Kuang W, Luo X, Wang J, Zeng X Research progress on Melkersson–Rosenthal syndrome. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2021; 50:148-154 https://doi.org/10.3724/zdxbyxb-2021-0103
Dodi I, Verri R, Brevi B A monosymptomatic Melkersson–Rosenthal syndrome in an 8-year old boy. Acta Biomed. 2006; 77:20-23
Chan YC, Lee YS, Wong ST, Lam SP, Ong BK, Wilder-Smith E Melkerrson-Rosenthal syndrome with cardiac involvement. J Clin Neurosci. 2004; 11:309-311 https://doi.org/10.1016/j.jocn.2003.06.003
Elias MK, Mateen FJ, Weiler CR The Melkersson–Rosenthal syndrome: a retrospective study of biopsied cases. J Neurol. 2013; 260:138-143 https://doi.org/10.1007/s00415-012-6603-6
Savasta S, Rossi A, Foiadelli T Melkersson–Rosenthal syndrome in childhood: report of three paediatric cases and a review of the literature. Int J Environ Res Public Health. 2019; 16 https://doi.org/10.3390/ijerph16071289
Cicardi M, Bellis P, Bertazzoni G Guidance for diagnosis and treatment of acute angioedema in the emergency department: consensus statement by a panel of Italian experts. Intern Emerg Med. 2014; 9:85-92 https://doi.org/10.1007/s11739-013-0993-z
Başman A, Gümüşok M, Değerli Ş, Kaya M, Akurt MT Melkersson–Rosenthal syndrome: a case report. J Istanbul Univ Fac Dent. 2017; 51:42-45 https://doi.org/10.17096/jiufd.96279
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Melkerrson-Rosenthal syndrome is a disease with a triad of clinical features: unilateral facial palsy; orofacial swelling; and a fissured tongue. It is a subset of orofacial granulomatosis. The authors present a case report to increase awareness of the syndrome among general dental practitioners, who may be the first to encounter its manifestations. The management and outcomes of this case are discussed. National and international guidance is lacking owing to the rarity of the condition.
CPD/Clinical Relevance: Early recognition of manifestations of the syndrome is important for timely diagnosis, appropriate referral, and multidisciplinary management to prevent complications.
Article
Melkersson–Rosenthal syndrome (MRS) is an uncommon neuro-mucocutaneous disorder with an unknown cause. It can begin at any age, from early childhood to late adulthood, and is primarily diagnosed through the clinical identification of a triad of symptoms: orofacial swelling; recurrent facial paralysis; and a fissured tongue.1,2,3
Melkersson first observed a female patient with lip oedema and intermittent facial palsy in 1928. Rosenthal subsequently noted the presence of a fissured tongue in these patients in 1931, and the condition was termed Melkerrson–Rosenthal syndrome.4
Oligosymptomatic or monosymptomatic presentations of this syndrome are more common than the classic triad, which occurs in up to 25% of patients.2,3,4,5
The most frequent monosymptomatic presentation of MRS is recurrent lip swelling, known as Miescher's syndrome or Miescher's cheilitis granulomatosa. Histological characteristics of this condition include lymphomonocytic infiltration, non-caseating epithelioid granulomas, multinucleated Langhans-type giant cells and fibrosis.3,6
The aetiology of MRS remains unclear, but may involve infections, immune deficiencies and genetic factors. Infectious conditions, such as orofacial herpes, can precede the onset of MRS.
Initially, the swelling is typically painless, intermittent and fluctuating, but it can persist over time. Differential diagnoses for this subtype of orofacial granulomatosis include angioedema, contact dermatitis, Crohn's disease, sarcoidosis, foreign body reaction and chronic granulomatous infections. Diagnostic delays are common, and histopathological examination via a labial biopsy may be crucial for diagnosis.2,3,4
Treatment primarily involves pharmacological therapy. Corticosteroids are commonly used, although optimal dosages and therapeutic effects are not well established among the international community.
Case study
A 34-year-old Asian woman, employed in healthcare, presented to the oral and maxillofacial surgery department with left-sided facial swelling and mild facial weakness (Figure 1). No fissuring of the tongue was noted. She had no known drug or food allergies, no significant medical history and was not taking regular medications. Additionally, there was no relevant family history.
Figure 1. Exta-oral view of left-sided orofacial swelling.
Upon initial presentation, no identifiable triggers were noted. Infection was ruled out and the cause of the swelling remained unknown. The working diagnosis was assumed to be of immune origin and a trial of 16 mg methylprednisolone (4 mg four times a day for 7 days) led to an improvement of symptoms.7 This is the standard oral dose given to patients for facial swelling at the department. The dose was then reduced to 8 mg methylprednisolone per day (2 mg four times a day) for another 7 days before discontinuing.
Eight months later, the patient developed a spontaneous swelling on her left lower lip after consuming seafood (Figure 2). This swelling progressed to her right lower lip and eventually affected her entire mid-face and lower lip over the course of 7 days. A mild weakness ensued that affected the lower and mid-third of the face bilaterally. The patient retained her ability to move the corner of the lips (levator anguli oris), although this was slightly weak. Complete eye closure was retained (House-Brackmann scale Class 2) and the upper third of the face was not affected.
Figure 2. Extra-oral view of left-sided lower lip swelling with partial involvement of the right lower lip.
Initially, a food allergy was suspected. She was investigated for food allergies, but none was detected. A trial of antihistamines showed no improvement.
She was treated with 10 mg of prednisolone once daily plus cetirizine (an anti-histamine) for 1 week, resulting in a noticeable but incomplete improvement of the facial swelling.8
The patient underwent a labial gland biopsy, which revealed non-caseating granulomas. MRS was suspected at this point. Further investigations were conducted to exclude other causes of non-caseating granulomatosis. No identifiable factors were found. A tapered course of methylprednisolone was initiated, which ultimately relieved her symptoms entirely over 6 weeks (Figure 3).7 When corticosteroids were discontinued, the symptoms of facial swelling reappeared. The patient is now on a life-long course of 5 mg prednisolone oral tablets per day and the mild facial weakness has resolved
Figure 3. Extra-oral view of resolution of orofacial swelling.
Discussion
MRS is an uncommon disorder affecting 0.08% of the global population.4 It is marked by three main symptoms: orofacial swelling; facial paralysis; and a fissured tongue.9 The classic triad is found in only 8–18% of cases, typically in individuals aged 25–40 years.10,11
Orofacial oedema, often mistaken for angioedema, is the most frequent symptom, primarily affecting the upper lip, unlike what happened with our patient.12 Facial paralysis occurs in 50%–60% of MRS patients and can precede the diagnosis by many years.12 The least frequent symptom, a fissured tongue, appears in 30–35% of cases.12
MRS is a subtype of orofacial granulomatosis, which is a clinico-pathological diagnosis. Both conditions are managed by immunosuppression.
The aetiology of MRS remains uncertain, making diagnosis and management challenging. Genetic predispositions, allergies and viral infections are suggested contributors to its development.9
MRS can present on its own or in conjunction with long-term conditions such as sarcoidosis and Crohn's disease.11 Owing to its complex presentation, a delay in diagnosis of 4 years is typically reported in the literature.4,5
Histological examination is essential, particularly in cases where the full clinical triad is not observed. This examination helps identify the hallmark of the disease: non-caseating perivascular granulomas.11 Understanding these factors is crucial for effectively diagnosing and managing MRS.
Given its unknown aetiology, there have been no definitive treatments for MRS to date. However, systemic steroids are commonly recommended as a first-line therapy, administered in short courses to minimize side effects. Intra-lesional steroid injections are also suggested.9 A combination of dapsone and local steroid therapy has been reported to be both safe and effective.13
Other treatments, such as topical tacrolimus, oral thalidomide, dapsone and doxycycline, have been used for their anti-inflammatory and immunomodulatory effects, although their efficacy is variable.9
In resistant cases, anti-tumour necrosis factor agents, such as adalimumab have been successfully employed. This approach was effective in treating a patient with non-caseating granulomatous cheilitis and neurological impairment after steroids, azathioprine and methotrexate failed.14
Antibiotics with anti-inflammatory properties, such as minocycline, have been used for granulomatous cheilitis.12,15 Cheiloplasty reduction is an option when lesions are stable and not progressing.12 For patients with recurrent facial paralysis, facial nerve decompression may be necessary.
Managing gingival hyperplasia in MRS is challenging, and gingivectomy is sometimes recommended. However, there can be recurrences and exacerbations of gingival swelling after surgical intervention.16
Conclusion
MRS is a rare neuro-mucocutaneous disorder characterized by variable symptoms, including orofacial swelling, facial palsy and a fissured tongue. Diagnosis can be challenging owing to the syndrome's heterogeneous presentation and unknown cause, which often delays management. Histopathological examination plays a crucial role in confirming diagnosis, particularly in atypical cases, through identifying non-caseating granulomas.
Treatment primarily involves corticosteroids for symptom management; a definitive cure is lacking.
This case underscores the importance of considering MRS in patients presenting with recurrent orofacial oedema and facial paralysis. Further research is needed to better understand the disease mechanisms and optimize therapeutic strategies. Increased awareness among health professionals can lead to earlier recognition and improved outcomes for individuals with MRS.
