Paulo Louzada Júnior

Hipogamaglobulinemia como fator de risco para infecção por Cryptococcus neoformans: a propósito de dois casos

Two HIV-seronegative patients with cryptococcal disease refractory to conventional antifungal therapy were submitted to an evaluation of the immune system. Hypogammaglobulinemia was found in both and associated with abnormal function of cell-mediated immunity. Hypogammaglobulinemia is considered as a possible predisposing factor for cryptococcal infection. The importance of the antibodies on the control of Cryptococcus neoformans infection is discussed.

Tibolone in postmenopausal women with systemic lupus erythematosus: A pilot study

OBJECTIVE To determine the influence of the use of tibolone on the frequency of flares of systemic lupus erythematosus (SLE) in postmenopausal patients. METHODS Thirty patients with inactive or controlled SLE were included in the study. Patients were randomized to receive a 12-month course of either tibolona (2.5 mg/day) or placebo. The following were investigated: hypoestrogenism symptoms by Kupperman index, weight; anti-dsDNA antibodies; SLE flares (frequency) assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI); and biochemical profile (total cholesterol, high-density lipoprotein cholesterol [HDL-C], triglycerides, complement components [C3/C4], alpha1-acid glycoprotein, urea, creatinine, 24-h proteinuria, C-reactive protein and erythrocyte sedimentation rate). RESULTS The reduction in Kupperman index was greater in the patients using tibolone than in those using placebo. The mean SLEDAI was not different between the groups during the study as well as SLE flare frequency (tibolone: 2/15 [13.3%] vs. placebo: 1/15 [6.7%]; p=0.54). All cases of flares were considered mild to moderate. Although the groups were similar at the baseline evaluation, after 6 and 12 months of treatment lower values were found in the tibolone group for triglycerides (6 months: 161.6+/-30.9 mg/dl vs. 194.4+/-46.5; p=0.04; 12 months 163.7+/-29.8 mg/dl vs. 204.1+/-49.9 mg/dl; p=0.02; tibolone vs. placebo group, respectively) and for HDL-C (6 months: 40.7+/-10.7 mg/dl vs. 53.4+/-16.5; p=0.02; 12 months: 47.2+/-7.9 mg/dl vs. 63.2+/-16.3mg/dl; p<0.01; tibolone vs. placebo group, respectively). There were no differences between the two groups in any of the remaining variables. CONCLUSION In patients with inactive or stable SLE, the short-term use of tibolone did not significantly affect the frequency of flares. In addition, tibolone was well tolerated and effective to control hypoestrogenism related symptoms in SLE patients.

Minimal change disease: a variant of lupus nephritis

Some patients with systemic lupus erythematosus (SLE) present with nephrotic syndrome due to minimal change disease (MCD). Histopathological diagnosis of patients with SLE and nephrotic-range proteinuria has shown that these patients present with diffuse proliferative glomerulonephritis and membranous glomerulonephritis, World Health Organization (WHO) classes IV and V, respectively, more frequently than the other classes. In the present study, we reported a case of nephrotic syndrome and renal biopsy-proven MCD associated with SLE. A complete remission occurred after steroid treatment, which was followed by a relapse 15 months later with a concomitant reactivation of SLE. A second biopsy showed WHO class IIb lupus nephritis. Prednisone treatment was restarted, and the patient went into complete remission again. The association of MCD and SLE may not be a coincidence, and MCD should be considered as an associated SLE nephropathy.

Hypogammaglobulinemia as predisposing factor for Cryptococcus neoformans infection: regarding two cases

Two HIV-seronegative patients with cryptococcal disease refractory to conventional antifungal therapy were submitted to an evaluation of the immune system. Hypogammaglobulinemia was found in both and associated with abnormal function of cell-mediated immunity. Hypogammaglobulinemia is considered as a possible predisposing factor for cryptococcal infection. The importance of the antibodies on the control of Cryptococcus neoformans infection is discussed.

Preliminary guidelines of the Brazilian Society of Rheumatology for evaluation and treatment of tuberculosis latent infection in patients with rheumatoid arthritis, in face of unavailability of the tuberculin skin test

A detecção e o tratamento da tuberculose infecção latente (TBIL) nos indivíduos com maior risco de progressão para tuberculose doença (TB) são estratégias recomendadas pela Organização Mundial de Saúde para controle dessa enfermidade. O teste tuberculínico, que usa o PPD (do inglês purified protein derivative), é um meio amplamente incorporado à prática clínica para diagnóstico de TBIL. Pacientes com artrite reumatoide têm risco aumentado para desenvolvimento de TB ativa, sobretudo quando em tratamento com biológicos inibidores do TNF. O Consenso 2012 da Sociedade Brasileira de Reumatologia (SBR) para tratamento de artrite reumatoide recomenda rastreamento e, quando indicado, tratamento de TBIL em todo paciente candidato ao uso de qualquer agente biológico. O rastreamento inclui, além de avaliação do risco epidemiológico, radiografia do tórax e teste tuberculínico. O tratamento de TBIL, após exclusão de TB doença, consiste em isoniazida, na dose de 5-10 mg/kg/dia, máximo de 300 mg/dia, por seis meses. Está indicado nos pacientes com teste tuberculínico ≥ 5 mm, positividade ao Igra (do inglês interferonrelease assays), alterações radiográficas compatíveis com TB prévia ou contato próximo com caso de TB. O tratamento da TBIL (quimioprofilaxia) deve ser instituído pelo menos um mês antes do início do biológico, porém excepcionalmente ambos os medicamentos podem ser iniciados concomitantemente, quando a urgência sintomática da situação o exigir. Em setembro de 2014, o Ministério da Saúde, por meio da Coordenação Geral do Programa Nacional de Controle da Tuberculose, publicou nota (n◦ 8 / CGPNCT / DEVEP / SVS / MS, de 10/09/2014) em que informou dificuldades na aquisição do PPD, por indisponibilidade no mercado internacional, o que deve implicar desabastecimento do sistema de saúde brasileiro, ainda sem previsão de normalização. A indisponibilidade do teste tuberculínico já é efetivamente percebida na rede assistencial. Por considerar a situação em curso, a exigir um rápido posicionamento com vistas a orientar a prática clínica, a Comissão de Artrite Reumatoide da SBR decidiu por divulgar as seguintes orientações preliminares, que foram elaboradas por consenso de especialistas. A Comissão sugere consulta às referências selecionadas, que estendem as discussões aqui desenvolvidas.1-12

Polimorfismo Val247Leu do gene β2-glicoproteína 1 pode justificar a gênese de anticorpos antiβ2GP1 e síndrome do anticorpo antifosfolípide na hanseníase multibacilar

BACKGROUND - Multibacillary (MB) leprosy may be manifested with antiphospholipid antibodies (aPL), among which anti-β2GP1 (β2-glycoprotein 1). High titers of aPL are associated with APS (Antiphospholipid Syndrome), characterized by thrombosis. The mutation Val247Leu in the domain V of β2GP1 exposes hidden epitopes with consequent development of anti-β2GP1 antibodies. OBJECTIVE: To evaluate the Val247Leu polymorphism of β2GP1 gene and its correlation with anti-β2GP1 antibodies in leprosy patients. METHODS: The Val247Leu polymorphism was performed by PCR-RFLP and anti-β2GP1 antibodies were measured by ELISA. RESULTS: The genotypic Val/Val was more prevalent in the leprosy group, compared to controls. Regarding the 7 MB patients with APS, four presented heterozygosis and three, Val/Val homozygosis. Although higher titrations of anti-β2GP1 IgM antibodies were seen in MB leprosy group with Val/Leu and Val/Val genotypes, there was no statistical difference when compared to Leu/Leu genotype. CONCLUSION: The prevalence of Val/Val homozygosis in leprosy group can partially justify the presence of anti-β2GP1 IgM antibodies in MB leprosy. The description of heterozygosis and Val/Val homozygosis in 7 patients with MB leprosy and thrombosis corroborates the implication of anomalous phenotype expression of β2GP1 and development of anti-β2GP1 antibodies, with consequent thrombosis and APS.

Síndrome do anticorpo antifosfolípide: estudo comparativo das formas primária e secundária

OBJETIVO: Tracar um perfil clinico e laboratorial da sindrome do antifosfolipide (SAF), comparando a primaria (SAFP) com aquela secundaria (SAFS) ao lupus eritematoso sistemico (LES). METODOS: Avaliamos 27 pacientes com SAFP e 32 com SAFS ao LES, acompanhados no Ambulatorio de Colagenoses do HC/FMRP/ USP, quanto a ocorrencia de trombose arterial, venosa, perda gestacional, livedo reticular, fenomeno de Raynaud, anemia hemolitica auto-imune, plaquetopenia, linfopenia, anticorpos anticardiolipina, anticoagulante lupico, antinucleares, anti-Sm e VDRL. Os anticorpos anticardiolipina e anti-Sm foram pesquisados por ELISA, os antinucleares por imunofluorescencia indireta e o anticoagulante lupico pelo tempo de protrombina diluida, tempo de coagulacao do caulin ou tempo do veneno de vibora de Russell diluido. Para analise estatistica utilizamos o teste exato de Fisher bicaudal. RESULTADOS: Observamos aumento da frequencia de trombose arterial na SAFP (59,3% vs 25,0%, p=0,009) e de trombose venosa na SAFS (53,1% vs 33,3%, p>0,05), enquanto nao houve diferencas entre as frequencias de perda gestacional (50,0% vs 56,7%), fenomeno de Raynaud (18,5% vs 18,8%), livedo reticular (18,5% vs12,5%), anticoagulante lupico (33,3% vs 37,5%) e anticardiolipina IgG (79,2% vs 72,4%) e IgM (58,4% vs 65,5%). Ademais, observamos aumento significante de linfopenia (71,2% vs 7,4%, p<0,0001), de anticorpos antinucleares (100% vs 7,4%, p<0,0001) e de VDRLpositivo (47,1% vs 5,0%, p=0,005) na SAFS ao LES quando comparada com a SAFP. CONCLUSOES: As manifestacoes clinicas e laboratoriais sao semelhantes na SAFP e na SAFS ao LES, sendo a trombose arterial mais comum na SAFP, enquanto a presenca de linfopenia, anticorpos antinucleares e VDRL positivo esta associada com a SAFS ao LES.

AB0417 Biological drugs in the treatment of rheumatoid arthritis: real life data in a brazilian multicentric study

Background Rheumatoid arthritis (RA) is a chronic disease, characterised by inflammatory involvement of the synovial joints. The ”treat to target” concept is well established in the rheumatologic community, however, in many patients, especially in developing countries, its implementation is not feasible. Considering the high costs of treatment com of RA and the limited national epidemiological data available on this disease, we sought to describe the profile of use of biological drugs in Brazilian patients with RA to help the decision-making process by public health managers. Objectives To describe the frequency and time of use of biological drugs in Brazilian patients with rheumatoid arthritis. Methods The REAL – RA in real life in Brazil – is a multicenter prospective cohort study, with twelve-month follow-up period. To be included in this study, consecutive patients from 11 tertiary rheumatology centres had to meet the 1987 ACR or the 2010 ACR/European League Against Rheumatism (EULAR) criteria. Data were collected during routine clinical care and previous medical records were used as secondary sources. The present study present data taken from the participants’ initial assessment. This research was approved by the Ethics Committees of each centre. Results A total of 1125 patients were analysed. 89% were women with a mean age of 56.6 years. The main clinic data were: DAS 28 (median)=3.52, HAQ (median)=0.87 and CDAI (median)=9. 1022 (90.84%) used synthetic DMARDs and 406 (36.09%) biologic therapy. The frequency of use of the biologic therapy was: abatacept (73 patients/6.49%), etanercept (66/5.87%), tocilizumab (60/5.33%), adalimumab (54/4.8%), infliximab (50/4.44%), rituximab (49/4.36%), golimumab (37/3.29%), certolizumab (17, 1.51%). The time of use of the biological drugs is presented in table 1.Abstract AB0417 – Table 1 Time (in years) of use of biological drugs in patients with rheumatoid arthritis DRUG MEAN MAXIMUM ABATACEPT 1.95 8 ADALIMUMAB 1.70 12 CERTOLIZUMAB 0.63 2.0 ETANERCEPT 1.49 9.0 GOLIMUMAB 0.65 2.0 INFLIXIMAB 1.56 9.0 RITUXIMAB 1.27 6.0 TOCILIZUMABE 2.0 6.0 Conclusions The therapeutic profile of this cohort of Brazilian RA patients shows some interesting results. The relatively high number of patients on biologics, compared to other studies, may be related to fact that the centres involved were reference centres, probably dealing with more difficult cases. References [1] Azevedo AB, Ferraz MB, Ciconelli RM. Indirect Costs of Rheumatoid Arthritis in Brazil. Value in Health2008;11(5):869–877. [2] Boonen A, Severens JL. The burden of illness of rheumatoid arthritis. Clin Rheumatol2011;30(Suppl 1):S3–S8. Disclosure of Interest None declared

Oral Nodular Lesions in Patients with Sjögren’s Syndrome: Unusual Oral Implications of a Systemic Disorder

Sjögrens syndrome (SS) is a systemic chronic autoimmune disorder affecting the lacrimal and salivary glands. SS may manifest as primary SS (pSS) or secondary SS (sSS), the latter occurring in the context of another autoimmune disorder. In both cases, the dry eyes and mouth affect the patients quality of life. Late complications may include blindness, dental tissue destruction, oral candidiasis and lymphoma. This paper reports two cases of SS, each of them presenting unusual oral nodular lesion diagnosed as relapsed MALT lymphoma and mucocele. The importance of the diagnosis, treatment and management of the oral lesions by a dentist during the care of SS patients is emphasized, as the oral manifestations of SS may compromise the patients quality of life.