Disseminated Histoplasmosis with Mucocutaneous Immune Reconstitution Inflammatory Syndrome in an HIV-Infected Patient

H istoplasma capsulatum is a dimorphic fungus that can affect both immunocompromised and immunocompetent individuals. The Americas, Africa, and Asia are endemic areas. ¹ A wide variety of clinical manifestations can occur depending on the host response, the virulence of the strain, and the extent of inoculation. ² Various districts can be involved during histoplasmosis. ³ Mucocutaneous manifestations may be caused by direct inoculation or by hematogenous spread: they are reported to occur in up to 25% of human immunodeficiency virus (HIV)-infected patients with disseminated histoplasmosis. ⁴

Figure 1 presents baseline radiological findings (a–b), skin lesion with histology (c–d) and cultural examinations showing Histoplasma capsulatum (e–f).

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FIG. 1.

Radiological (a–b), clinical (c), histological (d), and cultural (e–f) findings of the patient.

A 32-year-old HIV-infected male from Ecuador with a history of pulmonary tuberculosis (TB) incompletely treated in 2002 was referred to our hospital in 2010 due to fever, cough, weakness, weight loss, and sore throat. Chest x-ray showed a miliary TB-like involvement and combination therapy with rifampicin, isoniazid, ethambutol, and pyrazinamide was started. Diagnostic tests for active TB (acid-fast bacilli smear, Gen-Probe and cultures) were negative on sputum, bronchoalveolar lavage, blood, urine, and feces. The interferon gamma release assay and tuberculin skin test were also negative.

The patient was severely immunocompromised, with a lymphocyte CD4⁺ cell count of 35/mmc (8%) and plasma HIV-RNA of 46,600 copies/ml. Combined antiretroviral treatment (cART) with tenofovir/emtricitabine plus lopinavir/ritonavir was subsequently started after 2 weeks of antitubercular therapy. Rifampicin was replaced with linezolid due to known drug interactions. Despite this, the patient's clinical condition did not improve after 2 weeks on cART. He developed acute respiratory insufficiency with high oxygen supplementation and infiltrative necrotic papular lesions appeared on his face, throat, neck, and scalp. A skin biopsy and fine-needle aspiration for culture were conducted. Grocott's methenamine silver stain showed a fungal infection and amphotericin B lipid complex (ABLC) 5 mg/kg daily was started. Serological tests for Histoplasma capsulatum and Coccidioides immitis, plasmatic and liquoral cryptococcal antigen were negative, but tests for serum (1–3)-β-d-glucan and galactomannan were positive (>523 pg/ml and 0.69 OD index with a cut-off of 80 pg/ml and 0.5 OD index, respectively). Therefore a videothoracoscopic lung biopsy was performed demonstrating mycotic granulomatous pneumonia and antitubercular therapy was stopped.

Hyphal colonies appeared after 3 weeks of culture on Sabouroud dextrose agar and complete identification of Histoplasma capsulatum var. capsulatum was confirmed with conversion of the mold to the yeast at 37°C.

After 1 month of ABLC, the antifungal therapy was switched to itraconazole oral solution and lopinavir/ritonavir was replaced with raltegravir. The patient was discharged and continued itraconazole for 10 months, with regular therapeutic drug monitoring until the CD4⁺ cell count increased to 200 cells/mmc. Today he has attained good clinical status with a complete immunological recovery and radiological resolution. Mucocutaneous lesions are no longer appreciable.

In conclusion, the diagnosis of histoplasmosis may be challenging in a nonendemic country in which laboratory supports are not available in all centers and in the presence of atypical localizations. In particular, great attention should be given to a differential diagnosis or coinfection with TB, and immune reconstitution inflammatory syndrome must be considered when the clinical status worsens and mucocutaneous lesions appear.