Granulomatous cheilitis refers to an uncommon condition in which there is lumpy swelling of the lips. It is also known as cheilitis granulomatosa. There are many different causes, such as allergy, Crohn disease, sarcoidosis and orofacial granulomatosis. Rare causes are infections, cancers and genetic disorders.
Miescher-Melkersson-Rosenthal syndrome refers to recurrent chronic (long lasting) swelling and enlargement of one or both lips. Facial palsy (muscle weakness) and fissuring of the tongue may also occur. There is no known cause for this syndrome but genetics may have a role to play as members of a single family have been affected.
The condition is rare and it may occur in people of any race, sex and age, although onset is usually in early adulthood.
Melkersson-Rosenthal syndrome is the term used when cheilitis occurs with facial palsy and complicated tongue; this syndrome is occasionally a manifestation of Crohn disease or orofacial granulomatosis (OFG). The latter term is used when there is no evidence of Crohn disease, but some patients progress to manifest Crohn disease. Thus, the terminology can be confusing.
Dietary or other antigens are the most common identified cause of OFG. Contact antigens such as cobalt, gold, or mercury are sometimes implicated. 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.
A summary of possibilities follows:
- Genetics – Debate about link with HLA antigen
- 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, Mycobacteriumparatuberculosis, 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
Serum angiotensin-converting enzyme test may be performed to help exclude sarcoidosis. Patch tests may be used to help exclude reactions to metals, food additives, or other oral antigens ; some cases of granulomatous cheilitis may be associated with such sensitivities. If found, avoidance of the implicated allergen is recommended.
Gastrointestinal tract endoscopy, radiography, and biopsy may be used to help exclude Crohn disease. Chest radiography or gallium or positron emission tomography (PET) scanning may be performed to help exclude sarcoidosis and tuberculosis. Panorex dental films may be obtained to assess for the presence of a chronic dental abscess.
A biopsy of the swollen lip or orofacial tissues is indicated but often shows only lymphoedema and perivascular lymphocytic infiltration during the early stages and may only later show granulomas. A biopsy may help to exclude Crohn disease, sarcoidosis, lymphoma, and other conditions in the differential diagnosis.
What are the signs and symptoms?
In Miescher cheilitis, the changes are confined to the lip. The first symptom is a sudden swelling of the upper lip. In most cases this first episode goes away completely within hours or days. Swelling of the lower lip and one or both cheeks may follow in Melkersson-Rosenthal syndrome. Less commonly, the forehead, eyelids, or one side of the scalp may be involved. The swelling may feel soft, firm or nodular when touched.
Recurrent attacks may occur within days or even years after the first episode. At each episode the swelling may become larger, more persistent and eventually become permanent. At this time the lips may crack, bleed and heal leaving a reddish-brown colour with scaling. This can be painful. Eventually the lip takes on the consistency of hard rubber.
Other symptoms that may occur include:
- Fever, headache and visual disturbances
- Mild enlargement of regional lymph nodes in 50% of cases
- Fissured or plicated (pleat-like effect) tongue in 20-40% of cases
- Facial palsy (paralysis); intermittent, then possibly permanent and can be unilateral or bilateral, and partial or complete. It occurs in about 30% of cases. Other cranial nerves (eg, olfactory, auditory, glossopharyngeal, hypoglossal) are occasionally affected.
Skin biopsy of the affected tissue shows characteristic granulomas i.e. a mixed inflammatory cell infiltration in the dermis (the deeper layer of the skin).
What treatment is available?
If it is related to an allergy, responsible dietary components or causative substances should be avoided long term. If there is underlying disease, systemic treatment for this may also reduce the swelling of the lips.
The following measures have been reported to reduce the severity of Miescher cheilitis or Melkersson-Rosenthal granulomatous cheilitis in at least some cases.
- Topical corticosteroids
- Long term anti-inflammatory antibiotics e.g. a six to twelve month course of tetracycline, erythromycin or penicillin
- Corticosteroids injected into the lips to reduce swelling. Injections need to be repeated every few months.
- Non-steroidal antiinflammatory agents
- Mast cell stabilisers eg ketotifen
- Surgical reduction
Conditions to consider in the differential diagnosis of granulomatous cheilitis include the following:
- Dental abscess or infection
- Orofacial granulomatosis
- Angioedema, Acquired
- Angioedema, Hereditary
- Crohn Disease