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.

Detailed Follow-up Study of Pediatric Orofacial Granulomatosis Patients.

OBJECTIVES: Orofacial granulomatosis (OFG) is a chronic inflammatory condition affecting the orofacial area. Its connection to Crohn disease (CD) is debated. Our aim was to describe a cohort of pediatric patients with OFG in detail, study the long-term behavior of OFG, and evaluate factors predicting CD in patients with OFG. METHODS: We invited patients diagnosed with OFG at 2 university hospitals, Finland for a follow-up appointment. Patients (n = 29) were examined by a dentist and an otorhinolaryngologist using a structural schema. Orofacial findings were also recorded using digital photographing. Patients filled in questionnaires about general health and special diets. Patients' nutrition was evaluated from food records. The findings were compared between patients with OFG only and OFG with CD. RESULTS: Patients with CD had more findings in the orofacial area (total score for orofacial findings median 11) compared to patients with OFG only (total score median 7.5). There was no statistically significant difference in the type of lesions between these groups, except the upper lip was more often affected in patients with CD (n = 11) than in patients with OFG only (n = 0). Most of the patients had normal otorhinolaryngological findings. All patients with elevated anti-Saccharomyces cerevisiae antibody A levels had CD (n = 6) and they presented with more orofacial findings (total score) than patients with normal levels of anti-S cerevisiae antibody A (P = 0.0311). CONCLUSIONS: Long-term follow-up of pediatric-onset patients with OFG shows good prognosis. Patients with OFG do not seem to have otorhinolaryngological comorbidity. Anti-S cerevisiae antibody A may serve as a factor to indicate the possible presence of underlying CD in patients with OFG, but further studies are requested.

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.

Impact of chronic oral mucosal disease on daily life: preliminary observations from a qualitative study.

OBJECTIVE: To explore the experience of daily life of persons with chronic oral mucosal conditions. METHODS: Purposive sampling was used to recruit patients from the Oral Medicine Unit of Cork University Dental School and Hospital. An experienced independent facilitator convened the focus groups and conducted individual interviews in a non clinical setting. Focus groups were mixed with regard to gender, age, chronic oral mucosal condition, time since diagnosis and severity. A total of 24 patients took part, including patients with oral lichen planus, mucous membrane pemphigoid, pemphigus vulgaris, recurrent aphthous stomatitis and orofacial granulomatosis. RESULTS: Analysis of the interviews revealed that patient views could be divided into the following themes - biopsychosocial issues, treatment limitations and side effects, unpredictability of the conditions and the potential for malignant transformation and issues for the healthcare professionals. CONCLUSION: Chronic oral mucosal conditions impact upon the experience of daily life of patients in a variety of areas from physical health and functioning, to concerns about their future. The role of the oral medicine practitioner in treating patients with chronic oral mucosal diseases extends beyond active management and symptomatic relief to the management of all aspects of these conditions that impact upon their daily lives.

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.

Diagnosis and Treatment of Orofacial Granulomatosis.

Orofacial granulomatosis (OFG) is a chronic inflammatory disorder characterized by lip swelling and gingival alterations. OFG occurs either as a separate clinical entity or associated with a systemic disorder such as Crohn's disease (CD). The purpose of this paper is to report the case of a 13-year old boy who presented with marked granulomatous gingival inflammation and stomach discomfort. Periodontal therapy resulted in only slight reduction in gingival inflammation and enlargement. The diagnosis of OFG, which was evidently associated with inflammation in the bowel, was based on the gingival status and biopsy, self-reported symptoms, and laboratory markers of iron metabolism and fecal calprotectin level. The gingival and bowel inflammation was controlled with, strict adherence to a cinnamon- and benzoate-free diet combined with periodontal prophylaxis. At this point at the age of 17 years, the patient has avoided the use of immune modulatory treatments.

A Systematic Review of the Literature of the Three Related Disease Entities Cheilitis Granulomatosa, Orofacial Granulomatosis and Melkersson - Rosenthal Syndrome.

BACKGROUND AND OBJECTIVE: Melkersson Rosenthal syndrome (MRS) is a rare disorder of unknown etiology and comprises the triad: orofacial edema, recurrent facial paralysis and lingua plicata. In the current literature confusing heterogeneity exists, mixing together the historically grown terms cheilitis granulomatosa or granulomatous cheilitis, Melkersson Rosenthal syndrome and the umbrella term Orofacial Granulomatosis (OFG). METHODS: We provide a systematic review comprising all three disease entities of orofacial granulomatosis using the computerized database "Pubmed Medline" entering the keywords "orofacial granulomatosis" (141 references), "Melkersson-Rosenthal syndrome" (207 references), "granulomatous cheilitis" or "cheilitis granulomatosa" (102 references) back to 1956. Full-text journals and case studies were included, and data synthesis was performed individually. RESULTS: Etiology remains unclear for all three disease entities. Etiological relatedness to chronic inflammatory bowel disease is under discussion and effectiveness was found for different treatments, e.g. local triamcinolone injections, antibiotics, surgical interventions, TNF alpha blockers or exclusive enteral nutrition. No randomized controlled trial concerning the therapy of orofacial granulomatosis was found. As a consequence, the therapeutic conclusion is drawn mainly from small case series, thus limiting the evidence of therapeutic interventions. CONCLUSION: OFG with the sub-entities MRS and cheilitis granulomatosa is an etiological obscure disease process with various possible therapeutic interventions potentially alleviating the disease course but to broaden treatment knowledge further study in randomized controlled trials is needed.

Orofacial granulomatosis: A case report of three cases may be caused by apical periodontitis.

RATIONALE: Orofacial granulomatosis (OFG) is a rare disease characterized by noncaseating granulomatous inflammation. The most common clinical presentation is persistent swelling of the soft tissues in the oral and maxillofacial regions. The precise cause of OFG is unknown. Corticosteroids are the first-line and best treatment, but there is lack of uniform treatment prescription and standard. It is important to identify the pathogen in order to improve treatment specificity. PATIENT CONCERNS: Three patients presented with recurring lip swelling and cobblestone formation on buccal mucosa, complained of toothache or dental caries for many years. They had very similar and characteristic clinical signs, especially the corresponding location with infected teeth, which suffered from apical periodontitis. DIAGNOSES: The three patients were all diagnosed with typical clinical signs and non-caseating epithelioid cell granulomas histologically. INTERVENTIONS: The teeth with apical periodontitis were extracted or treated and corticosteroids were prescribed locally or/and systematically. OUTCOMES: A complete resolution of lip swelling and cobblestone formation were shown after treatment. LESSONS: This is the first report to highlight that apical periodontitis may intrigue the pathogenesis of OFG, which suggested that dental infection may be the direct and initial etiology of OFG. Removal of infected teeth should be performed as soon as possible in order to reduce the dosage of corticosteroids and occcurence rate of OFG.

Update on Orofacial Granulomatosis.

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.

The role of exclusive enteral nutrition in the management of orofacial granulomatosis in children.

BACKGROUND: Orofacial granulomatosis (OFG) is a term used to describe a persistent, painless swelling of lips and orofacial region. It can be associated with ulceration, gingival hypertrophy and cobble stone appearance of the buccal mucosa. OFG is commonly associated with Crohn's disease and can precede the intestinal manifestation of the disease. Exclusive enteral nutrition (EEN) is a recognized treatment for induction of remission for Crohn's disease. The aim of this study was to review the use of EEN in the management of OFG in children. METHODS: Retrospective review of medical records of all children diagnosed with OFG between 2007 and 2012 was conducted. Presence of comorbidities, progression to inflammatory bowel disease (IBD) and response to EEN was evaluated. RESULTS: Twenty-nine children were included, mean age at diagnosis was 9 years (standard deviation 3.9) years. Ten children had isolated OFG and 19 had OFG and IBD, of which 12 presented with OFG and IBD and 7 developed IBD later. Median time to progression to IBD was 33 months (inter quartile range: 9.8-85.5). Twenty-two children completed 6 weeks of EEN, and 19 showed clinical improvement in the OFG appearance. CONCLUSION: EEN appears to be an effective treatment option for children with isolated OFG or OFG and IBD.

Recurrent lip swelling: a diagnostic challenge.

A Caucasian woman in her late 20s was referred to the allergy/chest clinic by her general practitioner with an 8-month history of recurrent facial angio-oedema. She had no history of urticaria or airways symptoms and denied any similar problems previously. She had no family history of similar illness and was not on any regular medications. There was no history of atopy. Initially, a clinical diagnosis of idiopathic angio-oedema was made. Despite being treated with several antihistamines with doses equivalent to 40 mg of cetirizine/day, her problem had failed to respond satisfactorily. Later on, she also revealed history of intermittent gastrointestinal symptoms such as abdominal pain and diarrhoea. Routine investigations were unremarkable. The patient was referred to a dermatology clinic and a diagnosis of orofacial granulomatosis was suggested: a rare granulomatous disease presenting with lip enlargement, which may or may not be associated with Crohn's disease. A biopsy of the oral mucosa was consistent with this diagnosis.

Leishmaniasis cutáneo-mucosa: presentación de un caso con compromiso medio-facial / Mucocutaneous leishmaniasis: report of a case with midd lefacial commitment / Lehismaniasis mucocutânea: apresentação de um caso com o compromisso mid-facial

La leishmaniasis es una zoonosis parasitaria causada por protozoos. Puede afectar la piel y las mucosas o presentarse como una enfermedad visceral. La variedad mucocutánea conduce a la destrucción parcial o completa de las membranas mucosas de la nariz, las fauces y la faringe. Aproximadamente un 90% de los casos con afectación mucocutánea se producen en Brasil, Bolivia y Perú. En nuestro país afecta en forma endémica a las provincias del norte desde principios del siglo XX. Se relata el caso de un paciente de 53 años con odinodisfagia de aproximadamente 6 meses de evolución, asociado a formaciones granulomatosas medio- faciales, en el que se diagnosticó leishmaniasis cutaneomucosa mediante el rescate de amastigotes en muestras tomadas de lesiones de paladar blando para estudio anatomopatológico con tinción de Giemsa. Se realizó tratamiento con meglumina antimoniato con buena evolución clínica a partir de los quince días de instaurado el mismo.

Leishmaniasis is a parasitic zoonosis caused by protozoa. It can affect skin, mucous membranes or presented as visceral disease. Mucocutaneous variety leads to partial or complete destruction of the mucous membranes of the nose, mouth and pharynx. Approximately, 90% of cases with mucocutaneous involvement occurs in Brazil, Bolivia and Peru. In our country it affects endemic to the northern provinces since the beginning of the century. The case of a 53-year-old patient with odinodisphagia of approximately 6 months of evolution, associated with mid-facial granulomatous formations in which cutaneomucous leishmaniasis was diagnosed by rescue of amastigotes in samples taken from lesions of soft palate for anatomopathological study with Staining of Giemsa. Treatment with meglumina antimonia was carried out with good clinical evolution from the fifteen days of the same establishment.

A leishmaniose é uma zoonose parasitária causada por protozoários. Ele pode afectar a pele e membranas mucosas ou presente como doença visceral. variedade mucocutânea conduz à destruição parcial ou completa das membranas mucosas do nariz, boca e faringe. Aproximadamente 90% dos casos com envolvimento mucocutânea ocorrem no Brasil, Bolívia e Peru. Em nosso país que afeta endêmica para as províncias do norte, desde o início do século XX. O caso de um odinodisfagia 53 anos, aproximadamente, 6 meses evolução associada com formações granulomatosas mediofaciais em que a leishmaniose mucocutânea foi diagnosticada por resgatar amastigotas em amostras tomadas a partir de lesões do palato mole para estudo histopatológico contou Giemsa. O tratamento foi realizado com antimoniato de meglumina com boa evolução clínica a partir de quinze dias introduzidas ele.

Service evaluation of patients with orofacial granulomatosis and patients with oral Crohn's disease attending a paediatric oral medicine clinic.

AIM: Presenting features associated with orofacial granulomatosis (OFG) and oral Crohn's disease (OCD) are varied, making successful diagnosis and management difficult. The aim of this service evaluation was to establish a profile of patients with these conditions attending a paediatric oral medicine clinic and to determine their overall satisfaction with the care received. STUDY DESIGN: A retrospective case note analysis to establish the patient profile and a postal patient satisfaction questionnaire for service evaluation. METHODS: All patients with OFG and OCD who had attended the joint paediatric dentistry/oral medicine clinic at Charles Clifford Dental Hospital, Sheffield in the previous 14 years were included in the study. Hospital case notes were retrospectively reviewed and patient demographics, clinical features, investigations, diagnosis, treatment and outcomes of treatment were recorded. An anonymous patient satisfaction questionnaire using the Healthcare Satisfaction Generic Module of the Paediatric Quality of Life Inventory (PedsQLTM) was distributed to all patients by mail. RESULTS: A total of 24 patients (13 females and 11 males) were identified. Median age at presentation was 11 years (SD± 3.79, range 2-15). Fifteen patients (63%) were diagnosed with OCD, and 9 (37%) with OFG. Overall, the most common orofacial feature was oral ulceration (75%) followed by lip/facial swelling (71%), angular cheilitis (67%) and mucosal cobblestoning (67%). Differences in presentation were seen between the two conditions with oral ulceration (87%) and mucosal cobblestoning (80%) being the most frequently observed features of OCD and lip swelling (78%) and angular cheilitis (67%) being the most common features of OFG. 58% of patients reported relief of symptoms through treatment. Thirteen patient satisfaction questionnaires were completed (54%). 85% (n=11) felt the overall care received in the clinic was 'excellent'. CONCLUSIONS: This service evaluation highlights the variety of presenting features of OFG and OCD. Despite only a moderate response to treatment, patient satisfaction with the service was high, emphasising the importance of good communication when managing children with chronic, debilitating conditions.

Orofacial granulomatosis in children--a challenge for diagnosis and treatment.

The data on orofacial granulomatosis, OFG, in children are sparse. We describe here 8 pediatric patients presenting with OFG, 2 of these cases associating with Crohn's disease. Therapeutic agents included systemic immunosuppressants such as glucocorticoids, methotrexate, anti-TNF-alpha agent, dapsone, antibiotics (metronidazole), and local treatment with topical tacrolimus or intralesional injections of triamcinolone hexacetonide. The treatment response ranged from good to poor results. The number of young patients suffering from OFG is not currently known and there are no gold standards for treatment. Thus, prospective follow-up studies on these patients are needed to gain more experience of the therapeutic responses.

Orofacial granulomatosis associated with hypersensitivity to dental amalgam.

Orofacial granulomatosis is a clinicopathologic entity characterized by chronic swelling of the lip and possible soft tissues in the orofacial region owing to granulomatous inflammation of unknown cause. We present 3 cases of orofacial granulomatosis associated with allergic contact dermatitis to dental materials. Previous treatment with corticosteroids did not have any therapeutic effect. Patch testing revealed a positive reaction to several allergens, including dental amalgam and mercury in 2 cases. A lymphocyte transformation test modified for metals was used to evaluate lymphocyte reactivity. After the removal of the suspected allergens, all patients experienced recovery within 1 month, with the exception of the lip swelling, which gradually subsided over several months.