Dermatology Online Journal
- Author(s): Rose, Amy E
- Leger, Marie
- Chu, Julie
- Meehan, Shane
- et al.
Cheilitis granulomatosaDepartment of Dermatology, New York University, New York, New York
Amy E Rose MD, Marie Leger MD PhD, Julie Chu MD, Shane Meehan MD
Dermatology Online Journal 17 (10): 15
Melkersson-Rosenthal Syndrome (MRS) is a rare syndrome that is characterized by a triad of facial paralysis, chronic edema of the lip, and a fissured tongue. Most commonly, one element of the triad precedes the development of the other symptoms. We present a case of cheilitis granulomatosa (CG) as a manifestation of incomplete MRS. As the etiology remains unknown, treatment of CG is challenging. Intralesional glucocorticoids remain the first-line treatment, but recurrences are common. We discuss alternative treatment strategies that include combination therapy with other anti-inflammatory agents and biologics, such as infliximab.
A 43-year-old woman was referred to the Charles C. Harris Skin and Cancer Pavilion in October, 2010, for evaluation of a permanently swollen upper lip for the past 16 months. She also reported burning and flushing of the face when nervous and occasional papules on the face and neck. There had been no regression in lip swelling since its onset.
The patient was being treated by an allergist for rhinitis with monthly intramuscular allergen immunotherapy injections and oral antihistamines, which did not result in improvement of the lip swelling. She denied difficulty breathing, gastrointestinal symptoms, neurologic symptoms, or urticaria and was unable to identify a triggering event that was associated with the onset of lip swelling.
Past medical history included hypertension treated with valsartan. Prior to the onset of theswelling, she had never had a previous similar episode and there was no family history of cutaneous disorders. She had been treated with intralesional triamcinolone (TAC) one year prior to presentation with minimal response. Several months of treatment with tetracycline resulted in no improvement. The patient, who only has the cheilitis granulomatosa element of the Melkersson-Rosenthal syndrome, showed improvement after four injections with 10 mg/mL of intralesional TAC, but the injected volume was limited by patient discomfort. A punch biopsy of the upper lip was performed.
Mild erythema is noted on the cheeks, with a few scattered erythematous papules. The upper lip shows diffuse swelling, most prominent centrally with a rubbery consistency and palpable nodularity of the soft tissue. The lip is non-tender to palpation. Also noted are fissures of the oral commissures. There are no other findings of the tongue or oral mucosa.
A chest radiograph showed no abnormalities, and a Mantoux test was non-reactive. Evaluation for food allergies was negative. Magnetic resonance imaging of the head showed nodular enlargement of the lip and faint enhancement surrounding a small non-enhancing focus in the center of the lip. A colonoscopy and small bowel series were normal.
Within the dermis there are foci of non-caseating granulomas in a background of an infiltrate that is comprised of lymphocytes and plasma cells. The overlying squamous mucosa is uninvolved.
Melkersson-Rosenthal syndrome (MRS) is an uncommon, neurocutaneous disorder that is characterized by the triad of facial paralysis, chronic edema of the lip, and a fissured tongue (lingua plicata). The etiology remains unknown although reports suggest that some cases may demonstrate an autosomal dominant inheritance pattern, with the responsible gene mapping to chromosome 9p11 . Presentation of complete MRS, with all three elements of the triad is rare. The signs typically develop over a period of several years, with the patient seeking treatment for only one or two elements of the triad at initial diagnosis . The presence of cheilitis granulomatosa (CG) without lingua plicata or facial palsies also is called Miescher syndrome, which falls under the broader category of orofacial granulomatosis (OFG). In approximately 40 percent of cases, CG is the presenting sign of MRS, with subsequent development of the neurologic signs .
The presence of OFG in combination with other oral findings, such as facial swelling, angular stomatitis, ulcers, mucosal tags, or gingival hyperplasia has been associated with Crohn disease and may precede the diagnosis of inflammatory bowel disease (IBD) by several years . It has even been postulated that CG, OFG, and MRS are oligosymptomatic manifestations of Crohn disease . Because of the finding of CG in combination with angular cheilitis in our patient, a gastrointestinal evaluation for associated IBD was undertaken and was negative. In patients presenting with CG or MRS, it is important to perform an appropriate evaluation, which includes a chest radiograph and a Mantoux test to exclude other etiologies of granulomatous disease, such as sarcoidosis or Mycobacterium infection. Sensitivity to allergens in food or medication also has been proposed as a possible etiology of CG. Patch tests have implicated cobalt and the food additives cinnamaldehyde and benzoates in the pathogenesis of OFG and CG. A study of 32 patients with OFG demonstrated improvement in oral and lip .
The appropriate treatment for CG in MRS is debated and may depend on the presence of other elements of the MRS triad, such as nerve palsies or headaches. Some believe that intralesional triamcinolone (TAC) combined with dapsone yields the best result , whereas others report success using intralesional TAC alone . A case report described a patient treated with three injections of a higher dose of TAC (40 mg), with resolution of symptoms and no recurrence after 12 months. The patient was concomitantly injected with lidocaine 2 percent because the injections were associated with appreciable pain .
Although many agree that intralesional TAC is the first line of treatment for CG associated with MRS, some have found that the response is short-lived . Case series demonstrating complete or partial response after treatment with clofazimine have been reported [9, 10], which prompted speculation that combination therapy with clofazimine and intralesional TAC also may be a reasonable approach . Because of the link between CG and Crohn disease, it has been postulated that tumor necrosis factor-α production is involved in the pathogenesis of both conditions. A single case report describes the successful treatment of CG, which had been refractory to multiple standard therapies, with infliximab at doses that are used for Crohn disease . The patient in the case report did require maintenance infusions of 5 mg/kg to keep the swelling in remission. Other therapies, which include hydroxychloroquine, metronidazole, sulfasalazine, and macrolide antibiotics, have been described . Surgical intervention generally does not play a role in the management of CG except in cases of severe disfigurement and post-surgical relapses are common .
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