Coeliac disease appendix 6.6 Evidence tablesReference        Study        Number      Patient characteristics             ...
Effect size:N=6 excluded selective IgA deficiencyN=102 celiac disease diagnosed2Anti-t TG:CD, 70.6% (N=72/102) +veNon-CD, ...
(this study considered 2 commercial labs, there were significant differences in sensitivity and specificity values, the la...
-81                         3.5 in the                                                 defined as –ve                     ...
(a) TP 116 (b) FP 6 (c) FN 3 (d) TN 51IgAG-DGP/tTG >30sensitivity 100% (n/a), specificity 94.7% (88.9 to 100), PPV 97.5% (...
(a) TP 110 (b) FP 6 (c) FN 9 (d) TN 51IgAG-DGP >30sensitivity 97.5% (94.7 to 100), specificity 98.2% (94.8 to 100), PPV 99...
(a) TP 95 (b) FP 5 (c) FN 24 (d) TN 52IgA-DGP >30sensitivity 90.8% (85.6 to 96.0), specificity 94.7% (88.9 to 100), PPV 97...
(a) TP 105 (b) FP 8 (c) FN 14 (d) TN 49IgG-DGP >30sensitivity 95.0% (91.0 to 98.9), specificity 98.2% (94.8 to 100), PPV 9...
(a) TP 113 (b) FP 2 (c) FN 6 (d) TN 55IgA-tTG >30sensitivity 96.6% (93.4 to 99.9), specificity 100% (n/a), PPV 100% (n/a),...
(a) TP 5 (b) FP 0 (c) FN 114 (d) TN 57IgG-tTG >30sensitivity 12.6% (6.6 to 18.6), specificity 100% (n/a), PPV 100% (n/a), ...
Evidence    patients                                                                                                      ...
UK:0.00823; N=1,823, adults (IgA-AGA, IgA-EMA)(Johnston 1998)0.01917 (serology), 0.01000 (biopsy N=22/23); N=1,200, adults...
0.02667 (serology), N=150, mostly adults (IgA/IgG-AGA, IgA-tTG)(Jager 2001)Finland:0.01028 (serology), 0.00748 (biopsy), N...
All ages:N=1 study case-finding primary care clinics(entry criteria; irritable bowel syndrome, anaemia, family history of ...
N=93, outpatients with IDA, N=13 (14%) biopsy proven coeliac disease (Akerman 1996)N=71, asymptomatic, N=4 (5.6%) biopsy p...
N=403, mixed mostly children, N=6 (1.5%) biopsy proven coeliac disease (Schober 2000)Sensitivity/Specificity papers includ...
levelBdioui F,      Cohort      N=1418        Inclusion: unselected blood donors,        IgA EMA HU,Sakly N,              ...
Tunisia:                                                                           Those with IgAmass-                    ...
Biagi F,        Cohort     N=158       Inclusion: adult first degree of N=73         IgA-EMA,                     1-year, ...
Bingley PJ,    Cohort    N=5470      Inclusion: children participating in the   Two stage                   Those with tTG...
SD for height; 0.23 (-0.43 to 0.88) vs. -0.53 (-1.01 to -0.00), p<0.0001SD for weight; 0.18 (-0.45 to 0.86) vs. -0.36 (-1....
Agreement low, N=7/28 showed reactivity with only 1 method, N=12 with 2 methods, N=2 with 3 methodsOnly N=4 were +ve with ...
Effect size:N=1026, of these N=798 (77.8%) subclinical CD and N=228 (22.2%) silent CDN=192 (18.7%), N=101 children, N=91 a...
Bottaro G,      Retrospe   N=325       Inclusion: data from children from                                                 ...
Brandimarte      Cohort      N=298       Inclusion: N=81 male, N=217 female,            IgA4 and IgG       Participant    ...
Effect size: (CI 95%)N=167 referred due to GI symptoms (weight loss, diarrhoea, abdominal pain, flatulence, slow gastric e...
Carroccio A,      Cohort      N=273       Inclusion: consecutive patients              IgA EMA            Biopsy,         ...
Total N=81 adults and N=110 children CD diagnosisIgA EMA:2x2: (a) TP 159 (b) FP 1 (c) FN 33 (d) TN 81IgA anti-tTG:2x2: (a)...
non-CD patients (p<0.0001)Intestinal mucosal damage was less severe in the N=29 with CD with –ve EMA and –ve anti-tTG, non...
N=7 biopsied all had atrophy of intestinal villi with crypt hyperplasia, all carried coeliac disease risk-associated allel...
- autoimmune thyroid N=18, 5.4% (CD) vs. N=9, 2.7% (control), this included autoimmune hypothyreosis, N=11 (CD) vs. N=8 (c...
P. Infertility              ous         obstetric history who had undergone                                               ...
patients with                                                                    IgA   authorssuspectedceliacdisease.Journ...
Sensitivity: 100%Specificity: 92%PPV: 57NPV: 1002X2: (a) TP 4 (b) FP 3 (d) FN 0 (c) TN 36IgG AGA:Sensitivity: 100%Specific...
(a) TP 4 (b) FP 24 (d) FN 0 (c) TN 15Reference      Study      Number      Patient characteristics                    Inte...
Journal ofGastroenterology &Hepatology1997;9:559-62Effect size: (CI 95%)Indicators which prompted investigation for coelia...
(a)    TP    29    (b)    FP    0    (c)    FN    2    (d)    TN    284(no patient with villous atrophy and –ve EMA had an...
nal andLiverDiseases2008;17:141-6Effect size:Marsh I/II classed as lymphocytic enteritisMarsh III classed as CD71.4% class...
Anti-tTG antibody +ve 53% (N=8/15) of those with classical presentation, anti-tTG antibody +ve 0% (N=0/1) of those with no...
N=8 biopsied, N=5 Marsh Type IIIc, N=2 Type IIIb, N=1 normal mucosal histology this patient was considered latent coeliac ...
tographic sticks                                                                                     Stick results        ...
(a) TP 134 (b) FP 2 (c) FN 5 (d) TN 119IgA tTG ELISA adultssensitivity 83.3% (70.0 to 96.7), specificity 94.7% (84.7 to 10...
(a) TP 135 (b) FP 2 (c) FN 4 (d) TN 119IgA/G tTG stick adultssensitivity 83.3% (70.0 to 96.7), specificity 100% (n/a), PPV...
(a) TP 133 (b) FP 2 (c) FN 6 (d) TN 119IgA tTG tTG-AGA stick adultssensitivity 80.0% (65.7 to 94.3), specificity 100% (n/a...
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
CG86 Coeliac disease: full guideline - appendix 6.6
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CG86 Coeliac disease: full guideline - appendix 6.6

  1. 1. Coeliac disease appendix 6.6 Evidence tablesReference Study Number Patient characteristics Intervention Comparison Length of Outcome Source type/ of follow-up measures of Evidence patients funding levelAbrams JA, Cohort N=122 Inclusion: consecutive suspected celiac IgA anti-t TG Control group, Serological NotBrar P, disease, Jan 2000 to December 2003, (human) those with a testing at statedDiamond B, Adults 32.4% male, 67.6% female, 100% white, antibody normal biopsy commercial labsRotterdam 44.5yrs (SD 15.4) determination around theH, Green before upper Duodenal countryPH. Utility in USA Exclusion: <16years, selective IgA endoscopy for biopsy (furtherclinical deficiency (total serum IgA level duodenal details not Pathologicpractice of <0.05g/L), on a GFD, taking biopsies1 given) diagnosis of CDimmunoglob immunosuppressants, initial serological requiredulin a anti- testing at >1 lab Serological intrathelialtissue testing was lymphocytosistransglutami performed at and either partialnase various villous atrophyantibody for commercial (Marsh IIIA) orthe labs total villousdiagnosis of atrophy (Marshceliac IIIB and IIIC)disease.Clinical Diagnosis of CD,Gastroenter had to exhibitology & histologic orHepatology serologic2006;4:726- improvements30 after 6mths on GFD1 All duodenal biopsies reviewed blinded by a single pathologist who did not know the antibody statusNICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 1 of 136
  2. 2. Effect size:N=6 excluded selective IgA deficiencyN=102 celiac disease diagnosed2Anti-t TG:CD, 70.6% (N=72/102) +veNon-CD, 65.0% (N=13/20) –vePPV 91.1%NPV 30.2%2X2: (a) TP 72 (b) FP 7 (d) FN 30 (c) TN 13CD group:Total villous atrophy 90.0% (N=54/60) +ve anti-tTG, sensitivity 90.0 (79.5 to 96.2, 95% CI)Partial villous atrophy 42.3 (N=18/42) +ve anti-t TG, sensitivity 42.9 (27.7 to 59.0, 95% CI)(p< 0.0001 difference in sensitivity for total and partial villous atrophy)NS differences in sensitivity when comparing various modes of presentation2 Authors note that the high percentage of diagnosis probably due to being a referral centre for coeliac disease and that the patient population may not reflect thatseen by community gastroenterologistsNICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 2 of 136
  3. 3. (this study considered 2 commercial labs, there were significant differences in sensitivity and specificity values, the labs used different kits and the authors note thatthey were not aware of how the labs determined their cut-off rates or whether they used the manufacturer’s recommended values)Reference Study Number Patient characteristics Intervention Comparison Length of Outcome Source type/ of follow-up measures of Evidence patients funding levelAgardh D. Cohort N=176 Inclusion: children with suspected CD IgAG-DGP/tTG ‘Intestinal Diagnostic Faculty ofAntibodies admitted for an intestinal biopsy at a biopsy’ – no accuracy of the Medicine,against Children Department of Paediatrics (no further IgAG-DGP further details tests Lundsynthetic – age details reported) Universitdeamidated range 0.7 IgA-DGP CD diagnosed ygliadin to 19.0 Exclusion: none reported with ESPGANpeptides and years, IgG-DGP Skanetissue median (Other groups included patients with a Counciltransglutami 5.7 in the known diagnosis of celiac disease on a IgA-tTG Foundatinase for the biopsy GFD for a median of 4.5 years with on foridentification abnormal serologic analysis and healthy adult blood IgG-tTG Researchof childhood group donors – results not included in this table) Developceliac (75F, All QUANTA ment,disease. 44M), lite tests, used MalmoClinical age according to UniversitGastroenter range 0.9 manufacturer’s yology & to 14.6 instructions.Hepatology years, Kits2007;5:1276 median Cut-offs providedNICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 3 of 136
  4. 4. -81 3.5 in the defined as –ve free of biopsy if <20AU, charge normal weakly +ve if by group 20-30AU, and manufact (26F, +ve if >30 urer 31M) No details of Sweden blinding reported.Effect size: (CI 95%)N=119/176 (68%) diagnosed with coeliac disease, using ESPGAN criteriaIgA deficiency 0.04% (N=7/176)Of the 121 children with a diagnosis other than coeliac disease (ie biopsy results were normal), most frequent diagnoses were cow’s milk protein intolerance, foodallergy, IgA deficiency (5/7 above), lipase deficiency, Helicobacter pylori gastritis, transient EMA (1 with IDDM). Other reasons for investigation were failure to thriveor short stature, with remaining children having transient GI symptoms.PPV, NPV and all confidence intervals calculated from the 2x2 data presented in the paper.IgAG-DGP/tTG >20sensitivity 97.5% (94.7 to 100), specificity 89.5% (81.5 to 97.4), PPV 95.1% (91.2 to 98.9), NPV 94.4% (88.3 to 100)2X2:NICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 4 of 136
  5. 5. (a) TP 116 (b) FP 6 (c) FN 3 (d) TN 51IgAG-DGP/tTG >30sensitivity 100% (n/a), specificity 94.7% (88.9 to 100), PPV 97.5% (94.8 to 100), NPV 100% (n/a)2X2: (a) TP 119 (b) FP 3 (c) FN 0 (d) TN 54IgAG-DGP >20sensitivity 92.4% (87.7 to 97.2), specificity 89.5% (81.5 to 97.4), PPV 94.8% (90.8 to 98.9), NPV 85.0% (76.0 to 94.0)2X2:NICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 5 of 136
  6. 6. (a) TP 110 (b) FP 6 (c) FN 9 (d) TN 51IgAG-DGP >30sensitivity 97.5% (94.7 to 100), specificity 98.2% (94.8 to 100), PPV 99.1% (97.5 to 100), NPV 94.9% (89.3 to 100)2X2: (a) TP 116 (b) FP 1 (c) FN 3 (d) TN 56IgA-DGP >20sensitivity 79.8% (72.6 to 87.0), specificity 91.2% (83.9 to 98.6), PPV 95.0% (90.7 to 99.3), NPV 68.4% (58.0 to 78.9)2X2:NICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 6 of 136
  7. 7. (a) TP 95 (b) FP 5 (c) FN 24 (d) TN 52IgA-DGP >30sensitivity 90.8% (85.6 to 96.0), specificity 94.7% (88.9 to 100), PPV 97.3% (94.3 to 100), NPV 83.1% (74.0 to 92.2)2X2: (a) TP 108 (b) FP 3 (c) FN 11 (d) TN 54IgG-DGP >20sensitivity 88.2% (82.4 to 94.0), specificity 86.0% (76.9 to 95.0), PPV 92.9% (88.2 to 97.6), NPV 77.8% (67.5 to 88.0)2X2:NICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 7 of 136
  8. 8. (a) TP 105 (b) FP 8 (c) FN 14 (d) TN 49IgG-DGP >30sensitivity 95.0% (91.0 to 98.9), specificity 98.2% (94.8 to 100), PPV 99.1% (97.4 to 100), NPV 90.3% (83.0 to 97.7)2X2: (a) TP 113 (b) FP 1 (c) FN 6 (d) TN 56IgA-tTG >20sensitivity 95.0% (91.0 to 98.9), specificity 96.5% (91.7 to 100), PPV 98.3% (95.9 to 100), NPV 90.2% (82.7 to 97.6)2X2:NICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 8 of 136
  9. 9. (a) TP 113 (b) FP 2 (c) FN 6 (d) TN 55IgA-tTG >30sensitivity 96.6% (93.4 to 99.9), specificity 100% (n/a), PPV 100% (n/a), NPV 93.4% (87.2 to 99.7)2X2: (a) TP 115 (b) FP 0 (c) FN 4 (d) TN 57IgG-tTG >20sensitivity 4.2% (0.6 to 7.8), specificity 100% (n/a), PPV 100% (n/a), NPV 33.3% (26.3 to 40.4)2X2:NICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 9 of 136
  10. 10. (a) TP 5 (b) FP 0 (c) FN 114 (d) TN 57IgG-tTG >30sensitivity 12.6% (6.6 to 18.6), specificity 100% (n/a), PPV 100% (n/a), NPV 35.4% (28.0 to 42.8)2X2: (a) TP 15 (b) FP 0 (c) FN 104 (d) TN 57Reference Study Number Patient characteristics Intervention Comparison Length of Outcome Source type/ of follow-up measures ofNICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 10 of 136
  11. 11. Evidence patients funding levelAgency for Systemat Chapter 2: celiac 2: incidence and All included AHRQHealthcare ic review prevalence of CD studiesResearch wereand Quality Included: general populations from North conducted(2004) America or Western Europe, first-degree betweenCeliac relatives of patients with CD 1992 andDisease, 2003Evidence Excluded: studies of prevalence orReport/Tech incidence that used AGA tests conductednology prior to 1990 due to potential problemsAssessment with the reliability of older AGA assays;Number 104 reports which were not sufficiently explicit for data extractionEffect size:Included studies – prevalence in the general population:37 studies identified, duplicate publications removed, 30 unique articles – 3 USA, 3 UK, 1 Switzerland, 6 Sweden, 1 Spain, 1 Republic of San Marino, 1 Norway, 2Netherlands, 6 Italy, 1 Ireland, 1 Germany, 3 Finland, 1 Denmark and SwedenScreening test:Primary biopsy – adults, N=4,723 (2 studies), prevalence range 0.00515-0.00605IgA AGA – adults, N=443 (1 study), prevalence range 0.01129; children, N=3,022 (1 study), prevalence range 0.00629IgA/IgG AGA – adults, N=1,537 (1 study), prevalence range 0.01431IgA AGA, IgA EMA – adults, N=6,999 (5 studies), prevalence range 0.00152-0.01884; children, N=1,823 (1 study), prevalence range 0.00823IgA/IgG AGA, IgA EMA – adults, N=11,351 (5 studies), prevalence range 0.00195-0.01917; children, N=19,297 (2 studies), prevalence range 0.00645-0.00859IgA/IgG AGA, IgA tTG – mostly adults, N=150 (1 study), prevalence range 0.02667IgA EMA – adults (7 studies), prevalence range 0.00171-0.01028; children N=6,127 (1 study), prevalence range 0.01224IgA EMA, IgG tTG – adults, N=10,372 (2 studies), prevalence range 0.00949-0.01156; children N=6,385 (3 studies), prevalence range 0.00312-0.01259Prevalence by country:USA:0.00949; N=2,845, adults (EMA-ME, all +ve tTG-HU),0.00312; N=1,281, children (Fasano 2003)0.00515; N=1,749, adults (biopsy)(Green 2000)0.00400; N=2,000, adults (IgG/IgA-AGA, followed by IgA-EMA ME or HU)(Not 1998)NICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 11 of 136
  12. 12. UK:0.00823; N=1,823, adults (IgA-AGA, IgA-EMA)(Johnston 1998)0.01917 (serology), 0.01000 (biopsy N=22/23); N=1,200, adults (IgG/IgA-EMA ME)(Sanders 2003)0.01156; N=7,527, adults (IgA-EMA ME, IgA tTGA)(West 2003)Switzerland:0.00759 (serology), 0.00690 (biopsy N=10/11); N=1,450, children (IgA-EMA ME, IgA tTG, IgG/IgA-AGA)(Rutz 2002)Sweden:0.01452 (serology), 0.01867 (biopsy); N=482, adults, (biopsy, IgA/IgG-AGA, IgA-EMA ME)(Borch 2001)0.00589 (serology), 0.00375 (biopsy); N=1,866, adults (IgA-AGA, (IgA-EMA, prevalence not reported))(Grodzinsky 1996)0.00475 (serology), 0.00475 (biopsy); N=1,894, adults (IgA/IgG-AGA, IgA-EMA ME, serum IgA level)(Ivarsson 1999)0.01431 (serology), 0.00065 (biopsy, N=13/22), N=1,537, adults (IgG/IgA-AGA)(Sjoberg 1994)0.00152 (serology), 0.00152 (biopsy), N=1,970, adults (IgA-AGAIgA confirmed with EMA ME)(Sjoberg 1999)0.01884 (serology), 0.01594 (biopsy), N=690, children (AGA, EMA, biopsy)(Carlsson 2001)Spain:0.00171 (serology), 0.00256 (biopsy), N=1,170, adults (IgG/IgA-AGA, IgA-EMA)(Riestra 2000)Republic of San Marino:0.00179 (serology), 0.00179 (biopsy), N=559, adults (IgA-EMA, biopsy)(Corazzo 1997)Norway:0.00387 (serology), 0.00388 (biopsy), N=2,069, adults (IgA/IgG-AGA, IgA-EMA)(Hovdenak 1999)Netherlands:0.00300 (serology), 0.00300 (biopsy), N=1,000, adults (IgA-EMA)(Rostami 1999)0.01224 (serology), 0.00506 (biopsy N=57/75), N=6,127, children (IgA-EMA)(Csizmadia 1999)Italy:0.00195 (serology), 0.00195 (biopsy N=38/140), N=4,615, adults (IgA/IgG-AGA, IgA-EMA, biopsy)(Pittscieler 1996)0.00250 (serology), 0.00250 (biopsy), N=4,000, adults (IgA-EMA, biopsy)(Trevisiol 1999)0.00574 (serology), 0.00488 (biopsy), N=3,483, adults (mostly)(IgA-EMA HU, biopsy)(Volta 2001)0.00859 (serology), N=2,096, children (IgG/IgA-AGA, IgA-EMA)(Catassi 2000)0.00645 (serology), 0.00477 (biopsy), N=17,201, children (IgA/IgG-AGA, confirmed with EMA and biopsy)(Catassi 1996)0.00629 (serology), 0.00596 (biopsy), N=3,022, children (IgA-AGA, biopsy)(Di Pietralata 1992)Ireland:0.01129 (serology), N=443, adults (IgA-AGA)(Dickey 1992)Germany:NICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 12 of 136
  13. 13. 0.02667 (serology), N=150, mostly adults (IgA/IgG-AGA, IgA-tTG)(Jager 2001)Finland:0.01028 (serology), 0.00748 (biopsy), N=1,070 adults (EMA HU)(Kolho 1998)0.01259 (serology), 0.00739 (biopsy), N=3,654 children (IgA/IgG-tTG, IgA/IgG-EMA, if total serum IgA, HLA DR, DQ2, DQ8)(Maki 2004)0.00605 (serology), N=2,974, mostly adults (biopsy)(Collin 2002)Denmark & Sweden:0.00254 (serology), N=1,573 adults (serum IgA, IgG-AGA, EMA)(Weile 2001)Prevalence in patients with suspected coeliac disease:Adults:N=4 studies, N=3 Italy all from referral centres, N=1 USA at-risk and not-at-risk individuals clinical centre not reported(reasons for suspecting coeliac disease; anaemia, persistent iron deficiency, bowel disturbances, chronic intermittent diarrhoea, abdominal pain, constipation,dyspepsia, severe malabsorption, tiredness and weight loss, mineral metabolism deficienceies, osteoporosis, arthralgias, arthritis, dermatitis, hypertransaminasemia,type 1 diabetes mellitus, infertility, and gluten intolerance in childhood not further investigated)Prevalence:43.3%, N=60 (biopsy)(Bardella 1991), Italy50.0%, N=80 (biopsy)(Bardella 2001), Italy11.6%, N=207 (biopsy)(Carrocio 2002), Italy1.5%, N=1,910 (EMA)(Fasano 2003), USAChildren:N=9 studies, N=3 Canada, N=2 USA, N=1 Denmark, England, Italy, New Zealand(reasons for suspecting coeliac disease; abdominal pain, diarrhoea, failure to thrive/short stature, weight loss, vomiting, abdominal distension, chronic GI symptoms,inflammatory bowel disease, family history of coeliac disease, type 1 diabetes, iron deficiency anaemia, thyroid disease, trisomy 21, enamel hypoplasia, recurrentaphtous stomatitis, autoimmune diseases, IgA deficiency, occult hypertransaminasemia)Prevalence:13.0%, N=77 (biopsy), referral centre (Chan 2001), Canada17.0%, N=176 (biopsy), referral centre (Chartrand 1997), Canada1.1%, N=92 (EMA), community paediatricians (Fitzpatrick 2001), Canada4.0%, N=1,326 (EMA), clinical setting not reported (Fasano 2003), USA2.5%, N=1,008 (EMA), referral centre (Hill 2000), USA7.3%, N=191 (biopsy), referral centre (Bode 1993), Denmark4.6%, N=153 (biopsy), referral centre (Day 2000), New Zealand7.9%, N=381 (biopsy), referral centre (Thomas 1992), England7.5%, N=240 (biopsy), case-finding community paediatricians (Ventura 2001), ItalyNICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 13 of 136
  14. 14. All ages:N=1 study case-finding primary care clinics(entry criteria; irritable bowel syndrome, anaemia, family history of coeliac disease, malaabsorption syndrome, diarrhoea, fatigue, thyroid disease, diabetes mellitus,weight loss, short stature, failure to thrive, epilepsy, infertility, arthralgia, eczema)N=1,000, mean age 42.8yrs, 5.3% <10yrs, 3.1% 80-90yrsN=30 EMA +ve, all confirmed by biopsy (N=1 child)Prevalence in first-degree relatives of those with coeliac diseaseN=17 studies, N=5 directly evaluated with small bowel biopsy, N=12 serological screening of these N=7 had biopsies in >80% of those positiveARHQ included second-degree relatives studies, these have not been included hereFirst-degree relatives:Prevalence:20%, N=90 tested (biopsy), diagnostic criteria ESPGAN (Polvi 1996)10.7%, N=121 tested (biopsy), diagnostic criteria some VA (Holm 1993)10.3%, N=29 tested (biopsy), diagnostic criteria some VA (Robinson 1971)5.6%, N=72 tested (biopsy), diagnostic criteria not reported (Rolles 1974)22.5%, N=182 tested (biopsy), diagnostic criteria some VA (Stokes 1976)44.1%, N=111 tested (biopsy), diagnostic criteria Marsh I-IV (Tursi 2003)4.0%, N=328 tested (AGA), diagnostic criteria some VA (Corazza 1992)12.0%, N=92 tested (EMA, TTG), diagnostic criteria some VA (Pittschieler 2003)10.9%, N=338 tested (AGA, EMA, Hx) diagnostic criteria ESPGAN (Rostami 2000)8.3%, N=120 tested (AGA, EMA, TTG), diagnostic criteria some VA (Hogberg 2003)9.1%, N=943 tested (EMA), diagnostic criteria some VA (Korponay-Szabo 1998)5.6%, N=675 tested (AGA, EMA) diagnostic criteria some VA (Farre 1999)3.5%, N=151 tested (EMA) diagnostic criteria positive serology (Kotze 2001)4.5%, N=4508 tested (EMA) diagnostic criteria positive serology (Fasano 2003)2.8%, N=642 tested (AGA, EMA) diagnostic criteria positive serology (Vitoria 1994)9.4%, N=466 tested (AGA, EMA) diagnostic criteria positive serology (Mustalahti 2002)17.2%, N=163 tested (EMA, TTG) diagnostic criteria positive serology (Book 2003)Studies that required some degree of villous atrophy for diagnosis, mean prevalence 7.6% (range 4% to 12%), where Marsh I were also considered diagnosticprevalence was 44.1%Reported prevalence based on serology results, mean prevalence 4.3% (range 2.8% to 17.2%)Prevalence of coeliac disease in those with iron deficiency anaemia:8 studies included – all adult studies with biopsy proven coeliac disease, N≥50 participantsNICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 14 of 136
  15. 15. N=93, outpatients with IDA, N=13 (14%) biopsy proven coeliac disease (Akerman 1996)N=71, asymptomatic, N=4 (5.6%) biopsy proven coeliac disease (Annibale 2001)N=200, referred to haematology, N=10 (5%) biopsy proven coeliac disease (Corazzo 1995)N=258, IDA identified through the lab, N=12 (4.7%) biopsy proven coeliac disease (Howard 2002)N=50, outpatients with IDA, N=3 (6%) biopsy proven coeliac disease (McIntyre 1993)N=113, undergoing endoscopy for IDA, N=17 (15%) biopsy proven coeliac disease (Oxentenko 2002)N=484, referred to haematology, N=11 (2.3%) biopsy proven coeliac disease (Ransford 2002)N=59, pre-menopausal women with IDA, N=5 (8.5%) biopsy proven coeliac disease (Annibale 2003)Prevalence of coeliac disease in those with low bone mineral density:4 studies included – all adult studies with biopsy proven coeliac disease, N≥50 participantsN=92, consecutive patients with idiopathic osteoporosis, N=3 (3%) biopsy proven coeliac disease (Lindh 1992)N=127, postmenopausal women with osteoporosis, N=1 (0.9%) biopsy proven coeliac disease (Gonzalez 2002)N=96, idiopathic low BMD, N=0 biopsy proven coeliac disease (Mather 2001)N=255, females with osteoporosis, N=6 (2.4%) biopsy proven coeliac disease (Nuti 2001)Prevalence of coeliac disease in those with type 1 diabetes:21 studies included – all with biopsy proven coeliac disease, N≥50 participantsN=185, adults, N=4 (2.2%) biopsy proven coeliac disease (Talal 2002)N=211, mostly children, N=3 (1.4%) biopsy proven coeliac disease (Rossi 1993)N=62, adults, N=7 (11.3%) biopsy proven coeliac disease (Kaukinen 1999)N=848, adults, N=7 (0.8%) biopsy proven coeliac disease (Sjoberg 1998)N=383, adults, N=10 (2.6%) biopsy proven coeliac disease (Sategna-Guidetti 1994)N=263, children, N=12 (4.6%) biopsy proven coeliac disease (Frazer-Reynolds 1998)N=104, children, N=9 (8.2%) biopsy proven coeliac disease (Hansen 2001)N=776, children, N=19 (2.5%) biopsy proven coeliac disease (Saukkonen 1996)N=205, children, N=6 (2.9%) biopsy proven coeliac disease (Spiekerkoetter 2002)N=498, children, N=16 (3.2%) biopsy proven coeliac disease (Barera 1991)N=273, children, N=9 (3.3%) biopsy proven coeliac disease (Barera 2002)N=383, children, N=32 (3.4%) biopsy proven coeliac disease (Valerio 2002)N=141, children, N=4 (2.8%) biopsy proven coeliac disease (Carelo 1996)N=177, children, N=7 (4%) biopsy proven coeliac disease (Roldan 1998)N=93, children, N=6 (6.5%) biopsy proven coeliac disease (Juan 1998)N=459, children, N=21 (4.6%) biopsy proven coeliac disease (Sigurs 1993)N=162, children, N=6 (3.7%) biopsy proven coeliac disease (Agardh 2001)N=167, children, N=8 (4.8%) biopsy proven coeliac disease (Acerini 1998)N=233, children, N=14 (6%) biopsy proven coeliac disease (Gillett 2001)N=1114, mixed, N=63 (5.7%) biopsy proven coeliac disease (De Vitis 1996)N=491, mixed, N=28 (5.7%) biopsy proven coeliac disease (Not 2001)N=520, mixed mostly children, N=9 (1.7%) biopsy proven coeliac disease (Kordonouri 2000)N=218, mixed mostly children, N=10 (4.6%) biopsy proven coeliac disease (Aktay 2001)NICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 15 of 136
  16. 16. N=403, mixed mostly children, N=6 (1.5%) biopsy proven coeliac disease (Schober 2000)Sensitivity/Specificity papers included from AHRQ report for all serological tests:Included studies, biopsy proven, cohort based (sensitivity/specificity data in forest plots or ROC curves in appendices)IgA AGA, IgG AGA, children (Altunas 1998)IgA AGA, IgG AGA, children (Artan 1998)IgA AGA, IgG AGA, IgA EMA, children (Ascher 1996)IgA AGA, IgG AGA, children (Bahia 2001)IgA AGA, IgA EMA, IgA tTGA, adults (Bardela 2001)IgA AGA, IgG AGA, children (Bode 1993)IgA AGA, IgG AGA, IgA EMA, adults/children (Carroccio 2002)IgA EMA, IgA tTGA, adults (Carroccio 2002)IgA EMA, IgA tTGA, children (Chan 2001)IgA AGA, IgG AGA, children (Chartrand 1997)IgA AGA, IgG AGA, children (Chirdo 1999)IgA AGA, IgG AGA, children (Gonczi 1991)IgA EMA, children (Iltanen 1999)IgA AGA, IgG AGA, IgA EMA, IgA tTGA, adults (Kaukinen 2000)IgA EMA, children (Kumar 1989)IgA AGA, IgG AGA, combined IgA/IgG, children (Lindberg 1985)IgA AGA, IgA EMA, children (Lindquist 1994)IgA AGA, IgA EMA, children (Maki 1991)IgA AGA, IgG AGA, IgA EMA, IgG EMA, adults (McMillan 1991)IgA AGA, IgG AGA, children (Meini 1996)IgA AGA, children (Poddar 2002)IgA AGA, IgG AGA, children (Rich 1990)IgA AGA, IgG AGA, IgA EMA, children (Russo 1999)IgA AGA, IgG AGA, IgA EMA, IgA tTGA, adults/children (Tesei 2003)IgA EMA, IgA tTGA, IgG tTGA, adults/children (Troncone 1999)IgA AGA, IgA EMA, adults (Valdimarss 1996)IgA AGA, IgG AGA, IgA EMA, adults (Vogelsang 1995)IgA AGA, IgG AGA, IgA EMA, IgA tTGA, children (Wolters 2002)Reference Study Number Patient characteristics Intervention Comparison Length of Outcome Source type/ of follow-up measures of Evidence patients fundingNICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 16 of 136
  17. 17. levelBdioui F, Cohort N=1418 Inclusion: unselected blood donors, IgA EMA HU,Sakly N, N=1090 (77.3%) men, N=328 (22.7%), indirectHassine M, Tunisia mean age men 29yrs, mean age women immunofluoresSaffar H. 26yrs cencePrevalenceof celiacdisease in ThoseTunisian All lab analyses were performed, consideredblood validated and interpreted by the same +ve, ATG (anti-donors. investigator tissueGastroenter transglutaninasologie e) , ELISAClinique etBiologique2006;30:33-6Effect size:N=3 IgA EMA +ve, N=2 of these ATG +ve these N=2 had vilous atrophy classified Marsh IIIC and IIIA, the N=1 ATG –ve had no histological lesionsPrevalence:1/709, 1.4/1000 (95% CI, 0.17 to 5.08)Reference Study Number Patient characteristics Intervention Comparison Length of Outcome Source type/ of follow-up measures of Evidence patients funding levelBen Hariz Cohort N=6284 Inclusion: screening study based on IgA-tTGs, Antitissue NotM, Kallel- drawing lots with schoolchildren in a ELISA and IgA transglutaminase statedSellami M, Tunisia Tunisian (from a population of 22000), deficienct, serology wasKallel L, N=3175 boys, N=3109 girls, age immunodiffusio regarded asLahmer A, 9.7±3yrs, registered during the school n borderlineHalioui S, year of 2003-2004, study conducted Sept- between 15 andBouraoui S Dec 2003 Those +ve IgA- 20 Uet al. EMA, indiectPrevalence Required sample size was 6094, allowing immunofluoresof celiac for an expected refusal rate of 30%, the cencedisease in sample size was raised to 9080NICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 17 of 136
  18. 18. Tunisia: Those with IgAmass- N=2 known to have coeliac disease were deficiency thescreening not included in the serological screening IgG-EMA wasstudy in determinedschoolchildren. BiopsyEuropeanJournal of (To confirm theGastroenter quality of theology & ELISA N=500Hepatology sera –ve for2007;19:687 IgA-tTG were-94 tested for IgA- EMA)Effect size:IgA-TTG:N=139/6284 (2.2%) of these N=87 (1.4%) had a value above 20 U and N=52 (37.4%) had a borderline value between 15 and 20 UIgA-EMA, determined for all samples in the +ve and borderline groups:- +ve group: N=36/87 (41.3%) had +ve IgA-EMA and IgA-tTG rates vs. -ve group: N=51, p<0.001- borderline group: N=4 (7.7%) IgA-EMA +ve, significant difference compared with the +ve IgA-tTG group, p<0.001Total IgA was decreased in N=17 (0.27%, 1/370), of these N=3 had complete IgA deficiency (0.03%). None of the 17 had IgG-EMAN=107/139 returned, of these N=28 positive for both serological tests (IgA-tTG and IgA-AE) and were biopsiedN=26/28 signs of coeliac disease, N=23 had villous atrophy, N=3 rise in intraepithelial lymphocyte density, N=2 normal mucosaN=79 IgA-tTG positive, IgA-AE negative, N=26 biopsied, none had histology compatible with coeliac diseasePrevalence:N=26 biopsy proven, N=2 previously diagnosed, N=12 positive to both serological tests but not been biopsied, prevalence 1/157 (1/217 to 1/115, 95% CI)Biopsy proven prevalence 1/224 (1/333 to 1/154, 95% CI)Those who were biopsy proven, none had other autoimmune conditions, N=3 had an affected relative, N=11 were asymptomaticReference Study Number Patient characteristics Intervention Comparison Length of Outcome Source type/ of follow-up measures of Evidence patients funding levelNICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 18 of 136
  19. 19. Biagi F, Cohort N=158 Inclusion: adult first degree of N=73 IgA-EMA, 1-year, NotCampanella coeliac patients referred to an out-patient indirect participants statedJ, Bianchi Italy clinic, diagnosed by means of duodenal immunofluores recontactePI, Zanellati biopsy and coeliac antibodies, between cence d byG, Jan 1999 – June 2006, mean phone,Capriglione 46.4yrs±16.9 Those +ve meanI, Klersy C biopsied follow-upet al. The 51.5mthsincidence ofcoeliacdisease inadult firstdegreerelatives.[seecomment].Digestive &LiverDisease2008;40:97-100Effect size:N=130/158 initially tested and –ve, 1 year later N=63 retested, none +ve, N=1 had developed coeliac diseasePrevalence, N=28/158 (17.7%, 95% CI 12.1 to 24.6)Duodenal biopsy confirmed the diagnosis of coeliac disease in all those who were +veFollow-up:N=114/130 who had been EMA –ve, N=63 had a second EMA test, all –veN=1/64 had been diagnosed with coeliac disease prior to follow-upReference Study Number Patient characteristics Intervention Comparison Length of Outcome Source type/ of follow-up measures of Evidence patients funding levelNICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 19 of 136
  20. 20. Bingley PJ, Cohort N=5470 Inclusion: children participating in the Two stage Those with tTG CoeliacWilliams Avon Longitudinal Study of Parents and screening: antibodies below UK,AJK, UK Children (ALSPAC), population based radioimmunoas the 97.5th centile MRC,Norcross AJ, cohort study established in 1990 say for tTG were defined as WellcomUnsworth antibodies, antibody –ve e Trust,DJ, Lock RJ, positive UKNess AR et samples tested governmal. for IgA-EMA by entUndiagnose indirect departmed coeliac immunofluores nts anddisease at cence variousage seven: charitablePopulation Details of GI organisatibased symptoms and ons andprospective special diets commercibirth cohort were collected alstudy. by routine companieBritish questionnaire s,Medical at 6.75yrs ALSPACJournal is part of2004;328:32 the WHO2-3 initiated European Longitudi nal Study of Pregnanc y and Childhoo dEffect size:N=137 were tTG antibody +ve but IgA-EMA –veIgA-EMA:N=54 IgA-EMA +ve; 1.0% (95% CI; 0.8 to 1.4)IgA EMA more common in females, OR 2.12 (1.20 to 3.75)tTG antibody –ve controls (N=5333) compared with IgA-EMA +ve (N=54): at age 7.5yrs (interquartile range):Height; 126 (122.4 to 129.6) vs. 122.1 (118.25 to 125.33), p<0.0001Weight; 25.2 (22.8 to 28.0) vs. 23.4 (21.35 to 25.4), p<0.0001NICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 20 of 136
  21. 21. SD for height; 0.23 (-0.43 to 0.88) vs. -0.53 (-1.01 to -0.00), p<0.0001SD for weight; 0.18 (-0.45 to 0.86) vs. -0.36 (-1.01 to 0.28), p<0.0001Hb conc; 125 (120 to 130) vs. 123 (118 to 127), NSSymptoms: tTG antibody –ve (N=4285 questionnaires) compared with IgA-EMA +ve (N=42): at age 6.75yrs (95% CI):Any diarrhoea; 1450 (34%) vs. 21 (50%), OR 1.96 (1.06 to 3.59), no overall difference in the number of episodes of diarrhoeaAny vomiting; 1933 (45%) vs. 23 (55%), OR 1.47 (0.80 to 2.71)Any stomach pains; 2557 (60%) vs. 28 (66%), OR 1.35 (0.71 to 2.57)Any constipation; 435 (10%) vs. 6 (14%), OR 1.48 (0.62 to 3.52)≥3 GI symptoms; 931 (22%) vs. 17 (40%), OR 2.45 (1.33 to 4.5)Author comment: those with IgA-EMA shorter by more than 0.76 SD scores and lighter by 0.54 SD scores, this equates to about 9mths growth and weight gain in anaverage child around this age.Reference Study Number Patient characteristics Intervention Comparison Length of Outcome Source type/ of follow-up measures of Evidence patients funding levelBizzaro et al Cohort N=105 Inclusion: patients with primary biliary IgA anti-tTG 3 +ve for anti-tTG Not(2006) Low cirrhosis, N=91 female, N=14 male, mean (ELISA, 6 tested for statedspecificity of age 63yrs (range 39 to 94yrs), diagnosis methods)(2anti-tissue Adults based on lab findings, the presence of human IgA EMAtransglutami anti-mitochondrial antibodies and liver recombinant, IgG EMAnase histology, none had clear symptoms of 1human (ME)antibodies in Italy CD placenta, 1patients with human +ve EMAprimary (control group: N=40 with CD and N=40 erythrocytes, 2 advised biopsybiliary healthy subjects were also tested with all GP liver)cirrhosis the kits) +ve anti-tTG IgG anti-tTG and –ve EMA, (ELISA 3 kits)(2 HLA testing human recombinant, 1 human red blood cells)Effect size: (CI 95%)N=28/105 (26.7%) IgA anti-tTG +ve; N=6/105 (5.7%) IgG anti-tTG +ve; in at least one of the 6 ELISA methods3 Tests performed in a single lab according to the manufacturer’s instructions, including indicated cut-off levelsNICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 21 of 136
  22. 22. Agreement low, N=7/28 showed reactivity with only 1 method, N=12 with 2 methods, N=2 with 3 methodsOnly N=4 were +ve with all methods, N=3 were +ve with 5 methodsFor IgG the N=6 +ve were each with only 1 methodN=2/28 were IgA EMA +ve, N=2 biopsied both CDN=0/6 were IgG EMA +veHLA determined in N=24/26 tTG+ve and EMA –ve, N=5 HLA +ve, N=4 biopsiedIgA tTG, specificity range; 82.5% to 97.1%IgG tTG, specificity range; 95.1% to 100%Reference Study Number Patient characteristics Intervention Comparison Length of Outcome Source type/ of follow-up measures of Evidence patients funding levelBottaro G, N=1026 Inclusion: all subclinical/silent patients NotCataldo F, with celiac disease in 42 centres statedRotolo N, Mixed diagnosed between 1990 and 1994,Spina M, N=382 adults (mean age 24.4±12.5,Corazza Italy N=271 females, 70.9%, N=111 males,GR. The 29.1%), N=644 children (mean ageclinical 7.7±4.2, N=431 females, 66.9%, N=213pattern of males, 33.1%)subclinical/silent celiacdisease: ananalysis on1026consecutivecases.AmericanJournal ofGastroenterology1999;94:691-6NICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 22 of 136
  23. 23. Effect size:N=1026, of these N=798 (77.8%) subclinical CD and N=228 (22.2%) silent CDN=192 (18.7%), N=101 children, N=91 adults had a first-degree relativeN=365 (35.6%), N=234 children, N=131 adults, had >1 symptomFrequency of leading symptoms with subclinical:Iron-deficiency anaemia – total (N=314/798, 39.3%); adults (N=145/313, 46.3%); children (N=169/485, 34.8%)Short stature – total (N=153, 19.2%); adults (N=8, 2.5%); children (N=145, 29.9%)Dermatitis herpetiforms – total (N=73, 9.1%); adults (N=61, 19.5%); children (N=12, 2.5%)Anorexia – total (N=62, 7.8%); adults (N=0), children (N=62, 12.8%)Epilepsy/cerebral calcifications – total (N=26, 3.3%); adults (N=13, 4.2%); children (N=13, 2.7%)Neuropsychic complaints – total (N=25, 3.1%); adults (N=7, 2.2%); children (N=18, 3.7%)Constipation – total (N=21, 2.6%); adults (N=4, 1.3%); children (N=17, 3.5%)Recurrent apthous stomatitis – total (N=16, 2.0%); adults (N=9, 2.9%); children (N=7, 1.4%)Dyspepsia – total (N=12, 1.5%); adults (N=8, 2.5%); children (N=4, 0.8%)Thinnes – total (N=12, 1.5%); adults (N=3, 1.0%); children (N=9, 1.8%)Hypertransaminasemia – total (N=11, 1.4%); adults (N=5, 1.6%); children (N=6, 1.2%)Osteoporosis – total (N=11, 1.4%); adults (N=11, 3.5%); children (N=0)Others ≤N=10 total: arthromyalgia; delayed puberty; dental enamel hypoplasia; atopy; peripheral oedema; amenorrhoea-abortions; recurrent infections;hypoglycaemia; lipothymia; tetania; obersity; polyuria-polydipsy; onychodystrophy; hypothyroidism; hyperparathyroidismFrequency of celiac-associated disorders:Insulin-dependent diabetes – total (N=76, 7.4%); adults (N=27, 7.1%); children (N=49, 7.6%)Atopy – total (N=32, 3.1%); adults (N=10, 2.6%); children (N=22, 3.4%)Down’s syndrome – total (N=19, 1.9%); adults (N=1, 0.3%); children (N=18, 2.8%)IgA deficiency – total (N=15, 1.5%); adults (N=4, 1.0%); children (N=11, 1.7%)Others ≤N=10 total: Turner syndrome; thyroiditis; hyperparathyroidism; rheumatoid arthritis; alopecia; Berger’s disease; psoriasis; sarcodosis; livedo reticularis;Basedow’s disease; primary biliary cirrhosis; Plummer’s adenoma; rheumatic fever; medulloblastoma; immunoploferative intestinal diseaseReference Study Number Patient characteristics Intervention Comparison Length of Outcome Source type/ of follow-up measures of Evidence patients funding levelNICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 23 of 136
  24. 24. Bottaro G, Retrospe N=325 Inclusion: data from children from Age at onset of NotFailla P, ctive diagnosed at a Paediatric symptoms, age at statedRotolo N, Gastroenterology Service, children diagnosis, theSanfilippo G, Children grouped according to year of diagnosis, three majorAzzaro F, group A 1984 to 1986, group B 1987 to symptoms relatedSpina M et 1989, age range 3mths to 14yrs, N=176 to onset ofal. Changes Italy females, N=146 males coeliac diseasein coeliacdiseasebehaviourover theyears. ActaPaediatrica1993;82:566-8Effect size:Symptoms:- chronic diarrhoea; 75.2% in group A and 70.2% in group B- weight loss; 43.6% in group A and 59.6% in group B, p=0.0016- abdominal distension; 35.8% in group A and 28.4% in group B- growth failure; 30.8% in group A and 20.2% in group B- vomiting; 32.5% in group A and 26.1% in group B- anorexia; 25.6% in group A and 35.1% in group B- irritability; 10.3% in group A and 13.9% in group B- minor symptoms; 18.8% in group A and 24.5% in group BAuthor’s consider that no changes were noted in the trend of symptoms, notably for chronic diarrhoeaReference Study Number Patient characteristics Intervention Comparison Length of Outcome Source type/ of follow-up measures of Evidence patients funding levelNICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 24 of 136
  25. 25. Brandimarte Cohort N=298 Inclusion: N=81 male, N=217 female, IgA4 and IgG Participant NoneG, Tursi A, (CHECK) mean age 27.9yrs (range 15 to 65yrs), all AGA s statedGiorgetti were >15yrs and considered adults (measured by diagnosedGM. enzyme linked betweenChanging Exclusion: other causes of villous atrophy, innmunosorben 1988 totrends in before making the diagnosis of coeliac t assay) 2000clinical form diseaseof celiac IgA EMAdisease. Criteria were used and based on the (screened byWhich is characteristic histological finding of indirectnow the subtotal or severe partial villous atrophy immunofluoresmain form of and crypt hyperplasia on small bowel, cent method onceliac taking from the descending duodenum monkeydisease in and heamotoxylin-eosin stained for oesophagus)clinical histological evaluationpractice? - classical CD the presence of a gluten- Sorbitol H2-Minerva sensitive enteropathy accompanied by GI breath testGastroenter symptoms (diarrhoea, weight loss, using 5g ofologica e abdominal pain, vomiting) sorbitol inDietologica - subclinical CD the presence of a gluten 150ml of tap2002;48:121 sensitive enteropathy with extraintestinal water-30 symptoms - silent CD the presence of a gluten- sensitive enteropathy not accompanied by any symptoms, but identified during the course of screening of high-risk groups (first-degree relatives of coeliac patients, those with insulin dependent diabetes, Down syndrome, IgA deficiency, thyroid disorders)4 Serum levels of IgA were taken to exclude a condition of selective serum immunoglobulin A deficiencyNICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 25 of 136
  26. 26. Effect size: (CI 95%)N=167 referred due to GI symptoms (weight loss, diarrhoea, abdominal pain, flatulence, slow gastric emptying)N=131 referred by other specialists due to unexplained diseases, or diseases unresponsive to standard therapyN=155 (52%) classical presentation, N=115 (38.5%) subclinical presentation, N=28 (9.4%) silent presentation1988 classical features 100%, 1988 subclinical/silent 0%2000 classical features 26.2%, 2000 subclinical/silent 76.1%Extraintestinal markers (those in >5%): iron-deficiency anaemia N=29 (25%), alopecia N=11 (10%), dermatitis herpetiformis N=11 (10%), osteoporosis N=7 (6%),recurrent apthous stomatitis N=7 (6%), amenorrhoea/recurrent abortion N=6 (6%), hypertransaminasaemia N=6 (6%) (also dental enamel hypoplasia, short stature,atopy, depression, epilepsy/cerebral calcifications, lupus, Crohn’s disease, erithema nodosus, onycodystrophy, psoriasis, recurrent fractures, ulcerative colitis,addison’s disease, idrarto, long QT interval, mucoviscidosis, myositis)Silent disease: first-degree relatives N=10 (36%), hyperthyroidism N=6 (21%), insulin-dependent diabetes N=5 (18%) (also hypothyroidism, IgA deficiency, loss ofKerkring folds at endoscopy, Down syndrome)Classical form:- IgA AGA 83.22% +ve, IgG AGA 88.38% +ve, EMA 94.83% +veSubclinical form:- IgA AGA 78.26% +ve, IgG AGA 83.47% +ve, EMA 86.08% +veSilent form:- IgA AGA 57.14% +ve, IgG AGA 60.17% +ve, EMA 71.42% +veSorbitol H2-breath test, no differences in the overall positivity among the different forms of coeliac disease, positive in 98.37% (classical), 97.39% (subclinical),92.85% (silent)Presence of malabsorption (hypoalbuminemia, hypoproteinemia, low iron levels, hypoferritinemia: classical form N=127/155 (82%), subclinical form N=34/115 (34%),silent form N=4/28 (14%)Effect of GFD – improvements in GI symptoms and extraintestinal symptoms (disappearance of iron-deficiency anaemia, reversal of osteopenia, disappearance ofconvulsive crisis in epilepsy, regular pregnancy, better response to mesalazine therapy in ulcerative colitis, reduction of insulin units and insulin administration indiabetes)Reference Study Number Patient characteristics Intervention Comparison Length of Outcome Source type/ of follow-up measures of Evidence patients funding levelNICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 26 of 136
  27. 27. Carroccio A, Cohort N=273 Inclusion: consecutive patients IgA EMA Biopsy, Adult MinisteroDi Prima L, undergoing intestinal biopsy for suspected (immunofluores specimens patients dell’IstruzPirrone G, CD (pediatric gastroenterology clinic and cence method, obtained from followed as ione,Scalici C, an internal medicine clinic), January 2001 monkey the second outpatients, dell’UniveFlorena AM, Mixed to June 2003 oesophagus) duodenal children rsita eGasparin M Adults; N=153, N=54 male, N=99 female, (Anti- portion5 were dellaet al. Anti- median age 32yrs (range 17 to 80yrs) endomysium, hospitalise Ricercatransglutami Italy Children; N=120, N=50 male, N=70 Eurospital) d andnase female, median age 14mths (range 7mths Ministeroantibody to 14yrs) IgA anti-tTG delleassay of the (ELISA)(human Politicheculture Exclusion: patients who had undergone Eu-tTG IgA, Agricolemedium of previous histologic evaluation for Eurospital) eintestinal suspected CD (reference Forestalibiopsy values <7%specimens representing acan improve value >2SDthe accuracy above theof celiac mean of 850disease healthydiagnosis. individuals)ClinicalChemistry Serum IgA by2006;52:117 ELISA to5-80 exclude IgA deficiency (also included results from culture medium, not included here)Effect size: (CI 95%)None had IgA deficiencyN=166 +ve for serum IgA EMA and/or anti-tTG, of these N=162 confirmed coeliac disease with histologic findings and clinical follow-upN=4 (N=1 EMA +ve and anti-tTG +ve), (N=3 anti-tTG +ve)Those EMA and anti-tTG –ve and biopsied, CD diagnosed in N=13/83 adults and N=16/24 children5 Histologic analysis was performed by an examiner unaware of the clinical condition and lab test resultsNICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 27 of 136
  28. 28. Total N=81 adults and N=110 children CD diagnosisIgA EMA:2x2: (a) TP 159 (b) FP 1 (c) FN 33 (d) TN 81IgA anti-tTG:2x2: (a) TP 162 (b) FP 4 (c) FN 29 (d) TN 78CD patients with +ve EMA and/or anti-tTG showed more severe intestinal mucosal lesions, grade 3b (25%) and grade 3c (35%) vs. seronegative (P<0.001) or vs.NICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 28 of 136
  29. 29. non-CD patients (p<0.0001)Intestinal mucosal damage was less severe in the N=29 with CD with –ve EMA and –ve anti-tTG, none had total villous atrophyReference Study Number Patient characteristics Intervention Comparison Length of Outcome Source type/ of follow-up measures of Evidence patients funding levelCastano L, Cohort N=830 Inclusion: all healthy term newborns from FollowedBlarduni E, children normal deliveries occurring during regular up 1-1.5yrsOrtiz L, (N=1100 working hours (9-5) and approxNunez J, offered 2.5yrsBilbao JR, participati None of the children had a family historyRica I et al. on) of coeliac disease among first-degreeProspective relatives (N=8 parents had type 1population Spain diabetes, N=35 autoimmune thyroidscreening disease, N=7 chronic inflammatory bowelfor celiac disease, N=1 lupus, N=1 vitiligo)disease:highprevalencein the first 3years of life.Journal ofPediatricGastroenterology &Nutrition2004;39:80-4Effect size:1-1.5yrs:N=613/830 (74%) returned; N=0 +ve for anti-tTGase antibodies2.5yrs:N=484/830 (58.3%) returnedN=10 contained anti-tTGase autoantibodies, N=9 repeat +ve result referred to the paediatric GI unit, N=2 –ve AGA and EMANICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 29 of 136
  30. 30. N=7 biopsied all had atrophy of intestinal villi with crypt hyperplasia, all carried coeliac disease risk-associated allelesPrevalence:Prevalence in the cohort 8.4/1000 children or 1:118 healthy newborns (95% CI, 1:55 to 1:270)Prevalence if include only the N=484 who completed the study 1:69 (95% CI, 1:32 to 1:158)Reference Study Number Patient characteristics Intervention Comparison Length of Outcome Source type/ of follow-up measures of Evidence patients funding levelCollin P, Case N=335 Inclusion: adults with coeliac disease GrantsReunala T, control (N=335 diagnosed at a department of internal from thePukkala E, control medicine between 1980 to 1990, N=86 YrjoLaippala P, group) male, N=249 female, mean age at JahnssonKeyrilainen diagnosis 41.4yrs (range 16 to 79) FoundatiO, Adults on, thePasternack Control patients selected from outpatients EmilA. Coeliac who had upper GI endoscopy, age and Aaltonendisease-- Finland sex matched with cases Foundatiassociated on, thedisorders Finnishand survival. Foundati[see on forcomment]. GastroenGut terologica1994;35:121 l5-8 ResearchEffect size:Annual number of new coeliac patients 1980 to 1983, range 18 to 26; from 1983 on, range from 29 to 49N=274 diagnosed after clinical suspicion of coeliac disease, N=61 from serological screeningResults following 1-year follow-up after commencing gluten-free diet not reported hereAssociated disorders taken from past and present conditions diagnosed by GPs or in hospitals (associated disorders diagnosed during prospective follow-up notreported here)Endocrine disorders: 12% (CD) vs. 4.2% (control), p=0.0003- insulin dependent diabetes mellitus, N=18, 5.4% (CD) vs. N=5, 1.5% (control), p=0.0094NICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 30 of 136
  31. 31. - autoimmune thyroid N=18, 5.4% (CD) vs. N=9, 2.7% (control), this included autoimmune hypothyreosis, N=11 (CD) vs. N=8 (control) and Graves’ disease N=7 (CD)vs. N=1 (control)- parathyroid adenoma N=2 (CD) vs. N=0 (control)- Addison’s disease N=2 (CD) vs. N=0 (control)Connective tissue disorders: 7.2% (CD) vs. 2.7% (control), p=0.011- Sjogren’s syndrome, N=11, 3.3% (CD) vs. N=1, 0.3% (control), p=0.0059- rheumatoid arthritis, N=6, 1.8% (CD) vs. N=7, 2.1% (control)- ankylosing spondylitis, N=1 (CD) vs. N=1 (control)- scleroderma, N=2 (CD) vs. N=0 (control)- vasculitis, N=1 (CD) vs. N=0 (control)- systemic lupus erythromatous, N=1 (CD) vs. N=0 (control)- mixed connective tissue disease, N=1 (CD) vs. N=0 (control)Pulmonary disorders:- asthma, N=9 (CD) vs. N=12 (control)- sarcoidosis, N=5 (CD) vs. N=0 (control)Neurological disorders:- epileptic seizures, N=5 (CD) vs. N=3 (control)- dementia, N=5 (CD) vs. N=1 (control)Liver diseases, N=4 (CD) vs. N=0 (control)Glomerulonephritis, N=3 (CD) vs. N=1 (control)Inflammatory bowel disease, N=1 (CD) vs. N=7 (control)Psoriasis, N=4 (CD) vs. N=0 (control)Malignancy found before diagnosis of CD, N=4; N=7 in the control groupReference Study Number Patient characteristics Intervention Comparison Length of Outcome Source type/ of follow-up measures of Evidence patients funding levelCollin P, Case N=150 Inclusion: successive women examined IgA AGA, IgA AGA cut off MedicalVilska S, control with for infertility, women having two or more ELISA 0.20 EU/ml ResearchHeinonen infertility spontaneous abortions, between Fund ofPK, N=50 February 1993 and December 1994 (also reticulum, TampereHallstrom O, with not included UniversitPikkarainen spontane Control patients women with a normal here) yNICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 31 of 136
  32. 32. P. Infertility ous obstetric history who had undergone Hospitaland coeliac abortion laproscopic sterilisation +ve serologydisease.[see (N=contr had uppercomment]. ol group) gastrointestinalGut endoscopy1996;39:382 including-4 N=335 biopsy (N=335 control group) Adults FinlandEffect size:N=4/150 (2.7%) in the infertility group compared with none in the control group had coeliac disease, p=0.06All of those with coeliac disease had unexplained fertility so the prevalence of coeliac disease in this group was 4.1% (N=4/98), compared with control groupN=0/150, p=0.02All N=4 were AGA +veReference Study Number Patient characteristics Intervention Comparison Length of Outcome Source type/ of follow-up measures of Evidence patients funding levelDel Rosario Cohort N=107 Inclusion: untreated patients of the IgA EMA Biopsies from NotMA, gastroenterology, endocrinology, (indirect the third portion statedFitzgerald pulmonary and developmental paediatric immunofloures of theJF, Chong Children services whose symptoms raised cence) using duodenum orSK, Croffie suspicion of celiac disease, from one monkey proximalJM, Gupta USA hospital, March 1996 to July 1997, 67 oesophagus jejunum,SK. Further male, mean age 4.8yrs (5 to 16.7yrs) histologicalstudies of IgA/IgG AGA examanti- N=46 persistent GI symptoms, failure to (enzyme linked considered byendomysium gain weight or both – intestinal biopsy. immunosorbent paediatricand anti- Those screened by other services did not assay) pathologistsgliadin have a biopsy where serology was and reviewedantibodies in negative Total serum by studyNICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 32 of 136
  33. 33. patients with IgA authorssuspectedceliacdisease.Journal ofPediatricGastroenterology &Nutrition1998;27:191-5Effect size:N=107, EMAN=104, AGAN=46 /107 biopsy (total serum IgA measured in N=19 who had small bowel biopsy)EMA:Sensitivity, specificity, PPV, NPV all 100%2X2: (a) TP 5 (b) FP 0 (d) FN 0 (c) TN 17IgA AGA:NICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 33 of 136
  34. 34. Sensitivity: 100%Specificity: 92%PPV: 57NPV: 1002X2: (a) TP 4 (b) FP 3 (d) FN 0 (c) TN 36IgG AGA:Sensitivity: 100%Specificity: 38%PPV: 14NPV: 1002X2:NICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 34 of 136
  35. 35. (a) TP 4 (b) FP 24 (d) FN 0 (c) TN 15Reference Study Number Patient characteristics Intervention Comparison Length of Outcome Source type/ of follow-up measures of Evidence patients funding levelDickey W, Cohort/c N=318 Inclusion: patients attending IgA EMA Irrespective of IgA less than NotMcMillan ase gastroenterology clinics for suspected (indirect AGA or EMA 0.8g/l considered statedSA, McCrum control celiac disease, mean age 42yrs (range 11 immunofluores results patients low, <0.07g/lEE, Evans Mixed to 88yrs), N=192 (60%) female cence, monkey were biopsied, consideredAE. oesophagus) at least 3 undectableAssociation (Biogiagnostics biopsies takenbetween )(titre of ≥1:5 from the distalserum levels N Ireland taken as duodenum,of total IgA positive) assessed byand IgA (N=1959 controls from a previous study – experiencedclass results not reported here) IgA AGA histiopathologisendomysial (ELISA) tsand (Labmaster)antigliadinantibodies:implicationsfor coeliac Total IgA, IgMdisease and IgGscreening.EuropeanNICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 35 of 136
  36. 36. Journal ofGastroenterology &Hepatology1997;9:559-62Effect size: (CI 95%)Indicators which prompted investigation for coeliac disease: diarrhoea (N=163, 51%), anaemia (N=51, 16%), abdominal pain (N=39, 12%), chronic fatigue (N=23,7%), weight loss (N=20, 6%), abnormal liver biochemistry (N=15, 5%), dermatitis herpetiformis (N=4, 1%), family history of coeliac disease (N=3, 1%)N=31 (10%) had villous atrophy, of these N=27 (87%) had +ve EMAAll of those with +ve EMA had villous atrophy, AGA >100EU in N=20 (74%) and between 11 and 100EU in N=7 (26%)IgA EMA: sensitivity 87%, specificity 100%, PPV 100%, NPV 99%2x2: (a) TP 27 (b) FP 0 (c) FN 4 (d) TN 287IgA EMA (IgA <0.07g/l): sensitivity 94%, specificty 99%, PPV 91%, NPV 99%2x2:NICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 36 of 136
  37. 37. (a) TP 29 (b) FP 0 (c) FN 2 (d) TN 284(no patient with villous atrophy and –ve EMA had an AGA >100EU addition of AGA to protocols added nothing to sensitivity or PPV)Reference Study Number Patient characteristics Intervention Comparison Length of Outcome Source type/ of follow-up measures of Evidence patients funding levelEmami MH. Cohort N=350 Inclusion: consecutive patients with IgA tTG Upper GI Biopsies IsfahanDiagnostic suspected coeliac disease6, between April (ELISA) endoscopy, at evaluated using Universitaccuracy of 2004 and October 2006, research institute (ORG540 A, least 4 biopsies Marsh y ofIgA anti- Mixed Iran, N=195 (55.7%) female, mean age ORGENTEC from the medicaltissue 31.44yrs (range 2 to 83yrs), N=98 <18yrs Diagnostica second part of In a normal range Science,transglutami Iran GmbH) the duodenum study with serum Irannase in in all patients samples frompatients Serum levels of healthy blood Poursuspected of Biopsies were read by 2 expert IgA donors the cut-off Sinahaving histolopathologists who were blinded to of 10U/ml have Hakimcoeliac the serological results of the patients been established Researchdisease in with the anti-tTG InstitutionIran. Journal testofGastrointesti6 Group I, classical presentation including diarrhoea, weight loss, iron deficiency anaemiaGroup II, non-specific prolonged GI symptoms like abdominal pain, abdominal bloating, constipation, steatorrhoeaGroup III, atypical presentation determined during screening of high risk groupsNICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 37 of 136
  38. 38. nal andLiverDiseases2008;17:141-6Effect size:Marsh I/II classed as lymphocytic enteritisMarsh III classed as CD71.4% classical presentation, 4.7% atypical presentation, 23.8% non specific prolonged GI symptomsN=21 coeliac disease (62% female), Marsh IIIa 38%, Marsh IIIb 38%, Marsh IIIc 24%Prevalence 6% (21/350)N=8 lymphocytic enteritis (Marsh I, N=4, Marsh II, N=4), all tTG –vetTGSensitivity 38%, specificity 98%, PPV 57%, NPV 96%2X2: (a) TP 8 (b) FP 6 (d) FN 13 (c) TN 32 3NICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 38 of 136
  39. 39. Anti-tTG antibody +ve 53% (N=8/15) of those with classical presentation, anti-tTG antibody +ve 0% (N=0/1) of those with non specific GI presentation, tTG +ve 0%(N=0/5) of those with atypical presentation (p<0.05): - classical; sensitivity 47.9%, specificity 96.4% - non-specific GI; sensitivity 0%, specificity 100% - atypical; sensitivity 0%, specificity 98.2%Those with CD; 80% (N=4/5) with total villous atrophy, 25% (N=4/16) with partial villous atrophy had +ve anti-tTG antibodies (p<0.05)Marsh IIIc; sensitivity 80%, specificity 98%Marsh IIIa and IIIb; sensitivity 36.8%, specificity 98%(author conclusion: test sensitivity for tTG antibody is significantly lower in those with lesser degrees of histological damage)Reference Study Number Patient characteristics Intervention Comparison Length of Outcome Source type/ of follow-up measures of Evidence patients funding levelErtekin V, Cohort N=1,263 Inclusion: randomly selected by IgA-tTG NotSelimoglu children systematic sampling method, N=687 statedMA, Kardas (54.4%) male, N=5761 (45.6%) female, BiopsyF, Aktas E. Turkey mean age 11.9±3.4yrsPrevalenceof celiacdisease in None had a family history of coeliacTurkish diseasechildren.Journal of A pathologist blinded to the serologyClinical results examined all biopsy specimensGastroenter according to the modified Marsh criteriaology2005;39:689-91Effect size:None had IgA deficiencyN=11/1,263 +ve tTG (N=6 boys), total seropositivity was 0.87%N=5/11 of these were asymptomatic, N=4 had iron deficiency anaemia, N=5 failure to thrive, N=1 abdominal pain/diarrhoea/iron deficiency anaemia/failure to thriveSeropositive more frequent vs. seronegative for failure thrive (p=0.0001) and iron anaemia (p=0.04)NICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 39 of 136
  40. 40. N=8 biopsied, N=5 Marsh Type IIIc, N=2 Type IIIb, N=1 normal mucosal histology this patient was considered latent coeliac disease (elevated autoantibody titerswithout histologic abnormality)N=3 refused further investigationsPrevalence of coeliac disease 1:115, prevalence of biopsy proven, 1:158Reference Study Number Patient characteristics Intervention Comparison Length of Outcome Source type/ of follow-up measures of Evidence patients funding levelFerre-Lopez Cohort N=335 Inclusion: consecutive (retrospective) sera ELISA tests ‘Intestinal Diagnostic MinisterioS, Ribes- (286 from adults and children, intestinal biopsy biopsy’ – no accuracy of the deKoninckx C, children, to be performed within 1 month of serum IgA/AGA further details tests Ciencia yGenzor C, 49 sampling, no dietary restrictions homemade TecnoogiGamen S, adults) ELISA, or CAP a,Pena L, Exclusion: none reported gliadin IgA coordinatOrtigosa L Children fluorometric ed by theet al. – age (group 2: patients with a known diagnosis immunoassy group ofImmunochro range 0.9 of celiac disease on a GFD for >2yrs with ’taking into thematographic to 13 serologic analysis – results not included in account the Unidadsticks for years this table) cut-off levels of detissue Adults – each method Gluten,transglutami age for accurate Centronase and range 16 evaulation of Nacionalantigliadin to 65 results’ deantibody years Biotecnolscreening in IgA-tTG gia, andceliac Spain Celikey, with thedisease. cut-off of OperonClinical 6IU/ml CompanyGastroenter (inventorology & Stick tests s of theHepatology test)2004;2:480- tTG4 2-line immunochroma tographic sticks tTG-AGA 3-line immunochromaNICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 40 of 136
  41. 41. tographic sticks Stick results read blindly within 20 minuntes of testing by 2 independent observers Blood for serological tests taken within 1 month of the biopsyEffect size: (CI 95%)N=172/335 (51%, 142 children – 50% - and 30 adults – 61%) diagnosed with coeliac disease, using ESPGAN criteriaIgA deficiency 0.01% in children only (N=3/286), no cases reported in adultsOf the 121 children and 19 adults with a diagnosis other than coeliac disease (ie biopsy results were normal or minor histological changes of the mucosa), mostfrequent diagnoses were cow’s milk protein intolerance, giardiasis, postenteritis syndrome.PPV, NPV and all confidence intervals calculated from the 2x2 data presented in the paper.IgA tTG ELISA childrensensitivity 96.4% (93.3 to 99.5), specificity 98.3% (96.1 to 100), PPV 98.5% (96.5 to 100), NPV 96.0% (92.5 to 99.4)2X2:NICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 41 of 136
  42. 42. (a) TP 134 (b) FP 2 (c) FN 5 (d) TN 119IgA tTG ELISA adultssensitivity 83.3% (70.0 to 96.7), specificity 94.7% (84.7 to 100), PPV 96.2% (88.8 to 100), NPV 78.3% (61.4 to 95.1)2X2: (a) TP 25 (b) FP 1 (c) FN 5 (d) TN 18IgA/G tTG stick childrensensitivity 97.1% (94.3 to 99.9), specificity 98.3% (96.1 to 100), PPV 98.5% (96.5 to 100), NPV 96.7% (93.6 to 99.9)2X2:NICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 42 of 136
  43. 43. (a) TP 135 (b) FP 2 (c) FN 4 (d) TN 119IgA/G tTG stick adultssensitivity 83.3% (70.0 to 96.7), specificity 100% (n/a), PPV 100% (n/a), NPV 79.2% (62.9 to 95.4)2X2: (a) TP 25 (b) FP 0 (c) FN 5 (d) TN 19IgA tTG tTG-AGA stick childrensensitivity 95.7% (92.3 to 99.1), specificity 98.3% (96.1 to 100), PPV 98.5% (96.5 to 100), NPV 95.2% (91.5 to 98.9)2X2:NICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 43 of 136
  44. 44. (a) TP 133 (b) FP 2 (c) FN 6 (d) TN 119IgA tTG tTG-AGA stick adultssensitivity 80.0% (65.7 to 94.3), specificity 100% (n/a), PPV 100% (n/a), NPV 76.0% (59.3 to 92.7)2X2: (a) TP 24 (b) FP 0 (c) FN 6 (d) TN 19IgA AGA ELISA childrensensitivity 86.3% (80.6 to 92.0), specificity 89.3% (83.7 to 94.8), PPV 90.2% (85.2 to 95.3), NPV 85.0% (78.8 to 91.2)2X2:NICE clinical guideline 86 Coeliac disease: appendix 6.6 Page 44 of 136

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