Comment
Melkersson-Rosenthal syndrome usually presents sporadically, though there are reports of familial association,1-3 and only 8% to 25% of patients worldwide present with the complete triad of symptoms.4 The pathogenesis of the syndrome is controversial. Granulomatous changes have been found in patients experiencing chronic edema. However, according to Zimmer et al5 in a study of 42 MRS patients, only 46% (19/42) had granulomatous changes; 36% (15/42) had nonspecific inflammation, 11% (5/42) had incidental findings, and 7% (3/42) showed no histopathologic abnormalities. Granulomatous cheilitis is a subtype of orofacial granulomatosis, an idiopathic process that causes swelling of the face and lips as well as intraoral swelling and ulceration. Orofacial granulomatosis is referred to as granulomatous cheilitis when the lip is involved. Melkersson-Rosenthal syndrome is another subtype of orofacial granulomatosis that includes facial palsy and fissured tongue.6,7
In a clinical study of 7 patients with MRS, Liu and Yu1 found 3 (42%) patients to have dysarthria, dysphagia, and tongue muscle atrophy; 1 patient to have migrainelike headaches; 1 patient to have decreased vision and an ocular movement disorder; 1 patient to have ipsilateral hearing loss; and 1 patient to lack any other symptoms. Halevy et al8 suggested a possible association of MRS with psoriasis. In their review of 12 patients, 1 (8%) had psoriatic arthritis, 2 (17%) had skin biopsy–proven psoriasis, and 3 (25%) had a family history of psoriasis.8 Because the disease is quite rare, it is difficult to determine other symptoms that may be associated with the disease.
Tumor necrosis factor α (TNF-α) is needed for granuloma formation, and TNF-α antagonists have been used to treat a number of granulomatous conditions including Crohn disease and sarcoidosis.9-11 Two case reports indicate that infliximab, a mouse/human chimeric monoclonal antibody to TNF-α, has been used successfully to clear MRS.12,13 One report cited the use of adalimumab for maintenance therapy of MRS,12 and more recently, adalimumab has been reported for refractory MRS.14 However, there currently are no known reports regarding the efficacy of adalimumab as a first-line treatment of MRS.
Adalimumab is a fully human monoclonal antibody to TNF-α, which is administered via subcutaneous injections. Infliximab must be administered at an infusion center, making treatment logistically more difficult for patients, and can be associated with the development of infusion reactions, though the exact data on infusion reactions are difficult to estimate due to variations in reporting.15,16
In 2014, Stein et al14 reported a case of refractory MRS in a 29-year-old man associated with acute attacks of hearing loss. The patient’s symptoms were controlled with high-dose prednisolone but were unable to be maintained on methotrexate or azathioprine as steroid-sparing agents. The patient was loaded with adalimumab 80 mg subcutaneously once on day 1 and was continued on 40 mg subcutaneously once every 3 weeks, gradually extending to once every 4 weeks when symptoms improved. The patient was slowly weaned off prednisolone 16 months after starting adalimumab. After 20 months, adalimumab therapy was discontinued and the patient remained recurrence free at 4 years’ follow-up.14 In another case, adalimumab was utilized as maintenance therapy after initial improvement with infliximab.12 Kakimoto et al12 reported a previously healthy 19-year-old woman with edema of the bilateral eyelids and upper lip. The authors determined the patient had MRS despite the lack of fissured tongue or facial nerve palsy and started infliximab. The condition resolved after the patient’s second infusion of infliximab and completely cleared after the third infusion; however, she had logistical difficulties reaching the infusion center and disliked the flulike response she experienced with the treatment. She was started on once weekly subcutaneous injections of adalimumab 40 mg and did not relapse.12 Another patient with granulomatous cheilitis responded to adalimumab after corticosteroids, intralesional injections of triamcinolone, topical tacrolimus, roxithromycin, and clofazimine failed.17 The patient received adalimumab 80 mg for the first week and 40 mg for the second week and every 2 weeks thereafter. The patient began improving after the third dose and remained relapse free for at least 6 months of follow-up.17
Conclusion
We present a case of a 69-year-old woman who presented with facial nerve palsy, facial edema, and a fissured tongue, which is the classic triad of MRS, and all 3 symptoms improved with adalimumab.