Mete Enes UYSAL, Ece GÖKYAYLA, Çınar YILDIZ, İdil ÜNAL, Banu YAMAN
Turkish Journal of Dermatology - 2026;20(3):138-140
Cryopyrin-associated periodic syndromes (CAPSs) are rare autoinflammatory disorders caused by gain-of-function mutations in the NLRP3 gene, resulting in dysregulated interleukin-1-mediated inflammation. Although traditionally classified into three clinical subtypes according to disease severity and systemic involvement, increasing evidence supports the concept of CAPS as a continuous phenotypic spectrum. Low-penetrance NLRP3 variants may present with milder and atypical phenotypes, creating diagnostic challenges. A 19-year-old male patient presented with a three-month history of recurrent urticaria-like lesions triggered by cold exposure, accompanied by intense pruritus and burning sensation. The lesions appeared on the trunk and extremities, resolved within 24 hours without residual pigmentation, and were not associated with angioedema. The patient denied systemic symptoms such as fever, arthralgia, myalgia, fatigue, or weight loss. Family history was unremarkable. Initially diagnosed with chronic urticaria, he showed no significant response to high-dose second-generation antihistamines. Laboratory investigations during disease flares demonstrated neutrophilia and elevated C-reactive protein and serum amyloid A levels. Skin biopsy revealed superficial and deep perivascular neutrophilic infiltration without evidence of vasculitis. Genetic analysis identified a disease-associated NLRP3 variant, c.592G > A (p.Val198Met), supporting the diagnosis of CAPS. Following initiation of anakinra (100 mg/day), complete remission of cutaneous symptoms was achieved within two months. This case highlights an atypical CAPS presentation characterized by late onset and skin-limited inflammation without systemic manifestations. The findings support a spectrum-based understanding of CAPS and emphasize that isolated cutaneous phenotypes associated with low-penetrance NLRP3 variants should be considered in patients with antihistamine-resistant urticaria-like eruptions accompanied by neutrophilic inflammation and elevated acute-phase reactants.
