Oro-Facial Granulomatosis: Crohnʼs Disease or a New Inflammatory Bowel Disease?

<h3>Introduction</h3> Orofacial granulomatosis (OFG), which includes oral Crohn9s disease (CD) is a chronic inflammatory condition presenting characteristically with lip swelling but also affecting the gingivae, buccal mucosa, floor of the mouth and a number of other sites in the oral cavity. It can occur in combination with systemic conditions however, its true relationship with gut CD remains unclear. Previous studies using conventional endoscopy suggest that at least two-thirds of patients with OFG1 have asymptomatic intestinal inflammation. Capsule endoscopy offers a less invasive means of investigating the gut in these patients and not previously been evaluated in any detail in OFG. The aim was to use capsule endoscopy to determine the presence of gut CD in patients presenting with OFG with active oral inflammation but no gut symptoms. <h3>Methods</h3> 30 consecutive patients with biopsy-proven OFG were recruited from the multidisciplinary Oral Medicine/Gastroenterology out-patient clinic at Guy9s and St Thomas9 NHS Foundation Trust Hospital (London, UK) between January and August 2009. <h3>Result</h3> 26 full capsule endoscopies were performed. Three patients failed to attend three consecutive appointments. One capsule remained in the stomach for the first 24 h and failed to capture any images beyond the pylorus. From the completed recordings, small bowel abnormalities (terminal ileal ulceration and erythema) were only seen in one patient. While waiting for her capsule endoscopy, this patient had in fact developed diarrhoea, rectal bleeding and weight loss. A diagnosis of Crohn9s disease was made at subsequent colonoscopy and biopsy. The remaining recordings were completely normal. <h3>Conclusion</h3> OFG represents a spectrum of disease. Patients can have orofacial manifestations in isolation, but a small proportion have concomitant clinical CD. In patients without intestinal symptoms, a diagnosis of occult CD is very unlikely. GI surveillance using any diagnostic modality should be reserved for patients with GI symptoms or where CD is suspected from history or screening blood tests. Though video capsule endoscopy is attractive and less invasive, ileocolonoscopy with biopsy remains the gold standard in the appropriate patient.

Orofacial granulomatosis (OFG) is a clinical condition that presents with lip and facial swellings as a result of an underlying granulomatous inflammation. This can precede clinical gastrointestinal Crohn's disease by many years. The aetiology of OFG and it's relation to Crohn's disease remains unclear, however treatment of Crohn's usually proves effective in treating OFG. We have assessed the effect of nutritional therapy and dietary exclusion in treating OFG. We retrospectively reviewed clinical, histopathology and laboratory data of 15 patients who presented with lip swelling (age range 5 years to 19 years, median age 14 years, 7 female and 8 male), over a 7-year period. Out of the 15 children with OFG, 7 presented and continue to have only OFG whilst 5 patients subsequently developed Crohn's disease. 2 patients developed Crohn's disease first and OFG later and one patient had OFG and Crohn's at presentation. 14 children were initially treated with amino acid based formula (Elemental 028, SHS). 11/14 (79%) had complete resolution of their symptoms, 4 required adjunctive medications. 12/14 (86%) had a symptomatic relapse when cow's milk was reintroduced into their diet but responded to cow's milk elimination. All children had increased numbers of eosinophils in their colonic biopsies. 5 patients had increased IgE levels and 5 had positive RAST tests. We suggest that children with OFG are highly likely to have an element of food sensitivity in contributing to their disease which is responsive to dietary exclusion. OFG identifies a group of children with granulomatous inflammation which is exacerbated by food sensitivity. Treatment of individuals with OFG and OFG-Crohn's should comprise amino acid based rather than polymeric formula. Single food introductions and dietary exclusion(s) will be important after remission induction in individuals with OFG.

Background Orofacial granulomatosis (OFG) is an uncommon, chronic inflammatory disease characterised by relapsing and remitting lip swelling and ulceration of the buccal mucosa, gingiva and floor of the mouth. The histology is of non-caseating granulomas which are indistinguishable from those seen in Crohn’s disease (CD) and there is overlap with oral CD. There is a strong association between CD and OFG, with studies suggesting that up to 1/3 of patients with OFG either have or will develop CD. There is limited data on the phenotype of CD seen in association with OFG. A multicentre case series supported by ECCO suggested possible high rates of UGI and perianal CD (pCD) but the patient number was small (n = 28) 1. Methods The aim of the study was to characterise the phenotype of CD in a large cohort of patients with both CD and OFG using the Montreal classification. Patients with OFG and CD were identified from the databases of two UK tertiary referral centres for IBD. The case notes were reviewed and the pattern of disease classified. The surgical history and treatment history was also recorded. Results 132 patients were identified with CD and OFG. Clinical data was available for 109 patients. 49 were female and the median age was 42 (IQR 34-57). Median age at diagnosis was 20 (IQR 15-29) and median disease duration was 21 years (14-29). The Montreal classification (age at diagnosis, disease distribution and disease behaviour) is described in table 1. The prevalence of perianal disease (pCD) was 46% (50/109). 44 patients had undergone gastroscopy with 16 (15%) having findings thought to be consistent with upper gastrointestinal CD (UGI CD). Of these 16, 13 (12%) had oesophageal involvement with 10 (9%) having stricturing oesophageal disease. 82 (75%) patients received advanced therapy and 18 (17%) azathioprine alone. The median number of advanced therapies was one with anti-TNF being the most common (79 patients (72%)). 44 (40%) patients had undergone resectional surgery. Conclusion To our knowledge, this is the largest study to date of the phenotypic pattern of CD in patients with OFG and CD. Our study demonstrates that, compared to other published datasets for patients with CD alone, patients with OFG and CD are diagnosed at a young age (20 vs 29.52) and there are high rates of pCD (46% vs 20%3), (although acknowledging that this is an uncontrolled comparison). UGI involvement is relatively common, with high rates of oesophageal involvement (12% vs 4%4) and particularly oesophageal stricturing disease. Our results suggest that clinicians should have a low threshold for performing UGI endoscopy in all patients with CD/OFG and the high rates of UGI and pCD suggests that early escalation to advanced therapies is appropriate.

Orofacial granulomatosis (OFG) is a condition manifesting clinically with chronic swelling of the mouth and/or face, notably with swelling of the lips and oral mucosa, a full-thickness, erythematous gingivitis and mucosal ulceration of various clinical types. Some patients may also present with neurological findings, for example facial palsy. Biopsy of affected tissue shows lymphoedema, with or without granulomatous inflammation. The oral lesions in OFG are histologically indistinguishable from the oral lesions in Crohn's disease (CD) and other systemic granulomatous disorders. It is a condition which may respond to the exclusion of certain food-related chemicals from the diet in up to 60% of patients and, as such, is distinct from gastrointestinal CD. CD is a relapsing systemic inflammatory disease which predominantly affects the gut, and patients suffering from this disease frequently present with abdominal pain, fever and altered bowel habit. A proportion of patients with clinical OFG (without other systemic disease) may have asymptomatic gastrointestinal involvement or go on to develop gut CD suggesting an association between the two diseases. It is estimated that 1% of CD sufferers may have a diagnosis of OFG, but the majority of patients in specialist OFG clinics do not have gut symptoms.

Orofacial granulomatosis (OFG) is a chronic inflammatory disorder presenting characteristically with lip swelling but also affecting gingivae, buccal mucosa, floor of mouth, and a number of other sites in the oral cavity. Although the cause remains unknown, there is evidence for involvement of a dietary allergen. Patch testing has related responses to cinnamon and benzoate to the symptoms of OFG, with improvement obtained through exclusion diets. However, an objective assessment of the effect of a cinnamon- and benzoate-free diet (CB-free diet) as primary treatment for OFG has not previously been performed. Thus, this study was undertaken to investigate the benefits of a CB-free diet as first-line treatment of patients with OFG. Thirty-two patients with a confirmed diagnosis of OFG were identified from a combined oral medicine/gastroenterology clinic. All had received a CB-free diet as primary treatment for a period of 8 weeks. Each patient underwent a standardized assessment of the oral cavity to characterize the number of sites affected and the type of inflammation involved before and after diet. There was a significant improvement in oral inflammation in patients on the diet after 8 weeks. Both global oral and lip inflammatory scores improved (P<0.001), and there was significant improvement in both lip and oral site and activity involvement. However, improvement in lip activity was less marked than oral activity. Response to a CB-free diet did not appear to be site specific. A history of OFG-associated gut involvement did not predict a response to the diet. The impact of dietary manipulation in patients with OFG can be significant, particularly with regard to oral inflammation. With the disease most prevalent in the younger population, a CB-free diet can be recommended as primary treatment. Subsequent topical or systemic immunomodulatory therapy may then be avoided or used as second line.

<h3>Introduction</h3> Orofacial granulomatosis (OFG) is a rare chronic inflammatory disease of unknown aetiology sharing histological features with gut Crohn9s disease (CD). A notes review of 207 patients with OFG aimed to define the common presentation of this condition and establish differentiating features between those with and without concurrent diagnosis of CD. <h3>Methods</h3> Data were extracted for age of onset, gender, clinical features, blood parameters, concurrent CD and treatments used. Diagnosis of CD was established by standard criteria. <h3>Results</h3> Ninety-seven out of 207 patients (47%) were female. Median age of disease onset was 23 years (range 2–73 years). Referrals were mainly sourced from maxillo-facial surgeons (31%) and gastroenterologists (19%). The buccal mucosa (74%) and lower lip (68%) were the most common sites involved followed by gingivae (63.5%) and upper lip (61%). Forty-six (22%) had CD. Ulcers (46% vs 15%, p&lt;0.001) and mucosal scarring (20% vs 5%, p&lt;0.001) were more common in patients with CD than in those without as was a raised C reactive protein (73% vs 49%, p=0.016), abnormal full blood counts (46% vs 23%) and low haemoglobin (31% vs 11%). The sulcus (27% vs 13%, p=0.019) and fauces (4% vs 0%, p=0.008) were significantly more likely to be affected in those with CD. Of the patients with concurrent CD, half were diagnosed with this prior to onset of OFG symptoms. Conversely 42.5% had OFG symptoms prior to diagnosis of CD. The remaining patients (7.5%) presented with symptoms and were diagnosed with CD within the same year. The predominant treatment used (86%) was the cinnamon and benzoate free diet. Topical treatments including antifungal and steroidal creams, ointments, mouthwashes and intralesional steroid injections were used in 64% of cases. Azathioprine was used in 39% of patients and anti TNF α therapy in 7.5% of patients. Only 3% of patients required cheiloplasty. <h3>Conclusion</h3> OFG most commonly presents with buccal and lower lip involvement. Abnormalities in inflammatory markers, haematinic deficiencies and oral presentation of ulceration and scarring are all factors which can increase the likelihood of concurrent CD. Initial presentation of OFG is not necessarily predictive of further development of CD.

To increase awareness of the unusual manifestations of extraintestinal Crohn's disease by reporting a solitary granulomatous lesion of the lower lip in a patient with Crohn's colitis. A biopsy of the lower lip was taken from a patient with active Crohn's disease who complained of swelling of the lips. A 53 year old female with long standing Crohn's disease (CD) described several months of discomfort and swelling of the lower lip. Physical examination revealed a fissure of the median line of the lower lip with swelling, that, on palpation, had a superficial granular texture and rubbery non pitting edema. Her serum chemistries, liver enzymes, CBC and CRP, were normal. Biopsy of the lip revealed small noncaseating granulomas, subepidermal lymphaedema, and inflammatory infiltrates. Cheilitis granulomatosa (CG) or Miescher's cheilitis, swelling of the lips, was first described in 1945, but its causes remain unknown. Allergic reactions to cobalt or food additives have been implicated. CG may be considered a subtype of oroafacial granulomatosis (OFG), which is the chronic swelling of the lips and the lower half of the face with oral ulcerations and hyperplastic gingivitis. Alone it can be viewed as a monosymptomatic variant of the Melkersson- Rosenthal syndrome (facial paralysis, swelling of the face and lips and furrows in the tongue). It has also been noted in systemic diseases sarcoidosis and CD. Only.5% of patients with CD ever develop CG. Pathological specimens may reveal non-necrotizing granulomas, edema, lymphangiectasia, and/or perivascular lymphocytic infiltration. Nevertheless, the diagnosis is made clinically based on a patient's history, symptoms and physical examination. Some authors believe a topical anesthetic with systemic corticosteroids is the most effective, while others recommend intralesional steroids. Jenss recommended local steroid therapy in patients on low dose systemic steroids if OFG occurs without gastrointestinal signs. Surgical intervention may only be considered if the disease in the quiescent stage and there is pronounced disfigurement. Although pathologically, the two entities appear grossly similar, it is unclear what the relationship is between cheilitis granulomatosa and Crohn's disease. Further immunological, microbiological and histological testing must be performed to delineate the similarities and differences between these two entities and further define their relationship.

BackgroundOrofacial granulomatosis (OFG) causes chronic, disfiguring, granulomatous inflammation of the lips and oral mucosa. A proportion of cases have co-existing intestinal Crohn’s disease (CD). The pathogenesis is unknown but has recently been linked to dietary sensitivity. Although allergy has been suggested as an aetiological factor in OFG there are few published data to support this link. In this study, we sought clinical evidence of allergy in a series of patients with OFG and compared this to a series of patients with inflammatory bowel disease (IBD) without oral involvement and to population control estimates.MethodsPrevalence rates of allergy and oral allergy syndrome (OAS) were determined in 88 patients with OFG using questionnaires, skin prick tests, total and specific serum IgE levels. Allergy was also determined in 117 patients with IBD without evidence of oral involvement (79 with CD and 38 with ulcerative colitis (UC)).ResultsPrevalence rates of allergy in patients with OFG were significantly greater than general population estimates (82% versus 22% respectively p = <0.0005). Rates of allergy were also greater in those with CD (39%) and, interestingly, highest in those with OFG and concurrent CD (87%). Conversely, whist OAS was common in allergic OFG patients (35%) rates of OAS were significantly less in patients with concomitant CD (10% vs 44% with and without CD respectively p = 0.006). Amongst CD patients, allergy was associated with perianal disease (p = 0.042) but not with ileal, ileocolonic or colonic disease location. Allergy in UC (18%) was comparable to population estimates.ConclusionWe provide compelling clinical evidence for the association of allergy with OFG whether occurring alone or in association with CD. The presence of gut CD increases this association but, conversely, reduces the expression of OAS in those with atopy. Interestingly, there is no evidence of increased allergy in UC.

Introduction Orofacial Granulomatosis (OFG) is a rare chronic inflammatory condition of unknown aetiology, characterised by lip swelling, orofacial erythema and ulceration. A proportion of OFG patients present with perianal disease in conjunction with their oral disease (‘top and tail’ disease). Perianal disease occurs in approximately one-third of Crohn’s Disease (CD) patients and is associated with significant morbidity and a more severe disease course. 1 Perianal disease has been shown to occur in 12% of patients with ileal CD (L1), 41–92% of colonic CD (L2) and 15% of ileocolonic disease (L3). 2 Method We retrospectively analysed a database of OFG patients. Patients with perianal disease were identified and compared to patients without perianal disease. The Montreal classification was used to classify the sites of patient’s CD. We set out to determine how many of our OFG patients had concurrent perianal disease and how many of them developed intestinal CD. Results 263 patients with OFG were identified, of which 208 patients (79.09%) had OFG only and 55 patients (20.91%) had concurrent intestinal CD. 36 patients (13.69%) had intestinal CD and no perianal disease. 19 patients ((7.22%) 13 male, median age 38 (IQR 25–49)) had intestinal CD and concurrent perianal disease. Within the perianal group, all patients had concurrent intestinal CD. The commonest sites were colonic (L2)(8/19; 42.11%) and ileocolonic (L3)(8/19; 42.11%). The ileum (L1) was affected in 1 patient (1/19; 5.26%) and 2 patients had concomitant upper gastrointestinal CD with ileocolonic disease (L3+L4)(2/19; 10.53%). The presence of OFG and perianal disease significantly increased the chances of developing intestinal CD (OR = 222, p = 0.0002, 2-tail Fisher Test). In the perianal group, 11/19 patients (11/19; 57.89%) were diagnosed with CD prior to developing OFG. The median time to diagnosis of OFG was 10 years after the diagnosis of intestinal CD. Conclusion Perianal disease in Crohn’s disease is common and is associated with a more severe disease course. 1 Perianal disease in OFG patients is less common, however, where it does occur it is always associated with intestinal CD in our cohort. Therefore, these patients should be investigated accordingly. The diagnosis of OFG was usually made later in the course of intestinal Crohn’s suggesting it is a later development. Disclosure of interest None Declared. References Ardizzone S, Porro GB. Perianal Crohn’s disease: overview. Dig Liver Dis . 2007; 39 :957–958 Schwartz D, Loftus EV, Tremaine WJ, et al . The natural history of fistulising Crohn’s disease in Olmsted County, Minnesota. Gastroenterology 2002;122:875–880

IntroductionCrohn's disease is a disease involving the whole gastrointestinal tract from the mouth to the anus. Oral lesions are considered to be an important extraintestinal manifestation. Granulomatous cheilitis has been recognized as an early manifestation of Crohn's disease. It may follow, coincide with or precede the onset of Crohn's disease. The aim of this presentation is to describe a rare case of a patient with Crohn's disease in whom significant swelling of the lower lip not only preceded the diagnosis of Crohn's disease for two years, but it manifested as an early clinical index of the recurrence of the intestinal disease as well.Case presentationA man aged 25 was admitted in our department on August 1999 with chronic diarrhea and loss of weight. His bowel symptoms started in 1998 at the age of 24. However, two years previously (June 1996) he noticed a swelling of the lower lip, which contrasted significantly with the previously normal appearance of his mouth. A lip biopsy performed at that time was compatible with granulomatous cheilitis. Crohn's disease involving the terminal ileum and large bowel was diagnosed in 1998 and confirmed on the basis of colonoscopy, enteroclysis and histology findings of the small and large bowel. Conservative treatment resulted in clinical and laboratory improvement of the bowel symptoms and lip swelling. During the following years the disease was active with exacerbations and remissions of mild to moderate severity. The swelling of the lower lip occurred in parallel with the exacerbations of the bowel disease, returning to normal during periods of remission.ConclusionSignificant swelling of the lower lip due to granulomatous cheilitis could be the first manifestation of Crohn's disease, preceding intestinal symptoms. Exacerbation of the lip lesion could be an early clinical sign of a relapse of the underlying intestinal disease.

<h3>Introduction</h3> Orofacial granulomatosis (OFG), including oral Crohn9s disease (CD) is a chronic inflammatory condition presenting characteristically with lip swelling but also affecting a number of other sites in the oral cavity. Bouts of acute swelling and frequently reported atopy suggest an allergic component. There is evidence for dietary triggers with objective improvement on a cinnamon and benzoate-free diet.1 The Oral Allergy Syndrome (OAS) is a well recognised condition with a clear immunological pathogenesis.2 There are similarities between OAS and OFG in terms of symptoms, triggers and treatment regimes. The role of allergy in inflammatory bowel disease (IBD) remains unclear with conflicting data in the literature. <h3>Methods</h3> We performed skin prick tests to common allergens in a cohort of 88 patients with biopsy proven OFG between August 2007 and July 2009. We measured Specific serum IgE levels to relevant allergens and total serum IgE levels. The prevalence of OAS in patients with OFG was also determined. For comparison, a group of 121 consecutive patients with a confirmed diagnosis of IBD without oral involvement were also studied. <h3>Results</h3> The incidence of clinical allergy of 82% in the OFG cohort was considerably higher than the 4–20% incidence reported in the general population. OAS incidence was 28%, also significantly higher than population estimates. OFG patients with disease onset below 30 years and no concomitant CD had a significantly higher incidence of allergy (95%) and OAS (38%). ImmunCAP and total serum IgE levels also confirmed increased allergy. Allergy in CD (39%) was higher than the general population, especially in the colonic (43%) and ileocolonic (52%) compared to the ileal group (24%). Allergy in Ulcerative colitis was comparable to population estimates (18%). <h3>Conclusion</h3> Patients with OFG have an astonishingly high incidence of allergy. A large proportion of patients have OAS. A novel subepithelial dendritic B cell population demonstrating class switching to IgE, described in oral biopsies from patients with OFG by our group, could provide the link between dietary antigens, chronic oral inflammation and symptoms of hypersensitivity.3 The comparative significance of the differences in allergy in the different IBD groups remains unclear.

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

PERSISTENT LIP AND FACIAL SWELLING IN A 9 YEAR OLD BOY

Orofacial granulomatosis in children: Think about Crohn's disease

Orofacial granulomatosis (OFG) is a rare chronic inflammatory disease of unknown etiology sharing histological features with Crohn's disease (CD). This study aimed to 1) define the clinical presentation of OFG, 2) establish differentiating features for those with CD, 3) examine if onset of OFG is predictive of CD, and 4) establish differentiating features for children. Data were extracted from medical notes (n = 207) for demographics, clinical features, blood parameters, diagnosis of CD, and treatment's for patients with OFG. Ninety-seven patients (47%) were female. The lips (184/203; 91%) and buccal mucosa (151/203; 74%) were mainly affected. Forty-six (22%) had intestinal CD. Ulcers (24/46; 46% versus 29/159; 15%, P = <0.001) were more common in patients with CD as was a raised C-reactive protein (24/33; 73% versus 60/122; 49%, P = 0.016) and abnormal full blood count (19/41; 46% versus 35/150; 23%). The buccal-sulcus (12/44; 27% versus 20/158; 13%, P = 0.019) was more often affected in those with CD. Half the patients with CD were diagnosed prior to onset of OFG. The remainder were diagnosed after. The incidence of CD is similar for children (16/69; 23%) and adults (29/132; 22%), although oral onset in childhood is more likely to occur prior to diagnosis of CD. OFG mainly presents in young adults with lip and buccal involvement. Abnormalities in inflammatory markers, hematology and oral features of ulceration, and buccal-sulcal involvement are factors more commonly associated with CD. Initial presentation of OFG does not necessarily predict development of CD, although this is more likely in childhood.