Rationale
A patient presented in early April with fever and markers for acute inflammation that appeared to be cytokine storm from COVID-19. Molecular and antibody testing for COVID-19 and other infections were negative. Genetic testing was undertaken to identify a cause for his symptoms.
Case
The patient is a 49-year-old male who initially presented In April with a high fever, apparent pneumonia and elevated inflammatory markers suggestive of cytokine storm from COVID-19. His history was notable for a prolonged hospitalization complicated by hyponatremia, hypokalemia, pulmonary embolism and peripheral neuropathy. Extensive evaluation by Endocrinology, Rheumatology, Neurology and Infectious Disease failed to identify a cause for his symptoms. During our evaluation we obtained a history of cold sensitivity and frequent febrile illness during his childhood in Bulgaria. He also reported fever symptoms during winters in Michigan and after minor trauma, and these were associated with arthralgias.
Results
Screening of 201 immune associated genes revealed a variant in PLCG2; c.1596 G>T, which causes as sequence change replacing tryptophan with cysteine at amino acid 532 of the PLCG2 protein. While this variant has not been previously described, it is in an exon area associated with FCAS.
Conclusion
Patients with FCAS can have a clinical presentation compatible with COVID-19 cytokine storm. Broad ranging genetic screening is important to perform on patients with non-COVID-19, cytokine storm-like presentations to identify novel gene variants potentially causing these symptoms. The findings in this patient suggest that this variant may be pathogenic and associated with a FCAS phenotype.
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