Connective Tissue Disease Associated Vasculitis

Connective Tissue Disease Associated Vasculitis

Vasculitis is defined by inflammatory leukocytes and subsequent necrosis of blood vessel walls that can eventually lead to tissue ischemia. When vasculitis is associated with a connective tissue disease (CTD), it is defined as a secondary vasculitis. The connective tissue diseases that most commonly cause vasculitis include rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren syndrome (SS). Vasculitis rarely occurs in the setting of other connective tissue diseases, including systemic sclerosis (SSc), relapsing polychondritis, primary antiphospholipid syndrome, inflammatory myopathies, and mixed connective tissue disease. Vasculitis is typically classified into large, medium, and small vessel vasculitis. When associated with a connective tissue disease, any type of vasculitis can occur; however, small vessel vasculitis is most common.

Synonyms

• Connective tissue disorder–associated vasculitis
• CTD

Epidemiology & Demographics

• •Rheumatoid vasculitis: Estimated to occur in 1% to 5% of patients with RA, with no racial or ethnic predominance. Tends to occur in patients with longstanding uncontrolled RA. Incidence is decreasing, most likely because recognition is increasing, and treatment options are becoming more affordable and available.
• •Lupus-associated vasculitis: Estimates of the prevalence range from 11% to 36%.
• •Sjögren-associated vasculitis: Cutaneous vasculitis occurs in approximately 10% of patients with primary Sjögren; systemic vasculitis is rare.
• •Other CTD: Rare, but well described.

Physical Findings & Clinical Presentation

General

• •Constitutional symptoms—fatigue, myalgias, weight loss, fever
• •Skin manifestations—nail fold lesions (splinter hemorrhages), palpable purpura, leg ulcers, panniculitis, digital gangrene, livedo reticularis, urticaria, Janeway lesions, Osler nodes
• •Neurologic manifestations—mononeuritis multiplex, distal symmetric sensorimotor neuropathy, transverse myelitis
• •Ocular manifestations—episcleritis, scleritis, ulcerative keratitis
• •Cardiac manifestations—arrhythmias, pericarditis, aortitis
• •Gastrointestinal manifestations—pancreatitis, peritonitis, colitis
• •Pulmonary manifestations—pneumonitis, alveolar hemorrhage
• •Renal manifestations—glomerulonephritis

note: Any organ may be involved because vasculitis can disrupt the corresponding vasculature (an example would be kidney injury due to destructive inflammation of the renal vasculature).

Most Common Syndromes

• •Rheumatoid vasculitis:
  • 1.The most common clinical presentation of rheumatoid vasculitis includes skin lesions and peripheral neuropathy.
  • 2.Although a diagnosis of RA is needed to develop a secondary vasculitis, occasionally the vasculitic symptoms are the first manifestation of RA.
  • 3.Most patients with rheumatoid vasculitis have long-standing uncontrolled erosive RA, with rheumatoid nodules and high levels of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP).
  • 4.The diagnosis of rheumatoid vasculitis is usually confirmed by obtaining a biopsy of the clinically involved organ.
• •Lupus-associated vasculitis:
  • 1.Skin lesions are the most common manifestation.
  • 2.The most common types of skin lesions are palpable purpura, petechiae, papulonodular lesions, livedo reticularis, panniculitis, and splinter hemorrhages.
• •Sjögren-associated vasculitis:
  • 1.Vasculitis is one of the most common extraglandular manifestations of Sjögren syndrome.
  • 2.The most common skin lesions are palpable purpura, which most often represents a leukocytoclastic vasculitis.
  • 3.It can be quite difficult to tell the difference between vasculitis secondary to Sjögren disease and a concomitant primary vasculitis. Sjögren disease has been associated with several other primary vasculitides, including ANCA-associated vasculitis and polyarteritis nodosa. Should also assess for secondary cryoglobulinemia.

Etiology

The vasculitis usually reflects the pathophysiology of the underlying connective tissue disease.

Differential Diagnosis

• •Infection
• •Hypercoagulable states (thrombotic thrombocytopenic purpura, hemolytic–uremic syndrome)
• •Malignancy (leukemia, lymphoma)
• •Primary vasculitides

Workup

The diagnosis usually requires multiple modalities, including a full history and physical, as well as laboratory testing, imaging, and sometimes a biopsy of skin or other involved organ. In order to have a connective tissue disease–associated vasculitis, one must meet diagnostic criteria for an underlying connective tissue disease.

Laboratory Tests

• •Erythrocyte sedimentation rate/C-reactive protein
• •CBC with differential
• •Albumin
• •Complement studies
• •Blood urea nitrogen and creatinine
• •Urinalysis
• •Antinuclear antibodies, RF, anti-CCP antibodies, double-stranded DNA (dsDNA)
• •Antineutrophil cytoplasmic antibodies (ANCA) that include ANCA-specific antibodies (anti-proteinase-3 and antimyeloperoxidase antibodies)

Imaging and Other Studies

• •Imaging may be helpful depending on the clinical manifestations of the disease. For instance, in aortitis or renal artery vasculitis, an angiogram, computed tomography angiography, or magnetic resonance angiography may be useful.
• •Biopsy of the affected site may be very useful and has proven to be an indispensable tool. Skin, nerve, muscle, and kidney biopsies, depending on the affected organ system, will usually help to arrive at a final diagnosis and rule out vasculitis mimics.

Treatment

Initial treatment is aimed at the underlying connective tissue disease. Additional immunosuppressive therapy may be needed depending on the severity of the vasculitis.

Chronic Rx

May need extended immunosuppressive therapy to prevent relapse

Referral

Rheumatology

Pearls & Considerations

• •BiopsyPatients with a history of CTD who present with new cutaneous lesions orsystemic symptoms should be evaluated for vasculitis. Conversely, in patients who present with vasculitis, consideration should be given to the possibility of underlying CTD.
• •BiopsyIt is important not to confuse vasculitis with vasculopathy. The latter is a noninflammatory vascular process that is integral to the pathophysiology of some CTDs, such as SLE and SSc.

Seek Additional Information

• Barile-Fabris L., et al.: Vasculitis in systemic lupus erythematosus. Curr Rheumatol Rep 2014; 16 (9): pp. 440.
• Cozzani E., et al.: Vasculitis associated with connective tissue diseases. G Ital Dermatol Venereol 2015; 150: pp. 221-232.
• Makol A., et al.: Rheumatoid vasculitis an update. Curr Opin Rheumatol 2015; 27 (1): pp. 63-70.
• Scofield R.: Vasculitis in Sjögren’s syndrome. Curr Rheumatol Rep 2011; 13 (6): pp. 482-488.