Melkersson-Rosenthal Syndrome

Melkersson-Rosenthal syndrome is a rare neuromucocutaneous disorder defined by the triad of recurrent orofacial swelling, relapsing lower motor neurone facial palsy and fissured tongue. The complete triad is present in a minority, and monosymptomatic or oligosymptomatic forms are common.

Onset is usually in the second or third decade, and some cases are familial. Lip or facial swelling is the commonest and often the first feature, and the palsy is recurrent and may become permanent.

Pathophysiology. The cause is unknown. Granulomatous inflammation and oedema around the facial nerve in the stylomastoid canal, with compression and ischaemia of the nerve, are thought to produce the palsy.

Genetic susceptibility and an infective or allergic trigger have been proposed without confirmation.

Sudden painless swelling of the lips, cheeks, eyelids or forehead that resolves over days to weeks and recurs, with gradual persistence. Facial palsy can be unilateral or alternating, with forehead involvement, and can precede or follow the swelling by years.

Fissured tongue is present from childhood in many. Associated headache, migraine, altered taste, hyperacusis, lacrimation changes and paraesthesia of the face have been described.

Palsy needs same day assessment to exclude stroke, otitis media with cholesteatoma, Ramsay Hunt syndrome and parotid tumour, and eye protection if the eyelid does not close.

• Clinical diagnosis from the triad or from two features with biopsy support.
• Biopsy of a swollen lip or tongue: non-caseating granulomas, oedema and perivascular lymphocytes. Absent granulomas do not exclude the diagnosis.
• House-Brackmann grading of facial weakness at each visit, and document eyelid closure and corneal sensation.
• Exclusion workup for granulomatous disease: serum ACE, chest radiograph, calprotectin, tuberculosis testing and C1-esterase inhibitor.
• MRI of the brain and internal auditory canal with contrast for recurrent or progressive palsy, or any central or parotid concern.
• Serology for Lyme disease and varicella zoster virus where the history is relevant.

Differential diagnosis.

• Bell palsy without swelling
• Angioedema (hereditary, acquired or drug induced)
• Orofacial granulomatosis and cheilitis granulomatosa
• Crohn disease and sarcoidosis
• Ramsay Hunt syndrome
• Lyme disease
• Parotid or skull base tumour

• Facial palsy within 72 hours of onset: prednisolone 60 mg orally once daily for 5 days, then reduced by 10 mg each day to stop, in adults without a contraindication. Check glucose and blood pressure, and give a proton pump inhibitor when other risk factors for ulcer exist.
• Eye protection for incomplete closure: lubricating eye drops every 1 to 2 hours by day, ointment at night, and taping of the lid. Urgent ophthalmology referral for corneal injury.
• Swelling: intralesional triamcinolone acetonide 10 to 40 mg/mL, 0.1 to 0.5 mL at each site up to 40 mg in a session, repeated every 4 to 6 weeks. Systemic steroids, azathioprine, methotrexate, hydroxychloroquine, clofazimine or anti-TNF agents are used for disabling disease, with prednisolone 0.5 to 1 mg/kg (maximum 40 mg) each morning for 2 to 4 weeks then tapered, azathioprine 2 to 2.5 mg/kg daily after thiopurine methyltransferase testing, or methotrexate 7.5 to 15 mg once weekly with folic acid 5 mg once weekly, in specialist hands.
• Elimination of dietary additives for 6 to 12 weeks has helped some patients.
• Surgical decompression of the facial nerve is rarely done and the benefit is uncertain. Cheiloplasty or reduction surgery treats permanent lip enlargement once inflammation is stable.
• Physiotherapy and botulinum toxin for synkinesis after incomplete recovery, directed by the neurology or facial plastics team.

Monitoring. Review every 3 months in the first year for swelling, palsy grade and steroid effects, then every 6 to 12 months. Document recovery at 3 and 6 months after each palsy.

Referral and escalation. Refer to neurology, oral medicine and ENT. Urgent referral for a first palsy with additional deficits, bilateral palsy, ear vesicles, corneal exposure or any sign of airway swelling.