Isabella Lima

NK and NKT cell dynamics after rituximab therapy for systemic lupus erythematosus and rheumatoid arthritis

Biomarkers of clinical response to rituximab (RTX) therapy and early predictors of outcome are still under investigation. We report a flow cytometric immunophenotyping analysis from peripheral blood leukocyte subpopulations of two patients with systemic lupus erythematosus (SLE) associated thrombocytopenia and one patient with rheumatoid arthritis (RA), before and after 6 weeks of treatment with RTX. Our results show a reduced population of CD19+ expressing cells (B cells) after RTX treatment in all three patients. Increased frequency of peripheral regulatory CD4+CD25high T cell subset and the CD3−CD16−CD56bright NK cell subset after RTX therapy were also observed in all patients, the latter being more pronounced in the SLE patient with sustained clinical response. In addition, an increased population of NKT cell subsets was observed in the patients with clinical response. This is the first evaluation of NK and NKT cells as biomarkers of clinical response after rituximab therapy in rheumatic diseases.

Anti-C1q Antibodies: Association With Nephritis and Disease Activity in Systemic Lupus Erythematosus

Background: Anti‐C1q antibodies have been described in systemic lupus erythematosus (SLE) as well as in other connective tissue diseases. They have been considered as a marker for disease activity and presence of nephritis.

Prevalence and classification of headache in patients with systemic lupus erythematosus

Studies on the prevalence of headache in systemic lupus erythematosus (SLE) have shown that it varies from 32 to 78%. The purpose of our study was to determine the prevalence and characteristics of headache in SLE compared with patients with different types of diffuse connective tissue diseases (DCTD) and its relationship with clinical and laboratory manifestations of SLE. We studied patients with SLE (SLE group) and patients with DCTD (control group). All patients were made to answer questionnaire to assess the presence of headache, characterized by at least five episodes of headache during the last year, which was classified according to the International Headache Society criteria. A total of 207 patients were studied, 115 in SLE group and 92 in the control group. The 1-year prevalence of headache was 75.7% in SLE group and 66% in the control group. When the groups were analyzed, 66.1% met the diagnostic criteria for migraine in the SLE group compared with 52.2% in the control group (p=0.04) and 13.9% for tension-type headache in SLE group compared with 16.3% in the control group. The former was the only variable that reached statistical significance comparing the two groups. Both headache and migraine were associated with Raynaud’s phenomenon in SLE patients (odds ratio of 2.80, 95% confidence interval: 1.11–7.05, p=0.02 and odds ratio of 2.34, 95% confidence interval: 1.04–5.23, p=0.03, respectively). These results suggest that headache is a common manifestation in SLE and in other DCTD and we cannot exclude the possibility that it may be related to the emotional stress induced by such clinical situations.

Diretrizes para o tratamento da síndrome do anticorpo antifosfolipídeo

The antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial and venous thrombosis, gestational morbidity and presence of elevated and persistently positive serum titers of antiphospholipid antibodies. The treatment of APS is still controversial, because any therapeutic decision potentially faces the risk of an insufficient or excessive antithrombotic coverage associated with anticoagulation and its major adverse effects. This guideline was elaborated from nine relevant clinical questions related to the treatment of APS by the Committee of Vasculopathies of the Brazilian Society of Rheumatology. Thus, this study aimed at establishing a guideline that included the most relevant and controversial questions in APS treatment, based on the best scientific evidence available. The questions were structured by use of the PICO (patient, intervention or indicator, comparison and outcome) process, enabling the generation of search strategies for evidence in the major primary scientific databases (MEDLINE/PubMed, Embase, Lilacs, Scielo, Cochrane Library, Premedline via OVID). A manual search for evidence and theses was also conducted (BDTD and IBICT). The evidence retrieved was selected based on critical assessment by using discriminatory instruments (scores) according to the category of the therapeutic question (JADAD scale for randomized clinical trials and Newcastle-Ottawa scale for non-randomized studies). After defining the potential studies to support the recommendations, they were selected according to level of evidence and grade of recommendation, according to the Oxford classification.

Dosagem sérica de adenosina deaminase em lúpus eritematoso sistêmico: ausência de associação com atividade de doença

O lupus eritematoso sistemico (LES) e uma doenca inflamatoria auto-imune, que evolui intercalando periodos de atividade e remissao. OBJETIVO: avaliar a associacao da dosagem serica de adenosina deaminase (ADA) e atividade do LES, segundo os criterios do SLEDAI 2K - Systemic lupus erythematosus disease activity index. METODOS: avaliou-se 82 pacientes com LES atendidos em um hospital de referencia para o tratamento do LES em Salvador, BA, Brasil. A atividade de doenca foi determinada pelo SLEDAI 2K e a dosagem serica da ADA realizada por colorimetria. RESULTADOS: oitenta e uma pacientes (98,78%) eram do sexo feminino e a idade media foi de 35,07±11,73 anos. O escore de SLEDAI medio foi de 11,66±5,89; a media de ADA serica foi de 38,24±13,61U/l; C3 de 91,93±27,39 mg/dl; C4 de 15,17±5,77 mg/dl e a pesquisa de anticorpos anti-DNA nativo (aDNAn) foi positiva em 31 casos (37,8%). Nao houve correlacao entre os niveis sericos de ADA e escore do SLEDAI. A ADA serica correlacionou-se inversamente com C4 (r=-0,336 e p=0,001). CONCLUSOES: no presente estudo a dosagem serica de ADA nao se associou a atividade de doenca segundo os criterios do SLEDAI 2K, sugerindo que esse teste nao deve ser utilizado como marcador de atividade de doenca em LES. Esse resultado diverge da maioria dos trabalhos publicados, o que pode ser explicado pela dificuldade de padronizacao da tecnica de dosagem da ADA ou por diferenca nas diversas populacoes estudadas.

Guidelines for the treatment of antiphospholipid syndrome

The antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial and venous thrombosis, gestational morbidity and presence of elevated and persistently positive serum titers of antiphospholipid antibodies. The treatment of APS is still controversial, because any therapeutic decision potentially faces the risk of an insufficient or excessive antithrombotic coverage associated with anticoagulation and its major adverse effects. This guideline was elaborated from nine relevant clinical questions related to the treatment of APS by the Committee of Vasculopathies of the Brazilian Society of Rheumatology. Thus, this study aimed at establishing a guideline that included the most relevant and controversial questions in APS treatment, based on the best scientific evidence available. The questions were structured by use of the PICO (patient, intervention or indicator, comparison and outcome) process, enabling the generation of search strategies for evidence in the major primary scientific databases (MEDLINE/PubMed, Embase, Lilacs, Scielo, Cochrane Library, Premedline via OVID). A manual search for evidence and theses was also conducted (BDTD and IBICT). The evidence retrieved was selected based on critical assessment by using discriminatory instruments (scores) according to the category of the therapeutic question (JADAD scale for randomized clinical trials and Newcastle-Ottawa scale for non-randomized studies). After defining the potential studies to support the recommendations, they were selected according to level of evidence and grade of recommendation, according to the Oxford classification.

Hiperparatireoidismo primário em paciente com lúpus eritematoso sistêmico

Primary hyperparathyroidism (PHP) is a metabolic illness that results from autonomous secretion of parathyroid hormone and is one of the most common causes of hypercalcemia. We present the case of a 47-year-old female with a previous diagnosis of systemic lupus erythematosus (SLE) in whom clinical (diffuse bone pain, emotional lability, jaw tumor) and laboratory features (calcium= 13.5 mg/dL, phosphate= 1.8 mg/dL, alkaline phosphatase= 3028 U/L, PTH intact= 1472 pg/dL) prompted the diagnosis of PHP secondary to parathyroid adenoma as demonstrated by the anatomopathology. After treatment with calcitonin spray 400 UI per day, IV pamidronate 90 mg/week, and subtotal parathyroidectomy, the patient status improved with normal laboratory tests. This is the second report to describe the coexistence of these two disorders in a single patient. Although the pathophysiology of the association of PHP and SLE is not known, the recognition of this association has a practical implication since the therapeutical strategy is completely different.

Hodgkin lymphoma as a complication of primary Sjögren’s syndrome

Sjögren’s syndrome (SS) is a chronic autoimmune disease that is characterized by lymphocytic infiltration of the exocrine glands, mainly the salivary and lachrymal glands, usually manifesting with xerostomia and xerophthalmia. Around 50% of patients with primary SS develop systemic complications, lymphoma being the most feared of these. The majority of these neoplasias originate from B cells and are of the non-Hodgkin type. We describe here a rare case of SS in which the patient developed a Hodgkin lymphoma. We also review the literature on this subject.

Pesquisa de anticorpos antinucleossoma em lúpus eritematoso sistêmico

OBJECTIVE: to determine the frequency of antinucleosome (AN) antibodies in systemic lupus erythematosus (SLE) and their association with disease activity. METHODS: cross-sectional study to evaluate patients with diagnosis of SLE based on the American College of Rheumatology criteria. SLEDAI score was used as a disease activity index. AN antibodies were tested by ELISA (INOVA Diagnostics Inc). Systemic sclerosis (SSc) and myositis patients were also studied to determine the diagnostic performance of the ELISA system. RESULTS: a total of 82 SLE patients, 81 female, mean age 35 ± 11.7 years were included in the study. AN antibodies were positive in 48 SLE samples (58.5%), three with myositis (21.4%) and two with SSc (14.2%), determining a sensitivity and specificity of AN antibodies for the diagnosis of SLE of 58.5% and 82.14%, respectively. Utilizing a cut off of 40 U, test was positive in 45 SLE samples (53.65%), two with myositis (13.33%) and one with SSc (6.66%), determining a sensitivity and specificity of AN antibodies for the diagnosis of SLE of 53.65% and 90%, respectively. There were no correlation between AN antibodies and SLEDAI scores. On the other hand, it was observed a positive correlation between anti-DNA antibodies and disease activity (r = 0.42; p < 0.005). CONCLUSIONS: in the present study it was demonstrated a high specificity and moderate sensitivity of AN antibodies for the diagnosis of SLE. However, the lack of association with disease activity suggests that it has limited value in rheumatologic practice.

Amiloidose manifestando-se com pseudo-hipertrofia muscular

AL amyloidosis is a rare disease secondary to extracellular deposition of light chains fragments in organs and tissues. It can cause a wide variety of signs and symptoms, being the muscular pseudohypertrophy form a very rare finding. CASE 1 - a 61-year-old female had a history of myalgia and increase of muscular mass on pelvic and scapular girdle and cervical region. Besides the generalized muscular hypertrophy and discrete macroglossia, the rest of physical examination was normal. CASE 2 - a 51-year-old male complained of tiredness and progressive cutaneous thickening on his thorax, neck and arms for the last two years. Initially, he was misdiagnosed with either scleredema of Buschke or scleroderma. In February 2007 he was referred to our service, reporting symptoms of dysphagia and difficulty to move his tongue. On physical examination, besides the skin thickness, there was an evident muscle hypertrophy out of proportion the reported exercise practice. In both cases, subcutaneous biopsy was undertaken which revealed amyloid deposit by congo red dye.