From the Tufts Medical Center (SK, NVL), Department of Pathology, Boston; Tufts Medical Center (KH), New England Eye Center, Boston; and Umass Memorial Medical Group (BLB), Worchester, Massachusetts.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Nora V Laver, MD, Director, Ocular Pathology and Cytopathology Laboratories, Department of Pathology, Tufts Medical Center, 750 Washington Street, Box 802, Boston, MA 02111.
Melkersson–Rosenthal Syndrome (MRS) is a rare disorder of unknown etiology characterized by orofacial edema, facial palsy, and fissured tongue. The classic triad, however, is infrequently seen; mono- or oligo-symptomatic patients are observed more frequently, making the diagnosis challenging. Eyelid swelling is an uncommon clinical presentation of MRS.1–3 We present a patient with chronic right upper eyelid edema and fissured tongue. The pathology, clinical features, and management of this syndrome are discussed.
A 64-year-old man was referred for evaluation of chronic bilateral upper eyelid drooping and edema of the right upper eyelid. The swelling, present for over 15 years, was now interfering with vision. There was no history of trauma, infection, or drug allergies. His ocular history was remarkable for bilateral upper eyelid blepharoplasty was performed twelve years earlier to treat similar ocular symptomatology, diagnosed as involutional ptosis at the time. The swelling of the right upper eyelid recurred a few months after surgery. A history of macular degeneration with decreased visual activity in the right eye OD was present.
Ophthalmic examination revealed a best-corrected visual acuity of 20/60 OD and 20/20 left eye (OS), mild metamorphopsia by Amsler grid testing, equal pupils with no afferent pupillary defect, full extraocular movement bilaterally, intraocular pressures of 21 mm Hg in each eye, normal color vision, and no proptosis by Hertel measurements. Fundus retinal exam, optic nerves and slit lamp exams were normal bilaterally. External eyelid examination revealed marked painless non-pitting edema of the right upper eyelid (Fig. 1), 14 mm levator function on each side, marginal reflex distance of 0.5 mm OD and 3.5 mm OS, and overhanging edematous right upper eyelid dermatochalasis. Automated visual fields demonstrated a superior defect in the right eye and a full field in the left eye. The remainder of the face showed no swelling with normal motor function. However, examination of the patient’s tongue revealed a peculiar fissured appearance (Fig. 2).
Figure 1. Right Upper Eyelid Swelling, from the Medial to the Lateral Canthus.
Figure 2. Fissured Tongue, Showing Central Furrow with Radiating Fissures.
A diagnostic biopsy of the right upper eyelid revealed non-necrotizing granulomatous inflammation adjacent to blood vessels and lymphatic channels. A distinct finding was the presence of granulomatous inflammation within dilated lymphatic channels, in some areas causing occlusion (Fig. 3). Special stains for fungi, acid-fast microorganisms and bacteria were all negative. Immunohistochemistry showed CD68-positive epithelioid histiocytes within the granulomatous inflammation (Fig. 4). Clinical and histological findings were consistent with a diagnosis of MRS.
Figure 3. Non-Necrotizing Granulomatous Inflammation Adjacent to Lymphatic Spaces, Some Markedly Dilated and Occluded by Histiocytes.
Figure 4. CD68 Immunostain Demonstrates Histiocytes Within Lymphatic Channels.
Operative intervention was undertaken due to functional limitation. Repair of the right upper eyelid ptosis with debulking and advancement of the levator muscle were performed without complications. At 6 months after surgery the patient showed symmetrical eyelid position without edema.
The classic triad of orofacial edema, facial palsy, and fissured tongue in MRS is infrequently seen, with mono- or oligo-symptomatic clinical presentation being more common. Data from a Mayo clinic study showed that the most frequent initial signs were labial edema (75%), facial edema (50%), and Bell’s palsy (33%). Lingua plicata or fissured tongue is noted in one-third to one-half of patients with MRS.4,5 Clinical presentation with eyelid edema is uncommon, but has been previously described.1–3 When it occurs, it should be distinguished from angioedema, blepharochalasis, thyroid-associated ophthalmopathy, sarcoidosis, and insect bite. A biopsy is essential with appropriate histopathological diagnosis of this entity.
The etiology and pathogenesis of MRS is unknown. Associations with chronic infection, hypersensitivity reaction, environmental factors, and genetic predisposition, have been suggested. Viral etiology, especially herpes simplex infection, has also been proposed.1 No single treatment has produced uniform results, and all are associated with frequent remission and relapse of the orofacial swelling. Trials of corticosteroids, tetracycline, methotrexate, and various other drugs have been reported showing limited success. Focal external beam irradiation has not shown clear benefits. Surgical treatment with reduction blepharoplasty, cheiloplasty, or facial nerve decompression has been successful for symptom reduction, but long-term results vary due to the nature of the syndrome.1,4
Our case demonstrates an uncommon variant of MRS with prominent upper eyelid edema and lingua plicata, which was initially misdiagnosed. The biopsy with characteristic features of granulomatous lymphangitis is crucial for a definite diagnosis. The ptosis resulting from mechanical effect of the persistent and extensive eyelid edema required surgical treatment with good short-term results; however, the patient will most likely require additional treatment in the future.
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- Pierre-Filho PTP, Rocha EM, Natalino R, Cintra ML, Caldato R. Upper eyelid edema in Melkersson-Rosental syndrome. Clinical & Experimental Ophthalmol. 2004;32(4):439–440. doi:10.1111/j.1442-9071.2004.00852.x [CrossRef]
- Shapiro M, Peters S, Spinelli H. Melkersson-Rosenthal syndrom in the periocular area: a review of the literature and case report. Annals of Plastic Surgery. 2003;50(6):644–648. doi:10.1097/01.SAP.0000069068.03742.48 [CrossRef]
- Zimmer WM, Rogers RS III, Reeve CM, Sheridan PJ. Orofacial manifestation of Melkersson-Rosenthal syndrom. A study of 42 patients and review of 220 cases from literature. Oral Surg Oral Med Oral Pathol. 1992;74:610–619. doi:10.1016/0030-4220(92)90354-S [CrossRef]
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