Interleukin-10 receptor mutation presenting with severe nappy ulceration and infantile inflammatory bowel disease.

Inflammatory bowel disease (IBD) can be divided into Crohn disease, ulcerative colitis and inflammatory bowel disease unclassified (IBDU). In most patients, these disorders present in adolescence or early adulthood. Patients with infantile IBD can have an associated underlying immunodeficiency disorder caused by a mutation in interleukin (IL)-10 or its receptor. We describe a child presenting with intractable bloody diarrhoea since 2 weeks of age and with severe nappy ulceration, who was ultimately diagnosed as having inflammatory bowel disease (IBD) due to an immunodeficiency in the IL-10 receptor. This report highlights the importance of considering this rare immunodeficiency in patients with infantile IBD presenting with severe perianal disease to a dermatologist.

Extraintestinal manifestations in children with gastrointestinal food allergy.

OBJECTIVES: The presence of extraintestinal manifestations (EIM) in children with gastrointestinal (GI) food allergy (GIFA) is greatly debated. In the present study we assessed the prevalence of EIM in children with GIFA and investigated whether their presence is helpful in the allergy-focused history-taking process. METHODS: The medical records of all children with a proven diagnosis of GIFA were reviewed along with those of children diagnosed as having inflammatory bowel disease (IBD) as controls. Data regarding age at onset, age at diagnosis, atopic family history, atopic comorbidities, GI symptoms, and EIM were recorded. RESULTS: Data from 436 children with GIFA and 74 children with IBD were included in the analysis. EIM were documented in 368 children with GIFA, including fatigue (53.0%), allergic shiners (49.1%), mouth ulcers (39.0%), joint pain/hypermobility (35.8%), poor sleep (34.4%), night sweats (34.4%), headache (22.7%), and bed-wetting (17.7%). The proportion of patients with EIM was higher in the GIFA group compared with that in the IBD group (368/436 [84.4%] vs 40/74 [54.1%]; P < 0.001). Segregating the GIFA group into children with and without atopic comorbidities, both atopic (276/30; 89.9%) and nonatopic (93/130; 71.5%) children showed higher proportion of EIM than children with IBD ([40/74; 54.1%], P < 0.01 and <0.05, respectively). CONCLUSIONS: GIFA are commonly associated with a wide range of EIM, which appear to represent important and specific clinical features of this group of conditions. Their recognition in taking an allergy-focused history may play an important role for both diagnosis and management.

X-linked inhibitor of apoptosis (XIAP) deficiency: the spectrum of presenting manifestations beyond hemophagocytic lymphohistiocytosis.

X-linked inhibitor of apoptosis (XIAP) deficiency caused by mutations in BIRC4 was initially described in patients with X-linked lymphoproliferative syndrome (XLP) who had no mutations in SH2D1A. In the initial reports, EBV-associated hemophagocytic lymphohistiocytosis (HLH) was the predominant clinical phenotype. Among 25 symptomatic patients diagnosed with XIAP deficiency, we identified 17 patients who initially presented with manifestations other than HLH. These included Crohn-like bowel disease (n=6), severe infectious mononucleosis (n=4), isolated splenomegaly (n=3), uveitis (n=1), periodic fever (n=1), fistulating skin abscesses (n=1) and severe Giardia enteritis (n=1). Subsequent manifestations included celiac-like disease, antibody deficiency, splenomegaly and partial HLH. Screening by flow cytometry identified 14 of 17 patients in our cohort. However, neither genotype nor protein expression nor results from cell death studies were clearly associated with the clinical phenotype. Only mutation analysis can reliably identify affected patients. XIAP deficiency must be considered in a wide range of clinical presentations.

Systematic review of the evidence base for the medical treatment of paediatric inflammatory bowel disease.

OBJECTIVE: To systematically review the evidence base for the medical (pharmaceutical and nutritional) treatment of paediatric inflammatory bowel disease. METHODS: Key clinical questions were formulated regarding different treatment modalities used in the treatment of paediatric (not adult-onset) IBD, in particular the induction and maintenance of remission in Crohn disease and ulcerative colitis. Electronic searches were performed from January 1966 to December 2006, using the electronic search strategy of the Cochrane IBD group. Details of papers were entered on a dedicated database, reviewed in abstract form, and disseminated in full for appraisal. Clinical guidelines were appraised using the AGREE instrument and all other relevant papers were appraised using Scottish Intercollegiate Guidelines Network methodology, with evidence levels given to all papers. RESULTS: A total of 6285 papers were identified, of which 1255 involved children; these were entered on the database. After critical appraisal, only 103 publications met our criteria as evidence on medical treatment of paediatric IBD. We identified 3 clinical guidelines, 1 systematic review, and 16 randomised controlled trials; all were of variable quality, with none getting the highest methodological scores. CONCLUSIONS: This is the first comprehensive review of the evidence base for the treatment of paediatric IBD, highlighting the paucity of trials of high methodological quality. As a result, the development of clinical guidelines for managing children and young people with IBD must be consensus based, informed by the best-available evidence from the paediatric literature and high-quality data from the adult IBD literature, together with the clinical expertise and multidisciplinary experience of paediatric IBD experts.

Distribution of hemoglobinopathy disorders in Saudi Arabia based on data from the premarital screening and genetic counseling program, 2011-2015.

The prevalence rates of ß-thalassemia (ß-thal) and Sickle Cell Disease (SCD) in Saudi Arabia are considered one of the highest compared to surrounding countries in the Middle East (0.05% and 4.50%, respectively). In this study, Secondary data analysis was obtained from the premarital screening and genetic counseling program (PMSGC), and included 12,30,582 individuals from February 2011 to December 2015. Prevalence rates (per 1000 population) for ß-thal and SCD were calculated for carrier status, disease status and their combination. During the 5-year study period, the overall prevalence rate per 1000 population for ß-thal was 13.6 (12.9 for the trait and 0.7 for the disease). The prevalence rate for SCD was 49.6 (45.8 for the trait and 3.8 for the disease). Rates for ß-thal were found to decrease from 24.2 in 2011, to 12 in 2015. However, SCD rates remained rather constant and ranged from 42.3 in 2011 to 49.8 in 2015. The highest rate for both ß-thal and SCD was observed in the Eastern and Southern regions. This result reflects major accomplishment of the PMSGC. This study recommends further improvement in preventive measures in high-risk regions, and enhanced community awareness to provide the highest rate reduction for these disorders.

Progestogen for treating threatened miscarriage.

BACKGROUND: Miscarriage is a common complication encountered during pregnancy. The role of progesterone in preparing the uterus for the implantation of the embryo and its role in maintaining the pregnancy have been known for a long time. Inadequate secretion of progesterone in early pregnancy has been linked to the aetiology of miscarriage and progesterone supplementation has been used as a treatment for threatened miscarriage to prevent spontaneous pregnancy loss. OBJECTIVES: To determine the efficacy and the safety of progestogens in the treatment of threatened miscarriage. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (December 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2006, Issue 1), MEDLINE (January 1966 to April 2006), EMBASE (1980 to April 2006) and CINAHL (1982 to April 2006). We scanned bibliographies of all located articles for any unidentified articles. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials that compare progestogen with placebo, no treatment or any other treatment given in an effort to treat threatened miscarriage. DATA COLLECTION AND ANALYSIS: At least two authors assessed the trials for inclusion in the review and extracted the data. MAIN RESULTS: Two studies (84 participants) were included in the meta-analysis. In one study, all the participants met the inclusion criteria and in the other study, only the subgroup of participants who met the inclusion criteria was included in the meta-analysis. There was no evidence of effectiveness with the use vaginal progesterone compared to placebo in reducing the risk of miscarriage (relative risk 0.47; 95% confidence interval (CI) 0.17 to 1.30). AUTHORS' CONCLUSIONS: Based on scarce data from two methodologically poor trials, there is no evidence to support the routine use of progestogens for the treatment of threatened miscarriage. Information about potential harms to the mother or child, or both, with the use of progestogens is lacking. Further, larger, randomized controlled trials on the effect of progestogens on the treatment of threatened miscarriage, which investigate potential harms as well as benefits, are needed.

Efficacy of the neurokinin-1 receptor antagonist aprepitant in children with cyclical vomiting syndrome.

BACKGROUND: Aprepitant (Emend, Merck Sharp & Dohme Ltd, Haarlem, the Netherlands), a neurokinin-1 receptor antagonist, prevents vomiting in a range of conditions. No data are available on its use in children with cyclical vomiting syndrome (CVS). AIM: We investigated the efficacy of aprepitant as prophylactic treatment or acute intervention in CVS children refractory to conventional therapies. METHODS: Forty-one children (median age: 8 years) fulfilling NASPGHAN criteria treated acutely (RegA) or prophylactically (RegP) with aprepitant were retrospectively reviewed. Primary outcome was the clinical response (decrease in frequency and intensity of CVS episodes). Secondary outcomes were: number of CVS episodes/year, number of hospital admissions/year, CVS episode duration, number of vomits/h, symptom-free interval length (days), and school attendance percentage. The follow-up period was 18-60 months. RESULTS: Sixteen children received RegP and 25 RegA. One child on RegP stopped treatment due to severe migraine. At 12-months on intention-to-treat analysis, 13 children on RegP (81%) achieved either complete (3/16, 19%) or partial (10/16, 62%) clinical response. On RegA, 19 children (76%) had either complete (3/25, 12%) or partial (16/25, 64%) response (P = 0.8 vs. RegP). In both RegP and RegA, there was a significant decrease in CVS episodes/year, hospital admission number/year, CVS episode length, number of vomits/h, as well as an increase in symptom-free interval duration and school attendance percentage. Side effects were reported only in RegP (5/16, 31%) including hiccough (3/16, 19%), asthenia/fatigue (2/16, 12.5%), increased appetite (2/16, 12.5%), mild headache (1/16, 6%) and severe migraine (1/16, 6%). CONCLUSION: Aprepitant appears effective for both acute and prophylactic management of paediatric cyclical vomiting syndrome refractory to conventional therapies.

Management of fulminating ulcerative colitis in childhood with chimeric anti-CD25 antibody.

Fulminating acute ulcerative colitis (UC) is a potentially life threatening medical emergency. Up to 30% of individuals respond poorly to corticosteroids alone and second line medical or surgical therapies are indicated. We describe the successful use of chimeric anti-CD25 therapy in 4 such children poorly responsive to combined therapy with intravenous steroids and calcineurin inhibitors with a pretreatment predictive risk of colectomy of 85-100%. Clinical disease activity scores normalized within 72 hours of anti-CD25 administration and colonic histology provided evidence of mucosal healing within 10-14 days. None required emergency colectomy. Anti-CD25 is efficacious in fulminating UC and randomized placebo controlled trials appear indicated.

Diaphragmatic hernia in Down's syndrome.

Three Saudi children with Down's syndrome were found to have anterior diaphragmatic hernias. They all needed surgical correction. In Down's syndrome, besides congenital heart disease and recurrent chest infection, a diaphragmatic hernia should be looked for as a possible cause of respiratory distress and chest deformity.

Immunoglobulin therapy for severe thrombocytopenia complicating falciparum malaria.

A 12-year-old Saudi boy with falciparum malaria developed profound thrombocytopenia with associated significant bleeding. Immunoglobulin was used to treat this case.

Immunoregulatory CD4+ CD45R+ suppressor/inducer T lymphocyte subsets and impaired cell-mediated immunity in patients with Down's syndrome.

The monoclonal antibodies 2H4 and 4B4 allow CD4+ and CD8+ T lymphocytes to be subdivided into CD45R+ and CDW29+ functional subpopulations. The CD4+ CD45R+ lymphocytes are designated as suppressor/inducer and CD4+ CDW29+ as helper/inducer subsets. Peripheral blood lymphocytes from 19 patients with Down's syndrome and 19 age- and sex-matched normal controls were analysed for the CD45R+ and CDW29+ subsets from the CD4+ and CD8+ T lymphocytes. The percentage of CD4+ CD45R+ cells (suppressor inducer) was markedly increased and of CD4+ CDW29+ cells (helper/inducer) decreased in all patients with Down's syndrome. In contract, the percentage of CD8+ CD45R+ and CD8+ CDW29+ subsets showed no major differences between patients with Down's syndrome and normal controls. Moreover, an alteration in the CD4+ and CD45R+ and CD4+ CDW29+ T cell subsets was accompanied by a markedly reduced proliferative response to phytohaemagglutinin and concanavalin A stimulation of the CD4+ T lymphocytes. Thus, a deficiency exists in patients with Down's syndrome in the CD4+ CDW29+ helper/inducer T cell subset which may contribute to their impaired cell-mediated immunity.

A study of the axis of orientation of residual astigmatism.

The aim of this study was to determine the axis of orientation of residual astigmatism in a sample of human eyes applying the principle of astigmatic decomposition. Calculations were carried out on keratoscopic and refractive data collected from the right and left eyes of 70 subjects (37 male and 33 female students) of mixed race (including 25 Asians and 43 Caucasians). No statistically significant difference was found for mean levels of residual astigmatism measured in the right (0.46 DC x 98.2 degrees) and left (0.50 DC x 99.4 degrees) eyes. Residual astigmatism was predominantly against-the-rule (83% of right eyes and 66% of left eyes) and was within +/- 20 degrees of being perpendicularly disposed relative to the corneal astigmatic power axis in two thirds of the eyes measured. No statistically significant differences were found for either gender or race.

Determination of the influence of effectivity upon residual astigmatism.

PURPOSE: A computing scheme is described which allows determination of the astigmatic contribution of ocular surface effectivity towards residual astigmatism. METHODS: This involves paraxial raytracing through astigmatic surfaces at random axes and applies the principle of astigmatic decomposition. Calculations are shown for averaged data from 66 normal right eyes. Frequency distribution graphs demonstrate individual variations. RESULTS: The averaged ratio of corneal thickness:anterior chamber:lens thickness cylinder power contributions due to effectivity (1:5:17) did not match the ratio of their respective intraocular distances (1:7:7); a disproportionate amount of astigmatism arose from lens thickness effectivity. Although previous research has revealed that results for individual eyes are prone to accummulative experimental errors, frequency distribution graphs indicate that effectivity predominantly yelds direct astigmatism (axis 180 degrees +/- 22.5 degrees). CONCLUSIONS: This computing scheme offers a means of examining the functional ocular morphology of astigmatic eyes.

Measurement of astigmatism arising from the internal ocular surfaces.

A method is described for measuring internal ocular surface (posterior cornea, anterior and posterior crystalline lens) astigmatism. This involves the use of videokeratography, A-scan ultrasonography, and autorefractometry along with multi-meridional phakometric measurements of Purkinje images I(anterior corneal surface) II(posterior corneal surface) and IV(posterior lens surface). Data was collected from both eyes of 66 subjects. Right and left eyes exhibited similar mean levels of astigmatism from the posterior corneal surface (R + 0.21 DC axis 82 degrees; L + 0.22 DC axis 80 degrees), anterior lens surface (R + 0.52 DC axis 8 degrees; L + 0.49 DC axis 165 degrees) and posterior lens surface (R + 1.48 DC axis 99 degrees; L + 1.16 DC axis 90 degrees). It was generally found that astigmatism arising from the anterior corneal and lens surfaces in conjunction with intraocular distance effectivity are almost completely compensated for by the posterior corneal and lens surface. Repeatability was assessed on 20 subjects. Although the methods is prone to accumulated experimental errors, these are random in nature so that the difference between repeat group averaged data never exceeded +/- 0.27 DC cylindrical component and +/- 6 degrees cylinder axis.

T-cell abnormalities in antibody deficiency syndromes.

We studied two patients with hypogammaglobulinaemia, three with selective IgA deficiency, and four with selective extreme IgM deficiency for T-cell abnormalities in the circulating blood. Most patients had altered CD4+ helper/inducer and CD8+ suppressor/cytotoxic T-cell subsets, and an elevated percentage of HLA-DR+ and interleukin 2 (IL-2) receptor+ antigens on lymphocytes. One patient with the selective IgA deficiency had an absence of CD4+ T cells in blood. The lymphocytes of eight patients showed a diminished proliferative response and deficient IL-2 production in response to stimulation with phytohaemagglutinin or concanavalin A. The three patients with selective IgM deficiency were found to have a defective T-cell abnormality in IgM synthesis by B cells. It is interesting that CD8+ T cells of the two patients with IgM deficiency demonstrated suppressor cell function for IgM synthesis by the normal B and T cells.

A clinical trial of the SUN SK-2000 computer-assisted videokeratoscope.

A clinical trial was performed on 20 optometry students in order to evaluate the suitability of the SUN SK-2000 (SUN contact lens company, Japan) computer-assisted videokeratoscope for use in clinical practice. Suitability was assessed by observing three factors: the accuracy, repeatability and agreement for central mean corneal power (MCP) with a keratometer (Javal Schiotz). Measurements of eight peripheral points and the central radius of curvature were made on 20 optometry students and on an 8 mm calibration surface using the SUN SK-2000. The SUN SK-2000 accurately determined the 8 mm calibration surface (supplied by manufacturers) to be spherical (SD = +/- 0.013, P = 0.776). Careful alignment was found to be an important factor in determining the actual radius of the calibration sphere. Unfortunately, the system required measurements to be taken at a point which was not coincident with the line of sight. A simple improvement to this has been suggested. Readings were most repeatable for central corneal radii. Peripheral radii showed the most repeatability for the horizontal and inferior corneal radii. It has been suggested that the ocular adnexa may be a possible cause for the poor repeatability in the superior area of the cornea. The level of agreement between the Javal Schiotz keratometer and the SUN SK-2000 in terms of mean refractive error (MRE) was not found to be sufficient for the two instruments to be interchangeable (P = 0.011). The C0 and C45 components of corneal astigmatism were found to have little association with the keratometer.

Hemolytic-uremic syndrome in asir region.

INTRODUCTION: Hemolytic-Uremic Syndrome (HUS) is a worldwide disease and a common cause of acute renal failure in childhood. Recently the number of cases in our area seems to be increasing. AIM: The objective of this study was to look at epidemiology, clinical course and complications of hemolytic-uremic syndrome in the Southern region of Saudi Arabia. METHOD: The medical records of 24 patients with typical post diarrhea HUS who were seen in Asir Central Hospital (ACH) between January 1989 and December 1994 were retrospectively reviewed. RESULTS: Of the 24 patients 15 were boys and 9 were girls with sex ratio 1.7:1. Ages ranged from 7 months to 11 years with a mean of 38 months. Clustering of cases were during spring and autumn time. Shigella dysenteriae was the most commonly isolated micro-organism, found in the stools of 5 patients. Complications occurred in 8 patients (33%) in the acute phase, 5 (21%) had generalized tonic-clonic seizures, while 2 (8%) had depressed level of consciousness. Three of the patients who had generalized seizures developed permanent cortical blindness. One patient developed chronic renal failure. One patient (4%) died in the acute phase after prolonged generalised seizure and coma. The mean age of the group with complications was 3335 months while it was 41:03 months in the uncomplicated group and mean platelets count was 46±40 × 10(9)/L and 58 ± 35 × 10(9)/L, respectively. CONCLUSION: Males seem to be more affected than females and Shigella was the most commonly isolated organism. Cortical blindness was relatively more common than in other studies and patients with complications were generally younger and had lower platelet count than those without complications.