Last updated: October 31, 2014
ICD-9 Code: 447.6.
Definition: Rheumatoid vasculitis is inflammation of blood vessels in patients with RA. Vasculitis is considered a serious extraarticular manifestation of RA.
Etiology: Immune complexes, probably containing RFs, are passively deposited on blood vessel walls. All patients manifesting rheumatoid vasculitis have strongly positive titers of IgM-RF. Most of these RF-containing complexes also fix complement, which contributes to tissue damage.
Pathology: In small- to medium-sized vessels, the lesion may include an infiltrate consisting of both mononuclear and polymorphonuclear cells, and fibrinoid necrosis. In small vessels of the skin, leukocytoclastic vasculitis may be seen.
Demographics: Rheumatoid vasculitis is usually associated with aggressive and long-standing RA. The incidence in males is somewhat higher than in females. The vast majority of patients are positive for IgM-RF; cases of putatively seronegative patients may be associated with IgG-RF, which is not detected by routine clinical assays. This complication of RA appears to be decreasing in incidence. Limited cutaneous lesions are more common than severe necrotizing complications, which are rare. Autopsy studies suggest that the true incidence of vasculitis is higher, although most cases are subclinical and not detected during life.
Cardinal Findings: Nailfold lesions are most common and include prominent periungual vessels, localized infarction, splinter hemorrhages, and tender macules of the fingertips (which may be dark red or brown). Palpable purpura has been described. Larger vessel involvement often manifests as leg ulcers. Nerve involvement presents most commonly as a mononeuritis multiplex syndrome (e.g., with wrist or foot drop). Involvement of larger arteries, resulting in infarction of the myocardium, bowel, lung, and so on, is seen rarely.
Diagnostic Tests: Patients are universally seropositive with high titers of IgM-RF. ESR and CRP are usually very elevated. Complement levels (C3, C4) are usually decreased. Leukocytosis, anemia of chronic disease, cryoglobulinemia, and P-ANCA may be present. Nerve conduction velocity testing may indicate a mononeuritis multiplex.
Key to Diagnosis: A diagnosis of rheumatoid vasculitis should be questioned if the patient does not have severe seropositive RA of long-standing duration. However, active synovial inflammation does not correlate with the onset or activity of the vasculitis. In cases of specific organ or tissue involvement such as a mononeuritis syndrome, biopsy of the affected tissue (in this case the nerve) may be very useful in establishing a diagnosis. A skin biopsy should be performed if palpable purpura is seen.
Differential Diagnosis: Clinical and pathologic lesions may resemble those seen in association with subacute bacterial endocarditis, PAN, granulomatosis with polyangiitis, or cholesterol emboli syndrome.
Therapy: Leukocytoclastic vasculitis does not require aggressive therapy. Aggressive therapy with cyclophosphamide is reserved for rheumatoid vasculitis involving medium- to large-sized vessels. Cyclophosphamide may be administered as a daily oral dose or as an intermittent intravenous bolus infusion. Concomitant treatment with moderate doses of prednisone is required. Anecdotal reports of TNF inhibitor treatment of rheumatoid vasculitis have been favorable. The duration of therapy is unclear, although some require maintenance therapy for years. Foot and wrist drops are managed with splints.
Prognosis: Outcome depends on the organ system involved. Patients whose vasculitis is limited to fingertip lesions generally do well, whereas involvement of major nerves or arteries in organs such as the heart is associated with a poorer prognosis. The use of cyclophosphamide has had a major impact on reducing associated morbidity and mortality.
Bacon PA, Kitas GD. The significance of vascular inflammation in rheumatoid arthritis (review). Ann Rheum Dis 1994;53:621–623. PMID:7979572
Bacon PA, Moots RJ. Extra-articular rheumatoid arthritis. In: Koopman WJ, ed. Arthritis and allied conditions: a textbook of rheumatology, 13th ed. Baltimore: Williams & Wilkins,1997:1071–1088.