<p>Schnitzler Syndrome in a 27-Year-Old Man: Diagnostic and Therapeutic Dilemma in Adult Auto-Inflammatory Syndromes A Case Report and Literature Review</p>

Abstract

A 32-year-old-man, with a history of chronic urticaria from the age of 27, diagnosed with an adult-onset Still's disease and received a low dose of glucocorticoids, methotrexate and tocilizumab. Despite the long-term combined treatments, he suffered from chronic urticaria, lowgrade fever and bone pain. He was found to have high inflammatory markers, hypogammaglobulinemia, monoclonal IgM-kappa light chain in serum and increased radiotracer uptake in the whole bone scintigraphy. No pathological variants for monogenic autoinflammatory diseases were present in the genome exome sequencing. These investigations confirmed the diagnosis of Schnitzler syndrome, which is an exception before the age of 35. Switching from tocilizumab to interleukin 1 receptor inhibitor, anakinra led to a full clinical response and normalisation of inflammatory markers. Patients with a history of fever and chronic urticaria are routinely tested for monoclonal gammopathy in the context of malignancy, but it should also be considered as a sign of the autoinflammatory syndrome. The Schnitzler syndrome and the adult-onset Still's disease share common features, so the diagnosis requires a thorough investigation to establish an optimal treatment. In the diagnostic algorithm, monoclonal gammopathy is usually considered red flag for malignancy but might be overlooked as a criterion of Schnitzler syndrome, particularly in young adults. We confirm that the interleukin 1 inhibitor should be the first line of therapy in Schnitzler syndrome, and in the presented case we found it more effective than the interleukin 6 blockade. The main goal of this paper is to increase awareness of Schnitzler syndrome among health care professionals. We aim to present features which can be helpful in differential diagnosis.

Schnitzler Syndrome Presenting as a Fever of Unknown Origin with Elevated Alkaline Phosphatase Levels

“…50 years old (7,11). The absence of characteristic symptoms of CAPS, including cold-triggered episodes, sensorineural hearing loss, and chronic aseptic meningitis, is also important for differentiating the two conditions (11,12). Furthermore, monoclonal proteins have not been reported in CAPS (7).…”

“…The differential diagnosis of SchS is broad, but AOSD is perhaps the most important because it is relatively common and shares many clinical features with SchS ( 12 ). Some SchS cases meet the Yamaguchi criteria and are initially treated as AOSD, as in the present case, but SchS generally responds poorly to steroid therapy.…”

Case Report on the Rare Diagnosis of Schnitzler’s Syndrome

“…2 It is an extremely rare disorder, with the published literature mostly consisting of case series, with about 300 cases said to be reported worldwide. 3,4 This syndrome is characterized by a few cardinal clinical and laboratory features. The median onset of the syndrome is Immunoglobulin levels were IgG 20 g/L (normal 5-17 g/L), IgM 5.85 g/L (normal 0.44-2.47 g/L), and IgA 1.97 g/L (normal 0.87-3.94 g/L).…”

“…Recurrent fever 1 Objective findings of abnormal bone remodeling with or without bone pain 2 A neutrophilic dermal infiltrate on skin biopsy 3 Leukocytosis and/or elevated CRP. 4…”

Transformation of IgM-MGUS into Waldenström´s macroglobulinemia in two of six patients treated for Schnitzler´s syndrome

“…Léčba pomocí protilátky proti interleukinu-6 zvaná tocilizumab byla popsána taktéž jako účinná u syndromu Schnitzlerové, nicméně v roce 2021 je průběh léčby tocilizumabem popsán v nevelkém počtu popisů případů. V jedné publikaci je sice popsána kompletní léčebná odpověď, další publikace hodnotí léčebný efekt jako variabilní (42)(43)(44)(45)(46). V roce 2021 byla publikována berlínskými autory klinická studie, v níž bylo 9 pacientů léčeno tocilizumabem.…”