In 2016, a 33-year-old female was admitted with fever (40 C) and maculopapular cutaneous lesions involving the face and the trunk. The patient referred that these symptoms had started one month prior. The patient, native to Cuba (Camaguey Region), has been living in Italy for the last decade, and 4 months prior to admission, she had traveled to Cuba for a month. She did not report any past medical conditions, but she did have unprotected sex in the past. HIV serology resulted positive, HIV-RNA 2,150,000 copies/ml, the CD4+ count evidenced 2/muL cells (1%), and the CD4+/CD8+ ratio was zero. Empirical antibiotic therapy was started with piperacillin/tazobactam. Chest tomography (CT) detected a ground-glass pattern involvement of the lung parenchyma, multiple bilateral micronodules, mediastinal, supraclavicular, and lateral cervical lymphadenopathy. Suspecting Pneumocystis jirovecii pneumonia, the patient was referred to our Infectious Diseases Clinic.
Physical examination revealed fever (40 C), tachycardia (113 bpm), and tachypnea (40 breaths/min). Blood gas analysis on room air resulted in a pH of 7.49, pO2 of 70 mmHg, and pCO2 of 29 mmHg. Maculopapular cutaneous lesions were present on the face, trunk, and limbs (Figure 1); hepatosplenomegaly, lateral cervical lymphadenopathy, and fine crackles on both basal lung fields were also detected.
Laboratory findings showed pancytopenia (white blood cells 1 x 103/muL, platelets 137 x 103/muL, and haemoglobin 7.7 g/dL), alanine aminotransferase (ALT) 67 IU/L (normal value 0-45 IU/L), aspartate aminotransferase (AST) 446 IU/L (normal value 0-45 IU/L), gamma-glutamyl transferase (GGT) 147 IU/L (normal value 7-49 IU/L), alkaline phosphatase (ALP) 500 IU/L (normal value 80-320 IU/L), lactic dehydrogenase (LDH) 6752 IU/L (normal value 225-450 IU/L), gamma-globulin level 21%, C-reactive protein (C-RP) 24 mg/dL (normal value <= 0.5 mg/dL), ferritin >7500 ng/mL (normal value 11-307 ng/mL), and triglycerides 247 mg/dL (40-165 mg/dL). Routine blood and urine cultures, serology for syphilis, toxoplasma, and Leishmania, latex for Cryptococcus neoformans, and smear test for malaria resulted negative. Plasma Cytomegalovirus-DNA was positive with 83087 copies/mL, as well as Cytomegalovirus p65 antigen with 3 cells. Quantiferon-TB gold in the tube (Cellestis, Ltd., Carnegie, Australia) test was undetermined, while the tuberculosis skin test (TST) nonreactive. A broncoalveolar lavage (BAL) was performed, and microbiologic investigations resulted negative for bacteria and fungi including P. jirovecii.
The patient was started empirically on sulfamethoxazole-trimethoprim (800/160 mg tid, oral), ceftriaxone 2 g I.V. daily, and foscarnet 90 mg/kg I.V. twice daily without improvement. Three days later, ceftriaxone was substituted with tigecycline. After 3 more days, both a bone marrow biopsy and a bone marrow aspirate were performed. The latter (see Figure 2(a)) revealed inclusion bodies inside the cytoplasm monocytes, suggestive of H. capsulatum yeasts. An identical finding was observed from the peripheral blood smear (see Figure 2(b)). In the following days, from both the peripheral vein blood and bone marrow aspirate, cultures on Sabouraud dextrose agar incubated at 30 C and grew H. capsulatum (Figure 3).
Liposomal amphotericin B 3 mg/kg/day was administered, while tigecycline was discontinued and sulfamethoxazole-trimethoprim dosage was reduced to 800/160 mg daily. Over the next 3 days, the skin lesions disappeared. A week after this, the fever persisted at 38 C, platelet count was 19 x 103/muL, haemoglobin was 6.6 g/dL, and the CMV-p65 antigen resulted negative without evidence of CMV organ localization. In light of this, foscarnet was discontinued and voriconazole 200 mg bid orally was added to amphotericin. Two days later, the platelet count dropped to 8 x 103/muL, and at this point, amphotericin B was discontinued. The day after, the fever was resolved, while increases were observed for the platelet count (82 x 103/muL) and the haemoglobin value (10 g/dL) in the following 5 days. Voriconazole was administered for another 3 weeks and then substituted with itraconazole 200 mg tid for 3 days, followed by 200 mg bid as maintenance for 1 year. Antiretroviral therapy, including tenofovir disoproxil fumarate/emtricitabine and dolutegravir, was stared on the third week of antifungal treatment.
In 2017, one year after admission, CD4+ cell count was 207 cell/muL (17%) and HIV-RNA was undetectable; itraconazole was discontinued.
In 2019, the patient is on the same ART therapy, the CD4+ lymphocytes are 808 cells/muL (33.2%), and HIV-RNA remains undetectable.