STAT1 is a transcription factor that modulates cellular responses to interferon. This case represents the first relationship between autosomal dominant STAT1 deficiency and fungal infection. To date, AD STAT1 deficiency has not been reported with susceptibility to fungal agents.
We aimed to describe the very first case of Coccidioidomycosis as the clinical manifestation of STAT1 AD deficiency.
A female from northeast Mexico with no relevant family medical history, but with a personal history of adverse reactions on the skin to the BCG vaccination, pneumonia, chickenpox, herpes zoster reactivation, and SARS-CoV-2 infection was admitted to the emergency department with two soft-tissue tumors in the frontotemporal region accompanied by B-symptoms. Her tomography showed lytic lesions in the temporal area below the tumors and in the spine, a pulmonary nodule, and generalized lymphadenopathy. Because Coccidioidomycosis is endemic in her birthplace, this infection was ruled out. Elevated titers of serum immunoglobulins against Coccidioides imitis, and spherical images in microscopy suggestive of Coccidioides spp. were found, and additionally the cultures from the frontotemporal tumor were positive for Coccidioides spp. The patient received antifungals which resulted in radical clinical improvement. Due to the severity and recurrence of the infections, complete exome sequencing was performed in which a pathogenic variant was found in STAT1 [c.1228 A>G/WT (p.Lys410Glu)]; a pathogenic variant classified as a loss of function.
This patient showed shared clinical manifestations with AD STAT1 gain of function despite her actual diagnosis of AD STAT1 deficiency. This suggests a possible overlap between clinical manifestations of AD STAT1 GOF and AD STAT1 LOF, more research should be done into the immune response to fungi in patients with STAT1 alterations. Finally, patients with AD STAT1 deficiency living in areas of Coccidioidomycosis endemics should be screened to rule out this serious, invasive infection.