Cigarette smoking, disease severity and autoantibody expression in African Americans with recent-onset rheumatoid arthritis.

OBJECTIVE: To examine the association of smoking with clinical and serological features in African Americans with recent-onset rheumatoid arthritis (RA) and to explore whether this association is dependent on the presence of the HLA-DRB1 shared epitope (SE). METHODS: In African Americans with recent-onset RA (n = 300), we examined the association of cigarette smoking (current versus past versus never and pack-years of exposure) with anti-cyclic citrullinated peptide antibody, rheumatoid factor (RF) (IgM and IgA), rheumatoid nodules and baseline radiographic erosions using logistic and cumulative logistic regression (adjusting for SE status). We also examined for evidence of interaction between smoking status and SE for all outcomes. RESULTS: Although there was no association with RF-IgA seropositivity, current smokers were approximately twice as likely as never smokers to have higher IgA-RF concentrations (based on tertiles; OR = 1.74; 95% CI 1.05 to 2.88) and nodules (OR = 2.43; 95% CI 1.13 to 5.22). These associations were most pronounced in those with more than 20 pack-years of exposure. There was no association of smoking status or cumulative tobacco exposure with anti-cyclic citrullinated peptide antibody, IgM-RF or radiographic erosions. There was also no evidence of a biological or statistical SE-smoking interaction for any of the outcomes examined. CONCLUSIONS: This is the first study to systematically examine the association of cigarette smoking with RA-related features in African Americans. Cigarette smoking is associated with both subcutaneous nodules and higher serum concentrations of IgA-RF in African Americans with RA, associations that may have important implications for long-term outcomes in this population.

Parenteral gold therapy in the Felty syndrome. Experience with 20 patients.

Most of the patients with the Felty syndrome suffer from such complications as fevers, infections, cutaneous ulcers, and vasculitis. Unfortunately, there are no therapeutic interventions that are predictably beneficial. We report our experience with 20 patients who received parenteral gold therapy for 2 to 114 months (mean, 23.6 months). All had complications of the Felty syndrome. On parenteral gold therapy, 60% had a complete response, 20% had a partial response, and 20% were unresponsive by preselected criteria. No serious complications were encountered. We think that parenteral gold therapy should be considered early, before other agents, in the treatment of this condition.

Rheumatoid vasculitis: survival and associated risk factors.

We describe the clinical and laboratory characteristics of 52 patients with rheumatoid vasculitis whose condition was diagnosed at a tertiary care center between 1974 and 1981, and we report their survival and the factors that were associated with decreased survival. The patients with rheumatoid vasculitis had decreased survival in comparison with an age-, sex-, and region-matched general population. Their survival was also decreased in comparison to that of an incidence cohort of community patients with rheumatoid arthritis. In the latter cohort, decreased survival was confined to those patients with classic but not definite rheumatoid arthritis. After partial correction for referral bias, we found no difference in survival between the cohort with rheumatoid vasculitis and the cohort with classic rheumatoid arthritis. We found that the age at diagnosis of rheumatoid vasculitis, the therapeutic decisions before and at diagnosis, and the referral distance were the best predictors of survival. Abnormal urinary sediment and hypergammaglobulinemia also predicted poor survival, but because of a lack of specificity in a small number of clinically abnormal values, we urge a cautious interpretation of their importance.

Peripheral neuropathy in primary Sjögren's syndrome.

Sjögren's syndrome (dryness of eyes, mouth, and other mucous membranes) may be associated with disease of joints, blood, internal organs, skin, and central and peripheral nervous systems. We reviewed 33 cases of primary Sjögren's syndrome and peripheral neuropathy evaluated by neurologic examinations and EMG at the Mayo Clinic from 1976 to 1988, and studied sural nerve biopsy specimens in 11 of them. Symmetric sensorimotor polyneuropathy occurred most frequently, followed by symmetric sensory neuropathy. Autonomic neuropathy, mononeuropathy, or cranial neuropathy (especially trigeminal neuropathy) was superimposed on generalized neuropathy in approximately one-fourth of patients. The course generally was slowly progressive, except for a few patients who may have improved with prednisone therapy. Although spinal ganglion involvement might have accounted for some of the clinical and neurophysiologic findings, we found evidence that necrotizing vasculitis was involved in fiber degeneration. All nerve biopsies revealed perivascular inflammatory infiltrates and other vessel abnormalities, which were diagnostic in two cases and strongly suggestive of necrotizing vasculitis in six cases. Axonal degeneration predominated over demyelination and sometimes was focal or multifocal. In neuropathy of unknown cause, particularly if it is sensory, autonomic, or involves trigeminal nerve, consider Sjögren's syndrome.

Update on systemic necrotizing vasculitis.

The systemic necrotizing vasculitides are classified into vasculitic syndromes on the basis of the pattern of clinical and pathologic involvement. The vasculitides have certain common clinical and laboratory abnormalities. Systemic necrotizing vasculitis is diagnosed on the basis of clinical features, and the vascular nature of the disease is determined by biopsy of involved tissue or angiography. The outcome is dependent on the extent of visceral involvement. Vascular inflammation influences the physiologic features of the vessel and may trigger vasoconstriction. Although glucocorticoids combat the inflammation, they may augment vasoconstriction and platelet aggregation. These effects must be considered in designing a management approach and in evaluating the cause and management of ischemic complications.

Series on pharmacology in practice. 9. Glucocorticoids in rheumatic disease.

Glucocorticoids are potent anti-inflammatory agents that play an important role in the therapy of many patients with connective tissue diseases, including systemic lupus erythematosus, polymyalgia rheumatica, various types of vasculitis, and complications of rheumatoid arthritis. Glucocorticoids reduce the number and influence the function of lymphocytes, monocytes, and eosinophils in peripheral blood. Prolonged high doses of glucocorticoids result in decreased levels of immunoglobulins, particularly IgG. Granulocytes are increased in the peripheral blood, but their migration to sites of inflammation is diminished. Glucocorticoids inhibit release of lysosomal enzymes. Although they have no effect on the factor or factors that initiate inflammation, glucocorticoids have proved to be effective in the treatment of inflammatory manifestations of disease. Among significant adverse effects of glucocorticoid therapy are osteoporosis, aseptic necrosis of bone, and steroid myopathy.

Clinical features, prognosis, and response to treatment in polyarteritis.

Fifty-three patients with polyarteritis who were followed up for at least 2 years were defined clinically and studied retrospectively to determine the influence of clinical factors and treatment on the prognosis. There was a spectrum of severity of disease, and the 5-year survival in the group was 55%. A small number of patients had evidence of ongoing immune-complex disease, as indicated by the presence of cryoglobulins or hepatitis Bs antigen or by diminished serum complement. These markers were not associated with distinct clinical features and did not influence prognosis. Organ involvement that most adversely affected prognosis was that of the gut and the kidneys. Six of 8 patients with bowel infarction or serious gastrointestinal bleeding died, and 6 of 10 patients with renal insufficiency died. Hypertension and peripheral neuropathy did not influence the prognosis. Thirty-six patients were treated with corticosteroids alone and 14 with a combination of corticosteroids and cytotoxic agents (3 received no treatment); the outcome was the same in both groups. Twenty-two in the steroid-alone group and six in the combination group were alive when last seen. Early deaths were usually due to complications directly related to the vasculitis, and late deaths were often due to cerebrovascular or cardiovascular complications. At the last follow-up, 18 patients were in remission, and 13 had inactive vasculitic disease and were on maintenance treatment.

Lymphoid neoplasia following connective tissue disease.

A retrospective review was undertaken to ascertain whether there are distinctive histopathologic features of the lymphoid neoplasms that occur in patients with previous connective tissue disease. Of 29 patients studied, 12 had malignant lymphoma with diffuse large-cell cytomorphology. Only 1 of these 12 had an immunoblastic cell type. The remaining 17 patients had neoplasia of a widely diverse nature. Six had lymphocytic lymphoma (one nodular poorly differentiated, three diffuse poorly differentiated, and three diffuse well differentiated), two had Hodgkin's disease, three had plasma cell myeloma, and six had chronic lymphocytic leukemia. Data fail to confirm a relationship between lymphoid proliferations with immunoblastic morphology and connective tissue diseases.

Class of immunoglobulin deposition and prognosis in lupus nephritis.

In the three major morphologic groups of lupus nephritis--diffuse, focal proliferative, and membranous--glomerular deposition of immunoglobulins is usually a combination of IgG, IgM, and IgA and is not a good indicator of initial renal severity or outcome. In this study of 60 patients with systemic lupus erythematosus and nephritis, patients with exclusive or predominant glomerular deposition of IgG did not have more severe renal disease or a worse prognosis than those with combined IgG-IgM deposition.

Hypocomplementemic urticarial vasculitis: association with chronic obstructive pulmonary disease.

Since 1973, we have identified and collected follow-up data on 16 patients with hypocomplementemic urticarial vasculitis. Preliminary diagnostic criteria are the presence of typical urticarial skin lesions and low levels of serum complement (all components), plus two of the following: dermal venulitis, arthritis, glomerulo-nephritis, episcleritis or uveitis, recurrent abdominal pain, and C1q precipitin in plasma. Exclusions are systemic lupus erythematosus, mixed cryoglobulinemia, elevated antinuclear antibody titer, hereditary deficiency of a complement component or of C1 esterase inhibitor, and presence of anti-native DNA or hepatitis B antigen. The renal involvement is relatively benign, and generally the patients do well and respond to specific treatment when this is indicated. Eight of 10 smokers studied had evidence of chronic obstructive pulmonary disease, 1 of whom died of this complication. In three patients, severe chronic obstructive pulmonary disease developed at a young age after relatively low pack-year cigarette smoking histories. Lung disease probably results from the interaction of two major risk factors-smoking and an immunologically mediated process that has not been identified.

Immunologic mechanisms in systemic vasculitis.

Thirty-four patients with systemic vasculitis were studied to determine the possible type and frequency of associated immunologic abnormalities. The patients were divided into three clinical groups--those with systemic vasculitis without respiratory tract involvement, those with systemic vasculitis with respiratory tract involvement (particularly Churg-Strauss vasculitis and Wegener's granulomatosis), and those with limited vasculitis without visceral involvement. A diminished level of serum complement was found in half the patients with systemic vasculitis without respiratory tract involvement. These patients usually had diffuse skin disease that often was associated with the presence of rheumatoid factor and cryoglobulinemia and most likely represented an immune-complex induced disease. The serum IgE often was elevated in patients who had systemic vasculitis with respiratory tract involvement, particularly those with Churg-Strauss vasculitis and Wegener's granulomatosis, and may be a clue to the pathogenesis in this group of patients.

Skin fibrinolytic activity in cutaneous and systemic vasculitis.

Study of involved and uninvolved skin from patients with necrotizing vasculitis revealed diminished tissue fibrinolytic activity deposition of immunoreactants in involved skin. In these patients, the depletion of tissue fibrinolytic activity is probably the result of vessel injury secondary to the local deposit of immunoreactants. In addition, there was diminished tissue fibrinolytic activity in uninvolved skin from patients with and without clinical skin involvement, unassociated with the deposition of immunoreactants. The precise mechanism for diminished tissue lytic activity in these latter patients is not known, but it may be associated with generalized activation of the coagulation and fibrinolytic mechanisms that result in local depletion of tissue fibrinolytic activity. These local changes may aggravate the clinical course of the disease as well as inhibit the healing of the lesions.

Use of captopril as early therapy for renal scleroderma: a prospective study.

We conducted a prospective study of captopril therapy in patients with scleroderma and combined hypertension and renal insufficiency. In all seven patients studied during a 1-year period, control of blood pressure was achieved, and in six of the seven, renal function stabilized or improved. The total daily dosage of captopril ranged from 32 to 100 mg, divided into doses taken every 6 to 8 hours. Although one patient had a suspected captopril-induced rash for a short time, none of the other patients had any adverse side effects. Renal biopsies were performed in six patients; in three of them, specimens were obtained both at the beginning and at the end of the study. The initial biopsy specimens showed changes that were similar to those described in other reports. Findings on repeat biopsies were unchanged except for evidence of chronicity. In the six patients with controlled blood pressure and improved or stabilized renal function, the improvement was maintained for 1 1/2 to nearly 3 years on this drug therapy. Using specific measurements of skin compliance and vascular blood flow in the upper extremities, we could detect no evidence, however, of concomitant improvement in these other features of the disease. Although the blood pressure was controlled with captopril, one patient had progressive skin induration, one had progressive pulmonary insufficiency, and another had progressive renal failure.

In vivo platelet survival in rheumatoid arthritis.

We studied the in vivo consumption of chromate-labeled platelets in 14 patients with active rheumatoid disease and demonstrated shortened platelet survival in 8. We were unable to find significant relationships between diminished platelet survival and clinical features (including vasculitis), the presence of circulating immune complexes (as measured by both a monoclonal rheumatoid factor and the Raji cell assays), the presence of intravascular coagulopathy with fibrinolysis (as measured by the protamine gel test), other laboratory variables commonly obtained in rheumatoid patients, or various drug regimens.

Polyarteritis.

Polyarteritis is reviewed in detail including a discussion of the cause of arteritis and the effect on blood vessel physiology. The clinical feature of polyarteritis and an approach to the diagnosis are discussed. The controversies in the management of polyarteritis are reviewed, and new approaches to the management are introduced.

Vasculitis associated with rheumatoid arthritis.

Vasculitis may accompany rheumatoid arthritis. One must distinguish between vascular involvement associated with the pathogenesis of rheumatoid arthritis, isolated digital vasculitis, and the syndrome of clinical rheumatoid vasculitis. The cause of clinical rheumatoid vasculitis is unknown. High titers of rheumatoid factor, cryoglobulins, diminished circulating complement, an increased prevalence of HLA-DR4, and the pathologic findings suggest an immune etiology. However, similar, but perhaps less pronounced, abnormalities occur in uncomplicated rheumatoid arthritis, and these findings are not universal in complicating vasculitis. Classic cutaneous clinical manifestations include ischemic ulcers, digital gangrene, and palpable purpura. Mononeuritis multiplex is another classic presentation of rheumatoid vasculitis. Small digital infarctions may accompany other manifestations in clinical vasculitis or may occur alone as isolated digital arteritis, in which case the prognosis is relatively favorable. Weight loss, pleuritis, pericarditis, ocular inflammation, splenomegaly, hepatomegaly, and Felty's syndrome have also been reported in association with rheumatoid vasculitis. Although renal involvement has been considered unusual in rheumatoid vasculitis, several studies suggest that this may be more common than previously recognized. Ideally, a biopsy or an angiogram confirms the diagnosis of rheumatoid vasculitis, but often the diagnosis rests upon the clinical picture. In general, blind biopsies are not helpful, although one series indicated that a blind rectal biopsy may be an exception to this rule. An elevated erythrocyte sedimentation rate, increased C-reactive protein level, anemia, thrombocytosis, hypoalbuminemia, and a positive rheumatoid factor are common laboratory findings. Leukocytosis, hypergammaglobinemia, leukocytopenia, an elevated creatinine level, and minimal abnormalities of the urinary sediment also occur in patients with rheumatoid vasculitis. However, these abnormalities overlap in patients with uncomplicated rheumatoid arthritis, and their role in distinguishing rheumatoid vasculitis from uncomplicated rheumatoid arthritis is limited. Other immunologic tests have no established clinical role in diagnosing rheumatoid vasculitis. Therapy depends upon the clinical manifestation of rheumatoid vasculitis. Uncomplicated rheumatoid arthritis deserves appropriate therapy, and general attention to nutrition, cessation of tobacco, and control of blood pressure are indicated for all patients. Isolated digital vasculitis generally requires no more than the usual treatment for uncomplicated rheumatoid arthritis. Appropriate dermatologic management is indicated for ischemic ulcers. Most clinical experience in managing more symptomatic rheumatoid vasculitis has focused on glucocorticosteroids, D-penicillamine, and cytotoxic immunosuppressive drugs.(ABSTRACT TRUNCATED AT 400 WORDS)

Resolved: Low-dose prednisone is indicated as a standard treatment in patients with rheumatoid arthritis.

It is known and has been repeatedly demonstrated that low doses of prednisone or prednisolone (10 mg daily or 5 mg bid) will control most of the inflammatory features of early polyarticular rheumatoid arthritis (Table 2). Also, low doses of prednisolone are known to retard the bony damage of rheumatoid arthritis, and thus these are the original disease-modifying antirheumatic drugs. Glucocorticoids are potent antiinflammatory and immunosuppressive agents by virtue of their repression of the genomic expression by transcriptional interference, inhibiting such proinflammatory proteins as COX-2, IL-1, IL-2, IL-6, TNFalpha, and adhesion molecules. Nature has produced an ideal antiinflammatory and immunosuppressive agent, namely glucocorticoids, and it is up to us to use it in appropriate situations (e.g., active early inflammatory polyarticular rheumatoid arthritis) and in low doses, frequently daily divided doses. Low doses of glucocorticoids (prednisone or prednisolone) accomplish everything NSAIDs or COX-2 inhibitors accomplish but with more antiinflammatory effects, fewer side effects, and much less expense. It is certainly possible (but not precisely tested) that low doses of prednisone (prednisolone) enhance the effects of other DMARDs, including anti-TNF agents. The side effects of low-dose glucocorticoids are minimal. By using concomitant calcium and vitamin D and monitoring bone status with DEXA scans, the osteopenia potential of low doses of prednisone will be minimal. The use of low-dose prednisone without NSAIDs will put the patient at very little risk for stomach ulceration and bleeding.