Chronic urticarial eruption associated with monoclonal gammopathy
Authors: Naiara S. Barbosa, Jennifer J. Schoch, Michael D. Ringler, David A. Wetter
Journal: American Journal of Hematology (2014)

Schnitzler syndrome is a rare acquired autoinflammatory disease characterized by monoclonal immunoglobulin M gammopathy and urticaria. Clinical features include fever, urticarial rash, myalgia, arthralgia, hepatosplenomegaly, and enlarged lymph nodes. Schnitzler syndrome is often underdiagnosed and not usually suspected until more common autoimmune, neoplastic, and infectious etiologies are excluded. Anakinra, an interleukin-1 receptor antagonist, is the first-line treatment and has been shown to provide fast and sustained symptom relief 1-3. A 50-year-old man with presumed Castleman disease/POEMS syndrome (a multisystem syndrome combining polyneuropathy, organomegaly, endocrinopathy, M component, and skin changes) presented for evaluation of persistent hip pain and a “burning” rash of 3 years' duration. He had previously been treated with systemic corticosteroids, lenalidomide, rituximab, and bortezomib, and with an autologous stem cell transplant, resulting in initial improvement but eventual recurrence of symptoms. His physical examination revealed small, slightly edematous, pink plaques involving the back (Image 1A), trunk, and arms (Image 1B). Laboratory tests revealed elevated inflammatory markers, with an erythrocyte sedimentation rate of 75 mm/hr (reference range, 0–22 mm/hr) and C-reactive protein of 65 mg/L (reference range, 0–8 mg/L), and small monoclonal immunoglobulin M κ protein. Magnetic resonance imaging demonstrated patchy intramedullary osteosclerosis of the left iliac wing, with bone marrow edema in the left acetabulum and both knees. Whole-body fludeoxyglucose (FDG) positron emission tomography/computed tomography revealed mild increased 18F-FDG uptake and osteosclerosis in an identical anatomic distribution, as well as hepatosplenomegaly and prominent axillary and inguinal lymph nodes. The osteosclerosis was most clearly demonstrated upon review of the images from the whole-body FDG positron emission tomography/computed tomography (Image 1C). Bone marrow and lymph node biopsies were negative for hematologic abnormalities. Skin biopsy revealed primarily neutrophilic urticaria with scattered eosinophils (Image 1D). The cutaneous findings, monoclonal gammopathy, and characteristic radiological osteosclerosis led to a diagnosis of Schnitzler syndrome. Treatment was initiated with anakinra. Schnitzler Syndrome. A: Small, slightly edematous pink plaques on the back. B: Close-up of plaques on the arm. C: Axial computed tomography image of the pelvis from the whole-body FDG positron emission tomography/computed tomography. Patchy intramedullary osteosclerosis involving the left iliac wing (arrows). D: Skin histologic results showing predominant neutrophilic perivascular inflammation with scattered eosinophils (Hematoxylin–Eosin; original magnification, 20×). Since Schnitzler syndrome was first described in 1972, fewer than 250 cases have been reported 3. In addition to its severe impact on quality of life, it places patients at increased risk for lymphoproliferative malignancies that define prognosis. Lymphoma or Waldenström macroglobulinemia develops in ∼15–20% of these patients 1-3. The clinical hallmark of Schnitzler syndrome is a chronic, recurrent urticarial rash that is initially asymptomatic but can become pruritic over several years. Individual skin lesions are transient, appearing daily and completely resolving in 12 to 36 hr 1. Histologic findings reveal predominantly neutrophilic perivascular and interstitial inflammation 2. If Schnitzler syndrome is suspected, a bone scan can be a helpful screening tool. Typical findings of osteosclerosis, especially involving the knees and pelvis, can aid diagnosis 4. Given the multiple and broad features of Schnitzler syndrome, the diagnosis can be often made by a variety of specialties, including hematology, rheumatology, radiology, and dermatology. Any patient with a nonpruritic urticarial eruption, primarily with neutrophilic infiltrate and associated monoclonal gammopathy, especially immunoglobulin M κ, should be further evaluated for Schnitzler syndrome. Our case illustrates the importance of awareness and early recognition of this disease. Expedited treatment with anakinra can relieve symptoms and significantly improve quality of life 1-3. The authors thank Tania M. Gonzalez Santiago, MD, for assistance in obtaining the skin histology image.