Our patient was a 61-year-old Hispanic man who had not seen a health care provider in many years and presented with one month history of vague abdominal pain, 20 pound weight loss in 1 month, and generalized weakness with malaise as well as occasional cough that worsened and became productive of clear sputum over the last week before presentation. He also reported occasional episodes of nausea and nonbloody diarrhea. He denied any fevers, chills, or rash but reported some arthralgias. The patient was born in Chihuahua, Mexico, but had lived in Texas, USA, since age seven. He was divorced, estranged from his children, and lived alone. There was no significant tobacco or alcohol use but he confirmed exposure to high intensity dust when he used to work in a ceramic and tile factory without wearing a mask for the last five years.
He was evaluated by a private community physician a few days before presentation to our hospital who prescribed for him a combination of oral ciprofloxacin and metronidazole without specific diagnostic testing. The patient did not have any improvement so he presented to the emergency room.
In the emergency department, his temperature was 98.3 F, blood pressure 84/61 mmHg, pulse rate 128/minute, and respiratory rate 27/minute with pulse oximetry 92% on ambient air. He was acutely ill-looking but alert. While lung examination was limited on admission due to COVID-19 restrictions and the use of disposable stethoscopes, there were decreased air sounds but no rales. His abdominal examination was benign but positive findings were significant for large lymph nodes in the cervical, supraclavicular, inguinal, and axillary areas, some measuring more than 3 cm in diameter. Laboratory findings on admission showed white blood cell count was 8,900/mm3 with 80% neutrophils, 0.5% band forms, and 11% eosinophils, hemoglobin was 8.9 gm/dL, hematocrit was 27.6%, and platelet count was 447,000/mm3. Electrolytes showed bicarbonate of 17, blood urea 54, creatinine 1.5, albumin 2.2, lipase 14, lactic acid 2.5, ALT 57, and AST 139. Procalcitonin was 6.1.
His chest film on admission showed a diffuse micronodular pattern which triggered testing for COVID-19 which turned out to be negative. CT scan of the chest without contrast revealed extensive diffuse bilateral micronodules in a miliary pattern, mediastinal and axillary lymphadenopathy with pericardial thickening, while the CT scan of abdomen and pelvis revealed enlarged lymph nodes in the para-aortic, gastrohepatic, inguinal, external, and internal iliac chains (Figures 1(h) and 1(i)). While the patient was seen by many physicians to rule out lymphoma and tuberculosis, as well as to manage his respiratory failure, acute renal failure, and septic shock, the infectious disease physician suspected coccidioidomycosis and began a work up for the patient with serologic testing.
Since he was in shock, blood and urine cultures were sent and he was treated with IV isotonic fluid resuscitation with empiric intravenous vancomycin and cefepime along with intravenous methylprednisolone 60 mg every 8 hours and admitted to the intensive unit. Further testing showed that he was positive for HIV-1 with viral load 309,000 and CD4 count 38. We did not begin antifungal medications at the outset because we did not have a diagnosis of HIV at the time. Upon a diagnosis of HIV in the hospital, we expanded our differentials to miliary tuberculosis, histoplasmosis, and coccidioidomycosis. Histoplasmosis antigen, acid fast bacilli (AFB), and Cryptococcus antibody tests did not yield a positive result; however, sputum culture was positive for Candida albicans. Despite aggressive treatment with vasopressors, mechanical ventilation, and continuous renal replacement therapy, the patient died on hospital day 3. The family agreed to an autopsy which showed diffuse coccidioidomycosis with negative AFB stain and no evidence of malignancy. The cause of death was acute respiratory distress syndrome (ARDS) secondary to disseminated coccidioidomycosis secondary to HIV/AIDS infection.
At autopsy, there were bilateral pleural lung effusions (left: 300ml, right: 400ml), congestion of the lungs with areas of consolidation, and extensive intra-alveolar edema. There were innumerable diffuse tan nodules showing miliary spread in the upper and lower lung lobes with predominance in the upper lobes in the lungs bilaterally (see Figures 1(e) and 1(f). These nodules microscopically consisted of granulomatous inflammation. The lung alveolar spaces were filled with proteinaceous material and Coccidioides fungal microorganisms. Coccidioides fungal microorganisms have spherules that may be empty or filled with endospores. Coccidioides fungal microorganisms are accentuated with Grocott-Gomori's methenamine silver stain (GMS) (see Figures 1(c) and 1(d)).The decedent grossly had extensive cervical, supraclavicular, inguinal, and axillary lymphadenopathy. The lymph nodes grossly showed a cut tan surface (see Figure 1(g)). Microscopically, normal lymph node architecture was replaced with caseating granulomas with Coccidioides fungal microorganisms that are accentuated with Grocott-Gomori's methenamine silver stain (GMS) (See Figures 1(a) and 1(b)). It should be noted that acid fast bacilli (AFB) stain was performed and was negative for acid fast microorganisms on both lung and lymph node sections.
Autopsy Findings and Figures are presented in Figure 1.