Contributed by Kevin D Horn, MD, Jawad Ahmad, MD and Sydney Finkelstein, MDNECROTIZING LEUKOCYTOCLASTIC SMALL VESSEL VASCULITIS OF THE COLON, OF PROBABLE AUTOIMMUNE ETIOLOGY
Contributor's Note:
Rheumatoid arthritis (RA) is a systemic disorder of immune regulation which is characterized primarily by articular manifestations. Joint synovial linings demonstrate progressive proliferative changes which often ultimately progress to destruction of the joint space and underlying cartilage with loss of function of the articular unit. Rheumatoid nodules may also form in subcutaneous tissues overlying easily traumatized bone (such as upper extremity extensor surfaces) and may also be found in other tissues and organs (lung, skeletal muscle, etc.) These nodules demonstrate central paucicellular areas of eosinophilic necrosis which are flanked by rows, or palisades of histiocytes and other inflammatory cells. The pathogenesis underlying the formation of these nodules is not completely understood; they are noted in approximately 25% of patients with RA.
Rheumatoid vasculitis is a well-described entity in RA patients, and can be a serious threat to function and life, depending upon the size and location of the involved vessels. Blindness, peripheral neuropathies, cerebrovascular accidents, and skin ulceration with gangrene has been noted in these patients; this complication is most often noted in patients with the highest rheumatoid titers.
In the laboratory, a diagnosis of rheumatoid arthritis is supported (in the proper clinical context) by the identification of so-called Rh factor, an anti-self antibody noted in over 80% of RA patients. Most of these antibodies are of the IgM subtype, and show specificity for the Fc portion of the IgG molecule. These antibodies form circulating complexes with their respective IgG antibodies; these complexes form deposits in synovial membranes and are felt to contribute to the formation of the typical synovitis and pannus of RA through the activation of complement in situ. Similar activity in the extraarticular tissues (renal glomerulus, small systemic vessels, etc) cause many of the disease manifestations in these regions. In the absence of identifiable Rh factor in serum or synovial fluid, the diagnosis of "seronegative" RA is made on a clinical basis, with the findings of symmetrical arthritis affecting three or more areas and especially involving joints of the hand, typical radiologic findings of RA (narrowing of the joint spaces, marginal erosions, and digit deviations or subluxations), morning stiffness, and the identification of rheumatoid nodules (usually not identified in absence of elevated Rh titer). The disease course of RA is variable, with most cases of a chronic nature with periodic exacerbations. Death, if related to RA, is usually due to complications of vasculitis and chronic vessel changes (including amyloid depositions in vessel walls) and therapy-related complications (infections secondary to chronic immunosuppression, or coagulopathy secondary to NSAID overuse).
Systemic lupus erythematosus (SLE) is an autoimmune disorder seen predominantly in women of childbearing age (approximately 9:1 male:female ratio), in which there is a primary defect in the discrimination of self versus non-self antigens by the immune system. Various antibodies with self-directed specificity have been described and are considered diagnostic of SLE when in combination and in the appropriate clinical setting. Clinically, SLE commonly manifests in a myriad of systemic abnormalities, including skin rashes, polyarticular arthritis and myalgias, renal dysfunction, weight loss with fatigue, coagulation and other hematologic abnormalities, serositis involving heart and lungs, and localized or systemic vasculitides (as mentioned above). At least one group has correlated the rise in the serum of complement split products with increased risk of small vessel vasculitis in SLE patients (Abramson et al).
As a group, the self-directed immunoglobulins in SLE are referred to as anti-nuclear antibodies (ANA), noted in greater than 95% of SLE cases. Major subtypes include anti-double stranded DNA antibody (directed towards ds DNA in patient cells, with their subsequent destruction); anti-Smith (directed against core proteins in the small nuclear ribosomal complex); anti-histone antibodies, and anti-ribonucleoprotein antibodies (U1RNP). Although these and other antibodies can be seen in other autoimmune disorders (such as systemic sclerosis and Sjögren's syndrome), the combination of the proper clinical features with the presence of anti-ds DNA and anti-Smith antibody is considered virtually diagnostic of SLE. The course of the disease is variable, with a usual chronic course that tends to respond to antiinflammatory therapy in the event of periods of disease exacerbation. If patients with SLE succumb to their disease, the most common causes of death are renal failure and infections (often secondary to long term immunosuppressive therapy).
Secondary vasculitides in patients with primary autoimmune disorders, such as systemic lupus erythematosus and rheumatoid arthritis, are a well-recognized phenomenon. Although most commonly found to involve the small venules of the skin and subcutaneous tissue, a more severe systemic vasculitis, clinically indistinguishable from the polyarteritis nodosa group (PAN) can be seen. These variants are characterized by an often necrotizing leukocytoclastic vasculitis of systemic small to medium-sized muscular arteries which can affect any system or region. As in classic PAN, however, renal, musculoskeletal, and gastrointestinal arteries are most commonly involved. The presentation of the case described above is unusually florid, with diffuse vascular changes by endoscopy in the right colon, gangrenous changes in a digit (which may represent either severe Raynaud's phenomenon, as noted in many SLE patients, or localized vasculitis with attendant thrombosis of the vessels supplying the digit), a history of deep venous thromboses, and coronary artery disease (which may or may not be related to the patient's autoimmune disease). Further immunologic studies of patient sera and immunofluorescence microscopy of biopsy specimens from involved sites would have been of great interest in the further evaluation of this case, but clinical factors precluded such investigation.
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Contributed by Kevin D Horn, MD, Jawad Ahmad, MD and Sydney Finkelstein, MD
