Chronic intestinal pseudo-obstruction syndrome in pediatric patients.

The aim of this study was to report the presentation and outcome of 22 consecutive children (13 female) who presented with a syndrome of chronic intestinal pseudo-obstruction with or without urinary tract involvement. We analyse the main clinical and histopathological features and discuss therapeutic management. Ten patients had signs of intestinal obstruction at birth, in which 6 presented antenatally with megacystis on ultrasound. Six children presented with constipation and/or obstruction between 1 and 6 months of age and in 6 other patients diagnosis was made between the ages of 1 and 12 years. There was a family history in 4 patients. Investigations showed diffusely dilated gut on x-ray with slow transit on small bowel follow through. Absent or abnormal motor migrating complex with low amplitude contractions were demonstrated on duodeno-jejunal manometry in 12/13. Megacystis occurred in 15/21 and megaureter in 2/21. Full thickness biopsies (n = 22) revealed involvement of muscle layers in 8, and abnormal myenteric plexus on histochemistry in 13. In 1, the biopsies were inconclusive. Recurrent urinary tract infections occurred in all with structural urinary tract abnormality and most had bacterial overgrowth. Severe recurrent episodes of obstruction which required parenteral nutrition (PN) occurred in all patients. Drugs were unhelpful and decompression ileostomies or colostomies were performed in 20/22. Five children died from sepsis (n = 3) or sudden death. Eleven patients remain partially or totally dependent on PN despite decompression ileostomy in 10/11. Six patients underwent colectomy and ileorectal pull-through, 2 of which remain on long-term PN, while the others are totally orally fed. Despite careful histological study pointing to 2 main forms, myopathy and neuropathy, the etiology of primary intestinal pseudoobstruction syndromes remains unknown. It may present antenatally while most of the time the gut and the urinary tract are diffusely involved. The condition has a high morbidity with a percentage requiring long-term PN. Although the mortality rate is high (23%), careful treatment of urinary tract infections and bacterial overgrowth, decompression surgery and judicious use of PN allows survival to adult life.     

Recurrent pancreatitis in three patients with chronic idiopathic intestinal pseudo-obstruction

Chronic idiopathic intestinal pseudo-obstruction is a syndrome with substantial morbidity and mortality associated both with the syndrome and with its therapy. Standard therapy has included prokinetic agents and intravenous nutritional support when oral feedings are inadequate to maintain nutriture. We report three children with chronic intestinal pseudo-obstruction who experienced one or more attacks of pancreatitis. Two patients developed pseudocysts. One patient died. All three patients underwent cholecystectomy; one had stones, one had acalculous cholecystitis, and one had a normal gallbladder. All patients received prokinetic agents and total parenteral nutrition as therapy for their pseudo-obstruction. Candidate mechanisms to explain the etiology for pancreatitis in chronic intestinal pseudo-obstruction include biliary dysmotility associated with pseudo-obstruction and excessive cholinergic stimulation due to therapy with prokinetic agents.     

Role of immunoglobulin subclasses and specific antibody determinations in the evaluation of recurrent infection in children.

We studied humoral immune function in 267 children with recurrent respiratory infections referred to our immunology clinic to determine the most appropriate immunologic studies for evaluating recurrent infections in children. Of this highly selected population, 58% had a partial deficiency in one or more of the major immunoglobulin isotypes or IgG subclasses (defined as at least 2 SD below the normal age-adjusted mean). In none of the patients was there a total absence of an immunoglobulin isotype. The most common abnormality was partial IgA deficiency, which was found in one third of the patients. Twenty-six patients had only partial IgG subclass deficiencies, of which 20 were deficiencies of a single subclass. IgG1 was an isolated partial defect in three patients, IgG3 in five patients, and IgG2 and IgG4 were selective partial defects in six patients each. Tetanus toxoid and pneumopolysaccharide type 3 were the most immunogenic of the immunogens tested; hyporesponsiveness to pneumococcal polysaccharide types 7, 9, and 14 was common. Nineteen percent of the patients with normal immunoglobulin concentrations who were tested had lower-than-expected antibody titers; 42% of those tested with partial isotype deficiencies had deficient antibody responses. Of 25 patients with selective partial IgG subclass deficiencies or combined IgG subclass deficiencies, eight had antibody deficiencies. Our findings indicate that a high proportion of children referred to immunology clinics for recurrent infection have a demonstrable immunologic abnormality. Selective IgG subclass deficiency or a combined IgG subclass deficiency without an associated deficiency in a major immunoglobulin isotype is unusual. Identification of such patients is not predictive of the capacity to form antibodies to the antigens tested in this study and, in our opinion, adds little to the initial evaluation of immune function in such children.     

Mitochondrial myopathy (complex I deficiency) associated with chronic intestinal pseudo-obstruction.

We report a patient presenting with severe muscular impairment and chronic intestinal pseudo-obstruction (CIP) at the age of eight months. Due to the aggravated symptoms, assisted ventilation, an ileostomy and total parenteral nutrition were required. Later on, the patient developed a locked-in syndrome (Leigh's subacute necrotising encephalomyelopathy) and finally died due to recurrent pneumonia and chronic renal failure. The assessment of muscle biopsies revealed a moderate single-fibre type II atrophy, a variation of muscle fibre calibre with focal fatty degeneration and a decreased reactivity of cytochrome-c oxidase. Although ragged red fibres had not been found, mitochondrial enzyme activities were markedly decreased with the lowest residual activity detected for NADH:Q1 oxidoreductase and NADH:O2 oxidoreductase (complex I deficiency), thereby confirming the diagnosis of mitochondrial myopathy. A molecular genetic analysis could not identify known mutations of mitochondrial DNA. Gastrointestinal full-thickness biopsies revealed myenteric hypoganglionosis of the colon and stomach and hyperplasia of the submucosal plexus of the ileum. Some of the intestinal smooth muscle cells displayed bulbous protrusions filled with lateralised mitochondria. Mitochondrial myopathies are known to be associated with a variety of clinical syndromes including CIP. However, in contrast to previous reports in which CIP has been attributed to visceral intestinal myopathies, the present case is characterised by neuronal intestinal malformations. Therefore, a mitochondrial myopathy associated with CIP requires a subtle assessment of both the intestinal smooth muscle and the enteric nervous system to identify the underlying pathology.     

Antroduodenal motility in children with chronic intestinal pseudo-obstruction

Chronic intestinal pseudo-obstruction describes a heterogeneous group of disorders characterized by signs and symptoms of intestinal obstruction in the absence of a mechanical lesion. We studied antroduodenal motility in 13 children with pseudo-obstruction. The diagnosis was based on radiographic evidence in all, surgery in 11, and specific pathologic features in four. Antroduodenal motility was abnormal in all 13. Qualitative abnormalities in the patterns of antroduodenal contractions permitted separation into groups: (1) postprandial hypomotility (n = 3), (2) absent migrating motor complexes, with phase 3-like activity at the start of meals (neuropathic variety) (n = 5) (3) very low amplitude or absent contractions (myopathic variety) (n = 2); the remaining patients (n = 3) had other distinctive abnormalities. Cisapride, a new gastrointestinal prokinetic drug, stimulated proximal duodenal contractions in the 30 minutes after a meal in nine of 10 patients tested. These studies indicate that antroduodenal manometry is useful for characterizing intestinal pseudo-obstruction, and cisapride stimulates postprandial duodenal contractions in patients with pseudo-obstruction.     

Deficiency of IgG4 in children: association of isolated IgG4 deficiency with recurrent respiratory tract infection.

To study the relationship between serum IgG subclass deficiency and clinical host defense impairment, we reviewed the clinical and immunologic features of 123 patients with a history of recurrent infection who had been examined for immunodeficiency in our laboratory (group 1). We then compared immunoglobulin isotype levels with those in sera from 127 age-matched control subjects without recurrent infection from whom blood had been drawn for evaluation of atopy (group 2). There was a significantly higher prevalence of IgG4 deficiencies among patients with recurrent infections (17% vs 7%; p less than 0.02), solely because of a higher prevalence of isolated IgG4 deficiency (n = 9; 7.3%) than in atopic control subjects (n = 1; 0.8%; p less than 0.05); there was a comparable prevalence of multiple isotype deficiencies that included low levels of IgG4 (9.8% and 6.3%, respectively). All nine group 1 patients with isolated IgG4 deficiency had severe recurrent respiratory tract infections requiring multiple hospitalizations; in addition, five were atopic, five had asthma, and one had chronic diahrrea. Antibody responses to bacterial polysaccharide antigens were normal for age in all patients with isolated IgG4 deficiency; two had defective antibody responses to protein antigens. Isolated IgG4 deficiency appears to be associated with impaired respiratory tract defenses and may occur in the absence of an easily definable antibody deficiency state. This association suggests a physiologic defense role for mucosal IgG4.     

Spectrum of primary immune deficiency at a tertiary care hospital

Objective  To report various primary immune deficiencies diagnosed in children at a tertiary care hospital, their clinical manifestations and laboratory profile. Methods  Case records of children diagnosed to have primary immunodeficiency disorders over a period of 24 months at a tertiary care hospital in northern India were evaluated. Results  Twenty-seven children (M: F=3.5: 1) with mean age of 5.4 ± 4.6 yrs (2mo-16yr) were diagnosed to have primary immunodeficiency. Thirteen children had chronic granulomatous disease (CGD), 4 had severe combined immunodeficiency (SCID), 4 had hypogammaglobulinemia, 2 had Ataxia telangiectasia, and one each had DiGeorge syndrome, Wiskott Aldrich syndrome, hyper IgM syndrome and leukocyte adhesion defect. Common mode of presentation were recurrent/ persistent pneumonia in 19, recurrent/ persistent diarrhea in 10, deep seated abscesses in 8, allergy in 3, disseminated tuberculosis infection in 2, extensive fungal infections in 2 and 1 each of disseminated cytomegalovirus (CMV) infection, disseminated BCG disease, otitis media and meningitis. Family history of sibling deaths was elicited in 2 families. Infectious agents were isolated in 16 cases. Conclusion  From a single center 27 patients with primary immune deficiency could be identified by chart review, suggesting need for high index of suspicion for diagnosis of primary immune deficiency in India. Though the exact prevalence is not known there is need to make a registry to document the magnitude of problem of these disorders.     

Deficiencies in humoral immunity

B cell immune deficiencies are characterized by inadequate production of antibodies and/or low levels of one or more classes of immune globulins (IgG, IgA, IgM) or IgG sub-classes. They include: 1) severe deficiencies involving all the immune globulins (Bruton agammaglobulinemia, variable hypogammaglobulinemia); 2) selective deficiencies in immune globulins (IgA deficiency, IgM deficiency, deficiencies in IgG sub-classes, dysgammaglobulinemias); 3) transient infantile hypogammaglobulinemia; 4) B cell immune deficiencies with normal gammaglobulin levels. Symptoms of B cell immune deficiencies are variable but respiratory manifestations are usually more prominent than the other features that include digestive disorders, fungal infections, autoimmune conditions, joint manifestations, and severe bacterial or viral infections (pneumococcus, meningococcus, enterovirus). Management of IgM and IgA deficiencies rests on antimicrobial agents and non-specific measures. The prognosis of the other B cell immune deficiencies has improved dramatically since effective replacement immune globulin therapy has become available; this treatment combined with antimicrobial therapy and chest physiotherapy can usually prevent development of bronchiectases. The main risk is chronic enteroviral neuromeningeal infection.     

IgG subclass deficiency in children with recurrent bronchitis

We studied the incidence of IgG subclass deficiency in children with recurrent bronchitis. Recurrent bronchitis was defined as three or more episodes a year during at least 2 consecutive years, of bronchopulmonary infection, productive cough with or without fever and/or diffuse rales by physical examination in the absence of asthma or atopy. Fifty three children were selected, of whom 30 (57%) were deficient in one of the IgG subclasses. None had an IgG1 deficiency. Nine (17%) were deficient in IgG2, 9 (17%) in IgG3 and 20 (38%) in IgG4. Isolated IgG subclass deficiencies were most frequently seen for IgG4 (14, 26%), less for IgG3 (6, 12%) and even less for IgG2 (4, 7%). Nine (17%) children were IgA deficient and 8 (15%) IgG deficient with a combined IgG subclass deficiency in 8 and 7 of them respectively. By subdivision into different age groups most patients were encountered in the youngest group. The mean content of IgG2, IgG3 and IgG4 in 3- to 4-year-old children with recurrent bronchitis was significantly lower than in the age matched controls. The mean value for IgG4 in the 5- to 6-year-olds was significantly lower than in the control group. This study demonstrates the correlation between recurrent bronchitis in childhood and IgG subclass deficiency. IgG subclass deficiency and recurrent bronchitis are both quite prominent phenomena in young children but rare in older children, suggesting a transient immaturity of the immune system as one of the possible pathogenetic factors. An IgA or an IgG deficiency is highly suggestive for the existence of a combined IgG subclass deficiency.     

播散性卡介苗感染18例分析

目的 探讨播散性卡介苗感染的临床表现、免疫学异常以及治疗转归.方法 回顾性分析2000年1月至2007年12月首都医科大学附属北京儿童医院收治的18例播散性卡介苗感染患儿的临床资料.结果 18例患儿中男13例,女5例,播散首先发生于接种部位同侧腋下淋巴结,同时播散至肺15例次,纵隔和腹腔淋巴结18例次,皮肤和软组织5例次,骨骼4例次,肝4例次,脾8例次,肾和肾上腺各1例次,脑膜1例次.18例中诊断原发免疫缺陷病12例,其中严重联合免疫缺陷病3例,慢性肉芽肿(CGD)7例,白细胞介素12/干扰素γ通路缺陷2例.18例中11例死亡,7例随访1～9年仍存活,其中4例有反复活动性皮肤和骨结核表现,3例易患反复其他病原感染.结论 播散性卡介苗感染患儿多存在原发免疫缺陷病,其中CGD和IL-12/IFN-γ通路缺陷在此类患儿中比例较高,对此类患儿应进行特殊免疫功能检查.患儿多数预后不良,应尽早明确免疫缺陷类型,并进行针对性免疫治疗.     

Volvulus as a complication of chronic intestinal pseudo-obstruction syndrome

Chronic intestinal pseudo-obstruction syndrome (CIPS) is a severe motility disorder of the gastrointestinal tract that presents with continuous or recurrent symptoms and signs of intestinal obstruction without evidence of a structural lesion occluding the intestinal lumen. Mechanical obstruction might occur in these patients as well but is typically difficult to distinguish from an exacerbation of CIPS. We report two pediatric cases in which mechanical obstruction by volvulus mimicked an exacerbation of CIPS, requiring surgical intervention. Conclusion: Awareness of the possibility of true mechanical obstruction in CIPS patients during an exacerbation episode is needed, as this is a severe condition and usually requires surgical intervention.     

疑难病研究——遗传性巨十二指肠症

报道1例遗传性巨十二指肠症的病例,该病为一种以家族性空腔脏器肌病为特点的少见病,可能为常染色体显性遗传病。此病儿童发病罕见,临床表现为反复发作的假性消化道梗阻,以间断发生的呕吐、腹胀为主要症状,可造成营养障碍、发育迟缓。钡餐检查可见十二指肠扩张,食道测压显示食道蠕动功能受损。病理形态学上表现多样,可见肠壁的炎性浸润、平滑肌层变薄,纤维组织增生。确诊需结合家族史、病理检查及影像学和功能学检查方可作出。手术治疗可暂时缓解症状但无法治愈该病。     

Non-familial visceral myopathy: clinical and pathologic features of degenerative leiomyopathy

 Degenerative leiomyopathy (DL) is a distinctive form of acquired degenerative visceral myopathy of uncertain etiology that occurs largely in Africa and results in intestinal pseudo-obstruction (IP). In this review of 39 patients from the Western Cape region of South Africa, the mean age at presentation was 9.5 years (range 6 months to 16 years). Characteristic clinical features included a chronic, insidious history of repeated attacks of abdominal distension, abdominal pain, and vomiting. Marked gaseous distension with atony and IP, especially of the colon, was noted on X-ray films. Megacolon was the most common radiologic feature, but pseudo-obstruction extended proximally into the small intestine in some patients with advanced disease. In the majority of cases the condition was progressive and eventually affected the entire gastrointestinal (GI) tract. Accepted: 6 June 2001     

Discriminating pediatric condition falsification from chronic intestinal pseudo-obstruction in toddlers

Pediatric condition falsification may masquerade as chronic and serious digestive disease, including chronic intestinal pseudo-obstruction. The purpose of this study was to define clinical criteria to discriminate between these two conditions. We compared medical records of 8 pediatric condition falsification victims to those of 14 children with chronic intestinal pseudo-obstruction. Clinical features suggesting pediatric condition falsification in toddlers presenting with chronic and severe digestive complaints included (a) daily abdominal pain, (b) illness involving three or more organ systems, (c) an accelerating disease trajectory, (d) a reported history of preterm birth, (e) absence of dilated bowel on x-ray, (f) normal antroduodenal manometry, and (g) no urinary neuromuscular disease. These results suggest that a diagnosis of pediatric condition falsification may be suspected in toddlers presenting with a phenotype for enteric neuromuscular disorders by features in the clinical history, symptoms, and signs.     

Low immunoglobulin G3 levels in wheezy children

This study aimed to investigate the prevalence of IgG subclass deficiency in wheezy children aged <3y. Serum levels of IgA, IgE and IgG subclasses were measured in 310 children with recurrent wheezing and in 100 healthy controls. IgG3 levels were below the normal lower limit in 123 (39.6%) patients. This finding may reflect delayed maturation of the immune system, predisposing young children <3 y of age to wheezing.     

Urinary outputs of oxalate, calcium, and magnesium in children with intestinal disorders. Potential cause of renal calculi

24-hour urinary outputs of oxalate, calcium, and magnesium have been determined in a total of 62 children aged 3 months to 17 years who fell into the following groups: (i) 16 normal controls, (ii) 3 with primary hyperoxaluria, (iii) 9 with small and/or large intestinal resections, (iv) 9 with untreated coeliac disease, (v) 5 with pancreatic dysfunction, and (vi) a miscellaneous group of 20 children with a variety of intestinal disorders. Taken as a whole, 58% of patients with intestinal disorders had hyperoxaluria, and of these 7% had urinary outputs of oxalate which fell within the range seen in primary hyperoxaluria. The proportion of children with hyperoxaluria in the different diagnostic groups was as follows: intestinal resections (78%), coeliac disease (67%), pancreatic dysfunction (80%), and miscellaneous (45%). 35% of the patients with hyperoxaluria had hypercalciuria, whereas magnesium excretion was normal in all subjects studied. In 2 patients treatment of the underlying condition was accompanied by a return of oxalate excretion to normal. These results indicate that hyperoxaluria and hypercalciuria are common in children with a variety of intestinal disorders, and that such children may be at risk of developing renal calculi without early diagnosis and treatment.     

Urinary outputs of oxalate,calcium, and magnesium in children with intestinal disorders. Potential cause of renal calculi.

24-hour urinary outputs of oxalate, calcium, and magnesium have been determined in a total of 62 children aged 3 months to 17 years who fell into the following groups: (i) 16 normal controls, (ii) 3 with primary hyperoxaluria, (iii) 9 with small and/or large intestinal resections, (iv) 9 with untreated coeliac disease, (v) 5 with pancreatic dysfunction, and (vi) a miscellaneous group of 20 children with a variety of intestinal disorders. Taken as a whole, 58% of patients with intestinal disorders had hyperoxaluria, and of these 7% had urinary outputs of oxalate which fell within the range seen in primary hyperoxaluria. The proportion of children with hyperoxaluria in the different diagnostic groups was as follows: intestinal resections (78%), coeliac disease (67%), pancreatic dysfunction (80%), and miscellaneous (45%). 35% of the patients with hyperoxaluria had hypercalciuria, whereas magnesium excretion was normal in all subjects studied. In 2 patients treatment of the underlying condition was accompanied by a return of oxalate excretion to normal. These results indicate that hyperoxaluria and hypercalciuria are common in children with a variety of intestinal disorders, and that such children may be at risk of developing renal calculi without early diagnosis and treatment.     

Chronic non-specific diarrhoea.

Recurrent, unexplained diarrhoea is the most common intestinal complaint in children aged 6 months to 3 years. We studied 27 consecutive children with this complaint and followed them up until the age of 5 years. Diarrhoea began at the mean age of 9 months (range 4 to 16 months) and resolved in 21 children by 3 years of age. Twelve children had had infantile colic earlier. In six patients diarrhoea was caused by food allergy (cows'' milk allergy and allergy to fresh vegetables). Episodes of diarrhoea persisted in four of these six. Twenty one children had unexplained diarrhoea: this resolved in 19. Nutritional deficiencies were rare; only one child had iron deficiency. Relative weights of the children were significantly lower at 2 years than at 1 year of age. At 5 years of age six of the children continued to have episodes of diarrhoea, and abdominal pains, headaches, and atopy occurred more commonly than in the general population. We suggest that there are two major subgroups among children with recurrent diarrhoea--children with food allergy and those who react to environmental stresses with a variety of somatic symptoms.     

Immunological aspects of food intolerance in children during first years of life]

A study was made of the morphofunctional status and local defence of the gastrointestinal tract in 122 children aged 4 months to 6 years, suffering from food intolerance showed up by atopic dermatitis in 52 children and by chronic diarrhea in 70 children. Based on the allergological anamnesis, scarification cutaneous tests with food allergens, detection of antibodies to food antigens (RAST, HAIT) food allergy was revealed in all the children. Chronic gastroduodenitis was identified in all the children suffering from atopic dermatitis and in 95% of the children with chronic diarrhea. It should be mentioned that one-third of that group had a graver illness--diffuse duodenitis with sub-atrophy of the villi. The allergic genesis of the impairment of the gastroduodenal mucosa was confirmed. It was more remarkable in atopic dermatitis (tissue eosinophilia and high content of IgE-plasmacytes in the duodenal mucosa). The decrease of local immune defence of the mucous membrane, lactase deficiency, elevated growth of microorganisms in the duodenal contents promote the rise of intestinal barrier permeability for food antigens and enhancement of sensitization.     

Childhood idiopathic thrombocytopenic purpura in the Nordic countries: epidemiology and predictors of chronic disease

AIM: To describe the epidemiology of idiopathic thrombocytopenic purpura (ITP) in the Nordic countries, to define clinical subgroups and to investigate factors predicting chronic disease. METHODS: A prospective registration was done from 1998 to 2000, including all children with newly diagnosed ITP aged 0-14 y and at least one platelet count <30 x 10(9)/l. RESULTS: 506 children were registered and 423 followed for 6 mo. The incidence was 4.8/10(5) per year. Most children were aged 0-7 y (78%), with a predominance of boys, while patients aged 8-14 y had equal representation of the two sexes. There were seasonal variations determined by variations in postinfectious cases with sudden onset. The platelet count was <10 x 10(9)/l in 58%, but bleeding manifestations were mild or moderate in 97%. The insidious form (symptoms for more than 2 wk) was more frequent in older children and girls, showed little seasonal variation, had milder manifestations and ran a chronic course in more than half the cases. Intracranial haemorrhages did not occur in the first 6 mo after diagnosis. Chronic ITP developed in 25%. The strongest predictor of chronic disease was insidious onset of symptoms (OR 5.97). CONCLUSION: In the Nordic countries, ITP mainly affects children aged 0-7 y, with a winter bulk of postinfectious cases superimposed on a steady occurrence of non-infectious cases. Clinically, it may be useful to distinguish between children with sudden versus insidious onset of symptoms rather than between different age groups.