Desai, Madhav

Imran, Muhammad

Irum, Ayesha

Magadan III, Julian

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KANSAS JOURNAL of  M E D I C I N EPrimary Cutaneous Nocardiosis in a Patient Taking Adalimumab Therapy for Crohn’s DiseaseMadhav Desai, MBBS1, Muhammad Imran, M.D.1,2, Ayesha Irum3, Julian Magadan III, M.D. 1,2 University of Kansas Medical Center, Kansas City, KS1Department of Internal Medicine2Division of Allergy, Clinical Immunology and Rheumatology3Army Medical College, Rawalpindi, PakistanINTRODUCTIONThe introduction of biologic immunomodulators, in par-ticular antibodies targeted against tumor necrosis factor al-pha (TNF-alpha), has revolutionized treatment of Crohn’s disease. However, this comes at the expense of a higher risk for opportunistic infections due to a generalized immuno-suppressive effect. Bacterial and opportunistic infections are well-known complications of anti-TNF agents.1,2 Nocardia has been reported rarely among patients on anti-TNF agents.3 TNF plays a role in the clearance of norcardia in animal models.4 Immunosuppression, anti-TNF treatment in particu-lar, may favor growth and dissemination of nocardia. Pulmo-nary and cutaneous nocardiosis has been reported in Crohn’s disease patients on infliximab.5,6 Nocardiosis has been re-ported with adalimumab therapy in rheumatoid arthritis pa-tients.7,8 Our search did not reveal any cases of nocardiosis while on adalimumab therapy in Crohn’s disease patients. Crohn’s disease patients receiving biologic agents, in particular, tumor necrosis factor (TNF)-alpha inhibitors are immunosuppressed and are prone to develop oppor-tunistic infections. We report a rare case of primary cuta-neous nocardiosis in an immunocompromised patient on chronic anti-TNF for underlying severe Crohn’s disease.CASE REPORT A 36-year-old Caucasian gentleman with a history of Crohn’s disease treated with adalimumab presented with a cellulitis-like rash on his forehead (Figure 1). Five weeks pre-viously, he had struck his forehead on a construction pole, sustaining a laceration which required sutures. On presenta-tion, he had developed purulent discharge from the lacera-tion site, and he was started on doxycycline. After completing antibiotic treatment, he was seen by a dermatologist due to persistent rash and a punch biopsy was taken from the area.Figure 1. Cellulitis-like rash with draining and crusting.Histological examination of the biopsy showed granu-lomatous inflammation thought to be related to a foreign body. The lesion worsened with increasing pain, pruri-tus, erythema, and development of a furuncle with drain-age of yellow purulent material. A swab was sent for aero-bic culture which grew coagulase negative staphylococci. Viral and fungal cultures from this lesion were negative. Over the next several weeks, the lesion continued to worsen, growing in size and becoming more painful. The adalimumab therapy was stopped and pyoderma gangrenosum was consid-ered due to the patient’s underlying Crohn’s disease. The patient subsequently was admitted due to uncontrolled pain, and pro-gression of his forehead lesion. A comprehensive work-up for human immunodeficiency virus, syphilis, tuberculosis, hepati-tis, antinuclear antibody, rheumatoid factor, anti-cyclic citrulli-nated peptide, and serum protein electrophoresis were negative. Blood (bacterial and fungal), urine, and sputum cultures were negative.  Chest x-ray was negative. With IV antibiotics, there was some improvement in the forehead rash and the patient was discharged on oral antibiotics. He also was started on dap-sone and clobetasol for treatment of pyoderma gangrenosum. One week later, cultures from his biopsy grew Nocardia arthri-tidis (Figure 2). He was started on trimethoprim-sulfamethoxa-zole daily with follow-up with an infectious disease specialist. His rash improved significantly after a few weeks of treatment.20 KANSAS JOURNAL of  M E D I C I N EPRIMARY CUTANEOUS NOCARDIOSIScontinued.Figure 2. Nocardia asteroids staining and culture.Figure 2. Nocardia asteroids staining and culture. DISCUSSIONHuman nocardiosis is caused by nocardia species which is an ubiquitous soil inhabiting bacteria and considered an op-portunistic pathogen.8 It can affect the skin and classically dis-seminate to involve the lungs and brain. It is a difficult infection to treat and carries high mortality if disseminated.9 Nocar-diosis has been well known to affect AIDS patients, transplant recipients, and long term corticosteroid treated individuals. Now, it is being recognized increasingly in immunosuppressed patients on anti-TNF agents. Previous use of corticosteroids has been identified as a risk factor, as noted in our case, and was present in more than 50% of cases in earlier studies.10 Early diagnosis is essential and norcardia should be con-sidered in the differential diagnosis of any patient present-ing with draining skin lesion or painful rash who is receiving anti-TNF agents or has in the recent past. Anti-TNF therapy doubles the risk of opportunistic infections in inflammatory bowel disease patients.9,10 This underscores the importance of adherence to guidelines for their prevention and management. A high level of vigilance and scrutiny in examination and fol-low up are highly recommended for this group of patients.CONCLUSION A high level of suspicion must be enforced when patients re-ceiving TNF-alpha inhibitors present with skin manifestations, in particular, cellulitis-rash or draining lesion. Early identifica-tion and treatment of nocardia is pivotal to prevent disseminat-ed disease and mortality. REFERENCES 1xStrangfeld A, Listing J. Infection and musculoskeletal conditions: Bacterial and opportunistic infections during anti-TNF therapy. Best Pract Res Clin Rheumatol 2006; 20(6):1181-1195. PMID: 17127203.2xAli T, Kaitha S, Mahmood S, Ftesi A, Stone J, Bronze MS. Clinical use of anti-TNF therapy and increased risk of infec-tions. Drug Healthc Patient Saf 2013; 5:79-99. PMID: 23569399. 3xAbreu C, Rocha-Pereira N, Sarmento A, Magro F. Nocardia infec-tions among immunomodulated inflammatory bowel disease patients: A review. World J Gastroenterol 2015; 21:6491-6498. PMID: 26074688.4xSilva CL, Faccioli LH. Tumor necrosis factor and macrophage activa-tion are important in clearance of Nocardia brasiliensis from the livers and spleens of mice. Infect Immun 1992; 60(9):3566-3570. PMID: 1500164.5xVerma R, Walia R, Sondike SB, Khan R. Pulmonary no-cardiosis in an adolescent patient with Crohn’s disease treated with infliximab: A serious complication of TNF-al-pha blockers. W V Med J 2015; 111:36-39. PMID: 26050296. 6xSingh SM, Rau NV, Cohen LB, Harris H. Cutaneous nocardio-sis complicating management of Crohn’s disease with infliximab and prednisone. CMAJ 2004; 171(9):1063-1064. PMID: 15505269. 7xDoraiswamy VA. Nocardia infection with adalimumab in rheu-matoid arthritis. J Rheumatol 2008; 35(3):542-543. PMID: 18322980. 8xWendling D, Murad M, Mathieu S, Berger E, Rumbach L. Systemic nocardiosis in a case of rheumatoid arthritis treated with tumor necro-sis factor blockers. J Rheumatol 2008; 35(3):539-542. PMID: 18322977. 9xLerner PI. Nocardiosis. Clin Infect Dis 1996; 22(6):891-903; quiz 904-905. PMID: 8783685.10xMinero MV, Marin M, Cercenado E, Rabadan PM, Bouza E, Munoz P. Nocardiosis at the turn of the cen-tury. Medicine 2009; 88(4):250-261. PMID: 19593231. Keywords: nocardia infections, adalimumab, Crohn’s disease21

Primary Cutaneous Nocardiosis in a Patient Taking Adalimumab Therapy for Crohn’s Disease

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Primary Cutaneous Nocardiosis in a Patient Taking Adalimumab Therapy for Crohn’s Disease

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