Cheilitis Granulomatosa

Updated: May 02, 2017
  • Author: Alan Snyder; Chief Editor: William D James, MD  more...
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Overview

Background

Cheilitis granulomatosa (or granulomatous cheilitis) is characterized by persistent idiopathic swelling of the lip due to granulomatous inflammation. It is thought to be a subset of orofacial granulomatosa and is frequently used in the literature to describe the monosymptomatic presentation of Miescher cheilitis. [1, 2, 3, 4, 5]

Orofacial granulomatosis (OFG) represents a spectrum of disease characterized by granulomatous inflammation of the oral and maxillofacial region in the absence of systemic disease like Crohn disease. [1, 2, 5, 6] It is rare for patients to progress to symptoms of Crohn disease. [7, 8]

Miescher-Melkersson-Rosenthal syndrome is the term used when the cheilitis occurs as part of a symptomatic triad including facial palsy and plicated (fissured) tongue.

Miescher cheilitis is a term sometimes used when the granulomatous changes are confined to the lip. Miescher cheilitis is generally regarded as a monosymptomatic form of Miescher-Melkersson-Rosenthal syndrome. See the image below.

Labial swelling and angular cheilitis. Labial swelling and angular cheilitis.
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Epidemiology

While the actual frequency is unknown, one study estimated its incidence at 0.08% of the general population. [9] Onset of granulomatous cheilitis usually is in young adult life.

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Etiology

The cause of granulomatous cheilitis is unknown. [10] Normal lip architecture is altered by lymphedema and noncaseating granulomas in the lamina propria. Excessive permeability of facial cutaneous vessels resulting from abnormal regulation of the autonomic nervous system has been suggested as a potential cause. Hornstein proposed that nonspecific antigens may stimulate perivascular cells to form granulomas, causing obstruction of the vessels and subsequent facial swelling. [11]

Dietary or other antigens are the most common identified cause of orofacial granulomatosis (OFG). [12, 13] Contact antigens such as cobalt, gold, or mercury are sometimes implicated. [14] OFG may also result from reactions to some foods or medicaments, particularly cinnamon aldehyde and benzoates, but also butylated hydroxyanisole, dodecyl gallate, menthol, and monosodium glutamate. [15] Expression of protease-activated receptor 1 and 2 occurs in orofacial granulomatosis. Th1 immunocytes produce interleukin 12 and RANTES/MIP-1alpha and granulomas. HLA typing may show HLA-A2 or HLA-A11. [16]

Crohn disease, sarcoidosis, and OFG may present with similar histologic findings. Analogous findings have also been reported after liver transplantation in children. [17] Recent research has attempted to identify related genetic risk factors between Crohn disease and OFG to correlate their similar clinical presentation and sometimes comorbid development. [5, 18] Missense coding in NOD2-variant patients may indicate the concurrent development of OFG with intestinal disease, but not OFG alone. [19]

A genetic predisposition may exist in Miescher-Melkersson-Rosenthal syndrome; siblings have been affected, and a plicated tongue may be present in otherwise unaffected relatives. Paternal and maternal inheritance has been implicated in some cases. [20] A mutation in the FATP1 gene has been found in patients with this syndrome. [21] It may follow a pattern of autosomal dominant inheritance,e with the responsible gene being located on 9p. [22]

A summary of possibilities follows:

  • Genetics - Debate about link with HLA antigen and inheritance patterns of different subsets of the disease
  • Food allergy - Various food additives thought to cause or precipitant event; 60% of individuals with condition are atopic (eczema, IgE levels); prime causative agents or exacerbation of disease
  • Allergy to dental material - No conclusive evidence
  • Infection - Studies have focused on Mycobacterium tuberculosis, Mycobacterium paratuberculosis, Saccharomyces cerevisiae, and Borrelia burgdorferi but provide insufficient evidence
  • Immunological - Hypothesis that no single antigen causes disease, rather a random influx of inflammatory cells; delayed sensitivity reaction rather than super antigen; results reflect an immunological nature
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Prognosis

Swelling is typically chronic. Morbidity related to the disease depends also on whether an underlying organic disease, such as Crohn disease or sarcoidosis, [23] is present. Patients, especially children and adolescents, presenting with what appears to be granulomatous cheilitis or OFG should be very carefully evaluated for gastrointestinal symptoms, signs, and disease. [24]

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