Multicenter study of the natural history and therapeutic responses of patients with chikungunya, focusing on acute and chronic musculoskeletal manifestations - a study protocol from the clinical and applied research in Chikungunya (REPLICK network).

BACKGROUND: Chikungunya is associated with high morbidity and the natural history of symptomatic infection has been divided into three phases (acute, post-acute, and chronic) according to the duration of musculoskeletal symptoms. Although this classification has been designed to help guide therapeutic decisions, it does not encompass the complexity of the clinical expression of the disease and does not assist in the evaluation of the prognosis of severity nor chronic disease. Thus, the current challenge is to identify and diagnose musculoskeletal disorders and to provide the optimal treatment in order to prevent perpetuation or progression to a potentially destructive disease course. METHODS: The study is the first product of the Clinical and Applied Research Network in Chikungunya (REPLICK). This is a prospective, outpatient department-based, multicenter cohort study in Brazil. Four work packages were defined: i. Clinical research; ii) Translational Science - comprising immunology and virology streams; iii) Epidemiology and Economics; iv) Therapeutic Response and clinical trials design. Scheduled appointments on days 21 (D21) ± 7 after enrollment, D90 ± 15, D120 ± 30, D180 ± 30; D360 ± 30; D720 ± 60, and D1080 ± 60 days. On these visits a panel of blood tests are collected in addition to the clinical report forms to obtain data on socio-demographic, medical history, physical examination and questionnaires devoted to the evaluation of musculoskeletal manifestations and overall health are performed. Participants are asked to consent for their specimens to be maintained in a biobank. Aliquots of blood, serum, saliva, PAXgene, and when clinically indicated to be examined, synovial fluid, are stored at -80° C. The study protocol was submitted and approved to the National IRB and local IRB at each study site. DISCUSSION: Standardized and harmonized patient cohorts are needed to provide better estimates of chronic arthralgia development, the clinical spectra of acute and chronic disease and investigation of associated risk factors. This study is the largest evaluation of the long-term sequelae of individuals infected with CHIKV in the Brazilian population focusing on musculoskeletal manifestations, mental health, quality of life, and chronic pain. This information will both define disease burden and costs associated with CHIKV infection, and better inform therapeutic guidelines.

Th1 and Th2 polymorphisms in Sjögren's syndrome and rheumatoid arthritis.

BACKGROUND: Sjogren's syndrome is characterized by T-cell infiltration of exocrine glands leading to parenchymal destruction and impaired glandular function. This process is orchestrated by cytokines, whose secretion can be regulated by genetic polymorphisms. MATERIALS AND METHODS: The aim of this study was to investigate the influence of interleukin-6 -174G/C, interleukin-10 -1082G/A, tumor necrosis factor-α -308G/A, interferon-γ +874A/T gene polymorphisms in (RA) and secondary Sjögren's syndrome (sSS). A study sample that comprised of 138 Brazilian patients was divided into three groups: RA (n = 66), sSS (n = 20), and healthy controls - C (n = 52). Patients were subjected to Schirmer's test, unstimulated salivary flow rate, biopsy of minor salivary glands, and serological tests for diagnosing SS. Genomic DNA was obtained from saliva samples and submitted to genotyping. The association between genotypes/alelle frequency and SS susceptibility was tested, as well as their association with clinical features of SS. RESULTS: Tumor necrosis factorα (TNFα)-308GA polymorphisms differed significantly between AR, SS, and C patients (P = 0.008). IL-6 overall G carriers and TNFα A carriers had a higher risk of presenting SS (P = 0.021). IL-6 polymorphism distribution was also distinctive regarding lymphocytic infiltration at the minor salivary glands (P = 0.026) and Schirmer's test (P = 0.035). CONCLUSION: These results suggest that IL-6 -174GC and TNFα-308GA gene polymorphisms are associated with susceptibility to SS. Additionally, IL-6 polymorphism could influence lymphocytic infiltration of salivary glands and diminish lachrymal gland function.

Characterization of clinical, laboratory, IL-6 serum levels, and IL-6-174 G/C genetic polymorphisms in patients with rheumatoid arthritis and Sjögren's syndrome.

OBJECTIVE: This study aimed to characterize the clinical (disease activity and exocrine gland function), laboratory, interleukin 6 (IL-6) serum levels, and IL-6-174G/C (rs1800795) genetic polymorphisms among rheumatoid arthritis (RA), RA plus Sjögren's syndrome (RA+SS), and control subjects. METHODS: A case-control study enrolling 137 women (52±11 years old) were divided into three groups as follows: RA (n=70), RA+SS (n=29), and healthy control (C, n=38). Individuals underwent clinical evaluation composed of Schirmer's test, unstimulated salivary flow rate, and evaluation of disease activity and functional capacity (Disease Activity Score [DAS28] and Health Assessment Questionnaire [HAQ]). IL-6 serum levels and IL-6-174G/C polymorphisms were assessed. RESULTS: RA and RA+SS presented higher serum levels of IL-6 than controls (p<0.001). Also, higher IL-6 levels were related to swollen joints (p=0.038), limited functional capacity (p=0.004), and disease activity (p≤0.001). However, neither IL-6-174G/C genetic polymorphism nor its allele frequency was associated with RA or RA+SS. CONCLUSION: IL-6 serum is an important marker of RA activity and functional incapacity, but IL-6-174G/C genetic polymorphism did not differ among healthy controls and cases.

Analysis of helkimo and craniomandibular indexes for temporomandibular disorder diagnosis on rheumatoid arthritis patients.

AIM: The aim of this study was to evaluate the use of two indexes (Helkimo and Craniomandibular) for the diagnosis of temporomandibular disorder (TMD) in patients with Rheumatoid Arthritis (RA). PATIENTS AND METHODS: The sample was composed of 80 patients divided into two groups: patients with RA and patients without RA. In both groups the two indexes were used. For TMD diagnosis, the following signs and symptoms were evaluated: TMJ pain, limited mouth opening and joint sounds. RESULTS: Results showed that of the RA patients, 87.1% were females and 12.9% were males. Among the patients without RA, 70% were females and 30% were males. The age of these RA patients ranged between 24 and 78 years. Among patients without RA, the age of the patients ranged between 22 and 72 years. It was observed that the prevalence of TMD was higher in the group with RA (98.6%-Helkimo and 87.1%-Craniomandibular) when compared to the group without the disorder (80%-Helkimo and 50%-Craniomandibular). CONCLUSION: In summary, one could conclude that both indexes are capable to diagnose temporomandibular disorders in RA patients, although the Helkimo index is less accurate.

Juvenile Sjögren syndrome: distinctive age, unique findings.

Juvenile Sjögren's syndrome is a rare condition that affects children and adolescents with distinctive clinical features. Parotid swelling usually precedes regular oral and ocular symptoms, while typical serological findings may be absent. Hence, diagnosing juvenile Sjögren's syndrome may be challenging to the attending pediatric dentist, and long-term management without proper diagnosis may be jeopardized. The purpose of this report was to detail the features of an adolescent with primary Sjögren's syndrome diagnosed 12 years after the onset of the disease. An updated literature review highlighted the unusual aspects of the pediatric form of the disease.

Bisphosphonates can reduce bone hunger after parathyroidectomy in patients with primary hyperparathyroidism and osteitis fibrosa cystica.

OBJECTIVE: To assess the effect of bisphosphonates on post-parathyroidectomy hypocalcemia in patients with osteitis fibrosa cystica. METHODS: Review of the medical records of six patients using bisphosphonates preoperatively. RESULTS: Mean age was 35.6 ± 10.5 years; serum calcium = 13.51 + 0.87 mg/dL; iPTH = 1,389 + 609 pg/mL. The mean value of urine deoxypyridinoline (UDPD) of three patients was 131 ± 183 nmol/mmol Cr, and of C-telopeptide (CTX), 2,253 ± 1,587 pg/mL. The mean values of bone densitometry (T score) were as follows: 0.673 ± 0.150 g/cm(2) (-4.42 ± 1.23) in lumbar spine (L2-L4); 0.456 ± 0.149 g/cm(2) (-5.58 ± 1.79) in the femoral neck; and 0.316 ± 0.055 g/cm(2) (-5.85 ± 0.53) in radius 33. Patient 1 received oral alendronate, 30 mg/day for four weeks; his calcium decreased from 14 to 11.6 mg/dL, and his UDPD from 342 to 160 nmol/mmol Cr. Patient 2 received oral alendronate, 20 mg/day for six weeks; his calcium decreased from 14 to 11.0 mg/dL and his UDPD from 28.8 to 14 nmol/mmol Cr. Patient 3 received intravenous pamidronate, 90 mg prior to surgery. Patient 4 received oral alendronate, 140 mg/week for six weeks; her calcium decreased from 13.7 to 12.3 mg/dL and her CTX from 2,160 to 1,340 pg/mL. Patient 5 received oral alendronate, 140 mg/ week for six weeks; her calcium levels dropped from 14.3 to 14.1 mg/dL; her CTX did not change. Patient 6 received ibandronate, 150 mg, ten days prior to surgery; his CTX reduced by 62%. No patient developed severe hypocalcemia in the first postoperative week. One year after surgery, the mean gain in bone mineral density was 40% ± 29% in L2-L4, 86 ± 39% in the femoral neck, and 22% ± 11% in radius 33. CONCLUSION: The preoperative use of bisphosphonates seems to attenuate bone hunger without preventing a significant increase in bone mass in the follow-up of parathyroidectomy.

Bisfosfonatos podem minimizar a fome óssea após paratireoidectomia em pacientes com hiperparatireoidismo primário e osteíte fibrosa cística / Bisphosphonates can reduce bone hunger after parathyroidectomy in patients with primary hyperparathyroidism and osteitis fibrosa cystica

OBJETIVO: Avaliar o efeito dos bisfosfonatos na hipocalcemia pós-paratireoidectomia em pacientes com osteíte fibrosa cística. MÉTODOS: Foram revisados os prontuários de seis pacientes que fizeram uso pré-operatório de bisfosfonatos. RESULTADOS: A idade média foi de 35,6 ± 10,5 anos; cálcio sérico 13,51 ± 0,87 mg/dL; PTHi 1.389 ± 609 pg/mL. O valor médio de deoxipiridinolina urinária (UDPD) de três pacientes foi de 131 ± 183 nmol/mmol Cr; e do C-telopeptídeo (CTX) de 2.253 ± 1.587 pg/mL. Densitometria óssea (escore T) obteve média de 0,673 ± 0,150 g/cm² (-4,42 ± 1,23) em coluna lombar (CL); 0,456 ± 0,149 g/cm² (-5,58 ± 1,79) em colo de fêmur (CF) e 0,316 ± 0,055 g/cm² (-5,85 ± 0,53) em rádio 33 (RD). Um paciente recebeu alendronato oral 30 mg/dia por 4 semanas; o cálcio diminuiu de 14 para 11,6 mg/dL e UDPD de 342 para 160 nmol/mmol Cr. Outro usou alendronato oral 20 mg/dia por 6 semanas; o cálcio baixou de 14 para 11,0 mg/dL e UDPD de 28,8 para 14 nmol/mmol Cr. Um paciente recebeu pamidronato 90 mg endovenoso antes da cirurgia. Um paciente usou alendronato oral 140 mg/semana por 6 semanas; o cálcio diminuiu de 13,7 para 12,3 mg/dL e o CTX de 2.160 para 1.340 pg/mL. Outro usou alendronato VO 140 mg/semana por 6 semanas; o cálcio baixou de 14,3 para 14,1 mg/dL; o CTX não reduziu. Um paciente fez ibandronato 150 mg 10 dias antes da cirurgia; o CTX caiu em 62 por cento. Nenhum paciente desenvolveu hipocalcemia grave na primeira semana do pós-operatório. Um ano após a cirurgia, houve aumento de 40 ± 29 por cento em CL, 86 ± 39 por cento em CF e 22 ± 11 por cento em RD. CONCLUSÃO: O uso pré-operatório de bisfosfonatos parece atenuar a fome óssea sem impedir o marcante aumento de massa óssea no seguimento da paratireoidectomia.

OBJECTIVE: To assess the effect of bisphosphonates on post-parathyroidectomy hypocalcemia in patients with osteitis fibrosa cystica. METHODS: Review of the medical records of six patients using bisphosphonates preoperatively. RESULTS: Mean age was 35.6 ± 10.5 years; serum calcium = 13.51 + 0.87 mg/dL; iPTH = 1,389 + 609 pg/mL. The mean value of urine deoxypyridinoline (UDPD) of three patients was 131 ± 183 nmol/mmol Cr, and of C-telopeptide (CTX), 2,253 ± 1,587 pg/mL. The mean values of bone densitometry (T score) were as follows: 0.673 ± 0.150 g/cm² (-4.42 ± 1.23) in lumbar spine (L2-L4); 0.456 ± 0.149 g/cm² (-5.58 ± 1.79) in the femoral neck; and 0.316 ± 0.055 g/cm² (-5.85 ± 0.53) in radius 33. Patient 1 received oral alendronate, 30 mg/day for four weeks; his calcium decreased from 14 to 11.6 mg/dL, and his UDPD from 342 to 160 nmol/mmol Cr. Patient 2 received oral alendronate, 20 mg/day for six weeks; his calcium decreased from 14 to 11.0 mg/dL and his UDPD from 28.8 to 14 nmol/mmol Cr. Patient 3 received intravenous pamidronate, 90 mg prior to surgery. Patient 4 received oral alendronate, 140 mg/week for six weeks; her calcium decreased from 13.7 to 12.3 mg/dL and her CTX from 2,160 to 1,340 pg/mL. Patient 5 received oral alendronate, 140 mg/ week for six weeks; her calcium levels dropped from 14.3 to 14.1 mg/dL; her CTX did not change. Patient 6 received ibandronate, 150 mg, ten days prior to surgery; his CTX reduced by 62 percent. No patient developed severe hypocalcemia in the first postoperative week. One year after surgery, the mean gain in bone mineral density was 40 percent ± 29 percent in L2-L4, 86 ± 39 percent in the femoral neck, and 22 percent ± 11 percent in radius 33. CONCLUSION: The preoperative use of bisphosphonates seems to attenuate bone hunger without preventing a significant increase in bone mass in the follow-up of parathyroidectomy.

Rituximabe na síndrome de Felty refratária / Rituximab in the refractory Felty's syndrome

Os autores relatam o caso de uma paciente de 29 anos com diagnóstico de artrite reumatoide soropositiva que com seis meses de evolução desenvolveu granulocitopenia severa e esplenomegalia, embora mantivesse em remissão o quadro articular. Não apresentou resposta à corticoterapia oral e em forma de pulsos, além do metotrexato e leflunomida, tendo apresentado reação adversa ao uso do infliximabe e falta de resposta ao adalimumabe. Diante das infecções de repetição, apesar dos vários esquemas de antibióticos e uso crônico do G-CSF, dos altos títulos de fator reumatoide, dos níveis elevados da VHS e da PCR, utilizou-se o rituximabe no esquema clássico de tratamento da artrite reumatoide. Houve resposta clínica completa com aumento crescente do número de neutrófilos e normalização dos mesmos além da queda dos títulos de fator reumatoide, da VHS e da PCR. Atualmente, a paciente encontra-se em remissão clínica e laboratorial, em uso de prednisona 5 mg/dia e metotrexato 10 mg/semana.

The authors report a case of a 29 year old woman who has seropositive rheumatoid arthritis for six months, and developed severe granulocytopenia and important splenomegaly, however she didnït show any joint inflammation. She did not respond either to pulse or oral steroids, or to oral methotrexate and leflunomide. She also developed an adverse reaction to the use of infliximab and did not respond well to adalimumab. Although she has had repeated infections, despite the various forms of antibiotics and long-term use of G-CSF, with high titers of rheumatoid factor, and high levels of ESR and CRP, the classic Rituximab method for treating rheumatoid arthritis was used. There was a good clinical response with an increase in the number of neutrophils following normalization of them, together with the reduction of rheumatoid factor titers, ESR and CRP. At the moment, the patient is in remission, according to both clinical and laboratory criteria and taking 5mg of prednisone per day and 10mg of methotrexate per week.

Análise dos índices de Helkimo e craniomandibular para diagnóstico de desordens temporomandibulares em pacientes com artrite reumatóide / Analysis of helkimo and craniomandibular indexes for temporomandibular disorder diagnosis on rheumatoid arthritis patients

OBJETIVO: O estudo teve como finalidade avaliar a utilização de dois índices (Helkimo e craniomandibular) para o diagnóstico da desordem temporomandibular (DTM) em pacientes com Artrite Reumatóide (AR). MATERIAIS E MÉTODOS: A amostra foi de 80 pacientes divididos em dois grupos: pacientes com AR e pacientes sem AR. Em ambos os grupos os dois índices foram utilizados. No diagnóstico da DTM foram avaliados os seguintes sinais e sintomas: dor na ATM; limitação de abertura de boca e ruídos articulares. RESULTADOS: Os resultados mostram que dos pacientes com AR 87,1 por cento eram do gênero feminino e 12,9 por cento do masculino. Entre os pacientes sem AR, 70 por cento eram do gênero feminino e 30 por cento do masculino. A idade dos pacientes com AR variou de 24 a 78 anos. Entre os pacientes sem AR, a idade variou de 22 a 72 anos. Foi verificado que a prevalência de DTM foi mais elevada no grupo de pacientes com AR (98,6 por cento - Helkimo e 87,1 por cento - craniomandibular) do que no grupo sem a doença (80 por cento - Helkimo e 50 por cento - craniomandibular). CONCLUSÃO: Em resumo, temos que ambos os índices são capazes de diagnosticar a desordem temporomandibular em pacientes com AR, entretanto o índice de Helkimo é menos preciso.

AIM: The aim of this study was to evaluate the use of two indexes (Helkimo and Craniomandibular) for the diagnosis of temporomandibular disorder (TMD) in patients with Rheumatoid Arthritis (RA). PATIENTS AND METHODS: The sample was composed of 80 patients divided into two groups: patients with RA and patients without RA. In both groups the two indexes were used. For TMD diagnosis, the following signs and symptoms were evaluated: TMJ pain, limited mouth opening and joint sounds. RESULTS: Results showed that of the RA patients, 87.1 percent were females and 12.9 percent were males. Among the patients without RA, 70 percent were females and 30 percent were males. The age of these RA patients ranged between 24 and 78 years. Among patients without RA, the age of the patients ranged between 22 and 72 years. It was observed that the prevalence of TMD was higher in the group with RA (98.6 percent - Helkimo and 87.1 percent - Craniomandibular) when compared to the group without the disorder (80 percent - Helkimo and 50 percent - Craniomandibular). CONCLUSION: In summary, one could conclude that both indexes are capable to diagnose temporomandibular disorders in RA patients, although the Helkimo index is less accurate.

Índices de Helkimo e Craniomandibular para diagnóstico de desordens têmporo-mandibulares: revisão da literatura / The helkimo and craniomandibular indices for the diagnosis of temporomandibular disorders: a review of the eview of the literature

As Desordens Têmporo-mandibulares (DTM) estão definidas como um conjunto de alterações que afetam a ATM e/ou os músculos da mastigação como também estruturas da face, relacionadas ao complexo maxilomandibular. São encontradas numa estimativa de 50 a 60 por cento da população, sendo as mulheres três vezes mais afetadas que os homens, com tal distinção, tendendo a diminuir com o avanço da idade. Observa-se também, que a maioria dos pacientes acometidos encontra-se entre os 35 e 50 anos de idade. Embora o conhecimento da fisiopatologia das desordens têmporo-mandibulares tenha sofrido grande avanço, ainda existe controvérsia em relação à prevalência de cada condição patológica e quanto ao tratamento mais eficaz e apropriado a ser estabelecido para cada situação. A utilização de índices, como o de Helkimo e o Craniomandibular, é necessária para permitir que a severidade da desordem seja categorizada de forma individual, examinar a incidência do problema numa população específica, mensurar a efetividade das terapias e estudar fatores etiológicos, auxiliando o profissional no diagnóstico de DTM e na conduta do paciente. Este trabalho objetiva realizar uma revisão de literatura acerca dos índices de Helkimo e Craniomandibular como facilitadores do diagnóstico de desordens têmporo-mandibulares.