Published Web Locationhttps://doi.org/10.5070/D398d1x0m2
From the Ronald O. Perelman Department of Dermatology, New York University
Olympia I Kovich MD, and David E Cohen MD MPH
Dermatology Online Journal 10 (3): 10
A 54-year-old man presented with lip swelling, which was not altered by a trial of medication discontinuation. Patch tests showed reactions to bromonitropropane and gold, which were not clinically relevant. Treatment included topical and intralesional glucorticoids as well as tacrolimus ointment. Granulomatous chelitis an idiopathic disorder that is characterized by painless lip edema. It may be found as part of the triad of Melkersson-Rosenthal syndrome. Treatment includes intralesional glucocorticoids as well as systemic therapies.
History.—A 54-year-old man noted swelling of his lips in February 2003. At that time, his medications included rampiril, simvastatin, tamsulosin, and aspirin. Ramipril was discontinued, and amlodipine was substituted without a change in symptoms. Simvastatin was replaced with ezetimibia without effect, and tamsulosin was discontinued. In addition to the aforementioned medication changes, a methylprednisolone dose pack, and topical hydrocortisone, fluocinonide, fluocinolone, and erythromycin were used without benefit. Upon presentation to a dermatologist, patch tests with the North American Contact Dermatitis Group Standard Allergen Series were performed, which showed positive reactions to bromonitropropane and gold.
The patient was treated with intralesional triamcinolone acetonide and subsequently noted swelling of his lips and submandibular region 48 hours later. A concern for possible infection led to treatment with amoxicillin, cetirizine, and diphenhydramine. Subsequently, all medications were discontinued, with a 50 percent reduction in lip swelling. Due to elevated blood pressure, amlodipine was re-initiated. Evaluation by an otorhinolaryngologist was normal. Treatment with intralesional triamcinolone acetonide was continued on a monthly basis, with intermittent waxing and waning of lip swelling and scale. Tacrolimus ointment 0.03% was added to the regimen.
Physical Examination.—Erythema, edema, and scale were present on the lower lip. The tongue was normal in appearance. Erythematous plaques with scale were present on the elbows. Examination of the facial nerves was normal.
Laboratory data.—A complete blood count with differential analysis, basic metabolic panel, and liver function tests were normal.
Histopathology.—Below an unremarkable dermis there is a superficial and deep, perivascular infiltrate of lymphocytes and plasma cells. The edematous dermis contains several focal, non-caseating granulomas that are surrounded by lymphocytes. A periodic-acid-Schiff stain was negative for fungi and an acid-fast stain was negative for bacilli. Polarization does not show foreign material.
Granulomatous chelitis is an idiopathic disorder that presents with painless edema of one or both lips.  Episodic enlargement of the lips ultimately persists.  Granulomatous cheilitis is classified within the broader category of orofacial granulomatosis. The entities that comprise this category include Melkersson-Rosenthal syndrome, granulomatous chelitis, sarcoidosis, Crohn disease, and infectious disorders.  Melkersson-Rosenthal syndrome presents with the triad of peripheral facial nerve palsy, fissured tongue, and granulomatous chelitis. Therefore, granulomatous chelitis is sometimes considered a monosymptomatic form of this syndrome.  Although nonnecrotizing granulomas are the histopathologic hallmark of the entities that comprise orofacial granulomatosis, this finding is neither specific nor universally present.  Thus granulomatous chelitis is primarily a clinical diagnosis. Other possible etiologies, such as allergic contact dermatitis and Crohn disease, must be eliminated. Orofacial granulomatosis may precede Crohn disease and will wax and wane independent of the activity of gastrointestinal disease.  Treatment of Crohn disease may also improve the findings of orofacial granulomatosis. 
Granulomatosis chelitis occurs in 0.5 percent of patients with Crohn disease.  Depending on the patient's symptoms and a review of systems, evaluation may include a complete blood count, angiotensin-converting enzyme levels, C1 inhibitor level, serum iron, tuberculin skin test, RAST, patch tests, chest radiography, and colonoscopy.  Treatment consists of topical or intralesional glucocorticoids as well as systemic therapies, which include clofazimine, dapsone, hydroxychloroquine, metronidazole, and sulfasalazine.  A case report of remission after a course of treatment with thalidomide has been reported. 
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5. Thomas P, et al. Successful treatment of granulomatous cheilitis with thalidomide. Arch Dermatol 2003; 139:136.
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