Abstract

BACKGROUND: Familial Mediterranean fever is an auto-inflammatory disease caused by pyrin mutations. Glucocorticoids inhibit the production and secretion of inflammatory cytokines, including IL-6 and IL-1β, from inflammatory cells and suppress the activation of nuclear factor-κB in the nucleus. However, the functions of physiological glucocorticoids in the disease remain unknown.

CASE REPORT: We report the case of a Japanese man with familial Mediterranean fever complicated by isolated adrenocorticotropic hormone deficiency. Patient non-compliance with hydrocortisone replacement therapy led to a series of pericarditis and fever episodes. Subsequently, the regular administration of colchicine alone could not prevent auto-inflammation. The clinical course of treatment suggested that the absence of physiological levels of glucocorticoids is crucial for familial Mediterranean fever attacks. Because familial Mediterranean fever is a pyrin abnormality-induced auto-inflammatory disease that subsequently activates cytokines via the nucleotide-binding domain, leucine-rich repeat/pyrin domain-containing 3 inflammasomes and the absence of glucocorticoids can exacerbate the severity of the auto-inflammatory disease.

CONCLUSIONS: Physiological glucocorticoid levels appear to be essential for the regulation of inflammasome activation via IL-6-negative regulation. However, pharmacological levels of glucocorticoids are not currently used for the prevention of familial Mediterranean fever attacks. Physicians should be aware of adrenal insufficiency as a possible disorder when they encounter cases of refractory familial Mediterranean fever.

Keywords: adrenal insufficiency, Colchicine, Familial Mediterranean Fever, Glucocorticoids, Cytokines, Hydrocortisone, Inflammasomes