Immunohistochemical Examination of Cutaneous Vasculitis in a Case of Cogan's Syndrome.

Sir,

Cogan's syndrome is a systemic inflammatory disease that was first reported by David Cogan in 1945. Diagnostic criteria are a combination of Ménière disease-like audiovestibular dysfunction and ocular symptoms. This syndrome is occasionally complicated by dermatologic manifestations of leukocytoclastic vasculitis that vary in size. Herein, immunohistochemical analysis was performed for cutaneous vasculitis that developed in a patient with Cogan's syndrome.

This study presents the case of a 57-year-old Japanese woman who was evaluated for a 10-day history of erythema on her legs. She was diagnosed with Cogan's syndrome based on the diagnostic criteria proposed by Haynes et al.[1] She had no relevant family history. Physical examination revealed painful erythema (approximately 10 mm) on her lower legs bilaterally [Figure 1a]. Laboratory testing showed an increased white blood cell count (26,400/mm3 [normal 4000–10,000/mm3]) and C-reactive protein levels (31.36 mg/dL [normal ≤0.3 mg/dL]). Rheumatoid factor, myeloperoxidase anti-neutrophil cytoplasmic antibody (ANCA), proteinase 3 ANCA, and serologic tests for syphilis were negative. Hypocomplementemia was not detected. A computed tomography (CT) angiogram showed thickened aortic walls [Figure 2a]. Fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT showed a pathologic uptake in the aorta, bilateral carotid [Figure 2b], iliac arteries, and celiac artery. Histopathologic examination of the skin lesion showed septal panniculitis [Figure 1b]. At the interlobular area, infiltration of lymphocytes, neutrophils, macrophages, and granuloma formation were observed [Figure 2c]. Fibrinoid necrotizing vasculitis of a small artery was also detected [Figure 1c]. Elastica van Gieson stain showed destruction of the external elastic membrane [Figure 2d]. Direct immunofluorescence was negative. Immunohistochemical analysis showed infiltration of CD3+ and CD4+ T lymphocytes, myeloperoxidase-positive neutrophils, CD68+ and CD163+M2 macrophages around the small artery [Figure 3a, b, d, and 1d, e], as well as in the dermis and subcutaneous tissue [Figure 3e and f]. In contrast, CD8+ [Figure 3c], CD20+, CD56+, and CD86+ [Figure 1f] cells were rarely observed. Vasculitis was diagnosed as an accompanying symptom. Steroid pulse therapy and infliximab (5 mg/kg) were administered. Thereafter, the symptoms finally disappeared, and no recurrence has been observed under prednisolone (6 mg/day), methotrexate (6 mg/week), and golimumab (50 mg/month) treatment for 3 years.

Figure 1

(a) Erythema with tenderness on bilateral lower legs. (b) Histopathologic examination shows fibrinoid necrotizing vasculitis and septal panniculitis (hematoxylin–eosin stain). (c) Fibrinoid necrotizing vasculitis of a small artery in the interlobular area (hematoxylin–eosin stain). An immunohistochemical examination of CD68 (d), CD163 (e) and CD86 (f)

Figure 2

(a) Computed tomography angiogram shows thickened aortic walls (arrowhead). (b) Fluorodeoxyglucose (18F)–positron emission tomography (FDG-PET) revealed the uptake of FDG in the bilateral carotid arteries (arrow). (c) Histopathologic examination of a skin lesion specimen showed septal panniculitis with granuloma in the subcutaneous tissue (hematoxylin–eosin stain). (d) The external elastic membrane was destroyed (Elastica van Gieson staining)

Figure 3

Immunohistochemical examination of CD3 (a), CD4 (b), CD8 (c), MPO (d), CD68 (e) and CD163 (f)

In the present case, a dominant infiltration of neutrophils, CD4+ T lymphocytes, and M2 macrophages was observed in the skin lesions. M1 macrophages are proinflammatory, as they play a role in killing microbes and causing inflammation. Conversely, M2 macrophages have a role in resolving inflammation, angiogenesis, and tissue remodeling and repair. Vogelpoel et al.[2] showed that M2 macrophages on simultaneous exposure to Toll-like receptor ligands and immune complex produce proinflammatory cytokines and promote Th17 responses in rheumatoid arthritis. In addition, M2 macrophages have been reported to be associated with the pathogenesis of autoimmune diseases or vasculitis,[3] such as eosinophilic granulomatosis with polyangiitis.[4] Furthermore, increased secretion of granulocyte-macrophage colony-stimulating factors by macrophages and smooth muscle cells may trigger aortic wall structural deterioration in Cogan's syndrome.[5] Accordingly, we hypothesized that M2 macrophages may be associated with the pathogenesis of cutaneous vasculitis in Cogan's syndrome, although further research is required to clarify it.

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The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.