A 40 year-old Guatemalan man with HIV/AIDS (CD4 count 26) not on antiretroviral therapy for the last eight months presented with ten days history of weight loss, vomiting, cough and night sweats. On examination he looked cachectic and frail. The temperature was 103F (39.4  C), the blood pressure 106/93 mm Hg, the pulse 121/minute, the respiratory rate 27/minute, and the oxygen saturation 100% while he was breathing ambient air. He had generalized weakness and anasarca. A diffuse macular rash was present as well as tender splenomegaly and inguinal lymphadenopathy.
A CT scan of the chest, abdomen and pelvis revealed lower lobe pulmonary nodules, splenomegaly (22cm), enlarged axillary, inguinal and mesenteric lymph nodes. He was transferred to the ICU for suspected severe sepsis and disseminated intravascular coagulation (INR was 3, D-dimer 15 mcg/mL and fibrinogen 100 mg/dL). On complete blood count analysis he had a WBC 2.0 (normal 4.0-10.0 x 10/L), hemoglobin 7 (normal 14-18 g/dL), and platelets 30 (normal 150-450 x 10/L). His ferritin level was 4200 (normal 23.9-336.2ng/mL) and lactate dehydrogenase 1390 (normal 140-271 U/L). The level of interleukin 2 (IL-2) receptor alpha was elevated at 1314 (normal range 223-710 U/mL). Serum triglycerides level was normal. Routine blood culture showed no bacterial or fungal growth. Interferon-gamma release assay for tuberculosis was negative. Hepatitis A, B and C serologic tests were negative. Autoimmune workup included ANA, ANCA and rheumatoid factor were all negative. Cryptococcal Ag, Francisella tularensis IgG, Rickettsia rickettsii IgG and IgM, Trypanosoma cruzi IgM and Toxoplasma gondii IgM were all negative. Serology was positive to CMV IgG and PCR, but no baseline test was available to compare. Positive EBV IgG and EBV nuclear Ag IgG was consistent with past infection or a reactivated EBV infection. Acid-fast bacilli stain was negative and cultures remained negative for other common and opportunistic infections (PCP, CMV, HSV were all negative). Buffy coat fungal culture and stain was consistent with histoplasma. Bronchoscopy with BAL was positive for intracellular organisms with morphology consistent with histoplasmosis on Grocott-Gomori's methenamine silver stain.
Liposomal amphotericin B was added to the empiric antibacterials immediately after the buffy coat test was reported positive. Atovaquone was started later and he continued on Azithromycin for chemoprophylaxis. Acyclovir was added for suspected CMV infection. HAART therapy (Darunavir, Dolutegravir, Emtricitab-Tenofovir) was started for his uncontrolled HIV infection one month after initiation of antifungals.
A bone marrow biopsy was performed for evaluation of pancytopenia. The biopsy showed pancytopenia, increased iron stores, extensive intracytoplasmic fungi consistent with histoplasmosis and hemophagocytosis (Fig. 3). Cultures from the bone marrow aspirate confirmed disseminated Histoplasma capsulatum.
Dexamethasone was started sixteen days after initiation of HAART therapy when the patient developed acute changes in his mental status. Although he initially improved, few days later his condition deteriorated. He developed septic shock with multiorgan failure secondary to MRSA pneumonia and disseminated Candida lusitaniae infection. Two and a half months after the diagnosis of histoplasmosis-induced hemophagocytic syndrome, supportive care was withdrawn and he succumbed to his illness due to HLH overlap with severe sepsis syndrome with multi-organ failure.