A 35-year-old Samoan American male from California with congenital deafness, hypertension, and asthma presented to a university hospital in San Antonio, Texas, with worsening night sweats, rash, productive cough, shortness of breath, fevers, intermittent back pain, and enlarging neck nodule. The patient had been diagnosed with Valley Fever 2 months prior while living in California. His initial symptoms included night sweats, facial rash, fever, worsening hearing loss, cough, skin lesions, cervical lymphadenopathy, and shortness of breath. At that time, he was given a 1-month course of fluconazole 400 mg orally daily, and no further treatment was recommended. While on fluconazole, he had noted some improvement in his symptoms. Physical examination at the time of hospital admission revealed scaling plaques to the right forehead, small ulcerated lesions to the right lower mouth and posterior neck, coarse breath sounds in the left upper lung fields, and a 3.5 cm x 3.5 cm nontender lymph node to the left anterior neck. He had no neurological deficits on examination. He was afebrile and tachycardic (120 bpm) with SpO2 of 91% on room air.
Initial laboratory results were significant for leukocytosis with predominant neutrophilia, elevated erythrocyte sedimentation rate and C-reactive protein, elevated liver enzymes, total protein of 10.0 g/dL, albumin of 1.7 g/dL, corrected calcium of 11.0 mg/dL, elevated alkaline phosphatase of 167 U/L, elevated lactic acid of 2.7 mmol/L, elevated lactate dehydrogenase of 341 U/L, and ferritin of 3366 ng/mL. The patient also had anemia of chronic disease. A respiratory viral panel was positive for respiratory syncytial virus.
Our differential diagnosis included disseminated fungal diseases such as coccidioidomycosis, histoplasmosis, or blastomycosis, as well as tuberculosis, secondary hemophagocytic lymphohistiocytosis, HIV, and malignancy. Infectious Diseases was consulted given high likelihood of disseminated coccidioidomycosis.
Serum coccidioides IgG ELISA (enzyme linked immunosorbent assay) was 8.3 IV (reference range <=0.9 IV) and IgM ELISA was 3.0 IV (reference range <=0.9 IV). Direct microscopy of the sputum revealed spherules resembling coccidioides. Magnetic resonance imaging (MRI) was obtained to further workup the elevated alkaline phosphatase and hypercalcemia. MRI of the spine (Figures 1-3) revealed a diffusely abnormal signaling with numerous discrete variable sized hyperintense lesions throughout the spine, sacrum, and iliac bones. Indeterminate hyperintense lesions in the bilateral psoas muscles were also present. To confirm that these lesions represented infection and not a potential malignancy, a computed tomography-guided biopsy was performed of the right iliac crest and cervical lymph node. Both biopsies revealed spherules and cultures grew coccidioidomycosis, confirming the presence of a disseminated infection. Lumbar puncture revealed no evidence of cerebrospinal fluid involvement. Laboratory testing for blastomycosis, histoplasmosis, Epstein-Barr virus, cytomegalovirus, HIV, syphilis, tuberculosis, hemophagocytic lymphohistiocytosis, multiple myeloma, and other malignancies were all negative.
Initially, the patient was admitted to the general medicine floor. He required high-flow nasal cannula and multiple boluses of intravenous fluids to maintain mean arterial pressure of 65 mm Hg. Despite treatment with itraconazole, liposomal amphotericin B, and supplemental oxygen, his respiratory rate continued to increase, and he developed worsening hypoxemia. He was transferred to the intensive care unit, intubated, and given vasopressors. A chest X-ray at that time demonstrated diffuse bilateral reticulonodular opacities consistent with acute respiratory distress syndrome (Figure 4).
The patient required increased FiO2 and PEEP (positive end-expiratory pressure) while intubated; therefore, a computed tomography scan of the chest was done. The imaging found a miliary pattern of pulmonary nodules with focal consolidations posteriorly, along with prominent and confluent superior mediastinal lymphadenopathy obliterating the left upper bronchus resulting in postobstructive consolidation of the left upper lobe. In addition to antifungals, ceftriaxone and azithromycin were started for possible concomitant community-acquired pneumonia. Despite broad spectrum antifungals and antibiotics, his respiratory status continued to worsen. Liposomal amphotericin B treatment resulted in acute kidney injury with creatinine peaking at 4.2 mg/dL (patient's baseline 0.7 mg/dL). His course was further complicated by paralytic ileus, right internal jugular deep vein thrombosis, and a gluteal hematoma. After weeks of treatment with liposomal amphotericin B, voriconazole, and mechanical ventilation, the patient made a full pulmonary and renal recovery. On the day of discharge, his creatinine was within normal limits, and he did not need supplemental oxygen. He was discharged on an extended course of oral voriconazole with plans to reevaluate treatment after outpatient infectious disease specialist follow-up. He was discharged to an intensive inpatient rehabilitation program for severe physical deconditioning after a prolonged hospitalization.