The defining components of Melkersson-Rosenthal syndrome (MRS) are lingua plicata, facial nerve palsy that may be unilateral or bilateral, partial or complete [1] [2] and orofacial edema or granulomatous cheilitis [3] [4]. 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 [5]. 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 central nervous system may be involved in some cases, causing multiple sclerosis-like symptoms or miscellaneous psychiatric symptoms and autonomic disturbances.

• Recurrent Peripheral Facial Palsy

  Case Report A 23-year-old, right-handed female was admitted to our outpatient neurology clinic with recurrent peripheral facial palsy that took place three times a year. [archivesofrheumatology.org]

  Full Text Dear editor, Melkersson-Rosenthal syndrome (MRS)/orofacial granulomatosis is characterized by the triad of recurrent orofacial edema, recurrent peripheral facial palsy, and fissured tongue.1 The triad is found in 8% to 45% of cases; most patients [anaisdedermatologia.org.br]

  The association between recurrent peripheral facial palsy and orofacial oedema, and the idiopathic nature of facial palsy itself suggested a diagnosis of MRS. [mdpi.com]

• Surgical Procedure

  In this paper, we present different surgical procedures and their outcomes in a series of 4 cases with MRS. [ncbi.nlm.nih.gov]

  Adrenal Cortex Hormones Adult Cheilitis Cohort Studies Combined Modality Therapy Facial Paralysis Female Humans Injections, Intralesional Male Melkersson-Rosenthal Syndrome Middle Aged Postoperative Care Prognosis Reconstructive Surgical Procedures Tetracycline [unboundmedicine.com]

  Results: Patients did not agree on surgical procedure. Treatment with intralesional administration of triamcinolone was conducted with varying results. [thieme-connect.de]

• Rhinitis

  The patient had a personal history of chronic rhinitis and no relevant family history. [elsevier.es]

• Fissured Tongue

  Lingua plicata (or fissured tongue). [eurjmedres.biomedcentral.com]

  Melkersson-Rosenthal syndrome (MRS) is a rare disease characterized by a triad of relapsing or persistent orofacial edema, recurrent lower motor neuron facial nerve palsy and fissured tongue. [ncbi.nlm.nih.gov]

  Mel·kers·son-Ro·sen·thal syn·drome ( mel'kĕr-sŏn rō'zen-thahl ), [MIM*155900] cheilitis granulomatosa, fissured tongue, and recurrent facial nerve paralysis. [medical-dictionary.thefreedictionary.com]

• Cheilitis

  Niger J Clin Pract 2011 ; 14 : 477 – 8. 2 Cheilitis granulomatosa: a review. Head Neck Pathol 2014 ; 8 : 209 – 13. 3, et al. Exome sequencing identifies FATP1 mutation in Melkersson-Rosenthal syndrome. [academic.oup.com]

  An isolated granulomatous machrochelitis defines the cheilitis granulomatosa of Miescher (CGM). [ncbi.nlm.nih.gov]

  Granulomatous cheilitis — codes and concepts open What is granulomatous cheilitis? Granulomatous cheilitis refers to an uncommon condition in which there is lumpy swelling of the lips. [dermnetnz.org]

  J Am Acad Dermatol 49: 952-954 van der Waal RI et al (2001) Cheilitis granulomatosa. J Eur Acad Dermatol Venereol. 15: 519-523. Volz A et al (2010) Surgical lip reduction plasty for refractory cheilitis granulomatosa. [altmeyers.org]

  […] swelling (cheilitis granulomatosa or Miescher cheilitis), fissured tongue (lingua plicata or scrotal tongue) and facial paralysis. [elsevier.es]

• Lip Swelling

  […] is also known as scrotal tongue. 0:37 .5 Observe lip swelling in this boy 0:40 .7 Lower lip is more swollen as compared to upper lip. 0:44 .4 Based on presenting complaint and examination findings a provisional diagnosis of Melkersson-Rosenthal Syndrome [youtube.com]

  It is rarely described in otorhinolaryngology-related journals, although facial palsy, lip-swelling, and lingua plicata, are its most common presenting features. This classical triad however is not always present in MRS. [ncbi.nlm.nih.gov]

  […] normal lip size. [elsevier.es]

• Macroglossia

  A 48-year-old nonobese man with a diagnosis of MRS and marked macroglossia was evaluated because of clinically suspected obstructive sleep apnea (OSA). [ncbi.nlm.nih.gov]

  Melkersson-Rosenthal is a rare syndrome presenting with a triad of alternating or bilateral facial weakness, macroglossia, and, less commonly, fissured tongue, with features sometimes permanent.1,2 Download figure Open in new tab Download powerpoint Figure [n.neurology.org]

  […] wart Tongue Ankyloglossia Black hairy tongue Caviar tongue Crenated tongue Cunnilingus tongue Fissured tongue Foliate papillitis Glossitis Geographic tongue Median rhomboid glossitis Transient lingual papillitis Glossoptosis Hypoglossia Lingual thyroid Macroglossia [ipfs.io]

  On physical examination, the abnormal findings were a symmetrical upper lip oedema with a firm homogeneous consistency on palpation (Fig. 1A), macroglossia, and the presence of deep fissures on the dorsal and lateral surfaces of the tongue (Fig. 1B). [elsevier.es]

  […] physical examination disclosed a large increase in the volume of the lower lip and lip eversion (Figs. 1 and 2), which were associated with depapillation and transversal furrows on the dorsal tongue consistent with plicated tongue, as well as discrete macroglossia [scielo.isciii.es]

• Tongue Edema

  Initial symptom was unilateral localized non-painful tongue edema, followed by ipsilateral facial edema after 2-3 days, and subsequent development of facial palsy (grade 5 or 6). She had a mild lateral tongue keratosis, indurated on palpation. [bib.irb.hr]

  Fissured tongue: a sign of tongue edema?. Med Hypotheses, 82 (2014), pp. 709-712 [18] L. Nisa, R. Giger. Lingua plicata. CMAJ, 184 (2012), pp. E241 [19] C.M. Rivera-Serrano, L.X. Man, S. Klein, B.M. Schaitkin. [elsevier.es]

  (a) Labial edema, (b and c) right lower motor neuron seventh nerve palsy with labial edema and periorbital edema on right side. [ncbi.nlm.nih.gov]

• Lagophthalmos

  Associated ophthalmic symptoms include lagophthalmos, blepharochalasis, swollen eyelids, burning sensation of the eyes, corneal opacities, retrobulbar neuritis, and exophthalmos. Also called Melkersson's syndrome. [medical-dictionary.thefreedictionary.com]

  In thyroid orbitopathy, eyelid retraction and lagophthalmos often accompany bilateral eyelid edema. The skin may be erythematous, but is not thickened. [annsaudimed.net]

  The remainder of her ocular examination results were normal; proptosis and lagophthalmos were absent. Basal tear secretion was normal (18 and 20 mm on basic Schirmer testing). Her tongue appeared normal. [jamanetwork.com]

• Suggestibility

  A histological exam also revealed chronic sialadenitis of a minor salivary gland, although the patient has had no symptoms suggestive of exocrine gland dysfunction and no serological changes suggestive of an autoimmune disease. [elsevier.es]

  In this report we describe a 26-year-old female with the typical clinical symptoms and signs of Melkersson-Rosenthal syndrome, an autosomal dominant with variable expression, and a de novo t(9;21)(p11;p11), and suggest that the "Melkersson-Rosenthal gene [ncbi.nlm.nih.gov]

• Facial Edema

  IN 1928, Melkersson 1 wrote of a 35-year-old female patient afflicted with facial paralysis and facial edema. [jamanetwork.com]

  edema, facial nerve palsy, and furrowing of the tongue. [dovepress.com]

  Neurologists who observe a combination of facial edema and facial palsy in a patient should consider the diagnosis of MRS and proceed to a diagnostic skin biopsy and a trial of steroid treatment for their patient. [ncbi.nlm.nih.gov]

• Lip Edema

  The complete triad including lip edema, fissured tongue and facial nerve paresis was manifested in three patients, oligosymptomatic form with lip edema and fissured tongue was diagnosed in two patients and one patient had only lip edema (monosymptomatic [go.galegroup.com]

  Surgeries of lips may also be done for persistent lip edema. [dovepress.com]

  This is a report of six cases treated at the Department of Allergology and Immunology of the Clinical Center of Serbia, who had presented with the referral diagnosis of recurring or persistent lip edema, and who were diagnosed with Melkersson-Rosenthal [ncbi.nlm.nih.gov]

• Paresthesia

  The patients are admitted to hospital with several different symptoms such as headache, paresthesia on face, epiphora, keratitis, and tongue muscle atrophy [4]. [hindawi.com]

  One finds with descending frequency: Crohn's disease (6.8%) Migraine headache (5,7%) Paresthesias in the swelling area Lacrimal secretion disorders Redness Itching Nausea/vomiting Secretion disorders of the salivary glands or nasal mucosa Dizziness Tingling [altmeyers.org]

  […] and 11% of the family members also had fissuring.4 Besides the three cardinal symptoms, migraine, headache, and dizziness were present in half of the patients.9 Other neurological symptoms which may be seen in MRS include tinnitus, deafness, facial paresthesias [dovepress.com]

  Furthermore, other minor signs including dysgeusia/ageusia, neuralgic pain, tinnitus, vertigo, sudden deafness, anosmia, hyperesthesia, paresthesia, migraine headaches, nausea, vomiting, facial tics or spasms, can be found in the patients (9). [turkjem.org]

• Dysautonomia

  She had no symptoms of cranial neuropathy or dysautonomia. The patient had a personal history of chronic rhinitis and no relevant family history. [elsevier.es]

  Myotonia congenita, Thomsen disease, Neuromyotonia, Paramyotonia congenita ) congenital myopathy ( Centronuclear myopathy, Nemaline myopathy, Central core disease ) Mitochondrial myopathy periodic paralysis : Hypokalemic - Hyperkalemic Autonomic Familial dysautonomia [wikidoc.org]

  ( 29781258 ) Shalom G....Halevy S. 2018 6 Melkersson-Rosenthal Syndrome: A Rare Cause of Recurrent Facial Nerve Palsy and Acute Respiratory Distress Syndrome. ( 29984016 ) Kosovali BD...Bayar MK 2018 7 The Light at the End of the Tunnel: A Case of Dysautonomia [malacards.org]

• Irritability

  […] given orally at weekly intervals.21,27 Surgical management is an option reserved for severe or deforming CG,28 but recurrence is frequent29 and the risk of losing normal sensation in the affected lip must be weighted.28 A good oral hygiene, avoidance of irritating [elsevier.es]

  Other symptoms may be associated, which characterize the involvement of other cranial nerves, such as headache, tinnitus, difficulty speaking or eating, loss of taste, salivary hypersecretion or sialorrhea, lacrimal secretion disorder and conjunctival irritation [clinmedjournals.org]

• Cranial Neuropathy

  Periodontology 21:145–157 Article Google Scholar Subbarao NT, Jaiwal AK (2011) A case of leprosy with multiple cranial neuropathy mimicking Melkersson–Rosenthal syndrome. [link.springer.com]

  She had no symptoms of cranial neuropathy or dysautonomia. The patient had a personal history of chronic rhinitis and no relevant family history. [elsevier.es]

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 [6]. 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 [7], 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 [8].

• Lymphocytic Infiltrate

  […] filled with edema; fibrosis, small histiocytic aggregates, vascular structures with stasis, and a perivascular lymphocytic infiltrates, without granulomas. [dermsinica.org]

  Microscopically, it shows epithelioid non-caseous granulomas; however, edema and perivascular lymphocytic infiltrates have been described. Two different clinical forms of MRS are presented in this report. [ncbi.nlm.nih.gov]

  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. [symptoma.com]

  An inflammatory infiltrate consisting of lymphocytes and histiocytes was seen surrounding these vessels. One area of section showed intralymphatic histiocytic infiltration [Fig. 3]. [journals.lww.com]

• HLA-A2

  HLA typing may show HLA-A2 or HLA-A11. [16] Crohn disease, sarcoidosis, and OFG may present with similar histologic findings. [emedicine.medscape.com]

Treatment / Management The rarity of this disease explains the empiricism of therapeutic proposals and the absence of controlled studies. An effective medical treatment apparently is so not available at present. [ncbi.nlm.nih.gov]

The mainstay of treatment is corticosteroids. Intralesional triamcinolone acetonide may be used for the treatment of oro-facial edema. Another treatment option for oro-facial edema includes intralesional betamethasone, along with oral doxycycline. [dovepress.com]

The syndrome's pathophysiology is unclear and the treatment is challenging; corticosteroid therapy is the mainstay of treatment and is associated with clinical and histological improvement. [elsevier.es]

Click here to view The esthetic deformity can be very important so, the treatment is necessary. [dermsinica.org]

In our case local anesthetic cream allowed a good tolerance of treatment. [panafrican-med-journal.com]

Prognosis Melkersson-Rosenthal syndrome may recur intermittently after its first appearance. It can become a chronic disorder. [ninds.nih.gov]

Source MeSH Administration, Oral Adolescent Adrenal Cortex Hormones Adult Cheilitis Cohort Studies Combined Modality Therapy Facial Paralysis Female Humans Injections, Intralesional Male Melkersson-Rosenthal Syndrome Middle Aged Postoperative Care Prognosis [unboundmedicine.com]

Prognosis Melkersson-Rosenthal syndrome may recur intermittently after its first appearance. It can become a chronic disorder. Follow-up care should exclude the development of Crohn's disease or sarcoidosis. [brainfacts.org]

The difference was statistically significant (P CONCLUSION: Compared to recurrent Bell's palsy, recurrent facial palsy in MRS had much worse prognosis. © The Author(s) 2014. [ncbi.nlm.nih.gov]

Overview Symptoms and Causes Diagnosis and Tests Management and Treatment Prevention Outlook / Prognosis Living With Melkersson-Rosenthal Syndrome (MRS) Overview Symptoms and Causes Diagnosis and Tests Management and Treatment Prevention Outlook / Prognosis [my.clevelandclinic.org]

Etiology The etiology of CG is still unknown. Several etiologies of different orders have been evocated: genetic, inflammatory, allergic and microbial. There is not a clear etiological mechanism. [ncbi.nlm.nih.gov]

Etiology is not fully elucidated, genetic component plays an important role, but more data are needed. It is important to exclude other diagnoses, in order to establish a precise diagnosis and to initiate the treatment. [dermsinica.org]

Epidemiology: Rare. May be associated with Crohn's disease or sarcoidosis.[3] Microscopic Features: Granulomatous inflammation. DDx: Other causes of granulomatous inflammation. [librepathology.org]

The discussion covers the phenotype spectrum, epidemiology, mode of inheritance, pathogenesis, and clinical profile of each condition, all of which is accompanied by a wealth of illustrations. [books.google.com]

Epidemiology CG is an uncommon disease of undefined incidence and prevalence. One study estimated there incidence at 0.08% of the general population. It may have its onset at all ages. [ncbi.nlm.nih.gov]

You might also be interested in Allergology Occurrence/Epidemiology This section has been translated automatically. The incidence of Melkersson-Rosenthal syndrome (MRS) in adults is reported to be 1:1250 (Ziem et al. 2000). [altmeyers.org]

Epidemiology While the actual frequency is unknown, one study estimated its incidence at 0.08% of the general population. [9] Onset of granulomatous cheilitis usually is in young adult life. [emedicine.medscape.com]

Pathophysiology The pathogenesis of CG is unknown. Several factors could partially explain it: Genetic predisposition: The genetic origin has been evoked in front of the presence of family cases that nevertheless remain rare. [ncbi.nlm.nih.gov]

This chapter provides a review of the clinical features, hypothesized pathophysiology, and current management of this syndrome. [medlink.com]

Pathophysiology Probably of autoimmune origin related to HLA-DR histocompatibility complex. Normal lip architecture eventually is altered by the presence of lymphedema and noncaseating granulomas in the lamina propria. [accessanesthesiology.mhmedical.com]

The syndrome's pathophysiology is unclear and the treatment is challenging; corticosteroid therapy is the mainstay of treatment and is associated with clinical and histological improvement. [elsevier.es]

All the patients were surgically treated and received intralesional corticosteroids during surgery and tetracycline hydrochloride (500 mg, twice daily) after the operation to prevent recurrence. [unboundmedicine.com]

OBJECTIVE: To present our surgical experience in preventing further episodes of facial palsy and improving facial nerve recovery of patients with recurrent facial palsy in MRS. [ncbi.nlm.nih.gov]

Prevention Scientists don’t understand the causes of MRS, so there aren’t any proven strategies to prevent it. Outlook / Prognosis The outlook for people with MRS varies widely. [my.clevelandclinic.org]

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3. Vibhute NA, Vibhute AH, Daule NR. Cheilitis granulomatosa: a case report with review of literature. Indian J Dermatol. 2013;58(3):242.
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5. Campbell H, Escudier M, Patel P, et al. Distinguishing orofacial granulomatosis from Crohn's disease: two separate disease entities?. Inflamm Bowel Dis. 2011 Oct; 17(10):2109-2115.
6. Elias MK, Mateen FJ, Weiler CR. The Melkersson–Rosenthal syndrome: a retrospective study of biopsied cases. Neurol. 2013;260(1):138–143.
7. Banks T, Gada S. A comprehensive review of current treatments for granulomatous cheilitis. Br J Dermatol. 2012 May;166 (5):934-937.
8. Fitzpatrick L, Healy CM, McCartan BE, et al. Patch testing for food-associated allergies in orofacial granulomatosis. J Oral Pathol Med. 2011 Jan; 40(1):10-13.