CELIAC DISEASE AMONG CHILDREN PRESENTED WITH UNEXPLAINED Mohamed Sayed Hemeda, Ahmed Saad Eldeen Ibrahim, Mohamed Sami Elhakim, Kamel Soliman Hammad

CELIAC DISEASE AMONG CHILDREN PRESENTED WITH UNEXPLAINED SHORT STATURE

By

Mohamed Sayed Hemeda*, Ahmed Saad Eldeen Ibrahim*, Mohamed Sami Elhakim**, Kamel Soliman Hammad***

Pediatrics*, Pathology** and clinical Pathology*** departments, Faculty of Medicine, Al-Azhar University

ABSTRACT

Introduction: Celiac disease is a chronic autoimmune condition, in genetically susceptible persons, perpetuated by the ingested gluten from cereals, wheat and barley, its clinical spectrum is broad, varies from absence of symptoms to gastrointestinal (classic) and/or extra intestinal (non-classic) symptoms, patients without symptoms may have latent or silent celiac disease, because celiac disease can be atypical or even clinically silent, many patients remain undiagnosed and at risk for the long-term, sometimes serious complications of untreated celiac disease. Short stature is the most commonly encountered extra-intestinal (non –classical) symptoms of CD in children, being found in roughly one-third of all new pediatric celiac diagnoses, while it can be directly related to malabsorption of nutrients, it should completely reverse once a child is strictly adherent to Gluten free diet. Aim of the work: The goal of this study was to screen for coeliac disease in Egyptian children with unexplained short stature by estimating serum level of total IgA and tissue transglutaminase IgA. Methodology: Cross sectional analytical study for 100 child with short stature (males and females), attended the pediatric out-patient clinics of AL-Sayed Galal and Alhussen university hospitals in Cairo during the period from April 2017 to march 2019, any child aged 2- 18 years with undetectable cause of short stature whose Z score for height was less than -2 SD for the age and sex according to the WHO charts (WHO, 2006), not previously screened for Celiac disease was enrolled in the study, after approval of his care-giver, the medical records of patients evaluated for short stature include a proper detailed history and physical examination, growth analysis, followed by radiological (bone age), and Laboratory screening (including celiac serological screening and evaluation) , chromosomal analysis were performed when appropriate, followed by small intestinal biopsy for celiac seropositive patients and Growth hormone stimulation test was performed in suspected patients. Results: The demographic characteristics of all 100 cases regarding mean age in months was 80.85 ± 33.55 with range 36 – 179, Sex distribution of all cases was 52 (52.0%) female and 48 (48.0%) male, mean height in cm for all cases was 102.04 ±

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13.48 with range 84 – 141 and median height Z score for all study group was -3.4 (-3.6 – -3) with range -4.6 - -2.6. The results showed that 11(11%) cases were positive for TTG IgA antibodies with normal level of total IgA Identified celiac cases with mean age in months was 86.91 ± 37.58, female cases were 7 (63.6%) and 4 (36.4%) cases were males, mean Height in cm was 102.18 ± 14 and median height Z score was -3.6 (-4.3 – -3.4). Keywords: Short stature; Celiac disease; Children; Anti-tissue transglutaminase antibody, Idiopathic short stature.

INTRODUCTION followed by intestinal biopsy for 3 Celiac disease is a chronic histologic confirmation. autoimmune condition, in Short stature is the most genetically susceptible persons, commonly encountered extra- perpetuated by the ingested gluten intestinal manifestation of CD in from cereals, wheat and barley.1 children, being found in roughly Classic symptoms include one-third of all new pediatric gastrointestinal problems such as celiac diagnoses. While it can be chronic diarrhea, abdominal directly related to malabsorption distension, malabsorption, loss of of nutrients, it should completely appetite, and among children reverse once a child is strictly failure to grow normally. This adherent to a Gluten free diet 4 often begins between six months (GFD). and two years of age. Non-classic Around 2.5-3% of the children symptoms (eg, short stature, worldwide are short, 5 The , epilepsy, Egyptian Demographic and Health peripheral neuritis and iron Survey of 2008 (EDHS 2008) defiency anemia) are the most revealed that the prevalence of common, especially in people stunting among children under 5 older than two years.2 was 28.9%2, while that of the The standard method of EDHS 2014 was found to be 21% diagnosing celiac disease in while the prevalence of stunting symptomatic persons older than 2 among children aged 1-12 years years is the tissue attending the outpatient Pediatric transglutaminase (tTG) IgA test, clinic of Al-Azhar University

664 CELIAC DISEASE AMONG CHILDREN PRESENTED WITH UNEXPLAINED SHORT STATURE Mohamed Sayed Hemeda, Ahmed Saad Eldeen Ibrahim, Mohamed Sami Elhakim, Kamel Soliman Hammad Hospital (Al-Hussein), Cairo was recommendations or 15.8%.6 prescriptions. Endocrinological causes of 4- The aim of the study & all short stature accounted for 26% investigations as well as the while celiac disease (CD) risks & benefits of study have constituted 6.6% of children with been explained to parents of short stature in Egypt.7 the patients. In Egypt celiac disease is a 5- The authors declared no frequent disorder among children, potential conflicts of interest both in the general population with respect to the research, (0.53%) and in at-risk groups authorship and/or publication (6.4%).8 of this article. The only known effective 6- All data of patients & results of treatment is a strict lifelong study are confidential & gluten-free diet, which leads to patients have the right to keep recovery of the intestinal mucosa, it. improves symptoms, and reduced 7- The patient has the right to risk of developing complications withdraw from the study at 9 in most people, If untreated it any time. may result in cancers such as intestinal lymphoma and a slight increased risk of early death.10 Financial Disclosure/Funding: Ethical consideration: The authors received no 1- The ethical committees of Al- financial support for research, Azhar faculty of medicine & authorship, & or publication of pediatric department approved this article. the study. PATIENTS AND METHODS 2- Informed consent was obtained This study is a cross sectional from parents of all included study that was carried out on 100 children. children with short stature (males 3- The research protocol did not and females), The cases were interfere with any medical attending the pediatric out-patient clinic off AL-Sayed Galal and Alhussen university hospitals in 665 Al-Azhar Journal of Ped. Vol. 23 No. 47 Jan 2020

Cairo, any child fulfilled the Each child enrolled in the study inclusion criteria was enrolled in was subjected to the following:- the study after obtaining a written 1) Prestructured questionnaire. consent from the care giver during the period from April 2017 to 2) Anthropometric measurements. march 2019. 3) Detailed history (eg: personal, Inclusion criteria: dietetic, familial, gastrointestinal symptoms). 1- Age 2 - 18 years with undetectable case of short 4) Complete physical examination. stature whose Z score for 5) Radiological investigation: height was < -2 SD for the age Antero-posterior plain X-ray and sex according to the WHO film of left wrist was taken, and charts.11 bone age was determined 2. Not previously screened for according to Greulich and Pyle 12 Celiac disease. atlas. Exclusion criteria: 6) Laboratory investigations Short children with • Complete blood count by demonstrable cause such as; using cell counter (Diagon D cell 60, Hungary). 1) Familial and constitutional short stature. • Liver ((SGOT, SGPT) and renal (Blood urea and 2) Chronic illness. creatine) using biochemical 3) Disproportionate short stature. auto-analyzer (BT 1500, 4) Short stature of endocrinal Rome, Italy origin (eg, growth hormone • Total serum IgA by deficiency). nephlometry using a Behring 5) Turner syndrome. BNII nephelometer (Dade Behring, Milton Keynes, 6) Short stature with significant UK).level below10mg/dl congenital anomalies. considered deficient.13 7) Patients on gluten free diet. • IgA class serum human tissue transglutaminase antibody

666 CELIAC DISEASE AMONG CHILDREN PRESENTED WITH UNEXPLAINED SHORT STATURE Mohamed Sayed Hemeda, Ahmed Saad Eldeen Ibrahim, Mohamed Sami Elhakim, Kamel Soliman Hammad (IgA-TTGA) by enzyme deficient when the peak GH linked immunosorpant assay value during the stimulation (ELISA): test was equal to or higher Used kits: Enzyme-linked than 7 ng/ml Immunosorbent Assay Kit • KARYOTYPING for all for Tissue transglutaminase female patients with IgA (INOVA Diagnositics undetectable cause of short Inc., USA). stature to exclude turner Results: The result was syndrome considered weak positive if 7) Upper gastrointestinal the sample demonstrates 20– endoscopy for duodenal biopsy: 30U/ml or moderate to was done for the study group strong positive if the sample subjects who will have positive demonstrates >30U/ml.14 values on anti-tissue • Thyroid profile: TSH was transglutaminase (IgA) antibody estimated by estimation, Four to six biopsy immunoradiometric assay specimens were taken from the (IRMA), while FT3 and FT4 bulb and second parts of the were estimated by duodenum. Formalin-fixed biopsy radioimmunoassay kits from specimens stained with Diagnosis Product hematoxylin and eosin will be Corporation (Los Angeles, studied with the use of light CA, USA).15 microscopy, mucosal lesions were classified according to the criteria • Growth hormone of modified Marsh (Dr. Michael evaluation (IGF-1 and Marsh introduced the growth hormone provocation classification system to describe test for cases with low level the stages of damage in the small of IGF-1), IGF-1 was intestine as seen under a determined at diagnosis microscope).16 using solid phase IRMA, using kits from Diagnostic Statistical analysis: System Laboratories Inc., Data were analyzed using Texas, USA., Patients were IBM© SPSS© Statistics version considered not to be GH 23 (IBM© Corp., Armonk, NY,

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USA).Continuous numerical Chi-square test; •: Independent t- variables were presented as mean test; ≠: Mann-Whitney test and standard deviation (SD). *:

RESULTS

Our results are demonstrated in the following tables:

Table (1): Age and sex distribution of all cases with unexplained short stature Total cases

No. = 100 Mean ± SD 80.85 ± 33.55 Age (months) Range 36 – 179 Female 52 (52.0%) Sex Male 48 (48.0%)

Table (2): celiac serological screening of studied population Total cases

No. = 100 Normal 100 (100.0%) Total IGA deficient 0 (0.0%) Tissue Transglutaminase positive 11 (11%) IgA Negative 89 (89%)

This table shows Celiac disease present in 11% of cases with unexplained short staure.

668 CELIAC DISEASE AMONG CHILDREN PRESENTED WITH UNEXPLAINED SHORT STATURE Mohamed Sayed Hemeda, Ahmed Saad Eldeen Ibrahim, Mohamed Sami Elhakim, Kamel Soliman Hammad Table (3): Histopathological evaluation of celiac group Celiac group

no. = 11 II 2 (18.2%) Marsh classification of IIIA 3 (27.3%) celiac group* IIIB 6 (54.5%) *Marsh II: Lymphocytic enteritis with crypt hyperplasia Marsh IIIA: Partial villous atrophy Marsh IIIB: Subtotal villous atrophy Table (4): Intestinal and extra intestinal symptoms of celiac and non- celiac groups Non-celiac Celiac Test P- group group Sig. value value No. = 89 No. = 11 34.11 Diarrhea 1 (1.1%) 5 (45.5%) 0.000 HS 3 Vomiting 13 (14.6%) 4 (36.4%) 3.284 0.070 NS Constipation 15 (16.9%) 6 (54.5%) 8.383 0.004 HS 22.93 Gastro- Abdominal pain 8 (9.0%) 7 (63.6%) 0.000 HS intestinal 1 25.59 symptoms Abdominal distension 1 (1.1%) 4 (36.4%) 0.000 HS 5 Hematemesis 1 (1.1%) 0 (0.0%) 0.125 0.724 NS Oral ulcers 4 (4.5%) 2 (18.2%) 3.252 0.071 NS Rectal prolapse 2 (2.2%) 1 (9.1%) 1.576 0.209 NS Dental enamel hypoplasia 3 (3.4%) 3 (27.3%) 9.917 0.002 HS Skin Alopecia 2 (2.2%) 1 (9.1%) 1.576 0.209 NS symptoms Chest ASTHMA 11 (12.4%) 4 (36.4%) 4.424 0.035 S

symptoms Recurrent pneumonia 4 (4.5%) 0 (0.0%) 0.515 0.473 NS Skeletal Rachitic symptoms 8 (9.0%) 4 (36.4%) 6.947 0.008 HS

symptoms Cong anomaly 2 (2.2%) 0 (0.0%) 0.252 0.616 NS Head ache 4 (4.5%) 2 (18.2%) 3.252 0.071 NS CNS Epilepsy 5 (5.6%) 0 (0.0%) 0.651 0.420 NS symptoms Hearing loss 2 (2.2%) 0 (0.0%) 0.252 0.616 NS Developmental delay 3 (3.4%) 0 (0.0%) 0.382 0.536 NS

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This table shows that, the symptoms in celiac cases commonest gastrointestinal compaired to non-celiac cases in symptom in celiac group was chronic abdominal pain, chronic chronic abdominal pain diarrhea, chronic constipation, followed by chronic constipation abdominal distention and dental then chronic diarrhea, Results enamel hypoplasia with P value showed highly significant (0.00). difference in gastrointestinal Table (5): Anthropometric measurements of celiac and non-celiac groups

Non-celiac Celiac group Test P- group Sig. value value no. = 89 no. = 11

Mean ± SD 102.02 ± 13.48 102.18 ± 14.14 Height (cm) -0.037• 0.971 NS Range 84 – 141 84.5 – 129

Median (IQR) -3.3 (-3.6 – -3) -3.6 (-4.3 – -3.4) Height z-score - 3.000≠ 0.003 HS Range -4.1 – -2.6 -4.6 – -3.2

Mean ± SD 17.99 ± 5.33 17.12 ± 5.8 Weight (Kg) 0.505• 0.615 NS Range 10.7 – 34 11 – 31

Median (IQR) -1.7 (-2.5 – -1.1) -2.6 (-3.1 – -2.2) Weight z-score - 3.021≠ 0.003 HS Range -3.5 – 1.2 -3.2 – -1.7

Mean ± SD 17.01 ± 2.08 15.97 ± 1.15 BMI Kg/M(2) 1.610• 0.111 NS Range 14.1 – 24.2 14.9 – 18.6

Median (IQR) 0.6 (-0.3 – 1.4) -0.1 (-0.4 – 0.6) BMI z-score - 1.681≠ 0.093 NS Range -2 – 5 -0.9 – 1.5

Head circumference Normal 81 (91.0%) 11 (100.0%) 1.075* 0.300 NS

(cm) Microcephaly 8 (9.0%) 0 (0.0%)

Normal 78 (87.6%) 9 (81.8%) 0.293* 0.588 NS Tunner stage Delayed 11 (12.4%) 2 (18.2%)

Normal 70 (78.7%) 9 (81.8%) 0.059* 0.808 NS Bone age Delayed 19 (21.3%) 2 (18.2%)

670 CELIAC DISEASE AMONG CHILDREN PRESENTED WITH UNEXPLAINED SHORT STATURE Mohamed Sayed Hemeda, Ahmed Saad Eldeen Ibrahim, Mohamed Sami Elhakim, Kamel Soliman Hammad This table shows highly between celiac and non-celiac significant difference in height Z groups with P value (0.003) score and weight Z score Table (6): Comparison between celiac and non-celiac groups as regard C.B.C. Non-celiac Celiac group group Test value P-value Sig. No. = 89 No. = 11 Mean ± SD 10.01 ± 0.98 7.48 ± 0.85 Hb 8.159 0.000 HS Range 7.9 – 12.1 6.4 – 8.9 Mean ± SD 73.45 ± 5.5 57.45 ± 5.85 MCV 9.044 0.000 HS Range 59 – 89 49 – 68 Mean ± SD 28.99 ± 2.43 23.55 ± 2.34 MCHC Range 24 – 34 21 – 29 7.039 0.000 HS Range 0.2 – 0.7 0.3 – 0.6

This table shows high and non-celiac groups with p significant difference in Hb, value (0.000). MCV and MCHC between celiac

Table (7): Growth hormone evaluation of celiac and non-celiac groups

Total Non celiac Celiac Test P- cases group group Sig. value* value No. = 100 No. = 89 No. = 11 79 Normal 70 (78.7%) 9 (81.8%) (79.0%) ILGF1 0.059 0.808 NS 21 Low 19 (21.3%) 2 (18.2%) (21.0%) No 0 (0.0%) 0 (0.0%) 0 (0.0%) GH Normal 19 19 0 (0.0%) provocative response (90.5%) (100.0%) 21.000 0.000 HS test 2 Deficient 2 (9.5%) 0 (0.0%) (100.0%)

This table shows Cases of after provocation test and celiac disease with low level of diagnosed as Growth hormone ILGF-1 showed low level of GH deficiency, while non-celiac 671 Al-Azhar Journal of Ped. Vol. 23 No. 47 Jan 2020

group with low level of ILGF-1 after provocation test and this showed normal GH response consistent with ISS. Table (8): Marsh classification and level of Hb, ILGF-1, height and weight Z scores

Marsh classification Test P- Sig. value value II IIIA IIIB

2 2 Normal 5 (83.3%) (100.0%) (66.7%) ILGF1 0.917* 0.632 NS 1 Low 0 (0.0%) 1 (16.7%) (33.3%) Median -3.4 (-3.4 -3.5 (-4.5 -3.9 (-4.3 – Height z- (IQR) – -3.4) – -3.2) -3.6) 3.819≠ 0.148 NS score -3.4 – -4.5 – Range -4.6 – -3.5 -3.4 -3.2 Median -2.6 (-2.7 -2.2 (-3.1 -2.65 (-3.1 – Weight (IQR) – -2.5) – -1.9) -2.5) 0.565≠ 0.754 NS z-score -2.7 – -3.1 – Range -3.2 – -1.7 -2.5 -1.9 Mean ± 7.70 ± 8.13 ± 7.08 ± 0.51 HB SD 1.56 0.75 1.913• 0.209 NS Range 6.6 – 8.8 7.4 – 8.9 6.4 – 7.9

This table shows no weight Z scores and MARSH significant relation betweenlevel classification. of Hb, ILGF-1, height and

DISCUSSION was aimed to find out celiac This study is a cross sectional disease among children presented study that carried out on 100 with unexplained short stature. children with proportionate short The results showed that 11 stature who attended the pediatric (11%) cases from the total 100 out-patient clinics of ALSayed- (100%) cases with unexplained Galal and Alhussen university proportionated short stature were hospitals in Cairo, our objective positive for Tissue 672 CELIAC DISEASE AMONG CHILDREN PRESENTED WITH UNEXPLAINED SHORT STATURE Mohamed Sayed Hemeda, Ahmed Saad Eldeen Ibrahim, Mohamed Sami Elhakim, Kamel Soliman Hammad transglutaminase (TTG) IgA anemia were the significant antibodies with normal level of predictors of celiac disease. total IgA identified as positive In Egypt a study by El Dayem serological test for celiac disease et al., 2010 19 showed that celiac with mean age in months was disease in non-endocrinal short 86.91 ± 37.58 and range 48 – 168 stature account for (34.3%), these and female cases were 7 (63.6%) result agreed with De Lecea et and 4 (36.4%) cases were males. al., 1996, 20 who reported the Marsh classification for celiac percentage of CD in short children cases was Marsh class II in 2 ranging from 25 to 33.8%. In 2017 (18.2%) cases, IIIA in 3 (27.3%) a study by Hussein et al., 21 for cases and IIIB in 6 (54.5%) cases. etiological factors of short stature The low percentage of celiac in children and adolescents cases may be related to wide range (experience at a tertiary care of age group of studied population hospital) showed that celiac (2-18years), low socioeconomic disease constituted 6.6% of standard of most of studied children with short stature. population which contributed to Our data revealed the lack of early medical advice and demographic characteristics of all lack of specific nutritional 100 cases with unexplained short institutions for celiac disease. stature regarding mean age in Our finding is consistent with months 80.85 ± 33.55 with range other studies in Saudi Arabia and 36 – 179 while mean age for India, in Kingdom of Saudi Arabia celiac cases 86.91 ± 37.58 with studies showed that the percentage range 48 – 168 and for non-celiac of celiac disease among children cases was 80.1 ± 33.17 with range with short stature is approximately 36 – 179, with no significant 10%, 17 nearly 11% of patients difference between celiac and non- presenting with short stature in celiac groups The mean age for India have coeliac disease, in these celiac group 86.91 ± 37.58 can be patients chronic diarrhea and explained by the age of asking anemia were significant predictors medical advice for children with of coeliac disease, 18 while in our short stature due to comparing study chronic abdominal pain and with other children during entry the nursery or primary school. 673 Al-Azhar Journal of Ped. Vol. 23 No. 47 Jan 2020

A study by Savage et al There was significant decrease identified the age of diagnosis of in celiac cases in height Z score celiac disease to be 6 years for with P value (0.003) and weight Z girls and 7 years for boys. 22 score with P value (0.003) In Egypt a study by ELrefai et compared to non-celiac group, al, 2009 23 defined the average age these findings in celiac cases can for diagnosis of Celiac disease by be explained by the chronic 5.5 years, while another study El malabsorption state affecting Dayem et al., 2010 16 defined the celiac cases which in turn results mean age for diagnosis of celiac in various nutritional deficiencies disease in non-endocrinal short of macro- and micronutrients such stature by 7.9 ± 3.9 years. as minerals, , calories, dietary fiber and Hb. Sex distribution of all cases was 52 (52.0%) female and 48 A study Chishty, Singh, 2017 26 (48.0%) male, while in celiac proved that the mean values of group 7 (63.6 %) female and 4 weight z-score, Height z-score and (36.4%) male and non-celiac Hb were significantly lower in CD group 45 (50.6 %) female and 44 patients compared to non-celiac, 27 (49.4%) male, with no significant another study by Eren, 2018 difference between celiac and non- performed a comparison for celiac groups. anthropometric measurements in patients who were diagnosed at ≤ A study by Rubio-Tapia et al., 6 years of age and > 6 years of age 24 2016 showed that the clinical and proved that the height and presentation of celiac disease is weight z-scores of the patients not the same in men and women. who were diagnosed at > 6 years The disease is not only more of age were significantly lower frequent in women than in men than the younger group which but is also more severe and more mean the celiac disease is a rapid. progressive chronic malnutriting In Egypt a study by Shehab, disease and only the Gluten free 2013 25 observed equal sex ratio diet (GFD) compliance will among CD children. positively affect the patients’ all growth parameters.

674 CELIAC DISEASE AMONG CHILDREN PRESENTED WITH UNEXPLAINED SHORT STATURE Mohamed Sayed Hemeda, Ahmed Saad Eldeen Ibrahim, Mohamed Sami Elhakim, Kamel Soliman Hammad Bone age for all cases was of CD, which may be responsible normal in 79 (79.0%) cases and for growth failure. In particular, delayed in 21 (21.0%) cases, in before evaluating Growth celiac cases bone age delayed in 2 Hormone (GH) secretion in a short (18.2%) cases and normal in 9 child in whom GHD is suspected (81.8%) cases while in non-celiac on the basis of auxological data, cases normal bone age found in 70 CD must be excluded since false (78.7%) and was delayed in 19 GH responses to pharmacological (21.3%). stimuli have been observed, Celiac disease can be followed by their normalization complicated by metabolic bone after starting a GFD. Moreover, diseases like osteoporosis, Insulin-like growth factor I (IGF- secondary hyperparathyroidism, I), which is considered to be the and even without main peripheral GH mediator, is gastrointestinal complaints, these low in patients with insufficient bone disorders explained by both GH secretion, but is not a local and systemic mechanisms discriminating factor in the started with calcium evaluation of GH secretion, since malabsorption due to mucosal its level is influenced also by the atrophy, therefore, to avoid subject’s nutritional status. Low hypocalcemia parathyroid levels of insulin‐like growth factor hormone increases substantially 1 and Insulin‐Like Growth Factor (secondary hyperparathyroidism) Binding Protein (IGFBP) have and stimulates osteoclasts been reported in patients with 29 mediated bone degradation, CD. calcium is then obtained from the In non-celiac group 19 (21.3%) skeleton reservoir, but this high cases had delayed bone age and remodeling state can lead to low level of ILGF-1 with normal osteopenia and osteoporosis, Growth Hormone level on altering bone microstructure and provocation test, these cases increasing fracture risk. 28 diagnosed as Idiopathic short In celiac group 2 (18.2%) stature (ISS). cases had delayed bone age Tanner staging for all cases diagnosed later with dealing with was normal in 87 (87.0%) cases a short child must be the exclusion and delayed in 13 (13.0%) cases, 675 Al-Azhar Journal of Ped. Vol. 23 No. 47 Jan 2020

in celiac cases only 2 (18.2%) and the disruption of cases had delayed tanner staging, the hypothalamic control of aged 11 years (male with tanner growth hormone secretion which stage I) and 14 years( female with should be resolved on a GFD, tanner stage II) and 11 (12.4%) which should prevent any long- cases in non-celiac cases had term complications and restore delayed tanner staging normal maturation.30 The clinical findings can be The commonest explained by the lack effect of gastrointestinal symptom in celiac CD, deficient ILGF-1 and growth group was chronic abdominal hormone in the development of pain 7 (63.6%) cases followed by secondary sexual characters chronic constipation 6 (54.5%) Delayed puberty affecting cases and only chronic diarrhea roughly 10% of newly pediatric present in 5 (45.5%) cases, Rectal celiac patients, delayed puberty is prolapse found in one female case defined by lack of physical or aged 11ys. hormonal signs of puberty at the Results showed significant age of usual onset. Visible increase in the percentage of secondary sexual development gastrointestinal symptoms in usually begins when girls achieve celiac cases compaired to non- a bone age of 11 years and boys celiac cases in chronic abdominal achieve a bone age of 12 years. In pain with P value (0.000), chronic girls, a lack of breast development diarrhea with P value (0.000), by 13 years, or a lack of menarche chronic constipation with P value within three years after breast (0.004), abdominal distention with development or by 16 years is P value (0.000) and dental enamel considered to be abnormal. For hypoplasia with P value (0.002), boys, no testicular enlargement by chronic diarrhea in celiac disease 14 years or a delay in development is due to the maldigestion and for five years or more after onset malabsorption of nutrients. The of genitalia enlargement is stools might be watery or semi considered abnormal. In the case formed, light tan or gray and oily of CD, this delay in puberty is or frothy. The stools have a directly related to malabsorption, characteristic foul odour. In

676 CELIAC DISEASE AMONG CHILDREN PRESENTED WITH UNEXPLAINED SHORT STATURE Mohamed Sayed Hemeda, Ahmed Saad Eldeen Ibrahim, Mohamed Sami Elhakim, Kamel Soliman Hammad infants and young children, Rectal prolapse in celiac malabsorption of ingested fat disease occurred as a result of (steatorrhea) results in the delivery chronic constipation and increased of excessive dietary fat to the large of intra-abdominal pressure with bowel. This results in the weak pelvic floor muscles, 32 these production of hydroxy fatty acids findings consistent with findings by bacteria, which causes of Guandalini and Discepolo, secretion of fluids into the 2016 study. 33 intestinal lumen. Results showed significant Celiac disease causes damage increase in the percentage of to the intestinal villi that are extra-intestinal symptoms in celiac responsible for absorbing cases compaired to non-celiac nutrients, as food travels through cases in asthma with P value the digestive tract, the intestinal (0.035) and rachitic symptoms villi are unable to fully absorb with P value (0.008), The nutrients and may often absorb frequency of asthma increases in extra moisture from the stool celiac patients, possibly due to instead. This leads to hardened common genetic or environmental stool that is difficult to pass, factors contribute to the risk for resulting in constipation both and nutritional deficiencies Chronic abdominal pain in occurring due to celiac may help 34 celiac disease is common and incite asthma. maybe explained by the affection in celiac disease is of intestinal microbiota on the explained by the loss of villous complex gut-brain axis along with architecture leads to the enteric nervous system, malabsorption of calcium and immune system and external D leading to environment, and alterations in hypocalcemia and secondary this axis predispose to chronic hyperparathyroidism. In addition, pain in celiac disease, the release of proinflammatory maldigestion and bloating can cytokines, activating osteoblast cause abnormal swelling and represents the main locally acting feeling of a full or tight abdomen mechanisms responsible for bone and accompanied by abdominal derangement, this result agreed pain. 31 677 Al-Azhar Journal of Ped. Vol. 23 No. 47 Jan 2020

with the study by Assiri et al., Lower levels of mean 2016. 35 hemoglobin concentration, MCV The exact mechanism by which and MCHC were more prominent CD leads to headaches in is in celiac group than non-celiac unclear, but it is speculated that it group with P value (0.000) for all may be secondary to a lack of means, and this can be explained vitamins, macro elements, such as by (1) iron is predominantly magnesium, low levels of absorbed in the first portion of the serotonin, which are the direct small bowel, the duodenum, which result of the celiac associated is the main portion of the bowel malabsorption. An alternate affected by CD resulting in hypothesis is that the impaired duodenal inflammation which immune response results in an subsequently leads to the imbalance of pro-inflammatory malabsorption of iron and cytokines in response to ingested resultant iron-deficiency anemia, gluten, leading to altered vascular (2) occult blood loss in the tone, and subsequently, the onset gastrointestinal (GI) tract, occult of the headache. 27 gastrointestinal bleeding was detected in 25% to 54% of patients While alopecia has an with CD, depending on the degree association with pediatric CD, it is of villous atrophy, (3) Anemia of one of the less common extra- chronic disease, defined by intestinal manifestations seen, anemia with high ferritin levels occurring in roughly 1% of and inflammatory syndrome, has patients. It is presumed to occur been also described in CD, through an autoimmune reaction associated aplastic anemia has also involving T-cell dysregulation and been reported in isolated cases. autoantibodies directed against was anagen-stage hair follicle considered theoretically to be less structures and a direct association common in CD, as its absorption with the human leukocyte antigen takes place in the terminal ileum, (HLA)-DQB1*0201 allele, these which is infrequently involved. results consistent with the study However, studies have reported 36 done by Laurikka et al., 2018. significant proportions for B12 deficiency also, 37 these finding 678 CELIAC DISEASE AMONG CHILDREN PRESENTED WITH UNEXPLAINED SHORT STATURE Mohamed Sayed Hemeda, Ahmed Saad Eldeen Ibrahim, Mohamed Sami Elhakim, Kamel Soliman Hammad consistent with the study in Egypt CD children who did not show done by Abd El-Shaheed et al., catch up growth after at least 12- 2018. 38 months on a GFD, suggesting an The level of ILGF-1 for all autoimmune involvement between cases was normal in 79 (79.0%) the two entities, and these findings cases and low in 21 (21.0%) agreed with Nardecchia et al., 41 cases, but in celiac group 2 2019. (18.2%) cases showed low level CONCLUSION and in non-celiac group 19 • Celiac disease is important cause (21.3%) cases showed low level, for unexplained short stature these results contrasted with other study done by Giovenale et al., • Celiac disease could be 2006 39 who found that 0.23% of associated with GH deficiency celiac cases had GH deficiency RECOMMENDATIONS and these children did not grow after 1 year of GFD 1. Paediatricians and other health care professionals should strive to Cases of celiac disease with make celiac disease screening low level of ILGF-1 showed low readily available to all children level of GH after provocation test with short stature within their and diagnosed as Growth hormone community, especially for those deficiency, while non-celiac group infants most at risk. with low level of ILGF-1 showed normal GH response after 2. Educational programs focused provocation test and this on non-classic presentation of consistent with ISS. celiac disease. The presence of anti-pituitary 3. All short stature children should autoantibodies (AAPs) is reported be screened for celiac disease in children with CD and GH whether they are males or females, deficiency, Iughetti et al., 2006 40 had GIT symptoms or not, had found four out of five CD children delayed or normal bone age and with GH deficiency that resulted had already diagnosed cause for positive at high titers for AAPs, short stature or not. they also detected the presence of 4. Idiopathic short stature should both anti-pituitary and anti- be considered in cases with low hypothalamus antibodies in seven 679 Al-Azhar Journal of Ped. Vol. 23 No. 47 Jan 2020

level ILGF-1 and normal Growth 5. Phirke, D.S., Phirke, S.O. and Khot, hormone stimulation test. S., (2017): An aetiological evaluation of short stature. International Journal STUDY LIMITATIONS of Research in Medical Sciences, The current study had the 5(9), pp.3887-3890. following limitations: 6. Mahmoud, Amani Osman, Khaled Mahmoud Zayed, and Naglaa • The results were from a single Ahmed Shawky (2017): "Stunting medical Centre. among Children Attending a • The sample size was rather Pediatrics Outpatient Clinic in Cairo, Egypt." Egyptian Journal of small. Community Medicine 35, no. 3 • Refusal of some patients to enter (2017). the study. 7. Hussein, A., Farghaly, H., Askar, E., Metwalley, K., Saad, K., Zahran, A. REFERENCES and Othman, H.A., (2017): 1. National Institute for Health and Etiological factors of short stature in Care Excellence. Coeliac Disease – children and adolescents: experience Recognition, assessment and at a tertiary care hospital in Egypt. management (NG20). 2015. London Therapeutic advances in (2015): National Institute for Health endocrinology and metabolism, 8(5), and Care Excellence. pp.75-80. 2. Garnier-Lengline, H., Cerf- 8. Singh, P., Arora, A., Strand, T.A., Bensussan, N. and Ruemmele, F.M., Leffler, D.A., Catassi, C., Green, (2015): Celiac disease in children. P.H., Kelly, C.P., Ahuja, V. and Clinics and research in hepatology Makharia, G.K., (2018): Global and gastroenterology, 39(5), pp.544- prevalence of celiac disease: 551. systematic review and meta-analysis. 3. Jericho, Hilary, and Stefano Clinical Gastroenterology and Guandalini (2018): "Celiac Disease." Hepatology, 16(6), pp.823-836. Current Pediatrics Reports 6, no. 1 9. Kruzliak P, Ciccocioppo R, (2018): 40-49. Cangemi GC, et al (2015): "The 4. Jericho, H.; Sansotta, N.; Spectrum of Differences between Guandalini, S. (2017): Childhood and Adulthood Celiac Extraintestinal Manifestations of Disease". Nutrients; 7 (10): 873351. Celiac Disease: Effectiveness of the 10. Lebwohl, Benjamin, Jonas F. Gluten-Free Diet. J. Pediatr. Ludvigsson, and Peter HR Green. Gastroenterol. Nutr. 2017, 65, 75–79. (20150: "Celiac disease and non- [CrossRef] [PubMed]

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celiac gluten sensitivity." Bmj351 Advances. Gastroenterology Clinics, (2015): h4347. 48(1), pp.39-51. 11. WHO (2006): WHO child growth 17. Al-Jurayyan, N.A., Al Nemri, standards: length/height-for-age, A.M., Al Jurayyan, A.N. and Assiri, weight-for-age, weight-for-height and A.M., (2013): Celiac disease in body mass index-for-age: Methods children with short stature: A hospital and development. Geneva, based study. Journal of Taibah Switzerland: World Health University Medical Sciences, 8(2), Organization. pp.93-96. 12. GREULICH, W. and Pyle, S.L., 18. Singh P, Sharma PK, Agnihotri A, (1959): Radiographic atlas of skeletal Jyotsna VP, Das P, Gupta SD, et al. development of the hand and wrist. (2015): Coeliac disease in patients The American Journal of the Medical with short stature: a tertiary care Sciences, 238(3). centre experience. Natl Med J India. (2015) 28:176–80. 13. Bradwell, A.R., Harding, S.J., Fourrier, N.J., Wallis, G.L., 19. El Dayem, S.M.A., Aly, A.A., El Drayson, M.T., Carr-Smith, H.D. Gafar, E.A. and Kamel, H., (2010): and Mead, G.P., (2009): Assessment Screening for coeliac disease among of monoclonal gammopathies by Egyptian children. Archives of nephelometric measurement of medical science: AMS, 6(2), p.226. individual immunoglobulin κ/λ ratios. 20. De Lecea A, Ribes-koninclx C, Clinical chemistry, 55(9), pp.1646- Polanco I, Ferrer-Calvete J. (1996): 1655. Serological screening (antigliadin and 14. Sugai, E., Selvaggio, G., Vazquez, antiendomycium antibodies) for non- H., Viola, M., Mazure, R., Pizarro, overt coeliac disease in children of B. & Gomez, J. C. (2000): Tissue short stature. Acta Paediatr Suppl. transglutaminase antibodies in celiac 1996;412:54–5. disease: assessment of a commercial 21. Hussein, A., Farghaly, H., Askar, kit. The American journal of E., Metwalley, K., Saad, K., gastroenterology, 95(9), 2318. Zahran, A. and Othman, H.A., 15. Rege, V., Mojiminiyi, O., Wilcox, (2017): Etiological factors of short H., & Barron, J. (1996): Comparison stature in children and adolescents: of Kodak Amerlite FT4 and TSH-30 experience at a tertiary care hospital with T4 and TSH as first-line thyroid in Egypt. Therapeutic advances in function tests. Clinical biochemistry, endocrinology and metabolism, 8(5), 29(1), 1-4. pp.75-80. 16. Lagana, S.M. and Bhagat, G., 22. Savage MO, Backeljauw PF, (2019): Biopsy Diagnosis of Celiac Calzada R, Cianfarani S, Dunkel L, Disease: The Pathologist’s Koledova E, et al. (2016): Early Perspective in Light of Recent detection, referral, investigation, and 681 Al-Azhar Journal of Ped. Vol. 23 No. 47 Jan 2020

diagnosis of children with growth (2018): "Growth Hormone Deficiency disorders. Horm Res Paediatr (2016) and Related Endocrine Disorders in 85:325–32. doi:10.1159/000444525. Children with Celiac." (2018). 23. ELrefai, H.A., Nouh, H.H., Ali, 30. Jericho, H. and Guandalini, S., E.A., Zakaria, N.H. and El Kazzaz, (2018): Extra-intestinal manifestation A.M., (2009): PREVALENCE OF of celiac disease in children. CELIAC DISEASE IN SOME Nutrients, 10(6), p.755. EGYPTIAN PATIENTS WITH 31. Urikka, P., Salmi, T., Collin, P., SHORT STATURE. Bull. Alex. Fac. Huhtala, H., Mäki, M., Kaukinen, Med, 45(2). K. and Kurppa, K., (2016): 24. Rubio-Tapia, A., Jansson-Knodell, Gastrointestinal symptoms in celiac C.L., Rahim, M.W., See, J.A. and disease patients on a long-term Murray, J.A., (2016): Influence of gluten-free diet. Nutrients, 8(7), gender on the clinical presentation p.429. and associated diseases in adults with 32. Errázuriz, German. (2017): "Rectal celiac disease. Gaceta medica de prolapse as an unusual presentation of Mexico, 152(S2), pp.38-46. celiac disease. Report of two cases." 25. Shehab, D.I., (2013): Celiac disease. Revista chilena de pediatria 88, no. 6 The Egyptian Journal of Internal (2017): 798-802. Medicine, 25(2), p.53. 33. Guandalini, S. and Discepolo, V., 26. Chishty, S., & Singh, N. (2017): (2016): Celiac disease. In Textbook Nutritional status of celiac and non- of pediatric gastroenterology, celiac children from Rajasthan, India. hepatology and nutrition (pp. 453- Nutrition & Food Science, 47(2), 240- 469). Springer, Cham. 253. 34. Yavuzyilmaz, F., Ozdogan, S., 27. Eren, E. (2018): Effects of age of Urganci, N. and Usta, M.K., (2019): diagnosis and dietary compliance on Frequency of Asthma and Atopic growth parameters of patients with Diseases in Inflammatory Bowel celiac disease. Arch Argent Pediatr, Disease and Celiac Disease. Journal 116(4), 248-255. of the College of Physicians and Surgeons--Pakistan: JCPSP, 28. Zanchetta, M.B., Longobardi, V. and Bai, J.C., (2016): Bone and 35. Assiri, A., Saeed, A., Al Sarkhy, A., celiac disease. Current osteoporosis El Mouzan, M.I. and El Matary, reports, 14(2), pp.43-48. W., (2013): Celiac disease presenting as rickets in Saudi children. Annals of 29. Bozzola, Mauro, Chiara Saudi medicine, 33(1), pp.49-5. Montalbano, Elena Bozzola, Nicola Lazzaro, Filomena A. Stamati, 36. Laurikka, P., Nurminen, S., Pietro Ferrara, and Alberto Villani. Kivelä, L. and Kurppa, K., (2018):

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Extraintestinal manifestations of Bozzola M. (2006): The prevalence celiac disease: Early detection for of growth hormone deficiency and better long-term outcomes. Nutrients, celiac disease in short children. 10(8), p.1015. Clinical medicine & research. 2006 Sep 1;4(3):180-3. 37. Balaban, D.V., Popp, A., Ionita Radu, F. and Jinga, M., (2019): (40) Iughetti L, De Bellis A, Predieri Hematologic Manifestations in Celiac B, Bizzarro A, De Simone M, Balli Disease—A Practical Review. F, Bellastella A, Bernasconi S. Medicina, 55(7), p.373. (2006): Growth hormone impaired secretion and antipituitary antibodies 38. Abd El-Shaheed, Azza, Aly Ezz El- in patients with coeliac disease and Arab, Maha Abou-Zekri, Maged A. poor catch-up growth after a long El Wakeel, Ghada M. El-Kassas, gluten-free diet period: a causal Nabil A. Mohsen, and Mona association?. European journal of Anwar. (2018): "A novel gluten-free pediatrics. 2006 Dec 1;165(12):897- meal as a nutritional therapy for Iron 903. deficiency anemia in children with celiac disease." BIOSCIENCE (41) Nardecchia, S., Auricchio, R., RESEARCH 15, no. 1 (2018): 207- Discepolo, V. and Troncone, R., 214. (2019): Extraintestinal manifestations of coeliac disease in children: clinical (39) Giovenale D, Meazza C, features and mechanisms. Frontiers in Cardinale GM, Sposito M, pediatrics, 7, p.56. Mastrangelo C, Messini B, Citro G,Delvecchio M, Di Maio S,

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ﺍﻟﻣﺭﺽ ﺍﻟﻘﻠﻠﻲ (ﺍﻟﺳﻳﻠﻳﺎﻙ) ﻓﻲ ﺍﻷﻁﻔﺎﻝ ﺍﻟﺫﻳﻥ ﻳﻌﺎﻧﻭﻥ ﻣﻥ ﻗﺻﺭ ﻗﺎﻣﻪ ﻏﻳﺭ ﻣﻌﻠﻭﻡ ﺍﻟﺳﺑﺏ

ﻣﺣﻣﺩ ﺳﻳﺩ ﺣﻣﻳﺩﻩ- ﺍﺣﻣﺩ ﺳﻌﺩ ﺍﻟﺩﻳﻥ ﺍﺑﺭﺍﻫﻳﻡ ﻣﻧﺻﻭﺭ - ﻣﺣﻣﺩ ﺳﺎﻣﻲ ﺍﻟﺣﻛﻳﻡ - ﻛﺎﻣﻝ ﺳﻠﻳﻣﺎﻥ ﺣﻣﺎﺩ

ﻗﺳﻡ ﻁﺏ ﺍﻷﻁﻔﺎﻝ – ﻛﻠﻳﺔ ﺍﻟﻁﺏ – ﺟﺎﻣﻌﺔ ﺍﻷﺯﻫﺭ ﻗﺳﻡ ﺍﻟﺑﺎﺛﻭﻟﻭﺟﻳﺎ ﺍﻟﻌﺎﻣﻪ– ﻛﻠﻳﺔ ﺍﻟﻁﺏ – ﺟﺎﻣﻌﺔ ﺍﻷﺯﻫﺭ ﻗﺳﻡ ﺍﻟﺑﺎﺛﻭﻟﻭﺟﻳﺎ ﺍﻹﻛﻠﻳﻧﻳﻛﻳﻪ – ﻛﻠﻳﺔ ﺍﻟﻁﺏ – ﺟﺎﻣﻌﺔ ﺍﻷﺯﻫﺭ

ﺍﻟﻬﺪﻑ ﻣﻦ ﺍﻟﺪﺭﺍﺳﺔ:

ﺩﺭﺍﺳﺔ ﺍﻟﻤﺮﺽ ﺍﻟﻘﻠﻠﻲ(ﺍﻟﺴﻴﻠﻴﺎﻙ) ﻓﻲ ﺍﻷﻁﻔﺎﻝ ﺍﻟﻤﺼﺎﺑﻴﻦ ﺑﻘﺼﺮ ﻗﺎﻣﻪ ﻏﻴﺮ ﻣﻌﻠﻮﻡ ﺍﻟﺴﺒﺐ.

ﻣﻮﺍﺩ ﻭﺃﺳﺎﻟﻴﺐ ﺍﻟﺪﺭﺍﺳﺔ

ﺍﻹﻋﺘﺒﺎﺭﺍﺕ ﺍﻷﺧﻼﻗﻴﺔ:

ﺗﻤﺖ ﺍﻟﻤﻮﺍﻓﻘﺔ ﻋﻠﻰ ﺍﻟﺪﺭﺍﺳﺔ ﻣﻦ ﺟﺎﻧﺐ ﻟﺠﻨﺔ ﺍﻷﺧﻼﻗﻴﺎﺕ ﺑﻜﻠﻴﺔ ﻁﺐ ﺍﻷﺯﻫﺮ ﺑﻨﻴﻦ ﺑﺎﻟﻘﺎﻫﺮﺓ. ﻭﺗﻢ ﺍﻟﺤﺼﻮﻝ ﻋﻠﻰ ﻣﻮﺍﻓﻘﺔ ﻣﻜﺘﻮﺑﺔ ﺑﺎﻟﻠﻐﺔ ﺍﻟﻌﺮﺑﻴﺔ ﻣﻦ ﺟﻤﻴﻊ ﺍﻟﻤﺸﺎﺭﻛﻴﻦ .ﻭﺗﻀﻤﻨﺖ ﻫﺬﻩ ﺍﻟﻤﻮﺍﻓﻘﺔ ﻛﻞ ﺗﻔﺎﺻﻴﻞ ﺍﻟﺪﺭﺍﺳﺔ (ﺍﻟﻌﻨﻮﺍﻥ ،ﺍﻷﻫﺪﺍﻑ، ﺍﻷﺳﺎﻟﻴﺐ، ﺍﻟﻔﻮﺍﺋﺪ ﺍﻟﻤﺘﻮﻗﻌﺔ ﻭﺧﺼﻮﺻﻴﺔ ﺍﻟﺒﻴﺎﻧﺎﺕ).

684 CELIAC DISEASE AMONG CHILDREN PRESENTED WITH UNEXPLAINED SHORT STATURE Mohamed Sayed Hemeda, Ahmed Saad Eldeen Ibrahim, Mohamed Sami Elhakim, Kamel Soliman Hammad ﺗﺼﻤﻴﻢ ﺍﺍﻟﺪﺭﺍﺳﺔ:

ﻫﺬﻩ ﺍﻟﺪﺭﺍﺳﺔ ﺩﺭﺍﺳﺔ ﻣﻘﻄﻌﻴﺔ.

ﺍﻷﺷﺨﺎﺹ ﺍﻟﻤﺴﺘﻬﺪﻓﻴﻦ ﻭﺍﻟﻤﺪﺓ:

ﺃﺟﺮﻯ ﻫﺬﺍ ﺍﻟﺒﺤﺚ ﻋﻠﻰ ﻣﺎﺋﺔ ﻁﻔﻼ ﻭﻁﻔﻠﺔ ﻳﻌﺎﻧﻮﻥ ﻣﻦ ﻗﺼﺮ ﺍﻟﻘﺎﻣﺔ ﺍﻟﻐﻴﺮ ﻣﻔﺴﺮ، ﺗﻢ ﺍﺧﺘﻴﺎﺭﻫﻢ ﻣﻦ ﻋﻴﺎﺩﺍﺕ ﺍﻷﻁﻔﺎﻝ ﺍﻟﺨﺎﺭﺟﻴﺔ ﺑﻤﺴﺘﺸﻔﻰ ﺳﻴﺪ ﺟﻼﻝ ﻭ ﻣﺴﺘﺸﻔﻰ ﺍﻟﺤﺴﻴﻦ ﺍﻟﺠﺎﻣﻌﻲ ﺑﺎﻟﻤﻌﺎﻳﻴﺮ ﺍﻷﺗﻴﺔ:

ﻣﻌﺎﻳﻴﺮ ﺍﻻﺷﺘﻤﺎﻝ:

• ﻗﺼﺮ ﺍﻟﻘﺎﻣﺔ ﺍﻟﻐﻴﺮ ﻣﻔﺴﺮ.

ﻣﻌﺎﻳﻴﺮ ﺍﻻﺳﺘﺒﻌﺎﺩ:

• ﺍﻷﻁﻔﺎﻝ ﺍﻟﺬﻳﻦ ﻳﻌﺎﻧﻮﻥ ﻣﻦ ﻗﺼﺮ ﺍﻟﻘﺎﻣﺔ ﺍﻟﻤﻔﺴﺮ.

• ﺍﻻﻁﻔﺎﻝ ﺍﻟﺬﻳﻦ ﺳﺒﻖ ﺗﺸﺨﻴﺼﻬﻢ ﺑﻤﺮﺽ ﺑﻤﺮﺽ ﺍﻟﺴﻴﻠﻴﺎﻙ.

ﺗﻢ ﺗﺠﻤﻴﻊ ﺍﻟﺒﻴﺎﻧﺎﺕ ﻋﻦ ﻁﺮﻳﻖ:

1- ﻣﻮﺍﻓﻘﻪ ﻛﺘﺎﺑﻴﺔ ﻣﻦ ﺍﻟﻘﺎﺋﻢ ﻋﻠﻰ ﺭﻋﺎﻳﺔ ﺍﻟﻄﻔﻞ.

2- ﺍﻻﺟﺎﺑﻪ ﻋﻠﻲ ﺍﺳﺘﺒﻴﺎﻥ ﻣﻨﻈﻢ ﻣﺴﺒﻘﺎ.

3- ﺃﺧﺬ ﺍﻟﺘﺎﺭﻳﺦ ﺍﻟﻄﺒﻲ ﺍﻟﻤﺘﻌﻠﻖ ﺑﺎﻟﻄﻔﻞ ﺗﻔﺼﻴﻠﻴﺎ.

685 Al-Azhar Journal of Ped. Vol. 23 No. 47 Jan 2020

4- ﺍﻟﻘﻴﺎﺳﺎﺕ ﺍﻟﻤﺨﺘﻠﻔﺔ ﻟﻜﻞ ﻁﻔﻞ ﻣﻦ ﻧﺎﺣﻴﺔ ﺍﻟﻄﻮﻝ ﻭﺍﻟﻮﺯﻥ ﻭﻣﺆﺷﺮ ﺍﻟﻜﺘﻠﺔ ﺍﻟﺠﺴﺪﻳﺔ ﻭ ﺗﻨﺎﺳﺒﺎﺕ ﺃﻁﻮﺍﻝ ﺍﻟﺠﺴﻢ.

5- ﺍﻟﻔﺤﺺ ﺍﻟﻄﺒﻲ ﺍﻟﺸﺎﻣﻞ ﻣﻊ ﺍﻟﺘﺮﻛﻴﺰ ﻋﻠﻰ ﻭﺟﻮﺩ ﺃﻯ ﺃﻋﺮﺍﺽ ﻣﺘﻌﻠﻘﻪ ﺑﺎﻟﺠﻬﺎﺯ ﺍﻟﻬﻀﻤﻲ.

6- ﺍﻟﺘﺮﻛﻴﺰ ﻋﻠﻰ ﻭﺟﻮﺩ ﺃﻯ ﺃﻋﺮﺍﺽ ﻧﺎﺟﻤﺔ ﻋﻦ ﺍﻟﺨﻠﻞ ﺍﻟﻮﺭﺍﺛﻲ ﻟﻴﺘﻢ ﺍﺳﺘﺒﻌﺎﻫﺎ.

7- ﻋﻤﻞ ﺃﺷﻌﺔ ﺳﻴﻨﻴﺔ ﻋﻠﻰ ﺍﻟﺮﺳﻎ ﺍﻷﻳﺴﺮ.

8- ﻓﺤﺺ ﻋﻴﻨﺔ ﻣﻦ ﺍﻟﺪﻡ ﺍﻟﻮﺭﻳﺪﻱ ﻟﻌﻤﻞ ﺻﻮﺭﺓ ﺩﻡ ﻛﺎﻣﻠﻪ ﻭﻗﻴﺎﺱ ﻭﻅﺎﺋﻒ ﺍﻟﻜﻠﻲ ﻭﺍﻟﻜﺒﺪ.

9- ﻋﻤﻞ ﻭﻅﺎﺋﻒ ﺍﻟﻐﺪﻩ ﺍﻟﺪﺭﻗﻴﻪ.

10- ﻗﻴﺎﺱ ﻧﺴﺒﺔ ﻋﺎﻣﻞ ﺍﻟﻨﻤﻮ ﺷﺒﻴﻪ ﺍﻻﻧﺴﻮﻟﻴﻦ-1 ﻟﻺﺳﺘﺪﻻﻝ ﻋﻠﻲ ﻫﺮﻣﻮﻥ ﺍﻟﻨﻤﻮ ﻣﻊ ﻋﻤﻞ ﺍﺧﺘﺒﺎﺭ ﺗﺤﻔﻴﺰﻱ ﻟﻬﺮﻣﻮﻥ ﺍﻟﻨﻤﻮ ﻋﻨﺪ ﺍﻻﺷﺘﺒﺎﻩ ﻓﻲ ﻧﻘﺺ ﻫﺮﻣﻮﻥ ﺍﻟﻨﻤﻮ.

11- ﻓﺤﺺ ﻋﻴﻨﺔ ﻣﻦ ﺍﻟﺪﻡ ﺍﻟﻮﺭﻳﺪﻱ ﻟﻤﺴﺘﻮﻱ ﺍﻻﺟﺴﺎﻡ ﺍﻟﻤﻀﺎﺩﻩ ﺃ ﺍﻟﻜﻠﻴﻪ ﻭﻣﺴﺘﻮﻱ ﺍﻻﺟﺴﺎﻡ ﺍﻟﻤﻀﺎﺩﻩ ﺃ ﻟﻠﻺﻧﺰﻳﻢ ﻧﺎﻗﻞ ﺍﻟﻐﻠﻮﺗﺎﻣﻴﻦ.

12- ﺍﻟﺘﺼﻮﻳﺮ ﺍﻟﺼﺒﻐﻲ ﺍﻟﻜﺮﻭﻣﻮﺳﻮﻣﻲ ﻟﻼﻁﻔﺎﻝ ﺍﻻﻧﺎﺙ.

686 CELIAC DISEASE AMONG CHILDREN PRESENTED WITH UNEXPLAINED SHORT STATURE Mohamed Sayed Hemeda, Ahmed Saad Eldeen Ibrahim, Mohamed Sami Elhakim, Kamel Soliman Hammad 13- ﺍﻟﺘﻨﻈﻴﺮ ﺍﻟﻌﻠﻮﻱ ﻟﻠﺠﻬﺎﺯ ﺍﻟﻬﻀﻤﻲ ﻣﻊ ﺍﺧﺬ ﻋﻴﻨﺎﺕ ﻣﻦ ﺍﻻﺛﺘﻲ ﻋﺸﺮ ﻟﻼﻁﻔﺎﻝ ﺫﻭﻱ ﺍﻟﻤﺪﻟﻮﻝ ﺍﻻﻳﺠﺎﺑﻲ ﻟﻸﺟﺴﺎﻡ ﺍﻟﻤﻀﺎﺩﻩ ﺃ ﻟﻠﻺﻧﺰﻳﻢ ﻧﺎﻗﻞ ﺍﻟﻐﻠﻮﺗﺎﻣﻴﻦ.

ﻭﻛﺎﻧﺖ ﺍﻟﻨﺘﺎﺋﺞ ﻛﺎﻵﺗﻲ:

• ﻣﺘﻮﺳﻂ ﻋﻤﺮ ﺍﻻﻁﻔﺎﻝ ﺑﺎﻟﺸﻬﻮﺭ ﻣﻮﺿﻮﻉ ﺍﻟﺪﺭﺍﺳﻪ (80,85 ± 33,55) ﻭ ﻣﺘﻮﺳﻂ ﺍﻟﻄﻮﻝ (102.04 ± 13.48).

• ﺧﻼﻝ ﺍﻟﺪﺭﺍﺳﻪ ﺗﺒﻴﻦ ﺍﻥ ﻋﺪﺩ ﺍﻻﻁﻔﺎﻝ ﺍﻟﻤﺼﺎﺑﻴﻦ ﺑﻘﺼﺮ ﺍﻟﻘﺎﻣﻪ ﻧﺘﻴﺠﺔ ﺍﻻﺻﺎﺑﺔ ﺑﻤﺮﺽ ﺍﻟﺴﻴﻠﻴﺎﻙ ﻳﺼﻞ ﺍﻝ %11.

• ﻳﺘﺮﺍﻭﺡ ﻣﺘﻮﺳﻂ ﻋﻤﺮ ﺍﻻﻁﻔﺎﻝ ﺑﺎﻟﺸﻬﻮﺭ ﺍﻻﻁﻔﺎﻝ ﺍﻟﻤﺼﺎﺑﻴﻦ ﺑﻤﺮﺽ ﺍﻟﺴﻴﻠﻴﺎﻙ (86.91 ± 37.58) ﻭ ﻣﺘﻮﺳﻂ ﺍﻟﻄﻮﻝ .(14.14 ± 102.18)

• ﺗﻌﺪ ﺍﻻﻡ ﺍﻟﺒﻄﻦ ﺍﺷﻬﺮ ﺍﻋﺮﺍﺽ ﺍﻟﺠﻬﺎﺯ ﺍﻟﻬﻀﻤﻲ ﺍﻟﻤﻨﺘﺸﺮﻩ ﺑﻴﻦ ﺍﻻﻁﻔﺎﻝ ﻣﻮﺿﻮﻉ ﺍﻟﺪﺭﺍﺳﻪ ﺍﻟﻤﺼﺎﺑﻴﻦ ﺑﻤﺮﺽ ﺍﻟﺴﻴﻠﻴﺎﻙ ﻭﻳﺄﺗﻲ ﺑﻌﺪﻫﺎ ﺍﻻﻣﺴﺎﻙ ﺛﻢ ﺍﻻﺳﻬﺎﻝ.

• ﺑﻌﺾ ﺣﺎﻻﺕ ﺍﻻﻁﻔﺎﻝ ﺍﻟﻤﺼﺎﺑﻴﻦ ﺑﻤﺮﺽ ﺑﻤﺮﺽ ﺍﻟﺴﻴﻠﻴﺎﻙ ﻗﺪ ﺗﻜﻮﻥ ﻣﺼﺎﺣﺒﻪ ﻟﻨﻘﺺ ﻓﻲ ﺍﻓﺮﺍﺯ ﻫﺮﻣﻮﻥ ﺍﻟﻨﻤﻮ.

• ﺧﻼﻝ ﺍﻟﺪﺭﺍﺳﻪ ﺗﺒﻴﻦ ﺍﻥ ﻋﺪﺩ ﺍﻻﻁﻔﺎﻝ ﺍﻟﻤﺼﺎﺑﻴﻦ ﺑﻘﺼﺮ ﺍﻟﻘﺎﻣﻪ ﻣﻊ ﻧﻘﺺ ﻓﻲ ﻋﺎﻣﻞ ﺍﻟﻨﻤﻮ ﺷﺒﻴﻪ ﺍﻻﻧﺴﻮﻟﻴﻦ -1 ﻣﻊ ﺇﺳﺘﺠﺎﺑﻪ ﻁﺒﻴﻌﻴﺔ ﻟﺘﺤﻔﻴﺰ ﻫﺮﻣﻮﻥ ﺍﻟﻨﻤﻮ ﻳﻤﺜﻞ %19.

687 Al-Azhar Journal of Ped. Vol. 23 No. 47 Jan 2020

ﻭﺧﻠﺼﺖ ﺍﻟﺪﺭﺍﺳﺔ ﺇﻟﻰ ﻣﺎ ﻳﻠﻲ :

- ﺑﻤﺮﺽ ﺑﻤﺮﺽ ﺍﻟﺴﻴﻠﻴﺎﻙ ﻣﻦ ﺍﻻﺳﺒﺎﺏ ﺍﻟﻤﻬﻤﺔ ﻟﻘﺼﺮ ﺍﻟﻘﺎﻣﻪ ﺍﻟﻐﻴﺮ ﺍﻟﻤﻔﺴﺮ ﻓﻰ ﺍﻷﻁﻔﺎﻝ.

ﻭﻗﺪ ﺃﻭﺻﺖ ﺍﻟﺪﺭﺍﺳﺔ ﺑﺎﻵﺗﻲ:

1- ﺿﺮﻭﺭﺓ ﺃﻥ ﻳﻜﺎﻓﺢ ﺍﻷﻁﺒﺎء ﻭ ﻏﻴﺮﻫﻢ ﻣﻦ ﺍﻟﻌﺎﻣﻠﻴﻦ ﻓﻲ ﺍﻟﺮﻋﺎﻳﺔ ﺍﻟﺼﺤﻴﺔ ﻣﻦ ﺃﺟﻞ ﺗﻮﻓﻴﺮ ﺍﻟﻔﺤﻮﺻﺎﺕ ﺍﻻﺯﻣﻪ ﺑﻤﺮﺽ (ﺍﻟﺴﻴﻠﻴﺎﻙ) ﻟﻸﻁﻔﺎﻝ ﺍﻟﻤﺼﺎﺑﻴﻦ ﺑﻘﺼﺮ ﺍﻟﻘﺎﻣﻪ ﻓﻲ ﻣﺤﻴﻄﻬﻢ ﻭﺑﺨﺎﺻﺔ ﻟﺬﻭﻯ ﺍﻻﺣﺘﻴﺎﺝ ﺍﻟﺨﺎﺹ ﻟﻪ.

2- ﺃﻫﻤﻴﺔ ﺍﻟﺘﻮﻋﻴﺔ ﻋﻦ ﺍﻻﻋﺮﺍﺽ ﺍﻟﻐﻴﺮ ﺍﻟﻨﻤﻄﻴﻪ ﺑﻤﺮﺽ ﺍﻟﺴﻴﻠﻴﺎﻙ.

3- ﻳﺠﺐ ﻋﻤﻞ ﺍﻟﻔﺤﻮﺻﺎﺕ ﺍﻟﺨﺎﺻﺔ ﺑﻤﺮﺽ ﺑﻤﺮﺽ ﺍﻟﺴﻴﻠﻴﺎﻙ ﻟﻼﻁﻔﺎﻝ ﺍﻟﻤﺼﺎﺑﻴﻦ ﺑﻘﺼﺮ ﺍﻟﻘﺎﻣﻪ ﻣﻊ ﻋﺪﻡ ﺍﻻﻋﺘﺒﺎﺭ ﻟﻠﺠﻨﺲ ﺍﻭ ﺍﻻﻋﺮﺍﺽ ﺍﻭ ﺍﻟﻌﻤﺮ ﺍﻟﻌﻈﻤﻲ.

4- ﻗﺼﺮ ﺍﻟﻘﺎﻣﺔ ﻣﺠﻬﻮﻝ ﺍﻟﺴﺒﺐ ﻳﺠﺐ ﺍﻋﺘﺒﺎﺭﻩ ﻓﻲ ﺣﺎﻻﺕ ﻗﺼﺮ ﺍﻟﻘﺎﻣﻪ ﻣﻊ ﻧﻘﺺ ﻓﻲ ﻋﺎﻣﻞ ﺍﻟﻨﻤﻮ ﺷﺒﻴﻪ ﺍﻻﻧﺴﻮﻟﻴﻦ-1 ﻣﻊ ﺇﺳﺘﺠﺎﺑﻪ ﻁﺒﻴﻌﻴﺔ ﻟﺘﺤﻔﻴﺰ ﻫﺮﻣﻮﻥ ﺍﻟﻨﻤﻮ ﻭﻳﺤﺘﺎﺝ ﺍﻟﻲ ﺍﻟﺘﺸﺨﻴﺺ ﺑﻮﺍﺳﻄﺔ ﺍﻟﺘﺤﻠﻴﻞ ﺍﻟﺠﻴﻨﻲ.

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