The Diagnostic Utility of Lip Biopsy in Paediatric Crohn's Disease: A 10-year Single-centre Retrospective Study.

BACKGROUND: Oral manifestations of paediatric Crohn's disease (CD) are reported in up to 60% of cases. Lip biopsy can be used to histologically diagnose oral CD. We evaluated the utility of lip biopsy in children under initial investigation for potential CD. METHODS: A 10-year retrospective review of electronic patient records at a single tertiary paediatric surgery centre was performed. All patients aged ≤16 years who underwent lip biopsy were included. Clinical features, histology, and diagnostic details were extracted. RESULTS: Forty-two children underwent lip biopsy. Median age at biopsy was 13.3 years (11.0-14.9). Final diagnosis was CD in 21/42 (50%) children, indeterminant colitis in 3/42 (7%), orofacial granulomatosis (OFG) in 3/42 (7%), coeliac disease in 1/42 (2%), and eosinophilic oesophagitis in 1/42 (2%). Thirteen children (31%) received no formal diagnosis. The most common symptoms reported were oral ulceration (33/42, 79%), lip swelling (21/42, 50%), and abdominal pain (19/42, 45%). Lip biopsy histology was normal in 11/42 (26%). In 24/42 (57%), non-granulomatous inflammation was seen. In 7/42 (17%) lip biopsy identified granulomatous inflammation: three (7%) had endoscopic biopsies concordant for CD, three (7%) had negative endoscopic biopsies but were diagnosed with CD, and one was diagnosed with OFG (2%). Sensitivity was 29% and specificity was 95%. CONCLUSION: Lip biopsy has low sensitivity but high specificity for diagnosing CD. Lip biopsy diagnosed CD in 7% when endoscopic biopsies were negative, enabling treatment. LB is a useful diagnostic test for CD in children presenting with oral symptoms. LEVEL OF EVIDENCE: III.

Gingival Orofacial Granulomatosis Clinical and 2D/3D Microscopy Features after Orthodontic Therapy: A Pediatric Case Report.

Orofacial granulomatosis (OFG) represents a heterogeneous group of rare orofacial diseases. When affecting gingiva, it appears as a chronic soft tissue inflammation, sometimes combined with the enlargement and swelling of other intraoral sites, including the lips. Gingival biopsy highlights noncaseating granulomatous inflammation, similar to that observed in Crohn's disease and sarcoidosis. At present, the etiology of OFG remains uncertain, although the involvement of the genetic background and environmental triggers, such as oral conditions or therapies (including orthodontic treatment), has been suggested. The present study reports the results of a detailed clinical and 2D/3D microscopy investigation of a case of gingival orofacial granulomatosis in an 8-year-old male patient after orthodontic therapy. Intraoral examination showed an erythematous hyperplasia of the whole gingiva with a granular appearance occurring a few weeks after the installation of a quad-helix. Peri-oral inspection revealed upper labial swelling and angular cheilitis. General investigations did not report ongoing extra-oral disturbances with the exception of a weakly positive anti-Saccharomyces cerevicae IgG auto-antibody. Two- and three-dimensional microscopic investigations confirmed the presence of gingival orofacial granulomatosis. Daily corticoid mouthwashes over a period of 3 months resulted in a slight improvement in clinical signs, despite an intermittent inflammation recurrence. This study brings new insights into the microscopic features of gingival orofacial granulomatosis, thus providing key elements to oral practitioners to ensure accurate and timely OFG diagnosis. The accurate diagnosis of OFG allows targeted management of symptoms and patient monitoring over time, along with early detection and treatment of extra-oral manifestations, such as Crohn's disease.

Frequent Occurrence of Perianal Disease and Granuloma Formation in Patients with Crohn's Disease and Coexistent Orofacial Granulomatosis.

BACKGROUND: Orofacial granulomatosis (OFG) is an inflammatory disorder of the perioral region and oral cavity. Crohn's disease (CD) in conjunction with OFG (CD-OFG), has been suggested to constitute a phenotype of CD with distinct features at diagnosis. AIMS: The aim of this project was to investigate whether the distinct phenotypic features of CD-OFG persist in the years following the initial diagnosis of CD. METHODS: Clinical data were extracted from medical records covering the first 5 years post-diagnosis for a cohort of patients with CD-OFG, and were compared to those of references with CD without OFG. RESULTS: The clinical characteristics of our cohort of patients with CD-OFG (N = 25) were evaluated in comparison to references with CD without OFG (ratio 1:2). Five years post-diagnosis, more patients with CD-OFG had a phenotype with perianal disease (cumulative incidence: 16/25, 64% vs 13/50, 26%, P = 0.002) and intestinal granulomas (cumulative incidence: 22/25, 88% vs 24/50, 48%, P = 0.0009) than patients in the CD reference group. The patients with CD-OFG were also more likely to have undergone perianal surgery (12/25, 48% vs 4/50, 8%, P = 0.0002). At the end of the observation period, more of the patients with CD-OFG were receiving combination therapy, i.e., immunomodulators and tumor necrosis factor antagonists, than those in the CD reference group (9/25, 36% vs 5/50, 10%, P = 0.01). CONCLUSION: The results support the notion that CD in conjunction with OFG represents a specific phenotype of CD that is characterized by frequent perianal disease, pronounced intestinal granuloma formation and a need for extensive therapy.

Is orofacial granulomatosis a distinct clinical disorder?

Orofacial granulomatosis is a rare disorder that is heterogeneously defined in the published literature. Herein, we describe a patient with orofacial granulomatosis with clinical and histologic evidence, discuss differential diagnoses, and offer clinical pearls for diagnosing and assessing this disorder. Our case provides support that orofacial granulomatosis is a distinct disorder as opposed to a sequela of other systemic granulomatous diseases. This information will aid dermatologists in decision making and diagnosing the disorder.

Orofacial granulomatosis associated with gingival enlargement: a case report.

Orofacial granulomatosis (OFG) is an uncommon condition with varying clinical presentation. Gingival enlargement in children could be due to a varied etiology. The present case report is of an adolescent female with initial presentation of generalized gingival enlargement, lip swelling and perioral discoloration without any known etiopathological factors or systemic involvement. Conservative excision of the enlargement was performed and histopathological examination revealed a non caseating granulomatous lesion. Diagnosis of orofacial granulomatosis in context to sarcoidosis was arrived after excluding other granulomatous diseases. Follow up after 18 months showed no recurrence and regression of lip swelling and perioral discoloration. Gingival enlargement can be considered as one of the presenting features of sarcoidosis.

Orofacial Granulomatosis Associated with Crohn's Disease: a Multicentre Case Series.

BACKGROUND: Orofacial granulomatosis [OFG] is a rare syndrome that may be associated with Crohn's disease [CD]. We aimed to characterise this relationship and the management options in the biologic era. METHODS: This multicentre case series was supported by the European Crohn's and Colitis Organisation [ECCO], and performed as part of the Collaborative Network of Exceptionally Rare case reports [CONFER] project. Clinical data were recorded in a standardised collection form. RESULTS: This report includes 28 patients with OFG associated with CD: 14 males (mean age of 32 years, ±12.4 standard deviation [SD]) and 14 females [40.3 years, ±21.0 SD]. Non-oral upper gastrointestinal tract involvement was seen in six cases and perianal disease in 11. The diagnosis of OFG was made before CD diagnosis in two patients, concurrently in eight, and after CD diagnosis in 18. The distribution of OFG involved the lips in 16 cases and buccal mucosa in 18. Pain was present in 25 cases, with impaired swallowing or speaking in six. Remission was achieved in 23 patients, notably with the use of anti-tumour necrosis factors [TNFs] in nine patients, vedolizumab in one, ustekinumab in one, and thalidomide in two. A further five cases were resistant to therapies including anti-TNFs. CONCLUSIONS: OFG associated with CD may occur before, concurrently with, or after the diagnosis of CD. Perianal and upper gastrointestinal [UGI] disease are common associations and there is a significant symptom burden in many. Remission can be obtained with a variety of immunosuppressive treatments, including several biologics approved for CD.

Orofacial granulomatosis: Clinical and therapeutic features in an Italian cohort and review of the literature.

BACKGROUND: Orofacial granulomatosis (OFG) is characterized by granulomatous inflammation of the soft tissues of maxillofacial region. We explored OFG patients from 10 different Italian centers and summarized the most recent literature data. METHODS: A review of patients with OFG was carried out. An extensive online literature search was performed to identify studies reporting diagnosis and management of OFG. RESULTS: Thirty-nine patients were recruited between January 2018 and February 2020. Most of them (97.4%) displayed involvement of the lips, and 28.2% suffered from Melkersson-Rosenthal syndrome. Two patients received diagnosis of CD and one patient of sarcoidosis, suggesting secondary OFG. Oral aphthosis and cervical lymphadenopathy were also described. The mean diagnostic delay was 3.4 years. Histological evaluation was performed in 34/39 patients (87.2%); non-caseating granulomas were found in 73.5% of them. Neurological symptoms (28.2%), gastrointestinal symptoms in absence of overt inflammatory bowel disease (IBD) (20.5%), and atopy (35.9%) were also identified. Therapeutic approaches varied among the centers. Steroids (51.3%) were used with good or partial results. Anti-TNF-α and anti-IgE monoclonal antibodies were used in 6 (15.4%) and 1 (2.6%) patients, respectively, with variable results. Surgery was the choice for 2 patients with good response. CONCLUSIONS: OFG is a rare and neglected disease showing multiple clinical phenotypes. While early diagnosis is crucial, management is difficult and highly dependent on the expertise of clinicians due to the lack of international guidelines. There is a need to establish registry databases and address challenges of long-term management.

Clinical Profile of Melkersson-Rosenthal Syndrome/Orofacial Granulomatosis: A Review of 51 Patients.

BACKGROUND: Melkersson-Rosenthal syndrome (MRS) is a rare disease characterized by the triad of granulomatous cheilitis, fissured tongue, and facial paralysis. Publications concerning large series are rare in the literature. OBJECTIVES: To describe the clinical and histopathological characteristics of patients with complete and oligosymptomatic forms of MRS. METHODS: A retrospective records review was performed for the diagnoses of Melkersson-Rosenthal syndrome, granulomatous cheilitis, and orofacial granulomatosis at oral Diseases Clinic of the Department of Dermatology, University of São Paulo, Brazil (2003, 2017). RESULTS: A total of 51 patients were included, mean age at presentation 35.69 years. Four patients were younger than 18 years. The complete triad of was observed in 10 patients. The rare findings of granulomatous blepharitis, gingivitis and palatitis are presented. Comorbidities included Crohn's disease (5 patients), migraine headaches (1 patient) and convulsions (2 patients). Granulomatous inflammatory infiltrate was detected in 31 biopsies. Medical therapies included included oral and intralesional steroids, thalidomide, dapsone, azathioprine, tetracycline, methotrexate, and surgery, with variable responses. CONCLUSIONS: Our report meant to draw attention to the clinical spectrum of this rare disorder, mainly to oligosymptomatic forms and rarer presentations.

Orofacial Granulomatosis and Crohn Disease: Coincidence or Pattern? A Systematic Review.

BACKGROUND: To systematically review all cases of orofacial granulomatosis (OFG) and evaluate the association between OFG and Crohn disease (CD). SUMMARY: This review was conducted according to PRISMA guidelines and a search of the PubMed, MEDLINE, and Embase databases, and the Cochrane Library in March 2020, using keywords and MeSH terms associated with "orofacial granulomatosis," "Crohn disease," and their variants, with no language restrictions and across all age groups. All relevant articles were accessed in full text. Single case reports and articles on sarcoidosis, allergy, ulcerative colitis, and infectious diseases were excluded from the analysis. RESULTS: We retrieved 507 reports on OFG. The mean age at onset was 23.3 years (range 2-89 years). A total of 240 (47.3%) females and 267 (52.6%) males were included. CD was present in 93 children aged <16 years (68.3%) and in 43 adults (31.9%). In most cases, the OFG appeared before the CD. The most common clinical manifestations were intraoral mucosa abnormalities (n = 251; 49.5%), lower-lip swelling (n = 249; 49.1%), upper-lip swelling (n = 227; 44.7%), and gingivae (n = 193; 38.7%). Patients with concurrent CD were more likely to experience involvement of the buccal sulcus. Key Messages: OFG presents primarily as a solo entity. The OFG that was associated with CD was present in 93 children aged under 16 years (68.3%) and in 43 adults (31.9%). Childhood onset of OFG carries with it a higher risk of developing CD.

Un caso raro de lesiones faciales: granulomatosis orofacial / A rare case of facial injuries: orofacial granulomatosis

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Pediatric patients with orofacial granulomatosis likely to subsequently develop intestinal Crohn's disease: Brief Report.

Orofacial granulomatosis (OFG) is an uncommon chronic granulomatous condition presenting as perioral inflammation in the absence of systemic disease. There is continued debate regarding whether OFG is a distinct clinical disorder or a manifestation of orofacial Crohn's disease. Our retrospective review identified 7 patients diagnosed with OFG between 2000 and 2018 at a tertiary pediatric hospital. Four of the 7 patients subsequently developed Crohn's disease with a median delay of 3.1 years (range 0.4-6.9 years). This indicates that gastroenterology evaluation with long-term monitoring for intestinal Crohn's disease is warranted.

Oral Granulomatous Disease.

Granulomatous diseases are chronic inflammatory disorders whose pathogenesis is triggered by an array of infectious and noninfectious agents, and may be localized or a manifestation of systemic, disseminated disease. As in the skin, oral manifestations of granulomatous inflammation are often nonspecific in their clinical appearance. Thus, in the absence of overt foreign material or a recognizable infectious agent, identifying the underlying cause of the inflammation can be challenging. This article highlights various conditions known to induce granulomatous inflammation within the oral soft tissues.

Orofacial granulomatosis: a questionnaire study among Norwegian dental clinicians.

AIMS: To evaluate awareness on orofacial granulomatosis (OFG) and oral Crohn disease (oral CD) among Norwegian dental clinicians. METHODS: A precoded questionnaire (QuestBack) was sent electronically to dentists and dental hygienists treating children and adolescents in the public dental service (PDS) in Norway. Data on the clinicians' knowledge of OFG and oral CD related to working experience were analysed by Chi square tests and bivariate logistic regression analyses. RESULTS: A total of 1097 clinicians were invited to participate, 778 dentists and 319 dental hygienists; 48.2% returned the completed form. Fifty-four percent of the participants had ≥ 10 year experience of clinical practice. Two-thirds (68.4%) of the dentists and all but one of the dental hygienists graduated in Norway. Approximately half of the respondents were aware of OFG (41.2%) and oral CD (57.8%). One-quarter (24.6%) reported that they most likely had seen a patient with OFG and 20.6% with oral CD. Recently graduated dentists (≤ 10 years ago) were more aware of OFG and oral CD than those who graduated > 10 years ago (p ≤ 0.001). Regarding dental hygienists, this difference was observed for OFG only (p < 0.05). Country of education did not affect the clinicians' reported knowledge. Approximately 90% would refer a patient suspected of having OFG or oral CD either to a dental specialist or to a physician. CONCLUSION: The high prevalence of clinicians observing OFG and oral CD in this study may indicate that OFG and/or oral CD are under-reported and that OFG in particular is more common than hitherto believed. The high frequency of awareness was promising for the benefit of the patients.