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.

Obstructive sleep apnea in a patient with the Melkersson-Rosenthal syndrome.

INTRODUCTION: Melkersson-Rosenthal syndrome (MRS) is a rare disorder of unknown etiology. It is characterized by the triad of macrocheilitis, peripheral facial palsy, and lingua plicata. CASE REPORT: A 48-year-old nonobese man with a diagnosis of MRS and marked macroglossia was evaluated because of clinically suspected obstructive sleep apnea (OSA). Established causes of OSA such as anatomic abnormalities of the upper airways or the facial skeleton were not present in this patient. Furthermore, hypothyroidism and acromegaly were excluded as underlying diseases. Polysomnography revealed moderate-to-severe OSA. As the swelling of the tongue had been unresponsive to immunosuppressive pharmacotherapy and surgery did not seem to be a reasonable therapeutic option, the patient was finally treated by continuous positive airway pressure therapy. DISCUSSION: To the best of our knowledge, this is the first report of OSA occurring in a patient with MRS.

Melkersson-Rosenthal syndrome: lymphoscintigraphy-documented impairment and restoration of facial lymphatic drainage in the course of disease.

Melkersson-Rosenthal syndrome (MRS) is an idiopathic, rare disorder manifested by facial swelling, congenital plicated tongue and recurrent peripheral facial nerve palsy. Labial involvement alone is referred to as cheilitis granulomatosa. Differential diagnosis of MRS includes allergic angioedema, bacterial, viral or filarial infections as well as autoimmunological inflammation in the course of systemic lupus erythematosus, dermatomyositis, and others. We present 4 patients who experienced periodically painless edema of the face and/or lips. Lesions were diagnosed as recurrent Quincke's edema and were treated with antihistamine agents and glucocorticoids without improvement. In all four cases of MRS, we were able to document impaired lymphatic drainage from the swollen area using lymphoscintigraphy. We also documented in follow-up lymphoscintigraphy a restoration of lymphatic flow in three of the four patients with MRS and these results corresponded with clinical improvement. We have demonstrated that lymphatic pathology plays an important role in pathophysiology of chronic facial swelling in patients with Melkersson-Rosenthal syndrome.

Melkersson⁻Rosenthal Syndrome in Childhood: Report of Three Paediatric Cases and a Review of the Literature.

Melkersson-Rosenthal syndrome (MRS) in children is a rare condition, clinically characterised by a triad of synchronous or metachronous symptoms: recurrent peripheral facial palsy, relapsing orofacial oedema, and a fissured tongue; the most recent review published on the topic has reported 30 published patients. The aetiology of this disease is still unclear. However, genetic factors, as well as alterations in immune functions, infections, and allergic reactions have been postulated. We report three children suffering from MRS and perform a literature review of paediatric cases. Taking into account that clinical and laboratoristical criteria for the diagnosis of MRS are lacking, this syndrome is probably underestimated, and we suggest increasing awareness of such a rare syndrome. Close multidisciplinary follow-up of these children with a team composed by paediatricians, neurologists, neuro-ophthalmologists, dermatologists, and otolaryngologists is crucial to guarantee exhaustive management and treatment success, while minimising relapses.

Melkersson-Rosenthal syndrome and acquired C1 inhibitor deficiency.

BACKGROUND: Melkersson-Rosenthal syndrome (MRS) is a rare disease whose full-blown form is characterized by orofacial swelling, facial palsy and lingua plicata. OBJECTIVE: To investigate the complement system as well as its role in patients with MRS. METHODS: Seven patients presenting at this hospital between November 2002 and May 2003 and meeting the diagnostic criteria according to Hornstein were evaluated retrospectively. The investigations included clinical signs, an analysis of the complement system including levels of CH50, C3, C4, C1 inhibitor (INH) functions and C1-INH antigen detection. RESULTS: Two female patients showed isolated low levels of functional C1-INH as determined by duplicate tests. Both patients took estrogen-progestin contraceptives. CONCLUSION: Since deficiency in plasma protease C1-INH is known to lead to recurrent angioedema, we hypothesize that low levels of functional C1-INH may have contributed to the orofacial swelling in the 2 patients.

Case of cheilitis granulomatosa associated with apical periodontitis.

The etiology of cheilitis granulomatosa is unknown. In some cases, rapid improvement and/or complete elimination of swelling of the lips after dental treatment has been reported. Here, we describe another case of improvement following dental treatment. A 57-year-old woman had developed asymptomatic swelling of the lower lip 2 months previously. Histological examination revealed non-caseous giant cell granulomas. Neither facial nerve palsy nor fissuring of the tongue was present. Patch testing for metal allergy revealed only mild irritation to zinc ion. Although topical corticosteroid ointment and oral tranilast for 4 months were ineffective, rapid and remarkable improvement of the swelling was noted soon after treatment of two lesions of apical periodontitis. Thorough examination for foci of infection is necessary when treating a patient with cheilitis granulomatosa.

[Melkersson-Rosenthal syndrome--diagnostic and therapeutic problems]. / Zespól Melkerssona-Rosenthala - problemy diagnostyczne i lecznicze.

It is very difficult to differentiate Melkersson-Rosenthal syndrom and macrochelitis granulomatosa. Two neurologists: Ernt Melkersson and Curt Rosenthal in 1928 and 1931 described classical symptoms of this syndrom: recurring facial paralysis, swelling of the face and lips and the development of folds and furrows in the tongue. In 1945 Miescher described a few cases of primary interstitial inflammation of the lips and gave them the name macrochelitis granulomatosa. Some patients had paralysis of the facial nerve, others folds of the tongue. In the present study the etiopatho-genesis, diagnostic and therapeutic problems are presented.

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.

Idiopathic macrocheilia.

A 13-year-boy presented with painless swelling of upper and lower lips accompanied with gingival enlargement. The aetiology for these symptoms included vast pathological varieties but none of them could fit in. Clinical features were similar to orofacial graulomatosis but histopathological examination revealed chronic non-specific infection. Therefore, the final diagnosis was made as idiopathic macrocheilia through exclusion criteria. Management with intralesional triamcinolone acetonide 40 mg, twice a week for 3 weeks, resulted in significant remission in lip swelling without recurrence after a 6-month follow-up.

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.

CLINICAL CHARACTERISTICS AND TREATMENT OF MELKERSSON-ROSENTHAL SYNDROME--OVERVIEW OF SIX PATIENTS.

INTRODUCTION: Melkersson-Rosenthal syndrome is a rare disease of unknown etiology. Histopathologically, it presents as granulomatous cheilitis. From laboratory aspect, it is a nonspecific, differential diagnostically and therapeutically complex condition. CASE REPORT: This is a report of six cases treated at the Department of Allergology and Immunology of the Clinical Center of Serbia, who had presented with the referral diagnosis of recurring or persistent lip edema, and who were diagnosed with Melkersson-Rosenthal syndrome upon detailed evaluation. Three patients had complete triad of symptoms, two had the oligosymptomatic form and one manifested the monosymptomatic form of the disease. Histopathological findings of the oral mucosa specimens verified the presence of non-necrotic epithelioid granulomas in all patients. The patients were treated with the H1 and H2 antihistamines, corticosteroids, followed by anabolic drugs and antibiotics, resulting in transient and unfavorable effects. CONCLUSION: In differential diagnosis, Melkersson-Rosenthal syndrome diagnosis primarily refers to conditions of angioneurotic edema and hereditary angioedema, as well as granulomatous diseases such as sarcoidosis, tuberculosis and Chron's disease. It is necessary to follow-up these patients in view of monitoring the effects of the therapy and possible development of systemic granulomatous diseases.

The Melkersson-Rosenthal syndrome.

The Melkersson-Rosenthal syndrome consists of recurrent swelling of the lip or face, intermittent facial palsy, and fissured tongue. Lengthy intervals may occur between those various manifestations. Four white female patients with this disorder are described. First identified in Europe, the condition is now increasingly recognized in this country. The cause is unknown. The pathology, clinical features, and management of this unusual disorder are discussed.

The surgical management of Melkersson-Rosenthal syndrome.

A triad of facial palsy, orofacial edema, and furrowed tongue constitutes an uncommon condition known as Melkersson-Rosenthal syndrome (MRS). We report on 14 patients with Melkersson-Rosenthal syndrome. Two patients had facial palsy, 12 had orofacial edema, and 1 patient had a furrowed tongue. Nine patients were treated medically. Intralesional steroid therapy had a 75 percent recurrence rate. Systemic steroid therapy resulted in remission in two of three patients. Surgical excision and reconstruction were carried out in five patients with chronic lip or eyelid edema. This provided relief in all cases. The etiology, clinical presentation, and histologic features are discussed. Three illustrative cases are presented. An algorithm is provided that guides the surgeon with regard to both the medical and surgical treatment of the patient with Melkersson-Rosenthal syndrome.

Melkersson-Rosenthal syndrome--a challenge for dermatologists to participate in the field of oral medicine.

Melkersson-Rosenthal syndrome (MRS) is a neuro-muco-cutaneous disorder involving remittently both the oro-facial innervation and muco-cutaneous tissues in a pathosis of complex origin characterized by recurrent edema, facial or other palsies, and nerval dysfunctions frequently associated with plicated tongue. Biopsies taken from the edematous tissues often reveal a temporary pattern of moderate epitheloid granulomatous inflammation scattered scarcely within remarkable tissue edema. However, this histological pattern is not a prerequisite for the diagnosis of MRS. The disease usually runs an intermittent and unpredictable course over years or decades and may have, if the edemas involve the tongue or the central nervous system, an ambiguous outcome. Greatly disfiguring oro-facial swellings often result from secondary persistence of the primarily recurrent edemas. A classification on grounds of different 'major' and 'minor signs' of MRS is proposed in the present paper. In recent years, novel therapeutic approaches involving either oral clofazimine or laser beam acupuncture (according to the principles of traditional Chinese medicine) have proven to be successful in some cases of MRS. Dermatology could play a larger role in oral medicine by taking diseases such as MRS into account in studies among specialties dealing with oro-facial pathoses.

Case report: cheilitis granulomatosa with periodontitis.

We report a case of cheilitis granulomatosa with periodontitis in a 39-year-old Japanese man. Biopsy specimens from both areas showed noncaseating epithelioid cell granuloma. Dental examination revealed that the lower left first molar had periodontitis. The lower left first molar was removed, and antibiotics and anti-inflammatory drugs were administered. After 2 months of periodontitis therapy, the lips returned to normal size without recurrence and the swelling of the buccal mucosa regressed.

Melkersson-Rosenthal syndrome: review of the literature and case report of a 10-year misdiagnosis.

Melkersson-Rosenthal syndrome is classically described as a triad of orofacial swelling, facial palsy, and fissured tongue. More often this syndrome presents in its oligosymptomatic forms. Melkersson-Rosenthal syndrome may not be as rare as suspected but rather a syndrome that often goes undiagnosed. Presented is the case of a mentally challenged man who was eventually diagnosed with Melkersson-Rosenthal syndrome only after being misdiagnosed and incorrectly treated for an odontogenic infection for more than a decade.

[Melkersson-Rosenthal syndrome. Current data and a report of a case]. / Syndrome de Melkersson-Rosenthal. Données actuelles et rapport d'un cas.

The author reviews recent data from the literature in the light of a case of Melkersson-Rosenthal syndrome. It would appear that the triad (plicated tongue, macrocheilia and facial paralysis) forming the syndrome may be accompanied by other bucco-facial oedematous manifestations. The etiology remains unknown and treatment is symptomatic based upon the aesthetic and symptomatic requirements of each patient.

[Macrocheilitis and Melkersson-Rosenthal syndrome. Review of 19 cases]. / Macroqueilites e síndrome de Melkersson-Rosenthal. Revisão de 19 casos.

Melkersson-Rosenthal syndrome is an uncommon condition of unknown cause. The classical triad includes recurrent orofacial oedema involving predominantly the lips (macrocheilitis), intermittent peripheral facial palsy and scrotal tongue. Some authors consider Miescher's cheilitis as a monosymptomatic form of the syndrome. Nineteen cases (11 females and 8 males) of macrocheilitis seen at the Dermatologic Clinic, University of Coimbra, between 1966 and 1992, are reviewed. The complete triad of signs was present only in 4 patients (21%) and two features of the classic triad in 3 (16%) (macrocheilitis and lingua plicata in two; macrocheilitis and facial palsy in one). Twelve patients had only recorrent or persistent orofacial swelling. All 19 patients had macrocheilitis. Less commonly, the check, nose, forehead, eyelid, chin and buccal mucosa were also involved. Peripheral facial paralysis was present in 5 cases (26%), and scrotal tongue occurred in 6 (32%). Lip biopsies, performed in 17 patients, revealed the typical pathologic picture of granulomatous cheilitis only in 8 cases. Systemic corticosteroids and clofazimine were the most efficacious treatment.

Melkersson-Rosenthal syndrome: a retrospective study of 44 patients.

CONCLUSION: When patients with recurrent facial paralysis are encountered, otolaryngologists should check for fissured tongue, and question those patients about orofacial edema, minor symptoms, and family history. Histologic evidence is not necessary for the diagnosis of Melkersson-Rosenthal syndrome (MRS), while coronary high-resolution CT (HRCT) reconstruction of temporal bone and food allergen detection may be beneficial. Prophylactic decompression of the facial nerve for patients with appropriate electrophysiological indication may prevent further facial palsy attacks. OBJECTIVES: The objective of this study was to analyze the clinical features of a group of patients with MRS with major complaints of facial palsy treated at the Department of Otorhinolaryngology, and to comment on MRS from the perspective of otolaryngologists. METHODS: A retrospective review of patient database for the last 6 years in the Department of Otorhinolaryngology in Beijing Shijitan Hospital was performed to find patients diagnosed with MRS. RESULTS: A total of 44 MRS patients were included in this study. The mean age at onset was 14.1 years. A total of 13 (29.5%) patients had family history, 17 (38.6%) revealed broadened fallopian canal on coronary HRCT reconstruction of temporal bone, and 20/23 (87.0%) patients showed positive results in food allergen detection. Thirty-one patients accepted subtotal facial nerve decompression and only one patient had facial palsy recurrence on the same side as the operation.