SCHNITZLER SYNDROME – IS ANTI-IL-1 THERAPY ALWAYS THE RIGHT CHOICE?

Abstract

Introduction Schnitzler syndrome is a periodic fever syndrome presenting with urticarial skin rash, a monoclonal IgM component and at least two of the following: fever, joint or bone pain, lymphadenopathy, hepatosplenomegaly and elevated acute phase reactants. IL-1 is typically elevated, making anakinra a successful therapy. However, sarilumab (IL-6 antagonist) may be efficacious in certain patients. Case Description A 69-year-old female experienced monthly episodes of facial swelling and a non-pruritic, erythematous rash with high fevers, nausea, headache and neck pain over 1 year. During episodes, white cell count, neutrophils, monocytes, eosinophils, ESR and CRP were elevated but would resolve after episodes. Facial cellulitis, odontogenic and neurologic infections were excluded. Previous medical history was significant for breast cancer and uterine cancer in remission and Hashimoto's thyroiditis. Tryptase levels were normal, arguing against mast cell activation syndrome. Complement C2 (less than 1.3 mg/dL) and C4 (10mg/dL) levels were slightly low. The patient had normal immunoglobulin levels, IL-2, TNF-α, IL-1β levels and negative anti-SSA and anti-SSB, anti-Smith, anti- dsDNA, anti-mitochondrial and anti-actin antibodies but isolated elevated IL-6 levels and a monoclonal IgM component. Isolated elevated IL-6 made tocilizumab appropriate treatment with symptom resolution in days. However, after 4 months of therapy anaphylactic symptoms required changing to sarilumab with good effect. Discussion Although a decade older than expected and despite the presence of an atypical rash, symptoms were consistent with Schnitzler syndrome. Patients with elevated IL-6 levels who do not tolerate tocilizumab may respond well to other IL-6 antagonists such as sarilumab.