Primeiro caso de febre maculosa brasileira branda associada à artrite / First report of mild Brazilian spotted fever associated to arthritis

Descrevemos o primeiro caso brasileiro de Riquetsiose branda, agravada por monoartrite em joelho, em adulto jovem picado por carrapato na perna esquerda na região de Camburi, localizada no município de São Sebastião, sul da região costeira do estado de São Paulo, Mata Atlântica, Brasil. O paciente apresentou uma escara de inoculação no local da picada do carrapato, associada ao aumento ganglionar em virilha esquerda, febre, poliartralgia, cefaleia e erupção macular. Vinte dias após o episódio da picada de carrapato, o paciente apresentou monoartrite em joelho direito. O diagnóstico de Riquetsiose branda foi estabelecido pela análise imunológica sequencial em amostras de soro e líquido sinovial, tendo sido empregada a técnica de imunofluorescência (IF) indireta para anticorpos reativos contra Rickettsia parkeri e Rickettsia rickettsii. A Riquetsiose branda é uma zoonose emergente, que deve ser investigada pelos médicos, incluindo reumatologistas, em pacientes que apresentem erupção macular, febre e, eventualmente, artrite, após visita ao sul da região costeira da Mata Atlântica no Brasil.

We describe the first Brazilian case of mild Rickettsiosis, complicated by knee monoarthritis, in young adult bitten by a tick on his left leg in Camburi zone, located in São Sebastião municipality, southern coastal region of the State of São Paulo, in the Atlantic rainforest region, Brazil. The patient developed inoculation eschar at the tick bite site associated with enlarged lymph nodes in the left groin, fever, polyarthralgia, headache and macular rash. Twenty days after tick bite episode, he displayed monoarthritis in his right knee. The diagnosis of mild Rickettsiosis was established by sequential immunological analysis in serum and synovial fluid, using the indirect immunofluorescence (IF) assay for antibodies reactive with Rickettsia parkeri and Rickettsia rickettsii. The mild Rickettsiosis is an emerging zoonosis, that must be investigated by physicians, including rheumatologists, in patients that present macular rash, fever and eventually arthritis, after visiting the southern coastal Atlantic rainforest region in Brazil.

Estudo da vasculopatia pulmonar no modelo experimental de esclerodermia induzido pelo colágeno do tipo V / Study of pulmonary vasculopathy in the collagen V-induced systemic sclerosis experimental model

A esclerodermia sistêmica (ES) é caracterizada por fibrose da pele e órgãos internos, ativação imunológica e vasculopatia. Os modelos animais de ES sofrem com a falta de uma prova definitiva para o envolvimento vascular observado na doença humana. Um novo modelo induzido por colágeno do tipo V (COLV) reproduz muitas características da ES como fibrose e fenômenos imunológicos. No entanto, o estudo da vasculopatia ainda não foi abordado. O objetivo desse estudo foi investigar as alterações estruturais e funcionais das células endoteliais das artérias pulmonares do modelo de ES induzido pelo COLV, assim como determinar a doença pulmonar com ênfase especial no depósito de colágeno e síntese de RNAm de colágenos. Coelhos fêmeas Nova Zelândia (n = 8) foram imunizados com COLV humano emulsificado em adjuvante de Freund ou apenas com adjuvante de Freund (controle; n = 8). Após 7, 75 e 210 dias, os animais foram sacrificados e os pulmões foram analisados por microscopia eletrônica, hematoxilina e eosina, e marcações especiais incluindo imunomarcação para neovascularização (CD31), apoptose de células endoteliais (induzida pela caspase-3) e atividade endotelial (endotelina-1 e VEGF). A resposta vascular a acetilcolina (Ach) foi estudada em anéis de artéria pulmonar isolada. Para determinar o conteúdo de colágeno, expressão RNAm dos colágenos I, III e V e quantidade de colágeno (hidroxiprolina aminoácido específico), os pulmões foram submetidos a imunofluorescência, PCR em tempo real e análise bioquímica. Foi observado que os coelhos imunizados com COLV apresentaram um aumento progressivo de apoptose e atividade das células endoteliais a partir de 7 dias quando comparados aos coelhos controle (p 0,01). Em contrapartida, apenas aos 210 dias os coelhos imunizados com COLV apresentaram aumento significativo na neovascularização quando comparados com o grupo controle (p < 0,001). Coincidente com esses achados, a microscopia eletrônica mostrou alterações das células...

The hallmarks of systemic sclerosis (SSc) are fibrosis of skin and internal organs, immune activity and vasculopathy. Animal models of SSc suffer from lack of a definitive evidence for vascular involvement observed in human disease. A novel model induced by collagen type V (COLV) reproduces many features of SSc, however vascular study has not been addressed. The aim of the present study was therefore evaluate pulmonary arteries for structural and functional alterations in endothelial cells in the COLV-induced SSc model, as well as determine the lung disease with special emphasis on collagen deposition and mRNA collagen synthesis. Female New Zealand rabbits (n = 8) were immunized with human COLV/Freund´s adjuvant or Freund´s adjuvant alone (control; n = 8). After 7, 75 and 210 days, the animals were sacrificed and the lungs were examined by electron microscopy, hematoxylin&eosin and special stains including immunostaining for neovascularization (CD31), endothelial cells apoptosis (caspase-3 induced) and endothelial activity (endothelin-1 and VEGF). Vascular response to acetylcholine (Ach) on isolated pulmonary artery rings was evaluated. To determine collagen content, mRNA expressions of COL I, III and V, and the quantity of collagen-specific amino acid hydroxyproline, the lungs were submitted to immunofluorescence, real-time qPCR and biochemical examination. The COLV rabbits demonstrated an endothelial cells apoptosis and activity compared to control rabbits starting at day-7 (p 0.01). A significant increase in neovascularization was observed only in the COLV-rabbits at day-210 (p < 0,001). Coincident with these findings, the electron microscopy revealed extensive endothelial cells abnormalities characterized by apoptosis, degenerative organelle changes and cytoplasmic tumefaction. Endothelial cells appeared to be detached from the basement membrane. Ach dose required to achieve 50% maximum relaxation (EC50) of pulmonary artery rings was increased in COLV...

Decreased high-density lipoprotein cholesterol levels in polyarticular juvenile idiopathic arthritis

OBJECTIVES: To investigate the prevalence of dyslipoproteinemia in a homogeneous cohort of polyarticular juvenile idiopathic arthritis patients. METHODS: Based on the National Cholesterol Education Program, fasting lipoprotein levels and risk levels for coronary artery disease were determined in 28 patients with polyarticular juvenile idiopathic arthritis. The exclusion criteria included diabetes, thyroid dysfunction, smoking, proteinuria, lipid-lowering drugs, and hormone/diuretic therapy. Disease activity, disease duration, and therapy with corticosteroids and/or chloroquine were defined at the time of lipid measurements. RESULTS: Dyslipoproteinemia was identified in 20 of the 28 (71 percent) patients with polyarticular juvenile idiopathic arthritis. The primary lipoprotein risk factor was decreased high-density lipoprotein cholesterol (57 percent), followed by elevated levels of low-density lipoprotein cholesterol (18 percent), triglycerides (14 percent), and total cholesterol (7 percent). The male patients had decreased high-density lipoprotein cholesterol levels than the female patients (p<0.05). The incidence of decreased high-density lipoprotein cholesterol levels did not seem to be affected by disease activity or therapy because the incidence was similar in patients with active or inactive disease, with or without corticosteroid use and with or without chloroquine use. In addition, the frequency of decreased high-density lipoprotein cholesterol levels was similar in patients with short (≤5 years) vs. long (>5 years) disease duration. CONCLUSIONS: Dyslipoproteinemia is highly prevalent in patients with polyarticular juvenile idiopathic arthritis and is primarily related to decreased high-density lipoprotein cholesterol levels; therefore, early intervention is essential.

Doença de lyme-símile brasileira ou síndrome baggioyoshinari: zoonose exótica e emergente transmitida por carrapatos: [revisão] / Brazilian lyme-like disease or baggio-yoshinari syndrome: exotic and emerging brazilian tick-borne zoonosis: [review]

A Doença de Lyme (DL) é uma zoonose frequente no hemisfério Norte e considerada uma enfermidade infecciosa causada por espiroquetas do complexo Borrelia burgdorferi sensu lato e transmitida pela picada de carrapatos do grupo Ixodes ricinus. Os primeiros casos semelhantes à DL no Brasil foram descobertos, em 1992, em irmãos que após serem picados por carrapatos desenvolveram eritema migratório, sintomas gripais e artrite. Criteriosa análise da casuística brasileira, mostrou que os aspectos epidemiológicos, clínicos e laboratoriais no país, divergiam bastante dos exibidos pelos pacientes com DL nos Estados Unidos da América e Eurásia. Não foram encontrados carrapatos do complexo Ixodes ricinus hematófago ao homem nas áreas de risco; a enfermidade no país é recorrente; a Borrelia burgdorferi jamais foi isolada no Brasil e os ensaios sorológicos específicos exibem positividade baixa e oscilante. Além disso, o exame do sangue periférico dos pacientes quando analisados à microscopia eletrônica exibe estruturas sugestivas de Mycoplasma spp, Chlamydia spp e bacteroides. Na verdade, estas estruturas podem representar as formas latentes das espiroquetas (forma L ou bactérias desprovidas de parede), adaptadas a sobreviver em condições inóspitas em hospedeiros vertebrados e invertebrados. Assim, a zoonose presente no país recebeu a denominação de Síndrome Baggio-Yoshinari e definida como: "Enfermidade infecciosa nova e emergente brasileira, transmitida por carrapatos não pertencentes ao complexo Ixodes ricinus, causada por espiroquetas na sua morfologia atípica e latente, que origina manifestações clínicas semelhantes às observadas na DL, exceto pela ocorrência de recidivas clínicas e desordens autoimunes".

Lyme disease (LD) is a frequent zoonosis found in the Northern Hemisphere and is considered an infectious disease caused by spirochetes belonging sensu lato to the Borrelia burgdorferi complex transmitted by ticks of the Ixodes ricinus group. In 1992, first cases similar to LD were described in Brazil, when brothers, after a tick bite episode developed symptoms , as erythema migrans, general flu-like symptoms and arthritis. Careful analysis of Brazilian LD-like illness casuistry showed that epidemiological, clinical and laboratorial features in the country were very different from those exhibited by North American and Eurasian LD patients. Human blood-suckers Ixodes ricinus complex ticks were absent at risk areas; the disease is recurrent in the country; Borrelia burgdorferi was never isolated in Brazil and specific serologic tests have shown little positivity with inconsistent results. Furthermore, peripheral blood analysis of patients on electron microscopy exhibited structures resembling Mycoplasma spp, Chlamydia spp and spirochete-like microorganisms. In fact, they were assumed to be latent forms of spirochetes (L form or cell wall deficient bacteria) adapted to survive at inhospitable conditions in vertebrate and invertebrate hosts. For these reasons, the Brazilian zoonosis was named Baggio-Yoshinari Syndrome (BYS) and defined as: "Exotic and emerging Brazilian infectious disease, transmitted by ticks not belonging to the Ixodes ricinus complex, caused by latent spirochetes with atypical morphology, which originates LD-like symptoms, except for occurrence of relapsing episodes and auto-immune disorders".