PÁGINA DEL RESIDENTE

What should the diagnosis be?

¿Cuál sería su diagnóstico?

The case is presented of a 63-year-old female with symptoms that had been evolving for two years that included hemifacial and lip edema. The onset had been sudden and on some occasions she had had symptoms of palpitations* and sweating.

The episodes of swelling affecting the left side of her face and lip (Fig. 1 and 2) had occurred on four occasions and each episode had lasted 48-72 hours.

Of note in her medical history were two episodes of transitory facial palsy in 1978 and 1979 that had not reoccurred. Her tongue had lesions of a fibrous appearance (Fig. 3 and 4) particularly around the left border, and there were transverse fissures on the back of her tongue and slight macroglossia.

Her blood tests revealed slight eosinophilia of 1.2%. Her immunological tests were normal (C3, C4 and normal C1 inhibitor). IgE levels were slightly elevated (118, normal range 0-100).

Two biopsies were taken, one from the tongue and the other from the lip. The lesions of the tongue corresponded to pavement epithelium with slight acanthosis (Figs. 5 and 6). The biopsy report of the lip described glands with mucosal differentiation surrounded by unspecific lymphoid aggregates (Figs. 7 and 8).

Melkersson-Rosenthal syndrome

Síndrome de Melkersson-Rosenthal

L. Gallego López¹, S. Llorente Pendás², J.S. López-Arranz³

1 Médico Residente
2 Médico Adjunto
3 Jefe de Servicio
Servicio de Cirugía Oral y Maxilofacial. Hospital Universitario Central de Asturias, Oviedo. España

Dirección para correspondencia

Introduction

Melkersson-Rosenthal syndrome (MRS) is a clinical syndrome characterized by a triad: idiopathic facial paralysis, fissured tongue and orofacial edema, although the oligosymptomatic or monosymptomatic forms of the disease are more common. The monosymptomatic form that is most common is known are Meischer’s granulomatous cheilitis that entails recurrent labial edema of one or both lips that can become persistent.¹

Orofacial edema (Fig. 1 and 2) is the most common sign of the triad (it appears in practically all patients at some point during the course of the disease) and it tends to be the first manifestation of MRS in most cases.

Facial palsy can be bilateral or unilateral, the latter being more predominant, and it can be partial or complete. It is indistinguishable clinically from Bell’s idiopathic paralysis. It has a recurrent course with spontaneous recovery, although dyskinesias or residual paralysis may remain. It affects approximately a third of patients.

The plicated or fissured tongue (Fig. 3 and 4) is a more unspecific sign of MRS that appears in approximately 50% of patients, and it is frequently hereditary. It consists of a tongue that is slightly larger than normal, with large numbers of fissures crossing the back of it which are connected to a main fissure that is longitudinal.

In addition to these three main or major signs of MRS, there can be other minor signs,² such as other cranial nerve involvement (especially the 5th pair or trigeminal nerve), vertigo, buzzing, migraines, disturbance of the autonomic nervous system (nauseas, vomiting, spasms), even psychiatric disturbances.

The prevalence of MRS is estimated at around 0.08% of the general population, although it is believed to be underdiagnosed. It affects both sexes equally, there being a slight predominance in females, and it tends to appear in the second decade of life.²

The etiology behind MRS is still unknown, although numerous hypotheses have been put forward.³ There are certain signs of a genetic predisposition, and the existence of a MRS gene situated in chromosome 9 p11 has been discussed, although it appears applicable to just some cases of fissured tongues.² Other patterns that have been studied are autosomal dominant inheritance with variable expressivity and polygenic inheritance.⁴ Other authors defend the theory of infection, connected in particular with the herpes simplex virus.³ Finally, autoimmune factors seem also to have a role in the etiopathogenic development of this entity, as is indicated in its association with rheumatoid arthritis, and there are even authors that have considered it a clinical variant of sarcoidosis.³

The diagnosis is essentially clinical, although histopathologic confirmation should be carried out. The histopathology is characterized in a good number of cases by granulomatous inflammation, with non-caseating epithelioid granulomas being representative of the syndrome (indistinguishable from sarcoid granulomas), although its absence does not exclude the diagnosis. It is also possible for the histopathology of the inflammation to be completely unspecific, as is finding Langhans giant cells or perivascular mononuclear infiltrate.

Discussion

Facial palsy, recurrent facial swelling and a fissured tongue form a clinical triad that defines Melkersson-Rosenthal syndrome. The complete triad is more uncommon than the oligosymptomatic presentation of the diesease.⁵

The diagnosis should be based on clinical signs, although taking a biopsy is advisable for confirmation. The characteristic finding is non-caseating epithelioid granulomas, although their absence does not exclude the diagnosis, because MRS can adopt other different histopathologic manifestations, including totally unspecific inflammatory infiltrate, as occurred in the case presented.

The differential diagnosis has to be carried out with other entities (Table 1), such as vascular malformation of the lip, glandular cheilitis, recurrent erysipelas, hereditary angioedema (that is accompanied by edema of the upper airways and complement C1 inhibitor deficiency), Ascher syndrome,6 Crohn’s disease or sarcoidosis.

There is no standard therapy for this syndrome, as the etiopathogenic mechanisms behind it are still not understood, and numerous therapies have been tried with varying results (Table 2). The drugs that are most used are corticoid, ⁴ systemic, topical, or intralesional, on their own or combined with minocycline that appears to increase effectiveness, although this last drug is contraindicated in children under the age of 8. Clofazimine is an anti-microbial and anti-inflammatory agent that is commonly used for treating tuberculosis and leprosy. It has been used in recent studies with good results, but it has undesirable side effects such as orange-colored skin, corneal and intestinal problems.⁷ Thalidomide in 50 mg a day doses over 6-8 weeks has turned out to be an effective drug for managing MRS with very few side effects, such as drowsiness, although its use it totally contraindicated in pregnant patients due to its teratogenic potential.

Surgical therapy is an alternative in cases of residual deformities and a lip cheiloplasty⁸ or surgical decompression of the facial nerve⁹ can be carried out when there are recurrent episodes that leave residual paralysis. This alternative tends to be combined with corticoid treatment.

To conclude, patients suffering from MRS probably have to accept that their symptoms will recur for a large part of their lives, as the therapeutic alternatives tend not to be definitive. It is important for professionals in maxillofacial surgery to keep these symptoms in mind so that a correct diagnosis of this rare disease can be carried out.

Dirección para correspondencia:
L. Gallego López
Servicio de Cirugía Oral y Maxilofacial
Hospital Universitario Central de Asturias
C/ Celestino Villamil, s/n
33006 Oviedo, Asturias, España

References

1. Camacho Alonso F, Bermejo Fenoll A y cols. Queilitis granulomatosa de Meischer: Presentación de cinco casos. Med Oral Patol Oral Cir Bucal 2004;9:425-9.        [ Links ]

2. Gerressen M, Ghassemi A, Stockbrink G, y cols. Melkersson-Rosenthal syndrome: case report of a 30-Year Misdiagnosis. J Oral Maxillofac Surg 2005;63:1035-9.        [ Links ]

3. Ang KL, Jones NS. Melkersson-Rosenthal Syndrome. The Journal of Laryngology & Otology 2002;116:386-8.        [ Links ]

4. Shapiro M, Peters S, Spinelly HM. Melkersson-Rosenthal Syndrome in the periocular Area: A Review of the literature and Case Report. Ann Plast Surg 2003; 50:644-8.        [ Links ]

5. Wolfrang M, Zimmer DDS, Roy S, Rogers III, y cols. Orofacial manifeatations of Melkersson-Rosenthal syndrome. Oral Surg Oral Med Oral Pathol 1992;74:610-9.        [ Links ]

6. Michael A, Keefe MD, y cols. Ascher Síndrome. Otolaryngol Head Neck Surg 2001; 124:236-.        [ Links ]

7. Gerd Jürgen R, Milo F, Edwin L , y cols. Cheilitis Granulomatosa Miescher: Treatment with Clofamizine and Review of the Literature. Ann Otol Laryngol 2001; 110:964-67.        [ Links ]

8. Cederna PS, Fiala TGS, Smith DJ, y cols. Melkersson- Rosenthal Síndrome: Reduction Cheiloplasty Utilizing a Transmodiolar Labial Suspension Suture. Plastic Surgery. Aesthetic Plastic Surg 1998;22:102-5.        [ Links ]

9. Dutt SN, Showkat M, Irving RM, y cols. Total Decompression of facial nerve for Melkersson-Rosenthal syndrome. The Journal of Laryngology & Otology 2000;114: 870-3.        [ Links ]