Evaluación gastrointestinal en los pacientes con fiebre mediterránea familiar con dolor abdominal crónico y tratados con colchicina: serie de casos / Gastrointestinal evaluation in colchicine-treated familial Mediterranean fever patients with chronic abdominal pain: Cases series

El objetivo de este estudio fue evaluar a los pacientes con fiebre mediterránea familiar (familial Mediterranean fever, FMF) y dolor abdominal crónico resistentes al tratamiento con colchicina. Se incluyó a 48 pacientes diagnosticados en nuestro consultorio de reumatología pediátrica que tenían dolor abdominal a pesar del tratamiento con colchicina. A todos los pacientes se los derivó a un gastroenterólogo pediátrico. Se registraron las características del dolor, tales como aparición, duración y frecuencia; se planificó una endoscopía digestiva para obtener un diagnóstico diferencial. Se determinó la presencia de una mutación del gen MEFV en 46 pacientes. La mediana de la duración del tratamiento fue de 2,8 años. Aproximadamente el 60% de los pacientes tenían dolor abdominal todos los días o de dos a tres veces a la semana; en el 73% de los casos, duró menos de tres horas. A 41 pacientes se les realizó una endoscopía digestiva alta. La gastroduodenitis es un hallazgo frecuente en los pacientes con FMF y dolor abdominal persistente a pesar del tratamiento. Los pacientes con los puntajes más altos de severidad de la enfermedad tenían inflamación digestiva grave.

The aim of the study to evaluate familial mediterranean fever (FMF) patients with chronic abdominal pain unresponsive to colchicine treatment. Forty-eight patients who diagnosed in our Pediatric Rheumatology clinics and suffering from abdominal pain despite colchicine treatment were include. All patients were referred to a pediatric gastroenterologist. The pain characteristics such as onset, duration and frequency were recorded; gastrointestinal (GI) endoscopy was planned for differential diagnosis. MEFV mutation was determined in 46 patients. The median duration of treatment was 2.8 years. Approximately 60% of the patients suffered from abdominal pain every day or 2-3 times a week, in 73% of the cases it lasted less than three hours. Forty-one patients underwent upper GI endoscopy. Gastroduodenitis is a common finding in persisting abdominal pain despite therapy of FMF patients. The patients with the highest disease severity scores had severe inflammation within the entire GI system.

Triagem sorológica para doença celíaca em crianças com febre familiar do mediterrâneo colchicina-resistente / Serological screening for celiac disease in children with colchicine-resistant familial mediterranean fever

ABSTRACT BACKGROUND: Familial Mediterranean fever and celiac disease share some common clinical features such as abdominal pain, diarrhea, arthralgia and arthritis. Also, both of the diseases are associated with many inflammatory and autoimmune diseases. Previous studies have shown the association between familial Mediterranean fever (FMF) and different clinical conditions. OBJECTIVE: We aimed to investigate the relationship between celiac disease and colchicine-resistant familial Mediterranean fever (crFMF) disease. METHODS: This prospective study was conducted at the Department of Pediatric Gastroenterology and Pediatric Rheumatology from October 2015 to August 2016. A total of 24 patients with crFMF were included in the study. We used 60 sex- and age-matched healthy subjects as a control group. Levels of total IgA and tissue transglutaminase (tTG) IgA antibody were measured in both groups. Those with increased level of tTG IgA were tested for anti-endomysium IgA antibodies (EMA). Gastroduodenoscopy and intestinal biopsy were planned for a definite diagnosis of celiac disease in patients with positive EMA. RESULTS: Of the 24 patients in this study, 18 (75.0%) were female. Only 4 (16.6%) of 24 patients were positive for tTG IgA. Patients with positive tTG IgA were then tested for EMA IgA antibodies and none of them had a positive result. Only one (1.6%) subject from the control group was positive for tTG IgA but EMA positivity was not detected. CONCLUSION: We did not found celiac disease in 24 children with crFMF. Since crFMF disease is rarely seen in general population, further studies with more patients are needed to provide more precise interpretation.

RESUMO CONTEXTO: A febre familiar do Mediterrâneo e a doença celíaca compartilham algumas características clínicas comuns, tais como dor abdominal, diarreia, artralgia e artrite. Além disso, ambas as doenças são associadas a muitas doenças auto-imunes e inflamatórias. Estudos anteriores mostraram associação entre febre familiar do Mediterrâneo e diferentes condições clínicas. OBJETIVO: Investigar a relação entre doença celíaca e doença de febre familiar do Mediterrâneo colchicina-resistente (FMFcr). MÉTODOS: Foi realizado um estudo prospectivo no departamento de Gastroenterologia pediátrica e Reumatologia pediátrica de outubro de 2015 até agosto de 2016. Um total de 24 pacientes com FMFcr foram incluídos. Sessenta indivíduos saudáveis combinados por sexo e idade foram utilizados como um grupo de controle. Os níveis de IgA total e transglutaminase tissular (tTG) anticorpo IgA foram medidos em ambos os grupos. Aqueles com maior nível de tTG IgA foram testados para anticorpos de IgA antiendomísio (EMA). Gastroduodenoscopia e biópsia intestinal foram planejadas para um diagnóstico definitivo da doença celíaca em pacientes com EMA positivo. RESULTADOS: Dos 24 pacientes neste estudo, 18 (75,0%) eram do sexo feminino. Somente 4 (16,6%) de 24 pacientes foram positivos para tTG IgA. Pacientes com tTG IgA positivo então foram testados para anticorpos IgA de EMA, e nenhum deles teve um resultado positivo. Somente um (1,6%) indivíduo do grupo controle foi positivo para tTG IgA, mas a positividade EMA não foi detectada. CONCLUSÃO: Não encontramos a doença celíaca em 24 crianças com FMFcr. Desde que a doença FMFcr é raramente vista na população em geral, estudos com mais pacientes são necessários para fornecer interpretação mais precisa.

Clinical outcomes and survival in AA amyloidosis patients / Desfechos clínicos e sobrevida em pacientes com amiloidose AA

Abstract Aim Amyloid A amyloidosis is a rare complication of chronic inflammatory conditions. Most patients with amyloid A amyloidosis present with nephropathy and it leads to renal failure and death. We studied clinical characteristics and survival in patients with amyloid A amyloidosis. Methods: A total of 81 patients (51 males, 30 females) with renal biopsy proven amyloid A amyloidosis were analyzed retrospectively. The patients were divided into good and poor outcomes groups according to survival results. Results: Most of the patients (55.6%) had nephrotic range proteinuria at diagnosis. Most frequent underlying disorders were familial Mediterranean fever (21.2%) and rheumatoid arthritis (10.6%) in the good outcome group and malignancy (20%) in the poor outcome group. Only diastolic blood pressure in the good outcome group and phosphorus level in the poor outcome group was higher. Serum creatinine levels increased after treatment in both groups, while proteinuria in the good outcome group decreased. Increase in serum creatinine and decrease in estimated glomerular filtration rate of the poor outcome group were more significant in the good outcome group. At the time of diagnosis 18.5% and 27.2% of all patients had advanced chronic kidney disease (stage 4 and 5, respectively). Median duration of renal survival was 65 ± 3.54 months. Among all patients, 27.1% were started dialysis treatment during the follow-up period and 7.4% of all patients underwent kidney transplantation. Higher levels of systolic blood pressure [hazard ratios 1.03, 95% confidence interval: 1-1.06, p = 0.036], serum creatinine (hazard ratios 1.25, 95% confidence interval: 1.07-1.46, p = 0.006) and urinary protein excretion (hazard ratios 1.08, 95% confidence interval: 1.01-1.16, p = 0.027) were predictors of end-stage renal disease. Median survival of patients with organ involvement was 50.3 ± 16 months. Conclusion Our study indicated that familial Mediterranean fever constituted a large proportion of cases and increased number of patients with idiopathic amyloid A amyloidosis. Additionally, it was observed that patient survival was not affected by different etiological causes in amyloid A amyloidosis.

Resumo Objetivo: A amiloidose AA é uma complicação rara de condições inflamatórias crônicas. A maior parte dos pacientes com amiloidose AA apresenta nefropatia, que leva à insuficiência renal e à morte. Estudaram-se as características clínicas e a sobrevida em pacientes com amiloidose AA. Métodos: Analisaram-se retrospectivamente 81 pacientes (51 homens, 30 mulheres) com amiloidose AA comprovada por biópsia renal. Os pacientes foram divididos em grupos de desfecho bom e ruim de acordo com os resultados de sobrevida. Resultados: A maior parte dos pacientes (55,6%) tinha proteinúria na faixa nefrótica no momento do diagnóstico. Os distúrbios subjacentes mais frequentes foram a febre familiar do Mediterrâneo (FFM, 21,2%) e a artrite reumatoide (10,6%) no grupo de desfecho bom e a malignidade (20%) no grupo de desfecho ruim. Somente a pressão arterial diastólica no grupo de desfecho bom e o nível de fósforo no grupo de desfecho ruim foram mais elevados. Os níveis séricos de creatinina aumentaram após o tratamento em ambos os grupos, enquanto a proteinúria diminuiu no grupo de desfecho bom. O aumento na creatinina sérica e a diminuição na TFGe do grupo de desfecho ruim foram mais significativos no grupo de desfecho bom. No momento do diagnóstico, 18,5% e 27,2% de todos os pacientes tinham doença renal crônica avançada (estágios 4 e 5, respectivamente). A duração média da sobrevida renal foi de 65 ± 3,54 meses. Entre todos os pacientes, 27,1% iniciaram tratamento de diálise durante o período de seguimento e 7,4% de todos os pacientes foram submetidos a transplante renal. Níveis elevados de pressão arterial sistólica [taxas de risco (HR) 1,03, intervalo de confiança (IC) de 95%: 1 a 1,06, p = 0,036], creatinina sérica (HR 1,25, IC 95%: 1,07 a 1,46, p = 0,006) e excreção urinária de proteínas (HR 1,08, IC 95%: 1,01 a 1,16, p = 0,027) foram preditores de doença renal terminal. A mediana da sobrevida de pacientes com comprometimento de órgãos foi de 50,3 ± 16 meses. Conclusão: O presente estudo indicou que a FFM constituiu uma grande proporção de casos e crescente quantidade de pacientes com amiloidose AA idiopática. Adicionalmente, observou-se que a sobrevida do paciente não foi afetada pelas diferentes causas etiológicas na amiloidose AA.

Association of amyloidosis cutis dyschromica and familial Mediterranean fever

Abstract: Amyloidosis cutis dyschromica is a rare type of primary cutaneous amyloidosis characterized by reticulate hyper-pigmentation with discrete hypopigmented macules. Up to date, about 50 cases of amyloidosis cutis dyschromica have been reported and the majority are familial cases of Asian ethnicity. Various diseases, particularly autoimmune diseases such as systemic sclerosis and systemic lupus erythematosus, have been associated with amyloidosis cutis dyschromica. Herein, we report a case of amyloidosis cutis dyschromica accompanying familial Mediterranean fever with a delayed diagnosis of 40 years. To the best of our knowledge, this is the first report of the association of amyloidosis cutis dyschromica and familial mediterranean fever.

Familial Mediterranean Fever is associated with abnormal ventricular repolarization indices / La fiebre mediterránea familiar se asocia a anomalías en la repolarizacıón ventricular

Background: Cardiac arrhythmias can be a part of cardiovascular involvement in some rheumatic diseases, but data about familial Mediterranean fever (FMF) are conflicting. Aim: To search for abnormalities in ventricular repolarization indices in FMF patients. Patients and Methods: Seventy seven FMF patients and 30 age/gender comparable healthy controls were included. All patients were attack free and subjects with disease or drugs that are known to alter cardiac electrophysiology were excluded. Electrocardiographic data were obtained and analyzed. Results: Twelve FMF patients had amyloidosis. QT and QTc intervals were within the normal ranges and similar between FMF patients and healthy controls. QT dispersion, peak to end interval of T wave (Tpe), Tpe/QT and Tpe/QTc ratios were significantly higher in FMF patients than in healthy controls. Patients with amyloidosis had significantly higher QT dispersion, Tpe, Tpe/QT and Tpe/QTc than their counterparts without FMF. Levels of proteinuria were moderately correlated with QT dispersion, Tpe, Tpe/QT and Tpe/QTc. Conclusions: FMF patients may have an increased risk for arrhythmias.

Antecedentes: Las arritmias cardíacas pueden ser parte del compromiso cardíaco en enfermedades reumáticas, sin embargo, no se sabe con certeza si esto ocurre en la fiebre mediterránea familiar (FMF). Objetivo: Buscar anomalías en la repolarización ventricular en pacientes con FMF. Pacientes y Métodos: Sesenta y siete pacientes como FMF y 30 controles sanos pareados por edad y género fueron estudiados. Todos los pacientes estaban en período intercrítico y no usaban medicamentos o tenían enfermedades concomitantes que pudieran causar anomalías electrocardiográficas. Se analizaron los electrocardiogramas de estos participantes. Resultados: Veinte pacientes con FMF tenían amiloidosis. Los intervalos QT y QTc eran normales y similares entre pacientes y controles. La dispersión del intervalo QT, el intervalo desde el peak al final de la onda T (Tpe), las razones Tpe/QT y Tpe/QTc fueron significativamente más altos en los pacientes que en los controles. Los pacientes con amiloidosis tenían una dispersión de QT, Tpe, Tpe/QT y Tpe/QTc mayores que sus pares sin la condición. Los niveles de proteinuria se correlacionaron moderadamente con los parámetros antes mencionados. Conclusiones: Los pacientes con FMF tienen mayor riesgo de arritmias.

The prevalence ff celiac disease among patients with familial mediterranean fever / Prevalência da doença celíaca entre pacientes com Febre Familiar do Mediterrâneo

Background Familial Mediterranean Fever and celiac disease are both related to auto-inflammation and/or auto-immunity and they share some common clinical features such as abdominal pain, diarrhea, bloating and flatulence. Objectives We aimed to determine the association of these two diseases, if present. Methods Totally 112 patients diagnosed with Familial Mediterranean Fever and 32 cases as healthy control were included in the study. All participants were examined for the evidence of celiac disease, with serum tissue transglutaminase IgA levels (tTG IgA). Results Totally 144 cases, 112 with Familial Mediterranean Fever and 32 healthy control cases were included in the study. tTG IgA positivity was determined in three cases with Familial Mediterranean Fever and in one case in control group. In that aspect there was no significant difference regarding the tTG IgA positivity between groups (P=0.81). Duodenum biopsy was performed to the tTG IgA positive cases and revealed Marsh Type 3b in two Familial Mediterranean Fever cases and Marsh Type 3c in the other one while the biopsy results were of the only tTG IgA positive case in control group was Marsh Type 3b. In HLA evaluation of the celiac cases; HLA DQ2 was present in two celiac cases of the Familial Mediterranean Fever group and in the only celiac case of the control group while HLA DQ8 was present in one celiac case of the Familial Mediterranean Fever group. Conclusions We did not determine an association of Familial Mediterranean Fever with celiac disease. Larger studies with subgroup analysis are warranted to determine the relationship of these two diseases. .

Contexto A Febre Familiar do Mediterrâneo e a doença celíaca são ambas relacionadas com auto-inflamação e/ou auto-imunidade e partilham algumas características clínicas comuns tais como dor abdominal, diarréia, distensão abdominal e flatulência. Objetivo Determinar a associação destas duas doenças, se presente. Métodos Um total de 112 pacientes diagnosticados com Febre Familiar do Mediterrâneo e 32 casos como controle saudável foram incluídos no estudo. Todos os participantes foram examinados para a evidência da doença celíaca, com níveis de IgA séricos transglutaminase (tTG IgA). Resultados Um total de 144 casos, 112 com Febre Familiar do Mediterrâneo e 32 casos controle saudável foram incluídos no estudo. A positividade tTG IgA foi determinada em três casos com Febre Familiar do Mediterrâneo e em um caso no grupo controle. Neste aspecto não há nenhuma diferença significativa em relação a positividade tTG IgA entre os grupos (P= 0,81). Biópsia de duodeno realizado para os casos positivos de tTG IgA e revelou Marsh tipo 3b em dois casos de Febre Familiar e Marsh tipo 3C no outro, enquanto o resultado da biópsia do único caso positivo tTG IgA no grupo controle foi Marsh tipo 3b. Na avaliação de HLA dos casos de doença celíaca, HLA DQ2 esteve presente em dois casos de doença celíacas do grupo Febre Familiar do Mediterrâneo e no caso celíaco do grupo controle, enquanto HLA-DQ8 estava presente em um caso de doença celíaca do grupo Febre Familiar do Mediterrâneo. Conclusão Não se determinou uma associação de Febre Familiar do Mediterrâneo com doença celíaca. Maiores estudos com análise de subgrupo são necessários para determinar a relação entre estas duas doenças. .

A Case of Recurrent Abdominal Pain with Fever and Urticarial Eruption / 대한소화기학회지

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent episodes of fever and serosal, synovial, or cutaneous inflammation, caused by a dysfunction of pyrin as a result of mutation within the MEFV gene. It occurs mainly among Mediterranean and Middle Eastern populations, including Jews, Arabs, and Turks. However, FMF cases have been reported outside the Mediterranean and Middle Eastern countries in recent years. Although FMF has been relatively rare in Korea until now, proper recognition of FMF might lead to more frequent diagnoses of FMF. We experienced an interesting case, a 31-year-old Korean man who presented with recurrent abdominal pain with fever and urticarial eruption for 10 years. DNA analysis showed complex mutations (p.Leu110Pro, p.Glu148Gln) in the MEFV gene. To date, three cases have been reported, and this case of FMF with skin conditions is the first case in Korea.

Extensive Thrombosis in a Patient with Familial Mediterranean Fever, Despite Hyperimmunoglobulin D State in Serum: First Adult Case in Korea

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent episodes of fever accompanied by peritonitis, pleuritis, arthritis, or erysipelas-like erythema. It is known to occur mainly among Mediterranean and Middle Eastern populations such as non-Ashkenazi Jews, Arabs, Turks, and Armenians. FMF is not familiar to clinicians beyond this area and diagnosing FMF can be challenging. We report a 22-yr old boy who presented with fever, arthalgia and abdominal pain. He had a history of recurrent episodes of fever associated with arthalgia which would subside spontaneously or by antipyretics. Autosomal recessive periodic fever syndromes were suspected. Immunoglobulin D (IgD) level in the serum was elevated and DNA analysis showed complex mutations (p.Glu148Gln, p.Pro369Ser, p.Arg408Gln) in the MEFV gene. 3D angio computed tomography showed total thrombosis of splenic vein with partial thrombosis of proximal superior mesenteric vein, main portal vein and intrahepatic both portal vein. This is a case of FMF associated with multiple venous thrombosis and elevated IgD level. When thrombosis is associated with elevated IgD, FMF should be suspected. This is the first adult case reported in Korea.

Amyloid goiter: two cases and a review of the literature

Although involvement of the thyroid gland by amyloid is a relatively common phenomenon, clinically significant enlargement of the thyroid owing to amyloid deposition is an extremely rare occurrence. We describe two cases of amyloid goiter and review the relevant literature. The first case was systemic amyloidosis secondary to familial Mediterranean fever. The second case was a chronic renal failure patient who presented with an enlarged thyroid and upper airway obstructive symptoms. To date, true amyloid goiter secondary to amyloidosis associated with familial Mediterranean fever has only been reported in twelve patients

Postoperative respiratory distress in a patient with history of familial Mediterranean fever

Postoperative respiratory distress and pulmonary edema can be seen after a wide variety of serious clinical situations, or rare diseases such as familial Mediterranean fever [FMF]. FMF is a multisystemic disorder characterized by recurrent bouts of fever and pain due to inflammation of the peritoneum, synovia, or pleura. We report a case with history of FMF who developed postoperative respiratory distress after repairing the abdominal incisional hernia. Ten hours after administration of colchicine, the patient's symptoms were reduced. This rare disease should be included as a differential diagnosis for acute-onset respiratory distress in postoperative period

Fiebre mediterránea familiar: revisión de literatura / Familial mediterranean fever: review of the literature

La Fiebre mediterránea familiar corresponde a una enfermedad inflamatoria, de herencia autosómica recesiva, caracterizada por episodios febriles y serotisis, descrita mayoritariamente en grupos étnicos originarios de la costa mediterránea. La amiloidosis secundaria es la principal causa de mortalidad. El estudio de la mutación genética causante de esta enfermedad es útil para el diagnóstico, de no estar disponible, una prueba terapéutica con Colchicina es una herramienta valiosa. El uso de ésta droga es el tramiento de elección.

Fiebre mediterranea familiar en la ciudad de México / Familial mediterranean fever in Mexico city

Con el fin de difundir la existencia de pacientes con fiebre mediterránea familiar en la ciudad de México, se informan 47 casos en 9 familias, cuyas manifestaciones principales fueron: dolor abdominal en 46, fiebre en 45, dolor pleural en 10 y dolor articular en 8. Todas estas manifestaciones se presentaron en forma recurrente. Ninguno de los pacientes hasta la fecha tiene amiloidosis