Orofacial granulomatosis with gingival manifestation – A rare case report

Oro-facial granulomatosis (OFG) is a rare 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. Histologically, OFG resembles Crohn's disease (CD), and a number of patients with CD have oral involvement identical to OFG. However, the exact relationship between OFG and CD remains unknown. Thirty-five patients with OFG and no gut symptoms were identified from a combined oral medicine/gastroenterology clinic. All underwent a standardized assessment of the oral cavity and oral mucosal biopsy to characterize the number of sites affected and the type of inflammation involved. Hematological and biochemical parameters were also recorded. All 35 patients underwent ileocolonoscopy and biopsy to assess the presence of coexistent intestinal inflammation. Ileal or colonic abnormalities were detected in 19/35 (54%) cases. From gut biopsies, granulomas were present in 13/19 cases (64%). An intestinal abnormality was significantly more likely if the age of OFG onset was less than 30 years (P=0.01). Those with more severe oral inflammation were also more likely to have intestinal inflammation (P=0.025), and there was also a correlation between the histologic severity of oral inflammation and the histologic severity of gut inflammation (P=0.047). No relationship was found between any blood parameter and intestinal involvement. Endoscopic and histologic intestinal abnormalities are common in patients with OFG with no gastrointestinal symptoms. Younger patients with OFG are more likely to have concomitant intestinal involvement. In these patients, granulomas are more frequent in endoscopic biopsies than reported in patients with documented CD. OFG with associated intestinal inflammation may represent a separate entity in which granulomatous inflammation occurs throughout the gastrointestinal tract in response to an unknown antigen or antigens.

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.

Introduction: Extra-intestinal manifestations (EIMs) of inflammatory bowel disease (IBD) are rare complications that affect roughly 6-25% of IBD patients. Orofacial granulomatosis (OFG) is a rare manifestation that does not have reliable epidemiologic data and is characterized by orofacial swelling with non-caseating granulomas seen on pathology. Case Description/Methods: A 23-year-old male with a history of Crohn’s colitis presented with loose stools and hematochezia for 7 months and 1 year of left sided lip swelling. He was diagnosed with Crohn’s disease at age 15 and was maintained on oral mesalamine and 6-mercaptopurine (6-MP). At age 16, the patient was evaluated for supraglottic edema. Urgent tonsillectomy was performed, with pathology revealing necrotizing and non-caseating granulomas. He recovered without complication. He achieved endoscopic remission at age 18 and his medications were discontinued. Unfortunately, he was lost to follow-up. During this subsequent presentation, his vitals were within normal limits. Exam was notable for left-sided lip and cheek swelling without mass or lesion. Bloodwork was notable for an ESR of 19 and CRP of 7.5. Lip biopsy showed normal squamous epithelium and non-caseating granulomas, consistent with OFG. Patient was treated for a Crohn’s flare with oral prednisone as a bridge to 6-MP. His OFG was treated with intralesional corticosteroids without relief and has on-going outpatient follow up. His current treatment plan includes further cycles of steroid injections before considering alternative therapies. His most recent colonoscopy showed endoscopic and histologic remission of his luminal Crohn’s while on infliximab. (Figure) Discussion: OFG is frequently seen as a manifestation of a systemic condition such as IBD. OFG is diagnosed by biopsy and clinical suspicion. OFG specific treatments include topical steroids and calcineurin inhibitors. Recent data suggests that a cinnamon/benzoate free diet may provide modest benefit to patients. Adequate treatment of underlying IBD is equally important. This patient has the classic symptoms and histopathologic findings of OFG and likely had undiagnosed OFG for many years given his tonsillar pathology years prior. Despite treatment, this patient has persistent and refractory symptoms. This case highlights a classic presentation of a rare IBD extra-intestinal manifestation and demonstrates how EIMs can occur even with well controlled IBD.Figure 1.: Orofacial Granulomatosis: Lip and Cheek Swelling.

<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.

<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.

Cheilitis granulomatosa (CG) and plasma cell gingivitis (PCG) are uncommon inflammatory conditions affecting the oral regions. CG manifests as chronic lip swelling with granulomatous inflammation, while PCG presents as erythematous gingiva or gingival enlargement linked to hypersensitivity reactions. Their simultaneous occurrence is exceedingly rare, posing diagnostic and therapeutic challenges. A 32-year-old woman presented with recurrent upper lip swelling and gingival enlargement. Clinical examination revealed erythematous gingiva with a cobblestone texture and angular cheilitis. Biopsies confirmed orofacial granulomatosis with epithelioid granulomas and PCG with plasma cell infiltration. Management consists of diet modification and periodontal intervention. Postoperative outcomes demonstrated significant improvement, and allergen elimination strategies were implemented to reduce recurrence. At 9 months of follow-up of the patient, there was significant improvement in signs and symptoms with no signs of recurrence. This case highlights the rare co-existence of CG and PCG, emphasizing the need for a comprehensive diagnostic approach to exclude systemic causes. Successful management requires pharmacological treatment, surgical interventions, and dietary modifications. Long-term follow-up is essential to monitor recurrences and maintain clinical stability. Because of the rare co-occurrence of cheilitis granulomatosis (CG) and plasma cell gingivitis (PCG), which creates unique diagnostic and therapeutic hurdles, this case offers new information. Additionally, it presents an effective treatment plan that concurrently addresses both problems. A comprehensive strategy is necessary for the successful management of PCG and CG. Systemic disorders must be ruled out since they might exhibit similar symptoms. Dietary changes, nonsurgical, and surgical periodontal therapy are all part of the therapy plan. In order to avoid recurrence and guarantee a long-lasting recovery, long-term monitoring and regular elimination of allergens and irritants are essential. The possibility of the problem recurring is one of the main obstacles to this case's success. Reducing the chance of recurrence requires adhering to dietary changes and getting rid of allergens. Additionally, before initiating any kind of treatment, systemic disorders must be ruled out. Cheilitis granulomatosa (CG) and plasma cell gingivitis (PCG) are two uncommon conditions that affect the oral cavity. In this case report, a 32-year-old female patient presented with swelling of the lip and enlargement of the gums. There was a presence of cracks at the corners of the mouth, along with redness of gums with uneven texture. Investigations were done to rule out other possible causes of the same. Histopathological analysis of the lip and gums confirmed the diagnosis of CG and PCG. The patient was treated with non-surgical and surgical periodontal therapy, along with education to avoid possible allergens in her diet. Symptomatic relief occurred after the therapy. The patient was followed up for up to 9 months, and there were no signs of recurrence of the condition.

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.

Granulomatous cheilitis (GC) is a very rare disorder of unknown etiology. Clinically, GC is characterised by recurrent swelling of the labial tissues, which may be followed by a permanent enlargement. Histologically, the typical form of GC is characterised by the formation of scattered aggregates of non-caseating granulomas. GC is the most frequent sign of orofacial granulomatosis, a disorder under which also encompasses sarcoidosis, Crohn's disease, atypical tuberculosis, Anderson-Fabry disease, possibly some allergic reactions, and Melkersson-Rosenthal syndrome (MRS). Some consider GC as an oligosymptomatic or monosymptomatic form of MRS. In this study we examined the clinical records of six patients presenting with GC which were examined and treated in the Department of Oral Medicine and Pathology of the Dental School of Aristotle University of Thessaloniki (Greece) during a 16-year period. In five of six patients a persistent swelling of the lower lip was recorded, one of whom also developed swelling in the upper lip. In one case the swelling was present in both lips and in another the GC was the only clinical finding, while in the other five cases it was accompanied by at least one other feature of MRS. In five cases, the histological picture revealed non-caseating granulomas. The treatment with the intralesional infusion of corticosteroids in three cases and the oral administration of corticosteroids in two cases was successful. One of the patients refused to be treated. This patient also presented later with permanent swelling of the upper lip.

NOT ALL LIP SWELLING IS ANGIOEDEMA

Granulomatous cheilitis is a rare granulomatous disorder characterized by a recurrent firm swelling of one or both lips. This is called the cheilitis granulomatosa of Miescher (CGM) when it occurs in isolation. It is called Melkersson-Rosenthal syndrome (MRS) if the classical triad of recurrent or persistent orofacial edema, plicated or fissured tongue (lingua plicata), and relapsing peripheral facial nerve paralysis is present. A 40-year-old female patient came to the Dermatology Department with persistent painless swelling of both lips and perioral area for the last one year. On histopathological examination there was a nodular tuberculoid granulomatous inflammation in patchy pattern present throughout the submucosa. The granuloma consists of lymphocytes, histiocytes and occasional plasma cells. AFB stain and PAS stain were negative. Diagnosis of granulomatous cheilitis was made and patient was put on tab clofazimine and intralesional corticosteroids. The case is being reported due to its rarity and the role of dermatopathologist to make a diagnosis.

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.

Cheilitis granulomatosa (CG) is a cosmetically disturbing and persistent idiopathic lip swelling. It is one manifestation of orofacial granulomatosis (OFG), which is a clinical entity describing facial and oral swelling in the setting of non-caseating granulomatous inflammation and in the absence of systemic disease such as Crohn's disease and sarcoidosis. CG can occur by itself or as part of the Melkersson-Rosenthal syndrome, which includes facial palsy and a plicated tongue. Other proposed causes of OFG include dietary allergens such as cinnamon and benzoates. Similar orofacial swelling may be an early manifestation of Crohn's disease or sarcoidosis, and so clinical history is important in diagnosis. The cause of CG has not been wholly elucidated, but a current hypothesis holds that a random influx of inflammatory cells is responsible. Other granulomatous and edematous causes of lip swelling must be investigated prior to diagnosis. Options for treatment include dietary modifications, antibiotics, systemic or intralesional corticosteroids, and surgery, although treatment is not always necessary. CG should be considered in the differential of persistent lip swelling.

PERSISTENT LIP AND FACIAL SWELLING IN A 9 YEAR OLD BOY

Introduction: In 1985 Wiesenfeld et al., suggest the terminology of “Orofacial granulomatosis (OFG)” to explain a chronic granulomatous lesion that involving the orofacial area include the lip, face and oral cavity, the histopathological examination usually associated with noncaseating granulomas and multinucleated Langhans‑type giant cells Aim of Reporting This Case: The aim of reportioning this case is highlighting the awareness of orofacial granulomatosis disease after excluding all diseases that has granulomatous lesion Case presentation: A 30-year-old male patient was referred to the oral medicine clinic due to swelling of the upper lip and redness of the gingiva. Clinical examination revealed a nodular lesion in the central area of the upper lip with a firm sensation upon palpation. Additionally, there was slight redness in the gingiva. The patient was medically fit, and our clinical differential diagnoses included Crohn’s disease, Wegener's granulomatosis, sarcoidosis, and orofacial granulomatosis. Lab tests requested for the patient included CBC, ACE, ESR, and CRP. All investigations yielded negative results.The patient was also referred to internal medicine for endoscopy.A biopsy was taken from the inner area of the upper lip under local anesthesia (1.8 mL of lidocaine with epinephrine) and sent for histopathological evaluation. The histopathology report showed non-caseating granulomas, confirming the final diagnosis of orofacial granulomatosis. Intra-lesional injection of triamcinolone acetonide (40 mg/10 mL) was initiated. At the 2-week follow-up visit, the patient reported softening of the upper lip, though the redness persisted. Conclusion: Swelling in the upper lip can have various potential causes, including Crohn’s disease, Wegener’s granulomatosis, sarcoidosis, and orofacial granulomatosis. Greater awareness of the oral manifestations of these conditions is essential for accurate diagnosis and effective treatment.

Orofacial granulomatosis is a relatively recent term coined by Weinsfeld et al in 1995 to describe the presence of oral granulomatous lesions without intestinal involvement. It could manifest either as a triad involving facial nerve, lip swelling, fissured or furrowed tongue referred to as Melkerson Rosenthal Syndrome (MRS) or its monosymptomatic or oligosymptomatic forms referred to as Granulomatous Cheilitis (GC). 31-year-old Caucasian male with complaints of painful swelling of the lips with recurrent oral ulcers and difficulty eating for 3 years. Exam was significant for painful, right-sided lip, tongue, and facial swelling with an 8 mm shallow intraoral ulcer. ESR, quantiferon tb, celiac panel, ACE levels, heavy metal and food allergen test were negative ASCA antibodies were positive but EGD, CT- enterography and colonoscopy which showed no evidence of intestinal involvement. Biopsy of oral lesion revealed multiple non-caseating granulomas with multinucleated giant cells consistent with granulomatous cheilitis. Patient did not respond to dapsone, oral and intralesional corticosteroids, so infliximab 10 mg/kg induction dose followed by 10 mg/kg every 4 weeks was started with resolution of the swelling and ulcers. Granulomatous cheilitis is a persistent, relapsing remitting, idiopathic, non-tender swelling of one or both lips. The etiology is unknown, however relationship to crohn's disease, sarcoidosis and various infectious and allergens has been reported but none has been validated. There is a distinct clinical entity backed by genetic studies which have suggested that OFG may have a different HLA profile than Crohns disease. Topical, systemic and intralesional corticosteroids have been used with variable outcomes. Infliximab was first reported for the treatment of orofacial Crohns in 2001.There have been 5 other case reports that have described the use of Infliximab or adalimumab for the treatment of OFG. The dose of Infliximab used in most of those studies was 3-5 mg/kg and the duration of treatment varied from 3 weeks to 21 month. Our patient had resolution of lesions with 10 mg/kg of infliximab and has had sustained response for the past 8 months. In conclusion, we believe that OFG is a distinict entity seperate from Crohns disease and high dose Infliximab should be considered an alternative treatment options in patients who do not respond to other treatment regimens.