Articular inflammatory manifestations in patients with different forms of leprosy.

OBJECTIVE: To study the articular inflammatory manifestations of leprosy. METHODS: Sixty patients with leprosy from a public clinic in São Paulo, Brazil, participated in a study regarding their articular manifestations. The diagnosis and classification of leprosy were established by the clinical picture, skin smears, skin biopsy, and delayed hypersensitivity test to Mycobacterium leprae antigens (Mitsuda test). According to the Madrid and Ridley-Jopling classifications, 46 patients had lepromatous leprosy, 7 had borderline leprosy, 4 had tuberculoid leprosy, and 3 had indeterminate leprosy. History, general and articular examinations, and roentgenograms were employed and complemented in several cases by scintigraphic examinations with technetium methylene diphosphonate and computed tomographic studies. RESULTS: Three patients were excluded from study due to an association with a rheumatic disease. Among the 57 remaining patients, 44 had peripheral arthritis characterized by involvement of small joints (23/44), large joints (4/44), or both (17/44). The mean duration of arthritis was 11 years (range 1 mo to 51 yrs). Arthritis was detected in all subtypes of patients with leprosy. Supplementary radiological evaluation established the extent of inflammation and diagnosis of sacroiliitis. The diagnosis of sacroiliitis, based on the presence of sclerosis, erosions, and narrowing of the cartilage space in the sacroiliac joints, was established in 35 of 55 radiographs. Sacroiliitis varied from grade I to III, according to the Bennet and Wood classification, and was bilateral in most cases (30/35). There was no significant correlation between low back pain and the finding of sacroiliitis. CONCLUSION: Articular inflammatory manifestations may exist in patients with different forms of leprosy, and can follow a chronic course. In addition, sacroiliitis is a common, previously unrecognized manifestation in patients with leprosy.

Vasculite urticariforme hipocomplementêmica como primeira manifestaçäo do lúpus eritematoso sistêmico / Hypocomplementaemic urticarial vasculitis first manifestation of systemic lupus erythematosus

A síndrome vasculite urticariforme hipocomplementêmica é uma vasculite leucocitoclástica que se apresenta com lesöes urticariformes, associada a febre, artralgias, artrite e cólica abdominal. Outras manifestaçöes sistêmicas incluem a presença de glomerulonefrite, uveíte, episclerite, doença pulmonar obstrutiva e alteraçöes neurológicas. Alguns casos associados ao lúpus eritematoso sistêmico (LES) têm sido descritos, com o diagnóstico baseando-se na presença de critérios bem definidos de LES prévia ou concomitantemente ao aparecimento de vasculite urticariforme. A apresentaçäo de vasculite urticariforme precedendo o diagnóstico de LES é rara, o que motivou o relato destes dois casos. Enfatiza-se a positivaçäo do anticorpo anti-Ro/SS-A por ocasiäo do diagnóstico de LES, alertando para a necessidade de avaliaçäo periódica nos casos de vasculite urticariforme.

Possible mechanisms of chronic leprosy-related arthritis.

Microbial agents induce arthritis through mechanisms such as direct infiltration of tissue and by inducing autoimmune phenomena. The mechanisms involved in this last type of arthritis have been investigated. In experimental models of adjuvant and reactive arthritis, the involvement of T cells in some cases mycobacteria in the development of arthritis have been confirmed. Cross-reactivity between the 65 kD mycobacterial protein and cartilage proteoglycans has been postulated as a possible mechanism. In this study, chronic peripheral arthritis was observed in patients with Hansen's disease, in patients with resolved Hansen's and in those with paucibacillary forms. This arthritis was not related to reactional states (erythema nodosum leprosum and reversal reaction), in contrast to several reports in the literature. The mechanisms by which microbes could induce chronic arthritis are discussed herein.

[Intra-articular nitric oxide levels in patients with rheumatoid arthritis]. / Níveis intra-articulares de óxido nítrico em pacientes com doença reumatóide.

The aim of this study was the appraisal of the nitrite and nitrate levels in the synovial fluid of patients with rheumatoid arthritis (RA). The synovial fluid of patients with osteoarthritis (OA) was also evaluated by comparison. Demographic characteristics such as age and sex, and clinical and laboratorial parameters like duration of disease, functional class and erythrocyte sedimentation rate (ESR) were evaluated too. In the synovial fluid of all patients the total and differential leukocyte count, and the nitrite and nitrate levels determined by Griess reaction were analyzed. The results were statistically analyzed by Student's t test and correlation test. We found a significant increase in the intraarticular nitrite and nitrate levels in patients with RA when compared with OA patients (30.68 +/- 2.94 microM x 16.15 +/- 2.73 microM). We did not find any correlation between intraarticular nitrite and nitrate levels and the ESR or the total and differential leukocyte count in the RA synovial fluid. In this study we clearly found an increase in the intraarticular nitrite and nitrate levels in patients with rheumatoid arthritis.

[Hormonal and biochemical parameters in postmenopausal osteoporosis]. / Parâmetros bioquímios e hormonais na osteoporose pós-menopausa.

In the recent years, many authors had studied the relationship between the calciotropic and gonadotropic hormones actions on postmenopausal bone loss, named calcium negative balance, with different results (Riggs et al 1983; Prince et al, 1995). We evaluated 187 female patients, aged 40 to 80 with the following distribution: 24 normals, 49 patients with osteopenia and 114 patients with osteoporosis, according to WHO classification. The aim of this study was to analyse the relationship between biochemical parameters (seric and urinary calcium), gonadotropic (seric FSH-foliculi stimulant-hormone and seric oestradiol) and calciotropic hormone (PTH) and postmenopausal bone loss. The results had shown the diminution on bone mineral density was related with elevated levels of FSH (p < 0.00001), lower levels of oestradiol (p < 0.00001) and, however, no differences on seric and urinary calcium (respectively, p > 0.70 and p > 0.52) or PTH (p > 0.70) were demonstrated.

Nitric oxide synthase inhibitor influences prostaglandin and interleukin-1 production in experimental arthritic joints.

OBJECTIVE: To assess involvement of nitric oxide (NO) in the increase in eicosanoid and interleukin- 1 (IL-1) levels in the synovial fluid during antigen-induced arthritis (AIA) in rabbits treated with a competitive inhibitor of NO synthesis. SUBJECTS: Thirteen New Zealand White rabbits were sensitized with 5 mg of methylated bovine serum albumin (mBSA). Arthritis was induced in the knee joint by injecting 0.5 ml of a sterile solution of mBSA (2 mg/ml) into the intra-articular cavity. TREATMENT: Prior to the induction of arthritis, the animals received N-Omega-Nitro-L-Arginine Methyl Ester (LNAME) or N-Omega-Nitro-D-Arginine Methyl Ester (DNAME) for 2 weeks, both at a dose of 20 mg/kg/day mixed with drinking water. METHODS: Leukocyte efflux (total and differential white cell count), vascular permeability (Evans's blue method), synovial PMN cell infiltrate, and total nitrite (NO2.)/nitrate (NO3.) (HPLC), PGE2, TxB2, LTB4 (radioimmunoassay), and IL-1 beta (ELISA) levels were quantified in the synovial fluid. RESULTS: LNAME but not DNAME significantly suppressed leukocyte efflux and protein leakage into the articular cavity as well as synovial PMN cell infiltrate. Total NO2./NO3., PGE2 and IL-1 beta levels were significantly reduced in the synovial fluid of LNAME treated animals. TxB2 and LTB4 were not affected by LNAME treatment. CONCLUSION: These data clearly show NO involvement in the IL-1-induced PGE2 production in the synovial fluid of antigen-induced arthritis in rabbits.

[Low complement levels in urticarial vasculitis as first manifestation of systemic lupus erythematosus]. / Vasculite urticariforme hipocomplementêmica como primeira manifestação do lúpus eritematoso sistêmico.

Hypocomplementaemic urticarial vasculitis syndrome is a leukocytoclastic vasculitis characterized by urticarial lesions, associated with fever, arthralgias, arthritis and abdominal pain. Other systemic manifestations include glomerulonephritis, uveitis, episcleritis, chronic obstructive pulmonary disease and neurological abnormalities. Some case associated with systemic lupus erythematosus have been described and SLE diagnosis was made by previous or concomitant diagnostic criteria before onset of urticarial vasculitis. Urticarial vasculitis prior to SLE diagnosis is rare. The development of anti-Ro/SS-A antibody for the diagnosis of SLE is emphasized. The authors alert to the importance of periodically searching for this marker in patients with urticarial vasculitis.

Low dose methotrexate decreases intraarticular prostaglandin and interleukin 1 levels in antigen induced arthritis in rabbits.

OBJECTIVE: To investigate the effects of methotrexate (MTX) on inflammation variables of antigen induced arthritis (AIA) in rabbits, such as protein leakage to the articular cavity, synovial fluid (SF) leukocyte count, synovial membrane polymorphonuclear (PMN) cell infiltrate, and intraarticular production of eicosanoids and interleukin 1 (IL-1). Dexamethasone and indomethacin were used for comparison. METHODS: NZW rabbits were treated with the following drugs: MTX (0.25 mg/kg), dexamethasone (0.15 mg/kg), indomethacin (4 mg/kg), and sterile saline (control group). All drugs were given by intramuscular route before arthritis was induced and the animals were sacrificed 4 or 24 h later. Leukocyte migration, protein leakage (Evans blue method), synovium PMN cell infiltrate, and intraarticular concentration of prostaglandin E2 (PGE2), thromboxane B2 (TXB2), leukotriene B4 (LTB4) (radioimmunoassay), and IL-1 beta (ELISA) were quantified in SF. RESULTS: Significant reduction of leukocyte migration and protein leakage was observed in the joint fluid of all treated animals. Decrease in the intensity of synovium PMN cell infiltrate also occurred with all treatments. Intraarticular PGE2, TXB2, and IL-1 beta were significantly reduced after 4 h of arthritis induction in animals treated with MTX and dexamethasone. Treatment with indomethacin reduced only PGE2 and TXB2 in SF. Treatments did not change SF IL-1 beta concentration 24 h after arthritis induction. Treatment with dexamethasone increased inflammatory variables and SF LTB4 concentration 24 h after the synovial cavity was challenged with antigen. CONCLUSION: Our results show that MTX, like dexamethasone, reduces the intensity of leukocyte afflux, protein leakage, synovial membrane PMN cell infiltrate, as well as the intraarticular production of PGE2, TXB2, and IL-1 beta in the early phase of antigen induced arthritis in rabbits.

[Lyme disease in Mato Grosso do Sul State, Brazil: report of three clinical cases, including the first of Lyme meningitis in Brazil]. / Doença de Lyme em Mato Grosso do Sul: relato de três casos clínicos, incluindo o primeiro relato de meningite de Lyme no Brasil.

The authors report the occurrence of the first three clinical cases of Lyme disease in Mato Grosso do Sul State, including the first case of Lyme meningitis in Brazil. These were identified by clinical and laboratorial criteria. Anti-Borrelia burgdorferi antibody search was carried out through ELISA and Western Blotting techniques, the former providing identification of IgG class antibodies alone, in one only of those cases. Through Immunoblotting, the following features were found in serum: 5 IgG and 2 IgM bands for the first case; 7 IgG and 2 IgM bands for the second; and 5 IgG and 6 IgM bands for the third. In the latter, presence fo specific antibodies was searched in liquor, due to lymphomonocitary meningitis occurrence, and one IgM band was detected. After antibiotic therapy, all patients exhibited significant clinical and laboratorial improvement in their conditions along with symptom regression to the present moment.

Cardiac and skeletal muscle scintigraphy in dermato- and polymyositis: clinical implications.

To determine the role of scintigraphy in the detection of skeletal and cardiac involvement in dermato- and polymyositis (DM/PM), we studied 30 patients with a confirmed diagnosis of DM/PM (23 females, 7 males; mean age: 35 years). Technetium-99m pyrophosphate (99mTc-PYP) and gallium-67 scans showed similar sensitivity, specificity and accuracy in the detection of skeletal muscle involvement when compared with serum enzymes (70%, 100% and 80%, respectively). Compared with the clinical parameters, 99mTc-PYP showed 70% and 67Ga 65% accuracy. Abnormal PYP cardiac uptake was observed in 57% of patients, whereas abnormal 67Ga cardiac uptake was seen in only 15%. Electrocardiography was abnormal in 40%, rest gated blood pool study in 23%, and chest X-ray in 13%. In conclusion, both 99mTc-PYP and 67Ga can be useful in the detection of the active phase of muscle disease. However, 99mTc-PYP seems to be more effective than 67Ga in the early diagnosis of cardiac involvement.

Humoral immunity in Hansen's disease.

For many years immune response in leprosy has been studied. Since 1960 several reports dealing with humoral immunity have been described in the literature. Different autoantibody rates occur in leprosy. There is an increase in the prevalence of autoantibodies in elderly patients with long standing disease, in lepromatous leprosy and in those with reactional states. The differences in rates among various studies are attributed to different methods and variations among patient samples concerning age, gender, polar forms, therapy and other elements. The prevalence of numerous antibodies, immune complexes, cryoglobulins and complement levels have been studied by many authors. This also highlights the importance of the more recent reviews of anti-Mycobacterium leprae glycolipid antibodies such as the anti-phenolic glycolipid-I antibodies in which titers are variable and depend on genetic factors.

Influence of low doses of methotrexate on superoxide anion production by polymorphonuclear leukocytes from patients with rheumatoid arthritis.

OBJECTIVE: The mechanism of methotrexate (MTX) action in rheumatoid arthritis (RA) is unclear. We assessed the influence of MTX on neutrophil superoxide production evaluated by ferricytochrome c reduction. METHODS: Neutrophils were collected from MTX treated patients with RA (MTX-RA), patients with RA without medication (RA) and healthy donors, cocultured with MTX or MTX-RA serum. RESULTS: Polymorphonuclear leukocytes (PMN) from MTX-RA showed decreased superoxide production when compared with cells collected from patients with RA and controls. Control PMN superoxide production was inhibited (36%) by MTX-RA serum incubation. This reduction was accompanied by clinical improvement. MTX had no activity in the in vitro assays. CONCLUSION: MTX treatment may interfere with neutrophil superoxide production.

[Comparison between immunofluorescence techniques and ELISA, using whole neutrophil extract and primary granules, for the detection of antineutrophil cytoplasma antibodies (ANCA)]. / Comparação entre as técnicas de imunofluorescência e ELISA com extrato total de neutrófilos e com grânulos primários para a detecção de anticorpos contra o citoplasma de neutrófilos (ANCA).

The detection of antineutrophil cytoplasmic antibodies is a very important tool for the diagnosis of systemic vasculitis. The specificity and sensitivity of these antibodies depends on the assay utilized for their detection. Therefore we have compared the immunofluorescence test (IF) with the ELISA using two different antigens: total neutrophil extract and isolated primary granules. Two patterns of fluorescence were detected by IF: the classic pattern was highly specific for Wegener's granulomatosis. In contrast the perinuclear staining correlated with renal vasculitis but was also observed in other diseases. However the IF test was unable to differentiate low-positive from atypical patterns. Such distinction could be achieved by ELISA. The use of ELISA with isolated primary granules is a good alternative for if since it has a good specificity, sensitivity and reproducibility, moreover it is a quantitative method.

[Rheumatic involvement in Hansen's disease]. / Os comprometimentos reumatológicos na hanseníase.

The classical articular manifestations of Hansen's disease are the neurogenic or Charcot's arthropathy, osteitis and specific or non specific osteoarthritis. However, inflammatory mechanisms have been associated to arthritic episodes in leprosy patients, leading to rheumatoid-like picture as suggested by clinical, biopsy and laboratorial data. The extra-articular manifestations also mimicry those of some connective tissue diseases. The differencial diagnosis between rheumatic syndromes and hanseniasis is important for as early indentification of hanseniasis and prevention of severe sequelae and transmission.

[Non steroidal anti-inflammatory drugs and rheumatic diseases]. / Antiinflamatórios não esteróides e doenças reumatológicas.

Nonsteroidal anti-inflammatory drugs (NSAID) comprise an important class of medicaments that reduced the symptoms of inflamation in rheumatic disease. This article emphasizes similarities and class characteristics of the NSAID, mechanisms of action, and drug-interactions.

Comparison of five methods for the detection of antiribosomal P protein antibody.

1. We have compared the sensitivity and specificity of immunofluorescence, counterimmunoelectrophoresis, immunodiffusion, Western blotting and ELISA for the detection of antiribosomal P protein antibodies using 153 lupus sera. 2. Western blotting and ELISA were the 2 most sensitive and specific techniques for the detection of these antibodies. In contrast, cytoplasmic immunofluorescence was observed in only one third of the anti-P-positive patients. Immunodiffusion and counterimmunoelectrophoresis, although highly specific, detecting 14% and 29% of all anti-P-positive sera by Western blotting, were the least sensitive tests. 3. The frequency of anti-P in lupus patients, as detected by Western blotting analysis was 18%. The most frequently observed antibody in anti-P sera was anti-Ro/SSA (39%). Anti-P antibodies were also detected in the sera of 3 patients with negative nuclear immunofluorescence. 4. Anti-P is an additional serological marker for systemic lupus erythematosus and Western blotting is the method of choice for detecting this antibody due to the limited availability of the fusion protein in Brazil.

Quantificaçäo da interferência do soro na fagocitose de imunocomplexos nas espondiloartropatias soronegativas, lúpus eritematoso sistêmico e doença reumatóide / Quantification of serum interference in the immune complexes phagocytosis in seronegative spondylarthropaties, systemic lupus erythematosus and rheumatoid disease

Cinqüenta e cinco soros de pacientes portadores de espondiloartropatias soronegativas, lúpus eritematoso sistêmico e artrite reumatóide foram selecionados para o estudo. Todos os soros mostravam fator reumatóide negativo pela prova de látex. A determinaçäo da interferência na fagocitose de gamaglobulina agregada por macrófagos de cobaia foi obtida por uma fórmula. A caracterizaçäo dos soros foi discriminada pela reaçäo daqueles que mostraram resultados mais expressivos na interferência sobre a fagocitose, facilitando ou inibindo-a. Os resultados, em valores absolutos e percentuais, mostraram a predominância do fenômeno da interferência na fagocitose, com valores significantes estatisticamente (p<0,05), quando comparado com soro normal. A análise comparativa entre as doenças estudadas na quantificaçäo da interferência do soro na fagocitose de imunocomplexo näo mostrou diferença significativa. A inibiçäo da fagocitose ocorreu com mais predominância no soro de pacientes com síndrome de Reiter e artrite psoriática; no soro de pacientes com síndrome de Reiter houve uma diferença estatisticamente significante na inibiçäo da fagocitose (p=0,0247). A caracterizaçäo da fraçäo sérica responsável pela interferência na fagocitose näo foi demonstrada. No estado atual dos conhecimentos, näo há uniformidade nas curvas de diluiçäo estudadas. É enfatizada a possibilidade de existência de mais de um elemento interferindo na fagocitose de imunocomplexos.

Comparison of five methods for the detection of antiribosomal P protein antibody

1. We have compared the sensitivity and specificity of immunofluorescence, counterimmunoelectrophoresis, immunodiffusion, Western blotting and ELISA for the detection of antiribosomal P protein antibodies using 153 lupus sera. 2. Western blotting and ELISA were the 2 most sensitive and specific techniques for the detection of these antibodies. In contrast, cytoplasmic immunofluorescence was observed in only one third of the anti-P-positive patients. Immunodiffusion and counterimmunoelectrophoresis, although highly specific, detecting 14 per cent and 29 per cent of all anti-P-positive sera by Western blotting, were the least sensitive tests. 3. The frequency of anti-P in lupus patients, as detected by Western blotting analysis was 18 per cent . The most frequently observed antibody in anti-P sera was anti-Ro/SSA (39 per cent ). Anti-P antibodies were also detected in the sera of 3 patients with negative nuclear immunofluorescence. 4. Anti-P is an additional serological marker for systemic lupus erythematosus and Western blotting is the method of choice for detecting this antibody due to the limited availability of the fusion protein in Brazil