Melkersson–Rosenthal syndrome

Overview

Melkersson–Rosenthal syndrome (MRS) is a rare neurological disorder characterized by a triad of symptoms: recurrent facial swelling (especially of the lips), recurrent facial paralysis (similar to Bell's palsy), and a fissured tongue (lingua plicata). These three features may not always occur simultaneously, and some patients may present with only one or two symptoms, making diagnosis challenging.

First described in the 20th century by Ernst Melkersson and Curt Rosenthal, the syndrome typically presents in adolescence or early adulthood, although it can appear at any age. MRS is chronic and relapsing in nature, with episodes that may last from days to weeks. While the condition is not life-threatening, it can cause significant cosmetic and functional concerns.

Causes

The exact cause of Melkersson–Rosenthal syndrome is not fully understood, and it is likely multifactorial. Several theories and contributing factors have been proposed:

• Genetic predisposition: Familial cases have been reported, suggesting a hereditary component with possible autosomal dominant inheritance and variable penetrance.

• Immune dysregulation: MRS may be an immune-mediated inflammatory disorder involving granulomatous inflammation, similar to Crohn’s disease or sarcoidosis.

• Infectious triggers: Certain viral or bacterial infections may act as triggers in genetically predisposed individuals.

• Allergic reactions: Food allergies, dental materials, or environmental allergens have been suggested as potential contributing factors.

• Stress and hormonal factors: Emotional stress and hormonal fluctuations may exacerbate the condition.

Although the exact etiology remains elusive, the syndrome is considered a granulomatous cheilitis when lip swelling predominates, and it shares histological features with other chronic inflammatory diseases.

Symptoms

Melkersson–Rosenthal syndrome manifests with a variable combination of symptoms. The classic triad includes:

1. Orofacial Swelling

• Typically non-pitting, painless swelling of the lips (especially the upper lip), cheeks, eyelids, or other facial areas

• Swelling may be intermittent or become persistent and firm over time

• Chronic swelling can lead to cosmetic deformity

2. Facial Paralysis

• Unilateral or bilateral facial nerve palsy, resembling Bell’s palsy

• Recurrent in nature and may worsen over time

• Facial drooping, difficulty closing the eye, drooling, or slurred speech

3. Fissured Tongue (Lingua Plicata)

• Deep grooves or fissures on the dorsal surface of the tongue

• Usually asymptomatic, but may be associated with burning or irritation

• Often present from birth or childhood, and may not be recognized as part of MRS until other symptoms appear

Other Associated Features

• Headaches or migraines

• Dry mouth or eyes

• Loss of taste (ageusia)

• Cervical lymphadenopathy in some cases

The syndrome can be episodic, with periods of remission and flare-ups. Over time, repeated swelling and inflammation may cause permanent tissue changes.

Diagnosis

Melkersson–Rosenthal syndrome is diagnosed clinically, based on the presence of one or more characteristic features, and by ruling out other possible causes. Diagnostic steps include:

1. Clinical Evaluation

• History of recurrent facial swelling and/or facial nerve palsy

• Physical examination noting facial edema, asymmetry, and a fissured tongue

2. Imaging

• MRI of the brain and facial nerves: Used to exclude other causes of facial paralysis or swelling

• May show enhancement or inflammation of the facial nerve

3. Biopsy

• Performed on swollen lip or cheek tissue

• Shows non-caseating granulomatous inflammation, perivascular lymphocytic infiltration, and edema

• Helps differentiate MRS from Crohn’s disease, sarcoidosis, and angioedema

4. Laboratory Tests

• To rule out sarcoidosis (e.g., serum ACE), Crohn’s disease (e.g., CRP, fecal calprotectin), and infectious causes

Because the full triad is present in fewer than one-third of patients at onset, MRS is often misdiagnosed or recognized only after recurrent episodes.

Treatment

There is no definitive cure for Melkersson–Rosenthal syndrome. Treatment is symptomatic and focuses on reducing inflammation, preventing recurrences, and managing cosmetic or functional impairments. Therapeutic approaches include:

1. Corticosteroids

• Oral corticosteroids: Prednisone is commonly used during acute flare-ups to reduce swelling and inflammation

• Intralesional steroid injections: Especially effective for localized lip swelling

2. Immunosuppressive and Anti-inflammatory Medications

• Hydroxychloroquine

• Clofazimine

• Azathioprine or methotrexate in refractory cases

• Nonsteroidal anti-inflammatory drugs (NSAIDs) for mild cases

3. Antibiotics

• Tetracyclines (e.g., doxycycline) may have anti-inflammatory properties and are sometimes used in chronic swelling

4. Physical Therapy

• Facial muscle exercises to recover strength and prevent stiffness after facial paralysis

5. Surgical Management

• Cheiloplasty (lip reduction surgery) in cases of persistent disfiguring lip edema

• Decompression surgery for facial nerve palsy is rarely performed but may be considered in recurrent, disabling cases

6. Lifestyle and Supportive Measures

• Avoid known triggers such as allergens or stress

• Psychological support and counseling for chronic cosmetic or functional issues

Prognosis

The prognosis of Melkersson–Rosenthal syndrome varies. While the condition is benign and non-life-threatening, it can be chronic, relapsing, and cosmetically distressing. Key points include:

• Symptom control: Many patients experience improvement with medical therapy, though complete remission may not be achieved

• Recurrence: Swelling and facial paralysis may recur intermittently

• Permanent changes: Repeated episodes can lead to permanent lip swelling or facial asymmetry

Early recognition and treatment can help reduce the frequency and severity of flare-ups. While there is no cure, most patients can manage symptoms effectively with ongoing care and support.