Intralesional Injections of a TNF-α Inhibitor to Treat Orofacial Granulomatosis.

We present the first documented case of successful treatment of orofacial granulomatosis by intralesional injections of a tumor necrosis factor α inhibitor to the lip. Our patient had rapid symptomatic improvement after 3 injections, and near resolution within 4 months of anti-tumor necrosis factor α therapy.

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.

Primary Periocular Orofacial Granulomatosis: Case Series and Systematic Review.

PURPOSE: There is no known optimal treatment for primary periocular orofacial granulomatosis (PPOFG), a disorder that results in periocular edema. This case series and systematic review identifies management strategies and their reported improvement. METHODS: Systematic review and case series. PubMed and MEDLINE databases were searched following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines to identify published cases of PPOFG. Cases were included when edema involved the periocular tissues and when a biopsy was interpreted to be PPOFG. Cases were excluded when edema did not involve the periocular tissues or when the edema was secondary to another process. The electronic medical records of the pathology department were studied to identify cases that were in keeping with PPOFG. The clinical charts were examined to confirm the diagnosis and provide a local case series. RESULTS: There are 38 published cases of PPOFG. An additional 9 cases were identified locally. These cases were combined and analyzed. Most PPOFG has eyelid swelling in isolation, without other facial swelling (36/47; 76.6%). It is most commonly a bilateral disease (30/47; 63.8%). Fissured tongue and facial nerve palsy occur, just as they do in other cases of orofacial granulomatosis. Treatment with surgical debulking or intralesional steroids resulted in high rates of symptomatic improvement of eyelid swelling, but recurrences were common. CONCLUSIONS: In light of no curative or highly successful treatment currently available, intralesional steroids and/or surgical debulking are therapies in the treatment of eyelid swelling associated with PPOFG that demonstrate reasonable short- and medium-term results. There is no established therapy that can offer disease remission or long-term symptom improvement.

Identification of Putative Bacterial Pathogens for Orofacial Granulomatosis Based on 16S rRNA Metagenomic Analysis.

Orofacial granulomatosis (OFG) is a chronic inflammatory disease characterized by nontender swelling of the orofacial tissues, the underlying cause of which remains unknown. Our previous study demonstrated that tooth apical periodontitis (AP) is involved in the development of OFG. To characterize the AP bacterial signatures of OFG patients and identify possible pathogenic bacteria that cause OFG, the compositions of the AP microbiotas in OFG patients and controls were compared using 16S rRNA gene sequencing. Pure cultures of putative bacterial pathogens were established by growing bacteria as colonies followed by purification, identification, and enrichment and then were injected into animal models to determine the causative bacteria contributing to OFG. A specific AP microbiota signature in the OFG patients was shown, characterized by the predominance of phyla Firmicutes and Proteobacteria, notably members of the genera Streptococcus, Lactobacillus, and Neisseria, were found. Streptococcus spp., Lactobacillus casei, Neisseria subflava, Veillonella parvula, and Actinomyces spp. from OFG patients were isolated and successfully cultured in vitro and then injected into mice. Ultimately, footpad injection with N. subflava elicited granulomatous inflammation. IMPORTANCE Infectious agents have long been considered to play a role in the initiation of OFG; however, a direct causal relationship between microbes and OFG has not yet been established. In this study, a unique AP microbiota signature was identified in OFG patients. Moreover, we successfully isolated candidate bacteria from AP lesions of OFG patients and assessed their pathogenicity in laboratory mice. Findings from this study may help provide in-depth insights into the role of microbes in OFG development, providing the basis for targeted therapeutic approaches for OFG.

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.

Management of orofacial granulomatosis.

Orofacial granulomatosis is a chronic relapsing-remitting inflammatory condition that shares a similar phenotypic presentation to some other granulomatous diseases, particularly Crohn's disease. However, subtle clinical and pathological differences justify it as a separate disease entity. Previous studies have assessed the effectiveness of interventions used in the management of orofacial granulomatosis. This article reviews the management options available. A literature search was conducted to identify studies, in English, which assessed the effect of non-pharmacological and pharmacological interventions in the treatment of orofacial granulomatosis. The interventions were categorised into dietary modification, pharmacological (topical, intralesional and systemic therapy), surgery and psychological. A combination of interventions is often required to effectively manage each patient. There is convincing evidence that diet plays a role in disease severity. In patients where dietary manipulation alone is unsuccessful, topical, intralesional and/or systemic treatment may be considered to manage the condition.

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.

Diagnostic delay in autoimmune oral diseases.

Autoimmune diseases (ADs) affect about 5% of the general population, causing various systemic and/or topical clinical manifestations. The oral mucosa is often affected, sometimes as the only involved site. The misdiagnosis of oral ADs is an underreported issue. This narrative review focuses on diagnostic delay (DD) in oral ADs (oral lichen planus [OLP], oral Pemphigus Vulgaris, mucous membrane pemphigoid, oral lupus erythematosus, orofacial granulomatosis, oral erythema multiforme [EM], and Sjogren syndrome). Extensive literature research was conducted via MEDLINE, Embase and Google Scholar databases for articles reporting the time spent to achieve the correct diagnosis of oral ADs. Only 16 studies reported DD in oral ADs. Oral autoimmune vesiculobullous diseases are usually diagnosed after 8 months from the initial signs/symptoms, the Sjogren Syndrome diagnosis usually requires about 73 months. No data exist about the DD in OLP, oral lupus erythematosus, orofacial granulomatosis, and oral EM. The diagnosis of oral ADs can be difficult due to the non-specificity of their manifestations and the unawareness of dentists, physicians, and dental and medical specialists about these diseases. This can lead to a professional DD and a consequential treatment delay. The delay can be attributed to the physicians or/and the healthcare system (Professional Delay) or the patient (Patient's Delay).

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.

Disease-related burden and long-term outcome in orofacial granulomatosis: observations from a large single-centre cohort.

There is a lack of standardized treatment recommendations for orofacial granulomatosis, a chronic inflammatory condition aetiologically related to Crohn disease. To assess clinical baseline parameters and treatment strategies, we retrospectively analysed 61 consecutive cases from our institutional database. Disease-related functional/psychological impairment and long-term outcomes were descriptively evaluated using a standardized self-reporting questionnaire. The median age of patients was 45 (7-77) years. Oral steroids were given in 41.0% of cases, but only produced short-term disease control, while response to steroid-sparing agents was inconsistent. Only a minority of patients reported relevant disease-related functional impairment in eating (21.7%) or speaking (4.3%), but the majority perceived psychological distress due to the cosmetic aspects of the disease (69.6%), comments from others (65.2%) and/or general anxiety/insecurity (73.9%). Regardless of the initial treatment, long-term outcomes after 71 months (range 7-304 months) were beneficial, with most patients being in complete remission (52.2%) or reporting only mild residual swelling (43.5%).

Current treatment modalities in granulomatous cheilitis.

BACKGROUND: Granulomatous cheilitis (GC) is a poorly understood disorder of the labial mucosa, which is a subtype under an umbrella term "orofacial granulomatosis." Several treatment modalities have been tried in the management of GC with suboptimal to optimal results. OBJECTIVE: The objective of this article is to discuss various treatment modalities, whether medical or surgical, that have been tried for the management of GC with success. METHODS: A comprehensive literature search was performed to screen articles related to the successful treatment of GC. Articles published in journals indexed in PubMed were searched along with those in Google Scholar. There was no availability of systematic review or meta-analysis on treatment of GC in the literature search. Recent data has been collected and consolidated from various case reports and case series to provide a concise overview of various treatments applied in GC. RESULTS: Various treatment modalities have been used in GC including glucocorticoids, antibiotics, immunomodulatory, and biological agents, surgical debulking, and laser therapy. No treatment modality has provided a predictable success. Intralesional corticosteroid therapy has been used more frequently either alone or in combination with other modalities.

Orofacial Granulomatosis Treated With Combination of Intralesional Steroids and Hydroxychloroquine.

This article presents a case of a 39-year-old woman with spontaneous lip swelling with gingival erythema. The case report discusses orofacial granulomatosis, a condition that often poses diagnostic and management challenges. Additionally, the article emphasizes the importance of establishing a definitive diagnosis of this disease, which has similar clinical and histological features to other oral and systemic conditions. Finally, a successful management approach is discussed that uses combination therapy consisting of intralesional steroid injections and oral hydroxychloroquine.

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.