Melkersson-Rosenthal Syndrome: A Rare Cause of Recurrent Facial Palsy

What Is Melkersson-Rosenthal Syndrome?

Melkersson-Rosenthal Syndrome (MRS, 梅罗综合征) is a rare, chronic neurological and granulomatous disorder characterized by a classic triad of:

1. Recurrent facial palsy (复发性面神经麻痹) — episodic weakness or paralysis of one or both sides of the face
2. Orofacial granulomatous swelling (肉芽肿性唇炎 / 口面肿胀) — persistent, non-pitting swelling of the lips, face, or oral mucosa
3. Fissured tongue (裂纹舌 / 沟纹舌) — deep grooves or fissures on the tongue surface

The complete triad is present in only 8–25% of patients; many present with one or two features (oligosymptomatic or monosymptomatic forms). The monosymptomatic form most commonly presents as isolated orofacial swelling (cheilitis granulomatosa / Miescher's cheilitis) or isolated recurrent facial palsy.

MRS is estimated to affect approximately 0.08% of the general population, though true prevalence is likely underestimated due to frequent misdiagnosis. It can occur at any age but most commonly presents in the second to fourth decade of life, with a slight female predominance.

Pathophysiology: What Causes MRS?

The exact etiology of MRS remains incompletely understood. Current evidence points to a multifactorial pathogenesis involving:

• Granulomatous inflammation: Histopathology of affected tissue shows non-caseating epithelioid granulomas with lymphocytic infiltration — similar to sarcoidosis and Crohn's disease, suggesting a shared immunological mechanism
• Genetic predisposition: Familial cases are reported; associations with HLA subtypes and mutations in genes involved in inflammatory regulation (including NOD2/CARD15, also implicated in Crohn's disease) have been identified
• Infectious triggers: Herpes simplex virus (HSV), Borrelia burgdorferi, and other pathogens have been proposed as triggers in genetically susceptible individuals
• Allergic / hypersensitivity mechanisms: Contact allergens (cinnamon, benzoates, cobalt) have been implicated in some cases
• Autonomic nervous system dysfunction: Lymphatic drainage impairment and autonomic dysregulation may contribute to the persistent edema

Clinical Features in Detail

1. Recurrent Facial Palsy

• Typically lower motor neuron pattern (peripheral facial palsy), indistinguishable from Bell's palsy on first presentation
• May affect the same side repeatedly or alternate between sides
• Episodes may be complete or incomplete; recovery is usually good initially but may become incomplete with repeated episodes
• Bilateral simultaneous facial palsy (diplegia facialis) is rare but characteristic of MRS
• Onset is usually sudden; duration ranges from days to months

2. Orofacial Granulomatous Swelling

• Most commonly affects the lips (especially the upper lip), producing a firm, rubbery, non-tender swelling
• Initially episodic and fully resolving; with repeated episodes becomes persistent and non-resolving (permanent macrocheilia)
• May also involve cheeks, eyelids, gingiva, buccal mucosa, and tongue
• Skin overlying the swelling may appear normal, erythematous, or have a “peau d’orange” texture
• Intraoral involvement may cause difficulty eating, speaking, and maintaining oral hygiene

3. Fissured (Scrotal) Tongue

• Present in approximately 20–40% of MRS patients
• Deep grooves or fissures on the dorsal tongue surface; usually asymptomatic
• Also found in 5% of the general population, so its presence alone is not diagnostic
• May predispose to geographic tongue or candidal infection if oral hygiene is poor

Additional Features

• Headache and migraine-like episodes
• Facial pain or paresthesia
• Hypersalivation or dry mouth
• Taste disturbance
• Cervical lymphadenopathy
• Rarely: involvement of other cranial nerves (trigeminal, glossopharyngeal)

Diagnosis

MRS is a clinical and histopathological diagnosis. There is no single definitive test. The diagnostic workup aims to confirm the characteristic features and exclude other conditions.

Diagnostic Criteria

Diagnosis requires at least two of the three classic triad features, with histopathological confirmation of granulomatous inflammation on lip or facial biopsy.

Essential Investigations

• Lip or facial biopsy: Gold standard; reveals non-caseating epithelioid granulomas with lymphocytic infiltration in the lamina propria; multiple biopsies may be needed as granulomas can be focal
• MRI of the face and parotid glands: Assesses extent of soft tissue involvement; may show enhancement of the facial nerve
• MRI brain: To exclude central causes of facial palsy (MS, brainstem lesion)
• EMG / nerve conduction studies: Assess severity of facial nerve involvement and monitor recovery
• Blood tests: CBC, ESR, CRP, ACE (to exclude sarcoidosis), serum calcium, LFTs, renal function
• Chest X-ray / CT chest: To exclude pulmonary sarcoidosis
• Patch testing: To identify contact allergens if allergic etiology is suspected
• Colonoscopy / GI evaluation: If Crohn's disease is suspected (orofacial granulomatosis may precede intestinal Crohn's by years)

Key Differential Diagnoses

Treatment

There is no curative treatment for MRS. Management is aimed at reducing inflammation, preventing recurrence, and managing complications. Treatment must be individualized based on the dominant features and severity.

Corticosteroids

• First-line treatment for acute episodes of facial palsy and orofacial swelling
• Intralesional triamcinolone injected directly into the swollen lip is the most effective approach for orofacial swelling; repeated injections every 4–8 weeks
• Systemic prednisolone (0.5–1 mg/kg/day) for severe facial palsy or widespread involvement; tapered over 4–6 weeks
• Long-term systemic steroids are limited by side effects; not recommended for maintenance

Immunosuppressive and Anti-inflammatory Agents

• Hydroxychloroquine: Antimalarial with anti-inflammatory properties; used for maintenance; well-tolerated long-term
• Methotrexate: Steroid-sparing agent for refractory cases; requires monitoring of liver function and blood counts
• Clofazimine: Anti-leprosy drug with anti-granulomatous properties; used in refractory orofacial swelling
• Dapsone: Alternative anti-granulomatous agent
• TNF-α inhibitors (infliximab, adalimumab): Emerging evidence for refractory MRS, particularly in cases overlapping with Crohn's disease
• Thalidomide: Used in severe refractory cases; significant teratogenicity limits use

Antiviral Therapy

• If HSV is suspected as a trigger, acyclovir or valacyclovir prophylaxis may reduce recurrence frequency in some patients
• Evidence is limited but the risk-benefit ratio is favorable given the low side-effect profile

Surgical Treatment

• Cheiloplasty (lip reduction surgery): For permanent macrocheilia causing functional or cosmetic impairment; removes excess granulomatous tissue; recurrence is possible
• Facial nerve decompression: Controversial; considered in cases of severe, recurrent, or permanent facial palsy unresponsive to medical treatment; decompression of the facial nerve in the fallopian canal may reduce recurrence
• Parotid surgery: Rarely required for parotid gland involvement

Supportive Measures

• Eye care during facial palsy: lubricating eye drops, moisture chamber, taping the eye closed at night to prevent corneal exposure injury
• Physiotherapy and facial exercises to maintain muscle tone during palsy episodes
• Dietary modification: avoid identified food allergens (cinnamon, benzoates)
• Oral hygiene optimization to prevent secondary infection of fissured tongue
• Psychological support: chronic disfiguring facial swelling significantly impacts quality of life and self-esteem

Prognosis

• MRS is a chronic, relapsing-remitting condition; complete remission is uncommon
• Facial palsy generally recovers well in early episodes but may become permanent with repeated attacks
• Orofacial swelling tends to become permanent over time without treatment
• The condition does not affect life expectancy but significantly impacts quality of life
• Early diagnosis and treatment of swelling episodes may prevent permanent disfigurement

Where to Seek Specialist Care in Shanghai

MRS requires a multidisciplinary approach involving dermatology, neurology, and in some cases oral and maxillofacial surgery. The following Shanghai hospitals offer relevant specialist expertise:

Ruijin Hospital (瑞金医院), Shanghai Jiao Tong University — Dermatology

Ruijin Hospital's Dermatology Department is one of Shanghai's strongest, with expertise in granulomatous skin and mucosal conditions, autoimmune dermatoses, and rare inflammatory disorders — all directly relevant to the orofacial granulomatous component of MRS.

• Dermatology at Ruijin Hospital Shanghai — Overview of the department and how to access specialist care
• Dr. Zheng Jie (郑捷) — Director of Dermatology at Ruijin Hospital; nationally recognized expert in inflammatory and autoimmune skin conditions

Longhua Hospital (龙华医院) — Integrative Neurology

For patients seeking integrative management of recurrent facial palsy — including acupuncture-based facial nerve rehabilitation alongside conventional treatment — Longhua Hospital's integrative neurology department offers combined TCM and Western medicine protocols:

• Integrative Neurology at Longhua Hospital Shanghai — TCM-integrated neurological care including facial nerve rehabilitation programs

How CMCS Can Help

MRS is frequently misdiagnosed as recurrent Bell's palsy or allergic angioedema for years before the correct diagnosis is established. If you or a family member has experienced recurrent facial palsy, persistent lip swelling, or a combination of these features, CMCS can help you access the right specialist in Shanghai for accurate diagnosis and comprehensive management.

Our services include:

• Pre-consultation review of prior biopsy reports, MRI, and clinical history
• Priority appointments with dermatology and neurology specialists at Ruijin Hospital and Longhua Hospital
• Coordination of multidisciplinary evaluation (dermatology, neurology, oral surgery as needed)
• Medical interpretation during all consultations and procedures
• Long-term follow-up coordination for this chronic condition

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