Cheilitis granulomatosa G51.2

Miescher, 1945

Cosmetically disfiguring, initially chronically recurrent, then permanently persistent, granulomatous inflammation of the lip that may occur in isolation (idiopathic) or as a cutaneous partial manifestation of a granulomatous systemic disease. These include:

• Melkersson-Rosenthal syndrome
• Sarcoidosis
• M. Crohn's disease.

In children, especially in the constellation of oral aphthae and cheilitis granulomatosa, a high percentage of Crohn's disease is to be expected.

In individual cases, type I food allergies have also been causally blamed.

Orofacial granulomatosis occurs in both children and adults. The average age is 23 years, with men and women being equally affected.

Initially changing, later permanent, diffuse, inflammatory swelling of the lips, especially the upper lip and surrounding skin with bulging, sometimes proboscis-like protrusion of the lips (tapir mouth) and eraser-hard consistency proliferation.

• An associated lingua plicata (gfls. in combination with an exfoliatio areata linguae), a facialis paresis or a hyperplastic gingivitis indicate a Melkersson-Rosenthal syndrome.
• If the cheilitic changes occur in combination with persistent (especially large and deep) aphthae, Crohn's disease must be excluded (therapeutic consequences- see below Cushing K et al.2021).
• Ulcerative colitis may also be associated with these symptoms.

In the early oedematous inflammatory phase, dilated lymphatic and blood vessels are found with spongy, perivascular, lymphocytic infiltrates. In a later stadium, small epithelial cell granulomas with giant cells may appear in addition to a distinct fibrosis of the dermis. In the case of association with ulcerative colitis or Crohn's disease, dense mixed-cell inflammatory infiltrates with shot-shot-like distributed, non-keratinizing granulomas with epithelial and giant cells are found. Remark: Epitheloid cell granulomas must be searched for in serial sections. Often they are missing completely.

Clinical:

• Angioedema: Acute clinical picture with impressive edematous swellings; only of short duration, swellings disappear completely in the meantime, even in the case of a recurrent course.
• Herpes simplex recidivans: Development of typical herpes blisters. In the case of close recurrences, firm post-herpetic swellings may persist for a longer period of time; also limits the location of the herpes infection.
• Sarcoidosis: Localization is unusual. Lesions, mostly plaque-like, brownish-reddish coloration, histology with epithelioid cell granulomas is diagnostic.
• Foreign body granulomas: (anamnesis important!); after injection of filler substances: important differential diagnosis; injections may have been carried out a long time ago.
• Morbihan's disease: Chronic, diffuse, erythematous, symmetrical swelling; histology is uncharacteristic. No pathognomonic laboratory symptoms.

Differential diganosis Histology:

• Sarcoidosis: dense accumulation of "naked" non-caseating granulomas.
• Foreign body granuloma: epithelioid cell granulomas with numerous giant cells of the foreign body type.
• Infections (mycobacteriosis, leishmaniasis): mixed cell granulomatous infiltrates. Pathogen detection.

For Melkersson-Rosenthal syndrome: see there. Otherwise, treatment of the underlying disease if necessary, e.g. sarcoidosis, Crohn's disease.

In monosymptomatic cheilitis granulomatosa, intralesional triamcinolone acetonide injections (e.g. Volon A diluted with scandicain in a ratio of 1:3) at 1- or 2-week intervals over a few weeks (depending on the clinic) are recommended as the treatment of first choice.

Partial success is possible with early use of clofazimine (e.g. Lampren) 100 mg/day p.o. for 6 months (longer if necessary) and a repeat cycle after a 3-month break.

Alternative: Positive casuistic experience exists with the long-term (>6 months) high-dose use of fumaric acid esters. (Hauck G 2017). Dosage analogous to the schematic procedure for psoriasis therapy.

Alternative: If the dermatological symptoms are resistant to therapy and the gastroenterological symptoms are negligible, therapy with a TNF-alpha antagonist is indicated.

Alternative: If the dermatological symptoms are resistant to therapy, the use of vedolizumab is recommended (approved for Crohn's disease). Individual successes have also been described when a TNFα inhibitor is unsuccessful (Gueutier A et al. 2019).

Alternative: In the case of persistent, therapy-resistant swelling, an enoral surgical reduction plasty should be considered.

In the event of an association with regional enteritis (Crohn's disease), the underlying disease should be treated in collaboration with a gastroenterologist.

When cheilitis granulomatosa occurs in childhood, a frequent association with Crohn's disease is found in combination with oral aphthae. This clinical picture is called orofacial granulomatosis in pediatric and international literature. This term also seems to be used for cheilitis granulomatosa occurring in adults.

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