Melkersson-Rosenthal syndrome with isolated unilateral eyelid edema: an immunopathologic study.

Lymphedema is caused by defective drainage of the lymphatic system. In Melkersson-Rosenthal syndrome, involvement is predominantly of the lumens with blockage of lymphatic channels by histiocytic-epithelioid cell clusters accompanied by dermal granulomas and lymphocytes. It is a localized, painless, nonitching, and nonpitting form of lymphedema. Besides the eyelids, the disease can cause lip edema, facial palsy, and/or fissured tongue. It is rare and has received little attention in the ophthalmic literature, either in its complete triadic form, or more frequently, in its monosymptomatic forms. Pathogenesis is not well understood, and there is no effective therapy. The authors describe a case of Melkesson-Rosenthal syndrome in a 45-year-old Hispanic man with isolated unilateral upper eyelid edema. Histopathological and immunohistochemical evaluations of an eyelid biopsy specimen revealed intravascular and extravascular clusters of histiocytic-epithelioid cells that were CD68/163-positive. Variable numbers of mostly T-lymphocytes were found in the epidermis, dermis, and orbicularis muscle and by virtue of the associated granulomas established the diagnosis of Melkersson-Rosenthal syndrome. CD4 helper and CD8 suppressor T-lymphocytes were equally represented. CD20 B-lymphocytes were exceedingly sparse. Conspicuous CD1a-positive Langerhans' cells were present in the epidermis, sometimes formed subepithelial loose aggregates and were also incorporated in the granulomas. The differential diagnosis includes the far more common condition of acne rosacea. Management of Melkersson-Rosenthal syndrome, and of angioedema in general, is reviewed.

Skewed T-cell receptor variable ß repertoire and massive T-cell activation in idiopathic orofacial granulomatosis.

Orofacial granulomatosis (OFG) is a clinicopathologic entity describing oral lesions with noncaseating granulomas including a spectrum of diseases such as the Melkersson-Rosenthal syndrome. The involvement of abnormal T-cell responses has been suggested in the pathogenesis of OFG although few and contrasting data are currently available on this issue. In a patient with OFG, we observed virtually complete CD4 and CD8 T-cell receptor (TCR) ß-chain variable region (BV) repertoires at the lesion level and in circulation. However, oligoclonal profiles were found in CD4 and, to a greater extent, in CD8 subsets. These findings were seen in association with a massive peripheral T-cell activation, decreased naive T cells, reduced thymic output, altered cytokine production, and increased apoptosis. Our data, pointing to a random influx of T cells at the site of inflammation, argue against the hypothesis of a main allergen acting at the level of oral mucosa. The profound dysregulation of the peripheral T-cell compartment suggests that OFG should be regarded as a systemic disorder with localized manifestations.

Patch testing for food-associated allergies in orofacial granulomatosis.

BACKGROUND: Food-associated allergies, especially to benzoates and cinnamon-related compounds, have been associated with orofacial granulomatosis and both standard and urticarial patch testing have been used to detect such allergies. Elimination diets have also been shown to be effective in some patients. OBJECTIVES: To compare the results of standard and urticarial patch testing in a cohort of patients with orofacial granulomatosis. MATERIALS AND METHODS: Records of 120 cases seen in two hospitals were retrieved and examined for patch test details. RESULTS: Standard patch testing was much less likely to detect allergy to benzoates and cinnamon compounds (7%) than urticarial tests (55%). All urticarial tests that were positive had shown a reaction by 60 min. CONCLUSIONS: Both standard and urticarial patch tests are required to detect food allergies in orofacial granulomatosis. The difficulties of patient self-recording of urticarial tests can be eliminated by retaining patients in the testing unit for professional reading of patches at 60 min.

Melkersson Rosenthal syndrome: a histopathologic mystery and dermatologic challenge.

Melkersson Rosenthal syndrome (MRS) is rare disease of unknown etiology characterized by orofacial edema, facial nerve palsy and fissured tongue. Microscopically, it shows epithelioid non-caseous granulomas; however, edema and perivascular lymphocytic infiltrates have been described. Two different clinical forms of MRS are presented in this report. In the complete form (Case 1), the main histopathologic finding was a non-necrotizing granulomatous inflammation with 56% of the total number of cells composed of B cells (CD 20(+) ) principally located in the granuloma's center and 33% being T cells predominating in the surrounding area, of which 48% were CD 4(+) and 16% were CD 8(+) lymphocytes. In the monosymptomatic form (Case 2), the inflammatory cells were dispersed into the connective tissue without granulomatous formation. B cells were scanty, and 78% of the cells were CD 45(+) T cells, with 46% and 34%, CD 8(+) and CD 4(+) phenotype, respectively. These cases showed different clinical, histopathological and immunohistochemical forms of MRS, suggesting different host immune responses.

Melkersson-Rosenthal syndrome associated with parvovirus B19 viraemia and haemophagocytic lymphohistiocytosis.

We describe a 23-year-old patient who presented acutely with haemophagocytic lymphohistiocytosis (HL) and Melkersson-Rosenthal syndrome (MRS). MRS and HL are two unusual and complex clinical patterns that may present acutely and to our knowledge, an association between them has never been reported. The clinical investigations in this patient led to identification of parvovirus B19 (PB19) viraemia by PCR. Parvovirus infection has been reported as a cause of virus-associated HL, but the presence of PB19 has never been sought or reported as a possible trigger for MRS. This observation suggests a possible association between PB19 and HL, and opens the possibility of its association also with acute-onset MRS. Further investigations for the presence of PB19 in cases of MRS are warranted.

Melkersson-Rosenthal syndrome with coeliac and allergic diseases.

A 45-year-old man presented with a 10-year history of relapsing oedema of the lips. Moreover, he exhibited recurrent facial nerve palsy since the age of 10 years, coeliac disease since the age of 12 years, atopic eczema, allergic rhinitis and asthma. Physical examination revealed lip swelling and lingua plicata. Thus, he presented the classic triad of Melkersson-Rosenthal syndrome which includes recurrent orofacial oedema, facial nerve palsy and fissured tongue. A lip biopsy confirmed our clinical diagnosis.This case is particularly rare, as the classic triad is seen only in a minority of the cases. Moreover, allergic and coeliac diseases were observed concomitantly. This paper illustrates a potential pathophysiological interconnection between these pathologies in which interferon gamma could play a key role. To our knowledge, this is the first case report in which Melkersson-Rosenthal syndrome has been observed concurrently with coeliac disease.

Hashimoto's thyroiditis in Melkersson-Rosenthal syndrome patient: casual association or related diseases?

Melkersson-Rosenthal syndrome (MRS) is a rare disorder of unknown etiology. MRS is classically defined as a triad of recurrent orofacial edema, relapsing paralysis of the facial nerve, and fissured tongue. The authors present the case of a 52-year-old woman with orofacial swelling and facial pain attacks. The patient reported to suffer of hypothyroidism and laboratory findings disclosed free triiodothyronine (FT(3)), free thyroxine (FT(4)), and thyrotropin (TSH) altered. Endocrinological consult led to the diagnosis of Hashimoto's thyroiditis. Antithyroper-oxidase antibodies (anti-TPO) were highly elevated and thyroid function tests had evidenced a clinically significant hypothyroidism. A link between MRS and immunological disorders such as sarcoidosis, Crohn's disease, unilateral anterior uveitis and multiple sclerosis was documented. The literature did not report any association between Hashimoto's thyroiditis and Melkersson-Rosenthal syndrome. The presence of the anti-TPO antibodies in the case reported here could suggest a possible correlation between immunological alteration characteristic of autoimmune thyroiditis and MRS.

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.

Melkersson-Rosenthal syndrome with isolated immunoglobulin E hypogammaglobulinaemia.

Melkersson-Rosenthal syndrome (MRS) is a rare disorder classically presenting with a triad of recurrent orofacial swelling, facial palsy and a fissured tongue. This case report describes a case of MRS in a patient with isolated immunoglobulin E (IgE) hypogammaglobulinaemia. The 52-year-old woman presented with puffy eyelids, lower lip swelling and right facial nerve palsy. Fissures of the tongue were also noted. On investigation she was found to have a markedly low serum IgE level. This case report clearly indicates that IgE-mediated reactions do not play a significant role in the development of MRS.

Melkerson Rosenthal syndrome.

This case presentation of a facial swelling emphasizes the difficult and differential efforts of a team of doctors before we were able to reach a diagnosis of Melkerson Rosenthal Syndrome (MRS). This syndrome is an idiopathic, neurological disorder seen as a swelling of the face and lips, with folds and furrows of the tongue. Episodes are recurrent. This case is an example of positive networking by a dentist and physician to achieve the correct diagnosis of MRS.

Intralesional T lymphocyte phenotypes and HLA-DR expression in Melkersson-Rosenthal syndrome.

An immunohistochemical double-staining technique was used to characterize the infiltrating mononuclear lymphocytes in frozen sections from 3 patients with Melkersson-Rosenthal syndrome. The in situ expression of HLA-DR antigens on different cell types was also investigated. The majority of mononuclear cells could be classified as T-lymphocytes because of their Leu 4 antigen expression. Most of the T-lymphocytes were confined to the helper/inducer lymphocyte subset since they reacted with Leu 3a antibodies. However, big infiltrates of suppressor/cytotoxic lymphocytes with the Leu 2a phenotype were noted in some specimens. These cells were situated between the ducts of the salivary glands. Virtually all mononuclear infiltrating cells carried HLA-DR antigens. HLA-DR expressing keratinocytes were found in the biopsy from one patient. The present study indicates that a local immune response may be important in the pathogenesis of the oro-facial lesions in Melkersson-Rosenthal syndrome.

[Melkersson-Rosenthal syndrome. Presentation of a clinical case and review of the literature]. / Sindrome di Melkersson-Rosenthal. Presentazione di un caso clinico e revisione della letteratura.

Melkersson-Rosenthal syndrome is a rare form of hereditary angioedema characterised by a triad of symptoms of which incomplete (oligo- or monosymptomatic) forms have been described, frequently associated with dysreactive diseases or neoplasia. The authors describe the case of a 48-year-old man with an incomplete form which was successfully treated with steroids and, after a careful and detailed revision of the literature on the subject, they make a number of etiopathogenetic, histopathological, clinical and therapeutic comments.

[Early diagnosis and immunocorrective therapy of recurrent facial neuritis as a manifestation of Melkersson-Rosenthal syndrome in adults and children]. / Ranniaia diagnostika i immunokorrigiruiushchaia terapiia retsidivi- ruiushchego nevrita litsevogo nerva kak proiavlenie sindroma Mel'kerssona-Rossolimo-Rozentalia u vzroslykh i detei.

Clinical and immunological examinations of adults and children with Melkersson-Rossolimo-Rosenthal syndrome have revealed immunity deficiency: a decrease of the number of T and B cells, a low immunoglobulin content and the presence of the ++neuro-allergic syndrome according to the increased level of cerebral antibodies. The role of deembiogenetic stigmas in the diagnosis establishment has been demonstrated. The authors suggest the use of immunomodulating therapy including interferogens and immunostimulants of T and B cells (galascorbin and myelopide). Provide evidence for the efficacy of the treatment elaborated.

[Oral symptoms and immune status of patients with the Rossolimo-Melkersson-Rosenthal syndrome]. / Stomatologicheskie proiavleniia i immunnyi status bol'nykh sindromom Rossolimo-Melkersson-Rosenthal.

Clinical oral symptoms were studied in 210 patients with the Rossolimo-Melkersson-Rosenthal syndrome (RMRS); the immune status was evaluated in 17 of these. Oral status was characterized by high prevalence and intensity of caries and presence of chronic generalized periodontitis. Immunological studies revealed changes characteristic of immunodeficiency: increased counts of suppressor cytotoxic T-lymphocytes, decreased phagocytic activity of neutrophils, and dysimmunoglobulinemia; hence, RMRS was associated with secondary immunodeficiency.

[A study on the relationship between cheilitis granulomatosa and Melkersson-Rosenthal syndrome].

Serum anti Borrelia Burgdorferi (BB) antibody of 18 patients with cheilitis granulomatosa (CG) and 5 patients with Melkersson-Rosenthal syndrome (MRS) have been examined and positive results are present in 14 patients with CG(77.8%) and 4 patients with MRS(80%). According to histopathological features the lesions show characteristics of spirochetes diseases. It suggests that CG and MRS are all caused by spirochetes.

[Investigation of infiltrating lymphocytes and immunoglobulin by immunohistochemical method in cheilitis granulomatosa].

Category and distribution of infiltrating lymphocytes and immunoglobulin in 12 cases with cheilitis granulomatosa (CG) and 4 cases with Melkersson-Rosenthal syndrome (MRS) were investigated. The result was that infiltration of lymphocytes in granulomatous type was more severe than that in interstitial inflammtion type. Infiltrators mainly consisted of T helper lymphocytes and immunoglobulin was IgM. It was considered that local immunoreaction was enhanced suggesting that cyto-immunity was a dominant factor with participation of humoral immunity. The result will be helpful to elucidate the pathogeneses and the function of many immuno-factors in the CG. It helps to understand the clinical manifestations and may be a theoretic reference for seeking immuno-modulation for treatment.