What is the initial treatment for a patient presenting with Melkersson-Rosenthal syndrome characterized by lip swelling and aneurysms?

Initial Treatment for Melkersson-Rosenthal Syndrome with Lip Swelling and Aneurysms

The initial treatment for Melkersson-Rosenthal syndrome (MRS) presenting with lip swelling and aneurysms should be high-dose systemic corticosteroids, which can dramatically reduce orofacial inflammation and prevent progression of vascular complications.

Clinical Presentation and Diagnosis

Melkersson-Rosenthal syndrome is a rare neuro-mucocutaneous disorder characterized by:

• Recurrent orofacial swelling (most commonly lip edema)
• Facial nerve paralysis
• Fissured tongue

The complete triad is rarely seen together, with monosymptomatic or oligosymptomatic presentations being more common 1, 2. The presence of aneurysms in MRS represents a serious vascular complication that requires prompt attention.

Treatment Algorithm

First-Line Treatment

1. High-dose systemic corticosteroids:
   • Intravenous methylprednisolone 1,000 mg/day for 3 days 3
   • Follow with oral prednisolone maintenance therapy
   • This approach has shown dramatic response for persistent swellings 3

For Lip Swelling Management

• Apply white soft paraffin ointment to the lips every 2 hours 4
• Use mucoprotectant mouthwash three times daily (e.g., Gelclair) 4
• Clean the mouth daily with warm saline mouthwashes 4
• Consider benzydamine hydrochloride oral rinse for pain relief 4

For Aneurysm Management

• Immediate cardiovascular evaluation by a skilled cardiologist 4
• Echocardiogram to assess aneurysm size and location 4
• For aortic aneurysms:
  • Begin medical treatment with cyclophosphamide and corticosteroids before any intervention 4
  • Consider β-blockers to reduce aortic expansion rate 4
  • Consider angiotensin II receptor blockers (ARBs) as they may inhibit TGF-β signaling 4

Monitoring and Follow-up

• Echocardiogram every 6 months if aortic diameter >4.5 cm or rate of increase >0.5 cm/year 4
• Annual echocardiogram if diameter <4.5 cm and rate of increase <0.5 cm/year 4
• Consider cross-sectional imaging (CT or MRI) to establish baseline dimensions 4

Alternative Treatments for Refractory Cases

If corticosteroid therapy fails to produce adequate response:

1. Clofazimine: 100 mg 4 times weekly for 3-11 months 5

   • Complete remission achieved in 50% of patients
   • Clinical improvement in 30% of patients with moderate swelling

2. Immunosuppressives to consider:

   • Azathioprine 4
   • Monoclonal anti-TNF antibodies for severe or refractory cases 4

Important Caveats and Considerations

• Differential diagnosis: Rule out angioedema, Crohn's disease, sarcoidosis, and infections before confirming MRS 1, 6
• Biopsy confirmation: Lip biopsy showing non-caseating granulomas is essential for definitive diagnosis 5
• Surgical intervention: For vascular complications, surgery should not be delayed if the patient is symptomatic, despite medical therapy 4
• Spontaneous remission: Can occur in approximately 30% of untreated patients, but should not be relied upon when aneurysms are present 5

Pitfalls to Avoid

1. Misdiagnosis: MRS can be confused with hereditary or acquired angioedema, leading to inappropriate treatment 1
2. Delayed treatment: Facial nerve involvement may respond more slowly to corticosteroids than the swelling, requiring prolonged therapy 3
3. Inadequate monitoring: Failure to regularly monitor aneurysm size can lead to unexpected rupture or dissection 4
4. Monotherapy: Using only antihistamines or antivirals is ineffective for MRS 1

Early aggressive treatment with corticosteroids offers the best chance of controlling inflammation, preventing progression of vascular complications, and improving long-term outcomes in patients with this rare syndrome.