HYPERCALCEMIA DUE TO POLYMETHYLMETHACRYLATE INJECTIONS? (LITERATURE REVIEW AND CASE REPORTS).

Hypercalcemia is a common feature of malignancy, bone metabolic conditions and granulomatous disorders. In the latter, hypercalcemia is usually calcitriol-related. As eventual association of silicone and polymethylmethacrylate (PMMA) injections with granulomatous disease and hypercalcemia the condition has become an issue of recent interest. Authors report on two cases of calcitriol-related hypercalcemia where PMMA injections had been previously administered. The association, even though intriguing, requires additional confirmation by follow-up studies.

Anti-CCP antibodies have more diagnostic impact than rheumatoid factor (RF) in a population tested for RF.

To compare the diagnostic powers of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) in a population selected for its high statistical relevance, over a 6-month period, an informed consent to test for anti-CCP was obtained from 1,025 consecutive patients for whom RF was ordered at a University laboratory. Within 1 year, a diagnosis was obtained without informing the physician about the anti-CCP result. Extensive statistical analyses were performed. A total of 768 patients satisfied the inclusion criteria, and 132 were classified as having RA, yielding a pre-test probability of RA of 17%. The sensitivities for anti-CCP and RF were 62 and 64% (P = 0.83), and the specificities were 97 and 90% (P < 0.001), respectively. The positive predictive value (PPV) was 79% for anti-CCP and 56% for RF (P < 0.001), whereas the negative predictive value was 92% for both. The likelihood ratio (LR) was 17.9 for anti-CCP and 6.2 for RF (P < 0.005). Forty RA patients were diagnosed with RA of less than 2 years length, and the same significant statistic differences between anti-CCP and RF were observed. Placing the results of both tests together, or using different cutoff points, increased the diagnostic utility of the tests. The anti-CCP test has statistically shown significant higher specificity, PPV, and LR for RA than the RF test in a clinically diverse population. If new criteria are to be devised to help diagnose early RA, anti-CCP should be included because it has a greater diagnostic impact than RF.

Remission of systemic lupus and overlap syndrome after interferon therapy for chronic C hepatitis

O lúpus eritematoso sistêmico (LES) e a doença indiferenciada do conjuntivo são síndromes auto-imunes sistêmicas de etiologia complexa. Sua patogênese envolve fatores hormonais, ambientais e genéticos. Hepatite C tem sido diagnosticada com frequência crescente em pacientes com quadros de auto-imunidade. Os efeitos do interferon-alfa, antiviral usado rotineiramente na hepatite C, no sistema imunológico de pacientes com LES ou doenças correlatas tem constituído matéria de debate. Descrevem-se aqui duas pacientes com doenças auto-imunes que tiveram a doença básica melhorada após o uso de interferon-alfa para tratamento de hepatite C. A primeira paciente, 52 anos, branca, apresenta quadro de LES com artralgias, proteinúria, leucopenia, anticorpos antinucleares e anti-DNA desde 1996. Em diversas ocasiões esteve internada para corticoterapia endovenosa e imunossupressores. Na evolução, em novembro de 1996, apresentou elevação discreta de transaminases. Hepatite C foi diagnosticada através de sorologia, PCR e biópsia hepática. A terapêutica com interferon-alfa por seis meses foi altamente efetiva na hepatopatia. Concomitantemente, houve remissão clínico-laboratorial do LES. A segunda paciente, branca, 29 anos, apresenta quadro compatível com doença indiferenciada do conjuntivo desde 1990. Clinicamente, cursava com poliartralgias, neurite óptica, síndrome cerebelar, lapsos de memória recente e miopatia. Não havia marcadores sorológicos específicos de auto-imunidade. Em 1994, apresentou grande elevação de enzimas hepáticas. Hepatite C foi confirmada por PCR e biópsia hepática. O tratamento com interferon-alfa em 1995 foi eficaz na hepatite C, incluindo repetida negatividade na PCR, e também no quadro auto-imune. Em 1997 e 1999, os sintomas desmielinizantes recidivaram, mas foram responsivos a corticoterapia. A função permanece normal, com PCR negativo para HCV. Os efeitos do interferon-alfa no sistema imune são múltiplos e complexos. Em transplantados renais, seu uso na hepatite C pode causar rejeição do enxerto. Entretanto, possui, confirmadamente, ação antiproliferativa na leucose de células cabeludas e hemangiomas. De acordo com um estudo russo, o uso de interferons, principalmente se associados a ciclofosfamida, parece ser benéfico no LES. Por outro lado, outros relatos associam o interferon-alfa a induções de LES. Nas duas pacientes aqui reportadas, um potencial efeito imunosssupressor do alfa-interferon parece ter predominado

Anticorpos "anti-human T lymphotropic" vírus tipos I e II (HTLV-I/II) em pacientes com artrite reumatóide / Antibodies anti-human T lymphotropic virus types I and II (HTLV-I/II) in pacients with rheumatoid arthritis

HTLV-I/II são oncorretrovírus associados à leucemia de células T do adulto e à mielopatia crônica progressiva. Poliartrite crônica simétrica e complexo sicca são eventualmente encontrados em casos de infecções por HTLV-I/II. Um recente estudo japonês evidenciou prevalência de 20 por cento de anticorpos anti-HTLV-I em pacientes com artrite reumatóide (AR), um achado significante comparativamente a controles de banco de sangue. Tanto quanto os autores sabem, não há estudos brasileiros a esse respeito. Objetivo: Avaliar a prevalência de anticorpos anti-HTLV-I/II em pacientes com AR, usando um ensaio enzimático (ELISA) e, quando necessário, Western blot para confirmação de positividade. Métodos: Foram estudados 69 pacientes com AR (55 mulheres e 14 homens, todos caucasóides), diagnosticados de acordo com os critérios do Colégio Americano de Reumatologia. A média de idade dos pacientes foi de 51 anos, e a duração média da doença, de 8 anos. Os soros desses pacientes foram inicialmente testados para anticorpos anti-HTLV-I/II em ELISA de segunda geração (Ortho). A positividade foi confirmada através de Western blot (Gene Labs, kit 2.4). Os grupos-controles consistiram de 1.416 doadores de banco de sangue testados por ELISA e 33 pacientes consecutivos com lúpus eritematoso sistêmico (LES), também testados em ELISA. O teste de Fisher foi utilizado para análise estatística, sendo valores de p<0,05 considerados relevantes. Resultados: Anticorpos anti-HTLV-I/II foram detectados em 5 dos 69 pacientes com AR através de ELISA (7 por cento). Destes, 4 (5,7 por cento) tiveram resultados confirmatórios para anti-HTLV-I em Western blot. Os 4 pacientes eram soropositivos para fator reumatóide, mas nenhum apresentava doença ativa. Nos doadores de sangue, 18 soros (1,27 por cento) foram positivos para anti-HTLV-I/II em ELISA (p=0,004, significativo em relação ao grupo com AR testado em ELISA). Nos pacientes com LES, nenhum caso de positividade foi encontrado em ELISA (p=0,07, insignificante em relação aos pacientes com AR). Conclusão: No estudo, a prevalência de anticorpos contra HTLV-I/II em pacientes com AR foi estatisticamente relevante quando comparada com a de doadores de sangue, mas não-significativa quando comparada com a de pacientes com LES. O papel da infecção por HTLV-I/II na AR deve ser clareado em estudos adicionais

Fibrose pulmonar na esclerose sistêmica progressiva: frequência e associações clínicas / Pulmonary fibrosis in progressive systemic sclerosis: frequency and clinical associations

A esclerose sistêmica progressiva (ESP) é uma doença crônica caracterizada por vasculopatia disseminada e fibrose tecidual. O envolvimento intersticial pulmonar constitui uma de suas principais causas de morbimortalidade. Foram estudados 22 pacientes (20 mulheres, 2 homens) com ESP (14 com forma limitada, 8 com forma difusa) quanto à presença de fibrose pulmonar através de tomografia computadorizada (TC). Em 13 pacientes (59 por cento), fibrose pulmonar foi documentada tomograficamente. O RX de tórax foi normal em 6 destes 13 pacientes; nos outros 7 casos, as alterações tomográficas foram mais precoces e definidas do que as encontradas no RX de tórax. Em dois terços dos pacientes com fibrose pulmonar o espirograma simples foi alterado. A presença de estertores crepitantes bibasais constitui-se na anormalidade respiratória mais frequente nos pacientes com fibrose pulmonar. Variáveis como sexo, raça, presença de fatores antinucleares (FAN), padrões de FAN, tosse e dispnéia não foram estatisticamente distintos nos pacientes com ou sem fibrose pulmonar. A frequência de fibrose pulmonar nessa casuística de ESP foi intermediária, considerando-se os contrastantes dados de literatura. A TC foi claramente mais sensível do que o RX de tórax no diagnóstico de alterações fibróticas

Autoantibodies to the nucleolar organizer antigen NOR-90 in children with systemic rheumatic diseases.

OBJECTIVE: To determine the frequency of autoantibodies directed against the nucleolar organizer antigen NOR-90 [human upstream binding factor (hUBF)] in pediatric patients with systemic rheumatic diseases. Two children with antibodies to NOR-90 are reported. METHODS: Two hundred thirty-eight sera from children with systemic rheumatic diseases were screened for autoantibodies directed against hUBF by indirect immunofluorescence and immunoblotting using MOLT-4 cell extracts. Reactivity with hUBF was confirmed by immunoprecipitation of the recombinant hUBF protein. RESULTS: Two sera out of 238 (< 1.0%) with reactivity against hUBF were identified. One patient had recurrent abdominal pain, headache, and Raynaud's phenomenon. There has been no evidence of an active systemic rheumatic disease in more than 8 years of followup. The 2nd patient had Raynaud's phenomenon and systemic lupus erythematosus. CONCLUSION: Antibodies to hUBF are rare in children with systemic rheumatic diseases. Raynaud's phenomenon was a clinical feature common to both patients.

Antiphospholipid antibodies and HLA associations in primary Sjögren's syndrome.

Blood samples from 65 patients with primary Sjögren's syndrome were evaluated for the presence of antiphospholipid antibodies. Increased levels of antiphospholipid antibodies were found in 13 of 65 (20%) of patients. These antiphospholipid antibodies were predominantly of the IgA isotype, in contrast with the IgG isotype antiphospholipid antibodies found in patients with systemic lupus erythematosus (SLE). The presence of IgA antiphospholipid antibodies in the patients with primary Sjögren's syndrome was not significantly associated with arterial or vascular thrombosis, nor peripheral or central nervous system vasculitis. There was no association with laboratory determined features such as lupus anticoagulant or false positive results of the Venereal Disease Research Laboratory (VDRL) test. Oligonucleotide specific DNA amplification and hybridisation with allele specific probes was used to examine the HLA-D antigens occurring in this group of patients with primary Sjögren's syndrome. Of 13 patients with antiphospholipid antibodies, seven had the genotype HLA-DR2/DR3. However, compared with the whole group of 65 patients with Sjögren's syndrome, no increased occurrence of haplotype DR2 or DR3 was noted. These results suggest that gene interaction between DR2 and DR3 may play a part in the production of antiphospholipid antibodies in patients with Sjögren's syndrome. In contrast with patients with SLE, the IgA antiphospholipid antibodies in patients with Sjögren's syndrome are not risk factors for thrombosis or vasculitis. The presence of IgA antiphospholipid antibodies in patients with Sjögren's syndrome probably reflects its production at mucosal sites of inflammation and the absence of vasculopathy may be due to the inability of IgA antibodies to activate complement.

Infective endocarditis, rheumatoid factor, and anticardiolipin antibodies.

Serum samples from 22 patients with infective endocarditis were analysed for the presence of antibodies to cardiolipin, false positive Venereal Disease Research Laboratory (VDRL) test, and rheumatoid factor in order to determine the prevalence of anticardiolipin antibodies, their level, and to ascertain whether there was any correlation with the presence of rheumatoid factor. Although the latex test was positive in 10/22 (45%) patients, anticardiolipin antibodies, usually of a low level, were raised in only four (18%), and the VDRL test was positive in two patients in whom other antibodies were negative. These results show a clear discordance between these three tests, indicating that B cell production of these antibodies is separate and distinct. As with other infections which result in anticardiolipin antibody production, no thrombotic events were encountered.

Antibody to phosphatidylethanolamine in a patient with lupus anticoagulant and thrombosis.

Most patients with lupus anticoagulant (LA) activity have coincident antibodies to a group of negatively charged phospholipids, and its is suggested that LA and anticardiolipin tests detect antibodies with overlapping specificities. Some discordance between the two assays has been described, however. One patient presenting with severe thrombotic disease (recurrent deep vein thrombosis, pulmonary embolism, inferior venocaval obstruction, myocardial infarction, and digital gangrene) showed strong LA activity in February 1987. An enzyme linked immunosorbent assay (ELISA) showed no binding to the negatively charged phospholipids cardiolipin, phosphatidylserine, and phosphatidic acid, but binding to zwitterionic phosphatidylethanolamine (PE) was demonstrated. Inhibition studies and affinity purification confirmed this finding. Interestingly, the serum did not bind to the kaolin cephalin clotting time reagent when used as antigen in an ELISA. The pathogenic significance of anti-PE antibodies and their relation to LA remains to be clarified. Further studies of the occurrence of anti-PE antibodies in patients with LA activity who have negative anticardiolipin tests are suggested.

Transient global amnesia and antiphospholipid antibodies.

The patient, a 55 year-old man, developed an episode of transient global amnesia. He was a smoker and had hypercholesterolemia. He was found to have a positive rapid plasma reagin test and high levels of anticardiolipin antibodies. Other investigations were negative. The presence in this patient of antiphospholipid antibodies suggests a vascular mechanism for transient global amnesia.