Schnitzler syndrome: heterogeneous immunopathologicalfindings involving IgM-skin interactions

Abstract

The Schnitzler syndrome is the association of chronic urticaria, intermittent fever, osteosclerotic bone lesions and a monoclonal IgM gammopathy. It is not yet firmly established whether the monoclonal immunoglobulin component plays a part in the pathophysiology of the urticarial lesions. Immunoblotting on epidermal and dermal human skin extracts as well as immunoelectron microscopic (IEM) studies on Lowicryl K4M-embedded skin sections were performed in three patients with the Schnitzler syndrome. Western blotting on epidermal extracts showed the presence of IgM-kappa antiskin autoantibodies in two patients. These antibodies displayed the same isotype as the monoclonal components and recognized a 280-290-kDa antigen in one patient and a 200-kDa antigen in the other patient. IEM studies showed sparse IgM deposits in the epidermis, around the keratinocytes, near the desmosomes in one patient and dense deposits below the lamina densa, in the region of the anchoring fibrils, in another patient. Antiskin IgM autoantibodies of the same isotype as their monoclonal gammopathies can be present in the serum of some patients with the Schnitzler syndrome. These IgM antibodies seem to deposit in vivo in the epidermis and at the dermal-epidermal junction, in the region of the anchoring fibrils. These findings suggest that the monoclonal gammopathy plays a part in the pathophysiology of the skin rash. They also suggest patient heterogeneity both in the skin antigens that are recognized as well as in their localization.

Prompt response of refractory Schnitzler syndrome to treatment with anakinra

“…2,3,5 The exact pathogenesis of SS is unclear. 2,[6][7][8] Some hypothesize that the deposition of the IgM paraprotein, leading to the formation of immune complexes and the activation of the complement cascade, is responsible for the cutaneous manifestations. [6][7][8] Another proposed mechanism involves the uncontrolled activation of interleukin 1a (IL-1a).…”

Chronic Urticaria and Monoclonal IgM Gammopathy (Schnitzler Syndrome)

“…1 Similarly, antiskin autoantibody activity of the IgM could be documented by Western blotting in only few patients. 11 Conflicting data were also reported on potential anti-IL-1␣ autoantibody activity of the monoclonal immunoglobulin. 12,13 An alternative hypothesis would not implicate the monoclonal IgM by itself but rather the production of 1 or several cytokines or chemokines by clonal B-cell proliferation or by its cellular environment.…”

Schnitzler’s Syndrome: Monoclonal Gammopathy Associated with Chronic Urticaria

“…These data support a role of T lymphocytes in the pathogenesis of SS cutaneous lesions, whose mechanisms are still unclear. In particular, an uncontrolled activation of interleukin-1α (IL-1α) and paraprotein/skin interactions leading to the activation of the complement cascade have been proposed [3, 14, 15]. …”