Lichen Planus Pemphigoides Presenting Preferentially Over Preexisting Scars: A Rare Instance of Isotopic Phenomenon.

An 18-year-old girl presented with multiple itchy hyperpigmented papules and plaques, along with tense blisters over the lower limbs and buttocks for last 3 months. These papules, plaques, and bullae were mostly localized to preexisting scars. The histopathological findings from papule and bulla were consistent with lichen planus (LP) and bullous pemphigoid, respectively. Direct immunofluorescence (DIF) of perilesional skin around bulla showed linear deposition of IgG and C3. Considering clinical, histopathological and DIF findings, diagnosis of LP pemphigoides (LPP) was made. The preferential localization of LPP lesions over preexisting scars was a very interesting finding in our case an extremely rare instance of the isotopic phenomenon.

What was known?

Lichen planus pemphigoides (LPP) is considered to occur as a result of an autoimmune response to basement membrane antigens BPAg2 and BPAg1, unmasked due to basal layer damage in lichen planus

LPP is clinically characterized by tense bullous lesions over both lichenoid plaques and normal appearing skin.

Introduction

The term “isotopic response” connotes the occurrence of a new skin disorder at the site of another, unrelated, and already healed skin disease.[1] Since the introduction of this phenomenon in dermatology, a variety of dermatoses have been reported to demonstrate this response. We hereby describe a young girl who developed lesions of lichen planus pemphigoides (LPP) over preexisting atrophic scars, an example of “Wolf's isotopic response.” To the best of our knowledge, such a clinical presentation of lichen planus (LP) pemphigoides is not documented yet in the English literature.

Case Report

An 18-year-old girl presented with multiple itchy hyperpigmented papules and plaques, along with intermittent blisters over the lower limbs and buttocks for last 3 months [Figures 1 and 2]. There was no history of drug intake prior to the onset of skin lesions. Past history was significant for painful ulcers over the lower limbs and buttocks 6 years back. These ulcers were associated with fever, myalgia, and arthralgia. She had consulted another institute for these ulcers. The diagnosis of pyoderma gangrenosum was made (as evident from documents available with patient), and she was treated for a year, resulting in complete resolution of ulcers. The ulcers had healed leaving atrophic scars. Mucocutaneous examination revealed multiple atrophic scars over the buttocks and lower limbs. The surface of scars was notable for multiple lichenified plaques and tense bullae. The bulla was noted over both lichenified plaques and otherwise normal appearing skin of scars. Interestingly, most of the lichenified plaques and bullae were found over preexisting scars only [Figure 3]. Scalp, hairs, nails, and mucosae were spared. The clinical differentials were bullous LP and LPP. Skin biopsy was done from multiple sites, for both histopathological examination and direct immunofluorescence (DIF). The histological features of lichenified plaque were orthokeratotic hyperkeratosis, acanthosis, wedge shaped hypergranulosis, basal layer degeneration and band-like of infiltrate of lymphocytes in the papillary dermis; thus corroborating with a diagnosis of LP [Figure 4a–c]. Histopathology of bulla showed a subepidermal bulla with eosinophilic infiltrate; which were suggestive of bullous pemphigoid (BP) [Figure 5a–c]. The scar tissue was characterized histologically by the presence of abundant collagen fibers without any features of inflammation [Figure 6]. DIF from plaque showed a linear pattern of deposition of IgG and C3 along the basement membrane zone [Figure 7]. DIF from the perilesional skin surrounding a bulla showed linear IgG and C3 along basement membrane zone; a feature suggestive of BP [Figure 8]. Thus, in conjunction with the clinical, histopathological and DIF findings, the final diagnosis for our case was LP pemhigoides developing over preexisting scars, as an isotopic phenomenon.

Figure 1

Atrophic scars with overlying lichenoid papules and plaques; and tense bulla on lower limbs

Figure 2

Atrophic scars with overlying lichenoid papules and plaques on buttocks

Figure 3

Close-up of lesions on the leg. Lesions are restricted to area of scar only

Figure 4

Histopathology from plaque showing hyperkeratosis, hypergranulosis, saw toothing of rete ridges, band-like infiltration in upper dermis (a) (H and E, ×40) and (b) (H and E, ×100) with basal layer degeneration (c) (H and E, ×400)

Figure 5

Histopathology from bulla showing partial loss of epidermis including basal layer (a) (H and E, ×40) and (b) (H and E, ×100) and plenty of eosinophils in split (c) (H and E, ×400)

Figure 6

Histopathology from scar showing unremarkable epidermis, increased collagen in dermis and no inflammatory cells (H and E, ×40)

Figure 7

Direct Immunofluorescence from plaque showing linear deposition of Ig G and C 3 along basement membrane zone

Figure 8

Direct Immunofluorescence from perilesional skin of bulla showing linear deposition of Ig G and C3 along basement membrane zone

Discussion

LPP is an uncommon variant of BP, clinically manifested with bullous lesions over papules and plaques of LP, as well as on the uninvolved skin. It was first described by Kaposi in 1892 as a classical case of LP complicated by extensive bullous dermatosis; which was termed as “LPP.” It can be precipitated by certain medications like cinnarizine, captopril, ramipril, psoralen and ultraviolet A (PUVA), simvastatin, and antituberculous medications.[2] IgG autoantibodies against both BPAg2 and BPAg1 are thought to play a pivotal role in the development of the dermatosis. The widely accepted mechanism proposed is that LP or sometimes, PUVA causes damage to basal cells leading to unmasking of hidden antigens; thus paving the pathway for the formation of antibodies and development of lesions of BP.[34] A report described the correlation of levels of antibodies against BPAg2 with the disease activity in LPP.[5] The clinical differentials include bullous LP and LP in association with erythema multiforme. The salient points of difference between LPP and bullous LP have been summarized in Table 1.

Table 1

BLP and LPP: A comparison

Results

DIF testing show a smooth linear distribution of immunoreactants (C3, IgG, IgM, and IgA) along the basement membrane zone of dermoepidermal junction. However, a unique 200 kD antigen has been recognized on the epidermal side of salt split skin of patients with LPP and thus, LPP may represent a clinically distinct entity and not merely, a co-existence of LP and BP.[6] Effective treatment modalities include topical and systemic steroids, tetracycline, nicotinamide,[7] dapsone, isotretinoin, methotrexate and other immunosuppressive drugs.[8] The prognosis is good, with complete resolution achieved with on-time therapy. The recurrence rate is found to be low in comparison to BP. This could be explained by the hypothesis that LPP has a unique antigenic target and thus, represents a distinct entity from BP.[9]

Numerous atypical presentations and associations have been documented in the context of LPP. LPP has been reported in association with keratoacanthoma and colon adenocarcinoma.[10] A unilateral presentation has also been reported.[11] Another interesting report described the evolution of LPP into pemphigoid nodularis.[12]

The occurrence of a different or unrelated dermatological disease at the site of the healed disease is termed as an isotopic phenomenon.[1] The proposed etiologies of isotopic response include viral, immunologic, neural, vascular and locus minoris resistentiae (a site of lessened resistance). Most cases of isotopic response have been described in herpes zoster scars.[13] However, development of LPP over preexisting scars is extremely unique and to the best of our knowledge, is not described in the English literature.

It is a well-known fact that bulla formation in LPP is mediated by immunological damage against BP antigen along basement membrane zone. The predilection of the blisters to develop on the lower extremities could be explained by sluggish circulation in those regions. In our case, scars involving the dermis and subcutaneous tissue with largely unaffected epidermis might have altered the blood circulation in that particular area. This could explain the preferential deposition of immunoglobulins in the scar area and subsequent bulla formation.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

What is new?

Lichen planus pemphigoides in our case was largely restricted to preexisting atrophic scars. Wolf's isotopic response in LPP has probably not been described earlier in the medical literature. Furthermore, we have tried to explain Wolf's isotopic response in our case.