Connective Tissue Disease–Associated Vasculitis

Bradley Schlussel, M.D.

Basic Information

Definition

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’s syndrome (SS). Vasculitis rarely occurs in the setting of other connective tissue diseases, including systemic sclerosis (SSc), Behçet’s disease, 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.

Synonym

Connective tissue disorder–associated vasculitis
CTD

ICD 10-CM CODES
M35.9	Systemic involvement of connective tissue, unspecified

Epidemiology & Demographics

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Rheumatoid vasculitis: estimated to occur in 1% to 5% of patients with RA, with no racial or ethnic predominance.
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Lupus-associated vasculitis: estimates of the prevalence of vasculitis among SLE patients range from 11% to 36%.
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Sjögren’s-associated vasculitis: cutaneous vasculitis occurs in approximately 10% of patients with primary Sjögren’s disease.
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Other CTD: rare, but well described.

Physical Findings & Clinical Presentation

General

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

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

Etiology

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

Diagnosis

Differential Diagnosis

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Infection
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Hypercoagulable states (TTP, HUS)
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Malignancy (leukemia, lymphoma)
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Primary vasculitides

Workup

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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

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ESR/CRP
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CBC with diff. and platelets
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Albumin
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Complement studies
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Blood urea nitrogen and creatinine
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Urinalysis
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ANA, RF, Anti-CCP antibodies
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Double-stranded DNA (dsDNA) (if patient has a history suggesting SLE)
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Antineutrophil cytoplasmic antibodies (ANCA) that include ANCA-specific antibodies (anti-proteinase-3 and anti-myeloperoxidase antibodies)

Imaging and Other Studies

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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.
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Biopsy of the affected site may be very useful. 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

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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

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May need extended immunosuppressive therapy to prevent relapse

Referral

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Rheumatology

Pearls & Considerations

Comments

Patients with a history of CTD who present with new cutaneous lesions or systemic symptoms should be evaluated for vasculitis. Conversely, in patients who present with vasculitis, consideration should be given to the possibility of underlying CTD.

It 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.

Ferri – Connective Tissue Disease–Associated Vasculitis