Is It Inflammatory Bowel Disease?: A Case of Pediatric Intestinal Paracoccidioidomycosis Resembling Crohn’s Disease in an Immunocompetent Infant

To the Editors: Paracoccidioidomycosis (PCM), also known as South American blastomycosis, is a leading systemic mycosis endemic in the humid tropical and subtropical zones of continental Latin America, particularly in Brazil.1–3 It defines a broad spectrum of neglected human diseases caused by inhaling infectious propagules of the thermo-dimorphic fungus Paracoccidioides brasiliensis, which may lead to secondary foci in any organ.4 Due to its polymorphic presentation, the ability of PCM to mimic other diseases often leads to misdiagnosis and delayed treatment.3,5 We report the case of a previously healthy 4-year-old girl who was hospitalized with a 9-month history of dysentery. She had been experiencing nonspecific abdominal pain followed by progressive episodes of intense watery and bloody diarrhea (ranging from 4 to 6 times a day), postprandial vomiting, decreased food intake, halted weight and height gain [WHO’s body mass index (BMI)-for-age z-score less than −3] and lethargy, without fever. Her medical history was uneventful; she was born and lived in Machado, a 40,000-inhabitant rural city in Minas Gerais, Brazil. During this period, she was evaluated at several basic and specialized care services in Minas Gerais: the only consistent laboratory abnormalities were microcytic hypochromic anemia and elevated inflammatory activity markers (including C-reactive protein and erythrocyte sedimentation rate). Food allergens, oral lactose absorption and autoantibodies test results were normal. During the 2 previous hospitalizations, she received metronidazole and trimethoprim-sulfamethoxazole, respectively, with partial and transient improvement of the symptoms. Upon admission, the remarking clinical and laboratory findings included paleness, dehydration, emaciation, generalized inflammatory lymphadenopathy, hepatosplenomegaly, hypochromic microcytic anemia (hemoglobin: 5.7 g/dL, hematocrit: 22.3 g/dL), increased acute phase reactants (C-reactive protein = 5.7 mg/dL; erythrocyte sedimentation rate = 126 mm/min), hyponatremia (130 mEq/L) and hypokalemia (2.2 mEq/L). Parasitological stool microscopy, hemoglobin electrophoresis, detection of enteric protozoans, blood culture, serologies (including HIV, Chagas, EBV and CMV) and chest computed tomography scan were negative. Despite an empirical approach that included an extensively hydrolyzed diet and IV metronidazole, low-grade fever (maximum 38.2°C) started and rectal bleeding persisted. The preliminary endoscopic findings were dominated by extensive nonspecific colitis; therefore, pulse therapy with methylprednisolone (3 mg/kg/day) was promptly initiated, followed by oral prednisone and mesalazine. Chronic granulomatous colitis and yeast cells with multipolar budding (shaped as a ship’s pilot wheel) were secondarily described (Fig. 1), and treatment with liposomal amphotericin B (5 mg/kg/day) was started. Serum IgG antibodies against P. brasiliensis glycoprotein gp43 were detectable.FIGURE 1.: Microscopic examination revealing yeast phase of Paracoccidioides in hematoxylin and eosin (H&E) staining (black arrow) and Grocott-Gomori’s methenamine silver (GMS) staining (white arrows).After 21 days of antifungal therapy, the fever subsided, and she was discharged with oral trimethoprim-sulfamethoxazole for a 12-month course. Significant regression of lymph nodes, weight gain (+3.4 kg; minus one BMI-for-age z-score), and complete absence of fever and diarrhea were observed after 3 weeks. The reduction of circulating gp43 antibodies paralleled the clinical response to therapy. No relapses occurred during the 5-year follow-up. This case highlights the challenges in diagnosing an imported atypical PCM in a young preschooler living in a well-known endemic zone of the disease. Acute/subacute juvenile-type PCM occurs without clear environmental exposure, representing 3%–5% of the disease burden.4,6 PCM mimicking inflammatory bowel disease (IBD) is described in less than a quarter of these cases.7 Nodular mucosa and extensive granulomatous inflammatory process can resemble infections (tuberculosis and cytomegalovirus) and noninfectious causes (IBD, sarcoidosis and lymphoma).8 Since most clinicians in nonendemic countries are unfamiliar with systemic mycoses’ clinical picture, PCM should be considered in patients with indeterminate colitis (including a negative evaluation for IBD) living or traveling from endemic areas.3 Considering the long latency period (up to several years), the combination of histopathologic fungal staining with serologic testing provides adequate evidence for laboratory diagnosis of PCM and should be included in such scenarios. In our case, the timely discontinuation of immunosuppressive therapy and initiation of antifungal treatment for a minimum duration of 1 year were crucial in minimizing therapeutic failure, complications and relapses.5