TRPV1 participates in the protective effect of propolis on colonic tissue of ulcerative colitis / 中南大学学报(医学版)

OBJECTIVES@#Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) mainly characterized by inflammation, ulceration and erosion of colonic mucosa and submucosa. Transient receptor potential vanilloid 1 (TRPV1) is an important mediator of visceral pain and inflammatory bowel disease. This study aims to investigate the protective effect of water soluble propolis (WSP) on UC colon inflammatory tissue and the role of TRPV1.@*METHODS@#Male SD rats were randomly divided into 6 groups (n=8): a normal control (NC) group, an ulcerative colitis model (UC) group, a low-WSP (L-WSP) group, a medium-WSP (M-WSP) group, a high-WSP (H-WSP) group, and a salazosulfapyridine (SASP) group. The rats in the NC group drank water freely, and the other groups drank 4% dextran sulfate sodium (DSS) solution freely for 7 d to replicate the ulcerative colitis model. Based on the successful replication of the UC, the L-WSP, M-WSP, and H-WSP groups were given 50, 100, and 200 mg/kg of water-soluble propolis by gavage for 7 d, and the SASP group was given 100 mg/kg of sulfasalazine by gavage for 7 d. The body weight of rats in each group was measured at the same time every day, the fecal traits and occult blood were observed to record the disease activity index (DAI). After intragastric administration, the animals were sacrificed after fasted 24 h. Serum and colonic tissue were collected, and the changes of MDA, IL-6 and TNF-α were detected. The pathological changes of colon tissues were observed by HE staining, and the expression of TRPV1 in colon tissues was observed by Western blotting, immunohistochemistry, and immunofluorescence.@*RESULTS@#The animals in each group that drank DSS freely showed symptoms such as weight loss, decreased appetite, depressed state, and hematochezia, indicating that the model was successfully established. Compared with the NC group, DAI scores of other groups were increased (all P<0.05). MDA, IL-6, TNF-α in serum and colon tissues of the UC group were increased compared with the NC group (all P<0.01), and they were decreased after WSP and SASP treatment (all P<0.01). The results of showed that the colon tissue structure was obviously broken and inflammatory infiltration in the UC group, while the H-WSP group and the SASP group significantly improved the colon tissue and alleviated inflammatory infiltration. The expression of TRPV1 in colon tissues in the UC group was increased compared with the NC group (all P<0.01), and it was decreased after WSP and SASP treatment.@*CONCLUSIONS@#WSP can alleviate the inflammatory state of ulcerative colitis induced by DSS, which might be related to the inhibition of inflammatory factors release, and down-regulation or desensitization of TRPV1.

The effect of Niclosamide in acetic acid induce colitis: an experimental study

Ulcerative colitis is an idiopathic chronic inflammatory disease of the colon for which a lot of treatment modalities are present. However, significant side effects are associated with them, and there is a need for a search for other tretment options. This study was aimed to assess the contribution of niclosamide in experimentally established colitis in rats. Animals were categorized into 5 groups; the control group undergoes no induction of UC, colitis group in which UC was induced, and animals receive no treatment, the niclosamide group that received niclosamide and sulfasalazine group that received sulfasalazine. Each group was composed of 10 animals. After the completion of a one-month period of the experiment animals were sacrificed and the following meausres were done: the weight of the colon, determination of the area of mucosal damage by mm2, histological scoring after hematoxylin and eosin stain together with MAC score and immunohistochemistry of IL-6, TNF-alpha, MPO, MDA, CD62, and ICAM1. The results of the current study revealed that Nicosamide was able to reduce the area of mucosal damage, colon weight, histological and Mac scores and immunohistochemical scores of inflammatory and oxidative markers, significantly when contrasted to a group of colitis (P< 0.05). It has been concluded that Niclosamide was proved to have a significant effect as an adjuvant mode of therapy for colitis through its, anti-inflamatory and anti-oxidant effects (AU)

Informe de evaluación científica basada en la evidencia disponible: colitis ulcerosa / Scientific evaluation report based on available evidence: ulcerative colitis

INTRODUCCIÓN: La colitis ulcerosa es una enfermedad inflamatoria crónica que afecta la mucosa del colon en forma continua, comprometiendo el recto y una porción variable de la extensión del resto del colon, sin la presencia de granulomas en la biopsia. En esta enfermedad, el sistema inmune reconoce esta porción del colon como ajena al cuerpo y lo ataca generando úlceras que caracterizan a esta enfermedad. TECNOLOGÍAS SANITARIAS ANALIZADAS: Adalimumab, azatioprina, golimumab, infliximab, mesalazina, lansoprazol, omeprazol, sulfasalazina y colestiramina. EFICACIA DE LOS TRATAMIENTOS: Se extrajeron 31 revisiones sistemáticas que incluyen 11 ensayos controlados aleatorizados que evaluaban la eficacia de adalimumab, golimumab e infliximab en pacientes con colitis ulcerosa moderada a grave. El tratamiento con adalimumab aumenta ligeramente el número de pacientes que cicatrizan su mucosa e incrementan su score IBDQ (calidad de vida) en más de 12 puntos, a las 8 semanas. El tratamiento con golimumab probablemente aumenta el número de pacientes que responden clínicamente a las 6 semanas, mientras que probablemente aumenta ligeramente el número de pacientes que remite y cicatrizan su mucosa a las 6 semanas. Además, golimumab probablemente no genera diferencias en cuanto a la calidad de vida (cuestionario IBDQ) de pacientes con colitis ulcerosa. El tratamiento con infliximab aumenta el número de pacientes que presentan respuesta clínica a las 8 semanas, mientras que reduce ligeramente el número de pacientes que reciben colectomía a las 54 semanas. No se encontró evidencia de eficacia de los tratamientos sobre una menor hospitalización o una menor estadía hospitalaria, ni estudios que evaluaran la eficacia en niños con colitis ulcerosa. ANÁLISIS ECONÓMICO: Infliximab resultó ser la alternativa que presentó mayor efectividad. Sin embargo, la efectividad incremental en relación a adalimumab es sólo de 0,66 QALYs, superándolo en costes en aproximadamente un 45%. Infliximab y golimumab fueron los tratamientos que presentaron mayor costo en relación a adalimumab. En esto se incluyen los costos de efectos adversos serios, porcentaje de pacientes que se sometían a colectomía mientras estaban en terapia con algún biológico y los costos de administración de infliximab. Para este último se consideró un costo mayor, ya que como su administración es intravenosa se deben considerar las horas en que el paciente debe estar en una sala de observaciones para que se le administre el biológico. En cuanto a las agencias internacionales, Inglaterra recomienda el uso de adalimumab, infliximab o golimumab en pacientes con colitis ulcerosa moderada a grave, siempre y cuando la terapia convencional no funcione o no sea la adecuada. El impacto presupuestario calculado para el primer año de tratamiento fue de MM$1.810 para adalimumab, $MM2.424 para infliximab, y MM$353.378 para golimumab. CONCLUSIÓN: Para dar cumplimiento al artículo 28° del Reglamento que establece el proceso destinado a determinar los diagnósticos y tratamientos de alto costo con Sistema de Protección Financiera, según lo establecido en los artículos 7°y 8° de la ley N°20.850, aprobado por el decreto N°13 del Ministerio de Salud, se concluye que el presente informe de evaluación se considera favorable, de acuerdo a lo establecido en el Título III. de las Evaluaciones Favorables de la Norma Técnica N° 0192 de este mismo ministerio.

Perfil do uso de drogas modificadoras de doenca no Registro Brasileiro de Espondiloartrites / Profile of the use of disease modifying drugs in the Brazilian Registry of Spondyloarthritides

Introdução: Poucos estudos avaliaram o perfil do uso de drogas modificadoras de doença (DMD) em pacientes brasileiros com diagnóstico de espondiloartrite (EpA). Métodos: Um protocolo comum de investigação foi prospectivamente aplicado em 1505 pacientes classificados como EpA pelos critérios do Grupo Europeu de Estudo das Espondiloartrites (ESSG), acompanhados em 29 centros de referência em Reumatologia no Brasil. Variáveis clínicas e demográficas foram obtidas e avaliadas, analisando-se suas correlações com o uso das DMD metotrexato (MTX) e sulfasalazina (SSZ). Resultados: Pelo menos uma DMD foi utilizada por 73,6% dos pacientes, sendo MTX por 29,2% e SSZ por 21,7%, enquanto 22,7% utilizaram ambas as drogas. O uso do MTX foi significativamente associado ao acometimento periférico, e a SSZ foi associada ao comprometimento axial, sendo que as duas drogas foram mais utilizadas, isoladas ou combinadas, no comprometimento misto (p < 0,001). O uso de uma DMD esteve significativamente associado à etnia branca (MTX; p = 0,014), lombalgia inflamatória (SSZ; p = 0,002), dor em nádegas (SSZ; p = 0,030), cervicalgia (MTX; p = 0,042), artrite de membros inferiores (MTX; p < 0,001), artrite de membros superiores (MTX; p < 0,001), entesite (p = 0,007), dactilite (MTX; p < 0,001), doença inflamatória intestinal (SSZ; p < 0,001) e acometimento ungueal (MTX; p < 0,001). Conclusão: O uso de pelo menos uma DMD foi referido por mais de 70% dos pacientes numa grande coorte brasileira de pacientes com EpA, sendo o uso do MTX mais associado ao acometimento periférico e o uso da SSZ mais associado ao acometimento axial. .

Introduction: Few studies have evaluated the profile of use of disease modifying drugs (DMD) in Brazilian patients with spondyloarthritis (SpA). Methods: A common research protocol was applied prospectively in 1505 patients classified as SpA by criteria of the European Spondyloarthropathies Study Group (ESSG), followed at 29 referral centers in Rheumatology in Brazil. Demographic and clinical variables were obtained and evaluated, by analyzing their correlation with the use of DMDs methotrexate (MTX) and sulfasalazine (SSZ). Results: At least one DMD was used by 73.6 % of patients: MTX by 29.2 % and SSZ by 21.7%, while 22.7 % used both drugs. The use of MTX was significantly associated with peripheral involvement, and SSZ was associated with axial involvement, and the two drugs were more administered, separately or in combination, in the mixed involvement (p < 0.001). The use of a DMD was significantly associated with Caucasian ethnicity (MTX , p = 0.014), inflammatory back pain (SSZ, p = 0.002) , buttock pain (SSZ, p = 0.030), neck pain (MTX, p = 0.042), arthritis of the lower limbs (MTX, p < 0.001), arthritis of the upper limbs (MTX, p < 0.001), enthesitis (p = 0.007), dactylitis (MTX, p < 0.001), inflammatory bowel disease (SSZ, p < 0.001) and nail involvement (MTX, p < 0.001). Conclusion: The use of at least one DMD was reported by more than 70% of patients in a large cohort of Brazilian patients with SpA, with MTX use more associated with peripheral involvement and the use of SSZ more associated with axial involvement. .

Manejo de Crohn colónico refractario a corticoides y sulfazalazina: primer caso de uso pediátrico de infliximab en el Perú / Management of colonic Crohn disease with no response to corticoids and sulfazalazine: first case of pediatric use of infliximab in Peru

Presentamos el primer caso pediátrico peruano de uso de infliximab para inducir remisión en enfermedad de Crohn. Caso: niña de 9 años, con presencia de fístulas perianales desde los 8 meses de edad, además de diarreas recurrentes y pobre ganancia ponderal. Se le realizó una colostomía a los 4 años de edad, sin variación. A esa edad, una biopsia mostró colitis crónica severa superficial y profunda extensiva a la muscularis mucosae con áreas de fibrosis y atrofia glandular, planteándose enfermedad de Crohn. Recibió manejo con corticoides, sulfasalazina y antibióticos sin mejoría. A los 8 años de edad presentaba desnutrición crónica reagudizada, además de anemia moderada. Se decidió iniciar terapia con infliximab, 100 mg por dosis aplicada (5,5 mg/kg/dosis). A la cuarta infusión todas las fístulas perianales estaban inactivas, sin embargo, presentó exacerbación de la enfermedad a los 8 meses de tratamiento. Se decidió agregar azatriopina a 2 mg/kg/d VO y se acortaron las infusiones de mantenimiento a cada 4 semanas. Toda la sintomatología gastrointestinal se resolvió. Hasta el momento la niña no presenta eventos adversos a la administración de la terapia médica. Conclusión: El caso presentado corresponde a una presentación temprana, rara y agresiva de enfermedad de Crohn. El infliximab se constituye en herramienta clave para alcanzar la remisión.

We present the first Peruvian pediatric case of induction of remission and maintenance of Crohn’s disease with infliximab. Case: 9-year old female who presented with perianal fistulas, intermittent diarrhea and poor weight gain since 8 months of age. Due to lack of improvement with medical therapy she had a colostomy at 4 years of age. A surgical biopsy showed chronic colitis with inflammation extending to the muscularis mucosae, with areas of glandular atrophy. A diagnosis of Crohn’s disease was made. She received prednisone, sulfasalazine and antibiotics without significant improvement. She became undernourished, stunted, and anemic. Consequently, at 8 years of age we started infliximab, 100 mg per doses (5.5 mg/kg/doses). After 4 infusions her perianal fistulas closed. However, after 8 months of treatment she had a disease exacerbation with abdominal pain and diarrhea. Therefore, we added azathioprine (2 mg/kg/d PO) and shortened maintenance infliximab infusions from every 8 to every 4 weeks. Gastrointestinal symptoms resolved. So far the patient has had no adverse events secondary to therapy. Conclusion: This patient has a rare early onset and aggressive form of Crohn’s disease that responded to infliximab, who needed the addition of azathioprine to maintain remission.

A case of hemophagocytic syndrome in a patient with fulminant ulcerative colitis superinfected by cytomegalovirus

Hemophagocytic syndrome (HPS) is an uncommon hematological disorder that manifests as fever, splenomegaly, and jaundice, with hemophagocytosis in the bone marrow and other tissues pathologically. Secondary HPS is associated with malignancy and infection, especially viral infection. The prevalence of cytomegalovirus (CMV) infection in ulcerative colitis (UC) patients is approximately 16%. Nevertheless, HPS in UC superinfected by CMV is very rare. A 52-year-old female visited the hospital complaining of abdominal pain and hematochezia for 6 days. She was diagnosed with UC 3 years earlier and had been treated with sulfasalazine, but had stopped her medication 4 months earlier. On admission, her spleen was enlarged. The peripheral blood count revealed pancytopenia and bone marrow aspiration smears showed hemophagocytosis. Viral studies revealed CMV infection. She was treated successfully with ganciclovir. We report this case with a review of the related literature.

Guidelines for the Management of Ulcerative Colitis / 대한소화기학회지

Ulcerative colitis (UC) is a chronic inflammatory bowel disorder characterized by a relapsing and remitting course. The quality of life can decreases significantly during exacerbations of the disease. The incidence and prevalence of UC in Korea are still lower than those of Western countries, but have been rapidly increasing during the past decades. Various medical and surgical therapies are currently used for the management of UC. However, many challenging issues exist and sometimes these lead to differences in practice between clinicians. Therefore, Inflammatory Bowel Diseases (IBD) Study Group of Korean Association for the Study of Intestinal Diseases (KASID) set out the Korean guidelines for the management of UC. These guidelines are made by the adaptation using several foreign guidelines and encompass treatment of active colitis, maintenance of remission and indication for surgery in UC. The specific recommendations are presented with the quality of evidence. These are the first Korean treatment guidelines for UC and will be revised with new evidences on treatment of UC.

Guidelines for the Management of Crohn's Disease / 대한소화기학회지

Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) with uncertain etiopathogenesis. CD can involve any site of gastrointestinal tract from the mouth to anus and is associated with serious complications such as bowel strictures, perforations, and fistula formation. The incidence and prevalence rates of CD in Korea are still lower than those of Western countries, but have been rapidly increasing during the past decades. Although there are no definitive curative modalities for CD, various medical and surgical therapies are currently applied for diverse clinical situations of CD. However, a lot of decisions on the management of CD are made depending on the personal experiences and personal dicision of physicians. To suggest preferable approaches to diverse problems of CD and to minimize the variations according to physicians, guidelines for the management of CD are needed. Therefore, IBD Study Group of the Korean Association for the Study of the Intestinal Diseases has set out to develop the guidelines for the management of CD in Korea. These guidelines were developed using the adaptation methods and encompass the treatment of inflammatory disease, stricturing disease, and penetrating disease. The guidelines also cover the indication of surgery, prevention of recurrence after surgery, and CD in pregnancy and lactation. These are the first Korean guidelines for the management of CD and the update with further scientific data and evidences is needed.

Hepatotoxicidade induzida por sulfassalazina: relato de caso / Hepatotoxicity induced by sulfasalazine: case report

A sulfassalazina é ainda muito utilizada nas doenças inflamatórias intestinais, sobretudo na retocolite ulcerativa leve e moderada. Entretanto, seu uso é relacionado a vários efeitos colaterais, incluindo disfunção hepática grave.Este é um relato do caso de paciente masculino, 21 anos, portador de retocolite ulcerativa moderada, com queixa de inapetência, febre, artralgia e icterícia, há sete dias. Antecedente pessoal de uso de sulfassalazina 4 g/dia há seis semanas. Ao exame físico apresentava-se ictérico, com exantema em membros e edema de membros inferiores. Exames complementares mostravam aumento de bilirrubinas, enzimas hepáticas e canaliculares e da proteína C reativa. Com o diagnóstico de hepatotoxicidade por sulfassalazina, foi suspensa a medicação e introduzido prednisona 20 mg/dia e ciprofloxacino 1 g/dia. Recebeu alta no terceiro dia de internação após melhora clínica e laboratorial. Atualmente encontra-se assintomático e em uso de azatioprina 150 mg/dia.

The sulfasalazine is widely used in inflammatory bowel disease, especially in mild and moderate ulcerative rectocolitis. However, its use is related to several side effects, including severe liver dysfunction. We report the case of male patient, 21 years, with the moderate ulcerative rectocolitis, complaining of inappetence, fever, arthralgia and jaundice for seven days. Personal history includes use of sulfasalazine 4 g/day during six weeks. The physical examination revealed jaundiced, with members in rash and lower extremity edema. Laboratory exams showed an increase in bilirubin, liver enzymes and canalicular and C-reactive protein. With the diagnosis of hepatotoxicity by sulfasalazine, this medication was suspended, and introduced prednisone 20 mg/day and ciprofloxacin 1g/day. He was discharged on the third day of admission after clinical and laboratorial improvement. Currently, he is asymptomatic and in use of azathioprine 150 mg/day.

Fraturas do fêmur proximal no idoso: estudo de custo da doença sob a perspectiva de um hospital público no Rio de Janeiro, Brasil / Hip fractures in the elderly: cost of illness study in a public hospital perspective, Rio de Janeiro, Brazil

O artigo visa a estimar o custo direto médico do tratamento hospitalar de pacientes idosos com fraturas de fêmur proximal, no Hospital Municipal Lourenço Jorge, na cidade do Rio de Janeiro. Estudo observacional, prospectivo, para estimar a utilização de recursos e custos diretos médicos associados à hospitalização por fratura de fêmur proximal em idosos, em 2007 e 2008, sob a perspectiva do prestador de serviços. Foi utilizado um instrumento de coleta de dados através do qual foram registrados recursos identificados na revisão prospectiva dos prontuários. Aos recursos utilizados foram atribuídos custos em reais (R$) baseando-se em valores do ano 2010. Foram realizadas análises descritivas dos custos e utilização de recursos, bem como avaliada a associação de variáveis clínicas e demográficas com o custo final observado. Foram incluídos 82 pacientes, 81,7 por cento do sexo feminino, idade média de 76,96 anos, hospitalização média de 12,66 dias. A mediana de custo por paciente foi de R$ 3.064,76 (IC95 por cento: 2.817,63 a 3.463,98). Hospitalização clínica e procedimento cirúrgico foram responsáveis por 65,61 por cento e 24,94 por cento dos custos, respectivamente. Pacientes submetidos ao tratamento cirúrgico até o quarto dia de hospitalização apresentaram mediana de custos menor do que pacientes submetidos após o quarto dia (R$ 2.136,31 e R$ 3.281,45, p<0,00001). Observou-se também diferença significativa nos custos finais por tipo de procedimento cirúrgico realizado. O custo do tratamento das fraturas de fêmur proximal no idoso foi significativamente maior nos pacientes submetidos à cirurgia após o quarto dia de hospitalização. Hospitalização clínica e procedimento cirúrgico foram os principais componentes do custo final observado.

This paper aims to assess direct medical costs associated to hospital treatment of hip fractures in the elderly in the Municipal Hospital Lourenço Jorge (HMLJ), Rio de Janeiro. Observational, prospective study to assess resource utilization and direct medical costs associated to elderly hip fracture hospitalization in 2007 and 2008, under the health care provider perspective. A standard data collection instrument was used to register identified resources during prospective medical charts review. The resource utilization was converted into Brazilian Real (R$), based on 2010 prices. Descriptive analysis of costs and resource utilization and their association with clinical and demographic variables were performed. Eighty two patients were included, 81.7 percent female, mean age of 76.96 years, hospitalization mean time of 12.66 days. Median total costs per patient were R$ 3,064.76 (IC95 percent: 2,817.63 - 3,463.98). Clinical hospitalization and surgical procedure were responsible for 65.61 percent and 24.94 percent of costs, respectively. Median costs for patients submitted to surgical procedure until the fourth day of hospitalization were lower than median costs for patients submitted after the fourth day (R$ 2,136.45 and R$ 3,281.45, respectively, p<0.00001). A significant difference in average costs per type of surgical procedure was also observed. Cost associated to inpatient treatment of hip fractures in the elderly was higher in patients who performed surgery after the fourth day of hospitalization. Clinical hospitalization and surgical procedure were the main cost components observed.

A Case of Hemophagocytic Syndrome in an Ulcerative Colitis Patient / 대한소화기학회지

A case of hemophagocytic syndrome associated with ulcerative colitis is very rare. A 32-year-old man visited the hospital complaining of fever and severe abdominal pain for 7 days. He was diagnosed to have ulcerative colitis 2 years ago and had been treated with sulfasalazine. Three months ago, he had abdominal pain, weight loss, and hematochezia, so prednisolone and mercaptopurine were added to the treatment. On admission, the physical examination showed splenomegaly. Peripheral blood counts revealed pancytopenia, and bone marrow aspirate smears showed many histiocytes with active hemophagocytosis. There was no evidence of viral and bacterial infections and other neoplasms, which were commonly associated with hemophagocytic syndrome. He was successfully treated with high dose steroid. We report this case along with a review of the related literatures.

The effect of 677C>T and 1298A>C MTHFR polymorphisms on sulfasalazine treatment outcome in rheumatoid arthritis

Despite the availability of several new agents for the treatment of rheumatoid arthritis (RA), sulfasalazine remains the mainstay because of both cost and experience with its use. Methylenetetrahydrofolate reductase (MTHFR) is involved in folate metabolism and several polymorphisms have been described in the MTHFR gene. Of these, the 677C>T and 1298A>C polymorphisms have been associated with altered enzyme activity. To examine the association between 677C>T and 1298A>C MTHFR polymorphisms and sulfasalazine efficacy for the treatment of RA, a total of 117 RA patients treated with sulfasalazine (1 g daily; duration of treatment 17 ± 5 months) were analyzed. The 677C>T and 1298 A>C polymorphisms were detected using a PCR-RFLP method. RA was diagnosed according to the criteria of the American College of Rheumatology (ACR). The remission of RA symptoms was evaluated according to the ACR 20% response criteria. Allele and genotype frequencies were compared by the two-sided Fisher exact test. The frequency of remission was 47.2% and 44.6% in carriers of 677T and 1298C alleles, compared to 40.7% and 42.0% in carriers of 677C and 1298A alleles, respectively. These differences were statistically non-significant. When the multivariate analysis was additionally adjusted for patients’ age, gender and RA duration, the association of the MTHFR 677T allele with increased frequency of remission was statistically significant. Although RA remission rate in carriers of the MTHFR 677T and 1298C alleles was more frequently observed, it does not seem that 677C>T and 1298A>C MTHFR polymorphisms have a major influence on treatment outcome in RA patients treated with sulfasalazine.

Tema de Atualização e Revisão em Clínica Médica: Artrite reumatoide: Como eu trato / Theme of Updating and Revision in Medical Clinic: Rheumatoid arthritis: How I treat

Na última década, o tratamento da artrite reumatoide evoluiu imensamente. Graças à elucidação e ao melhor conhecimento dos mecanismos patogênicos, o que propiciou disponibilidade de medicamentos que, além de melhorarem a sintomatologia dolorosa, reduzsem ou interrompem a progressão das erosões ósseas e destruição articular. Também colaboram para esse progresso a melhora dos testes laboratoriais e provas de imagem, auxiliando o diagnóstico e a avaliação da atividade da artrite, aliada à insistência em se tratar agressivamentea doença assim que o diagnóstico é confirmado e a disponibilidade de parâmetros objetivos de avaliação da atividade da doença.

The treatmento of rheumatoid arthritisenvolved immensely in the past decade. Thanks to the elucidation and better understanding of the pathogenic mechanism that hindered the availability of drugs that not only improve the pain symptoms, but also decrease or interrupt the bone erosion progression and joint destruction. The improvement of laboratory and imaging tests for diagnosis and evaluation of disease flare-up, in addition to the insistency in start treating aggressively as soon as the diagnosis is confirmed and the utilization of objective disease evaluation tools, also helped in the progress of rheumatoid arthritis treatment.

A new strategy of drug treatment in NSAID-unresponsive ankylosing spondylitis: combination of pamidronate and methylprednisolone monthly intravenous infusions on the background of a combination of disease modifying drugs sulfasalazine and methotrexate.

OBJECTIVES: To assess short term efficacy and tolerability of a therapeutic strategy in patients with ankylosing spondylitis (AS) unresponsive to nonsteroidal anti-inflammatory drugs (NSAIDs) or coxibs and unable to take anti-tumour necrosis factor-alpha (anti-TNFalpha) biological treatment. METHODS: Established AS patients were given a background treatment consisting of subcutaneous injections of methotrexate weekly (MTX, dose stepped up to a maximum of 20 to 25 mg), weekly 12-16 mg of methylprednisolone orally 30 mts before methotrexate dose (for nausea prevention), sulfasalazine (SSZ, 1 gm orally twice per day) with folic acid supplementation (5 mg daily except on the day of MTX). Additionally, they were given monthly cycles of intravenous (IV) methylprednisolone 'pulse' (MPP) and pamidronate infusions (MPP 500 mg 3 consecutive days + pamidronate 60 mg in a slow IV infusion on day 2 of the MPP infusion). A minimum of six treatment cycles at monthly intervals were given. Adjunct treatment consisted of 1 gm elemental calcium supplementation, paracetamol 650 mg 'as-and-when-required' for symptomatic pain relief, amitriptyline 10 mg 2 hours before bed time daily. RESULTS: Of a total of 46 intent-to-treat patients, 39 patients achieved ASAS-20 and BASDAI-50 response (85%, 95% CI, range 71% to 94%); 7 (15 %) patients failed to improve. The expense involved in 6 months of treatment was approximately 10-fold less than anti-TNFalpha treatment over the same period of time. CONCLUSION: For AS patients unresponsive to standard NSAIDs/coxibs and unable to take anti-TNF biological agents a combination therapeutic strategy showed efficacy and good tolerability in a majority of patients evaluated over a short-term.

Pathogenesis and Treatment of Intestinal Behcet's Disease / 대한소화기학회지

Intestinal Behcet's disease (BD) refers to colonic ulcerative lesions documented by objective measures in patients with BD. Although the causes of intestinal BD are unknown, genetic, environmental, and immunological factors have been suggested. Intestinal BD is common in BD patients from Far East, while it is uncommon in those from the Middle East. The reasons for such peculiar geographic distribution in intestinal BD are unknown, but may provide clues for the elucidation of putative etiological agents or genetic factors that might be associated with intestinal BD. Although the treatment of Crohn's disease has improved significantly during past decade, the treatment of intestinal BD is still problematic. Corticosteroids, sulfasalazine, immunomodulators, and colchicines have been used to treat intestinal BD with varying degree of success. Thalidomide and its analogues also appear to be applicable. Monoclonal antibodies to TNF-alpha have recently been focused as a novel therapeutic option for patients with intestinal BD.

Pyoderma gangrenosum associated with osteomyelitis in a paediatric patient: a case report / Pioderma Gangrenoso Asociado con Osteomielitis en un Paciente Pediátrico Reporte de Caso

Pyoderma gangrenosum is a rare ulcerative skin disorder mainly occurring in adults. It is seen less frequently in children. The cause is unknown but it may occur in association with several disorders. Osteomyelitis is a very rare association. We report a case of pyoderma gangrenosum associated with osteomyelitis in a two-year-old girl

El pioderma gangrenoso es un raro trastorno cutáneo ulcerativo que se produce principalmente en adultos. Se observa con menos frecuencia en los niños. La causa es desconocida, pero puede ocurrir en asociación con varios desórdenes. Su asociación con la osteomielitis es rara. Reportamos un caso de pioderma gangrenoso asociado con osteomielitis en una niña de dos años de edad.

Doença de Behçet na adolescência: relato de um caso com boa resposta à sulfasalazina / Behçet's disease in adolescence: case report with a good response to sulfasalazine

As autoras relatam a história, o diagnóstico e a evolução de um caso de um menino de 14 anos com doença de Behçet. Trata-se de uma vasculite crônica, multissistêmica, de causa desconhecida, que se caracteriza por úlceras orais recorrentes, úlceras genitais, uveíte e lesões de pele. O tratamento desta doença varia de acordo com os autores, dependendo das manifestações clínicas do paciente. Dentre as drogas utilizadas incluem-se esteróides tópicos, colchicina e agentes citotóxicos tais como azatioprina, clorambucil e ciclofosfamida. O interferon e, mais recentemente, um bloqueador TNF-α também vêm sendo prescritos. Os benefícios da sulfasalazina no tratamento da vasculite intestinal têm sido relatados há bastante tempo (2,19,20,21). No entanto, na literatura revisada, não se encontrou nenhum artigo que referisse o uso desta droga em adolescentes portadores de Behçet. A boa resposta à sulfasalazina e a baixa ocorrência de efeitos colaterais motivaram o relato deste caso (AU)

The authors report a case of Behçet's disease in a 14 year-old boy with history, diagnosis and evolution of this pathology. Behçet's disease is a multistemic vasculitis of unknow cause, with recurrent oral and genital ulcers, uveitis and skin lesions. The treatment varies according to different authors, taking into consideration the patients' clinical manifestations. The drugs that can be used in these cases are topic steroids, colchicine, cytotoxic agents such as azatioprine, clorambucil and ciclofosfamide. Interferon and a TNF-α blocker have also been used. The benefits of sulfasalazine in the treatment of patients with intestinal vasculitis have been reported before (2,19,20,21). Nevertheless, no data was found referring to the use of this drug in adolescents with Behçet's disease. The satisfactory response to sulfalazine and the rare occurrence of side effects were the motivations to report this case (AU)