Coriorretinopatia de Birdshot: relato de caso e perspectivas sobre o tratamento / Birdshot chorioretinopathy: a case report and perspectives on its treatment

RESUMO A coriorretinopatia de Birdshot é uma uveíte posterior bilateral crônica rara que acomete, preferencialmente, mulheres de meia-idade. O quadro clínico é composto de pouco ou nenhum processo inflamatório de segmento anterior, associado a vitreíte e lesões coriorretinianas ovoides branco-amareladas de característica hiperfluorescente na angiofluoresceinografia e hipofluorescente na angiografia com indocianina verde. O tratamento se dá por meio de corticoides e outras drogas imunossupressoras. Todavia, em alguns casos, a doença é refratária a tal terapêutica, sendo necessário lançar mão de outras drogas, como os agentes biológicos. O presente artigo busca relatar um caso de coriorretinopatia de Birdshot em ajuste de terapia imunossupressora que evoluiu com má resposta às drogas iniciais e bom controle após uso de imunobiológico e discutir as opções terapêuticas disponíveis atualmente.

ABSTRACT Birdshot chorioretinopathy is a rare chronic bilateral posterior uveitis that preferentially affects middle-aged women. The clinical picture is composed of little or no anterior segment inflammatory process, associated with vitritis and yellowish-white ovoid chorioretinal lesions with hyperfluorescent characteristics on fluorescein angiography and hypofluorescent characteristics on green indocyanine green angiography. Treatment is with corticosteroids and other immunosuppressive drugs. However, in some cases, the disease is refractory to such therapy, making it necessary to resort to other drugs such as biological agents. The present article seeks to report a case of Birdshot chorioretinopathy in an adjustment of immunosuppressive therapy that evolved with poor response to the initial drugs and good control after the use of immunobiologicals and discuss the currently available therapeutic options.

Associação entre HLA e leucemia em uma população brasileira de etnia mista / Association between HLA and leukemia in a mixed Brazilian population

OBJETIVOS: O objetivo deste estudo foi investigar a freqüência de antígenos HLA Classe I e de alelos HLA Classe II em 164 pacientes com vários tipos de leucemias: 35 pacientes com LLA (leucemia linfóide aguda), 50 com LMA (leucemia mielóide aguda) e 78 com LMC (leucemia mielóide crônica). MÉTODOS: A tipagem HLA Classe I foi realizada por microlinfocitotoxicidade e a de Classe II por PCR-SSP (polymerase chain reaction - sequence specific of primers), ambas da One Lambda (Canoga Park, CA, US). RESULTADOS: Em pacientes com LLA, as freqüências das variantes HLA-B45 e HLA-B56 foram maiores (P = 0,02; OR = 3,13; 95 por centoIC = 0,94-10,44; P = 0,03; OR = 3,61; 95 por centoIC = 0,47-27,64, respectivamente), quando comparadas com controles. Nos pacientes com LMA, a freqüência de HLA-B7 (P = 0,01; OR = 2,41; 95 por centoIC = 1,25-4,67) foi maior que em controles. A presença de HLA-B45 (P= 0,01; OR = 3,29; 95 por centoIC = 1,46-7,40) e de HLA-DRB1*04 (P = 0,002; OR = 2,17; 95 por centoIC = 1,36-3,46) e HLA-DRB1*08 (P = 0,004; OR = 2,36; 95 por centoIC = 1,34-4,16) foi associada ao maior risco de desenvolver LMC. CONCLUSÃO: Nossos resultados sugerem que variantes HLA conferem susceptibilidade a algumas formas de leucemia e podem prover novas ferramentas para a investigação da genética e etiologia desta doença.

OBJECTIVE: The main purpose of this study was to investigate the class I HLA antigens and class II HLA allele frequencies in 164 patients with leukemia: 35 patients with ALL (acute lymphoid leukemia), 50 with AML (acute myeloid leukemia) and 78 with CML (chronic myeloid leukemia). METHODS: The genotyping of class I HLA was performed by microlymphocytotoxicity and of class II by PCR-SSP (polymerase chain reaction - sequence specific of primers) (One Lambda, Canoga Park, CA, USA). RESULTS: In patients with LLA, frequencies of HLA-B45 and HLA-B56 were higher (P = 0.02; OR = 3.13; 95 percentIC = 0.94-10.44; P = 0.03; OR = 3.61; 95 percentIC = 0.47-27.64, respectively), than in controls. In patients with AML, the frequency of HLA-B7 (P = 0.01; OR = 2.41; 95 percentIC = 1.25-4.67) was higher than in controls. The presence of HLA-B45 (P= 0.01; OR = 3.29; 95 percentIC = 1.46-7.40), HLA-DRB1*04 (P = 0.002; OR = 2.17; 95 percentIC = 1.36-3.46) and HLA-DRB1*08 (P = 0.004; OR = 2.36; 95 percentIC = 1.34-4.16) was associated to increased risk of CML developing. CONCLUSION: Our results suggest that variants of HLA confer susceptibility to the same forms of leukemia, and could provide new tools for the investigation of genetics and etiology of this disease.

Preliminary study of HLA-ABCDR antigens in CML, ANLL, thalassemia and severe aplastic anemia in Thais.

The objective of this study was to analyse human leukocyte antigen (HLA) and disease association in common blood diseases [chronic myelogenous leukemia (CML), acute nonlymphocytic leukemia (ANLL), thalassemia and severe aplastic anemia] in Thais. The subjects were patients from the Hematological Clinic, Departments of Medicine and Pediatrics, Ramathibodi Hospital who were referred for HLA typing for bone marrow transplantation (BMT) at the Histocompatibility Laboratory from March 1988 to September 1997. A total of 129 patients had complete HLA-ABC typing. The patients included 45 CML, 40 ANLL, 26 thalassemia (Thal) and 18 severe aplastic anemia (SAA). Of these, 88 patients were typed for HLA class II. The HLA class I (ABC) and II (DR, DQ) typings were performed by microlymphocytotoxicity test. It was found that HLA class I was associated with CML, ANLL and Thal, whereas, HLA class II was associated with SAA. HLA-B8 and HLA-B18 were increased in CML with R.R. values of 12.2 and 3.9, respectively, whereas, HLA-B18 was increased in ANLL with R.R. value of 4.5. In addition, HLA-DR2 and DR3 were increased in SAA with R.R. values of 3.8 and 4.8, respectively. For Thal, HLA-A2 and B46 were increased in Thal in Central Thais with R.R. values of 3.3 and 6.1, respectively, whereas, HLA-B13 was increased in Thal in Northern Thais with R.R. value of 8.5. On the other hand, HLA-B7 was absent in CML. HLA-Cw7 was decreased in CML and SAA, whereas, HLA-DR6 was decreased in ANLL and SAA. Furthermore, HLA-Cw6 was also decreased in CML, whereas, HLA-A33 and Bw4 were decreased in SAA. Although the sample size of each disease was small, the increase of HLA-DR2 was observed in SAA in Thais which was similar to other studies in different ethnic groups. These preliminary data may be useful for further study in HLA and blood disease association.

Human leucocytic antigens (HLA) in breast cancer.

HLA frequencies of fifty (50) female breast cancer patients were compared with 200 age matched female controls. A total of 20 HLA-A locus, 35 HLA-B locus and 8 HLA-C locus antigens were studied. The HLA-A2, A11, Aw19 and A30; HLA-B8, B14 and HLA Cw6 were found significantly higher than the controls. The HLA-A11, HLA-Aw19 and HLA-B8 were found protective whereas, HLA-A2, HLA-B14 and HLA-Cw6 were a risk for breast cancer. The prective antigens' probable involvement through immunogenic mechanism in breast cancer is emphasized in this article.

Distribution of HLA-A and B antigens in northeastern-Thais.

The phenotype and gene frequencies of HLA class I were studied in the Northeastern Thai population. Blood samples were collected from 100 unrelated healthy Northeastern Thais. HLA-A and B antigens were typed by using the standard microlymphocytotoxicity test. Twelve HLA-A and twenty-five HLA-B antigens were found in this population. HLA-A2, A24, A11 and the HLA-B46, B15, B22 antigens are commonly found in this group. Linkage disequilibrium analysis indicated the existence of fifteen haplotypes. The HLA-A2, B46 haplotype was the most common. These results will be useful for further studies in anthropology, organ transplantation and MHC associated disease in Northeastern Thais.

HLA association with sarcoidosis and diffuse interstitial pulmonary fibrosis.

HLA typing was performed on 18 patients suffering from sarcoidosis and 30 patients suffering from diffuse interstitial pulmonary fibrosis. One hundred normal healthy people ethnically matched served as the controls. On statistical analysis, the corrected 'p' value of all the HLA antigens for both the patient groups was non significant. The results therefore suggest that there is no particular HLA antigen associated with sarcoidosis and diffuse interstitial pulmonary fibrosis.

Análise de associação entre cardiopatia chagásica crônica e antígenos HLA de classe I (HLA-A, -B e -C) e de classe II (HLA-DR e -DQ) / Analysis of association between chronic Chagas Cardiomyopathy and antigens HLA of class I (HLA It, - B and - C) and of class II (HLA-DR and - DQ)

Considerando que o sistema HLA contem genes que controlam a resposta imune, bem como genes de susceptibilidade genética a diversas doenças, temos como objetivo a realização de um estudo de associação entre os antígenos HLA e a doença de CHAGAS, forma cardíaca. Foram analisadas as freqüências dos antigenos HLA-A, -B, -C, -DR E -DQ em 47 pacientes com cardiopatia chagásica crônica e 95 indivíduos controles. Essas amostras iniciais são constituídas por caucasóides e negroides. As analises estatísticas mostram um aumento estatisticamente significante da freqüência de HLA-DR2 nos pacientes, quando comparados com os controles. a significativo ns freqüências de dr-2, cujas freqüências nos pacientes e controles são de 48,3por cento e 12,3por cento, respectivamente (pc=0,0058). Os resultados sugerem uma associação positiva do antígeno DR-2 com cardiopatia chagásica crônica. Embora os resultados indiquem uma possível associação com DR-2 também em negroides, os nossos dados não são conclusivos para esse grupo racial, devido ao pequeno tamanho da amostra analisada

Lack of association between paracoccidioidomycosis and HLA histocompatibility antigens

Foi realizado um estudo de associaçäo HLA e doença, onde 40 pacientes com diagnóstico clínico e laboratorial de Paracoccidioidomicose (PCM) e, 80 indivíduos brancos, clinicamente saudáveis, usados como controles, foram tipados para os antígenos HLA-A, -B, -Cw, -DR e - DQ. Os resultados obtidos mostraram uma associaçäo positiva dos antígenos HLA-A1 (P = 0.050), -A3 (P = 0.014), -B8 (P = 0.014), -Cw7 (P = 0.020), - DQw2 (P = 0.014) e DQw3 (P = 0.019) nos pacientes e uma associaçäo negativa dos antígenos HLA-Cw3 (P = 0.032), -DR1 (P = 0.019) e -DQw1 (P = 0.003) no mesmo grupo, comparados aos controles e, sem correçäo pelo número de antígenos testados (50). Os resultados sugerem uma fraca associaçäo destes antígenos HLA com a doença, uma vez que outros fatores podem também estar influenciando na susceptibilidade genética à PCM. Se corrigido o valor de P, segundo Svejgaard e Ryder (HLA and disease, J, Dausset and A. Svejgaard, eds., 1977), nenhuma associaçäo é demonstrada neste estudo

Quantitation of HLA antigens on red cells by immunoradiometric assay.

Immunoradiometric assay was employed to quantitate HLA antigens on red cells. Using this technique HLA-B7, HLA-B17 and HLA-A28 were detected on the red cells of all individuals studied irrespective of the serological status of the Bennett-Goodspeed (Bg) antigens. However, HLA antigenic sites for serologically Bg positive red cells were significantly more than that for Bg negative red cells (P less than 0.001). Bga positive red cells possessed maximum number of antigenic sites as compared to Bgb and Bgc positive red cells.

HLA-B5 and B21 antigens in aortoarteritis.

The distribution of class I HLA antigens (HLA-A, B) were determined in 50 patients of Aortoarteritis in an Indian population. This included 29 females and 21 males. The difference in antigen frequency was observed between patients and controls with reference to HLA-A19, B5 and B21 antigens. A decreased frequency of HLA-A19 was observed in the patients as compared to controls (14% vs 33.25%, X2 = 6.81, P less than 0.025). Of the B locus antigens, an increased frequency of HLA B5 was observed in the patients as compared to controls (48% vs 29.5%, X2 = 6.2, P less than 0.025). HLA-B21 was also increased in the patients as compared to the controls (18% vs 6.5%, X2 = 6.67, P less than 0.025). These data suggest the involvement of genetic factor (s) in the aetiopathogenesis of this disease. Further, the observations indicate that HLA-B5 and B21 may be associated with Aortoarteritis.

Spectrum of seronegative spondarthritides (SSA) with special reference to HLA profiles.

The present study describes the profile of seronegative spondarthritides (SSA) in young servicemen. SSA was diagnosed in 63 patients from a prospective study on spondyloarthropathy. The SSA group consisted of ankylosing spondylitis (AS, 40 patients), Reiter's syndrome (RS, 6) and SSA undifferentiated (SSA-U, 17). The chief clinical and radiological features of the group were due to sacro-iliitis/spondylitis, peripheral arthritis and enthesopathy. Except for RS, extra-articular features were sparse. Mucosal lesions were not evident. Radiologically, sacro-iliitis varied from 24% in SSA-U to 100% in AS, and was disproportionately less when compared to its clinical extent. Dominant lower limb arthritis (poly and oligo) was seen in AS (40%), SSA-U (88.2%) and RS (100%). HLA A and B were typed in patients and controls. HLA AI had a significant negative association (p less than 0.05) with AS and the SSA group, and its relative risk (R) was consistently low (0.2-0.3). HLA B27 was present in 65.7%, 73%, 67%, 41% and 9% of the SSA group, AS, RS, SSA-U and controls respectively (p less than 0.05). Significant R values of A and B loci antigens in disease groups are presented. When compared with available Indian literature, this study highlights the variability and overlap in the disease. Disease markers currently available have limitations in defining the various subsets of SSA.

HLA antigens in Indian population with non-specific aortoarteritis.

HLA typing of Class I antigens (HLA - A & -B loci) was done for 65 patients suffering from nonspecific aortoarteritis, in Indian population. The diagnosis of these patients was based on clinical findings and confirmed by angiographic studies. Decreased phenotype frequency of HLA-A19 (p less than 0.005, relative risk 0.28), increased frequency of HLA-B5 (p less than 0.005, relative risk 2.46) and B21 (p less than 0.005, relative risk 3.25) was observed when compared with the control group. A decreased frequency of two other alleles of B locus i.e. B35 (p less than 0.005, relative risk 0.27) and B40 (p less than 0.05, relative risk 0.04) was seen in patient group as compared to control. The data indicate the possible association of HLA-B5 and B21 antigens with the nonspecific aortoarteritis.

Enfermedad injerto contra huesped asociada a transfusiones reconocimiento de dos casos infantiles por la biopsia del piel / Graft versus host disease associated with transfusions. Detection of 2 infantile a report o 2 cases by skin biopsy

Se presentaron dos casos de enfermedad injerto contra huésped asociada a transfusiones (Eichat) en los que la biopsia de piel jugó un papel central en la orientación diagnóstica. El primero correspondió a una niña de 2 años con anemia de Blackfan-Diamond que desarrolló el proceso inmune dos semanas después de recibir dos transfusiones de glóbulos rojos sedimentados. El estudio del HLA linfocitario mostró la presencia de 3 HLA-A, dos de los cuales estaban en los dadores. El segundo caso transfusiones de sangre completa.Ambos casos se acompañaron de un grave compromiso medular y en la biopsia de piel se reconoció el patrón de apoptosis de queratinocitos con satelitosis linfocitaria. Estos hallazgos histológicos, aunque altamente sugestivos, deen ser evaluados en el contexto clínico del paciente