”. Clin. Microbiol. Rev. 23 (2): 367–81.
Kim, Eun Ran (2014). “Colorectal cancer in inflammatory bowel disease: The risk, pathogenesis, prevention and diagnosis”. World Journal of Gastroenterology. 20 (29): 9872. doi:10.3748/wjg.v20.i29.9872. ISSN 1007-9327.
Hanauer, Stephen B. (1996). “Inflammatory bowel disease”. New England Journal of Medicine. 334 (13): 841–848. PMID 8596552. Retrieved 2006-11-10.
Kuhajda I, Zarogoulidis K, Tsirgogianni K, Tsavlis D, Kioumis I, Kosmidis C, Tsakiridis K, Mpakas A, Zarogoulidis P, Zissimopoulos A, Baloukas D, Kuhajda D (2015). “Lung abscess-etiology, diagnostic and treatment options”. Ann Transl Med. 3 (13): 183. doi:10.3978/j.issn.2305-5839.2015.07.08. PMC 4543327. PMID 26366400.
Soper DE (2010). “Pelvic inflammatory disease”. Obstet Gynecol. 116 (2 Pt 1): 419–28.
– Cunha, F., Sousa, D.L., Trindade, L. et al. Disseminated cutaneous Actinomyces bovis infection in an immunocompromised host: case report and review of the literature. BMC Infect Dis 22, 310 (2022).
Do you mean spreading pyemic abscesses in the DD you mentioned!
Otherwise well done.
yes the other DD can have the same presentation as actinomycosis
An a-61-year-old female patient presented with a 3-month history of multiple sinuses in the right side of the face (see below) without fever 7 months after receiving a kidney transplant from his 32-year-old son. She is on Tacrolimus-based triple immunosuppression with excellent graft function.
A case of oropharyngeal actinomycosis post kidney transplant which is not common infection which is considered a rare and heterogeneous infection involving Gram-positive anaerobic bacteria, which are commensals in the oral cavity and digestive tract.
What is your differential diagnosis?
– Cervicofacial actinomycosis
– Nontuberculous mycobacterial skin infection
– Mucor mycosis
– Osteomyelitis
– Mycetoma
– Cancer (metastatic)
Is it a common site for this form of infection?
Yes,
It is characterized by contiguous spread, suppurative and granulomatous inflammation, and the formation of multiple abscesses and sinus tracts that may discharge sulfur granules. The most common clinical forms of actinomycosis are cervicofacial (i.e., lumpy jaw).
There are 4 primary subtypes of actinomycosis infection:
– Cervical-oral (60 %)
– Abdominal (20 %)
– Pulmonary (15 %)
– Pelvic (5 %)
Actinomycosis is caused by branched, filamentous anaerobic Gram-positive bacteria called Actinomyces.
It is a chronic granulomatous and suppurative infectious disease.
In healthy individuals, actinomycosis is a commensal of the oral cavity, colon, and vagina. Actinomycosis becomes pathological in immunocompromised patients.
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
Clinical diagnosis must be confirmed by histopathologic and bacteriologic examinations (samples of sputum, pus, or tissue), If the infection is present the pus or tissue will usually contain yellow sulfur granules.
Only few cases of actinomycosis have been reported in renal transplant recipients to date.
Treatment Actinomycosis need Long-term treatment with antibiotics, such as penicillin, is common. It may last from 8 weeks to over 12 months.
Surgical drainage, debridement and resection may be required.
In some cases, a surgeon may drain an abscess or remove an infected part. After this, the person may need a 3-month course of antibiotics to resolve the problem.
Actinomycosis is differentiated from other diseases with acid-fast negative ray-like bacilli and sulphur granules being pathognomonic.
Immunosuppressive medications may need to be adjusted to the minimal possible doses (guided by drug levels) to control infection guard against possible rejection.
References
Rousseau, C., Piroth, L., Pernin, V., Cassuto, E., Etienne, I., Jeribi, A., … and Mousson, C. (2018). Actinomycosis: an infrequent disease in renal transplant recipients? Transplant Infectious Disease, 20(6), e12970.
Miladipour et al., Mucormycosis After Kidney Transplantation, Iranian Journal of Kidney Diseases | Volume 2 | Number 3 | July 2008
Paolo Bortoluzzi , Gianluca Nazzaro, Serena Giacalone, Stefano Veraldi, Cervicofacial actinomycosis: a report of 14 patients observed at the Dermatology Unit of the University of Milan, Italy, International Journal of Dermatology, First published: 13 May 2020 https://doi.org /10.1111/ijd.14934
Well done.
5. An a-61-year-old female patient presented with a 3-month history of multiple sinuses in the right side of the face (see below) without fever 7 months after receiving a kidney transplant from his 32-year-old son. She is on Tacrolimus-based triple immunosuppression with excellent graft function.
====================================================================
====================================================================
====================================================================
Differential Diagnosis
The other important differential diagnosis to consider are the following:
====================================================================
Is it a common site for this form of infection?
Cervicofacial
====================================================================
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
Laboratory Studies
CBC
The gold standard test for diagnosis is tissue biopsy culture with anaerobic pus cultures, which can be falsely negative.
Chest radiography and CT scanning can reveal a poorly defined mass or pneumonitis or cavitary lesion, with or without pleural involvement. Hilar adenopathy is uncommon.
===================================================================
Treatment
If the patient is allergic to penicillin, alternatives include:
====================================================================
Check up of level of tacrolimus
===========================
Prevention
==================================================================
Reference
Well done as usual.
1-What is your differential diagnosis?
-Cervicofacial actinomycosis (most likely)
-Nocardia infection
–Mucormycosis
-Granulomatous diseases including tuberculosis
-Skin malignancy
-Odontogenic Abscess
-Fungal infection (Blastomycosis)
-Suppurative dermatosis
2-Is it a common site for this form of infection?
–Cervicofacial involvement is the most common manifestation of actinomycosis, accounting for 50 % of all cases, while central nervous system, thoracic, abdominal, and pelvic actinomycosis occur less frequently.
-Cervicofacial actinomycosis may involve almost any tissue or structure surrounding the upper or lower mandible.
-However, the mandible itself is consistently the most commonly identified site of infection.
-In one study of 317 patients reported from Cologne between 1952 and 1975, the presenting sites were identified as :
*Mandible – 53.6 %
*Cheek – 16.4 %
*Chin – 13.3 %
*Submaxillary ramus and angle – 10.7 %
*Upper jaw – 5.7 %
*Mandibular joint – 0.3 % .
3-Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
Definitive diagnosis;
-Actinomycosis is usually diagnosed by culturing the organism, although the specimens must be handled properly and , cultures held for at least 14 days.
Culture;
-Confirmation of the diagnosis requires the recovery of Actinomyces species from an appropriately cultured specimen, typically by needle aspiration of an abscess, fistula, or sinus tract or from a large biopsy specimen.
Histology;
-Multiple sections of a biopsy specimen from different tissue levels are suggested to improve histologic diagnosis.
-Sections of biopsy material typically reveal acute or chronic inflammatory granulation tissue with infiltration by neutrophils, foamy macrophages, plasma cells and lymphocytes, and a surrounding dense fibrosis.
-Healing lesions tend to demonstrate profound fibrosis, even avascular in nature, often in proximity to areas of acute suppuration.
-Sulfur granules may comprise no more than 1% of total tissue in a given lesion, and hence are easily missed by routine tissue staining.
-Often, a series of biopsies is required to confirm a pathologic diagnosis.
Treatment;
-High-dose penicillin is the treatment of choice for actinomycosis.
-Alternative agents include (Amoxicillin or Amoxicillin-clavulanate or Doxycycline).
-Management of cervicofacial actinomycosis often requires prolonged courses of antibiotics.
-Surgical intervention may also be necessary in more complicated cases.
-In severe periapical actinomycosis resistant to conventional therapy, root-end surgery with bone grafting may be required.
Prevention;
-There are no defined measures for preventing cervicofacial actinomycosis. However, maintenance of good oral hygiene and appropriate dental plaque removal can limit the tendency of Actinomyces to establish dense colonization and subclinical periodontal infection, an important precipitating event for more extensive disease.
Reduction of I.S.;
-Decrease dose of antimetabolite or holding it temporarily
-keep pt on CNI + steroid (target of Tac. trough 4-6 ng/ml)
References;
–Schaal KP, Beaman BL. Clinical significance of actinomycetes. In: The Biology of the Actinomycetes, Goodfellow M, Mordarski M, Williams ST (Eds), Academic Press, New York 1983. Vol 389.
–Kwartler JA, Limaye A. Pathologic quiz case 1. Cervicofacial actinomycosis. Arch Otolaryngol Head Neck Surg 1989; 115:524.
–Könönen E, Wade WG. Actinomyces and related organisms in human infections. Clin Microbiol Rev 2015; 28:419.
–Lerner PI. The lumpy jaw. Cervicofacial actinomycosis. Infect Dis Clin North Am 1988; 2:203.
–Smego RA Jr, Foglia G. Actinomycosis. Clin Infect Dis 1998; 26:1255.
–Gilbert DN, Moellering RC Jr, Sande MA. The Sanford Guide to Antimicrobial Therapy. Antimicrobial Therapy, Inc 2001; 31:70.
–Asgary S, Roghanizadeh L. Grafting with Bone Substitute Materials in Therapy-Resistant Periapical Actinomycosis. Case Rep Dent 2021; 2021:6619731.
Well done for mentioning the ORAL HYGENE issue which can be neglected for the recipient.
What is your differential diagnosis?
Is it a common site for this form of infection?
Important criteria of this disease includes
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
Diagnosis
Treatment
A- Reduction of immunosuppression
B- Antibiotics
C- Surgical debridement may be required in some severe cases
References
Among specific criteria is the very long persistent duration which needs an equivalent long coarse of treatment
What is your differential diagnosis?Differential diagnoses of angle jaw multiple sinuses 4 months after kidney transplantation include:
1. Cervicofacial ctinomycosis
2. Nocardiosis
3. Odontogenic Abscess
4. Fungal infection (Blastomycosis)
5. Malignancy
6. Tuberculosis
7. Rare: brucellosis, anthrax, toxoplasmosis and infectious mononeucleosis
Is it a common site for this form of infection?o Actinomycosis is a gram positive bacilli, anaerobic or microphilic characterized by purulent granulomatosis disease accompany by sinus tract. The most common species in humans is Actinomyces israelii
o Yes, The classic lesion located at the angle of the jaw is the most frequent location (submandibular)
o In up to 15%-20% of the cases it involves throat and in 10%-20% cases it involves the pelvic area
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!o Detailed history and comprehensive examination including oral cavity and and cervical examination for lymphadenopathy
o ENT consultation
o CBC, CRP, ESR, RFT & electrolytes, PT, PTT
o Soft tissue sonography of the neck/CT scan
o Tuberculin skin test/IGRA
o Draining sinus sample for gram stain and culture (sulfur granulesare characteristic for actinomycosis but grains are seen inmycetoma and butriomycosis)/PCR/tissue histopathology
o Drain sinus AFB stain and culture
o Excisional biopsy and histopathology
o Intravenous Penicillin therapy 4 million units, every 4 hours, for 2-6 weeks, followed by oral therapy with PNC-V 500 mg every 6 hours for 6-12 months (successful in 90% of the cases). Antibiotic treatment in transplant patients produces results similar to those in immunocompetent patients. If patient is allergic to penicillin, tetracycline and erythromycin are suitable alternatives
References
1. Avijgan M et al. A case report of cervicofacial actinomycosis. Asian Pacific Journal of Tropical Medicine (2010)838-840.
2. María Isabel Sáez et al. Actinomyces viscosus infection in a kidney–pancreas trasplanted patient. Nefrolgia. 2017;37(4): 429–449.
Thankyou.
-Differential diagnosis
-Is it a common site for this form of infection?
-Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
Reference
A case series of actinomycosis from a single tertiary care center in Saudi ArabiaAuthor links open overlay panel by Fatehi Elzein et al.
Thankyou Ben but scc is clinically unlikely as seen in this index case (multiple sinuses)!
Thankyou Ben I reviewed your article ,very unusual sites!
I have another article , let me look at prof
Yes, prof, just to keep in mind
What is your differential diagnosis?actinomycosis
nocardiasis
blastomycosis
TB
suppurative dermatosis
malignancy
Is it a common site for this infection
Yes,
It is characterized by contiguous spread, suppurative and granulomatous inflammation, and the formation of multiple abscesses and sinus tracts that may discharge sulfur granules. The most common clinical forms of actinomycosis are cervicofacial (ie, lumpy jaw).
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
Diagnosis is made through cytologic or histologic examination,
of samples of sputum, pus, or tissue to send for microscopic investigation in a laboratory. Sometimes, the laboratory will make a culture of the bacteria. If the infection is present, the pus or tissue will usually contain yellow sulfur granules.
TreatmentActinomycosis can persist for a long time. Long-term treatment with antibiotics, such as penicillin, is common. It may last from 8 weeks to over 12 months.
In some cases, a surgeon may drain an abscess or remove an infected part. After this, the person may need a 3-month course of antibiotics to resolve the problem.
It may be necessary to reduce the dosage of immunosuppressant drugs to the lowest effective level in order to prevent and treat infections and minimize the risk of organ rejection.
Rousseau, C., Piroth, L., Pernin, V., Cassuto, E., Etienne, I., Jeribi, A., … & Mousson, C. (2018). Actinomycosis: an infrequent disease in renal transplant recipients? Transplant Infectious Disease, 20(6), e12970.
Thankyou
Differential diagnosis
Is it a common site for this infection
Diagnosis
Cervicofacial actinomycosis has been dubbed the “great masqueraded” of the head and neck, hence a high index of suspicion is required
Treatment
References
Thankyou
What is your differential diagnosis?
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Is it a common site for this form of infection?
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Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
References
Well done.
What is your differential diagnosis?A case of oropharyngeal actinomycosis post kidney transplant which is not common infection which is considered a rare and heterogeneous infection involving Gram-positive anaerobic bacteria, which are commensals in the oral cavity and digestive tract.
Is it a common site for this form of infection?In one study done on seven cases post kidney transplant showing 2 cases in this site.
Locations of actinomycosis were cervicofacial (n = 2), pulmonary (n = 2), abdominopelvic (n = 2), or cutaneous (n = 1)
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!Diagnosis was made possible by microbiology or histopathology (filaments and sulfur granules) (of the infection site.
Adjust immunosuppression and decreasing or stopping MMF.
Initial parenteral therapy is typically given for four to six weeks. Switching from intravenous to oral therapy is usually possible after there is significant improvement in the patient’s condition.
Patients should be treated with amoxicillin for long time with median duration of 115 days.
Some patient treated with surgical intervention.
References:
1- Rousseau C, Piroth L, Pernin V, et al. Actinomycosis: An infrequent disease in renal transplant recipients?. Transpl Infect Dis. 2018;20(6):e12970. doi:10.1111/tid.12970.
2- Treatment of actinomycosis – UpToDate 2023.
Thankyou.
What is your differential diagnosis?Varicella Zoster is the main hypothesis associated with this condition.
Other lesions such as streptococci, ecthyma, skin neoplasia, and vasculitis can be considered as a differential diagnosis.
Is it a common site for this form of infection?No, the most common is to occur in thoracic dermatomes, but they can occur in any region, including the face, evolving into complications such as Ramsay Hunt Syndrome
Outline the principle of diagnosis and treatment of this condition regarding immunosuppressed patients!
Diagnosis is clinical and treatment includes:
Acyclovir 800 mg orally five times daily (omitting the morning dose) or 10 mg/kg/dose three times daily.
In facial infections in immunosuppressed patients, prioritize venous treatment.
Pain control with neuropathic pain medications such as pregabalin depending on the pain status
Treatment should be carried out for at least seven days and all lesions should be healed or crusted over. The presence of vesicles defines disease activity.
Thanks, Filipe
Remember, there are multiple sinuses in an area of the angle of the jaw.
Please review your differential diagnosis.
Sorry, Professor. I did not include Actinomyces.
Thanks, Filipe