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

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

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

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

An uncommon case of lip swelling: Granulomatous cheilitis associated with Crohn's disease.

Unbeknownst to most otolaryngologists, there is quite a range of oral manifestations which commonly manifest in the context of inflammatory bowel disease. As providers who will encounter such patients in consultation it is beneficial to be aware of that association. Lip swelling (granulomatous cheilitis) is just one such presentation, which is often otherwise mistaken for angioneurotic edema and can lead to unwarranted testing and misdirected treatment. We present such a case to highlight the educational value of this patient encounter.

Oral lymphangiectasia and gastrointestinal Crohn disease.

Lip edema with non-caseating granulomas or lymphangiectasia pose a clinical and pathological challenge. These findings can be attributed to cheilitis granulomatosa (CG), Melkersson-Rosenthal syndrome (MRS), or Crohn disease (CD) depending on the appropriate clinical context. Lymphangiectasis, in particular, is a common pathological finding in CD due to lymphatic obstruction by granulomas and intralymphatic granulomas. Because oral symptoms can precede gastrointestinal symptoms of CD or be seen in patients with asymptomatic gastrointestinal disease, the identification of lymphangiectasia should raise the possibility of underlying CD. We present a case of a young woman with several years of lip swelling, with notable lymphangiectasia and subtle granulomas on pathological evaluation. The patient was diagnosed with MRS at an outside institution and treated with systemic steroids, without further systemic evaluation. We believe that early recognition of lymphangiectasia and consideration of CD early in the work-up are critical for early diagnosis and appropriate management. Neither clinical nor histopathological findings should be used in isolation to diagnose GC, MRS, or CD as there is significant debate as to the etiology and overlapping findings of these conditions. We highlight the importance of lymphangiectasia in diagnosing underlying CD in the appropriate clinical context.

Radiofrequency therapy as an effective treatment for granulomatous cheilitis: A CARE case report.

INTRODUCTION: Granulomatous cheilitis is a rare disorder characterized by recurrent, idiopathic, and painless lip swelling. The diagnosis is proven by histopathological examination. The unknown aetiology and poorly understood underlying mechanism contribute to the difficulty in establishing an effective treatment. This case study proposes the effectiveness of radiofrequency therapy in the management of refractory granulomatous cheilitis. CASE SUMMARY: A 68-year-old patient presented with hypertrophy and swelling of the lower lip, and a biopsy revealed actinic cheilitis. The patient underwent lip shaving and an advancement mucosal flap, and definitive histologic examination confirmed the diagnosis of granulomatous cheilitis. No other signs of orofacial granulomatosis were observed, and the complementary aetiological study was negative for systemic disease. The lip swelling reappeared and persisted, which interfered with the quality of life. Hence, radiofrequency therapy was performed in the submucosal and subdermal layers of the lip, resulting in significant aesthetic and functional improvement and no further relapses after five years. DISCUSSION: The management of granulomatous cheilitis is challenging. The current mainstay treatment is corticotherapy or reduction cheiloplasty in severe cases. Radiofrequency has potential as a treatment option in debilitating macrocheilia, presenting worthy long-lasting functional and aesthetical results, with minimal morbidity.

Specific Oral Manifestations in Adults with Crohn's Disease.

Background: Oral manifestations of Crohn's disease (CD) include non-specific lesions and specific lesions directly related to intestinal inflammation. Oral lesions that can be overlooked in CD are sometimes challenging to treat. Methods: In this retrospective single-center study, patients with CD aged over 18 years who complied with follow-up and treatment were included. Clinical definitions of specific oral lesions included pyostomatitis vegetans, glossitis with fissuring, lip swelling with fissuring, cobblestoning, and orofacial granulomatosis. Experienced dentists confirmed the specific lesions in each case. Three groups of patients were identified: those without oral lesions, those with non-specific oral lesions, and those with specific oral lesions. The groups were compared based on demographics, disease extent and behavior (based on the Montreal classification), extraintestinal involvement, biologic and steroid treatment, and the requirement of resective surgery. Results: A total of 96 patients (14.2%) with oral lesions were found among the 676 patients with CD (59.7% male, median age 38 years) who were followed for 6.83 years (IQR 0.5-29.87 years). Eight patients (1.2%, 9 lesions) had specific oral lesions, while eighty-eight patients (13%) had non-specific lesions. Orofacial granulomatosis (n = 3), cobblestoning (n = 2), glossitis with fissuring (n = 2), and lip swelling with fissuring (n = 2) were among the specific lesions. The majority of patients (75%) with specific lesions were male, and their median age was 46.5 years (range: 23-68 years). Disease localization was commonly ileocolonic (50%), and perianal disease was present in 25% of patients. Three patients were active smokers. Extraintestinal manifestations were peripheral arthritis/arthralgia (n = 7) and sacroiliitis (n = 1). All specific lesions were associated with moderate-to-severe disease. Five patients improved with biologic therapy, and two patients with immunomodulatory therapy. Conclusions: Specific oral lesions in CD were associated with active disease and improved with immunomodulators or biologic therapy. Close cooperation between gastroenterologists and dentists is essential for early diagnosis and optimal management of CD.

Edema localized to the lips as a novel manifestation of myositis.

Polymyositis (PM) and dermatomyositis (DM) are idiopathic inflammatory myopathies with presumed autoimmune pathogenesis, characterized by the features of proximal skeletal muscle weakness and evidence of muscle inflammation. Skin manifestations usually prompt earlier recognition and diagnosis of DM than PM, which has no rash. Associated delayed diagnosis and treatment in PM lead to worse outcomes. Therefore, an accumulation of case reports regarding initial symptoms suggestive of PM has been required to obtain an earlier diagnosis and better clinical outcomes in PM patients. We herein report a PM patient with an unusual presentation of edema restricted to the lips, which was clinically suggestive of granulomatous cheilitis but histologically verified as a manifestation of myositis. In this patient, no myositis-specific antibodies including anti-nuclear matrix protein 2 antibodies, were detected, and histological analysis on the muscle biopsy specimen revealed CD4-dominant lymphocyte infiltration but no C5b-9 deposition nor myxovirus resistance protein A expression. Further analysis with MRI (magnetic resonance imaging) scan of the lips showed increased signal intensity in the muscle layer on short TI inversion recovery images, and these suggest the potential of MRI as a useful tool for exploring the inflammatory site and the possibility of myositis in swollen lips. Thus, our report indicates the importance of suspecting myositis in the case of unusual edema restricted to the lips.

Treatment of Orofacial Granulomatosis-9-Month Follow-up: A Case Report.

Orofacial granulomatosis is a condition that manifests clinically as painless labial enlargement, perioral and mucosal edema, oral ulcers, and gingivitis. It is characterized by non-necrotizing granulomatous inflammation of the oral and maxillofacial region. When the swelling only affects the lips, the pathology is called Miescher's granulomatous cheilitis; however, when it also causes facial paresis and lingua plicata, it is known as Melkersson-Rosenthal syndrome. We report a case that was successfully treated with a combination of a local (intralesional) steroid, a systemic antibiotic, and a systemic steroid. After 6 months of therapy, we observed improvement in gingival hyperplasia and buccal mucosa and lip edema.

Granulomatous Cheilitis or Tuberculid?

The granulomatous cheilitis (GC) presents a heterogeneous group of disorders characterised by a granulomatous inflammation/reaction of the lips to various stimuli. Numerous etiologies have been proposed, including genetic, immunologic, allergic and infectious. Among the secondary causes of GC, an infection by Mycobacterium tuberculosis (MBT) should be considered. In such cases, the GC could be the clinical presentation of a tuberculid resulting from a hypersensitivity reaction to an underlying focus of active (ATBI) or latent tuberculosis infection (LTBI). This communication describes an immunocompetent patient diagnosed with GC resulting from tuberculid, who responded well to Isoniazid monotherapy.

Photobiomodulation and Miescher's cheilitis granulomatosa: case report.

BACKGROUND: Miescher's cheilitis granulomatosa (MCG) is a rare chronic inflammatory disease and is known as the monosymptomatic clinical form of Melkersson-Rosenthal syndrome (MRS). It is characterised by swelling of one or both lips and more frequently affects the upper lip. Histopathological findings show the presence of numerous inflammatory infiltrates and granuloma formations. Pharmacological treatments and surgery have provided results that are positive yet insufficiently stable in the long term. The clinical case described is of a 68-year-old female patient with a diagnosis of MCG of the upper lip. CASE PRESENTATION: The patient was diagnosed and treated at the Oral Medicine and Oral Pathology outpatient clinic of Maxillofacial and Odontostomatology Unit, Fondazione Cà Granda IRCCS Ospedale Maggiore Policlinico. The patient was recommended localised treatments of photobiomodulation (PBM) using a diode laser with a 635 nm and 980 nm dual-wavelength (λ) approach, a 600-micron fibre, and a handpiece with a 1-cm-diameter lens at 300 mW. Three treatments a week were administered for four weeks for a total of 12 treatment sessions (T 1-T 12). After that, the patient had a long follow-up period of about 2 years. The therapeutic results were clear from the initial stages of treatment. There was an immediate, gradual, and consistent reduction in labial swelling. A reduction in the size of the lip by about 35% at T 10-T 12 was observed, returning the size and volume of the upper lip within the normal clinical range. The painful symptoms subsided after the seventh treatment (T 7). The histopathological check at 3 months and the follow-up in particular confirmed the disease was in remission with satisfactorily stable treatment results. Moreover, the patient did not use any other treatments on the area from the early laser treatments through to the end of the follow-up period. CONCLUSIONS: Our experience describes a clinical case of MCG treated with PBM and effectively resolved with a reduction of the lip swelling. The real success of the treatment emerged over time, showing that the tissue healing was stable. In absence of any collateral phenomena, this confirms the effective and documented therapeutic potential of PBM for chronic inflammatory infiltrates.

Recurrent granulomatous cheilitis associated with Crohn's disease successfully treated with ustekinumab: case report and literature review.

Granulomatous cheilitis, characterized by persistent inflammation of the lips and a granulomatous histology, is sometimes associated with Crohn's disease and is a therapeutic challenge. Reported evidence indicates treatment with an anti-TNF agent (mainly infliximab) is the most recommended therapeutic option after failure of conventional treatments. The clinical case reported the effectiveness of ustekinumab, a monoclonal antibody against interleukins 12/23, to induce the remission of severe and recurrent granulomatous cheilitis in a patient with Crohn's disease.

Characterizing disease manifestations and treatment outcomes among patients with orofacial granulomatosis in China.

BACKGROUND: Racial variation exists in the incidence of orofacial granulomatosis (OFG). The epidemiology and clinical characteristics of OFG in Asian countries are poorly described. OBJECTIVE: To describe the epidemiologic and clinical features of OFG in China from data collected on chronic odontogenic infection and studied in actual practice regarding the long-term outcome of OFG patients receiving different treatments. METHODS: Data on demographics, medical history, chronic odontogenic infection, and the extent of disease were collected, and long-term outcomes after the end of treatments were evaluated. RESULTS: Of the 165 OFG patients, 118 (71.5%; 95% CI 64.6%-78.5%) had a chronic odontogenic infection. There was a variety of difference between OFG with and without chronic odontogenic infection. Approximately 98.3% (95% confidence interval 94.8%-100%) of OFG patients with chronic odontogenic infection who received dental treatment showed a marked response, of whom 31 patients (53.4%; 95% confidence interval 40.2%-66.7%) had complete remission. LIMITATIONS: Endoscopic investigations were not performed for most of the patients, and more detailed data were not collected, which might have demonstrated additional systemic problems. CONCLUSIONS: OFG with chronic odontogenic infection is the major clinical pattern of OFG in China, which may be a subtype of OFG. Dental treatment should necessarily be the preferred first-line therapy for such patients.

Lymphoplasmacytic Granulomatosis Cheilitis Treated with Cheiloplasty.

Orofacial granulomatous (OFG) also known as granulomatous cheilitis, is a condition that causes the lips or mouth to become edematous due to a granulomatous inflammatory process. The underlying cause of the disease is unknown; however, it has been linked to other granulomatous pathologies, including sarcoidosis and Crohn's disease. Due to the lack of evidence regarding the etiology of OFG, treatment options vary depending on the symptoms associated with the presentation of OFG and patient medical history. We present a case of long-standing idiopathic OFG in a 65-year-old African-American man. This case highlights a chronic case of OFG, associations with other disorders, the diagnostic strategy used, and management options for OFG.

Allergic and Immunologic Perspectives of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic immune-mediated inflammatory condition primarily involving the gastrointestinal tract. It includes Crohn's disease (CD), ulcerative colitis (UC), and a less common phenotype-indeterminate colitis. It is thought to result from a complex interplay of environmental, microbial, and host factors including genetic factors, although the exact mechanism is not known. Dietary factors have been shown to play a role in the pathogenesis of IBD and can potentially alter the intestinal microbiota as well as disrupt the immune function in the gut. CD is characterized by transmural inflammation, sometimes associated with granulomatous lesions, and involves the entire gastrointestinal tract but often spares the rectum. UC is characterized by mucosal inflammation typically confined to the colon and rectum. Although IBD is mostly seen in western world, recent data suggests that the incidence and prevalence are increasing worldwide. Enteral nutrition has been shown to be effective in inducing remission in pediatric population with CD; however, there is mixed data in adult population. Nutritional deficiencies such as vitamin D and zinc deficiency are often noted in IBD patients. Several extraintestinal manifestations are noted in patients with IBD. Some of them parallel with the disease activity and others are independent of the disease course. Assessment of IBD disease activity clinically, radiologically, if indicated, biochemically and endoscopically is important to guide therapy in IBD. To ensure comprehensive care, it is important to assess associated conditions such as nutritional and psychological well-being, as well as age appropriate health maintenance status prior to starting treatment for IBD. Several biologic agents including anti-tumor necrosis factor alpha (anti-TNF-α) drugs, anti-integrins, and antibodies to the p40 subunit of IL12/23 are approved for induction and maintenance of remission of IBD. Steroids are also often used for induction. Anti-metabolites and thiopurines are also useful either as monotherapy or in combination regimens. Potential side effects of anti-TNF-α drugs such as serious infections, malignancy, worsening of heart failure, and infusion-related reactions should be considered prior to starting these drugs. Anti-TNF-α drugs with or without immunomodulators (azathioprine, 6-mercaptopurine, methotrexate) are often used for the induction and maintenance of remission. Treating to target of endoscopic and clinical remission provides the best long-term outcomes. Our knowledge and understanding of IBD has grown significantly. However, there are several unanswered questions on pathogenesis, disease behavior, and drivers of inflammation in various patient subgroups which require further research.

Queilitis granulomatosa, a propósito de dos casos / Granulomatous cheilitis, regarding two cases

La queilitis granulomatosa es una entidad granulomatosa no infecciosa, poco frecuente, que se presenta como un aumento de volumen persistente de la región orofacial. El estudio histológico, junto con la exclusión de otras patologías granulomatosas son necesarios para su diagnóstico, especialmente cuando no se presenta con la triada clásica del Síndrome de Merkelsson Rosenthal. Presentamos dos casos de queilitis granulomatosa y una revisión de la literatura disponible.

Granulomatous cheilitis is a rare, non-infectious, granulomatous entity that presents as a persistent swelling of the orofacial region. Histological study together with the exclusion of other granulomatous diseases are necessary for the diagnosis, especially when the presentation is not the classic triad of Merkelsson Rosenthal Syndrome. We present two cases of granulomatous cheilitis and a review of the available literature.

Leishmaniasis recidiva cutis of the lips mimicking granulomatous cheilitis.

Leishmaniasis recidiva cutis (LRC) is an unusual form of acute cutaneous leishmaniasis. Herein, we present a case of LRC of the lips mimicking granulomatous cheilitis. An 8-year-old, Syrian child admitted with a swelling and disfigurement of his lips for 4 years. Abundant intra and extracellular Leishmania amastigotes were determined in the smear prepared from the lesion with Giemsa stain. Histopathology showed foamy histiocytes and leishmania parasites within the cytoplasm of macrophages in the epidermis and a dense dermal mixed type inflammatory cell infiltrate composed of lymphocytes, foamy histiocytes with multinucleated giant cells. On the basis of anamnestic data, the skin smears results, clinical and histopathologic findings, LRC was diagnosed. The patient was treated with meglumine antimoniate intramuscularly and fluconazole orally. Cryotherapy was applied to the residual papular lesions. The lesion improved markedly at the first month of the treatment.

Orofacial Granulomatosis.

Orofacial granulomatosis (OFG) is an uncommon chronic inflammatory disorder of the orofacial region. It is characterized by subepithelial noncaseating granulomas and has a spectrum of possible clinical manifestations ranging from subtle oral mucosal swelling to permanent disfiguring fibrous swelling of the lips and face. Etiopathogenesis is unknown. A range of systemic granulomatous disorders, including Crohn disease and sarcoidosis, may cause orofacial manifestations that cannot be distinguished from those of OFG. Treatment of OFG has proven difficult and unsatisfactory, with no single therapeutic model showing consistent efficacy in reducing orofacial swelling and mucosal inflammation.

Granulomatous cheilitis.

A 19-year-old labourer presented with progressively worsening swelling of both lips. Clinical assessment and investigations led to the diagnosis of granulomatous cheilitis.

[Macrocheilia, granulomatous cheilitis and Crohn's disease]. / Macroquelia, queilitis granulomatosa y enfermedad de Crohn.

Granulomatous cheilitis is a rare disease included among the orofacial granulomatoses. It is characterized by a idiopathic chronic inflammation of the labial mucosa (macrochelia), which takes the form of episodic and progressive outbreaks. In 10% of patients, it is associated with Crohn's disease. We report the presentation, evaluation and treatment of a case of granulomatous cheilitis which appearted two years after the onset of Crohn's disease. We conclude that granulomatous cheilitis is rare in children, with few reported cases, although probably underdiagnosed because of lack of awareness. The diagnosis of granulomatous cheilitis is clinical, although the histological evaluation is a determining factor. After making the diagnosis a comprehensive assessment of the patient is recommended, to rule out the other associated syndromes described in the literature.