Clinical Challenge: Enlarged and Swollen Lips


  • Cheilitis Granulomatosa 1_1013 Derm Dx

  • Cheilitis Granulomatosa 2_1013 Derm Dx

  • Cheilitis Granulomatosa 3_1013 Derm Dx

A 53-year-old presents complaining of lip swelling for many months. She is otherwise healthy.

Cheilitis granulomatosa, also called granulomatous cheilitis, is a granulomatous disorder of the lips that is found predominantly in young adults. It is non-infectious and non-caseating. Its origin is idiopathic.1, 3, 4This condition is characterized by chronic persistent diffuse enlargement of...

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Cheilitis granulomatosa, also called granulomatous cheilitis, is a granulomatous disorder of the lips that is found predominantly in young adults. It is non-infectious and non-caseating. Its origin is idiopathic.1, 3, 4

This condition is characterized by chronic persistent diffuse enlargement of the lips or face, sometimes accompanied in later stages by oral ulcers, mucosal hypertrophy, gingivitis, cervical lymphadenopathy or gingival enlargement. The lips may become erythematous, and the enlargement can cause midline lip fissuring or angular cheilitis.

In most cases, only either the upper or lower lip is affected, although both can be affected simultaneously. Despite the enlargement, the condition is painless and asymptomatic.  When cheilitis granulomatosa presents along with a fissured tongue and facial nerve palsy, the condition is termed Melkersson-Rosenthal syndrome.1, 3, 4

Crohn’s disease may also present as non-caseating granulomas in the lips and oral cavity. Additionally cobblestoning and mucosal tags may accompany cheilitis granulomatosa, much like the intestinal lesions of Crohn’s disease. This suggests cheilitis granulomatosa may be an early presentation of Crohn’s disease in some patients.1, 2, 3, 4

Cheilitis glandularis is characterized by inflammatory hyperplasia of the lower-lip salivary glands, and manifests as swelling and eversion of the lips. Increased mucous secretions can cause the lips to stick together during the night.

The lower lip enlargement ranges from slight hypertrophy to nodular enlargement and may result from chronic irritation, possibly from chronic sun exposure. This condition affects mostly in adult men. As the epithelium shows dysplasia, cheilitis glandularis is associated with an increased risk for squamous cell carcinoma.1, 3, 4

Actinic cheilitis is a common condition characterized by scaling, roughness or erosions of the vermilion zone of the lower lip. Early changes include atrophy and blurring of the skin/vermilion zone margin, which progresses to fissuring and painful erosions. Scaling and roughness may be signs of precancerous change. It typically affects fair-skinned individuals aged older than 40 years and is associated with increased and prolonged exposure to ultraviolet light.1, 3, 4

Angular cheilitis, also called perlèche, is characterized by inflamed painful fissures that extend downward and outward from the angles of the mouth. Both corners of the mouth are usually affected, and fissures may be confined to the lip mucosa or extend to perioral skin. It can be caused by excessive wetness or dryness, and secondary infection with Candida albicans or Staphylococcus aureus is possible.

It is seen in many contexts, especially in elderly denture-wearing individuals. Other associated conditions include riboflavin deficiency, anorexia nervosa, intraoral candidiasis, Down syndrome, AIDS, chronic mucocutaneous candidiasis, Sjögren syndrome, atopic dermatitis or orthodontic treatment. Treatment varies depending on the inciting condition.1, 3, 4

Diagnosis & Treatment

Biopsy can confirm the cheilitis granulomatosa diagnosis. Biopsy results reveal an inflammatory reaction of lymphocytes, macrophages and plasma cells with non-caseating granulomas. The differential diagnosis may include Crohn’s disease, sarcoidosis, infectious granulomas, Ascher syndrome, allergic contact dermatitis or angioedema. 1, 3, 4

The mainstay of treatment is intralesional corticosteroids, although beneficial effects may be transient and require repeated injections. TNF-alpha inhibitors, such as adalimumab or infliximab, have been reported to be successful.

Other possible treatments include systemic agents like dapsone, clofazimine, hydroxychloroquine, thalidomide, tetracyclines, sulfasalazine, roxithromycin or systemic corticosteroids. Despite the many treatment options, outcomes are not always satisfactory. 1, 3, 4

Michael Montuno, BS, is a senior medical student at University of Florida College of Medicine.  

Adam Rees, MD, is a graduate of the University of California Los Angeles School of Medicine and a resident in the Department of Dermatology at Baylor College of Medicine also in Houston.


  1. Leao JC, Hodgson T, Scully C et al. “Review article: orofacial granulomatosis.” Aliment Pharmacol Ther. 2004 Nov 15; 20(10):1019-27.
  2. Zbar AP, Ben-Horin S, Beer-Gabel M et al. “Oral Crohn’s disease: is it a separable disease from orofacial granulomatosis? A review.” J Crohns Colitis. 2012 Mar; 6(2):135-42.
  3. Bolognia J, Jorizzo JL, Rapini RP. “Chapter 72: Oral Disease.” Dermatology. St. Louis, Mo.: Mosby/Elsevier, 2008.
  4. James WD, Berger TG, Elston DM et al. “Chapter 34: Disorders of the Mucous Membranes.” Andrews’ Diseases of the Skin: Clinical Dermatology. Philadelphia: Saunders Elsevier, 2006.