Frank B. Vasey

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 Reiters 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 Reiters 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 Reiters syndrome or other form of spondyloarthropathy should be tested for HIV.

A Safety Assessment of Tumor Necrosis Factor Antagonists During Pregnancy : A Review of the Food and Drug Administration Database

Objective. To present any congenital anomalies with respect to tumor necrosis factor (TNF) antagonists reported to the US Food and Drug Administration (FDA) to determine if there are common findings. Methods. A review of the FDA database of reported adverse events with etanercept, infliximab, and adalimumab from 1999 through December of 2005 was performed. Key words for congenital anomalies were employed as search tools. Duplicate reports were eliminated. Any concomitant medicines were recorded. Results. Our review of > 120,000 adverse events revealed a total of 61 congenital anomalies in 41 children born to mothers taking a TNF antagonist. Of these mothers, 22 took etanercept and 19 took infliximab. There were no reports in women taking adalimumab. The most common reported congenital anomaly was some form of heart defect. Twenty-four of the 41 (59%) children had one or more congenital anomalies that are part of vertebral abnormalities, anal atresia, cardiac defect, tracheoesophageal, renal, and limp abnormalities (VACTERL) association. There were 34 specific types of congenital anomalies in total, and 19 (56%) of those are part of the VACTERL spectrum. Nine of these 19 (47%) types of VACTERL anomalies were observed statistically significantly more than historical controls (p < 0.01); in 4 of these 9 the p value was ≤ 0.0001. Thirteen (32%) of the children had more than one congenital anomaly; 7 of these 13 children had 2 defects that are part of the VACTERL spectrum. However, only 1 child was diagnosed with VACTERL. In 24/41 cases (59%) the mother was taking no other concomitant medications. Conclusion. A seemingly high number of congenital anomalies that are part of the VACTERL spectrum have been reported. These congenital anomalies are occurring at a rate higher than historical controls. This commonality raises concerns of a possible causative effect of the TNF antagonists.

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.

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.

Chlamydiae as etiologic agents in chronic undifferentiated spondylarthritis.

OBJECTIVE The majority of patients with Chlamydia-induced reactive arthritis do not present with the classic triad of arthritis, conjunctivitis/iritis, and urethritis. Moreover, acute chlamydial infections are often asymptomatic. The aim of the present study was to assess the prevalence of synovial Chlamydia trachomatis and Chlamydia pneumoniae infections in patients with chronic undifferentiated spondylarthritis (uSpA). METHODS Study patients met the European Spondylarthropathy Study Group criteria for SpA, without evidence of ankylosing spondylitis, psoriasis, inflammatory bowel disease, or preceding dysentery. Symptoms were present for >or=6 months. Each patient underwent a synovial biopsy; tissue and concomitantly obtained peripheral blood mononuclear cells (PBMCs) were analyzed by polymerase chain reaction (PCR) for C trachomatis and C pneumoniae DNA. Other data collected on the day of the biopsy included standard demographic information and medical history, including any known history of C trachomatis or C pneumoniae. Physical examination (including joint count, evaluation for dactylitis and/or enthesitis, and skin examination) and HLA-B27 typing were performed. Synovial tissue (ST) samples from 167 patients with osteoarthritis (OA) were used as controls. RESULTS Twenty-six patients met the entry criteria and underwent synovial biopsy (25 knee, 1 wrist). Sixteen of them (62%) were positive for C trachomatis and/or C pneumoniae DNA (10 for C trachomatis, 4 for C pneumoniae, and 2 for both). PCR analysis of ST revealed the presence of Chlamydia significantly more frequently in patients with uSpA than in OA controls (P<0.0001). No specific clinical characteristics differentiated Chlamydia-positive from Chlamydia-negative patients. PBMCs from 4 of the 26 uSpA patients (15%) were positive for Chlamydia, and Chlamydia was found in ST from 2 of these 4 patients. No significant correlation between PCR positivity and HLA-B27 positivity was found. CONCLUSION The frequency of Chlamydia-positive ST samples, as determined by PCR, was found to be significantly higher in patients with uSpA than in patients with OA. Our results suggest that in many patients with uSpA, chlamydial infection, which is often occult, may be the cause.

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.

Histocompatibility typing in the seronegative spondyloarthropathies: A survey

T HE FIRST association of a human disease (Hodgkin disease) and increased prevalence of a histocompatibility (HLA) antigen was described by Amiel in 1967.’ Since then, a large number of other diseases have been associated with increased or decreased frequencies of various HLA antigens.2-5 A number of different correlations have emerged; some are detectable at the population level, while some are detectable only at the haplotype level within families. The most significant and reproducible associations, however, have been reported in the seronegative group of rheumatic diseases. HLA-B27 has been shown to be a frequent genetic marker for rheumatic disease characterized by axial (spondylitis) types of arthritis. Ankylosing spondylitis (AS),“” Reiter syndrome (RS),“,‘* psoriatic spondylitis (PsS),“~‘~ and spondylitis associated with inflammatory bowel disease (IBD)15 are all characterized by significant increases in HLA-B27. Recently, we and others’6-‘9 reported a significantly increased prevalence of HLA-Bw38 in patients with peripheral psoriatic arthritis (PsA) in whom the frequency of HLA-B27 was within normal limits. Because HLA-Bw38 is a recently identified antigen, we concluded that it was useful to evaluate in other conditions characterized by seronegative peripheral arthritis. In this study of the association among HLAB27, Bw38, the DR antigens and seronegative arthritis, we evaluated clinically, radiologically, and by means of HLA typing, a large number of patients with seronegative arthritis. We confirmed the significant association of B27 and spinal involvement in the spondyloarthropathies and the association of Bw38 and DRw4 with psoriatic arthritis. Additionally, Bw38 and DRw4 were not found to be elevated in any other form of arthritis. No abnormal elevation and/or depression of a given HLA antigen was observed in patients with seronegative rheumatoid arthritis or osteoarthritis. MATERIALS AND METHODS

Reactive arthritis induced by parasitic infestation.

Arthritis developed in two patients during the course of parasite infestation with Strongyloides stercoralis and Taenia saginata, respectively. The joint involvement was polyarticular and symmetrical but seronegative and nonerosive radiologically. We found evidence of abnormal humoral immunity to the parasites, immune complexes in serum and synovial fluid, and immunoglobulin deposits in the synovia. Nonsteroidal anti-inflammatory agents proved ineffective but specific antiparasitic treatment resulted in resolution of the symptoms and immunologic abnormalities. Our findings provide further documentation of the interaction between the bodys immune system and parasites and suggest that arthritis induced by parasitic infestation may be mediated by immune complex formation in susceptible hosts.

V2 regions of 16S ribosomal RNA used as a molecular marker for the species identification of streptococci in peripheral blood and synovial fluid from patients with psoriatic arthritis

OBJECTIVE To detect the 16S ribosomal RNA (rRNA) of 3 streptococcal species in the peripheral blood and synovial fluid of patients with psoriatic arthritis (PsA). METHODS Reverse transcription-polymerase chain reaction (RT-PCR) detection targets bacterial 16S rRNA, which is present in bacteria at high copy numbers. The 3 species-specific primers for group A streptococci (GAS; Streptococcus pyogenes), group B streptococci (GBS; Streptococcus agalactiae), and Streptococcus pneumoniae were designed from the fragments of highly variable V2 regions of 16S rRNA. Total RNA was prepared from whole peripheral blood and joint fluid obtained from patients with PsA and rheumatoid arthritis (RA). All positive PCR reactions were then sequenced with a Pharmacia ALF DNA sequencing system. RESULTS Our data in 19 PsA patients showed that 7 peripheral blood samples were positive for GAS (P = 0.006 versus GAS-positive RA patients [n = 0], by Fishers exact test), and 2 were also positive for GBS. One synovial fluid sample from a PsA patient was positive for GAS. S pneumoniae was absent from all specimens. Seventeen patients with RA were PCR negative for the 3 streptococcal species. Peripheral blood from a patient with inflammatory bowel disease was positive for GAS. CONCLUSION The presence of GAS 16S rRNA in the peripheral blood and synovial fluid of patients with PsA supports the concept that PsA is a reactive arthritis to certain streptococci.

Cholesterol embolism: A pseudovasculitic syndrome

T HE ORIGINAL description of atheromatous embolism was credited by Panum in 1862, although it has been justly noted that he only described the necropsy of the famous Danish sculptor Thorwaldsen performed two decades earlier by Dahlerup and Fenger.’ Cholesterol embolism remained a pathologic curiosity until the 1960s when its clinical similarity to a multisystern disorder was recognized. One factor that increased the awareness of the entity was Flory’s* demonstration of cholesterol crystals in small arteries of experimental animals after injection of human atheromatous material into their circulation. Despite the various descriptions in the literature, both the failure to recognize this clinical phenomena and the subsequent institution of improper therapy continue to occur and contribute to patient morbidity. Cholesterol microembolism may produce a variety of signs and symptoms resembling a multisystem disorder such as a systemic vasculitis. Laboratory abnormalities contributing to the diagnostic confusion include leukocytosis, eosinophilia, hypocomplementemia, and erythrocyte sedimentation rate (ESR) elevation. Our current series demonstrated the additional finding of antinuclear antibody (ANA) and rheumatoid factor positivity, whose presence should not automatically implicate a systemic vasculitis or connective tissue disease.