Cheilitis Granulomatosa

Cheilitis granulomatosa is persistent or recurrent firm swelling of one or both lips caused by granulomatous inflammation, with no or minimal involvement of other oral tissue.

It is the monosymptomatic, lip limited form of the orofacial granulomatosis spectrum. It appears most often in adolescents and young adults, and the upper lip is the commonest site.

Pathophysiology. Lymphatic obstruction from perivascular non-caseating granulomas and lymphocytes causes lymphoedema and later fibrosis of the lip.

The trigger is unknown, and allergy, infection and genetic factors have been suggested. Over time, repeated oedema produces permanent enlargement.

Painless, rubbery, non-pitting swelling of the lip beginning as short episodes lasting days to weeks, with progression to a continuous swelling. The vermilion may be fissured, scaly or red, and angular cheilitis is frequent.

Look for cranial nerve VII palsy, fissured tongue and other oral features that would place the patient in a wider syndrome. Ask about gut symptoms, skin disease and drug history (ACE inhibitors).

• Wedge or incisional biopsy including labial minor salivary tissue: non-caseating granulomas with oedema and fibrosis.
• Special stains and culture for acid fast bacilli and fungi, and polarisation for foreign material.
• Bloods and tests to exclude Crohn disease, sarcoidosis and tuberculosis: full blood count, C-reactive protein, serum ACE, faecal calprotectin, chest radiograph and interferon gamma release assay.
• Patch testing and dietary assessment, for a food or contact allergen.
• C4 and C1-esterase inhibitor level and function to exclude hereditary angioedema.

Differential diagnosis.

• Orofacial granulomatosis with other oral sites
• Melkersson-Rosenthal syndrome
• Hereditary or acquired angioedema
• Actinic cheilitis and contact cheilitis
• Crohn disease and sarcoidosis
• Lymphangioma, haemangioma or salivary tumour of the lip
• Cellulitis or insect bite

• Elimination of cinnamon and benzoate additives for 6 to 12 weeks, with a dietitian. Response is variable.
• Intralesional triamcinolone acetonide 10 to 40 mg/mL, 0.1 to 0.5 mL at each site, up to 40 mg in one session, repeated every 4 to 6 weeks as needed. This is the most used first line treatment for the lip.
• Topical tacrolimus 0.1% ointment twice daily or a potent topical steroid for scaling and fissuring.
• Persistent or disabling swelling: hydroxychloroquine 200 mg orally twice daily (not more than 5 mg/kg of actual body weight daily, with annual retinal screening after 5 years and dose reduction when eGFR is under 60), clofazimine, methotrexate or an anti-TNF agent under specialist direction. Evidence is limited to case series.
• Cheiloplasty, with reduction of fibrotic tissue, when inflammation has been controlled for at least 6 to 12 months and the patient has residual deformity.
• Treat angular cheilitis with miconazole oral gel 20 mg/g applied twice daily for 7 to 14 days.

Monitoring. Review every 3 months in the first year, and measure lip dimensions and photographs. Reassess for Crohn disease every 6 to 12 months.

Referral and escalation. Refer to oral medicine or dermatology, and to maxillofacial or plastic surgery for reduction. Urgent review for facial palsy, airway involvement or sudden swelling with systemic symptoms.