SCEDOSPORIUM INFECTION IN A PATIENT WITH ANTI-TNFα THERAPY.

Patients on anti-TNFα therapy are at increased risk for rare opportunistic infections. Here we are reporting a case of Scedosporium apiospermum infection in a patient treated with anti-TNF for 5 years. Patients on anti-TNFα need close follow-up and clinicians should be suspicious for atypical infections in these immunocompromised hosts.

Introduction

Currently anti-TNF agents are widely used for cutaneous and systemic autoimmune diseases. For dermatologists most common indications for anti-TNF use are psoriasis and psoriatic arthritis. We describe a case of Scedosporium apiospermum infection in a patient receiving long-term treatment with etanercept, a TNF-α inhibitor. S. apiospermum is a ubiquitous filamentous fungus found in soil, polluted water, and contaminated ambient air in hospital isolation rooms. In immunocompromised patients, S. apiospermum can lead to life-threatening pulmonary or disseminated infections. Increasing reports of S. apiospermum infection in the past few years suggests that S. apiospermum is an emergent opportunistic pathogen.[1]

TNF-α inhibitors have had a significant impact in the treatment of inflammatory rheumatologic disease.[2] However, these drugs have immunosuppressive effects. Infectious diseases including tuberculosis, atypical mycobacteria, histoplasmosis, coccidioidomycosis, and various opportunistic infections in patients receiving TNF-a inhibitors have been reported in the literature and postmarketing surveillance.[34] A PUBMED search resulted in one report of Scedosporium infection as a complication of infliximab therapy for ankylosing spondylitis.[5] To the best of our knowledge, this is the first reported case of S. apiospermum infection in a patient receiving etanercept.

Case Report

Our patient is a 64-year-old man with spondyloarthropathy of undetermined origin. The patient did not have peripheral arthritis. Neither he had active psoriasis lesions, but he had pitting and ridging on nails. He had sacroiliitis and ankylosis of cervical vertebrae. After extensive workup, we narrowed our differential diagnosis to ankylosing spondylitis and psoriatic arthritis. The patient was previously treated with sulfasalazine and NSAID. In 2002, he was started on methotrexate because of continued neck and lower back pain with morning stiffness. In 2004, etanercept was initiated at the dose of 50 mg/week and sulfasalazine was discontinued. He did remarkably well with etanercept in respect to back pain and morning stiffness. In 2008 he presented with increasing and persistent pain in the left orbit. A CT showed chronic left ethmoid sinus disease and sphenoid sinus opacification. He was started on moxifloxacin for 3 weeks with little improvement of symptoms. As he was receiving an anti-TNF agent, we actively pursued investigation for opportunistic and rare infectious agents. A flexible endoscopic examination of the sinuses demonstrated mucopurulent ethmoid disease. He underwent surgery for bilateral sinus sphenoidotomies and left ethmoidectomy. Tissue specimens of the right and left nasal turbinates and nasal washes were sent for evaluation and culture. The tissue isolates showed chronic inflammatory edematous respiratory tissue without any significant pathology in the underlying bones and GMS stains showed no evidence of fungus. However, cultures of the specimen from the sphenoid sinuses returned positive for S. apiospermum. A MRI of head and sinuses did not demonstrate any evidence for invasive rhinocerebral fungal disease. We consulted our infectious disease colleagues and the patient was started on voriconazole 200 mg BID. He completed a 10-week course of antibiotic therapy. His sinus symptoms completely resolved after surgery and antibiotic treatment. Repeat endoscopic examination demonstrated that the ethmoidectomies and sphenoidotomies were patent and clean. Follow-up MRI and CT of the brain and sinuses did not show any evidence for sinusitis or invasion of the adjacent anatomical structures. As there was no histopathological or radiological evidence for invasive fungal infection we felt comfortable to continue etanercept. The patient has continued to take both etanercept and methotrexate for more than 1 year with no signs of re-infection or complication.

Discussion

Scedosporium apiospermum has been associated with mycetoma, keratitis, endophthalmitis, osteomyelitis, and brain abscesses. S. apiospermum conidia enter via the respiratory tract and germinate with hyphae invasion. A wide range of pulmonary manifestations exists, ranging from simple colonization as seen in patients with cystic fibrosis to fungus ball formation in patients with cavitary lesions and invasive disease, simulating aspergillosis.[56] Sinusitis may present in both immunocompetent and immunocompromised patients with variable severity.[1] As the clinical presentation of Scedosporium infection, including fever, cough, and dyspnea is nonspecific, diagnosis can be based on cytology, histopathology, and isolation of the fungus in culture. Culture confirmation is important as the histological appearance and clinical presentation of S. apiospermum are difficult to distinguish from that of the Aspergillus species on pathological examination. In a case report of three lung transplant patients, mean-time from specimen collection to positive-culture identification for sputum culture was 4.5 days compared to 9.5 days with bronchoalveolar lavage culture. In our patient, positive culture was identified in 10 days.[7]

Treatment for Scedosporium infection continues to be challenging. S. apiospermum has been shown to have intrinsic resistance to many anti-fungal agents, including fluconazole and amphotericin B, the traditional antifungal of choice for disseminated hyalohyphomycoses.[8] Much of the data on the treatment of S. apiospermum pertains to the use of voriconazole. A retrospective review of 107 patients treated for Scedosporium infection with voriconazole showed 57% of patients achieved a successful response after a median of 103 days of therapy.[9] In vitro studies have demonstrated that voriconazole is more active against S. apiospermum than either itraconazole or amphotericin B.[6] The optimal choice and duration of therapy remain unknown. Surgical debridement or drainage for limited disease in combination with antifungal therapy, as was done successfully with our patient, is recommended now.[5610]