Elliott L. Semble

Sucralfate treatment of nonsteroidal anti-inflammatory drug-induced gastrointestinal symptoms and mucosal damage

In a randomized, double-blind trial, sucralfate therapy, 1 g four times daily, was compared with placebo in 143 symptomatic patients to assess the treatment of gastrointestinal symptoms and gastric mucosal damage associated with nonsteroidal anti-inflammatory drugs (NSAIDs). All patients followed a fixed regimen of NSAIDs, were assigned to one of two groups based on the presence or absence of gastric erosions at baseline endoscopy, and were then assigned randomly to receive sucralfate or placebo for four weeks. Patients were then followed for up to six months while receiving open-label sucralfate 1 g twice daily to up to 1 g four times daily. After four weeks of double-blind therapy, patients taking either nonsalicylate NSAIDs or long half-life NSAIDs and who were treated with sucralfate experienced a significant reduction in both peptic symptom frequency and intensity (p less than 0.03) as compared with patients receiving placebo. Sucralfate-treated patients with baseline endoscopic lesions showed a significant reduction in lesion scores (p less than 0.005) at four weeks as compared with baseline, whereas no improvement was observed in gastric mucosal lesions of patients given placebo. Long-term sucralfate therapy resulted in continued improvement in gastrointestinal symptoms and gastric lesion scores in patients receiving all types of NSAIDs. The results indicate that sucralfate used in conjunction with NSAIDs may allow patients to continue therapy by relieving gastrointestinal symptoms and mucosal damage associated with NSAID therapy.

Therapeutic exercise for rheumatoid arthritis and osteoarthritis

Therapeutic exercise in rheumatoid arthritis and osteoarthritis may be useful in improving aerobic capacity, strengthening muscles, improving endurance and increasing flexibility. This article reviews the major studies of exercise in these conditions and summarizes the authors recommendations regarding the use of therapeutic exercise in the treatment of rheumatoid arthritis osteoarthritis.

Rheumatoid papules: Lesions showing features of vasculitis and palisading granuloma

Whether palisading granuloma formation occurs with leukocytoclastic vasculitis in rheumatoid nodules and in histopathologically similar conditions is debatable. Patients with high titers for rheumatoid factor and severe erosive rheumatoid arthritis are at risk for both rheumatoid vasculitis and rheumatoid nodules. A patient with all of these features developed a papular eruption. These papules showed clinicopathologic features both of leukocytoclastic vasculitis and of early palisading granuloma. Lesions resolved slowly with low-dose oral corticosteroid therapy. It is proposed that these lesions be called rheumatoid papules and that they may represent a link between vasculitis and the palisaded granulomatous reaction seen in rheumatoid nodules.

Antiinflammatory Drugs and Gastric Mucosal Damage

N ONSTEROIDAL antiinflammatory drugs (NSAIDs) are among the most often used medications in the United States and throughout the world. Fifteen to 20 billion aspirin tablets are consumed each year in the United States.’ Prescriptions for nonsalicylate NSAIDs represented over 4% of the total prescription market in 1983, with consumers spending over a billion dollars for these medications.’ Approximately 3% of the United States population requires treatment for a rheumatic disorder, and NSAIDs are prescribed in most types of noninfectious arthritis.3,4 NSAIDs may cause gastrointestinal (GI) symptoms, erosions and/or ulcers, and upper GI tract bleeding. Therefore, gastric mucosal damage resulting from NSAID use is potentially a major health problem. Corticosteroids are used in a wide variety of medical conditions, including rheumatoid arthritis (RA), bronchial asthma, allergic disorders, and dermatologic diseases. The relationship of corticosteroids to gastric mucosal damage is controversial. Corticosteroids may increase the incidence of peptic ulcer disease and GI hemorrhage’ and potentiate gastric mucosal injury when used in combination with NSAIDs such as aspirin.6*7 This review is divided into two sections. The first part surveys data regarding NSAID induced gastric mucosal injury, and the second portion discusses the role of corticosteroids in causing gastric mucosal damage.

Rheumatoid arthritis: New approaches for its evaluation and management

Rheumatoid arthritis is a chronic, progressive disease with a long-term outcome characterized by significant morbidity, loss of functional capacity, and increased mortality. The cornerstone of therapy includes the appropriate melding of pharmacological, rehabilitative, and surgical treatments. New developments in the care of patients with rheumatoid arthritis have focused on aggressive pharmacological therapy early in the course of the illness, ongoing assessment of disease activity and patient function, and a better understanding of the role of rehabilitative techniques such as therapeutic exercise and behavioral approaches to education. This article synthesizes information from studies on recent advances in the management of rheumatoid arthritis outlining diagnosis and assessment, disability issues, outcome studies, current status of traditional and experimental pharmacological therapies, and new strategies of nonpharmacological treatments aimed at the clinician challenged by this fascinating disorder.

Oral lesions in systemic lupus erythematosus: Do ulcerative lesions represent a necrotizing vasculitis?

BACKGROUND It has been suggested that oral lesions in patients with systemic lupus erythematosus (SLE) may be grouped clinically as erythema, discoid lesions, or oral ulcerations. Oral ulcerations have been said to foretell a severe systemic disease flare and the proposal that oral ulcers represent a mucosal vasculitis has been suggested to explain this hypothesis. OBJECTIVE Our objective was to test the hypothesis that oral ulcers in patients with SLE result from vasculitis. METHODS We studied 10 patients with American College of Rheumatology (ACR) criteria for a diagnosis of SLE who had oral lesions of lupus (six prospectively and four retrospectively) clinically and by routine and immunofluorescence microscopy. Biopsy specimens were reviewed in a single-blinded fashion. RESULTS In our patients, no oral lesion, regardless of morphology, demonstrated vasculitis histologically. All lesions demonstrated an interface mucositis. CONCLUSION Our data strongly contradict the hypothesis that leukocytoclastic vasculitis explains a possible unproven correlation between oral ulceration and disease flares in patients with SLE.

Human parvovirus B19 arthropathy in two adults after contact with childhood erythema infectiosum

An arthropathy has been recently described in association with human parvovirus infection (HPV-B19). Human parvovirus B19 has also been implicated as the etiologic agent in erythema infectiosum, a childhood exanthem that may occur in adults in association with joint manifestations. In this study, two adults are described, in whom an acute arthropathy and rash developed after contact with children with erythema infectiosum.

Prostaglandins in the gut and their relationship to non-steroidal anti-inflammatory drugs.

Prostaglandins are long-chain, saturated, oxygenated fatty acids. Relatively large quantities of prostaglandins have been found in gut mucosa, suggesting that these substances play an important role in gastrointestinal physiology. Non-steroidal anti-inflammatory drugs (NSAIDs) cause damage to the gastric, intestinal, and colonic mucosa in experimental animals and in humans. Prostaglandins protect the gastric mucosa against injury induced by NSAIDs, and this property has been labelled cytoprotection. The mechanisms of cytoprotection have been extensively evaluated and are probably multifactorial, including effects on the gastric mucosal barrier, gastric blood flow, mucus, bicarbonate, and fluid section, ionic transport, cyclic AMP, and surface-active phospholipids. Prostaglandins may also prevent NSAID-induced injury in the small intestine and colon. The mechanisms responsible for prostaglandin protection in the lower gut against injurious agents are unknown. Further studies of the role of prostaglandins in the gut and their relationship to the effects of NSAIDs are needed. The results of these investigations may lead to a better understanding of the importance of prostaglandins in the physiology of the gastrointestinal tract, and may provide information regarding actions of NSAIDs on the functional integrity of the gastric, intestinal, and colonic mucosa.

Antirheumatic Drug Effects on Neutrophil Response to Chemotactic Factors: A Comparison of Analytical Techniques

Abstract A recently reported technique employing the leukotactic index which represents all migrating cells in in vitro neutrophil chemotaxis systems, was compared to the leading front technique for assaying antirheumatic drug effects on this important neutrophil function. Normal human neutrophils were treated with therapeutic concentrations of aspirin, gold sodium thio-malate, D-penicillamine, and azathioprine. The responses of these cells and of control cells to neutrophil-immune complex-serum-derived chemotactic factors were assayed in Boyden chambers. Significant (P < 0.05) inhibition was observed by the leading front technique only for D-penicillamine at high concentrations. Significant (P < 0.01) inhibition was seen with D-penicillamine at therapeutic plasma levels with the leukotactic index technique. Gold sodium thiomalate and aspirin at high concentrations also produced significant (P < 0.01 and P < 0.05) inhibition of chemotaxis as assayed by the leukotactic index procedure. Azathioprine had no significant effects when studied with either technique. These results indicate that the leukotactic index may be a more sensitive technique for quantitating neutrophil migration in response to chemotactic factors and may therefore provide useful additional information for determining the effects of antirheumatic drugs on this important neutrophil function.

Vasculitis. A practical approach to management.

Vasculitis encompasses a wide variety of diseases. Because diagnosis may be difficult, a careful evaluation is essential, including a detailed patient history, thorough physical examination, and appropriate laboratory studies. Diagnosis is based on clinicopathologic features that permit identification of the condition. Biopsies are often necessary to confirm a diagnosis. It is important to accurately categorize the vasculitic disorders, since prompt, aggressive therapy with potentially toxic drugs is necessary to avoid irreversible organ system dysfunction.