Revisão sistemática e meta-análise das tendências de frequência e reclassificação da doença inflamatória pediátrica intestinal - não classificadas

BOLIA, Rishi; GOEL, Akhil Dhanesh

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Sumário

REVIEW • Arq. Gastroenterol. 59 (4) • Oct-Dec 2022 • https://doi.org/10.1590/S0004-2803.202204000-92 copiar

Revisão sistemática e meta-análise das tendências de frequência e reclassificação da doença inflamatória pediátrica intestinal - não classificadas

Autoria SCIMAGO INSTITUTIONS RANKINGS

RESUMO

Contexto:

O termo doença inflamatória intestinal não classificada (DIINC) é usado quando um indivíduo tem colite crônica, mas não pode ser sub tipificado em colite ulcerativa (UC) ou doença de Crohn (DC) com base nas características clínicas, endoscópicas, de imagem e histopatológicas. No acompanhamento, uma proporção de pacientes com DIINC são reclassificadas como DC ou UC. Houve considerável variabilidade nas taxas de frequência e reclassificação de DIINC pediátrico na literatura publicada.

Métodos:

Foram procuradas publicações no PubMed e Scopus relacionadas à doença inflamatória pediátrica intestinal publicadas entre janeiro de 2014 e julho de 2021. Dois revisores pesquisaram e selecionaram estudos independentemente relatando a frequência da DIINC e/ou sua reclassificação. A prevalência agrupada foi expressa em proporção e para IC95%. A meta-análise foi realizada utilizando o modelo de heterogeneidade de variância inversa.

Resultados:

Foram identificados 2.750 estudos por meio de uma busca sistemática, dos quais 27 estudos foram incluídos nesta revisão sistemática. A frequência total agrupada da DIINC (n=16064) foi de 7,1% (IC95% 5,8-8,5%). Não houve variação na frequência da DIINC por localização geográfica. Sete estudos (n=5880) foram incluídos na análise de reclassificação da DIINC. No geral, 50% (IC95% 41-60%) foram reclassificadas no seguimento. Entre esses 32,7% (95% 21-44%) foram reclassificados para UC e 17% (IC95%12-22%) foram reclassificados para DC.

Conclusão:

DIINC compreende 7,1% da doença inflamatória pediátrica intestinal no diagnóstico inicial. Metade dessas crianças são reclassificados em UC ou DC no seguimento com maior probabilidade de reclassificação para UC em comparação com o DC.

Palavras-chave:
Doença inflamatória intestinal; não classificado; doença inflamatória intestinal pediátrica; doença de Crohn; colite ulcerativa

Author (reference)	Study Period	IBD n	UC n (%)	CD n (%)	IBDU n (%)	IBDU age at diagnosis	IBDU gender (male)	IBDU median follow-up duration
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Jakobsen C⁸8. Jakobsen C, Cleynen I, Andersen PS, Vermeire S, Munkholm P, Paerregaard A, et al. Genetic susceptibility and genotype-phenotype association in 588 Danish children with inflammatory bowel disease. J Crohns Colitis . 2014;8:678-85. doi: 10.1016/j.crohns.2013.12.010. https://doi.org/10.1016/j.crohns.2013.12... 2014, Denmark, Multicentre Retrospective	1982 onward	588	318 (54%)	244 (41.4%)	26 (4.4%)	10.9 years (9.3-14.5)	54%	4.7 years
Hradsky O⁹9. Hradsky O, Copova I, Zarubova K, Durilova M, Nevoral J, Maminak M, et al. Seroprevalence of Epstein-Barr Virus, Cytomegalovirus, and Polyomaviruses in Children with Inflammatory Bowel Disease. Dig Dis Sci. 2015;60:3399-407. 2015, Czech - Prague, Single-centre Prospective	2014	106	31 (29.2%)	72 (68%)	3 (2.8%)	-	-	-
Urlep D¹⁰10. Urlep D, Blagus R, Orel R. Incidence Trends and Geographical Variability of Pediatric Inflammatory Bowel Disease in Slovenia: A Nationwide Study. Biomed Res Int. 2015;2015:921730. 2015, Slovenia, Multicentre Retrospective	2002-2010	279	105 (37.6%)	167 (59.8%)	7 (2.5%)	-	57%	-
Oliva-Hemker M¹¹11. Oliva-Hemker M, Hutfless S, Al Kazzi ES, Lerer T, Mack D, LeLeiko N, et al. Clinical Presentation and Five-Year Therapeutic Management of Very Early-Onset Inflammatory Bowel Disease in a Large North American Cohort. J Pediatr. 2015;167:527-32.e1-3. 2015, USA, Multicentre Prospective	2002-2012	1928	513 (26.6%)	1305 67.7%	110 (5.7%)	-		3.25 years
Cakir M¹²12. Cakir M, Unal F, Dinler G, Baran M, Yuksekkaya HA, Tumgor G, et al. Inflammatory bowel disease in Turkish children. World J Pediatr. 2015;11:331-7. 2015, Turkey, Multicentre Retrospective	2004-2012	127	90 (70.9%)	29 22.8	8 (6.3%)	10.5±5.7 years	50%	-
Buderus S¹³13. Buderus S, Scholz D, Behrens R, Classen M, De Laffolie J, Keller KM, et al. Inflammatory bowel disease in pediatric patients: Characteristics of newly diagnosed patients from the CEDATA-GPGE Registry. Dtsch Arztebl Int. 2015;112:121-7. 2015, Germany and Austria, Multicentre Prospective	2004-2014	958	278 (29%)	616 64.3	64 (6.7%)	11.9 years (0.4-17.6)	51.5%	-
Arcos-Machancoses JV¹⁴14. Arcos-Machancoses JV, Donat-Aliaga E, Polo-Miquel B, Masip-Simó E, Ribes-Koninckx C, Pereda-Pérez A. Retraso diagnóstico en la enfermedad inflamatoria intestinal pediátrica. Descripción y estudio de los factores de riesgo [Description and study of risk factors for the diagnostic delay of pediatric inflammatory bowel disease]. An Pediatr (Barc). 2015;82:247-54. 2015, Spain, Single-centre Retrospective	2000-2012	53	19 (35.8%)	31 (58.4%)	3 (5.7%)	-	-	-
Dimakou K¹⁵15. Dimakou K, Pachoula I, Panayotou I, Stefanaki K, Orfanou I, Lagona E, et al. Pediatric inflammatory bowel disease in Greece: 30-years experience of a single center. Ann Gastroenterol. 2015;28:81-6. 2015, Greece, Single-centre Retrospective	1981-2011	483	267 (55.2%)	167 (34.5%)	49 (10%)	8.9 years (4.8-13.7)	38.6%	-
Schwarz J¹⁶16. Schwarz J, Sýkora J, Cvalínová D, Pomahačová R, Klečková J, Kryl M, et al. Inflammatory bowel disease incidence in Czech children: A regional prospective study, 2000-2015. World J Gastroenterol. 2017;23:4090-4101 2017, Czech - Pilsen, Multicentre Prospective	2000-2015	170	48 (28.2%)	105 (61.7%)	17 (10%)	14.1 years (2.5-17.7)	53%	-
Paul SP¹⁷17. Paul SP, Sandhu BK. Long-term Outcome of Inflammatory Bowel Disease-Unclassified in Children. Indian Pediatr. 2017;54:742-5. 2017, UK, Single-centre Retrospective	2004-2011	344	119 (34.5%)	199 (58%)	26 (7.5%)	10.1 years (1.4-16.1)	64%	51(34-87) months
Lopez RN¹⁸18. Lopez RN, Evans HM, Appleton L, Bishop J, Chin S, Mouat S, et al. Point Prevalence of Pediatric Inflammatory Bowel Disease in New Zealand in 2015: Initial Results from the PINZ Study. Inflamm Bowel Dis . 2017;23:1418-24. 2017, New Zealand, Multicentre Retrospective	2015	212	32 (15.1%)	161 (75.9%)	19 (9%)	12.7 years (9.5-14.0)	68.4%	-
El Mouzan MI¹⁹19. El Mouzan MI, Al Mofarreh MA, Al Sarkhy AA, Assiri AM, Hamed YM. Pre-illness diet as risk factor in pediatric inflammatory bowel disease in Saudi Arabia. Saudi J Gastroenterol. 2017;23:287-90. 2017, Saudi, Single-centre Prospective	-	52	14 (27%)	38 (73%)	0	-	-	-
Bequet E²⁰20. Bequet E, Sarter H, Fumery M, Vasseur F, Armengol-Debeir L, Pariente B, et al. Incidence and Phenotype at Diagnosis of Very-early-onset Compared with Later-onset Paediatric Inflammatory Bowel Disease: A Population-based Study [1988-2011]. J Crohns Colitis . 2017;11:519-26. 2017, France, Multicentre Prospective	1988-2011	1412	343 (24.2%)	1032 (73.1%)	37 (2.6%)	-	-	-
Rinawi F⁵5. Rinawi F, Assa A, Eliakim R, Mozer-Glassberg Y, Nachmias Friedler V, Niv Y, et al. The natural history of pediatric-onset IBD-unclassified and prediction of Crohn’s disease reclassification: a 27-year study. Scand J Gastroenterol. 2017;52:558-63. 2017, Israel, Single-centre Retrospective	1986-2013	723	188 (26%)	482 (66.6%)	53 (7.3%)	12.8 years (9.5-15.6)	56.6%	6.8 years
Ong C²¹21. Ong C, Aw MM, Liwanag MJ, Quak SH, Phua KB. Rapid rise in the incidence and clinical characteristics of pediatric inflammatory bowel disease in a South-East Asian cohort in Singapore, 1994-2015. J Dig Dis. 2018;19:395-403. doi: 10.1111/1751-2980.12641. https://doi.org/10.1111/1751-2980.12641... 2018, Sinagpore, Multicentre Retrospective	1994-2015	228	69 (30.3%)	139 (61%)	20 (8.7%)	13.1 years (IQR 5.53)	45%	-
Chandradevan R²²22. Chandradevan R, Hofmekler T, Mondal K, Harun N, Venkateswaran S, Somineni HK, et al. Evolution of Pediatric Inflammatory Bowel Disease Unclassified (IBD-U): Incorporated With Serological and Gene Expression Profiles. Inflamm Bowel Dis . 2018;24:2285-90. 2018, United States and Canada, Multicentre Prospective	2008-2012	1411	-	-	136 (9.6%)	12.51±3.64 years	57.3%	2 years
Ziade F²³23. Ziade F, Rungoe C, Kallemose T, Paerregaard A, Wewer AV, Jakobsen C. Biochemical Markers, Genotype, and Inflammation in Pediatric Inflammatory Bowel Disease: A Danish Population-Based Study. Dig Dis. 2019;37:140-6. 2019, Denmark, Multicentre Retrospective	1998-2006	235	112 (47.6%)	108 (46%)	15 (6.4%)	8.6 years (3.1-13.5)	80%	-
Harris RE²⁴24. Harris RE, Sim W, Sutton H, Garrick V, Curtis L, Gervais L, et al. Using a Steroid-sparing Tool in Paediatric Inflammatory Bowel Disease to Evaluate Steroid Use and Dependency. J Pediatr Gastroenterol Nutr . 2019;69:557-63. 2019, Scotland, Single-centre Retrospective	2017-2018	229	31 (13.5%)	181 (79%)	17 (7.4%)	-	-	-
Ashton JJ²⁵25. Ashton JJ, Borca F, Mossotto E, Coelho T, Batra A, Afzal NA, et al. Increased prevalence of anti-TNF therapy in paediatric inflammatory bowel disease is associated with a decline in surgical resections during childhood. Aliment Pharmacol Ther. 2019;49:398-407. 2019, UK, Single-centre Prospective	1997-2017	825	272 (32.9%)	498 (60.3%)	55 (6.6%)	-	-	-
Zhang R²⁶26. Zhang R, Zhong XM, Gong YZ, Ma X, Zhu D, Ning HJ, et al. [Analysis of clinical characteristics and drug treatment of inflammatory bowel disease in children: a single center study]. Zhonghua Er Ke Za Zhi. 2020;58:570-5. 2020, China, Single-centre Retrospective	2009-2018	87	25 (29%)	50 (57%)	12 (14%)	-	-	-
IvkoviÄ‡ L²⁷27. Ivković L, Hojsak I, Trivić I, Sila S, Hrabač P, Konjik V, et al. Incidence and Geographical Variability of Pediatric Inflammatory Bowel Disease in Croatia: Data From the Croatian National Registry for Children With Inflammatory Bowel Disease. Clin Pediatr (Phila). 2020;59:1182-90. 2020, Croatia, Multicentre Prospective	2016-2017	51	28 (56%)	19 (38%)	8 (15.6)	14.5 years (12.8-16.7)	75%	-
Mouratidou N²⁸28. Mouratidou N, Malmborg P, Sachs MC, Askling J, Ekbom A, Neovius M, et al. Adult height in patients with childhood-onset inflammatory bowel disease: a nationwide population-based cohort study. Aliment Pharmacol Ther . 2020;51:789-800. 2020, Sweden, Multicentre Retrospective	1990-2014	4201	2201 (52.3%)	1640 (39%)	360 (8.5%)	-	-	Range 1.3 to 27.2 years
Dhaliwal J²⁹29. Dhaliwal J, Walters TD, Mack DR, Huynh HQ, Jacobson K, Otley AR, et al. Phenotypic Variation in Paediatric Inflammatory Bowel Disease by Age: A Multicentre Prospective Inception Cohort Study of the Canadian Children IBD Network. J Crohns Colitis . 2020;14:445-54. 2020, Canada, Multicentre Prospective	2014-2017	1092	316 (30%)	687 (62%)	89 (8%)	-	-	1 year
Arai K³⁰30. Arai K, Kunisaki R, Kakuta F, Hagiwara SI, Murakoshi T, Yanagi T, et al. Phenotypic characteristics of pediatric inflammatory bowel disease in Japan: results from a multicenter registry. Intest Res. 2020;18:412-20. 2020, Japan, Multicentre Prospective	2012-2015	243	146 (60.1%)	91 (37.4%)	6 (2.4%)	4.3±5.6 years	50%	-
Larrosa-Haro A³¹31. Larrosa-Haro A, Abundis-Castro L, Contreras MB, Gallo MJ, Peña-Quintana L, Targa Ferreira CH, et al. Epidemiologic trend of pediatric inflammatory bowel disease in Latin America: The Latin American Society for Pediatric Gastroenterology, Hepatology and Nutrition (LASPGHAN) Working Group. Rev Gastroenterol Mex (Engl Ed). 2021;86:328-34. 2020, Latin America - 9 Countries, Multicentre Retrospective	2005-2016	607	475 (78.3%)	104 (17.1%)	28 (4.6%)	-		-
Srivastava A³²32. Srivastava A, Sathiyasekharan M, Jagadisan B, Bolia R, Peethambaran M, Mammayil G, et al. Paediatric inflammatory bowel disease in India: a prospective multicentre study. Eur J Gastroenterol Hepatol. 2020;32:1305-11. 2020, India, Multicentre Ambispective	2016-2019	325	91 (28%)	212 (65.2%)	22 (6.7%)	3.3 years (IQR 2.3)	67%	-

Excluded study	Pooled prevalence	LCI 95%	HCI 95%	Cochran Q	I²	I² LCI 95%	I² HCI 95%
Aloi M	0.066	0.050	0.083	148.401	83.828	77.182	88.538
Jakobsen C	0.067	0.052	0.084	143.393	83.263	76.306	88.177
Cakir M	0.067	0.051	0.083	148.840	83.875	77.255	88.568
Arcos-Machancoses JV	0.067	0.051	0.083	148.836	83.875	77.255	88.568
Buderus S	0.066	0.050	0.084	148.832	83.874	77.254	88.568
Oliva-Hemker M	0.068	0.051	0.086	145.589	83.515	76.698	88.338
Hradsky O.	0.067	0.052	0.083	146.127	83.576	76.792	88.377
Urlep D.	0.067	0.052	0.083	138.216	82.636	75.330	87.778
Dimakou K.	0.066	0.050	0.082	140.526	82.921	75.774	87.960
Paul SP	0.066	0.051	0.083	148.284	83.815	77.162	88.530
Schwarz J	0.066	0.051	0.082	145.958	83.557	76.762	88.365
Lopez RN	0.066	0.051	0.082	146.983	83.672	76.940	88.438
El Mouzan MI	0.067	0.052	0.083	141.069	82.987	75.877	88.002
Bequet E	0.071	0.058	0.085	90.188	73.389	60.513	82.066
Rinawi F	0.066	0.050	0.083	148.215	83.807	77.150	88.525
Ong C	0.066	0.051	0.083	147.134	83.688	76.966	88.449
Ziade F	0.067	0.051	0.083	148.837	83.875	77.255	88.568
Harris RE	0.066	0.051	0.083	148.521	83.841	77.202	88.546
Ashton JJ	0.066	0.050	0.084	148.834	83.875	77.254	88.568
Zhang R	0.066	0.051	0.082	143.304	83.252	76.289	88.171
IvkoviÄ! L	0.066	0.051	0.082	143.867	83.318	76.391	88.212
Mouratidou N	0.060	0.048	0.073	118.827	79.803	70.869	85.996
Dhaliwal J	0.065	0.049	0.083	144.823	83.428	76.562	88.283
Arai K	0.067	0.052	0.083	139.513	82.797	75.581	87.881
Larrosa-Haro A	0.067	0.052	0.084	144.232	83.360	76.457	88.239
Srivastava A	0.066	0.051	0.083	148.808	83.872	77.250	88.566

Excluded study	Pooled prevalence	LCI 95%	HCI 95%	Cochran Q	p	I²	I² LCI 95%	I² HCI 95%
Paul SP	0.308	0.183	0.442	30.119	0.000	83.399	65.234	92.073
Chandradevan R	0.313	0.154	0.484	33.638	0.000	85.136	69.518	92.752
Schwarz J	0.292	0.165	0.428	33.876	0.000	85.240	69.772	92.793
Lopez RN	0.302	0.174	0.440	33.296	0.000	84.983	69.146	92.691
Oliva-Hemker M	0.264	0.128	0.414	28.012	0.000	82.151	62.097	91.594
Rinawi F	0.327	0.218	0.443	19.670	0.001	74.581	42.262	88.809
Dhaliwal J	0.263	0.138	0.401	25.250	0.000	80.198	57.107	90.858

Excluded study	Pooled prevalence	LCI 95%	HCI 95%	Cochran Q	p	I²	I² LCI 95%	I² HCI 95%
Paul SP	0.194	0.099	0.300	25.177	0.000	80.141	56.958	90.837
Chandradevan R	0.225	0.114	0.348	21.697	0.001	76.956	48.617	89.665
Schwarz J	0.192	0.103	0.292	23.727	0.000	78.927	53.808	90.387
Lopez RN	0.197	0.102	0.304	26.063	0.000	80.816	58.696	91.090
Oliva-Hemker M	0.203	0.086	0.336	25.952	0.000	80.734	58.486	91.059
Rinawi F	0.170	0.121	0.223	7.753	0.170	35.509	0.000	74.216
Dhaliwal, J.	0.217	0.110	0.337	21.964	0.001	77.236	49.359	89.767

Authors	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20
Zhang R	Y	Y	D	Y	D	Y	N	Y	Y	Y	Y	Y	D	D	Y	Y	Y	Y	N	D
Ziade F	Y	Y	N	Y	Y	Y	D	Y	Y	Y	Y	Y	D	D	Y	Y	Y	Y	N	Y
Paul SP	Y	Y	N	Y	Y	Y	D	Y	Y	Y	Y	Y	D	D	Y	Y	Y	Y	N	D
IvkoviÄ‡ L	Y	Y	D	Y	Y	Y	D	Y	Y	Y	Y	Y	D	D	Y	Y	Y	Y	N	Y
Chandradevan	Y	Y	D	Y	Y	Y	D	Y	Y	Y	Y	Y	D	D	Y	Y	Y	Y	N	Y
Schwarz J	Y	Y	N	Y	Y	Y	D	Y	Y	Y	Y	Y	D	D	Y	Y	Y	Y	N	Y
Cakir M	Y	Y	D	Y	Y	Y	D	Y	Y	Y	Y	Y	N	D	Y	Y	Y	Y	N	Y
Aloi M	Y	Y	D	Y	Y	Y	D	Y	Y	Y	Y	Y	D	D	Y	Y	Y	Y	N	Y
Arcos-Machancoses	Y	Y	D	Y	Y	Y	D	Y	Y	Y	Y	Y	D	D	Y	Y	Y	Y	N	Y
Lopez RN	Y	Y	N	Y	Y	Y	D	Y	Y	Y	Y	Y	D	D	Y	Y	Y	Y	N	Y
Buderus S	Y	Y	N	Y	Y	Y	D	Y	Y	Y	Y	Y	D	D	Y	Y	Y	Y	N	Y
El Mouzan MI	Y	Y	D	Y	Y	Y	D	Y	Y	Y	Y	Y	D	D	Y	Y	Y	Y	N	Y
Bequet E	Y	Y	N	Y	Y	Y	D	Y	Y	Y	Y	Y	D	D	Y	Y	Y	Y	N	Y
Oliva-Hemker M	Y	Y	N	Y	Y	Y	D	Y	Y	Y	Y	Y	D	D	Y	Y	Y	Y	N	Y
Rinawi F	Y	Y	D	Y	Y	Y	D	Y	Y	Y	Y	Y	D	D	Y	Y	Y	Y	N	Y
Mouratidou N	Y	Y	D	Y	Y	Y	D	Y	Y	Y	Y	Y	D	D	Y	Y	Y	Y	N	Y
Harris RE	Y	Y	D	Y	Y	Y	D	Y	Y	Y	Y	Y	D	D	Y	Y	Y	Y	N	Y
Ashton, J.J.	Y	Y	D	Y	Y	Y	D	Y	Y	Y	Y	Y	D	D	Y	Y	Y	Y	N	Y
Dhaliwal, J.	Y	Y	D	Y	Y	Y	D	Y	Y	Y	Y	Y	D	D	Y	Y	Y	Y	N	Y
Arai, K.	Y	Y	D	Y	Y	Y	D	Y	Y	Y	Y	Y	D	D	Y	Y	Y	Y	N	Y
Larrosa-Haro,	Y	Y	D	Y	Y	Y	D	Y	Y	Y	Y	D	D	D	Y	Y	Y	Y	N	Y
Srivastava, A.	Y	Y	D	Y	Y	Y	D	Y	Y	Y	Y	Y	D	D	Y	Y	Y	Y	N	Y
Jakobsen, C.	Y	Y	D	Y	Y	Y	D	Y	Y	Y	Y	Y	D	D	Y	Y	Y	Y	N	Y
Hradsky, O.	D	Y	N	Y	Y	Y	D	Y	Y	D	Y	Y	D	D	Y	Y	Y	Y	N	Y
Urlep, D.	Y	Y	N	Y	Y	Y	D	Y	Y	Y	Y	Y	D	D	Y	Y	Y	Y	N	Y
Ong C	Y	Y	D	Y	Y	Y	D	Y	Y	Y	Y	Y	D	D	Y	D	Y	Y	N	Y
Dimakou, K.	Y	Y	D	Y	Y	Y	D	Y	Y	Y	Y	Y	D	D	Y	Y	Y	Y	N	Y

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[1] Corresponding author: Rishi Bolia. Email - rishi.bolia@health.qld.gov.au