Idiopathic macrocheilia

Abstract

A 13-year-boy presented with painless swelling of upper and lower lips accompanied with gingival enlargement. The aetiology for these symptoms included vast pathological varieties but none of them could fit in. Clinical features were similar to orofacial graulomatosis but histopathological examination revealed chronic non-specific infection. Therefore, the final diagnosis was made as idiopathic macrocheilia through exclusion criteria. Management with intralesional triamcinolone acetonide 40 mg, twice a week for 3 weeks, resulted in significant remission in lip swelling without recurrence after a 6-month follow-up.

Background

Idiopathic macrocheilia is such a rare entity that there is no specific previous literature on it. Here, we have discussed all the possible associated disorders and excluded them scientifically as well as elaborated treatment for the same.

Case presentation

A 13-year-old male patient came to Department of Oral and Maxillofacial Surgery, Faculty of Dental Science, Dharmsinh Desai University, with a painless swelling of upper and lower lips, which has increased in size over a period of time with swelling on gums since last 2 years. There were no other associated symptoms but a sense of disfigurement. A detailed medical history, dental history, family history or history for allergy were unremarkable. There was neither history of trauma nor any insect bite. The systemic review of the respiratory and gastrointestinal tract was also non-significant. Patient had taken tablet cetrizine 10 mg two times a day and tablet pheniramine maleate 22.5 mg one time a day as prescribed by dermatologist but it was completely non-beneficial.

On examination, both lips were competent. The upper lip was swollen and everted. The labial mucosa appeared stretched and dry with no change in colour. The lower lip was less swollen comparatively. Vertical cracks were present on both lips. There was loss of philtrum and nasolabial folds due to swollen lips. Melanin pigmentation was evident on upper lip. Crusting of lip was absent. Sensations were completely normal on both the lips. On palpation, both the lips were soft, oedematous, non-pulsatile and non-tender (figures 1 and 2). Intraoral examination revealed generalised diffuse gingival enlargement which was markedly evident on the labial aspect covering one-half of the clinical crown and extending to involve the attached gingiva up to the mucogingival junction. Gingival enlargement was in decreasing manner anteroposteriorly starting from incisors to molars. The gingiva were pale pink and fibrous, which did not bleed on probing (figures 3 and 4). Gemination of lower right central and lateral incisors was an accidental finding (figure 5).

Figure 1.

Preoperative facial profile showing upper and lower lip swelling.

Figure 2.

Preoperative lateral profile showing upper and lower lip swelling.

Figure 3.

Preoperative gingival enlargement.

Figure 4.

Preoperative gingival enlargement.

Figure 5.

Intraoral radiograph indicating gemination of lower right central and lateral incisors.

Investigations

Blood investigations, ECG and chest radiograph did not suggest any systemic abnormality. IgE count was within normal range (75.2 kUI/L). MRI of upper lip gave impression of mucosal hypertrophy of lips and gingival hypertrophy. There was no other significant finding in the MRI report. Mantoux test showed induration at 4 mm (normal range ≤4 mm). ACE assay revealed a value of 52.72 IU/L (normal value 8–55 IU/L). Ultrasonography of abdomen and pelvis revealed multiple subcentimetre-sized non-specific mesenteric lymph nodes in paraumbilical region. Histopathology report of an incisional biopsy of upper lip and gingiva suggested chronic non-specific infection and hypertrophy of gingiva (figures 6–8).

Figure 6.

Histopathology picture of mandibular gingiva showing parakeratinised stratified squamous epithelium, dilated blood vessels and inflammatory cell infiltration.

Figure 7.

Histopathology picture of maxillary gingiva showing hyperplastic hyperparakeratinised stratified squamous epithelium, dilated blood vessels and inflammatory cell infiltration.

Figure 8.

Histopathology picture of lip showing non-keratinised stratified squamous epithelium with vacuolated cells, dilated blood vessels and numerous dilated capillaries.

Differential diagnosis

Possibility of any cystic changes and vascular malformations was ruled out by MRI of upper lip. Normal chest radiograph and negative Mantoux test excluded the chances of tuberculosis. Patient did not have gastrointestinal symptoms as well as ultrasonography of abdomen did not suggest any possibility of Crohn’s disease. Sarcoidosis was excluded as patient did not suffer from trigeminal neuropathy, salivary or lacrimal gland swelling, xerostomia and having normal ACE assay. Allergic angioedema was ruled out as history of allergen exposure was absent and IgE count was normal. Patient did not exhibit any mucosal or cutaneous lesions, respiratory or renal symptoms thereby chances of Wegener’s granulomatosis were abolished. Histopathology report showed chronic non-specific infection eliminated a possibility of schwannoma of lip, cheilitis glandularis, amyloidosis, minor salivary gland tumours and other granulomatous infection such as orofacial granulomatosis, leprosy and deep fungal infection. Due to the absence of facial nerve palsy and fissured tongue, Melkersson-Rosenthal syndrome was ruled out. The possibility of Ascher’s syndrome was diminished as blepharochalasis and thyroid abnormalities were not detected. Andersson-Fabry disease was ruled out as angiokeratomas of skin or painful extremities were absent on clinical examination. After analysing all clinical features and laboratory investigations, the diagnosis of idiopathic macrocheilia was made.

Treatment

An informed written consent was taken from patient’s parents. The management protocol composed of intralesional injection 0.1 mL of triamcinolone acetonide (40 mg/dL) given at three equidistant points on the vermilion border of upper lip and lower lip using 31 gauge syringe (figure 9). Care was taken to inject triamcinolone acetonide deep into the musculature to avoid lip skin ischaemia. The dose was given at an interval of 3 days for 3 weeks which resulted in significant resolution of the condition. The gingival enlargement was managed later by gingivectomy and gingival contouring after 1 month of lip therapy (figures 10 and 11).

Figure 9.

Intralesional injection 0.1 mL of triamcinolone acetonide (40 mg/dL).

Figure 10.

Specimen from maxillary gingiva.

Figure 11.

Specimen from mandibular gingiva.

Outcome and follow-up

There was no recurrence of the lip swelling after 6 months of follow-up (figures 12 and 13). However, generalised gingival enlargement was encountered especially in anterior region and surgical periodontal therapy has been planned for the same (figure 14). Instructions for oral hygiene maintenance are reinforced. Fresh gastrointestinal or respiratory symptoms were absent till last follow-up.

Figure 12.

Follow-up after 6 months showing significant remission in lip swelling—facial profile.

Figure 13.

Follow-up after 6 months showing significant remission in lip swelling—lateral profile.

Figure 14.

Follow-up after 6 months showing reduction in gingival enlargement.

Discussion

Chronic lip enlargement or macrocheilia is a challenging problem because it leads to major disfigurement and rarely impairs the normal daily function of the lips. Both local and systemic conditions can contribute to macrocheilia and chronic macrocheilia may even herald a systemic disease.

There are several conditions causing lip enlargement, most of them presenting with few distinguishing local signs and symptoms leading to definitive diagnosis. However, some patients present with progressive enlargement of one or both lips and the lack of any other signs or symptoms often poses a diagnostic challenge for the physician.¹

Chronic macrocheilia has a varied aetiology, but granulomatous conditions, both infective and non-infective, comprise a significant proportion of patients. In 2003, Handa et al presented a clinic-pathological study of 28 patients having chronic macrocheilia. Out of 28 patients, 13 patients (46.4%) had granulomatous cheilitis and diagnosis of non-specific macrocheilia was made by exclusion criteria in two patients.¹ In 2017, Miest and his colleagues presented a retrospective study of 104 patients of orofacial swelling. 76 out of 104 patients had lip swelling and 85 patients who had biopsies performed, 40 (47%) had granulomatous inflammation.²

Idiopathic macrocheilia cannot be termed as definitive diagnosis; such a condition is not based on any specific clinical symptoms. The diagnosis of idiopathic macrocheilia can be coined by exclusion criteria, where every other condition or disease with respect to lip swelling is ruled out. Moreover, the rarity of this condition is extremely high that it is difficult to find it in the previous literature. However, in this case, the clinical symptoms mimics this condition to orofacial granulomatosis whereas the histopathological reports suggestive of chronic non-specific infection. Therefore, the diagnosis of idiopathic macrocheilia is determined through the process of exclusion criteria.

Actual term of orofacial granulomatosis was first coined by Wiesenfeld in 1985.³ Orofacial granulomatosis is best defined as a group of conditions characterised by granulomatous inflammation in oral and maxillofacial regions.⁴ In orofacial granulomatosis, there is persistent and/or recurrent labial swelling, oral ulcers and a variety of other orofacial features, which is localised to orofacial region. Granulomatosis causes lymphatic blockage, which leads to a diffuse swelling of the lips and other sites because of lymphoedema.⁵ The aetiopathogenesis of orofacial granulomatosis remains elusive, but it includes hereditary and genetic predisposition, hypersensitivity to food or food additives or various dental materials, microbiological factors, inflammatory/immunological factors, Crohn’s disease, sarcoidosis and Melkersson-Rosenthal syndrome.⁶

The management of orofacial granulomatosis is challenging but the ultimate aims of treatment is to lessen and hopefully resolve orofacial swelling and other features of the disease. Conservative management includes administration of broad-spectrum antibiotics, antituberculous drugs, antilepromatous agent like clofazimine, sulfa drugs (sulfasalazine), antimalarials (hydroxycholoroquine), infliximab, thalidomide and systemic or intralesional corticosteroids.^7–9 In 1993, Sakuntbhai et al treated five patients of orofacial granulomatosis with high-volume intralesional triamcinolone acetonide injections (3–10 mL of 10 mg/mL) where the lip size returned to normal in four patients and was reduced in fifth.¹⁰ In 2003, Sciubba et al successfully treated 13 cases of orofacial granulomatosis using intralesional triamcinolone acetonide.⁴ In 2004, El-Hakim et al presented retrospective study of six patients of orofacial granulomatosis where he successfully treated five out six patients with intralesional steroids injection.⁵ In 2004, Mignogna et al concluded that small volume, highly concentrated, extended release intralesional triamcinolone acetonide injection appears to be effective in orofacial granulomatosis followed by long disease free period.¹¹ In 2014, Fedele presented a cohort study of 22 patients with orofacial granulomatosis showing statistically significant decrease in disease severity until 48 months post treatment with use of triamcinolone acetonide.¹² Therefore, it was observed that intralesional triamcinolone injections showed great influence in normalising the lip size in cases of lip enlargement. Following the literature, the treatment we applied gave us satisfactory result with significant reduction in lip swelling and gingival enlargement was managed surgically by gingivectomy and gingival contouring.

Ridder et al in 2001 and Barry et al in 2005 suggested the use of clofazimine and infliximab, respectively, in difficult cases of orofacial granulomatosis refractory to corticosteroids.^{7 8} In 2017, Innocenti et al published a case report of Miescher’s cheilitis which was treated surgically to recover both functional and satisfactory aesthetic appearance using Conway’s reduction cheiloplasty as the patient developed resistance towards medical corticosteroids as well as infliximab.¹³

Learning points.

• Lip enlargement is a symptom of many disorders, so that such cases should be thoroughly reviewed before concluding any specific diagnosis.

• After excluding all the possible disorders, diagnosis of idiopathic macrocheilia should be made.

• Before planning any surgical interventions, conservative therapy should be considered and applied in idiopathic lip enlargement cases.