Lichen Planus Pemphigoides in Childhood

Dear Editor, Lichen planus pemphigoides (LPP) is a rare autoimmune subepidermal blistering disorder associated with lichenoid lesions and the presence of autoantibodies targeting BP180 (Collagen XVII) and other dermo-epidermal junction (DEJ) proteins. The diagnosis of LPP relies on the correlation of clinical, histopathological, and immunological findings. The prevalence of LPP is approximately 1 per million population. To date, only very few pediatric cases of LPP have been documented worldwide, including three from India.1-3 A 12-year-old boy presented with recurrent itchy skin lesions on his trunk and extremities for 2 months. These lesions were followed by fluid-filled lesions that appeared 2 weeks ago. There was no history of vaccination or infections. Cutaneous examination revealed blanchable dusky red erythema on his trunk and multiple discrete and coalescing flat-topped lichenoid papules on his extremities Figure 1a and 1b. A few clear, flaccid vesicles and bullae were noted on lichenoid base on the elbows Figure 1c, arms, and helix of both ears. Palms and soles showed erythema, desquamation, and tenderness. Nails, oral, and genital mucosa were unaffected. Nikolsky’s sign was negative.Figure 1: (a) Multiple erythematous and lichenoid papules on the anterior trunk with bullae on the chest (b) multiple coalescing lichenoid papules on the dorsum of the right hand (c) few vesicles and bullae on normal skin and lichenoid lesions (black arrow) on left forearmSkin biopsies were taken from a vesicle and a lichenoid papule, both of which showed hyperkeratosis, a conspicuous granular layer, mild irregular acanthosis, basal vacuolar degeneration, and colloid bodies. The upper dermis showed pigment incontinence, moderate perivascular and interstitial lympho-histiocytic infiltrate, admixed with conspicuous eosinophils. Histopathology from the vesicle, in addition, showed subepidermal cleft Figure 2a and 2b. Direct immunofluorescence (DIF) showed linear deposits of IgG and C3 along the basement membrane zone (BMZ) Figure 2c. Indirect immunofluorescence (IIF) on BIOCHIP (Dermatology mosaic 7 BIOCHIP, Euroimmun, Germany) showed BP180 and BP230 positivity Figure 2d and 2e, and salt splitting showed a roof pattern. Based on clinical, histopathology, DIF, and IIF correlation, a diagnosis of LPP was made. The patient was treated with oral prednisolone at an initial dose of 20 mg, that was subsequently tapered over 2 months and stopped. In addition, he was prescribed methotrexate at a dose of 7.5 mg (0.2 mg/kg/dose) once every week. After 4 weeks, the lichenoid lesions and bullae resolved with post-inflammatory hyperpigmentation.Figure 2: (a): Biopsy from lichenoid papule: hyperkeratosis, wedge-shaped hypergranulosis (yellow arrow), basal vacuolar damage (red arrow), Civatte bodies (star) (Hematoxylin and eosin, 100x) (b) biopsy from vesicle: subepidermal blister containing fluid and dermal band of lymphocytic infiltrate (Hematoxylin and eosin, 40x) (c) direct immunofluorescence shows 3+, linear basement membrane zone staining with IgG (40×) (d) indirect immunofluorescence on BIOCHIP mosaic shows a positive reaction with BP 180 (200×) (e) indirect immunofluorescence on BIOCHIP mosaic shows a positive reaction with BP 230 (200×)LPP is a rare autoimmune blistering dermatosis with a prevalence of approximately 1 per million population.4 It was first described by Kaposi as bullous eruptions in lichen planus (LP) in 1892.4 It commonly affects adult males in their third to fourth decades and rarely presents in children. The mean age of onset of childhood LPP is 12 years, with a male-to-female ratio of 3:1.2 In a recent Indian study by De et al., which included both pediatric and adult LPP, the male: female ratio was found to be 1:2.3 A summary of pediatric LPP cases has been mentioned in Table 1.1,2,5-9Table 1: Summary of pediatric lichen planus pemphigoides 1 , 2 , 5-9 The exact pathogenesis of LPP is still unclear. A few authors consider LPP as a variant of bullous pemphigoid (BP) or an overlap of LP and BP. Given the onset of a lichenoid lesion followed by a bullous lesion, another proposed hypothesis is “epitope spreading”. The primary lichenoid inflammation causes damage to the BMZ, exposing the sequestered antigens of DEJ, leading to a secondary immune response against these newly exposed antigens. Auto-antibodies are predominantly directed against type XVII collagen; however, a variety of other DEJ antigens can be targeted.4 Other factors associated with LPP include drugs (angiotensin-converting enzyme inhibitors), infections (hepatitis B, varicella), vaccinations, phototherapy, and internal malignancies.4 Clinically, it is characterized by pruritic lichenoid lesions and bullae on the lichenoid lesions, as well as on clinically normal skin. The mean interval between the development of lichenoid lesions and bullae is approximately 7.9 weeks. In the pediatric age group, the bullae develop more commonly in the distal extremities, involving the palms and soles.8 The diagnosis of LPP is based on clinical, histological, and immunological correlation. The gold standard for diagnosing LPP in patients with lichenoid lesions and tense blisters is IgG and C3 deposition along the dermal-epidermal junction in DIF. Histopathology of lichenoid lesions shows lichen planus-like changes, while biopsy from the bulla reveals a subepidermal blister. IIF detects circulating antibodies to BP180 and BP230 antigens with a roof pattern in salt-split skin.4 LPP must be differentiated from bullous lichen planus (BLP). In LPP, bullae are present on normal skin in addition to pre-existing LP lesions, whereas vesicles and bullae form only on LP lesions in BLP. Histopathology of BLP reveals subepidermal blisters with a mixed inflammatory infiltrate. In LPP, biopsy from a lichenoid lesion reveals LP-like changes, and biopsy from a bulla shows features of bullous pemphigoid. In DIF, LPP typically demonstrates linear IgG and C3 deposits along the BMZ, and BLP may display fibrinogen deposits along the BMZ. IIF is negative in BLP, whereas positivity to BP180 or BP230 antigens may be observed in LPP. LPP has a variable course, usually less protracted and milder than BP.10 The treatment modalities include the use of topical or systemic corticosteroids, dapsone, acitretin, mycophenolate mofetil, or tetracycline with nicotinamide.1 Authors’ contributions We confirm that all authors have read and approved the manuscript for submission. All authors meet authorship criteria, and the manuscript represents honest work. Declaration of patient consent The authors certify that they have obtained all appropriate parent consent forms. In the form a parent has given their consent for his images and other clinical information to be reported in the journal. The parent understands that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. Use of artificial intelligence (AI) The preparation of this manuscript was carried out entirely by the authors without the use of artificial intelligence technologies.