Melkersson-Rosenthal syndrome (MRS) is a rare genetic condition characterized by recurrent nonpitting orofacial edema, especially of one or both lips (granulomatous cheilitis), lower motoneuron facial paralysis and fissured dorsal tongue (lingua plicata). It is inherited in an autosomal dominant pattern and may have incomplete penetrance.
The defining components of Melkersson-Rosenthal syndrome (MRS) are lingua plicata, facial nerve palsy that may be unilateral or bilateral, partial or complete   and orofacial edema or granulomatous cheilitis  . The disease has a recurrent character, with intermittent relapses and asymptomatic periods. Episodes tend to become worse and more prolonged as the disease progresses. It is sometimes associated with other conditions, such as sarcoidosis, tuberculosis, leprosy, histoplasmosis, foreign body reactions, granulomatosis with polyangiitis, mixed connective tissue disease, Bell's palsy and Crohn's disease, in which case patients also exhibit symptoms of the underlying pathology. Some patients may have only one or two of the three components of the disease. Melkersson-Rosenthal syndrome can be a manifestation of Crohn's disease, sarcoidosis, and orofacial granulomatosis, so these entities should be ruled out first when a patient presents.
Granulomatous cheilitis manifests as diffuse or nodular, soft or firm swelling of the lips and/or surrounding tissues. The lips may appear cracked and discolored and eventually become painful. If the syndrome appears as part of Crohn's disease, affected mucosa takes the typical "cobblestone" appearance and may ulcerate . Cheilitis can be asymmetric or unilateral and can also become permanent. The edema may involve neighboring structures, such as the eyelids, palate, gingiva, larynx and pharynx. The affected lip becomes painful, firm, changes color over time and becomes fissured. The initial symptoms usually resolve while subsequent episodes may be more severe, last longer or fail to disappear. The patient may also exhibit fever, headache, and visual disturbances. Additional facultative traits include diminished salivary gland secretion, decreased gustatory sensation, mask-like facies, thick lower lip vermilion, furrowed tongue, abnormal temperature regulation and other autonomic nervous system abnormalities, lymphadenopathy, and nystagmus. The olfactory, auditory, glossopharyngeal and hypoglossal nerves may also be affected.
The diagnosis of Melkersson-Rosenthal syndrome is based on clinical findings. If needed, skin biopsies may be performed and they reveal different features, depending on the stage of the disease. In early stages, lymphedema and perivascular lymphocytic infiltration are found, while later in the evolution of the disease non-caseating granulomas around vessels have been described . However, it is important to rule out Crohn's disease and sarcoidosis, and that is achieved by performing a biopsy of the lip or surrounding tissues. If the result is unsatisfactory, a colonoscopy is indicated to exclude Crohn's disease , and gallium or positron emission tomography scans are recommended to rule out sarcoidosis and tuberculosis. A serum angiotensin-converting enzyme test can also be used to detect sarcoidosis. Granulomatous cheilitis may occur as a result of metal or food additives sensitivity, and patch tests with these antigens are useful to diagnose it .