Bullous Lichen Planus of Oral Mucosa: A Case Report

Introduction

Skin, oral mucosa, vaginal mucosa, scalp, and nails are all affected by the chronic, inflammatory, autoimmune illness known as lichen planus (LP). The flexor surfaces of the wrists, forearms, and legs are the most susceptible areas, and it usually develops abruptly. These lesions typically have Wickham's striae, which are lacy, reticular, white lines.¹ Lichen planus presents in a variety of forms such as patches, hyperkeratosis, bullous or ulcerative lesions. However, the histologic findings remain characteristic in all the variants; thus a secure diagnosis can be made.² A rare kind of lichen planus is bullous lichen planus. Bullae or vesicles, which typically appear with the preexisting lichen planus lesions are the defining features of this variant. The characteristic feature of bullous lichen planus is blistering during acute eruptions.² Among the different clinical variants of oral mucosal lichen planus, bullous lichen planus is infrequent showing blisters that increase in size and rupture, leaving an ulcerated and painful surface. This lesion should be differentiated from other forms of bullous diseases.³ The diagnosis is confirmed by histopathology and immunofluorescence.² All types of lichen planus, including those with cutaneous, vaginal, and mucosal lesions, respond well to topical corticosteroids. Severe, widespread lichen planus, however, may require systemic corticosteroids. Lichen planus that affects the mucous membrane is more likely to recur and may be more difficult to treat.¹ Here we present a case of bullous lichen planus of oral cavity.

Case Presentation

A 36-year-old female patient presented with a complaint of fluid filled blisters that burst open to form ulcer inside the mouth and burning sensation on consumption of hot and spicy food since six months. Patient noticed a fluid filled blister that had burst open to form an ulcer inside the mouth six months ago, which was insidious in onset, gradually progressing, non-tender and was associated with burning sensation which was insidious in onset, and aggravated on having hot and spicy food.

The patient was a known diabetic since six years with a history of hypothyroidism since 16 years and was under medication for the same. Dental and family histories were non-contributory.

Extra oral manifestation revealed keratotic lacy reticular lesions on the upper and lower vermilion border of lip (Figure 1) and presence of hyper pigmented macules and patches on the right and left leg.

On intra oral examination, solitary mixed red and white lesions were noticed on the right and left buccal mucosa and dorsal surface of tongue. Lesions on left and right buccal mucosa were irregular in shape, had well defined margins with lacy white striations, measuring 3X3 cm in greatest diameter, non-scrappable, extended anterioposteriorly from right and left retro commissure region to retro molar region and superior inferiorly from upper vestibule to lower vestibule, respectively (Figure 2). White lesion on the dorsal surface of tongue was roughly oval in shape, well defined, measuring 2x2 cm in greatest diameter with depapillation seen at the center of the lesion (Figure 3). On palpation, the lesion was non tender, non-scrapable, and did not disappear on stretching. Since the lesions were bilateral and showed typical features of lichen planus preceded by a history of blistering, a provisional diagnosis of bullous lichen planus was given and a differential diagnosis of Lichenoid reaction and Lichen planus pemphigoid were considered.

Investigations included a full hemogram, blood sugar test, and an incisional biopsy of the right buccal mucosa. The results of all the conducted investigations were found normal, and the biopsies revealed hyperparakeratinized epithelium with irregular rete ridges, basal cell degeneration, intraepithelial clefts and juxta epithelial chronic dense inflammatory infiltrate, thus confirming the diagnosis of oral bullous lichen planus (Figure 4).

Patient was treated with topical Triamcinolone acetonide 0.1%, applied three times daily for oral lesions. For extra oral lesions, the patient visited a dermatologist and was advised Tezcort cream (clobetassol proprionate), Elavel moisturizer cream, (Glycerine, Aloevera extract, Shea butter, Vitamin E etc.), Tab Glotret-10 (Isotretinoin) once a day for 30 days and Tab Covel (antihistamine) 5 mg once a day for five days.

A follow up visit after one month revealed decrease in white lesions and burning sensation of oral lesions (Figure 5) by 60% (measured with Visual Analogue Scale) and the patient was asked to continue with topical Triamcinolone acetonide 0.1% for another one month and is currently under follow-up.

Discussion

The mouth is a mirror of health or disease. Since numerous systemic disorders present oral signs, the oral cavity could be considered a window to the body. Oral involvement typically occurs before the occurrence of additional symptoms or lesions in other locations. Erasmus Wilson, an English physician, was the first to name and describe the pathology, Lichen planus in 1866. He believed it to be the same disease as "lichen ruber," which was first described by Hebra and defined it as "an eruption of pimples notable for their colour, form, structure, and habits of isolated and aggregated development." Lichen ruber pemphigoides, the initial clinical symptom of the illness, was first identified by Kaposi in 1892. Wickham originally observed the Wickham striae, or reticulate white lines, on the surface of LP papules in 1895. Darier was the first to formally describe the histological alterations associated with LP.⁴

The specific cause of this illness is uncertain. According to the current research, the pathogenesis of oral lichen planus (OLP) primarily involves T cell-mediated immunological mechanisms. Oral lichen planus can have both non-specific and antigen-specific pathogenesis. Antigen presentation of basal keratinocytes is an antigen-specific mechanism, but mast cell degranulation and the activation of matrix metalloproteinase (MMP) in OLP lesions are nonspecific processes. Together, these two strategies may result in the buildup of CD8+ cytotoxic T-cells in the superficial lamina propria, as well as the rupturing of the basement membrane, intraepithelial T-cell migration, and apoptosis of keratinocytes. Chronicity of OLP could be caused by a lack of antigen-specific Transforming growth factor-β TGF-b1-mediated immunosuppression.⁵ Oral lichen planus associated with blisters is rare and can be due to severe liquefactive degeneration of cells forming the basal layer. This form of OLP is called bullous lichen planus (BLP).³

Prevalence of oral lichen planus in Indian population is 2.6%.⁶ Classic LP (CLP) is a reddish purple, lustrous flat papule. Wickham's striae, or white lacy lines, can be visible on the surface of the papule. Vesiculobullous, hypertrophic, actinic, linear, annular, zoster form, nail, atrophic, inverse, eruptive, erosive, pigmentosus, planopilaris, vulvovaginal, erythematous, overlap syndrome, pemphigoides and oral LP are some of the 17 various subtypes of LP that can occur anywhere on the body. Reticulopapular, papular, plaque-like, erosive, atrophic, and bullous are six of the subtypes of OLP.⁷ Reticular type is the most common type whereas erosive type of lichen planus is the second most common type.⁸

The five Ps of cutaneous lesions of LP are plaque, pruritic, papules, polygonal and purple lesions. LP typically begins as a cutaneous and mucosal eruption, though it can also appear on the lips or nails. LP generally starts as small, flat-topped papules with a diameter of 3 to 15 mm that can consolidate into bigger plaques. As the illness worsens, they quickly change colour from red to reddish purple or violaceous. The papule's surface is covered in Wickham striae, which are extremely thin, greyishwhite lines. The centre of the papule could be slightly umbilicated. The skin lesions can appear anywhere on the surface of the skin, although they are more frequently found on the flexor surfaces of limbs, the inside sides of knees and thighs, the trunk, as well as on trauma lines.⁹ Usually the face is not involved. Pruritis is the major symptom of LP which can be mild or severe.⁴

Clinically, lesions in the oral cavity with radiating white, grey, velvety, thread-like papules arranged in a linear, annular, and retiform fashion result in recognizable lacy, reticular patches, rings, and streaks that differ considerably from those on the skin. In contrast to the Wickham striae on the skin, a little elevated white dot can be seen at the intersection of the white lines known as the striae of Wickham. The lesions can develop bilaterally or symmetrically, in any place in the oral cavity. However, they are more common on the buccal mucosa, tongue, lips, gingiva, floor of mouth, and palate.¹⁰

The present case was of bullous lichen planus type. BLP is usually sporadic compared to other clinical types and is found at a rate of 1%.¹¹ There are two types of BLP, familial and non-familial. Compared to non-familial BLP, familial type has an earlier onset and a longer course. BLP is a subtype of LP and an illness with an immunological basis. It commonly affects the legs and oral mucosa, with blisters growing next to or over LP lesions that have already been present. It can manifest on the nails which may result in hemorrhagic crusting and complete loss of the nail plate resulting in nail atrophy. BLP can be seen associated with ulcerative lesions, on the feet and cicatrical alopecia. It was reported to have developed with systemic sclerosis, in association with scabies in a child and also with hepatitis B vaccination.³

Lichen planus pemphigoides, pemphigus, bullous pemphigoid, lichenoid stomatitis and chronic ulcerative stomatitis are all possible differential diagnoses for bullous lichen planus.¹²

In pemphigus and bullous pemphigoid, the absence of typical greyish white striations differentiates it from BLP. Lichenoid reactions will be always associated with history of allergens or drug reactions.

It is important to distinguish lichen planus pemphigoides (LPP) from BLP.¹ In lichen planus pemphigoides, blisters form on both unaltered skin and pre-existing LP lesions. To distinguish between BLP and LPP, histology is essential. Without histologic evidence of LP, sub-epidermal bullae occur in LPP. In BLP, along with the typical features of lichen planus, there is an extensive inflammatory infiltrate, with formation of large Max-Joseph spaces in cutaneous lesions that alter the dermoepidermal junction and cause liquefactive eruption of the basal layer cells. As a consequence, there is formation of tense bullae that are intrabasal due to separation of basal layer cells from the underlying basal membrane.³

The diagnosis of oral lichen planus is usually made with the aid of clinical examination and a comprehensive history, followed by tissue biopsy. The confirmatory diagnosis of lichen planus can be obtained by histopathological evaluation of the biopsy specimen obtained from the disease site. Direct immunofluorescence demonstrates a "Linear pattern" in the basement zone and a positive antifibrinogen fluorescence. Colloid bodies contain IgA, IgG, and complement C3. Antibodies in the bloodstream of lichen planus patients can be detected via indirect immunofluorescence. The "annular fluorescence" or "string of pearls" appearance is caused by circulating antibodies reacting with and binding to the basal epithelial cells.¹³

Management

Numerous treatment modalities are employed in the treatment of symptomatic oral lichen planus; however, it is difficult to achieve complete resolution. Topical corticosteroids are used as a first-line of therapy. High-potency topical steroids are very effective, with excellent response rates. Only the cases of severe, extensive oral lichen planus and those involving other mucocutaneous regions are acceptable for systemic corticosteroids such as oral prednisone (30-60 mg/ day for six weeks).¹⁴ Tacrolimus and pimecrolimus (Elidel), topical calcineurin inhibitors, can be considered as second-line of treatment for oral lichen planus.¹⁵ Carbon-dioxide laser evaporation offered long-term symptom remission,¹⁶ and Aloe vera gel use demonstrated a noticeable improvement in clinical signs and symptoms.¹⁷ These treatment modalities may be tried as primary treatment in individuals with uncomfortable oral lichen planus.¹ Biostimulation with a pulsed diode laser employing 904-nm pulsed infrared rays, low-dose excimer 308-nm laser with UV-B rays, and photodynamic treatment (PDT) have all been explored. Protein denaturation causes all types of lasers to damage the superficial epithelium housing the target keratinocytes. The underlying connective tissue with the inflammatory component along the epithelium is destroyed by a deeper penetrating beam like the diode laser.¹⁸

BLP is considered as the hyper-reactive form of LP and there is no clear effective treatment for this lesion. Just like any other type, potent topical corticosteroids have been used as first line of therapy. Moderate to severe oral BLP can be effectively treated with oral betamethasone minipulse therapy.¹⁹ Systemic corticosteroids are used for severe or refractory cases not responding to topical therapy. Dapsone (especially used in children)²⁰ and mycophenolatemofetil have also been tried effectively.²¹ Topical application of tretinoin 0.025% in combination with triamcinolone 0.1% has also been successfully used for treating bullous lichen planus of the lip.²² Acitretin monotherapy (contraindicated in child bearing and pregnant women due to its teratogenicity),^1,23 and antimalarial drugs are other treatment options.³ Systemic isotretinoin was found to be very successful in the treatment of cutaneous and oral erosive lichen planus, since it reduces burning sensation/pruritus and hyperpigmentation, effectively.²⁴ In the above discussed case, oral and extra oral lesions were managed successfully with a combination of topical steroids and low dose isotretinoin.

OLP's malignant metamorphosis was first described by Koberg et al. It is uncertain whether OLP is a standalone risk factor for the development of Oral squamous cell carcinoma OSCC. The existence of other risk factors (tobacco, alcohol), the varying inclusion of oral lichenoid lesions and the lack of evidence for whether the malignancy formed is due to OLP or was merely associated with it, have not been established. Patients with OLP are recommended to avoid risk factors like tobacco and alcohol.^1,25 A relatively higher risk of oral lichen planus developing into oral cancer was observed in tobacco users and atrophic variants.⁶ Erosive, atrophic and bullous lichen planus have shown malignant transformation. Malignant transformation rate of erosive lichen planus was reported to be less than 0.4-3.7%.²⁶

Conclusion

OLP is one of the most common mucosal pathologies encountered by dental and oral physicians and BLP represents a rare form of LP. Making an accurate diagnosis of the lesions and establishing effective treatment as soon as possible is critical. There is presently no cure for OLP; all the existing treatment modalities have local and systemic side effects, and the lesions might recur once the treatment is stopped. In the present case, a combination of potent topical steroids (Triamcinolone acetonide 0.1%) were used for oral lesions and systemic Isotretinoin was used for extra oral lesions which reduced the symptoms and indicators of the lesions, thereby fulfilling the treatment goals such as relieving unpleasant symptoms, repair of ulcerative and atrophic lesions, lowering the risk of malignant transformation, and extension of symptom-free intervals.

Conflict of interest

None