<scp>IgA</scp> λ‐Type Schnitzler Syndrome With Edema and Numbness

An Asian woman in her 40s presented to our department with a 2-year history of recurrent edematous erythema, typically resolving with post-inflammatory pigmentation within 10 days (Figure 1a). Each episode was accompanied by transient eyelid and facial edema (Figure 1b), distal numbness, myalgia, and general fatigue, without fever. Topical corticosteroids and systemic antihistamines failed to improve the erythema, and acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs) did not relieve pain or fatigue. Neurological examinations were unremarkable, and neither systemic computed tomography (CT) nor pelvic magnetic resonance imaging (MRI) revealed muscle or joint inflammation, sclerotic bone lesions, or solid tumors. A biopsy specimen from an upper arm erythematous lesion revealed neutrophilic infiltration in the upper dermis with vacuolar change and no vascular fibrinoid change or erythrocyte extravasation (Figure 1c), while direct immunofluorescence revealed no immune complex deposition along vessels or the basement membrane. Blood tests showed C-reactive protein (CRP) 4.95 mg/dL, ferritin 143 ng/mL, serum IgA 668 mg/dL, and serum VEGF 601.6 pg/mL (reference ranges: < 0.14, 6.2–138.0, 93–393, and < 1000, respectively). Serum protein electrophoresis revealed an M-peak, and immunoelectrophoresis identified an IgA λ-type M-protein (Figure 1d). Alkaline phosphatase (ALP) was normal (68 U/L), and ALP3 isoform was not elevated (15.5%). Based on the chronic urticarial lesions, gammopathy, neutrophilic dermal infiltration, and elevated CRP, the patient met Strasbourg criteria for Schnitzler syndrome (SchS), despite the atypical IgA subtype gammopathy and absence of fever [1]. Hematologic and rheumatologic diseases were excluded due to normal blood counts and serum β2-microglobulin, the absence of bone lesions, and unremarkable antinuclear antibody and complement levels. Treatment with colchicine 1.5 mg/day, dapsone 25 mg/day, and loxoprofen 120 mg/day improved symptoms and reduced CRP to < 0.5 mg/dL. However, relapses with CRP approximately 3.0 mg/dL were occasionally triggered by intercurrent infections, such as the common cold. SchS is an acquired autoinflammatory disease characterized by chronic urticarial skin lesions with monoclonal gammopathy [1]. While most cases involve IgM and, less often, IgG, IgA-type SchS is rare, with five cases, including ours, reported [2]. Notably, in the present case, the patient exhibited numbness and edema, which are not typically reported in SchS, regardless of gammopathy type [2, 3]. These symptoms may reflect the underlying gammopathy, such as neuronal and vascular damage from direct antibody deposition, disruption of myelin sheaths and vessels by potential autoantibodies, or VEGF-driven edematous inflammation, as observed in POEMS syndrome. POEMS syndrome is another monoclonal gammopathy-associated disorder, more frequently associated with λ-type M-protein than SchS [3, 4]. In the present case, although the diagnostic criteria for POEMS syndrome were not met (no obvious neuropathy; serum VEGF < 1000 pg/mL; no typical skin changes, organomegaly, or sclerotic bone lesions), an elevation of serum VEGF above some healthy-control ranges (e.g., 78.4 ± 75 pg/mL) may contribute to numbness and edema [5]. While SchS often requires systemic corticosteroid or IL-1 targeted treatments, this case responded to less aggressive treatment. Exacerbations coincided with minor respiratory infections, and similar worsening, particularly following COVID-19, has been reported in another IgA-type SchS case [2], potentially reflecting mucosal immune activation with expansion of IgA-producing plasma cells. Prof. Daisuke Tsuruta is an editorial board member of the Journal of Dermatology and a coauthor of this article. To minimize bias, he was excluded from all editorial decision-making related to the acceptance of this article for publication. The other authors have no Conflicts of Interest to declare. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.