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Observation
July 2016

Refractory Subcutaneous Sweet Syndrome Treated With Adalimumab

Author Affiliations
  • 1Duke University School of Medicine, Durham, North Carolina
  • 2Department of Pathology, Duke University School of Medicine, Durham, North Carolina
  • 3Department of Dermatology, Duke University School of Medicine, Durham, North Carolina
JAMA Dermatol. 2016;152(7):842-844. doi:10.1001/jamadermatol.2016.0503

Subcutaneous Sweet syndrome (SSS) is a rare febrile neutrophilic dermatosis, distinct from classic Sweet syndrome. There is insufficient literature guidance regarding treatment options for SSS besides corticosteroids or effective alternatives if steroids fail to manage disease.

Report of a Case

A man in his 50s presented with tender nodules on his buttocks and proximal extremities of 6 months’ duration and associated with fevers, joint pain, and swelling of the hands and feet. He had been previously hospitalized for fever, arthritis, and skin eruption. His erythrocyte sedimentation rate was 65 mm/h; C-reactive protein level, 14 mg/L; ferritin, 555 ng/mL; but findings were negative on an autoimmune workup (including serum protein electrophoresis [SPEP] and the anti–cyclic citrullinated peptide antibody test [anti-CCP], normal complement levels, and negative findings for antinuclear antibody, creatine kinase, antineutrophil cytoplasmic antibody, anti-Jo1, anti-Scl70, anti-dsDNA, antiribosomal P, antichromatin, anticentromere, and cryoglobulins). While infection was considered, findings from extensive testing were all negative (blood cultures, human immunodeficiency virus, hepatitis, Bartonella, Q fever, Rocky Mountain spotted fever, Lyme disease, and Epstein-Barr virus), and he failed to improve under treatment with multiple antibiotics.

Dermatology was not consulted during his inpatient stay, and no biopsy was performed. He responded to treatment with intravenous methylprednisolone and oral prednisone and was discharged with a diagnosis of adult Still disease. He was then treated with methotrexate and hydroxychloroquine for about 6 weeks; both treatments were discontinued secondary to lack of response. The patient continued to experience recurrence of fevers, lesions, and constitutional symptoms and was referred for further evaluation.

On presentation, he had multiple tender subcutaneous nodules, about 1 cm in diameter, on the buttocks, posterior thighs, and upper arms with overlying erythema and faint violaceous change (Figure 1). Given his previously negative infectious disease findings, failure of treatment with several antibiotics, and complete response to prednisone, biopsy for culture was not performed. Pathologic analysis of a representative nodule showed a mixed infiltrate of lymphocytes, histiocytes, and neutrophils in the subcutaneous tissue in lobules and around vessels. There was no infiltration of larger vessels by neutrophils and no evidence of vasculitis. Myeloperoxidase staining highlighted the predominantly neutrophilic subcutaneous infiltrate (Figure 2). The findings supported the final diagnosis of SSS. Bone marrow biopsy, cytogenetic analysis, and peripheral blood smears to rule out myelodysplastic syndrome and acute myeloid leukemia failed to show clonal abnormalities, increased blasts, or dysplastic cells.

Figure 1.
Subcutaneous Sweet Syndrome Clinical Presentation
Subcutaneous Sweet Syndrome Clinical Presentation

This case shows tender, erythematous to violaceous subcutaneous nodules on the patient’s bilateral posterior thighs.

Figure 2.
Pathologic Findings From a Representative Lesion
Pathologic Findings From a Representative Lesion

A, Mixed, predominantly neutrophilic infiltrate involving subcutaneous adipose tissue (original magnification ×2). B, Numerous neutrophils in the infiltrate are highlighted (original magnification ×20).

The patient had complete remission under treatment with mid-dose oral corticosteroids, but tapering below 20 mg/d resulted in recurrent relapses despite the addition of dapsone up to a dose of 200 mg/d. Because of this ongoing activity despite long-term systemic therapy, after negative findings of a tuberculosis test, he was started on a regimen of adalimumab, 40 mg every other week, given its effectiveness in other neutrophilic dermatoses.1 He demonstrated a dramatic, robust clinical response to this single agent with lasting resolution of all symptoms. At last follow-up, he was without any relapses for 6 months.

Discussion

Subcutaneous Sweet syndrome is a rare disease entity characterized by a subcutaneous neutrophilic panniculitis. Positive criteria found in almost all reported cases include (1) nodules or plaque lesions, (2) systemic symptoms such as fever and malaise, (3) histologic evidence of a subcutaneous lobular neutrophilic infiltrate, (4) association with myelodysplasia, and (5) sensitivity to systemic corticosteroids.2,3 Although SSS is distinct from classic Sweet syndrome, patients may present with a mix of both classic and subcutaneous lesions, and it is likely that these exist along a spectrum. Classic Sweet syndrome can appear prior to or concurrent with development of hematologic malignancy and often responds to dapsone (neutrophil-inhibiting agent) and anti–tumor necrosis factor (anti-TNF) agents.1 This patient’s disease relapsed at doses of oral prednisone below 20 mg/d and did not respond to dapsone.

To our knowledge, we have described the first case of SSS treated with adalimumab, an agent with proposed and documented benefit in autoimmune dermatologic diseases refractory to traditional agents.4,5 The patient demonstrated lasting disease remission with adalimumab monotherapy, providing evidence for use of this agent in treating SSS. Although case studies have suggested a potentially increased incidence of lymphoma in patients with rheumatoid arthritis treated with adalimumab, large cohort studies have not reproduced this finding.6 Interestingly, while anti-TNF agents have proven helpful in a variety of inflammatory and autoimmune disorders, rarely, treatment with these agents can lead to paradoxical development of autoimmune phenomena, though it was well tolerated in this patient. Adalimumab offers a new approach for patients with debilitating disease refractory to lower-dose corticosteroid therapy or traditional steroid-sparing agents.

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Article Information

Corresponding Author: Matilda W. Nicholas, MD, PhD, Department of Dermatology, Duke University School of Medicine, DUMC 3135, Durham, NC 27710 (matilda.nicholas@dm.duke.edu).

Published Online: March 30, 2016. doi:10.1001/jamadermatol.2016.0503.

Conflict of Interest Disclosures: None reported.

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