NK cell dysfunction and hypogammaglobulinemia in a patient presenting with invasive rhinocerebral mucormycosis

Abstract

Rationale Invasive mucormycosis is an invariably fatal disease usually seen in diabetics and immunosuppressed patients. We report a seemingly immunocompetent patient presenting with rhinocerebral mucormycosis who was found to have NK cell dysfunction and hypogammaglobulinemia. Methods A case report. Results A 47-year-old non-diabetic male with a history of chronic sinusitis and multiple sinus surgeries presented with headache, double vision, and periorbital swelling. Invasive rhinocerebral mucormycosis was diagnosed; he had a glucose of 288 upon admission. He continued to deteriorate with aggressive cerebral invasion despite IV amphotericin, hyperbaric oxygen therapy, and left orbital exenteration. Immunological evaluation revealed normal neutrophil respiratory burst, IgG 341 (694-1618), IgM 37 (60-263), normal IgA, and a barely detectable NK cell killing activity. IVIG, at 600mg/kg, failed to induce any clinical improvement. Interferon-α (IFN-α) was started with minimal improvement of his NK cell activity but with continued cerebral invasion. Due to severe adverse effects, IFN-α was stopped; GM-CSF was started. The patient's course stabilized after the initiation of GM-CSF; the cerebral infection was “walled off” and no new invasion was noted. The patient was discharged on anti-fungal therapy and GM-CSF. He continues to be stable five months later. His NK activity stabilized at the low end of the normal range. Conclusions Hypogammaglobulinemia is usually not associated with invasive mucormycosis suggesting that NK cell dysfunction was probably responsible for the patient's course. NK cell deficiency has been reported to be associated with recurrent mucosal candidiasis, suggesting an important role for these cells in the control of some fungi.