Cutaneous Vasculitis in Primary Sjögren Syndrome

Abstract

To analyze the different clinical and histologic types of cutaneous vasculitis in patients with primary Sjögren syndrome (SS), we investigated the clinical and immunologic characteristics of 558 consecutive patients with primary SS from our units and selected those with clinical evidence of cutaneous lesions, excluding drug reactions and xeroderma. All patients fulfilled 4 or more of the diagnostic criteria for SS proposed by the European Community Study Group in 1993. A total of 89 (16%) patients presented with cutaneous involvement (88 female patients and 1 male; mean age, 51.8 yr). The main cutaneous involvement was cutaneous vasculitis, present in 52 (58%) patients. There were 51 (98%) female patients and 1 (2%) male, with a mean age at diagnosis of cutaneous vasculitis of 51 years (range, 20-80 yr). Fourteen presented with cryoglobulinemic vasculitis, 11 with urticarial vasculitis, and the remaining 26, with cutaneous purpura not associated with cryoglobulins. A skin biopsy specimen was obtained in 38 patients (73%). Involvement of small-sized vessels was observed in 36 (95%) patients (leukocytoclastic vasculitis), while the remaining 2 (5%) presented with medium-sized vessel vasculitis (necrotizing vasculitis). Patients with cutaneous vasculitis had a higher prevalence of articular involvement (50% vs 29%, p = 0.044), peripheral neuropathy (31% vs 4%, p < 0.001), Raynaud phenomenon (40% vs 15%, p = 0.008), renal involvement (10% vs 0%, p = 0.028), antinuclear antibodies (88% vs 60%, p = 0.002), rheumatoid factor (78% vs 48%, p = 0.004), anti-Ro/SS-A antibodies (70% vs 43%, p = 0.011), and hospitalization (25% vs 4%, p = 0.005) compared with SS patients without vasculitis. Six (12%) patients died, all of whom had multisystemic cryoglobulinemia.In conclusion, cutaneous involvement was detected in 16% of patients with primary SS, with cutaneous vasculitis being the most frequent process. The main characteristics of SS-associated cutaneous vasculitis were the overwhelming predominance of small versus medium vessel vasculitis and leukocytoclastic versus mononuclear vasculitis, with a higher prevalence of extraglandular and immunologic SS features. Small vessel vasculitis manifested as palpable purpura, urticarial lesions, or erythematosus maculopapules, with systemic involvement in 44% of patients in association with cryoglobulins in 30%. Life-threatening vasculitis was closely related to cryoglobulinemia.

Dermatologic Manifestations of Sjögren Syndrome

“…18 Cryoglobulinemia can also be associated with an increased risk of lifethreatening multisystem vasculitis involving the central nervous system, kidneys, lungs, mesentery, and pancreas and severe cutaneous lesions, including ulcers and digital ischemia. 16 In summary, these findings underscore the importance of identifying palpable purpura and cryoglobulinemia in primary SS as an indicator of severe disease and poor prognosis.…”

“…16,17 In this condition, urticarial lesions appear as erythematous urticariform macules and are commonly seen on the upper extremities, face, and trunk. 16 Unlike common urticaria, the lesions of urticarial vasculitis in SS often persist for days, demonstrate petechiae, are painful to the touch instead of pruritic, and may heal with hyperpigmentation. 9,11 In a study of 52 patients with SS, 94% of those patients with histologically confirmed cutaneous vasculitis had leukocytoclastic vasculitis and 73% of these patients presented with palpable purpura.…”

“…16 The vasculitis of primary SS predominantly involves the small vessels, 10,16,17 with only rare reports of medium-sized vasculitis. 16 Cutaneous vasculitis is a marker of more severe disease because patients with this manifestation are more likely to have comorbid systemic manifestations. Although these comorbidities may include arthritis, peripheral neuropathy, and Raynaud phenomenon, more prognostically significant is the fact that such patients are at increased risk of glomerulonephritis, being at higher risk for developing and dying from non-Hodgkin lymphoma, 15,18,19 and have more hospitalizations than SS patients without vasculitis.…”

“…16 In patients with primary SS, livedo reticularis should be considered a distinct cutaneous manifestation in the absence of an underlying vasculitic or thrombotic disease. 16 One skin manifestation associated with SS, erythema annulare, appears to preferentially affect one ethnic group. Erythema annulare of SS is believed to be the Asian equivalent of subacute cutaneous lupus erythematosus in whites.…”

Conventional Therapy of Sjogren’s Syndrome

“…The latter is related to the presence of cryoglobulinemia and high titers of rheumatoid factor and clinically manifests as ulcerative skin lesions, digital gangrene, mononeuritis multiplex, mesenteric arteritis, myositis, and glomerulonephritis [56]. Prednisone (1 mg kg −1 day −1 ), cyclophosphamide (0.5-1 g/m 2 monthly), and plasmapheresis are the mainstay of treatment [29].…”