DP23 Paraprotein negative Schnitzler syndrome: a new clinical entity?

Abstract

Abstract Schnitzler syndrome (SchS) is a rare autoinflammatory condition with prominent cutaneous features. The genetic basis of the condition is not understood. The Strasbourg Criteria outline the clinical diagnosis of SchS, requiring an IgM or IgG monoclonal gammopathy and an urticarial rash (Simon A, Asli B, Braun-Falco M et al. Schnitzler’s syndrome: diagnosis, treatment, and follow-up. Allergy 2013; 68:562–8). We report two cases of SchS, the first with a 5-year delay in the development of a paraprotein and the second with complete absence of a paraprotein, despite 12 years of symptoms. Case one was a 47-year-old female who attended with a 4-year history of a dusky-red urticarial rash and polyarthralgia. Inflammatory markers were persistently raised, in the absence of any identified cause. Investigations demonstrated thrombocytosis, hypocomplementaemia and an isolated elevated IgM (3.07 g L–1), with no monoclonal band. Serum free light chain κ : λ ratio was normal. The patient had a working diagnosis of hypocomplementaemic urticarial vasculitis, despite skin biopsy demonstrating a lack of fibrinoid necrosis. She failed to improve symptomatically on high-dose antihistamines, corticosteroids or azathioprine and had minimal improvement with omalizumab. Repeat serum electrophoresis identified the development of a new IgM κ paraprotein 5 years after the initial symptom onset. Interleukin (IL)-1 blockade resulted in rapid clinical and biochemical improvement. Case 2 was a 55-year-old woman with a 4-year history of recurrent urticaria. A diagnosis of urticarial vasculitis was made; skin biopsy was incongruent but displayed a neutrophilic infiltrate. She had a poor response to high-dose antihistamines and withdrew from services for 3 years. Subsequent therapy with ciclosporin, azathioprine, omalizumab, dapsone and colchicine yielded no clinical benefit. Laboratory investigations repeatedly showed elevated inflammatory markers and an elevated IgA (3.9 g L–1) in the context of inflammatory bowel disease but no IgM or IgM paraprotein. Serum free light chain κ : λ ratio was normal. Clinical suspicion of an autoinflammatory condition was high given the longstanding treatment-resistant urticaria and systemic inflammation. A trial of IL-1 blockade led to immediate clinical and biochemical resolution. This treatment was continued and has resulted in the eradication of a cumulative 12 years of symptoms. There are several reports of SchS with no monoclonal band responding to IL-1 antagonism. As these cases do not fulfil the obligatory criteria for SchS, we propose a new clinical entity, paraprotein-negative IL-1-mediated inflammatory dermatosis (PANID). It is not yet clear if PANID is a precursor to SchS, although published cases demonstrating delayed paraprotein development could support this. Clinicians should consider this diagnosis in patients with treatment-refractory urticaria and systemic inflammation.