Schnitzler syndrome patient successfully treated with tofacitinib and colchicine

Man Li et al reported a case of late-onset Schnitzler syndrome successfully treated with Janus activated kinase (JAK) inhibitors and colchicine. The article has been published in ‘International Journal of Rheumatic Diseases.’

The authors commented “Schnitzler syndrome should be considered for recurrent chronic urticaria when accompanied by fever, fatigue, rapid weight loss, and poor response to antihistamine treatment. Skin biopsy, bone marrow biopsy, and electrophoresis help confirm the diagnosis. Early diagnosis and treatment can lead to complete resolution of symptoms. Besides interleukin (IL)-1 and IL-6 inhibitors, JAK inhibitors and colchicine may be considered as other choices of treatment.”

A 68-year-old Chinese man with well-controlled diabetes and hypertension presented with itchy urticarial-like lesions over trunk and bilateral thighs for 3 months. The associated symptoms were general malaise, poor appetite, intermittent fever (up to 38.5°C) and unintentional weight loss of 8 kg in 3 months. The patient was negative for oral ulcers, eye or mouth dryness, joint pain, or numbness in extremities. He was diagnosed with chronic idiopathic urticaria by a general practitioner and was treated with antihistamine but in vain. There was no similar family history of urticarial lesions or recurrent fever for this patient.

Blood tests showed leukocytes, hemoglobin, platelet counts were within normal range, but increased percentage of large unstained cells 1.01 × 109 /L (normal range:0-0.4 × 10 9 /L). CRP was elevated at 23.1 mg/L, ESR was elevated at 106 mm/h, and ferritin was elevated at 599 ng/mL (normal range 11-306.8 ng/mL) Procalcitonin and tumor markers were within normal range. Antinuclear antibodies were negative. Extractable nuclear antigens, rheumatoid factor, anti-cyclic citrullinated peptide, and antineutrophil cytoplasmic antibodies were all negative. Immunology showed elevated immunoglobulin G (IgG) of 17.2 g/L (normal range: 8-16 g/L) IgA and IgA of 5.8 g/L (normal range: 0.7-3.3 g/L). T-SPOT test and labs for human immunodeficiency, hepatitis B and hepatitis C, syphilis were negative.

Electrocardiogram, abdominal sonography, chest computed tomography and whole body bone scan were all unremarkable. A skin biopsy was obtained which showed perivascular infiltration of lymphocytes, histiocytes, and neutrophils, without vasculitis change, consistent with neutrophilic dermatosis. Considering the elevated percentage of unstained cells, bone marrow biopsy was conducted which revealed hyperactive bone marrow without abnormal hemopoietic progenitor cells. Flow cytometry was unremarkable. Serum protein electrophoresis showed M protein and IgG-κ gammopathy.

Chronic urticaria rash, monoclonal IgG gammopathy, neutrophilic dermal infiltration on skin biopsy, elevated CRP level, and recurrent fever fulfilled 2 obligate criteria and 3 minor criteria of the Strasbourg criteria. The patient was thus diagnosed with Schnitzler syndrome.

Schnitzler syndrome is a rare acquire systemic inflammatory disease, characterized by chronic urticarial-like rash and monoclonal gammopathy (IgM or IgG). The median onset age is 59 years. It was first reported by French dermatologist Dr. Liliane Schnitzler in 1972 and was primarily reported in Caucasian populations. A study by Mayo Clinic reported about 74% of the patients were misdiagnosed. Current first-line treatment for Schnitzler syndrome is anakinra, an IL-1 inhibitor. Second-line treatment includes tocilizumab, an IL-6 inhibitor, which had shown partial response.

Due to unavailability of IL-1 antagonist agents in China, tofacitinib 5 mg and colchicine 0.5 mg twice a day were administered after the diagnosis. The urticarial rash subsided and left only post-inflammatory hyperpigmentation 3 weeks after the regimen. The patient was afebrile and his appetite was restored. CRP, ESR, IgG, IgA, returned to normal limits. Colchicine was discontinued after 8 weeks of treatment and tofacitinib 5 mg twice a day was maintained thereafter. The followed-up serum protein electrophoresis at 20 weeks of the treatment showed no M protein or IgG-κ gammopathy.

The authors commented that – “Early diagnosis and treatment can lead to complete resolution of symptoms. Besides IL-1 and IL-6 inhibitors, JAK inhibitors and colchicine may be other choices of treatment.”

Further reading:

Case report: Successful treatment with tofacitinib and colchicine in a patient with Schnitzler syndrome. Li M, Chen Y-W, Shen A, et al. Int J Rheum Dis. 2023;26:160-163. doi: 10.1111/1756-185X.14457