Successful treatment of Sweet syndrome complicated by Behcet disease with adalimumab.
A 15-year-old girl presented with recurrent aphthous stomatitis, acneiform papules, genital ulcers, and arthritis for 5 years. Uveitis was not detected. She was diagnosed with incomplete Behcet disease (BD), based on the revised diagnostic criteria proposed by the Behcet Disease Research Committee of Japan. Colchicine was initiated but was only partially effective. At 14 years old, she presented with recurrent fever, painful erythema, edematous purpura of the extremities, and polychondritis consistent with menstrual cycles (Figure 1a–d). Results of the laboratory examination indicated white blood cell count of 9600/mm3 with 65% neutrophils, 13 mm/h erythrocyte sedimentation rate, and 0.46-mg/dL C-reactive protein (CRP). HLA-B51 and A26 were neither negative. No mutation of the PSTPIP1 gene, which is responsible for PAPA (pyogenic arthritis, pyoderma gangrenosum, and acne syndrome) syndrome, was detected. Skin biopsy revealed neutrophilic inflammatory cell infiltration from the dermis to the adipose tissue; in particular, the perivascular infiltration in the adipose tissue was remarkable. Furthermore, fibrinoid necrosis or leukocytoclastic vasculitis was not detected (Figure 1e). Eventually, she was diagnosed with Sweet syndrome (SS). Prednisolone (0.3 mg/kg/day) was initiated in combination with colchicine. However, the patient's condition was not improved. After the dose of prednisolone increased to 0.6 mg/kg/day, aphthous stomatitis was improved. However, recurrent fever with skin manifestations and polychondritis consistent with menstrual cycles continued. Thus, adalimumab (ADA) (40 mg every other week) was added. After the first dose of ADA, fever, polychondritis, and arthritis disappeared. CRP became negative and never elevated. Skin manifestations, aphthous stomatitis, and genital ulcers disappeared 2 months after starting ADA. She is now in complete remission with ADA for 2 years. The patient and his parents signed written informed consent for publication. Sweet syndrome is a noninfectious inflammatory disease that is clinically characterized by fever and skin manifestations, including painful erythema, with histopathological evidence of intense neutrophilic infiltration of the dermis without evidence of leukocytoclastic vasculitis. Contrarily, BD is a chronic inflammatory disease that is characterized by recurrent oral aphthae, genital ulcer, ocular inflammation, and various potential systemic manifestations. Most clinical manifestations of BD are caused by vasculitis affecting the small and large arteries and veins. SS and BD are called neutrophilic dermatoses, and the clinical symptoms sometimes overlap. This causes difficulty in differentiating SS from BD, and patients often meet the diagnostic criteria for both diseases. Regarding BD, treatment is selected based on the affected organ and severity of that organ system. For oral aphthae and genital ulcers, topical corticosteroids are recommended, and in cases refractory to topical corticosteroids, colchicine, or systemic glucocorticoids, apremilast is considered. ADA, a humanized anti-tumor necrosis factor (TNF) monoclonal antibody, is used for the intestinal involvement of BD, but it is still being investigated for patients with other organ lesions refractory to corticosteroids and/or colchicine.1 Contrarily, corticosteroids and colchicine are the first-line treatments for SS. Immunosuppressants such as cyclosporine, methotrexate, and biologics, including anakinra, can be chosen as second-line treatments for patients with refractory SS. Overexpression of TNF-α is closely associated with neutrophil infiltration into the subcutaneous tissue and mucous membrane in the pathogenesis of SS.2 Recent studies have reported the clinical effect of TNF inhibitors, including infliximab3 and ADA,4 in adult patients with refractory SS. We report the first pediatric case of SS complicated by BD successfully treated with ADA. SS sometimes overlaps with BD. ADA may be an effective treatment option for patients with refractory SS complicated by BD. However, paradoxical SS-like symptoms after ADA administration have also been reported.5 Further studies involving a larger sample size are warranted to validate the results of this case. M.H. and M.S. wrote the manuscript; M.H., S.K., H.I., and M.S. collected data; and all authors read and approved the final manuscript. We thank Dr. Yuko Hayashi for engaging in helpful discussions. No specific funding was received from anybody in the public, commercial, or not-for-profit sectors to perform the work described in this article. The authors declare no conflict of interest.
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