Accuracy in Diagnosis of Celiac Disease Without Biopsies in Clinical Practice.

BACKGROUND & AIMS: The guidelines of the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition allow for diagnosis of celiac disease without biopsies in children with symptoms and levels of immunoglobulin A against tissue-transglutaminase (TGA-IgA) 10-fold or more the upper limit of normal (ULN), confirmed by detection of endomysium antibodies (EMA) and positivity for HLA-DQ2/DQ8. We performed a large, international prospective study to validate this approach. METHODS: We collected data from consecutive pediatric patients (18 years or younger) on a gluten-containing diet who tested positive for TGA-IgA from November 2011 through May 2014, seen at 33 pediatric gastroenterology units in 21 countries. Local centers recorded symptoms; measurements of total IgA, TGA, and EMA; and histopathology findings from duodenal biopsies. Children were considered to have malabsorption if they had chronic diarrhea, weight loss (or insufficient gain), growth failure, or anemia. We directly compared central findings from 16 antibody tests (8 for TGA-IgA, 1 for TGA-IgG, 6 for IgG against deamidated gliadin peptides, and 1 for EMA, from 5 different manufacturers), 2 HLA-DQ2/DQ8 tests from 2 manufacturers, and histopathology findings from the reference pathologist. Final diagnoses were based on local and central results. If all local and central results were concordant for celiac disease, cases were classified as proven celiac disease. Patients with only a low level of TGA-IgA (threefold or less the ULN) but no other results indicating celiac disease were classified as no celiac disease. Central histo-morphometry analyses were performed on all other biopsies and cases were carefully reviewed in a blinded manner. Inconclusive cases were regarded as not having celiac disease for calculation of diagnostic accuracy. The primary aim was to determine whether the nonbiopsy approach identifies children with celiac disease with a positive predictive value (PPV) above 99% in clinical practice. Secondary aims included comparing performance of different serological tests and to determine whether the suggested criteria can be simplified. RESULTS: Of 803 children recruited for the study, 96 were excluded due to incomplete data, low level of IgA, or poor-quality biopsies. In the remaining 707 children (65.1% girls; median age, 6.2 years), 645 were diagnosed with celiac disease, 46 were found not to have celiac disease, and 16 had inconclusive results. Findings from local laboratories of TGA-IgA 10-fold or more the ULN, a positive result from the test for EMA, and any symptom identified children with celiac disease (n = 399) with a PPV of 99.75 (95% confidence interval [CI], 98.61-99.99); the PPV was 100.00 (95% CI, 98.68-100.00) when only malabsorption symptoms were used instead of any symptom (n = 278). Inclusion of HLA analyses did not increase accuracy. Findings from central laboratories differed greatly for patients with lower levels of antibodies, but when levels of TGA-IgA were 10-fold or more the ULN, PPVs ranged from 99.63 (95% CI, 98.67-99.96) to 100.00 (95% CI, 99.23-100.00). CONCLUSIONS: Children can be accurately diagnosed with celiac disease without biopsy analysis. Diagnosis based on level of TGA-IgA 10-fold or more the ULN, a positive result from the EMA tests in a second blood sample, and the presence of at least 1 symptom could avoid risks and costs of endoscopy for more than half the children with celiac disease worldwide. HLA analysis is not required for accurate diagnosis. Clinical Trial Registration no: DRKS00003555.

Endoscopic Mucosectomy in a Child Presenting with Gastric Heterotopia of the Rectum.

Gastric mucosal heterotopia has been described in all levels of the gastrointestinal tract. Its occurrence in the rectum is uncommon. We report the case of a 4-year-old boy referred to Pediatric Gastroenterology for intermittent rectal bleeding for the past 2 years. Total ileocolonoscopy revealed a flat, well-circumscribed lesion of 4 cm, with elevated margins, localized at 10 cm from the anal verge. Histologic examination showed typical gastric mucosa of the oxyntic type. Treatment with proton pump inhibitors was started without resolution of the symptoms and, therefore, an endoscopic mucosal resection was performed. Heterotopic gastric mucosa represents a rare cause of rectal bleeding in children and endoscopic evaluation is fundamental for diagnosis. Although not usually performed in pediatric ages, endoscopic mucosectomy allows complete resolution of the problem avoiding surgery.

A heterotopia da mucosa gástrica pode ocorrer em qualquer local do trato gastrointestinal, mas a localização retal é invulgar. Apresenta-se o caso clínico de uma criança de 4 anos, referenciada à consulta de Gastroenterologia Pediátrica por retorragia intermitente com cerca de 2 anos de evolução. Foi realizada ileocolonoscopia total com visualização de lesão plana de bordos elevados e bem delimitada, com cerca de 4 cm, localizada 10 cm acima da margem anal. O exame histológico revelou a presença de mucosa gástrica do tipo oxíntico. Iniciou terapêutica oral com inibidor da bomba de protões, sem resposta, pelo que se procedeu a mucosectomia endoscópica. A heterotopia da mucosa gástrica é uma causa rara de retorragias em idade pediátrica sendo a avaliação endoscópica fundamental para o diagnóstico. A utilização de técnica endoscópica de ablação da mucosa, pouco usual em idade pediátrica, permite a resolução definitiva do problema evitando a cirurgia.

Caustic Esophageal Stenosis: A Case Report of Endoscopic Dilation With a Dynamic Stent.

INTRODUCTION: The management of esophageal strictures has evolved from surgical treatment to the endoscopic dilation and, more recently, esophageal stenting. CLINICAL CASE: We describe a case of a two-year-old boy with a double stenosis of the esophagus resulting from accidental ingestion of strong alkaline liquid. After several unsuccessful endoscopic dilations for three years and even topical mitomicin, it was decided to place a dynamic stent developed by the Digestive Surgery and Endoscopic Unit of the Bambino Gesù Hospital, Rome. The stent is a custom silicon device built coaxially on a nasogastric tube that is inserted after stricture dilations, by endoscopic guidance, and then fixed outside the nose. The device was removed after seven weeks with good clinical outcome (no dysphagia more than a year of follow-up). CONCLUSION: This case confirms that the dynamic stent is a simple device that may avoid aggressive surgical substitution in cases of refractory strictures.

INTRODUÇÃO: O tratamento das estenoses esofágicas tem evoluído desde a correção cirúrgica, à dilatação endoscópica e, mais recentemente, à colocação de stents esofágicos. CASO CLÍNICO: Descrevemos o caso de um doente que aos dois anos ingeriu acidentalmente um cáustico e desenvolveu duas estenoses esofágicas recidivantes. Após numerosas dilatações endoscópicas e aplicação tópica de mitomicina, ao fim de três anos, foi decidido colocar um stent dinâmico, desenvolvido pela Unidade de Cirurgia e Endoscopia do Hospital Bambino Gesù, Roma. O dispositivo consiste numa sonda nasogástrica com uma área de maior calibre (stent) que foi posicionada por via endoscópica na zona das estenoses e fixada por via nasal. O dispositivo foi retirado passadas sete semanas com melhoria clínica sustentada (ausência de disfagia mais de um ano após). CONCLUSÃO: Este caso demonstra que o "stent" dinâmico é tecnicamente simples e permite evitar uma solução cirúrgica mutilante em casos de estenose esofágica de difícil controlo.

Tracheitis - A Rare Extra-Intestinal Manifestation of Ulcerative Colitis in Children.

INTRODUCTION: Inflammatory bowel disease may cause both intestinal and extraintestinal manifestations. Respiratory symptoms in ulcerative colitis are rare and tracheal involvement is exceedingly rare in children. CASE 1: Sixteen year-old female with a 4-week-complaint of abdominal pain, bloody diarrhea, fever and cough. The investigation was consistent with the diagnosis of concomitant ulcerative colitis/coinfection to Escherichia coli. On day 4 respiratory signs persisted so azithromycin and inhaled corticosteroids were added. By day 6 she progressed to respiratory failure and was diagnosed with necrotic tracheitis so started on intravenous steroids with fast clinical improvement. CASE 2: Twelve-year-old male adolescent with ulcerative colitis and sclerosing cholangitis started dry cough and throat pain 10 days after diagnosis. Laboratory investigations showed increased inflammatory signs and normal chest X-ray. He started treatment with azithromycin without clinical improvement and on day five he presented dyspnea and fever. Laryngeal fibroscopy suggested tracheitis and so systemic steroids where added with fast clinical and analytic improvement. DISCUSSION: Tracheitis should be suspected if there are persistent respiratory symptoms even when exams are normal. Early recognition and early treatment are essential for a good prognosis preventing progression to respiratory failure.

INTRODUÇÃO: A doença inflamatória intestinal pode ser causa de complicações intestinais e extraintestinais. As manifestações respiratórias de colite ulcerosa são raras e o envolvimento traqueal é extremamente raro em crianças. CASO 1: Adolescente do sexo feminino, de dezasseis anos de idade, com queixas de dor abdominal, diarreia sanguinolenta, febre e tosse seca com 4 semanas de evolução. A investigação realizada foi compatível com o diagnóstico de colite ulcerosa/co-infecção a Escherichia coli. No 4ª dia de internamento, por persistência das queixas respiratórias, iniciou azitromicina e corticoterapia inalada. Dois dias mais tarde evoluiu para insuficiência respiratória; foi-lhe diagnosticada traqueíte necrotizante pelo que iniciou corticóides endovenosos com rápida melhora clínica. CASO 2: Adolescente do sexo masculino de 12 anos de idade com colite ulcerosa e colangite esclerosante que inicia queixas de odinofagia e tosse seca 10 dias após o diagnóstico. O estudo analítico revelou aumento dos parâmetros inflamatórios e radiografia de tórax normal. Nesta altura inicia azitromicina, sem melhora clínica, iniciando, no quinto dia de doença, dispnéia e febre. A fibroscopia laríngea foi sugestiva de traqueíte pelo que iniciou corticoterapia sistémica com rápida melhoria clínica e analítica. DISCUSSÃO: A traqueíte é uma entidade que deve ser equacionada em doentes com doença inflamatória intestinal na presença de sintomas respiratórios persistentes, mesmo com estudo complementar normal. O seu reconhecimento e tratamento precoces são essenciais para um prognóstico favorável e prevenção da progressão para insuficiência respiratória.

Severe IgG4-Related Disease in a Young Child: A Diagnosis Challenge.

Immunoglobulin G4-related disease (IgG4-RD) is an increasingly recognized syndrome that can appear with multiple organ involvement, typically with tumor-like swelling, lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, and elevated serum IgG4 concentrations. We report the case of a 22-month-old female child with failure to thrive and recurrent respiratory tract infections since 8 months of age. Physical examination was normal except for pulmonary auscultation with bilateral crackles and wheezes. Laboratory tests revealed elevated erythrocyte sedimentation rate, and elevated serum IgG and IgG4 with polyclonal hypergammaglobulinemia. Thoracic CT and MRI showed multiple mediastinal lymphadenopathies and a nodular posterior mediastinal mass in right paratracheal location with bronchial compression. Initial fine needle aspiration biopsy was compatible with reactive lymphadenopathy but after clinical worsening a thoracoscopic partial resection of the mass was performed and tissue biopsy revealed lymphoplasmacytic infiltrate and increased number of IgG4-positive plasma cells and a ratio of IgG4/IgG positive cells above 40%. Glucocorticoids therapy was started with symptomatic improvement, reduction in the size of the mass, and decrease of serum IgG4 levels after 6 weeks. There are very few reports of IgG4-RD in children. Long-term follow-up is necessary to monitor relapses and additional organ involvement.

Accidental Ingestion of Dentistry Material - Report of Cases and Challenges from the Pediatrician Point of View.

INTRODUCTION: Aspiration or ingestion of foreign bodies may occur during dental procedures. Diagnosis and management of these accidents is sometimes challenging. The authors present a small series of clinical cases. CASE 1: Adolescent observed due to suspected accidental bracket ingestion, not visible on x-ray, removed by upper digestive endoscopy. CASE 2: Adolescent observed after accidental ingestion of a dental file. Conflicting results in image exams and absence of object progression led to enteroscopy for extraction. CASE 3: Adolescent observed due to accidental ingestion of a surgical blade, visualized on image study but not accessible by endoscopy, resulting in latter spontaneous elimination. DISCUSSION: Image study is frequently useful when metallic object ingestion is suspected, but has some limitations. In some cases, mucosal protections must be used during removal procedures. Prevention of such accidents is the best approach, using appropriate protections to secure airway and digestive tract during dental procedures.

INTRODUÇÃO: A aspiração ou ingestão de corpos estranhos pode ocorrer durante qualquer procedimento dentário. O diagnóstico e a resolução destas situações podem colocar desafios. Os autores apresentam três casos clínicos. CASO 1: Adolescente observada por suspeita de ingestão acidental de um bracket de aparelho fixo de ortodontia, não visualizado na radiografia e removido por endoscopia digestiva alta. CASO 2: Adolescente com história de ingestão acidental de uma lima de dentista. Os exames complementares realizados não foram esclarecedores e, dado não haver progressão do corpo estranho, foi necessária a sua remoção por enteroscopia. CASO 3: Adolescente que recorre à urgência por ingestão acidental de uma lâmina de dentista, inacessível por endoscopia e que acabou por ser eliminada espontaneamente. DISCUSSÃO: Os exames imagiológicos são habitualmente úteis na suspeita de ingestão de corpos estranhos metálicos mas a informação que fornecem é limitada. A natureza cortante do material dentário deglutido exige que se tomem cuidados adicionais na sua remoção, utilizando auxiliares protectores. A prevenção destes acidentes deve ser promovida, recorrendo a protecções da via aérea e digestiva durante a realização de procedimentos dentários.

Expanding the phenotype of IFAP/BRESECK syndrome: a new case with severe hypogammaglobulinemia.

The ichthyosis follicular with atrichia and photophobia syndrome (IFAP) is a rare X-linked multiple congenital malformation syndrome. Some male patients have additional features including brain anomalies, intellectual disability, ectodermal dysplasia, skeletal deformities, ear or eye anomalies and kidney dysplasia/hypoplasia (BRESEK syndrome) sometimes associated with Hirschsprung disease and cleft palate or cryptorchidism (BRESHECK syndrome). We report a 5 months-old male patient with the p.R429H mutation in MBTPS2 protein, which has been reported to be associated with the most severe phenotype of patients with IFAP/BRESHECK syndrome. This patient presented with a severe IFAP/BRESHECK phenotype including ichthyosis follicular, atrichia, photophobia, brain anomalies, global developmental delay, Hirschsprung disease and kidney hypoplasia. Additional features not previously reported in IFAP syndrome, include severe hypogammaglobulinemia and congenital rectourethral fistula.

Sydenham's chorea in a family with Huntington's disease: case report and review of the literature.

CONTEXT: Sydenham's chorea affects almost 30% of patients with acute rheumatic fever. It is more frequent in females and is rare in the first decade of life, and genetic vulnerability underlies it. Because of easy access to antibiotics, it is now rare in so-called developed countries. CASE REPORT: A 6-year-old boy with a family history of Huntington's disease, who was the only child of an unscreened and asymptomatic mother, was brought for a consultation because of migratory arthralgia, depressed mood, and rapid, abrupt and unintentional movements of his right arm and leg, that had evolved over a three-week period. On physical examination, he presented a grade III/VI systolic heart murmur and right-side choreic movements, giving rise to a deficit of active mobilization. Laboratory tests revealed elevated erythrocyte sedimentation rate (63 mm/h), C-reactive protein (25 mg/l) and antistreptolysin O titer (1,824 U/ml). Cardiovascular evaluation showed mild aortic insufficiency, moderate mitral insufficiency and a prolonged PR interval. A clinical diagnosis of Sydenham's chorea/acute rheumatic fever was made, and therapy consisting of penicillin, haloperidol, captopril and furosemide was instituted, with excellent results. CONCLUSION: In developed countries, Sydenham's chorea seems forgotten and, because of this, little is known about its clinical course and controversy surrounds the therapeutic options available. This occurrence of rheumatic chorea in a family with Huntington's disease highlights the importance of the differential diagnosis for the different forms of chorea.

Sydenham's chorea in a family with Huntington's disease: case report and review of the literature / Coreia de Sydenham numa família com doença de Huntington: relato de caso e revisão da literatura

CONTEXT: Sydenham's chorea affects almost 30 percent of patients with acute rheumatic fever. It is more frequent in females and is rare in the first decade of life, and genetic vulnerability underlies it. Because of easy access to antibiotics, it is now rare in so-called developed countries. CASE REPORT: A 6-year-old boy with a family history of Huntington's disease, who was the only child of an unscreened and asymptomatic mother, was brought for a consultation because of migratory arthralgia, depressed mood, and rapid, abrupt and unintentional movements of his right arm and leg, that had evolved over a three-week period. On physical examination, he presented a grade III/VI systolic heart murmur and right-side choreic movements, giving rise to a deficit of active mobilization. Laboratory tests revealed elevated erythrocyte sedimentation rate (63 mm/h), C-reactive protein (25 mg/l) and antistreptolysin O titer (1,824 U/ml). Cardiovascular evaluation showed mild aortic insufficiency, moderate mitral insufficiency and a prolonged PR interval. A clinical diagnosis of Sydenham's chorea/acute rheumatic fever was made, and therapy consisting of penicillin, haloperidol, captopril and furosemide was instituted, with excellent results. CONCLUSION: In developed countries, Sydenham's chorea seems forgotten and, because of this, little is known about its clinical course and controversy surrounds the therapeutic options available. This occurrence of rheumatic chorea in a family with Huntington's disease highlights the importance of the differential diagnosis for the different forms of chorea.

CONTEXTO: A coreia de Sydenham surge em cerca de 30 por cento dos casos de febre reumática aguda. É mais frequente no sexo feminino, é rara na primeira década de vida e tem por base uma vulnerabilidade genética. Devido ao fácil acesso aos antibióticos, é uma doença rara atualmente nos países ditos desenvolvidos. RELATO DO CASO: Criança de seis anos, sexo masculino, com história familiar de coreia de Huntington, único filho de mãe assintomática e não rastreada, foi trazido à consulta por artralgias migratórias, humor deprimido e movimentos rápidos, abruptos e não intencionais dos membros superior e inferior direitos, com três semanas de evolução. Ao exame físico, apresentava um sopro cardíaco sistólico grau III/VI, e foram presenciados movimentos coreicos à direita, condicionando um défice de mobilização activa. Os exames laboratoriais mostraram aumento da velocidade de sedimentação (63 mm/h), proteína C-reativa (25 mg/L) e título de antiestreptolisina O (1.824 U/mL). O exame cardiovascular revelou insuficiência aórtica ligeira e insuficiência mitral moderada e aumento do intervalo PR. Foi feito o diagnóstico de coreia de Sydenham/febre reumática aguda, tendo sido instituída terapêutica com penicilina, haloperidol, captopril e furosemida, com excelente resultado. CONCLUSÃO: Nos países desenvolvidos, a coreia de Sydenham parece esquecida e, por isso, pouco se sabe quanto ao seu curso clínico e as opções terapêuticas disponíveis são controversas. A ocorrência de um caso de coreia reumática numa família com doença de Huntington realça a importância do diagnóstico diferencial das diferentes formas de coreia.