Melkersson-Rosenthal syndrome is a rare chronic disease of an unexplained nature, accompanied by the appearance of orofacial edema, facial nerve neuropathy, folded tongue. Along with the classical triad of signs, low-symptom forms are often found. Pathology is prone to relapses, is associated with other systemic diseases. The basis of the diagnosis is clinical data and the results of histological examination of biopsies. There is no specific treatment, a complex of medical and surgical methods is used to eliminate local changes.
ICD 10
G51.2 Rossolimo-Melkersson syndrome
General information
Melkersson-Rosenthal syndrome (Rossolimo-Melkersson-Rosenthal, recurrent facial nerve paralysis) was first described by the Russian neurologist G.I. Rossolimo in 1901, later the Swedish physician E.G. Melkersson (1928) and the German neurologist G. Rosenthal (1931) studied the disease in more detail. Pathology is considered quite rare – its prevalence in the general population is 0.08%. In total, about 300 cases have been described, but many may remain unaccounted for due to a low-symptom course. The onset of the disease usually occurs at a young age (14-40 years). The frequency of the syndrome in both sexes is the same, but some researchers report a clear predominance of women.
Causes
The etiology of Melkersson-Rosenthal syndrome remains unknown. The genetic conditionality of the disease with an autosomal dominant type of inheritance is assumed. This is confirmed by the registration of family cases, the identification of a mutation of the 9p11 locus or its translocation to chromosome 21. Genetic predisposition is realized when the body is exposed to various provoking factors:
- Infections. The most common triggers are infectious agents, in particular, staphylococci, streptococci, herpesviruses. The development of the disease is associated with an exacerbation of chronic inflammatory processes (oropharyngeal, odontogenic and rhinogenic).
- Allergic reactions. Hyperplasia and swelling of soft tissues occur in response to the action of food allergens. Special importance is given to chemical additives (cobalt, sodium glutamate, dyes). The effect of hypersensitivity is confirmed by the detection of immune complexes in the blood.
- Autoimmune pathology. The relationship of the syndrome with autoimmune disorders – sarcoidosis, Crohn’s disease, systemic lupus erythematosus is described. Quite often, a combination with Hashimoto’s thyroiditis is detected, but other autoimmune conditions can also have an effect.
The disease is recognized as multifactorial, but there is no convincing evidence of its infectious, immuno-mediated or hereditary origin. Stressful situations, injuries of the soft tissues of the face and head, primary lymphedema can provoke the occurrence of the disease. A potential etiological factor is considered to be constitutionally conditioned or acquired insufficiency of the hypothalamic system, the involvement of lymphoproliferative conditions is assumed.
Pathogenesis
The mechanisms of development of Melkersson-Rosenthal syndrome still need to be studied. Several theories have been proposed to explain the clinical picture – allergic, angioedema, infectious. Cellular sensitization to microbial or other antigens can serve as an important etiopathogenetic moment, which is confirmed by immunopathological shifts. Insufficiency of the function of T-suppressors and phagocytosis, the presence of immune complexes and lymphocytic infiltrates, which are often explained by delayed-type hypersensitivity, were revealed.
The theory of angioedema disorders is closely related to the allergic one. It presupposes the presence of congenital or acquired disorders of parasympathetic regulation of vasomotor reactions. Functional autonomic shifts lead to increased vascular permeability, which provokes swelling of the soft tissues of the head and neck, especially in areas innervated by the facial nerve. In parallel, the immune response is activated with the development of cellular reactions. In addition to this, some authors take into account the neurodystrophic genesis of the syndrome.
Histopathological changes are represented by nonspecific inflammation of connective tissue, accompanied by vascular exudative reactions. In the foci, the number of fibroblasts, plasmocytes, mast cells located mainly perivascularly and in a state of degranulation increases. Along with edema, vasodilation and endothelial proliferation, signs of a specific process with small limited non-caseous granulomas formed by epithelioid cells and lymphocytes are found in paravasal tissues.
Classification
The uncertainty of the systematization criteria makes many cases of Melkersson-Rosenthal syndrome unrecognized. Some authors attribute pathology to neurostomatological conditions, considering it symptomatic or idiopathic cheilitis. Others see it in the structure of neuroangiotrophic syndromes or chronic dermatoses. Being at the junction of several disciplines, the disease can occur in several forms:
- Classic (full). It is characterized by the presence of a triad of signs – macroheilia, recurrent neuropathy or neuritis of the facial nerve, edematous-folded tongue. But this combination occurs only in 20-25% of cases.
- Oligo- or monosymptomatic. Oligosymptomatic forms usually occur without damage to the facial nerve. Recurrent swelling of the lips, also known as granulomatous Micher’s cheilitis, is considered by many authors to be a monosymptomatic variant of the disease.
Symptoms
The leading manifestation of Melkersson-Rosenthal syndrome, present in 95% of patients, is macroheilia or recurrent swelling of the lips. The lips increase in size (2-3 times), become tightly elastic, take a bluish-pink color. The red border turns outwards, making the lips look like a tapir trunk. Non-inflammatory swelling is painless, the skin above it is not changed. At the same time, other areas of the face (cheeks, tongue, eyelids), genitals may swell. Repeated short episodes of edema have been experienced by patients for many years.
The second most common symptom is facial nerve neuritis, which is present in 35-40% of cases, sometimes preceding macroheilia. It is characterized by one- or two-sided paresis of facial muscles, often takes a recurrent character. There is a smoothness of the nasolabial fold, a drooping corner of the mouth, lagophthalmos on the side of the lesion. Patients have a vasomotor runny nose, lacrimation and salivation are disturbed, hyperacusis and dysgeusia are detected. Other nerves (trigeminal, lingual, oculomotor) may also be involved in the process.
Half of the patients are characterized by the third sign – edematous-folded tongue, which is considered by a number of authors as an individual developmental anomaly. But confirmation of the granulomatous nature of glossitis allows it to be included in the structure of the pathological syndrome. The tongue looks unevenly thickened and swollen, becomes sedentary. Its surface is covered with deep furrows, becomes bumpy and bluish-red, tooth prints are visible at the edges. On the mucous membrane there are foci of turbidity in the form of uneven spots and stripes, similar to leukoplakia.
Patients are often concerned about primary migraine headaches, which allows them to be considered another symptom of pathology or a minor diagnostic criterion. Other neurological disorders are also detected – oculomotor (diplopia), sensory (ringing in the ears, sudden deafness, anosmia), dizziness. The course of the disease can be remitting or progressive, but with age, the intensity and frequency of exacerbations decrease.
Complications
The disease has a benign character and has no sharply negative consequences for health. Enlarged lips and tongue, along with paresis of the facial muscles, make it difficult to articulate, eat, and create emotional and psychological problems. Patients often suffer from acute anterior uveitis, gastroenterological disorders, and psychotic disorders. It is noted that Melkersson-Rosenthal syndrome increases the likelihood of developing psoriasis, atopic dermatitis, rosacea.
Diagnostics
The disease is accompanied by a clear clinical picture, and therefore the diagnosis can be established on the basis of physical examination data. But given the high frequency of low-symptomatic forms, this may not be enough. Methods of laboratory control and instrumental visualization provide essential assistance to the neurologist in the diagnosis of pathological syndrome:
- Blood test. The standard diagnostic algorithm includes a hemogram supplemented by a biochemical blood test (for acute phase indicators, liver samples). According to the results of a comprehensive immunological study, the presence of CEC, an imbalance of lymphocytic reactions, and a decrease in phagocyte activity are revealed.
- Histological examination. Analysis of biopsy material from lip tissues is often crucial in the diagnostic process. Non-caseous perivascular granulomas, dilation of lymphatic vessels, fibrosis are considered important histological signs of pathology.
- Tomographic methods. For noninvasive determination of the granulomatous nature of edema, CT imaging can be used to determine the densification of a heterogeneous structure. An MRI scan shows an expansion of the periseptal space with an inhomogeneous signal amplification.
Differential diagnosis of Melkersson-Rosenthal syndrome has to be carried out with a wide range of conditions. It should be distinguished from sarcoidosis, Wegener’s granulomatosis, Crohn’s disease. It is necessary to exclude isolated facial nerve neuropathy (Bell’s palsy), Hunt syndrome, contact dermatitis. Macrocheilia often mimics angioedema, cavernous hemangioma, Meige’s trophedema, and requires separation from cheilitis.
Treatment
Conservative therapy
Given the lack of common views on etiopathogenesis, the treatment of patients presents certain difficulties. It is based on drug correction, which assumes an impact on the probable mechanisms of pathology development and its symptoms. As initial options, systemic and topical corticosteroids (prednisolone, triamcinolone) are prescribed, which can reduce the severity of edema and the inflammatory process.
As an alternative to corticosteroids, cytostatics (methotrexate), derivatives of salicylic acid (sulfasalazine) and aminoquinoline (hydroxychloroquine) are proposed to be used. In complex therapy, antihistamines, antibiotics (tetracycline, roxithromycin, clindamycin) can be prescribed. Among the general measures, the oral cavity is sanitized, the nature of nutrition is corrected. Chronic slowly progressing pathology requires dynamic monitoring of patients, if necessary, treatment is adjusted.
Surgical treatment
Edema accompanied by pronounced defiguration of the maxillofacial region and resistant to drug correction is treated by surgical excision of the compacted areas. To improve the cosmetic effect, reconstructive operations are recommended to be performed in combination with intraocular administration of corticosteroids. In some cases, surgical decompression of the facial nerve and its electrical stimulation are resorted to.
Experimental treatment
Standardized approaches to therapy have not been developed, and existing methods are considered insufficiently effective due to the high frequency of relapses. This creates the need to search for new ways of therapeutic correction of the pathological process. There are reports of the effectiveness of antilepromatous drugs (dapsone, clofazimine) that reduce the phenomena of granulomatosis. Anticytokine therapy (infliximab, adalimumab) can be considered a promising direction, which in studies has shown rapid results and the ability to reduce the frequency of relapses.
Prognosis and prevention
The prognosis for life and ability to work against the background of Melkersson-Rosenthal syndrome is favorable, but structural changes in the facial area are an unpleasant cosmetic defect, disrupt the function of speech and chewing. The disease has a chronic relapsing character, even against the background of ongoing therapy, it is prone to progression and periodic exacerbations. For preventive purposes, concomitant pathology is treated, chronic foci of infection are eliminated, and contact with suspected allergens is excluded.