Ângela Luzia Branco Pinto Duarte

A importância dos níveis de vitamina D nas doenças autoimunes

Alem do seu papel na homeostase do calcio, acredita-se que a forma ativa da vitamina D apresenta efeitos imunomoduladores sobre as celulas do sistema imunologico, sobretudo linfocitos T, bem como na producao e na acao de diversas citocinas. A interacao da vitamina D com o sistema imunologico vem sendo alvo de um numero crescente de publicacoes nos ultimos anos. Estudos atuais tem relacionado a deficiencia de vitamina D com varias doencas autoimunes, como diabetes mellitus insulino-dependente (DMID), esclerose multipla (EM), doenca inflamatoria intestinal (DII), lupus eritematoso sistemico (LES) e artrite reumatoide (AR). O artigo faz uma revisao da fisiologia e do papel imunomodulador da vitamina D, enfatizando sua participacao nas doencas reumatologicas, como o lupus e a artrite reumatoide.In addition to its role in calcium homeostasis, it is believed that the active form of vitamin D has immunomodulatory effects on cells of the immune system, particularly T lymphocytes, as well as on the production and action of several cytokines. The interaction of vitamin D with the immune system has been the target of a growing number of publications in recent years. Current studies have linked the deficiency of vitamin D with different autoimmune diseases, including insulin-dependent diabetes mellitus (IDDM), multiple sclerosis (MS), inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). This article reviews the physiology and immunomodulatory role of vitamin D, emphasizing its involvement in rheumatic diseases such as SLE and RA.

Increased Serum Interleukin 22 in Patients with Rheumatoid Arthritis and Correlation with Disease Activity

Objective. To analyze the role of interleukin 22 (IL-22) in rheumatoid arthritis (RA). Methods. IL-22 serum levels were measured in 83 patients with established RA under treatment with disease-modifying antirheumatic drugs and in 30 healthy controls matched for age and sex. Patients were assessed for clinical and laboratory variables. Correlations of IL-22 serum levels with disease activity measures [Clinical Disease Activity Index (CDAI) and Disease Activity Score for 28 joints (DAS28)], serological markers, bone erosions, and demographic factors were assessed. Peripheral blood mononuclear cells (PBMC) from 30 patients with RA and 14 controls were purified and stimulated in vitro with phorbol myristate acetate (PMA)/ionomycin. IL-22 production by PBMC and in serum was investigated by ELISA. Results. IL-22 levels were increased in patients with RA compared with controls (mean 432.37 pg/ml and 67.45 pg/ml, respectively; p < 0.001). Levels of IL-22 correlated with DAS28 and CDAI measures. Rheumatoid factor (RF) positivity was correlated with higher levels of IL-22 in patients with RA (mean 575.08 pg/ml; p = 0.001). The presence of bone erosions was associated with high IL-22 levels (p = 0.0001). PBMC stimulated with PMA/ionomycin expressed higher levels of IL-22 in patients with RA than controls but this was not significant (mean 584.75 pg/ml and 295.57 pg/ml; p = 0.553). Conclusion. IL-22 is elevated in the serum of patients with established RA. Elevated serum IL-22 allows discrimination between patients with different clinical and laboratory measures and indicates the potential of IL-22 as an additional tool for assessment of activity in RA, particularly in patients with RF antibodies and longterm disease. IL-22 is associated with bone-destructive disease.

Echocardiographic Abnormalities and Antiphospholipid Antibodies in Patients with Systemic Lupus Erythematosus

OBJECTIVE Lupus anticoagulant and anticardiolipin antibodies (aCL) have been associated with thrombosis, recurrent abortion, and thrombocytopenia in patients with systemic lupus erythematosus (SLE), but their relationship with cardiac disease is less clear. The purpose of this study was to evaluate the association between antiphospholipid antibodies (aPL) and echocardiographic abnormalities in patients with SLE. METHODS A total of 70 consecutive patients and 42 control subjects underwent M-mode, 2-dimensional and Doppler echocardiography and tests for lupus anticoagulant, aCL IgG, IgM, and IgA. Lupus anticoagulant was assayed with the dilute Russell viper venom time, and aCL IgG, IgM, and IgA were measured by an enzyme-linked immunosorbent assay (ELISA). RESULTS Lupus anticoagulant showed a prevalence of 10%. As a whole, aCL had a prevalence of 44.3% and aPL had a prevalence of 50%. Patients with echocardiographic abnormalities had a prevalence of 54.3% and showed a trend towards an association with aCL IgG (P=0.06). The presence of pulmonary hypertension (PH) was significantly associated with aCL IgG (p=0.02). CONCLUSION aCL IgG was significantly associated with PH and showed a strong trend towards an association with echocardiographic abnormalities taken together. These findings suggest a role for aCL IgG in the development of lupus cardiovascular disease.

Evaluation of an interferon gamma assay in the diagnosis of latent tuberculosis infection in patients with rheumatoid arthritis.

The tuberculin skin test is not an ideal screening test for the patients with rheumatoid arthritis to identify cases of latent tuberculosis infection (LTBI) prior to the start of treatment with anti-TNFs, as it responds inadequately to late hypersensitivity, which is fundamental for producing a response to the inoculated antigen. Assays based on detection of the production of IFNγ in vitro by mononuclear peripheral cells stimulated by specific antigens are more specific than PPD in detecting LTBI. The aim of this study was to evaluate the performance of T-SPOT.TB in diagnosis of LTBI in patients with rheumatoid arthritis, comparing with the PPD. The specificity of the T-SPOT.TB varied from 87 to 90% and the negative-predictive value (NPV) from 94.4 to 100%. It can be concluded that the T-SPOT.TB showed high specificity and NPV, proving the capability of identifying false-negative cases of PPD, raising the level of safety for the use of anti-TNFs.

Bisfosfonatos podem minimizar a fome óssea após paratireoidectomia em pacientes com hiperparatireoidismo primário e osteíte fibrosa cística

OBJECTIVE To assess the effect of bisphosphonates on post-parathyroidectomy hypocalcemia in patients with osteitis fibrosa cystica. METHODS Review of the medical records of six patients using bisphosphonates preoperatively. RESULTS Mean age was 35.6 ± 10.5 years; serum calcium = 13.51 + 0.87 mg/dL; iPTH = 1,389 + 609 pg/mL. The mean value of urine deoxypyridinoline (UDPD) of three patients was 131 ± 183 nmol/mmol Cr, and of C-telopeptide (CTX), 2,253 ± 1,587 pg/mL. The mean values of bone densitometry (T score) were as follows: 0.673 ± 0.150 g/cm(2) (-4.42 ± 1.23) in lumbar spine (L2-L4); 0.456 ± 0.149 g/cm(2) (-5.58 ± 1.79) in the femoral neck; and 0.316 ± 0.055 g/cm(2) (-5.85 ± 0.53) in radius 33. Patient 1 received oral alendronate, 30 mg/day for four weeks; his calcium decreased from 14 to 11.6 mg/dL, and his UDPD from 342 to 160 nmol/mmol Cr. Patient 2 received oral alendronate, 20 mg/day for six weeks; his calcium decreased from 14 to 11.0 mg/dL and his UDPD from 28.8 to 14 nmol/mmol Cr. Patient 3 received intravenous pamidronate, 90 mg prior to surgery. Patient 4 received oral alendronate, 140 mg/week for six weeks; her calcium decreased from 13.7 to 12.3 mg/dL and her CTX from 2,160 to 1,340 pg/mL. Patient 5 received oral alendronate, 140 mg/ week for six weeks; her calcium levels dropped from 14.3 to 14.1 mg/dL; her CTX did not change. Patient 6 received ibandronate, 150 mg, ten days prior to surgery; his CTX reduced by 62%. No patient developed severe hypocalcemia in the first postoperative week. One year after surgery, the mean gain in bone mineral density was 40% ± 29% in L2-L4, 86 ± 39% in the femoral neck, and 22% ± 11% in radius 33. CONCLUSION The preoperative use of bisphosphonates seems to attenuate bone hunger without preventing a significant increase in bone mass in the follow-up of parathyroidectomy.

Resposta atenuada ao PPD no diagnóstico de infecção tuberculosa latente em pacientes com artrite reumatoide

INTRODUCTION: With the introduction of Tumor Necrosis Factor Inhibitors (anti-TNFs) into rheumatological practice, it has become obligatory to identify cases of latent tuberculosis infection (LTBI) prior to the start of treatment, using PPD, chest radiography and clinical history of tuberculosis contact. Patients with Rheumatoid Arthritis (RA) have an abnormality of the cellular immune function, characterized by decreasing responsiveness of peripheral mononuclear cells (T Reg lymphocytes), leading to a loss in delayed hypersensitivity, which is fundamental for the recognition of antigens, such as PPD. OBJECTIVES: The purpose of our study was to evaluate the response to PPD in patients with RA, compared with healthy people, in an area where tuberculosis is endemic, as is the state of Pernambuco. METHODOLOGY: We studied 96 patients, 48 with RA and 48 healthy subjects, most of them females. All patients were given an interdermic injection of 0.1 mL PPD RT-23. The reading of the PPD result was carried out 72 hours after application, by way of palpation of maximum transverse diameter of induration, and the result was expressed in millimeters. RESULTS:In the RA group, the average time of diagnosis was 10.2 years, the average dosage of methotrexate was 15.5 mg / week, the average dosage of prednisone 12.7 mg / day and the average activity of the disease, measured using CDAI, was 30.4. In the healthy subjects group there was a greater number of positive PPD results (33.3%) when compared with the results for the RA group (14.6%), with a statistically significant difference (p = 0.034). CONCLUSION:The performance of PPB in LTBI diagnosis is poor in patients with RA. These results suggest that more careful screening needs to be undertaken before treatment with an anti-TNF drug.

Análise dos índices de Helkimo e craniomandibular para diagnóstico de desordens temporomandibulares em pacientes com artrite reumatóide

AIM: The aim of this study was to evaluate the use of two indexes (Helkimo and Craniomandibular) for the diagnosis of temporomandibular disorder (TMD) in patients with Rheumatoid Arthritis (RA). PATIENTS AND METHODS: The sample was composed of 80 patients divided into two groups: patients with RA and patients without RA. In both groups the two indexes were used. For TMD diagnosis, the following signs and symptoms were evaluated: TMJ pain, limited mouth opening and joint sounds. RESULTS: Results showed that of the RA patients, 87.1% were females and 12.9% were males. Among the patients without RA, 70% were females and 30% were males. The age of these RA patients ranged between 24 and 78 years. Among patients without RA, the age of the patients ranged between 22 and 72 years. It was observed that the prevalence of TMD was higher in the group with RA (98.6% - Helkimo and 87.1% - Craniomandibular) when compared to the group without the disorder (80% - Helkimo and 50% - Craniomandibular). CONCLUSION: In summary, one could conclude that both indexes are capable to diagnose temporomandibular disorders in RA patients, although the Helkimo index is less accurate.

Analysis of helkimo and craniomandibular indexes for temporomandibular disorder diagnosis on rheumatoid arthritis patients

AIM The aim of this study was to evaluate the use of two indexes (Helkimo and Craniomandibular) for the diagnosis of temporomandibular disorder (TMD) in patients with Rheumatoid Arthritis (RA). PATIENTS AND METHODS The sample was composed of 80 patients divided into two groups: patients with RA and patients without RA. In both groups the two indexes were used. For TMD diagnosis, the following signs and symptoms were evaluated: TMJ pain, limited mouth opening and joint sounds. RESULTS Results showed that of the RA patients, 87.1% were females and 12.9% were males. Among the patients without RA, 70% were females and 30% were males. The age of these RA patients ranged between 24 and 78 years. Among patients without RA, the age of the patients ranged between 22 and 72 years. It was observed that the prevalence of TMD was higher in the group with RA (98.6%-Helkimo and 87.1%-Craniomandibular) when compared to the group without the disorder (80%-Helkimo and 50%-Craniomandibular). CONCLUSION In summary, one could conclude that both indexes are capable to diagnose temporomandibular disorders in RA patients, although the Helkimo index is less accurate.

Envolvimento macrovascular e esclerose sistêmica

Este artigo tem como objetivo revisar os aspectos descritos na literatura sobre o acometimento da macrovasculatura na esclerose sistemica e avaliar a ocorrencia e distribuicao das alteracoes macrovasculares nos pacientes com esclerose sistemica atraves do eco-Doppler e do indice tornozelo-braco, alem da associacao desses achados com as caracteristicas demograficas, forma clinica, tempo de evolucao da doenca, fenomeno de Raynaud (FR), alteracoes digitais, ulceracoes de membros, reabsorcao de falange, amputacao, bem como fatores de risco e antecedentes da doenca ateromatosa. O estudo foi prospectivo, do tipo serie de casos, constituido de 20 pacientes, sendo 19 do sexo feminino, com idade media de 46,30 anos. Todos os pacientes tinham fenomeno de Raynaud objetivo, 85% a forma clinica difusa, 55% alteracao de polpa digital, 15% ulcera atual de membros, 25% reabsorcao de falange, nenhuma amputacao e 70% de um a quatro fatores de risco. Foram estudadas pelo eco-Doppler as arterias aorta e carotida, dos membros inferiores e superiores, para a avaliacao de espessamento do complexo intimo-medial e presenca de placas e aneurismas. Nas arterias dos membros inferiores, foi tambem realizado o indice tornozelo-braco. O indice tornozelo-braco foi normal em todos os pacientes; entretanto, 12 (60%) destes apresentaram doenca macrovascular pelo eco-Doppler, sendo nove (45%) na aorta, seis (30%) nas carotidas, uma (5%) nas arterias dos membros superiores e sete (35%) nas dos membros inferiores. Observou-se associacao entre doenca macrovascular e alteracoes de polpas digitais (p = 0,0045). A doenca macrovascular foi identificada em 60% dos pacientes atraves do eco-Doppler, mas nao pelo indice tornozelo-braco, que foi normal em todos. Verificou-se associacao significante da doenca macrovascular com as alteracoes atuais de polpas digitais, o que nao ocorreu com as demais variaveis estudadas.

Manifestações musculoesqueléticas nos pacientes em programa de hemodiálise

A large diversity of ostearticular complaints has been described in patients in long-term hemodialysis. OBJECTIVE: To verify the proportion and the type of musculoskeletal complaints in patients in maintenance hemodialysis, at three centers of metropolitan Recife, and to relate these complains to the following variables: sex, ethnic group, patients current age and when the dialysis began, and dialitic treatment time. METHODS: Firstly, questionnaires were applied to 197 patients, distributed at the three centers from March 2001 to January 2002. After excluding 35 patients with previous diagnosis of rheumatic disease, we investigatied the presence of musculoskeletal signs and/or symptoms in 162 patients. The average age was 47,3 years old, and 43,8 years old was the average age at the beginning of the treatment; 94 patients (58%) were men and 120 patients (74.1%) were not Caucasian. The average time of the dialitic treatment was 44,1 months, and polysulphone membrane was used in all of them. RESULTS: Musculoskeletal manifestations were observed in 55 (34%) of the patients on this research. One type of manifestation was presented by 38 of these patients, and 17 patients presented more than one type (16 presented two and 1 presented three types), making up a total of 73 manifestations, distributed among joints (44), bones (18), neuromuscular (6) and periarticular (5) structures. Arthralgia was responsible for 46.6% of all musculoskeletal complaints and the knee was the joint most injured (52.9% of all cases). Bone pain was the second common complaint (21.9%), periarticular changes were responsible for 6.8% of musculoskeletal manifestations, and carpal tunnel syndrome, bone deformities and joint tumours occurred in 4.1%, 2.7% and 2.7% of all manifestations, respectively. Among 55 patients, joint changes were found in 72.7% of them, bone changes in 32.7%, neuromuscular complaints in 10.8% and periarticular in 9.1% of the patients. The relation between the dialitic treatment time (59,8 months) and the development of the musculoskeletal manifestations (p < 0.001) was observed in this research. CONCLUSIONS: According to this information, we can conclude that the proportion of musculoskeletal complaints on our patients was 34%; the joint problems were the most frequently observed; and arthralgia was the most common complaint. Except for the dialitic treatment time, all the other variables were not associated with the musculoskeletal manifestations.