Human immunodeficiency virus associated spondyloarthropathy: lessons from the Third World.
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Africa↗
Biomedical subjects
M L Cuéllar
Publications and source records attributed to M L Cuéllar.
Use of antipolymer antibody assay in recipients of silicone breast implants.
BACKGROUND: Local complications (encapsulation, rashes, rupture, and leakage) can occur after placement of silicone gel-containing breast implants (SBI). Whether SBI exposure results in systemic manifestations in some recipients is controversial. We have carried out a blinded study to assess whether there is any difference between SBI recipients and non-exposed controls in the proportions positive for serum antibodies directed against polymeric substances. METHODS: We recruited female SBI recipients (including those without symptoms) who presented to a single rheumatology clinic. A physician global assessment was used to classify SBI recipients who did not meet criteria for specific autoimmune diseases according to the severity of local and systemic signs and symptoms. Controls were recruited from among clinic staff and their acquaintances. Results of the antipolymer antibody (APA) assay were compared with those of an assay for antinuclear antibodies (ANA) and with the severity of the signs and symptoms. FINDINGS: Positive APA results were found in one (3%) of 34 SBI recipients with limited symptoms, two (8%) of 26 with mild symptoms, seven (44%) of 16 with moderate symptoms, and 13 (68%) of 19 with advanced symptoms. Four (17%) of 23 healthy non-SBI-exposed controls and two (10%) of 20 non-exposed women with classic autoimmune diseases were positive for APA. Thus, women with moderate or advanced symptoms were significantly more likely than those with limited or mild symptoms, or non-exposed controls to have APA (p < 0.001). The proportion with positive ANA results was higher for women with classic autoimmune diseases 14 (70%) of 20 than for any SBI-exposed subgroup (0-33%). INTERPRETATION: The APA assay can objectively contribute to distinguishing between SBI recipients with limited or mild signs and symptoms. SBI recipients with more severe manifestations, and patients with specific autoimmune diseases. Further studies will be needed to define the signs and symptoms associated with exposure to SBI.
Adult↗
Pancytopenia secondary to methotrexate therapy in rheumatoid arthritis.
OBJECTIVE: To assess the frequency of methotrexate (MTX)-induced pancytopenia in rheumatoid arthritis (RA). METHODS: A MEDLINE literature search was conducted to identify articles published during the last 15 years (1980-1995) that presented data on MTX-associated pancytopenia. Two case reports of our own experience are also presented. In addition, articles that examined risk factors associated with MTX-related pancytopenia were identified. RESULTS: A total of 70 patients with pancytopenia related to MTX therapy were identified (68 reported in the literature, 2 from our own experience). Sixty-one of the patients were described in published case reports, 7 patients were from 5 long-term prospective studies. In many of these cases, predisposing factors for the development of pancytopenia were described. The 5 long-term prospective studies reported toxicity data on patients who had been treated with MTX for at least 13 weeks. A total of 511 patients were included in the prospective trials, yielding an overall incidence of pancytopenia of 1.4% (7 of 511). Of the 70 cases reported, 12 patients died (17%). Most of them had impaired renal function, hypoalbuminemia, concurrent infection, and/or concomitant medication with more than 5 drugs. The minimal cumulative MTX dose leading to fatal pancytopenia was 10 mg, observed in one of our patients. CONCLUSION: Pancytopenia is not an uncommon side effect of low-dose pulse MTX therapy in RA. It can lead to serious complications, including death.
Administration, Oral↗
Prolactin-induced immunoglobulin and autoantibody production by peripheral blood mononuclear cells from systemic lupus erythematosus and normal individuals.
Prolactin (PRL) has been shown to have immunoregulatory effects on a variety of immune responses. Its effect on B cell immune responses is suggested by in vitro data demonstrating a direct effect on B cell activation and differentiation, and also in vivo data demonstrating a biphasic stimulation of antibody production to sheep red blood cells. In addition, it has been shown both in animal models and patients with hyperprolactinemia that PRL may influence the presence of certain autoantibodies. The objective of this work was to study the effect of PRL on the induction of immunoglobulins, and anti-DNA and rheumatoid factor (RF) autoantibody production from peripheral blood mononuclear cells (PBMCs) from normal individuals and systemic lupus erythematosus (SLE) patients. Six female SLE patients and 10 normal individuals (5 females and 5 males) were studied. Ficoll-Hypaque-isolated PBMCs (1x10(6) cells/ml) with high concentrations of PRL (10(-4)-10(-8)M) and pokeweed mitogen (PWM) diluted to 1:400. An ELISA assay was used for immunoglobulins, RF and anti-dsDNA antibodies. PRL stimulated IgG and IgM production in a biphasic manner in normal PBMCs. Enhanced synthesis was observed at 10(-6) M, and a stimulatory effect was again observed at higher doses of PRL (10(-4))M. In contrast, only a mild stimulatory effect was observed in IgG synthesis by SLE PBMCs. These changes in Ig synthesis, however, did not reach statistical significance. PRL also induced IgG and IgM anti-dsDNA antibodies by both normal and SLE lymphocytes, but no differences were observed when compared to PWM stimulation. PRL induced IgM RF synthesis by normal lymphocytes but had no effect on SLE PBMCs. This study demonstrates that PRL induced immunoglobulin synthesis by normal and to a lesser degree by SLE lymphocytes, and also induced anti-dsDNA antibody by normal and SLE PBMCs, and IgM RF by normal PBMCs. However, the exact mechanism(s) of PRL action on the immune response awaits elucidation.
Adult↗
Prolactin and systemic lupus erythematosus: prolactin secretion by SLE lymphocytes and proliferative (autocrine) activity.
Accumulated evidence suggests that prolactin (PRL) is an important immunoregulator and might have a role in the pathogenesis of systemic lupus erythematosus (SLE). Moreover, a PRL-like molecule is secreted by normal human lymphocytes and acts as an autocrine growth factor for lymphoproliferation. The objective of this study was to explore the PRL-like peptide production by peripheral blood mononuclear cells (PBMC) from patients with SLE. We investigated the PRL secretion by PBMC from six female SLE patients and nine normal subjects (5 women and 4 men). Ficoll-Hypaque isolated PBMC (1 x 10(6) cells/ml) were cultured with and without maximal stimulatory doses of PHA (1 mg/ml) or PWM (1/200). At 72 h of culture supernatants were harvested and used to determine PRL immunoreactivity by a radioimmunoassay (NIDDK-reagents). Cell extracts and concentrated supernatants were prepared to determine PRL by Western blot analysis (NIDDK-reagents). SLE non-stimulated PBMC secreted significantly higher levels of PRL than normal non-stimulated PBMC (8.09 +/- 4.15 ng/ml vs. 3.48 +/- 2.36 ng/ml, P = 0.02 by Mann-Whitney test). High levels of PRL were secreted by SLE-PHA stimulated PBMC (6.88 +/- 4.53 ng/ml) and SLE-PWM stimulated PBMC (16.57 +/- 16.39 ng/ml) compared with normal-PHA stimulated PBMC (5.83 +/- 5.27 ng/ml) and normal-PWM stimulated PBMC (8.54 +/- 5.49 ng/ml), respectively, but the differences were not significant. The maximal production of PRL was found in PWM-stimulated lymphocytes in both groups. Cells extracts prepared from SLE non-stimulated and stimulated PBMC contained a 11 KDa PRL immunoreactive material. Concentrated supernatants from SLE non-stimulated and stimulated PBMC contained both a 11 KDa and a 24-27 KDa PRL immunoreactive material. Our data indicate that PBMC from patients with SLE have an increased production of PRL-like immunoreactive material. This PRL is released in vitro as two different molecular weight forms, and appears to be derived from B rather than T lymphocytes.
Adult↗
Cryoglobulinemia and other dysproteinemias, familial Mediterranean fever, and POEMS syndrome.
The introduction of newer technology in the past few years, especially the use of second-generation enzyme-linked immunosorbent assays, recombinant immunoblot assays, reverse transcriptase, and DNA amplification, have clearly defined the role of hepatitis C virus as the most important etiologic factor in the development of mixed cryoglobulinemia. This has led to a better understanding of the pathogenic mechanisms involved in disease expression, particularly vasculitis, and also has provided a rationale for the use of interferon alfa and other antiviral drugs in the therapy of these disorders. The clinical manifestations of the syndrome also have been well characterized, as well as some of the risk factors. There also has been an improvement in our understanding of the pathogenic mechanisms involved in multiple myeloma and related monoclonal gammopathies, as well as several attempts to improve early recognition of bone disease with magnetic resonance imaging. The susceptibility gene for familial Mediterranean fever has been better characterized, as have risk factors for colchicine toxicity. The role of cytokines has been better delineated for both monoclonal gammopathies and POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome.
Blood Protein Disorders↗
Serum antinuclear antibodies in women with silicone breast implants.
OBJECTIVE: Recent evidence suggests that immunologic abnormalities are not uncommon in individuals with silicone breast implants. The purpose of our study was to evaluate in a consecutive manner, the prevalence of autoimmunity as assessed by the presence of antinuclear antibodies in a larger number of patients with silicone breast implants. METHODS: Antinuclear antibody (ANA) testing using an indirect immunofluorescence technique was performed on 813 individuals with silicone breast implants. All subjects except for 3 transsexual males, were female. The overwhelming majority, over 99%, were white. The average age of the subjects was 46.2, with a range of 17 to 72 years. RESULTS: ANA positivity was found in 244 of 813 individuals (30%) using a mouse kidney substrate; and in 470 of 813 (57.8%) using a HEp-2 cell line. The most common immunofluorescent pattern found using HEp-2 was speckled, present in 341 (72.5%) individuals, followed by homogeneous pattern in 113 (24%), nucleolar in 63 (13.4%), and 5 (1.06%) were anticentromere. Anti-dsDNA antibodies measured by an ELISA assay were found in 6 of 71 patients (8%). Rheumatoid factor and C-reactive protein were found above healthy controls in less than 10% of cases studied. The high prevalence of ANA found in patients with silicone breast implants agrees with similar observations by others. The finding of anticentromere and nucleolar patterns has great interest and relevance. These fairly distinct ANA patterns are most commonly seen in the idiopathic form of scleroderma and related conditions. CONCLUSION: These findings suggest that ANA positivity is relatively common in individuals with silicone breast implants, and may support the existence of autoimmune mechanisms in the pathogenesis of the clinical manifestations seen in this population.
Adolescent↗
Coexistence of human immunodeficiency virus infection and systemic lupus erythematosus.
A variety of rheumatic disorders has been reported during the course of human immunodeficiency virus (HIV) infection; however, its association with systemic lupus erythematosus (SLE) is extremely rare. The effect of HIV infection on CD4 lymphocytes may ameliorate SLE activity and spur remission. We observed 2 patients with SLE who later developed HIV infection. Both patients' lupus went into remission, and their course was complicated by aseptic necrosis of the bone. These findings suggest that HIV infection may have an important effect on the natural course of SLE and may also have a pathogenic role in avascular necrosis.
Adult↗
Poststreptococcal reactive arthritis, clinical course, and outcome in 6 adult patients.
OBJECTIVE: To analyze the clinical course and laboratory features, as well as the outcome of 6 adult patients with articular manifestations, and evidence of streptococcal infection. METHODS: A retrospective review was performed of all patients seen in a rheumatology clinic at Louisiana State University Medical Center, with a diagnosis of poststreptococcal reactive arthritis (PSReA) to summarize the clinical features, laboratory findings, and clinical outcome between July 1991 and August 1994. RESULTS: Six patients were identified with PSReA. All had acute, severe inflammatory articular involvement that began shortly after a sore throat, with serological evidence of streptococcal infection, and accompanied by extraarticular clinical manifestations including glomerulonephritis and vasculitis, and poor response to aspirin and other nonsteroidal antiinflammatory drugs. In all cases the echocardiogram was negative, and on followup there was no evidence of cardiac involvement. In these patients antibiotic prophylaxis was not required. CONCLUSION: The clinical picture and serologic abnormalities exhibited by this group of patients suggest a diagnosis of PSReA rather than acute rheumatic fever. These cases also emphasize the resurgence of poststreptococcal infection related articular manifestations in our clinic population.
Adult↗
Treatment of psoriatic arthritis.
The treatment of psoriatic arthritis has acquired relevance in the past few years because of advances and better understanding of the pathogenetic mechanisms implicated in the disease, and also because of recognition that this disorder is not a benign disease as was previously thought. The general principles of management for any inflammatory arthritis, including pharmacological, surgical and rehabilitative treatment, are to be used, with concomitant therapeutic management of skin involvement. Non-steroidal anti-inflammatory drugs constitute the mainstay of pharmacological therapy for most patients, with a good clinical response observed in 75-85%. Early use of remittive agents, especially methotrexate, is indicated in patients with a poor response to NSAIDs or those with polyarticular and progressive joint involvement. Patients who are refractory to conventional therapy should be considered for newer and potentially more toxic therapeutic modalities such as cyclosporin A and retinoids.
Arthritis, Psoriatic↗
Recent developments in psoriatic arthritis.
Psoriatic arthritis affects 5% to 7% of patients with psoriasis. Genetic, immunologic, and environmental factors play a role in its pathogenesis. The role of inflammatory cytokines has been better defined, and recent immunohistochemical studies of the synovial membranes have shown important differences and similarities between psoriatic arthritis and rheumatoid arthritis. The association of psoriatic arthritis with infection, particularly HIV, remains an interesting observation. The most common clinical presentation appears to be peripheral polyarticular, and extra-articular manifestations including the SAPHO (synovitis, acne, pustulosis, hypertosis, and osteitis) syndrome are not common. Methotrexate and sulfasalazine therapy are effective in patients who do not respond to nonsteroidal anti-inflammatory drugs.
Arthritis, Psoriatic↗
Silicone breast implants and connective tissue disease.
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Adult↗
Hyperprolactinemia in Reiter's syndrome.
OBJECTIVE: Accumulated evidence suggests that certain immunoregulatory hormones including prolactin (PRL) may play a role in the pathogenesis and disease expression of certain autoimmune diseases. Our objective was to investigate the possible role of PRL in the pathogenesis and disease expression of the spondyloarthropathies, including Reiter's syndrome (RS). METHODS: Basal levels of PRL (serum) were determined by radioimmunoassay in patients with various types of spondyloarthropathies, patients with acute anterior uveitis (AAU), and healthy controls. Clinical manifestations at the time of serum collection were correlated with PRL levels. RESULTS: Hyperprolactinemia (PRL > 20 ng/ml) was found in 9 of 25 (36%) patients with RS. In contrast, only 1 of 34 (2.9%) (p < 0.001) patients with ankylosing spondylitis and none of the patients with psoriatic arthritis, AAU or healthy controls had hyperprolactinemia. The frequency of conjunctivitis, urethritis, dysentery, and uveitis was higher in hyper than in normoprolactinemic patients with RS. CONCLUSION: Our results suggest a possible role for this immunoregulatory hormone in the pathogenesis and disease expression of RS.
Acute Disease↗
Fibroblast function in psoriatic arthritis. I. Alteration of cell kinetics and growth factor responses.
OBJECTIVE: To explore the potential role of fibroblasts in the pathogenesis of psoriasis and its related arthritis. Specifically, we analyzed the cell cycle of psoriatic fibroblasts obtained from skin and synovium by flow cytometry, and we also studied their response to several growth factors. METHODS: Fibroblast cultures were established from normal and psoriatic skin, uninvolved and involved, and synovium. NIH-3T3 cells were also used as indicator cells in some of the experiments. Fibroblasts DNA cell cycle analysis was performed by flow cytometry, and the data was analyzed by using the "Cytologic DNA applications software version 2." In addition, fibroblasts were stimulated with growth factors including epidermal growth factor, transforming growth factor-beta, and platelet derived growth factor. RESULTS: A significant increase of S and G2-M phase values in confluent cultures of psoriatic fibroblasts in both skin and synovium compared to normal fibroblasts was found. Psoriatic fibroblasts also exhibited a greater proliferative response to growth factors compared to normal fibroblasts. CONCLUSION: Data obtained clearly showed a significant intrinsic in vitro alteration in skin and synovium fibroblasts from patients with psoriasis.
3T3 Cells↗
Fibroblast function in psoriatic arthritis. II. Increased expression of beta platelet derived growth factor receptors and increased production of growth factor and cytokines.
OBJECTIVE: The main objective was to investigate the expression of platelet derived growth factor (PDGF) receptors, and production of growth factors and cytokines from psoriatic skin and synovium derived fibroblasts. METHODS: Fibroblast cultures were established from normal and psoriatic skin and synovium. Confluent cultures of fibroblasts were used for a receptor binding assay for PDGF, and then extracts were run on Western blot. The amount of immunoreactive A and B chain peptides present was determined with specific A or B chain antisera. Production of interleukin 1 beta and PDGF-beta was accomplished by neutralization with the use of commercially available antisera. A functional assay was used to measure transforming growth factor-beta (TGF-beta). RESULTS: There was an increased expression of the beta PDGF receptor in the psoriatic fibroblasts. Interleukin 1 beta and PDGF-beta production by psoriatic fibroblasts was also increased. However, TGF-beta production was similar in normal and psoriatic fibroblasts. CONCLUSION: Our data demonstrate an increased expression of beta PDGF receptor, and production of IL-1 beta and PDGF by psoriatic fibroblasts. The findings provide further support for an active role of this cell line in the pathogenesis of psoriasis and psoriatic arthritis.
Adult↗
Chlamydia-induced reactive arthritis.
Chlamydia trachomatis infection is now recognized as the most prevalent veneral disease in the Western World. The majority of cases of Reiter's syndrome, one type of reactive arthritis, are secondary to sexually transmitted infections. Evidence of urogenital C. trachomatis infection is found in 36% to 61% of cases of Reiter's syndrome. We investigated the prevalence of infection by this organism in a group of patients with spondyloarthropathies. Positive cultures were obtained in 39.4% of patients with Reiter's syndrome, as well as in 22.2% of patients with psoriatic arthritis and in 20% of patients with ankylosing spondylitis. An important percentage of patients also had positive serum antibodies against C. trachomatis (62.1% of patients with Reiter's syndrome), suggesting presence of infection at some point during the course of the disease. Our findings and those from other authors support the use of long-term antibiotic therapy in patients with reactive arthritis, mainly in those in whom positive culture for C. trachomatis has been obtained as well as in their sex partners.
Adolescent↗
Candida arthritis.
Septic arthritis can be caused by Candida species. Its true incidence is unknown because only a few cases have been reported. Two clinical syndromes have been identified. The first is an isolated monarthritis caused by the direct intra-articular inoculation of fungi that inhabit the skin, by means of an injection, or during surgery. The second is the development of a mono- or polyarthritis as a complication of hematogenously disseminated candidiasis. The optimum treatment of this condition is not yet known, although the combination of medical and surgical treatment seems to be the most convenient therapeutic modality. Amphotericin-B continues to be the drug of choice.
Arthritis, Infectious↗