Fig. 12.1 Palpable purpura.

Purpuric lesions are the most common manifestation of vasculitis in Sjögren’s syndrome. These lesions can be either palpable or non-palpable. Direct immunofluorescence studies on skin biopsies are usually necessary to distinguish the small-vessel vasculitis associated with Sjögren’s syndrome from that of Henoch-Schönlein purpura, microscopic polyangiitis, and other disorders that can cause leukocytoclastic vasculitis

effects of the intensive treatment sometimes required to manage vasculitis. The occurrence of vasculitis along with certain other clinical and serologic features (e.g., salivary gland enlargement and low C4 levels) are markers for patients at increased risk for B cell lymphoma development.

12.2Epidemiology

The prevalence of vasculitis among patients with primary SjS is estimated to be between 9% and 15%, based upon studies that have employed the new AmericanEuropean criteria for the diagnosis of SjS [1, 2]. Approximately half of the cutaneous lesions associated with SjS are attributable to vasculitis [3]. Vasculitis is generally a late clinical complication of SjS, with a median time to appearance approximately 10 years after the diagnosis [4]. However, vasculitis is occasionally the presenting feature of SjS.

In the vast majority of SjS patients in whom vasculitis occurs, small-vessel disease predominates [3]. Small blood vessels include capillaries and post-capillary venules, and in SjS there is a major predilection for involvement of the skin (Fig. 12.1). In a significant minority of SjS patients – approximately 5% of those patients who develop vasculitis – the disease involves medium-sized blood vessels. The occurrence of medium-vessel disease (Fig. 12.2), which frequently resembles polyarteritis nodosa or rheumatoid vasculitis, signals a more serious development and the need for intensive therapy.

Fig. 12.2 Cutaneous ulceration. Sjögren’s syndrome causes a medium-vessel vasculitis if approximately 5% of patients in whom vasculitis occurs. This medium-vessel vasculitis resembles polyarteritis nodosa. In addition to this cutaneous ulceration on the lower extremity, the patient also has a severe sensorimotor vasculitic neuropathy

12.3Histopathology

Several histopathologic types of vasculitis have been described in SjS. There is overlap among these types, and more than one type of histopathology can be found in the same patient. The four histopathologic types described are leukocytoclastic vasculitis, lymphocytic vasculitis, acute necrotizing vasculitis, and endarteritis obliterans.

Leukocytoclastic vasculitis is the most common pattern observed. This histopathology is characterized by infiltration of the blood vessel wall by polymorphonuclear leukocytes, fibrinoid necrosis, karyorrhexis (scattered nuclear debris; “nuclear dust”), and extravasation of erythrocytes (Fig. 12.3). Leukocytoclastic vasculitis is a non-specific finding that must be distinguished in SjS from other causes of smallvessel vasculitis that can cause identical histopathology on light microscopy. Other causes of this histopathology include the drug-induced (“hypersensitivity” vasculitis); the pauci-immune vasculitides (e.g., those associated with antineutrophil cytoplasmic antibodies [ANCA]); Henoch-Schönlein purpura; hypocomplementemic urticarial vasculitis; essential cryoglobulinemia; and others. The diagnosis

Fig. 12.3 Histopathology of leukocytoclastic vasculitis. The histopathology associated with most often with vasculitis in Sjögren’s syndrome is leukocytoclastic vasculitis, characterized by neutrophilic invasion of blood vessel walls, degranulation, karyorrhexis, and red blood cell extravasation

Fig. 12.4 Lymphocytic vasculitis. A small minority of patients Sjögren’s syndrome have a lymphocytic vasculitis as opposed to a leukocytoclastic vasculitis. Lymphocytic vasculitis is generally less destructive of the blood vessel wall than is leukocytoclastic vasculitis

of SjS-associated vasculitis is rendered generally on the basis of the clinical context, the exclusion of mimickers through appropriate testing, and the performance of direct immunofluorescence on skin biopsies. Direct immunofluorescence on biopsies from patients with SjS-associated vasculitis generally shows signs of immune complex deposition.

In contrast to leukocytoclastic vasculitis, the infiltrates in lymphocytic vasculitis consist of lymphocytes and monocytes. Lymphocytic vasculitis, generally less destructive than leukocytoclastic vasculitis, does not usually cause vessel wall necrosis (Fig. 12.4). Lymphocytic vasculitis is far less common than the leukocytoclastic histopathology. In a study by Ramos-Casals et al. [3], only 1 of 52 patients with SjS had lymphocytic vasculitis. Lymphocytic vasculitis has been observed in tissues other than skin, such as peripheral nerves and muscles [4].

In the third type of histopathology, acute necrotizing vasculitis, the entire vascular wall is infiltrated by inflammatory cells and the degree of fibrinoid necrosis is profound [4] (Fig. 12.5). This form of vasculitis, although rare, is a very serious complication of SjS and is usually associated with internal organ involvement. Acute necrotizing vasculitis can affect medium-sized blood vessels as well as small blood vessels. In the study by Ramos-Casals et al. [3], acute necrotizing vasculitis resembling polyarteritis nodosa was reported in only 2 of 52 patients.