Abstract
Disseminated coccidioidomycosis is a rare but serious complication of fungal illness, with immunocompromised patients more susceptible to severe illness. Here we report a unique case of disseminated coccidioidomycosis in a patient on mycophenolate for treatment of polymyositis.
Keywords: Coccidioides, coccidioidomycosis, disseminated coccidioidomycosis, immunosuppressed, mycophenolate
Coccidioidomycosis, a fungal infection, is typically limited to the lungs but can disseminate to various tissues including the central nervous system, skin, musculoskeletal system, and genitourinary system. Immunosuppressed patients are at a higher risk of severe coccidioidomycosis. However, treatment guidelines regarding patients on immunosuppressive therapy who acquire coccidioidomycosis are limited. We present a case of coccidioidomycosis in an immunosuppressed patient requiring de-escalation of immunosuppressive therapy.
CASE PRESENTATION
A 19-year-old Caucasian man was admitted for treatment of persistent fevers. He was diagnosed with seronegative polymyositis 5 months prior to admission. A more thorough description of this patient’s polymyositis diagnosis is provided by Aldrete et al.1 The patient was being treated with mycophenolate mofetil (MMF) and prednisone by the rheumatology service. He presented with a month of fevers with left-sided abdominal and lower sternal pain. He was tachycardic, febrile, and hypoxemic with an oxygen saturation of 91% on room air. On exam, he was ill-appearing in moderate distress with mild left lower quadrant tenderness.
Computed tomography (CT) of his abdomen and pelvis on hospital day (HD) 1 showed multiple rim-enhancing fluid collections concerning for abscesses in the small bowel, pericolic area, and chest wall. The chest wall abscess was drained of 60 cc purulent fluid. He was started empirically on vancomycin and meropenem for suspicion of bacterial infection while cultures were pending. On HD 3, his fever had resolved and symptoms were improving. On HD 5, chest wall abscess fluid cultures were positive for fungal growth. On HD 7, the patient became febrile and oral voriconazole was started. On HD 8, fungal cultures revealed growth of Coccidioides spp. Voriconazole was discontinued and the patient was started on oral fluconazole 400 mg daily. On HD 9, repeat CT chest, abdomen, and pelvis showed interval development of left upper and lower lobe consolidation as well as bilateral pleural effusions, hepatic fluid collections, and inflammatory changes surrounding the cecum (Figure 1). The decision was made to discontinue fluconazole and start intravenous amphotericin B lipid complex. Within minutes of starting the infusion, the patient developed chest pain, tachycardia, and shortness of breath with worsening hypoxia, at which point amphotericin B was discontinued due to suspected infusion reaction. He was started on oral fluconazole 800 mg daily. He improved over the following days and was ultimately discharged on HD 15 with fluconazole and hydrocortisone with plans for tapering. MMF was discontinued.
Figure 1.
CT of the chest, abdomen, and pelvis with contrast on hospital day 9 showing (a) a nodule in the right upper quadrant of the liver (1) and fluid collection in the 10th to 12th ribs (2) and (b) a small bowel abscess.
DISCUSSION
Most individuals exposed to Coccidioides spores are asymptomatic.2 Of those who become symptomatic, about 1% will develop disseminated disease, defined as positive culture or histology of Coccidioides in an extrapulmonary location. Dissemination typically presents with skin lesions, vertebral osteomyelitis, and central nervous system infection, with less common involvement in the abdomen, kidneys, or genitourinary system.3,4 Coccidioidomycosis has been known to cause infection at higher rates in the elderly, pregnant women, the immunosuppressed, diabetics, transplant recipients, prisoners, and certain ethnicities.2 About 30% to 50% of immunocompromised patients will develop disseminated disease.
Polymyositis is an idiopathic inflammatory myopathy that often presents with proximal symmetrical muscle weakness and is identified with laboratory findings including elevated creatine kinase, inflammatory infiltrates on muscle biopsy, and autoantibodies.5 Treatment is with corticosteroids as well as immune-modulatory agents. Disease-modifying antirheumatic drugs (DMARDs) and biological response modifiers (BRMs) have significantly improved outcomes for patients via immunological suppression through a variety of mechanisms.
To our knowledge, this case is the only report of severe disseminated coccidioidomycosis in a patient with polymyositis receiving MMF.3 MMF is a steroid-sparing treatment, with side effects of myelosuppression, hypertension, and tremors. It works by inhibiting de novo purine synthesis but has a delayed onset of activity for up to 3 months.5 Reports on fungal illness in patients receiving MMF are rare. We note a case of a 70-year-old man taking MMF and tacrolimus for a kidney transplant 2 years before developing Coccidioides pneumonia.6 As in our case, a combination of MMF with other immunosuppressive medication makes it difficult to determine the impact of MMF alone. Most cases of coccidioidomycosis in patients on immunosuppressive therapy involve patients on tumor necrosis factor alpha blockade.7 Immunosuppressive therapy may increase rates of fungal infection, specifically coccidioidomycosis.8,9
The Infectious Diseases Society of America (IDSA) recommends screening for Coccidioides serology before initiating BRMs, although it does not recommend antifungal prophylaxis in asymptomatic patients.8 Some institutions in endemic areas perform annual serologic testing.9
Treatment is a challenge due to the continued need for immunosuppression to prevent graft rejection. IDSA has noted that there are no clear data regarding adjustment of immunosuppressants in transplant patients with coccidioidomycosis, although it recommends considering reduction when the patient does not respond to antifungals.8 There is limited evidence in managing coccidioidomycosis while on DMARDs and BRMs. Studies have reported discontinuing immunosuppressive therapy in patients with coccidioidomycosis. A study found no complications in 20 patients who restarted DMARD or BRM therapy after receiving treatment for coccidioidomycosis.9
Physicians should be aware of serious and atypical presentations of fungal diseases that can occur in patients who are immunosuppressed, and workup of these patients should include fungal etiologies with a low index of suspicion in endemic areas due to the severity and varying presentation.
DISCLOSURE STATEMENT
The authors report no funding or conflicts of interest. The patient provided oral and written consent for this case to be published.
References
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