Cheilitis Granulomatosa (Miescher Melkersson Rosenthal Syndrome)

Article Author:
Amani Gharbi
Article Editor:
Sidharth Sonthalia
Updated:
11/28/2017 9:38:13 AM
PubMed Link:
Cheilitis Granulomatosa (Miescher Melkersson Rosenthal Syndrome)

Introduction

Cheilitis granulomatosa (CG) is a rare chronic disease characterized by a recurrent firm swelling of one or both lips, and, histologically, by a granulomatous infiltrate of the chorion.

An isolated granulomatous machrochelitis defines the cheilitis granulomatosa of Miescher (CGM).

The Melkersson-Rosenthal syndrome (MRS) is characterized, in its complete form, by a classical triad of symptoms: recurrent or persistent orofacial edema (facial and lip edemas), plicated or fissured tongue (lingua plicata), and relapsing peripheral facial nerve paralysis. Most of the cases of MRS present with few symptoms. CGM is so the most common monosymptomatic form of MRS.

Other diagnoses, which are also, part of the orofacial granulomatosis group, must be eliminated. The orofacial granulomatosis, first individualized in 1985, by Wiesenfeld et al., is a syndrome grouping noninfectious and nonnecrotizing granulomatous involvement of the lips, oral cavity, and face, in addition to the CG, sarcoidosis, and Crohn disease.

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.

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. It appears in adults, preferentially those between 20 and 40 years. It rarely affects the children. However, in two recently published articles, 30 cases in pediatric-age patients have been described in the international literature. The most of the authors indicate an equal sex distribution, while some authors claim that CG appears more frequently in females. Rare familial cases have also been reported.

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. In addition, no HLA association was found in patients with CG compared to the general population.
  • Immunologic factors: CG is a chronic inflammatory condition, characterized by a predominant T helper 1-mediated immune response. The main anomaly is probably a local alteration of innate immunity of lip mucosa in response to various antigens whose insufficient purification leads to a persistent granulomatous reaction.
  • Allergic factors: Allergy to dental materials, foodstuffs and food additives, has been suspected, but the causal relationship is not well established.
  • Microbial factors: Several microbial agents have been incriminated, as eventual factors of de-regulation of the immune response. Studies have included especially Mycobacterium tuberculosis and paratuberculosis, Borrelia burgdorferi, Saccharomyces cerevisiae, and Candida albicans. Nevertheless, with conflicting results, the role of these germs in the pathogenesis of CG remains uncertain.

Histopathology

Histological examination is not necessary for the diagnosis of the complete form of MRS, which can be easily established based on clinical findings. Nevertheless, the histological analysis is necessary for incomplete forms including CGM, especially to eliminate the differential diagnosis of sarcoidosis and  Crohn's disease.

The histological characteristics of CG (including CGM and MRS) are granulomatous infiltrate constituted by epithelioid cells and multinucleate giant cells, without caseous necrosis, associated with some degree of lymphedema and fibrosis. These histopathological features are not constant, and their absence should not formally exclude the diagnosis of CG.

History and Physical

MRS consists of a triad of recurrent or persistent orofacial (lips and/or face) swelling, peripheral facial nerve paralysis, and fissural or scrotal tongue.

Labial swelling is initially edematous recurrent mimicking angioedema, then after many episodes, it becomes persistent and indurated. It is a firm non-erythematous non-painful affecting one or both lips. Only in few cases, the labial swelling can cause difficulties in drooling or speech.

The full classical triad is uncommon; it can only be observed 25% of the patients. In the complete form of MRS, all symptoms rarely appear simultaneously, and long intervals between the occurrence of paralysis and the first swelling have been reported. The disease evolves by flare-ups; nevertheless, a permanent edema of the lips, and sometimes on the face, can gradually be observed. The oligosymptomatic and monosymptomatic forms are most frequent at the beginning of the disease, and they represent 40% of the cases.

CGM or Miescher syndrome corresponds to an incomplete form of MRS in 28% of the cases. Thus, it represents the most common form of MRS. It generally affects the upper lip and less frequently the lower lip. In addition, changes in the buccal, palatal, sublingual, and gingival mucosa are anecdotally reported.

Oral manifestations of sarcoidosis and Crohn’s disease may mimic those of CGM or MRS.

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. The proposed symptomatic treatments are simply intended to avoid or space recurrences, particularly in the edematous stage. The treatment aims to relieve these patients and to improve their quality of life often very disturbed by the unsightly and distressing nature of macrocheilitis and oro-facial edema. The spontaneous disappearance of the disease is rare but has already been reported.

Corticosteroid therapy is a classic treatment for CG. It may be administered locally, topically or intralesionally, more rarely, the systemic corticosteroid for short courses (prednisolone: 0.3 to 0.7 mg/kg/d; 25 to 50 mg/d). Other treatments have also been tried for their anti-inflammatory or immunomodulatory effects such as topical tacrolimus, or oral thalidomide, dapsone, and doxycycline, with inconsistent efficiency.

Finally, immunosuppressive treatments such as mycophenolate mofetil, and azathioprine, as well as inhibitors of tumor necrosis factor-alpha (TNF-alpha) have been tried, alone or in combination, in isolated cases and small series with inconsistently positive results.

The cheiloplasty reduction is possible when the lesions are fixed and not evolving.

Pearls and Other Issues

CG is a rare disorder with a difficult diagnosis, characterized by recurrent or persistent idiopathic swelling of the one or both lips due to granulomatous inflammation. When isolated, it defines the Miescher syndrome. However, other clinical signs may be associated such as facial nerve paralysis and fissured tongue, which complete the triad of MRS. The etiopathogenesis and the etiology of CG are still obscure, and the treatment, therefore, remains random.

In addition to the unsightly nature of this condition and the significant psychological impact that can induce the local complications (excessive lacrimation, dry eyes, disorders of salivary secretion and dysgeusia), that’s why they should be avoided because they may have a significant emotional impact on the patient.

Possible familial cases should be searched. Further studies are needed to explain the pathophysiology and find other more effective therapeutic alternatives.