Systematic Reviews
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World J Gastroenterol. Jun 21, 2014; 20(23): 7497-7504
Published online Jun 21, 2014. doi: 10.3748/wjg.v20.i23.7497
Association between orofacial granulomatosis and Crohn’s disease in children: Systematic review
Marzia Lazzerini, Matteo Bramuzzo, Alessandro Ventura
Marzia Lazzerini, Matteo Bramuzzo, Alessandro Ventura, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, 34137 Trieste, Italy
Matteo Bramuzzo, Alessandro Ventura, University of Trieste, 34137 Trieste, Italy
Author contributions: Lazzerini M, Bramuzzo M and Ventura A contributed equally to the work; Lazzerini M conceptualized and designed the review together with Ventura A; Lazzerini M and Bramuzzo M carried out the analysis; Lazzerini M drafted the initial manuscript; all authors reviewed and approved the final manuscript as submitted.
Correspondence to: Marzia Lazzerini, PhD, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Via dell’Istria 65/1, 34137 Trieste, Italy. marzia.lazzerini@burlo.trieste.it
Telephone: +39-40-3785555 Fax: +39-40-3785260
Received: September 27, 2013
Revised: January 17, 2014
Accepted: April 1, 2014
Published online: June 21, 2014
Abstract

AIM: To review pediatric cases of orofacial granulomatosis (OFG), report disease characteristics, and explore the association between OFG and Crohn’s disease.

METHODS: We conducted a systematic review according to the PRISMA guidelines. We searched Medline, LILACS, Virtual Health Library, and Web of Knowledge in September 2013 for cases of OFG in the pediatric age range (< 18 years), with no language limitations. All relevant articles were accessed in full text. The manual search included references of retrieved articles. We extracted data on patients’ characteristics, disease characteristics, association with other diseases, and treatment. We analyzed the data and reported the results in tables and text.

RESULTS: We retrieved 173 reports of OFG in children. Mean age at onset was 11.1 ± 3.8 years (range: 2.0-18 years). Prevalence in males was significant higher than in females (P < 0.001), with a male:female ratio of 2:1. Gastrointestinal signs or symptoms were present in 26.0% of children at the time of OFG diagnosis. Overall, 70/173 (40.4%) children received a concomitant diagnosis of Crohn’s disease. In about half (51.4%) of the cases the onset of OFG anticipated the diagnosis of Crohn’s disease, with a mean time between the two diagnoses of 13.1 ± 11.6 mo (range: 3-36 mo). Overall, 21/173 (12.1%) of the children with OFG had perianal disease, while 11/173 (6.4%) had a family history of Crohn’s disease. Both perianal disease and a family history of Crohn’s disease were significantly associated with a higher risk of Crohn’s disease diagnosis in children with OFG [relative risk (RR) = 3.10, 95% confidence interval (CI): 2.46-3.90; RR = 2.74, 95%CI: 2.24-3.36, P < 0.0001 for both). Treatment of OFG included steroids (70.8% of children) and other immunosuppressive drugs (42.7%), such as azathioprine, thalidomide and infliximab.

CONCLUSION: High prevalence of Crohn’s disease in children with OFG suggests that OFG may be a subtype of Crohn’s disease.

Keywords: Orofacial granulomatosis, Melkersson-Rosenthal syndrome, Cheilitis granulomatosa, Crohn’s disease, Children, Systematic review

Core tip: This systematic review of children with orofacial granulomatosis (OFG) resulted in the following main findings: (1) 40.4% of children with OFG were affected by Crohn’s disease during their life; (2) 12.1% of children with OFG had perianal disease; (3) 6.4% had a positive family history for Crohn’s disease; (4) both OFG and Crohn’s disease were more prevalent in boys; and (5) both diseases had a long-term course, and treatment resembled the treatment used for Crohn’s disease. Taken together, these findings suggest that OFG may be a subtype of Crohn’s disease.