Cheilitis Granulomatosa of Miescher

 

Granulomatous cheilitis is a chronic swelling of the lip due to granulomatous inflammation. Miescher cheilitis is the term used when the granulomatous changes are confined to the lip. Miescher cheilitis is generally regarded as a monosymptomatic form of the Melkersson-Rosenthal syndrome, although the possibility remains that these may be 2 separate diseases. Melkersson-Rosenthal syndrome is the term used when cheilitis occurs with facial palsy and plicated tongue

Melkersson-Rosenthal syndrome is occasionally a manifestation of Crohn disease or orofacial granulomatosis (OFG)

 

 

Cheilitis granulomatosa is episodic with nontender swelling and enlargement of one or both lips. Occasionally, similar swellings involve other areas, including the periocular region.

The first episode of edema typically subsides completely in hours or days. After recurrent attacks, swelling may persist and slowly increase in degree, eventually becoming permanent. Recurrences can range from days to years. Attacks sometimes are accompanied by fever and mild constitutional symptoms (eg, headache, visual disturbance). Cranial nerve palsies may be associated. Melkersson-Rosenthal syndrome is the association with facial nerve palsy.^8,9

Physical

The earliest manifestation of granulomatous cheilitis is sudden diffuse or occasionally nodular swellings of the lip or the face involving (in decreasing order of frequency) the upper lip, the lower lip, and one or both cheeks. The forehead, the eyelids, or one side of the scalp may be involved (less common). The upper lip is involved slightly more often than the lower lip, and it may feel soft, firm, or nodular on palpation.

Once chronicity is established, the enlarged lip appears cracked and fissured with reddish brown discoloration and scaling. The fissured lip becomes painful and eventually acquires the consistency of firm rubber. Swelling may regress very slowly after some years. Regional lymph nodes are enlarged (usually minimally) in 50% of patients.

A fissured or plicated tongue is seen in 20-40% of patients. Its presence from birth (in some patients) may indicate a genetic susceptibility. Patients may lose the sense of taste and have decreased salivary gland secretion.

Facial palsy of the lower motor-neuron type occurs in about 30% of patients. Facial palsy may precede attacks of edema by months or years, but it more commonly develops later. Facial palsy is intermittent at first, but it may become permanent. It can be unilateral or bilateral, partial or complete. Other cranial nerves (eg, olfactory, auditory, glossopharyngeal, hypoglossal) are occasionally affected.

Central nervous system involvement has been reported, but the significance of resulting symptoms is easily overlooked because they are very variable (sometimes simulating multiple sclerosis but often with a poorly defined association of psychiatric and neurologic features). Autonomic disturbances may occur.

Causes

The cause of granulomatous cheilitis is unknown.¹⁰ A genetic predisposition may exist in Melkersson-Rosenthal syndrome; siblings have been affected, and a plicated tongue may be present in otherwise unaffected relatives. Crohn disease, sarcoidosis, and orofacial granulomatosis may present in a similar clinical fashion, and with identical histologic findings. Dietary or other antigens are the most common identified cause of orofacial granulomatosis (OFG).^11,12 Contact antigens are sometimes implicated.¹³ OFG may result from reactions to some foods or medicaments, such as cinnamon aldehyde and benzoates

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Laboratory Studies

Serum angiotensin-converting enzyme test may be performed to help exclude sarcoidosis.

Patch tests may be used to help exclude reactions to metals, food additives, or other oral antigens. Some cases may be associated with such sensitivities. If found, avoidance of the implicated allergen is recommended.

Imaging Studies

Gastrointestinal tract endoscopy, radiography, and biopsy may be used to help exclude Crohn disease.

Chest radiography or gallium or positron emission tomography (PET) scanning may be performed to help exclude sarcoidosis and tuberculosis.

Panorex dental films may be obtained to assess for the presence of a chronic dental abscess

Histologic Findings

Histologic changes are not always conspicuous or specific in many cases of long duration; the infiltrate becomes denser and pleomorphic, and small focal granulomas are formed that are indistinguishable from Crohn disease or sarcoidosis. Small granulomas occur in the lymphatic walls in some cases. Similar changes may be present in cervical lymph nodes

Medical Care

Simple compression for several hours daily may produce significant improvement. Compression devices may reduce lip edema. Orofacial granulomatosis may improve with implementation of a cinnamon- and benzoate-free diet. Intralesional corticosteroids may be helpful in some patients.¹⁵ Success with other treatments has been reported anecdotally. None of the agents listed below has been systematically evaluated.

Immunomodulatory agents are as follows:

• Nonsteroidal anti-inflammatory agents
• Mast cell stabilizers¹⁶
• Clofazimine¹⁷
• Methotrexate¹⁸
• Tacrolimus
• Infliximab¹⁹
• Dapsone
• Triamcinolone and dapsone injections²⁰

Antimicrobials are as follows:

• Tetracycline (used for anti-inflammatory activity)
• Minocycline²¹
• Roxithromycin²²
• Antibiotic treatment of dental abscess - Resulted in remission in anecdotal cases

Surgical Care

Surgery and radiation have been used. Surgery alone is relatively unsuccessful.

Reduction cheiloplasty with intralesional triamcinolone and systemic tetracycline offer the best results.²³ Give corticosteroid injections periodically after surgery to avoid an exaggerated recurrence.

Consultations

Consult a gastroenterologist, an immunologist, and an oral medicine specialist.

Medication

Clofazimine or metronidazole may produce resolution in granulomatous cheilitis. Intralesional corticosteroid (triamcinolone) injections may reduce swelling. Systemic corticosteroids are rarely indicated and not all cases respond.

Azathioprine, dapsone, sulfapyridine, or sulfasalazine may be helpful.

Long-term penicillin, tetracycline, erythromycin, and ketotifen are other management approaches that are occasionally helpful.

No randomized controlled trials have yet been recorded with possible therapies such as tacrolimus, thalidomide, or infliximab.

Antibiotics

Therapy must be comprehensive and should cover all likely pathogens in the clinical setting.

Clofazimine (Lamprene 50- or 100-mg cap)

Inhibits mycobacterial growth, binds preferentially to mycobacterial DNA. Has antimicrobial properties, but mechanism of action is unknown.

Dapsone (Avlosulfon)

Bactericidal and bacteriostatic against mycobacteria. Mechanism of action is similar to that of sulfonamides where competitive antagonists of PABA prevent formation of folic acid, inhibiting bacterial growth.

Anti-inflammatories

These agents decrease inflammatory responses and systemically interfere with events leading to inflammation.

Sulfapyridine (Dagenan)

Competitive antagonist of PABA. Mechanism of action in linear IgA dermatosis is unknown.

Sulfasalazine (Azulfidine)

Decreases inflammatory response and systemically inhibits prostaglandin synthesis.

Corticosteroids

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. In addition, these agents modify the body's immune response to diverse stimuli.

Triamcinolone (Aristocort)

For inflammatory dermatosis responsive to steroids. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing capillary permeability.

Immunosuppressants

These agents inhibit key factors that mediate immune reactions, which, in turn, decrease inflammatory responses.

Azathioprine (Imuran)

Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, which results in lower autoimmune activity.