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Oral cavity & oropharynx

Inflammatory / immune mediated (noninfectious)

Melkersson-Rosenthal syndrome


Editorial Board Member: Molly Housley Smith, D.M.D.
Deputy Editor-in-Chief: Kelly Magliocca, D.D.S., M.P.H.
Pooja Sharma Kala, M.D.

Last author update: 9 October 2024
Last staff update: 9 October 2024

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PubMed Search: Melkersson-Rosenthal syndrome

Pooja Sharma Kala, M.D.
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Prognostic factors | Case reports | Treatment | Clinical images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Polarization microscopy description | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1
Cite this page: Kala PS. Melkersson-Rosenthal syndrome. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/oralcavityMRsyndrome.html. Accessed December 25th, 2024.
Definition / general
  • Rare neuromucocutaneous syndrome characterized by recurrent orofacial swelling, relapsing facial paralysis and fissured tongue (lingua plicata)
  • Cheilitis granulomatosa is its most common monosymptomatic form
Essential features
  • Classic clinical triad of recurrent orofacial swelling, recurrent facial nerve paralysis and fissured tongue
  • Histopathological examination of the swollen tissue shows granulomatous inflammation, lymphomononuclear inflammation and edema
Terminology
  • Melkersson-Rosenthal syndrome (MRS): named after neurologists Ernst Melkersson and Curt Rosenthal, who described the classic symptoms of MRS
  • Melkersson syndrome
  • Cheilitis granulomatosa, also known as Miescher granulomatous cheilitis
  • Orofacial granulomatous disease: not recommended; broad entity comprising noninfectious granulomatous involvement of lips, oral cavity and face
    • Causes may include sarcoidosis, Crohn's disease, cheilitis granulomatosa, etc.
ICD coding
  • ICD-10: G51.2 - Melkersson syndrome
  • ICD-11: 8B88.Y - other specified disorders of facial nerve
Epidemiology
Sites
  • Characterized by triad of nonpitting orofacial edema, fissured tongue and recurrent lower motor neuron facial paralysis (Curr Pediatr Rev 2018;14:196)
  • Orofacial edema: lips are most commonly affected; gingiva, buccal mucosa, cheeks, tongue and eyelids can also be affected
  • Tongue swollen and fissured
  • Recurrent lower motor neuron facial paralysis (Curr Pediatr Rev 2018;14:196)
Pathophysiology
  • Orofacial swelling is caused by fluid accumulation due to vasomotor and other autonomous disturbances
  • Tissue edema, due to vasomotor disturbances, damages the nerve branches and can compress the facial nerve, leading to facial paralysis (J Dermatol 1997;24:281)
  • Later, the microgranulomas appear
  • Repeated episodes may be followed by persistent orofacial swelling or facial paralysis
Etiology
Clinical features
  • Recurrent facial swelling is the most common feature and may be the first and only presentation (80 - 100% of cases) (Allergy Asthma Clin Immunol 2021;17:8)
    • Often asymmetric or unilateral, sudden onset, nontender, nonpruritic, lasts for hours to weeks and can sometimes persist; resistant to antihistamines
  • Recurrent facial nerve paralysis (50 - 60% of cases) (Pan Afr Med J 2023;44:72)
    • Can occur months or years before or after the onset of facial edema
    • Can be unilateral or bilateral, partial or complete, resolves in initial episodes but later may become permanent
  • Fissured tongue (30 - 80% of cases) (Am J Otolaryngol 2009;30:33)
    • Also known as scrotal tongue, lingua plicata, furrowed tongue or cerebriform tongue
    • Swollen tongue with irregular clefts and protuberance; fissured tongue is the presence of grooves on the tongue about 2 mm deep and 15 mm long (Odontol Revy Suppl 1976;36:1)
  • 8 - 25% of cases have all 3 components (Braz J Otorhinolaryngol 2007;73:132)
  • Other symptoms may include migraines, tinnitus, sudden deafness, dry mouth, altered taste, facial neuralgia, dysphagia, diverticulitis and uveitis
Diagnosis
  • Classic clinical triad of recurrent orofacial swelling, recurrent facial paralysis and fissured tongue is seen in 8 - 25% of cases (Braz J Otorhinolaryngol 2007;73:132)
  • Classified as complete or incomplete (oligosymptomatic) by Hornstein (J Dermatol 1997;24:281)
    • Complete: classic triad + some minor signs
    • Incomplete / oligosymptomatic
      • Recurrent orofacial swelling (supportive histology) + ≥ 2 minor signs (plicated tongue may or may not present) or
      • Recent or current facial palsy (≥ 1 episode) + recurrent orofacial swelling (insignificant histology) + ≥ 2 minor signs + plicated tongue
  • Minor signs include orofacial hyperesthesia / dysesthesia, hemicrania-like frontal headache, cluster headache, unilateral hyperacusis, statoacoustic dysfunctions, recurrent pharyngeal neuralgia, recurrent dysphagia, recurrent dry eye, recurrent dry mouth, etc. (J Dermatol 1997;24:281)
  • Granulomatous cheilitis is the most common monosymptomatic form of Melkersson-Rosenthal syndrome (Braz J Otorhinolaryngol 2007;73:132)
  • If the criteria are not met, then the patient should follow up for any presentations of components of the syndrome later in life
Laboratory
  • Except for histological examination, there are no specific laboratory findings
  • Can help exclude other differential diagnoses
Radiology description
Prognostic factors
Case reports
Treatment
  • Treatment is difficult; no standardized therapy scheme exists
  • Local intralesional / systemic corticosteroids, nonsteroidal anti-inflammatory agents and antibiotics are commonly used (Curr Pediatr Rev 2018;14:196)
  • Thalidomide was successful in one report (Ann Allergy Asthma Immunol 2002;88:421)
  • Surgery for facial nerve decompression, cosmetic surgery for persistent lip edema (cheiloplasty)
Clinical images

Images hosted on other servers:
Diffuse swelling of lip

Diffuse swelling of lip

Lip swelling, deviation of mouth angle to the left

Lip swelling, deviation of mouth angle to the left

Orofacial swelling

Orofacial swelling

Fissured tongue   Fissured tongue

Fissured tongue

Microscopic (histologic) description
  • Typical histology is seen in the biopsies from the swollen lips and other edematous tissue during acute episode
  • Tuberculoid (lymphoepithelioid) granulomas in dermis or muscularis propria - epithelioid cell granulomas, surrounded by lymphocytes and other mononuclear cells, edematous connective tissue
  • Less commonly, perivascular or paravascular lymphonodular plasmacytic inflammation with central lymphocytic nodules surrounded by plasma cells and histiocytes in an edematous connective tissue (J Dermatol 1997;24:281)
  • Nonspecific inflammation, fibrosis
Microscopic (histologic) images

Contributed by Pooja Sharma Kala, M.D.
Mild interface change

Mild interface change

Lymphocytic infiltrate

Lymphocytic infiltrate

Microgranuloma

Microgranuloma

Epithelioid cell granuloma near blood vessel

Epithelioid cell granuloma near blood vessel

Perivascular / paravascular epithelioid cell granuloma

Perivascular / paravascular epithelioid cell granuloma

Dermis with nodular infiltrates

Dermis with nodular infiltrates

Positive stains
Negative stains
Polarization microscopy description
Molecular / cytogenetics description
Sample pathology report
  • Lip, skin biopsy:
    • Granulomatous cheilitis, in favor of Melkersson-Rosenthal syndrome in the appropriate clinical setting (see comment)
    • Comment: Skin biopsy shows epidermis with basket weave orthokeratosis and mild dermoepidermal interface changes. Dermis shows multiple epithelioid cell granulomas with moderate lymphomononuclear inflammatory infiltrate and edema. A few of the granulomas are seen in the perivascular location. No necrosis / fungal elements are seen. Ziehl-Neelson, Fite-Faraco, PAS and GMS stains are negative.
Differential diagnosis
  • Crohn's disease:
    • Labial swelling is rare; granulomatous inflammation in the intestine is a more prominent feature
  • Angioneurotic edema:
    • Labial swelling occurs rapidly and is transient
    • Swelling of oral mucosa, tongue, larynx, joints
    • Other features of Melkersson-Rosenthal syndrome are lacking
  • Sarcoidosis:
    • Solid nodules on the gingiva, oral mucosa can occur
    • Epithelioid cell granulomas of other organs
    • Other features of sarcoidosis are present (raised serum angiotensin converting enzyme [ACE] levels)
    • Heerfordt syndrome, a subset of sarcoidosis, has preauricular edema, facial palsy and injury to other cranial nerves
  • Tuberculosis:
    • Caseating epithelioid cell granulomas are classic, while in Melkersson-Rosenthal syndrome, the granulomas are nonnecrotizing and related edema is present
    • Ziehl-Neelson stain is positive; other ancillary tests for tuberculosis should be done to rule out tuberculosis
  • Insect bite:
    • Clinically, Melkersson-Rosenthal syndrome and insect bite may mimic each other; histology differentiates the 2 entities
    • Granulomas absent in insect bite
Board review style question #1
BRQ image


A 29 year old woman presented with recurrent orofacial swelling from the past few months. On examination, she had a fissured tongue and right sided facial weakness. The rest of the systemic examination was normal. A biopsy of the swollen lip was performed and a representative microphotograph is shown above. The cell counts were within normal limits and serum angiotensin converting enzyme (ACE) level was 7 U/L. Which of the following is correct about the disease condition?

  1. Cytoplasmic antineutrophil cytoplasmic antibodies (cANCA) levels will be raised
  2. Facial paralysis is due to vasomotor disturbances
  3. Granulomas lead to the orofacial swelling
  4. Nodular infiltrates will be seen in magnetic resonance imaging (MRI) of the head and neck region
Board review style answer #1
B. Facial nerve paralysis is due to vasomotor disturbances. The diagnosis is Melkersson-Rosenthal syndrome with facial nerve paralysis and orofacial swelling occurring because of the edema caused by vasomotor disturbances. Answer C is incorrect because the granulomas occur after orofacial swelling. Answer A is incorrect because cANCA levels are raised in granulomatosis with polyangiitis; it is unrelated to Melkersson-Rosenthal syndrome. Answer D is incorrect because radiology is near normal in Melkersson-Rosenthal syndrome. The presence of nodular infiltrates may indicate another diagnosis.

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Reference: Melkersson-Rosenthal syndrome
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