We report a previously healthy 4-year-old female presenting with a diffuse, recurrent, pruritic, erythematous rash involving the entire body with eight episodes over 2 years, each lasting 7–10 days. The rash reliably appears 2–3 days before the fever begins. Other symptoms include cough, rhinorrhea, or sore throat, and during her most recent episode, oral ulcers and conjunctivitis. The rash starts on the face and spreads caudally to involve the entire body. It intensifies during the febrile phase and persists for several days after the fever resolves. Individual lesions last longer than 24 hours, and antihistamines (loratadine, diphenhydramine) have provided minimal benefit.
Family denies noticing signs of joint pain or identifiable triggers for the rash. Her growth is normal with no weight loss, diarrhea, or bloody stools. She has no history of atopy or recurrent or severe infections. Family history is notable for psoriasis, eczema, and hypertension in an older sister, and lupus in a maternal cousin.
Immunologic evaluation showed normal T, B, and natural killer (NK) cell counts and normal IgG, IgA, and IgM levels. Tetanus IgG level was protective. Streptococcus pneumoniae IgG levels were nonprotective, with post-vaccination levels pending. HSV PCR and throat cultures for group A Streptococcus were repeatedly negative.
Genetic testing via a gene panel for autoinflammatory and autoimmune syndromes identified a variant of uncertain significance in NLR-family CARD domain-containing protein 4 (NLRC4) at c.1363C>T (p.Leu455Phe). NLRC4 mutations are associated with autosomal-dominant familial cold autoinflammatory syndrome 4 (FCAS 4) and periodic fever-infantile enterocolitis-autoinflammatory syndrome. This is a missense variant that has not been previously reported; it has a gnomAD (v4.1.0) frequency of 0.000006815, a high Combined Annotation Dependent Depletion [CADD] score of 23.6, and a PolyPhen score of 0.994 (which categorizes it as probably damaging).
