Association between orofacial granulomatosis and Crohn’s disease in children: Systematic review

Table 1 Demographic characteristic of children with orofacial granulomatosis n (%)

Patient characteristics	Value (n = 173)	P value
Age, mean ± SD (range, yr)	11.1 ± 3.8 (2-18)
Sex
Male	69 (39.9)	< 0.0011
Female	34 (19.6)
Unspecified	70 (40.5)
Ethnic group
Caucasian	19 (11.0)	< 0.0011
African	3 (1.7)
Indian	2 (1.2)
Unspecified	149 (86.1)

¹Indicate similarities with Crohn’s disease.

Table 2 Clinical manifestations in children diagnosed with orofacial granulomatosis n (%)

Clinical features	Value (n = 104)2
Lips
Present	104 (100.0)
Lip swelling	97 (93.3)
Only upper lip	27 (26.0)
Only lower lip	15 (14.4)
Both lips	26 (25.0)
Preset but unspecified	29 (27.9)
Angular cheilitis	22 (21.1)
Intra-oral manifestation1
Present	50 (48.1)
Oral ulcerations	24 (23.1)
Gingival hyperemia/hypertrophy	22 (21.1)
Tongue abnormalities	8 (7.7)
Oral cobble-stoning lesions	8 (7.7)
Facies
Perioral/cheek swelling	19 (18.3)
Neck
Cervical lymphadenopathy1	6 (5.8)
Gastrointestinal
Present	27 (26.0)
Perianal disease1	21 (20.2)
Abdominal pain1	7 (6.7)
Diarrhea1	7 (6.7)
Intestinal bleeding1	6 (5.8)
Nutritional status
Impaired growth1	5 (4.8)
Obesity	1 (1.0)
Ocular
Conjunctivitis1	1 (1.0)
Genitalia
Vulvar oedema1	2 (2.0)
Scrotal swelling1	1 (1.0)

¹The asterisks indicate similarities with Crohn’s disease;

²All cases with a detailed description of clinical signs and symptoms are reported in the table.

Table 3 Diagnostic process in children reported with orofacial granulomatosis n (%)

Characteristics	Value (n = 173)
Physicians involved in the diagnosis
Stomatologist/dentist/maxillo surgeon	112 (64.7)
Gastroenterologist	86 (49.7)
Dermatologist	38 (22.0)
Pediatrician	32 (18.5)
Otorhinolaryngologist	13 (7.5)
Allergologist	4 (2.3)
Plastic surgeon	3 (1.7)
Internal Medicine	1 (0.6)
Composition of the team
One single specialty	60 (34.7)
More than one specialty	113 (65.3)
Differential diagnosis considered at time of OFG presentation
Crohn’s disease	137 (79.2)
Sarcoidosis	36 (20.8)
Tuberculosis	25 (14.4)
Allergy	19 (11.0)
Infection	17 (9.8)
C1q esterase deficiency	10 (5.8)
Melkersson–Rosenthal syndrome	4 (2.3)
Autoimmunity	3 (1.7)
Vasculitis	1 (0.6)
Foreign body	1 (0.6)
Enteropathic acrodermatitis	1 (0.6)

OFG: Orofacial granulomatosis.

Table 4 Concomitant diseases diagnosed in children with orofacial granulomatosis and associated characteristics n (%)

Disease	Value(n = 173)	RR (95%CI), P
Crohn’s disease
Total children	70 (40.4)
At presentation	34 (19.6)
During follow-up	36 (20.8)
Time from OFG diagnosis to Crohn’s diagnosis (mean ± SD, range)	13.1 ± 11.6 (3-36)
Presence of perianal disease
Total	21/173 (12.1)	3.10 (2.46-3.90), 0.0001
In children with Crohn’s	21/70 (30.0)
In children without Crohn’s	0/103 (0)
Familiarity for inflammatory bowel diseases
Total	11/173 (6.4)	2.74 (2.24-3.36), 0.0001
In children with Crohn’s	11/70 (15.7)
In children without Crohn’s	0/103 (0)
Allergy/atopy
Any allergy	19 (10.9)
Asthma	7 (4.0)
Atopy	6 (3.5)
Rhinitis/rhinoconjunctivitis	6 (3.5)
Eczema	6 (3.5)
Hives	1 (0.6)
Other diagnosis
Tuberculosis	3 (1.7)
Sarcoidosis	2 (1.1)
Other diseases	10 (5.7)
Erythema nodosum	3 (1.7)
Insulin dependent diabetes	1 (0.6)
Celiac disease	1 (0.6)
Alopecia	1 (0.6)
Low CD4/CD8 ratio	1 (0.6)
Epilepsy	1 (0.6)

Table 5 Treatments of children with orofacial granulomatosis n (%)

Treatment characteristics	Value(n = 104)1
A treatment was prescribed2
Yes	89 (96.7)
No	3 (3.2)
Unspecified	12 (11.5)
Number of treatment attempts reported2
One	38 (55.8)
Two	18 (26.4)
Three or more	12 (17.6)
Unspecified	21 (23.5)
More than one drug in the same treatment attempt2
Yes	36 (53.7)
No	31 (46.2)
Unspecified	22 (24.7)
Type of treatments prescribed2
Antibiotics	26 (29.2)
Anti-histaminic	10 (11.2)
Steroids-total	63 (70.8)
Topical	27 (30.3)
Intralesional	24 (27.0)
Oral	39 (43.8)
Other immunosuppressive-total	38 (42.7)
Azathioprine/6MP	11 (12.3)
Thalidomide	9 (10.1)
Infliximab	8 (9.0)
Dapsone	4 (4.5)
Tacrolimus (topic)	4 (4.5)
Methotrexate	3 (3.4)
Tacrolimus (systemic)	3 (3.4)
Hydroxychloroquine/chloroquine	2 (2.2)
Colchicine	2 (2.2)
Other treatments
5ASA	13 (14.6)
Chlorhexidine (topic)	4 (4.5)
Enteral nutrition	2 (2.2)
Fumaric acid esterase	1 (1.1)
Surgery	8 (9.0)

¹All cases that provided a detail description of clinical signs are reported in the table;

²Percentages are calculated on the number of children for which the treatment was specified. 5-AZA: 5-aminosalicylic acid.