Combination antibiotics as a treatment for chronic Chlamydia-induced reactive arthritis: a double-blind, placebo-controlled, prospective trial.

OBJECTIVE: Chlamydia trachomatis and Chlamydophila (Chlamydia) pneumoniae are known triggers of reactive arthritis (ReA) and exist in a persistent metabolically active infection state in the synovium, suggesting that they may be susceptible to antimicrobial agents. The goal of this study was to investigate whether a 6-month course of combination antibiotics is an effective treatment for patients with chronic Chlamydia-induced ReA. METHODS: This study was a 9-month, prospective, double-blind, triple-placebo trial assessing a 6-month course of combination antibiotics as a treatment for Chlamydia-induced ReA. Eligible patients had to be positive for C trachomatis or C pneumoniae by polymerase chain reaction (PCR). Groups received 1) doxycycline and rifampin plus placebo instead of azithromycin; 2) azithromycin and rifampin plus placebo instead of doxycycline; or 3) placebos instead of azithromycin, doxycycline, and rifampin. The primary end point was the number of patients who improved by 20% or more in at least 4 of 6 variables without worsening in any 1 variable in both combination antibiotic groups combined and in the placebo group at month 6 compared with baseline. RESULTS: The primary end point was achieved in 17 of 27 patients (63%) receiving combination antibiotics and in 3 of 15 patients (20%) receiving placebo. Secondary efficacy end points showed similar results. Six of 27 patients (22%) randomized to combination antibiotics believed that their disease went into complete remission during the trial, whereas no patient in the placebo arm achieved remission. Significantly more patients in the active treatment group became negative for C trachomatis or C pneumoniae by PCR at month 6. Adverse events were mild, with no significant differences between the groups. CONCLUSION: These data suggest that a 6-month course of combination antibiotics is an effective treatment for chronic Chlamydia-induced ReA.

Silicone breast implants. History, safety, and potential complications.

The purpose of this study is to review the background, safety, and potential complications of silicone breast implants. Relevant studies were identified using a MEDLINE search of the English-language literature, followed by a manual search of the references of all identified articles and a review of abstracts from the 1992 American College of Rheumatology meeting. Review of the literature suggests that silicone does not appear to fulfill the characteristics of an ideal synthetic soft-tissue substitute, although it may be the best substitute available. Silicone breast implants are associated with local inflammation and tissue fibrosis with breast fibrous capsule contracture developing in 10% to 40% of the patients. There are no epidemiologic data that establish a direct link between silicone and cancer or rheumatic disease. However, scleroderma appears to be overrepresented among the published articles on patients with silicone breast implants and rheumatic disease. Autoantibodies of unclear significance may be found in 5% to 30% of women with silicone breast implants. Large, longitudinal, population-based studies that include patients who have had implants for 5 to 15 years may be necessary to fully understand the relationship of silicone implants and immune dysfunction.

Pancreatic pseudocyst: a complication of necrotizing vaculitis (polyarteritis nodosa).

Pancreatic pseudocyst formation leading to fatal outcome was observed during the active phase of polyarteritis nodosa in a 48-year-old patient. Persistent hepatitis B antigenemia and high levels of circulating immune complexes were present during his illness. Prednisone and azathioprine therapy was not able to control the manifestations of the basic disorder.

Immune complex-mediated renal involvement in relapsing polychondritis.

A patient with relapsing polychondritis who presented with rapidly progressive glomerulonephritis is described. This is the fourth case in which this association is reported. Crescentic glomerulonephritis was found on renal biopsy. Evidence for immunologic participation in the pathogenesis of this condition is suggested by the demonstration of circulating immune complexes, immunoglobulin and complement deposition by immunofluorescence, and electron dense deposits by electron microscopy of the kidney. Favorable response followed therapy with prednisone and dapsone.

Rheumatic manifestations of human immunodeficiency virus infection.

PURPOSE: The prevalence and characteristics of the rheumatic and extra-rheumatic manifestations of human immunodeficiency virus (HIV) infection were determined in a prospective manner. PATIENTS AND METHODS: One hundred one patients with HIV infection were consecutively interviewed and examined. The prevalence of autoantibodies and their association with rheumatologic symptoms were also determined. RESULTS: The musculoskeletal system was involved in 72 patients. Thirty-five patients had arthralgias, 10 had Reiter's syndrome, two had psoriatic arthritis, two had myositis, and one had vasculitis. Also found were two previously unreported syndromes. The first, occurring in 10 patients, consisted of severe intermittent pain involving less than four joints, without evidence of synovitis, of short duration (two to 24 hours), and requiring therapy (ranging from nonsteroidal antiinflammatory drugs to narcotics). The second, occurring in 12 patients, consisted of arthritis (oligoarticular in six patients, monoarticular in three patients, and polyarticular in three patients) involving the lower extremities and lasting from one week to six months. The synovial fluid of five patients (three with arthritis, one with Reiter's syndrome, and one with psoriatic arthritis) was sterile and inflammatory. CONCLUSION: Musculoskeletal complications are common in advanced stages of HIV infection. Persons in a high-risk group for HIV infection who manifest oligoarthritis with or without any other extra-articular manifestation suggestive of Reiter's syndrome or other form of spondyloarthropathy should be tested for HIV.

Controlled evaluation of nabumetone in the treatment of active adult rheumatoid arthritis. Nabumetone versus naproxen double-blind parallel study.

Nabumetone is a new nonsteroidal anti-inflammatory agent. Therapy with nabumetone 1,000 mg given at bedtime was compared with naproxen 250 mg given twice daily in a prospective double-blind study of patients with rheumatoid arthritis. Both drugs were found to be efficacious in a comparable fashion. Both drugs were well tolerated in terms of patient withdrawal rates, which were 5 and 8 percent, respectively. Gastrointestinal side effects were the most commonly encountered problem. Nabumetone holds promise as an important new therapeutic approach in arthritis.

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.

Musculoskeletal syndromes in parasitic diseases.

Parasitic infestation can induce a variety of rheumatic syndromes as a result of infiltration of musculoskeletal structures by parasites or an immune mediated mechanism. Parasite-induced symptoms should be considered when arthritis, enthesitis, myositis, or vasculitis develop in patients residing in endemic areas and in certain subsets of the population of developed countries, for example, migrants, travelers, and immunocompromised individuals. Diagnosis is based on the demonstration of infection with a pathogenic parasite, lack of response to anti-inflammatory agents, and improvement following antiparasitic therapy. Treatment consists of erradication of the parasite.

Vesiculopustular eruption of ulcerative colitis.

Many cutaneous disorders that have been described in association with ulcerative colitis (UC), including certain pustular eruptions, probably represent early, evolving lesions of pyoderma gangrenosum (PG). Several nonspecific, often poorly delineated pustular eruptions apparently unrelated to pyoderma gangrenosum have also been reported to occur with ulcerative colitis. A patient had an evanescent, vesiculopustular eruption with a course paralleling that of his UC. Histologic examination of biopsy material from the skin revealed intraepidermal and subcorneal neutrophilic abscess formation and a mixed dermal, perivascular inflammatory cell infiltrate with notable sparing of the follicles. An IgG deposition in a bandlike pattern was identified at the dermoepidermal junction by direct immunofluorescence microscopy. This vesiculopustular eruption may represent a distinct entity or another case or variant of similar pustular eruptions previously described in association with UC.

Human adjuvant disease following augmentation mammoplasty.

Two patients are described in whom a progressive systemic sclerosis-like illness developed several years after silicone augmentation mammoplasty. Both had removal of breast implants, followed by marked-to-complete recovery from clinical abnormalities. This entity is increasingly recognized and has become known as human adjuvant disease.

Methotrexate: its use in the rheumatic diseases.

Methotrexate in a low dose intermittent regimen has become popular as a therapeutic choice for refractory psoriatic arthritis, polymyositis, Reiter's disease and more recently rheumatoid arthritis. As a folate analogue, it inhibits the formation of reduced folate cofactors which participate in a host of important reactions including DNA synthesis. It has been shown to have both immunosuppressive and anti-inflammatory properties although its precise mechanism of action in these diseases is not known. It may be variably absorbed especially in psoriatics and its action may be antagonized by folate supplements. Its major route of metabolism appears to be via the enterohepatic circulation. Numerous drugs, including salicylates, may increase serum levels by displacing the drug from protein binding sites and by competing for renal excretion. It has fewer short term side effects than the other immunosuppressives used in rheumatic disease. Its major long term toxicity is liver fibrosis or cirrhosis which appears to increase with greater cumulative dosage and treatment duration. Several recent reports of hypersensitivity pneumonitis reinforce the previous literature on this topic. Pulmonary toxicity may be more common than suggested as more patients are treated with methotrexate for rheumatic diseases. Clinical studies in general have been uncontrolled and lacking in scope and size. Nevertheless, the literature to date appears to show this to be an excellent drug for use in the diseases mentioned. Prospective double blind controlled studies on psoriatic arthritis and rheumatoid arthritis should help establish this drug as the immunosuppressive of choice in these diseases.

Immunological studies of the arthritis of acne conglobata and hidradenitis suppurativa.

The etiology and pathogenesis of acne arthritis and the arthritis of hidradenitis suppurativa remain unknown. Some patients have an asymmetrical pauciarticular arthritis compatible with the 'reactive' peripheral and central forms of Reiter's syndrome, whereas others have a symmetrical polyarthritis/polyarthralgias syndrome. The cutaneous disease is clinically manifest as acne conglobata or hidradenitis of axilla or groin. We determined human leukocyte antigens (HLA), levels of immunoglobulins, C3, C4 and circulating immune complexes from six patients with acne arthritis. Four of six patients had HLA antigens of B7 Creg group (B7, BW22, B27, BW40, BW42) and all six possessed DRW4. Isolated elevations of immunoglobulins, C3 and C4 were observed. Immune complexes were elevated uniformly. These observations suggest that immunogenetic mechanisms may play a role in the systemic manifestations of these skin diseases.

Hyperprolactinemia in systemic lupus erythematosus: association with disease activity.

This study was designed to determine the prevalence and clinical significance of hyperprolactinemia in systemic lupus erythematosus (SLE) and other rheumatic diseases. Basal levels of prolactin were determined in 130 nonselected sera from patients with rheumatic diseases including 45 with SLE, 31 with rheumatoid arthritis, 23 with osteoarthritis, 18 with fibromyalgia, and 13 with polymyalgia rheumatica. Serum samples of 28 healthy subjects were used as normal controls. Serum prolactin was measured by radioimmunoassay. ANA, anti-DNA, RNP, Sm, Ro, La, and anticardiolipin antibodies were determined by standard techniques. Elevated serum levels of prolactin (PRL greater than 20 ng/ml) were found in a subset of SLE patients. In addition, a direct correlation with clinical disease and serological (ANA) activity was also found. These findings suggest a potential role for this immunoregulatory hormone in SLE pathogenesis.

The major histocompatibility complex.

The major histocompatibility complex on the sixth chromosome controls expression of a complex series of cell surface antigens which comprise the human leukocyte antigen (HLA) system. These markers, beyond their importance in human organ transplantation, have been demonstrated to occur with an increased prevalence in certain disease states. The group of conditions showing the closest association with specific HLA antigens are the "spondyloarthropathies." These include ankylosing spondylitis (AS), Reiter's syndrome (RS), psoriatic arthritis (PsA), and the arthritis of inflammatory bowel disease (AIBD). Clinical and radiographic studies were made of 310 unrelated caucasoid patients with seronegative arthritis. HLA-A, B, C, and DR typing were performed using the microdroplet lymphocyte cytotoxicity test. Statistically increased prevalences of A26, B27, and Bw38 were observed, while B27 was associated with spinal involvement regardless of diagnosis (90 percent in AS p less than 0.0001). Experiments found A26 (23 percent p less than 0.001) and Bw38 (38 percent p less than 0.0001) in patients with PsA. Spondyloarthritis patients with spinal involvement who lacked B27 frequently had B7. The HLA DR typing for seven specificities was carried out in 196 patients. It was found that DRw4 (52 percent p less than 0.03) and DRw7 (39 percent p less than 0.04) were increased in the PsA patients. This study further confirms the close association of HLA antigens and the spondylarthropathies.

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.

Diflorasone diacetate ointment 0.05 percent in conjunction with UVB and tar in a modified outpatient Goeckerman regimen.

Nineteen patients with psoriasis were treated with a modified Goeckerman regimen tailored to enhance patient compliance. Treatment consisted of daily coal tar emulsion baths at bedtime, followed by the application of 0.05 percent diflorasone diacetate ointment. Patients received increasing suberythemal dosages of short ultraviolet radiation (UVB) three times weekly at our outpatient phototherapy center. The duration of therapy ranged from three to twenty-eight weeks. The average number of phototherapy treatments was twenty-nine. Eight patients had total clearing of their lesions. Of the remainder, seven had at least 75 percent clearing and one had less than 25 percent clearing of psoriasis. One patient with psoriatic erythroderma experienced no improvement. Two patients did not complete the study. There were no side effects encountered during treatment other than periodic excessive erythema. If the two patients who did not complete the study are excluded from the results, 88 percent (fifteen of the remaining seventeen) had 75 percent or greater resolution of their psoriatic eruption and 47 percent (eight of seventeen) had total clearing. This outpatient modification of the Goeckerman regimen eliminates the use of cosmetically unacceptable topical agents during working hours, promotes patient compliance, and presumably contributes to enhanced therapeutic efficacy.

A safety analysis of oral prednisone as a pretreatment for rituximab in rheumatoid arthritis.

The administration of 100 mg of methylprednisolone intravenously (IV) 1/2 h prior to rituximab decreases the incidence of acute infusion reactions (AIRs). However, this pretreatment adds considerable time and conveys potential risk. We performed an open-label prospective assessment of oral prednisone as a pretreatment to rituximab. This was a 26-week open-label trial of 40 mg of oral prednisone given 1/2 h prior to rituximab as a prophylaxis against AIRs in patients with rheumatoid arthritis (RA). The primary endpoint was AIRs in the first 24 h after their initial infusion. Secondary endpoints include AIRs during the 24 h following their second infusion and any adverse events experienced during the 26-week study; efficacy measures were also followed as secondary endpoints. Sixty-four subjects were screened, and 50 subjects qualified. Fourteen out of the 50 (28 %) subjects had AIRs within 24 h of their first infusion. There were four AIRs (8.3 %) within 24 h of their second infusion. One of day 0 AIRs required drug discontinuation (wheezing/bronchospasm). Forty out of 50 (80 %) subjects experienced an adverse event during the 26 weeks. There were three SAEs deemed not to be study-drug related. The DAS28 and HAQ-DI all improved significantly at weeks 8, 16, and 26 compared to baseline. Historical controls demonstrate that 27 % of RA subjects experience AIRs with their first rituximab infusion. Our data suggest a smaller dose of oral prednisone is an effective alternative to IV methylprednisolone as a pretreatment for rituximab in patients with RA.