Charcot-like arthropathy: A newly-recognized subset of psoriatic arthritis.

OBJECTIVE: The aim of the study is to describe a group of patients with a highly destructive and asymptomatic form of psoriatic arthritis, mimicking a Charcot-like joint disease. METHODS: We studied 180 patients with psoriatic arthritis and identified 4 patients with arthritis mutilans mimicking a Charcot-like joint disease. Clinical history, physical exam, and immunological testing were performed as well as X-ray of affected joints. Synovial membrane and sural nerve biopsies were performed and diagnosis of psoriasis was confirmed by skin biopsy. RESULTS: Four patients with psoriatic arthritis mutilans according to Moll and Wright classification criteria (1) and Charcot-like joint disease were identified and evaluated. There were 2 males and 2 females, all Caucasians. The mean age +/- SD was 57.8 +/- 14.2 years. Mean arthritis duration +/- SD was 6 +/- 4.6 years and mean cutaneous duration +/- SD was 13 +/- 10.4 years. All patients had polyarthritis and a sudden onset of bilateral, painless, and highly destructive arthropathy involving large, non-weight bearing (elbows) and weight bearing (knees), and also small joint of hands and feet. Synovial membrane biopsy showed findings similar to those found in Charcot joint disease, including ischemic neuropathy. CONCLUSION: A newly-recognized subset of patients with psoriatic arthritis and Charcot-like joint disease according to clinical, radiographic and histological features is described. The proposed neurovascular theory may explain the pathogenesis of this presentation.

Poststreptococcal reactive arthritis in adults: long-term follow-up.

BACKGROUND: Poststreptococcal reactive arthritis (PSReA) is a recognized inflammatory articular syndrome that follows group A streptococcal infection in persons not fulfilling the Jones criteria for the diagnosis of acute rheumatic fever. Characteristic features include nonmigratory arthritis, lack of response to aspirin or nonsteroidal anti-inflammatory agents, and the presence of extra-articular manifestations, including vasculitis and glomerulonephritis. Whether or not patients with PSReA develop carditis is a point of contention. METHODS: We analyzed the clinical features, laboratory findings, response to therapy, and outcome in patients diagnosed with PSReA between 1983 and 1998 and observed through April 2000. All patients were contacted, reexamined, and repeat antistreptolysin, rheumatoid factor, C3 and C4 complement components, and echocardiograms were performed. RESULTS: Seventeen patients (4 men and 13 women) were included. All were of low socioeconomic status. All patients had acute severe arthritis that began shortly after a sore throat episode. Extra-articular involvement including tenosynovitis, vasculitis, and glomerulonephritis was relatively common. More importantly, none exhibited clinical and/or echocardiographic evidence of cardiac involvement. Longterm antibiotic therapy was not given. CONCLUSION: Cardiac involvement did not occur in this group of patients with PSReA. Prolonged prophylactic antibiotic therapy may not be required for adult patients presenting with PSReA.

Laboratory testing in the evaluation and diagnosis of vasculitis.

A multitude of tests are available for the diagnosis and management of the vasculitides. Most of them are nonspecific but provide useful information that, when appropriately used in conjunction with the patient's history and physical examination can be of great assistance in arriving at a final diagnosis. In addition, information gathered may be of great help in monitoring disease activity and clinical response to therapy, in indicating the presence of specific organ system involvement, in monitoring toxicity of medication used, and in assessing prognosis. Serial measurements of acute phase reactants, complete blood cell count with differential, biochemistry profiles, urinalysis, and C3 and C4 levels should be obtained in all patients. Antineutrophil cytoplasmic antibodies (ANCA) determination provides valuable information and is highly specific for the diagnosis of small-vessel vasculitides, particularly Wegener's granulomatosis and microscopic polyangiitis. ANCA levels can be particularly useful to assess disease activity in these disorders. Hepatitis-B and, more importantly, hepatitis-C testing is extremely useful, particularly in the presence of liver involvement and associated risk factors. Angiographic studies may confirm the diagnosis, particularly if there is laboratory and clinical evidence of specific organ involvement. It should be noted, however, that angiography may be normal even when vasculitis is present, or the findings may be nonspecific. A definite diagnosis is provided by a tissue biopsy. This should be performed whenever there is access to clinically affected tissue.

Rheumatic manifestations of HIV-AIDS.

Infection by human immunodeficiency virus is characterized by a myriad of clinical manifestations affecting almost every organ system in the body. If untreated, it follows an inexorable course, leading to a profound state of immunosuppression and eventually death from opportunistic infection and/or development of lymphoproliferative malignancy and Kaposi's sarcoma. Rheumatic manifestations may develop at any time of the clinical spectrum, but usually are more often seen in late stages. A variety of disorders may be seen, particularly Reiter's syndrome and undifferentiated spondyloarthropathy. Most patients do well with conventional anti-inflammatory therapy, but some will require the use of immunosuppressive-cytotoxic therapy.

Ensayo de ecotoxicidad miniaturizado en Chlorella vulgaris utilizando diferentes parámetros de expresión / Miniaturized ecotoxicity assay with Chlorella vulgaris using differents endpoints

La exigencia actual de valoraciones medioambientales, requiere la utilización de métodos con relación coste/beneficio adecuado. En este trabajo presentamos el desarrollo y utilización de la Fluorescencia como medida de la inhibición del crecimiento, utilizando un monocultivo de Chlorella vulgaris var. Viridis. Se estimó las CI50 48 h de los siguientes compuestos: Glifosato, Amitrol, paraquat, Sulfato de Cobre, 3,4-Dicloroanilina y Cloruro de Cadmio, utilizando la Fluorescencia, la Densidad Celular y la Absorbancia, como parámetros de expresión. Los resultados aportan información sobre efectos fitotóxicos para los herbicidas Glifosato, Amitrol y Paraquat, con CI50 48 h de 100,85, 13, 82 y 0,04 mg/mL respectivamente, que ofrecen CI50 48 h en el mismo orden de magnitud, en cada uno de los compuestos ensayados para Densidad Celular, Absorbancia y Fluorescencia. Se discuten las ventajas que la Fluorescencia tendría frente a los otros parámetros de expresión, en ensayos de ecotoxicidad (AU)

Insights into the pathogenesis of psoriasis and psoriatic arthritis.

Psoriasis and its related arthritis are chronic inflammatory disorders affecting predominantly the skin and synovium. Although their etiology remains to be established, multiple factors seem to play important roles in their pathogenesis. These environmental (eg, infectious agents and trauma), genetic, and immunologic factors are reviewed in this article.

HIV infection-associated inflammatory musculoskeletal disorders.

Inflammatory musculoskeletal complaints are relatively common during the course of HIV infection, although they tend to be more frequent during late stages. The clinical spectrum is varied, ranging from arthralgias to distinct rheumatic disorders, such as Reiter's syndrome and psoriatic arthritis. The therapeutic management often poses a challenge, although most patients respond to conventional first- and second-line anti-inflammatory medications.

Methotrexate use in psoriasis and psoriatic arthritis.

Methotrexate is an extremely effective drug in the treatment of psoriasis and psoriatic arthritis. In addition, it possesses a very high benefit-to-toxicity ratio compared with other therapies and immunosuppressive agents used in these disorders. Fortunately, most adverse events related to methotrexate are mild, but serious and life-threatening reactions, particularly liver toxicity, may occur. Careful monitoring is essential to prevent most undesirable side effects.

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.

Management of spondyloarthropathies.

Better understanding of the etiopathogenic mechanisms and increasing recognition of the natural course of the spondyloarthropathies are leading to a more rational therapeutic approach to several of the disorders included within this large group of arthritides. Our traditional therapeutic approach to these conditions is being challenged, and a more aggressive therapeutic regimen is being advocated in a manner not too much different from that advocated for the treatment of rheumatoid arthritis. Combination therapy with either methotrexate and sulfasalazine or methotrexate and cyclosporine is being used more often and earlier, particularly in psoriatic arthritis. An issue, however, that remains unresolved is the proper use of antibiotic therapy.

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.

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.

Silicone breast implant--associated musculoskeletal manifestations.

Three hundred consecutive women with silicone breast implants (SBI), referred to the arthritis clinic with a variety of musculoskeletal complaints, were evaluated for the presence of underlying connective tissue disease. A complete history and physical examination were performed, as well as laboratory testing for C-reactive protein, rheumatoid factor; and autoantibody determination by indirect immunofluorescence and immunodiffusion. The group mean age was 44.4 years (range 25-69), the mean time from initial implant surgery to appearance of symptoms was 6.8 years (range: 6m-19y) and 83.3% of women studied had clinical manifestations highly suggestive of an underlying connective tissue disorder. Fifty-four percent met criteria for fibromyalgia and/or chronic fatigue syndrome, distinct connective tissue diseases was detected in 11%, undifferentiated connective tissue disease or human adjuvant disease was found in 10.6%, and a variety of disorders such as angioneurotic oedema, frozen shoulder, multiple sclerosis-like syndrome were present. Several other miscellaneous conditions including recurrent unexplained low grade fever, hair loss, skin rash, sicca symptoms, Raynaud's phenomenon, carpal tunnel syndrome, memory loss, headaches, chest pain, and shortness of breath were also seen accompanying specific and non-specific conditions. Seventy percent of patients who underwent explanation of the implants reported improvement of their systemic symptomatology. A significant proportion of SBI patients referred for rheumatic evaluation have clinical manifestations highly suggestive of an underlying connective tissue disease. Furthermore, improvement of their symptomatology follows explanation of the implants in over half of the patients.

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.

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.

Early onset of autoimmunity in MRL/++ mice following immunization with beta 2 glycoprotein I.

Antiphospholipid antibodies (aPL) are associated with thrombosis, thrombocytopenia and recurrent fetal loss in humans and in some animal models. Immunization with beta 2 glycoprotein I (beta 2GPI) induced aPL production in normal rabbits and mice. However, the association of these antibodies with disease manifestations remains controversial. To determine whether induction of aPL by beta 2GPI immunization in an autoimmune strain of mice (MRL/++) would result in acceleration of clinical and serological autoimmune disease manifestations, three groups of 8-week-old female mice were studied. One group was immunized with beta 2GPI, and one with ovalbumin (OVA); the third was not immunized. After two booster injections, sera were analysed for the presence of anticardiolipin (aCL) and anti-DNA by ELISA and anti-nuclear antibody (ANA) by immunofluorescence. Mice were studied for thrombocytopenia, proteinuria, fecundity rates, litter sizes and the development of central nervous system dysfunction. Elevated levels of aCL, anti-DNA and ANA were detected in all beta 2GPI-immunized, in three OVA-immunized, and in none of the unimmunized mice. The anti-DNA antibodies were inhibited by CL micelles, suggesting cross-reactivity between aCL and anti-DNA. Platelet counts, fecundity rates and litter size were reduced in beta 2GPI-immunized but not in OVA-immunized or unimmunized mice. None of the mice developed neurological dysfunction or significant proteinuria over a 10-week period post-immunization. These findings suggest that beta 2GPI immunization induces aPL in MRL/++ mice associated with accelerated autoimmune manifestations resembling the antiphospholipid syndrome.