Esophagitis associated with the use of alendronate.

BACKGROUND: Alendronate, an aminobisphosphonate and a selective inhibitor of osteoclast-mediated bone resorption, is used to treat osteoporosis in postmenopausal women and Paget's disease of bone. Aminobiphosphonates can irritate the upper gastrointestinal mucosa. METHODS: We describe three patients who had severe esophagitis shortly after starting to take alendronate and also analyze adverse esophageal effects reported to Merck, the manufacturer, through postmarketing surveillance. RESULTS: As of March 5, 1996, alendronate had been prescribed for an estimated 475,000 patients worldwide, and 1213 reports of adverse effects had been received. A total of 199 patients had adverse effects related to the esophagus; in 51 of these patients (26 percent), including the 3 we describe in case reports, adverse effects were categorized as serious or severe. Thirty-two patients (16 percent) were hospitalized, and two were temporarily disabled. Endoscopic findings generally indicated chemical esophagitis, with erosions or ulcerations and exudative inflammation accompanied by thickening of the esophageal wall. Bleeding was rare, and stomach or duodenal involvement unusual. In patients for whom adequate information was available, esophagitis seemed to be associated with swallowing alendronate with little or no water, lying down during or after ingestion of the tablet, lying down during or after ingestion of the tablet, continuing to take alendronate after the onset of symptoms, and having preexisting esophageal disorders. CONCLUSIONS: Alendronate can cause chemical esophagitis, including severe ulcerations, in some patients. Recommendations to reduce the risk of esophagitis include swallowing alendronate with 180 to 240 ml (6 to 8 oz) of water on arising in the morning, remaining upright for at least 30 minutes after swallowing the tablet and until the first food of the day has been ingested, and discontinuing the drug promptly if esophageal symptoms develop.

Allergen-specific IgE levels and mite allergen exposure in children with acute asthma first seen in an emergency department and in nonasthmatic control subjects.

BACKGROUND: Sensitization to allergens has been shown to be a risk factor for adults with acute asthma first seen in the emergency department. OBJECTIVE: The purpose of this study was to evaluate the prevalence of specific IgE to common aeroallergens in children with asthma first seen in the emergency department and in control subjects. METHODS: Fifty-four children, aged 3 to 16 years (mean age, 8.34 years) who visited the emergency department for treatment of acute bronchospasm or other illness, were evaluated. Specific IgE to seven common aeroallergens and four common storage mites was determined. Group I consisted of 29 patients who had acute bronchospasm and histories of recurrent asthma. Group II consisted of 25 control subjects who had no clinical history of atopic disease. Group I and II were compared for differences in the prevalence of positive RAST responses to the 11 allergens tested. Dust samples were collected from 17 homes of subjects in group I and from 13 homes of subjects in group II and were analyzed for levels of Der p 1 and Der f 1. RESULTS: Statistically significant differences in the prevalence of positive RAST results between groups I and II were found in response to: Dermatophagoides pteronyssinus, 89.6% versus 36% (p = 0.0001); Blattella germanica, 45.8% versus 9.5% (p = 0.018); Alternaria tenuis, 44.8% versus 4% (p = 0.001); and the storage mites Aleuroglyphus ovatus, 39.2% versus 4% (p = 0.002); Blomia tropicalis, 42.8% versus 0% (p = 0.0002); Chortoglyphus arcuatus, 46.4% versus 0% (p = 0.0001); and Lepidoglyphus destructor, 32.1% versus 0% (p = 0.0019). Mean specific IgE levels, expressed as percent of the total counts bound, were significantly higher in group I compared with group II only in response to D. pteronyssinus, 21.9% versus 2.1% (mean percent of total counts bound) (p = 0.0001). Analysis of dust samples revealed no significant differences between the two groups, except for a higher concentration of Der f 1 in the sofas of subjects in group II. CONCLUSION: Sensitization to D. pteronyssinus, storage mites, and, to a lesser extent, to A. tenuis and B. germanica is associated with acute childhood asthma that requires emergency treatment in Florida.

Comparison of oral pulse methotrexate with placebo in the treatment of severe glucocorticosteroid-dependent asthma.

BACKGROUND: This study compared the efficacy of weekly oral administration of methotrexate and placebo in treatment of 24 subjects with chronic glucocorticosteroid-dependent asthma. METHODS: The 33-week randomized, double-blind, placebo-controlled crossover trial compared once weekly 15 mg doses of methotrexate with placebo. At the time of entry, the subjects' mean dosage of prednisone was 23.8 mg/day (range, 12.5 to 85 mg) and glucocorticosteroid therapy had been used continuously for a mean duration of 78 months (range, 5 to 360 months). RESULTS: Of the 21 subjects who completed the study, 13 tolerated lower daily prednisone doses during methotrexate treatment compared with placebo. When treated with methotrexate, subjects required 14.2% less prednisone than when treated with placebo (p = 0.0447), their subjective symptom scores improved 21.4% (p < 0.05), and mean forced expiratory volume in 1 second values tended to improve. Mean serum theophylline levels did not change significantly between the methotrexate and placebo arms of the study. Adverse effects were minimal, with nausea and headache occurring twice as often during methotrexate therapy compared with placebo. CONCLUSION: Short-term, low-dose, pulse therapy with orally administered methotrexate results in a decrease in the daily glucocorticosteroid requirement in a majority of subjects with severe asthma and is accompanied by improvement in subjective symptom scores without unacceptable side effects or deterioration of pulmonary function.

Clinical findings in symptomatic women with silicone breast implants.

We report the clinical findings in a series of women with silicone breast implants (SBI) and rheumatic disease. These findings represent the first 50 patients seen at the University of South Florida Medical Clinic between March 1977 and January 1991. The average age was 44 years with a range of 30 to 66 years. The most common clinical findings included chronic fatigue, muscle pain, joint pain, joint swelling, and lymphadenopathy. Seventeen women with an average Steinbrocker functional class of 1.8 decided not to remove the implants. An average of 14 months later, follow-up showed no change in their condition. Thirty-three women, with an average functional class of 2.5 underwent implant removal. Twelve of the 33 had documented implant rupture. During an average follow-up of 22 months after implant removal, 24 women improved clinically, 8 did not change, and 1 worsened. We believe this series supports a relationship between silicone breast implants and rheumatic disease signs and symptoms. Although this report is not a definitive epidemiological study, findings suggest that physicians should inform women about the possible benefit of implant removal.

Scurvy resembling cutaneous vasculitis.

Various conditions can imitate cutaneous vasculitis. Scurvy is a less appreciated cause of rash that can resemble vasculitis. Three patients were referred to our rheumatology service for "vasculitis," who subsequently were found to have scurvy. Findings included a purpuric skin rash, myalgias, and malaise. The patients had low vitamin C levels and findings on skin biopsy specimens indicative of scurvy. The three patients were on idiosyncratic diets deficient in vitamin C, and the two patients who allowed us to administer vitamin C therapy improved clinically. We emphasize the importance of a careful dietary history. Early recognition of scurvy is important because it can be treated specifically, and toxic treatment of vasculitis can be avoided.

The health status of women following cosmetic surgery.

A retrospective study was performed to determine the frequency of new symptoms and diseases after silicone breast implantation. Questionnaires were mailed to 826 women who made up a breast implant group (n = 516) and a control group who had undergone blepharoplasty (n = 124), liposuction (n = 111), or rhinoplasty (n = 75). Responses were obtained from 370 women (45 percent); however, 68 of these patients (18 percent) were considered ineligible. The overall response rate was 59 percent for the breast implant group and 46 percent for controls. The 302 eligible women included patients with silicone breast implants (n = 222) and controls (n = 80). Women with implants were significantly younger than controls, the median age of women with breast implants being 37 years compared with 46.5 years for controls (p < 0.0001). We compared the incidence of 23 symptoms and 4 connective-tissue diseases after cosmetic surgery in the two groups. The symptoms of swollen glands under arms (p < 0.05) and tender glands under arms (p < 0.01) were statistically more frequent in the breast implant group. The symptom change in skin color was more common in the controls (p < 0.001). The Bonferroni correction for multiple (27) endpoints adjusts the 5 and 1 percent significance cutoff points to 0.00185 and 0.00037, respectively, leaving only change of skin color significant at the 5 percent level on the adjusted data. No cases of scleroderma or lupus were found, and the incidence of arthritis was not significantly different between the implant and control groups.

Tumor markers.

The past decade has seen many advances in the detection, characterization, and clinical applications of tumor markers. Although cancer screening applications have been limited by low disease prevalences in asymptomatic populations, tumor markers may be of diagnostic value in specific situations. The major use of tumor markers in primary care is in monitoring disease recurrence and the response to therapy. These uses may obviate the need for second-look surgery as it has with CA 125 elevations in ovarian carcinoma. On the other hand, tumor markers may indicate a need for second-look surgery as when CEA levels are elevated in colorectal carcinoma. Despite the apparent usefulness of markers in detecting cancer recurrence, the clinician is reminded of the conditions justifying treatment with the discovery of an abnormal laboratory value as put forth by Fries and Holman: (1) the treatment should be known to be effective, (2) early treatment should be known to be more effective than therapy given after the disease is clinically apparent (or early treatment carry the risk of less toxicity), and (3) prediction of impending deterioration must be consistently accurate. When these criteria are met, the planning of therapeutic regimens on the basis of marker levels may be rationally considered. Until these criteria are met, elevated markers can only stimulate the clinician to be more vigilant in the search for response to therapy or recurrence. Exciting developments are on the horizon with respect to the use of tumor markers in radionuclide imaging, radioimmunoguided surgery, and development of drug delivery systems. Further research into the structure and function of these substances may provide further insights into the phenomena of malignant transformation, tumor invasion, metastasis, and the development of new therapeutic options. With new advances in molecular biology and with the identification of oncogenes, it may be possible in the future to detect mutant oncoproteins that are specific for early cancers and premalignant conditions. Delecting these oncoproteins may provide a basis for development of truly sensitive and specific markers that can be used to detect cancer at an early and curable stage.

Prevention of anticardiolipin antibody-related pregnancy losses with prednisone and aspirin.

PURPOSE: Prevention and treatment of pregnancy loss associated with the antiphospholipid syndrome (APS) are controversial. Successful pregnancies have been reported with prednisone and low-dose aspirin in patients with lupus anticoagulant and anticardiolipin antibodies (aCL), but failure has also been reported. The purpose of this prospective study was to define the efficacy of such combination therapy in the prevention of pregnancy loss related to aCL. PATIENTS AND METHODS: Consecutive pregnant patients with a minimum of one pregnancy loss and at least two positive aCL determinations more than 3 months apart, and in whom other causes of pregnancy loss were ruled out, were included in the study. aCL concentrations were determined by enzyme-linked immunosorbent assay before and during therapy. Patients received prednisone, at a dosage of 40 mg/d, for 4 weeks. The dose was then tapered down 10 mg every 4 weeks, and then to a maintenance dose of 5 mg/d. They also received aspirin, 81 mg/d, throughout the pregnancy. Babies were evaluated during the pregnancy by measurement of fetal heart rate and ultrasonography, and after the delivery by measurement of weight and Apgar scores, and, in some cases, by arterial gasometry. RESULTS: Eleven patients with a mean (+/- SD) age of 33.2 +/- 5.01 years were included. Prior to therapy, the rate of live-born babies was 15.6% (32 previous fetal losses and 5 live-born babies), and, after therapy, it was 100% (12 pregnancies and 12 live-born babies). There were no significant adverse effects to either mothers or babies. All the patients had positive aCL determinations. Nine patients had positive IgG aCL. The levels of the antibodies decreased during treatment in these nine patients. IgM aCL determinations were positive in nine patients. The levels of this isotype decreased in eight patients (90%) during treatment. CONCLUSIONS: Treatment with prednisone and aspirin appears to be efficacious, safe, and economic in the prevention of pregnancy loss and fetal growth retardation in patients with aCL.

Respiratory allergies and skin test reactivity in high school students in Tenerife, Canary Islands, Spain.

The prevalence of skin test reactivity to 22 aeroallergens and of allergic respiratory diseases was determined in 501 high school students on the island of Tenerife, Spain. Two hundred seventy-seven students (55.2%) had at least one positive prick skin test (wheal > or = 2 mm). Two hundred sixteen students (43.1%) had symptoms of upper or lower respiratory tract allergies [24 (4.7%) had asthma with or without rhinitis and 192 (38.3%) seasonal or perennial rhinitis alone]. Two hundred eighty-five students (56.8%) were asymptomatic. One hundred per cent of the students with asthma, 87.5% of the students with rhinitis and 27.7% of the asymptomatic students had at least one positive skin test. The prevalence of positive skin tests was significantly higher in symptomatic than in asymptomatic students (p = 0.0001). One hundred seventy students (33.9%) had a family history of respiratory allergic diseases. The prevalence of positive skin tests among these students was significantly higher than in students without such history (p = 0.0001). Thus, there is a high prevalence of allergic respiratory diseases and skin test reactivity to aeroallergens among high school students in Tenerife. Significant correlations were found between family history, positive skin tests and respiratory allergic symptoms.

Aspirin alters methotrexate disposition in rheumatoid arthritis patients.

Intravenous methotrexate (MTX) (10 mg), either alone or with oral aspirin (ASA) (3,900 mg/day), was administered to 15 patients with rheumatoid arthritis. Systemic and renal clearance of MTX were lower, and the unbound fraction of MTX was higher when patients were also receiving ASA than when taking MTX alone. No acute hematologic, renal, or hepatic toxicity was observed with either treatment. The findings of this study therefore indicate that concomitant aspirin therapy acutely alters the clearance of low-dose MTX in patients with rheumatoid arthritis.

Treatment of the eosinophilia-myalgia syndrome.

The eosinophilia-myalgia syndrome (EMS) is a unique entity associated with products that contain L-tryptophan (L-trp). Studies of the underlying etiopathogenic processes are underway. EMS is a distinct syndrome, but shares features with eosinophilic fasciitis and other variants of systemic sclerosis. A wide spectrum of clinical manifestations has been described, but there is no consensus regarding treatment. We report the clinical and laboratory features of 12 patients. All were treated with nonsteroidal antiinflammatory drugs (NSAIDs) and analgesics with transient or minimal effect. Two received D-penicillamine (DP) and colchicine, with minimal improvement; one had no response to azathioprine (AZA). Eleven received corticosteroids and had improvement of general symptoms, arthralgias, arthritis, myalgias, skin changes, eosinophilia, and leukocytosis. Nevertheless, all but the latter two findings recurred when corticosteroids were tapered. Seven patients who were unresponsive to the former treatments received low-dose pulse oral methotrexate. Six exhibited continued improvement after a mean follow-up of 4.5 months, with good drug tolerance. Corticosteroids were tapered and, in some instances, discontinued without relapse or complications. One patient improved but later died of aspiration pneumonia. We conclude that methotrexate (MTX) is a therapeutic alternative for patients with severe or refractory EMS.

Variables associated with decreased survival in systemic lupus erythematosus.

Fifty-one deaths occurred among 310 patients with systemic lupus erythematosus (SLE) observed for 1,234 patient-years. Twenty-one of 97 entry variables at first clinic visit were associated with an increased risk of mortality. When corrected for multiple comparisons, the only risk factor that retained statistical significance was systolic blood pressure. Each millimeter unit increase in systolic blood pressure corresponded to a 2% increase in mortality risk. Stepwise covariance and recursive partitioning analyses tended to identify nonspecific prognostic variables, rather than the classic serological and diagnostic features of SLE. These data suggest that hypertension is a more significant risk factor for mortality in SLE than the more specific measures of disease severity.

Avascular necrosis associated with anticardiolipin antibodies.

The association between antiphospholipid antibodies (aPL) and venous and arterial thromboses has been well described. However the association between aPL and avascular necrosis has not been widely reported. We report the association of avascular necrosis with the primary anticardiolipin antibody syndrome in a patient with a history of hemiplegic migraine and cerebrovascular infarcts. This phenomenon appears to be secondary to hemostatic abnormalities associated with the presence of aPL.