LAUSR

A 1-year-old boy presented with an asymptomatic fleeting erythematous rash, which had been recurring since 6 h after his birth, and manifested without fever and with a poor response to high-dose antihistamines. The lesions, which disappeared within hours, appeared when the child was undressed or bathed, suggesting cold as a trigger. He was otherwise well, growing and developing normally, and there was no relevant personal or family history. Physical examination showed multiple small scattered urticarial rash on the child’s trunk and extremities (Fig. 1). Laboratory investigations revealed low haemoglobin (109 g/L; normal range 117–137 g/L) and raised white blood cells (19.6 9 10/L; 5.0–16.0 9 10/L), platelets (512 9 10/L; 150–400 9 10/L), C-reactive protein (32 mg/L; 0–10 mg/L) and erythrocyte sedimentation rate (85 mm/h; 0–9 mm/h). Other than a slightly low IgD level (0.03 g/L; 0.05–0.20 g/L), immunoglobulins were within normal limits. Histological examination of a representative lesion showed a neutrophilic urticarial dermatosis characterized by perivascular and interstitial neutrophilic infiltrate with leucocytoclasia but without vasculitis or dermal oedema (Fig. 2). These findings prompted further laboratory investigations, which demonstrated raised serum amyloid A protein (15.5 mg/L; < 5–10 mg/L). Genetic studies were carried out after ethics approval and informed consent were obtained. The patient was found to have a previously described pathogenic heterozygous mutation in exon 3 of NLRP3, Asp303Asn (D303N), which was absent in his parents and siblings, signalling a diagnosis of cryopyrin-associated periodic syndrome (CAPS). Treatment with anakinra led rapidly to complete resolution of the symptoms and serological abnormalities, and the patient was still well at 2.5 years of age. CAPS, sometimes termed the cryopyrinopathies, is caused by dominantly inherited or de novo gain-offunction mutations in the NLRP3 gene located on