Cheilitis granulomatosa: a case report with review of literature.

Cheilitis granulomatosa (CG) is a chronic swelling of the lip due to granulomatous inflammation. It is a rare inflammatory disorder first described by Miescher in 1945. It is a monosymptomatic form or an incomplete variant of Melkersson-Rosenthal syndrome; a triad of recurrent orofacial edema, recurrent facial nerve palsy and fissuring of the tongue. As the etiology remains unknown, treatment of CG is challenging. We present a case of CG in a 43-year-old female patient secondary to allergy to certain food items. The present case highlights the importance of thorough investigations in the diagnosis of this lesion as the findings mimic many other granulomatous conditions.

What was known?

Cheilitis Granulomatosa is a rare inflammatory disorder with unknown etiology. This renders this granulomatous condition difficult to treat.

Introduction

Cheilitis granulomatosa (CG) is a rare and unique disorder. This condition is characterized by chronic swelling of one or both the lips due to granulomatous inflammation. It is a rare inflammatory disorder first described by Miescher in 1945.[12] It is a monosymptomatic form or an incomplete variant of Melkersson-Rosenthal syndrome (MRS); a triad of recurrent orofacial edema, recurrent facial nerve palsy and fissuring of the tongue. CG is also considered a subset of an uncommon disease Orofacial granulomatosis, which was introduced by Wiesenfeld in 1985.[3]

Case Report

A 43-year-old woman patient presented with persistent, painful upper lip swelling since one week [Figure 1]. There was no history of applied irritants, local trauma or atopy. She also reported burning and peeling off in perioral area. Past history revealed that patient had been treated for similar condition with various different modalities including ayurvedic medication, homeopathy and topical steroids in past three years. On examination the upper lip and perioral area showed painful swelling, with areas of crusting and fissuring [Figure 2]. Neither facial nerve palsy nor fissuring of the tongue nor lymph node involvement was present. No such lesions were seen intraorally.

Figure 1

Patient with upper lip swelling and peeling in perioral area

Figure 2

Upper lip and perioral area showing swelling and areas of crusting and fissuring

The biopsy revealed hyperplastic epithelium of variable thickness covered by fibrinopurulent exudate [Figure 3]. The superficial lamina propria was loose and edematous. The underlying fibrocellular connective tissue revealed with abundant non caseating granulomas with Langhans type multinucleated giant cells and perivascular lymphocyte aggregations [Figure 4]. In other investigations, chest radiograph showed no abnormalities, and a Mantoux test was non-reactive. Evaluation for food allergies revealed higher allergen quantity for the following food items (normal range being 0-0.35 Ku/L):

Figure 3

Section showing hyperplastic epithelium and dense inflammatory infiltrate in underlying connective tissue (H and E, ×10)

Figure 4

Section under higher magnification showing fibrocellular connective tissue with abundant non - caseating granulomas with Langhans type multinucleated giant cells (H and E, ×40)

Almond: 1.90

Cashew nut: 1.30

Urad dal: 1.30

Rajma: 1.20

Cabbage: 1.80

Tomato: 2.00

From all these findings a diagnosis of CG secondary to certain food items was made.

Discussion

CG is a chronic swelling of the lip due to granulomatous inflammation. It is a monosymptomatic form or an incomplete variant of MRS which is a triad of recurrent orofacial swelling, relapsing facial paralysis and fissuring of the tongue (lingua plicata). Presentation of complete MRS with all three elements of the triad in a single patient is rare, being reported in only 10-20% of cases, and bilateral facial palsy in MRS is even rarer.[4] In approximately 40% of cases, CG is the presenting sign of MRS, with subsequent development of the neurologic signs.[4]

The presence of CG without lingua plicata or facial palsies also is called Miescher syndrome or Miescher's Cheilitis.[12] In 1985, Wiesenfield[3] introduced the concept of Orofacial granulomatosis (OFG). Today both CG and MRS are considered subsets of OFG.

The etiology of CG continues to remain a mystery. Reports suggest that some cases may demonstrate an autosomal dominant inheritance pattern, with the responsible gene mapping to chromosome 9 p11.[5] Other authors have proposed a wide range of causes including allergic reactions, chronic infectious odontogenic foci, autoimmune mechanism, as an association with Crohn's disease and sarcoidosis or even as oral manifestation of systemic diseases.[6]

The age of onset is usually young adulthood with no racial or sexual predilection.

Zimmer,[7] et al. in their analyses of 42 patients and review of 220 cases they showed female predilection and a wide range of onset with a mean of 33.8 years.

Granulomatous cheilitis should be considered in children as well according to Oliver, et al.[8] who reported Granulomatous Cheilitis in an eight-year-old girl, which persisted for more than one year.

In patients presenting with CG it is important to perform an appropriate evaluation, which includes a chest radiograph and a Mantoux test to exclude other etiologies of granulomatous disease, such as sarcoidosis or Mycobacterium infection. Gastrointestinal tract endoscopy and radiography may be used to exclude Crohn's disease. Patch tests have implicated cobalt and the food additives cinnamaldehyde and benzoates in the pathogenesis of CG.[3]

Treatment

Various treatments for CG have been reported, including antibiotics like tetracycline and clofazimine[89] tranilast,[10] oral and intralesional steroids,[1112] and surgical resection.[13] Rapid improvement and/or complete resolution after dental treatment have been reported.[14-16]

Some believe that intralesional triamcinolone (TAC) combined with dapsone yields the best result, whereas others report success using intralesional TAC alone; incidentally TAC has also been successfully combined with clofazimine.[1011]

Because of the link between CG and Crohn disease, it has been postulated that tumor necrosis factor-α production is involved in the pathogenesis of both conditions. A single case report describes the successful treatment of CG, which had been refractory to multiple standard therapies, with infliximab at doses that are used for Crohn disease.[17]

Surgical intervention and radiation have been proposed in the management of CG in cases of severe disfigurement and post-surgical relapses are common.[18]

Conclusion

According to new concepts, “diagnosis” is not merely naming the disease but should also include probable etiological factor/s. In this case diagnosis of CG was made by correlation of patient's history, clinical features, investigations and histopathological findings. The present case highlights the importance of thorough investigations in the diagnosis of this lesion as the findings mimic many other granulomatous conditions.

What is new?

Comprehensive approach in differential diagnosis of granulomatous lesions is highlighted. This is important in prompt treatment planning and better prognosis.