Lichen planus pemphigoides L43.10

Rare, regarding its entity, still controversial blistering disease (S.a.u. Lichen ruber bullosus). Some authors interpret lichen ruber pemphigoides as "lichen ruber bullosus" combined with a "bullous pemphigoid-like dermatosis". Other authors point out that the epitope mapping can distinguish lichen ruber pemphigoides from bullous pemphigoid because region 4 within the C-terminus of the NC16A domain of the BP180 antigen (see COL17 A1 gene below) is thought to be specific for lichen ruber pemphigoides (Zillikens D et al. 1999).

Lichen ruber pemphigoides does not appear to be a coincidence of lichen ruber and bullous pemphigoid, but a separate entity. The disease is distinguishable from bullous lichen planus in that no deposits of pathogenic autoantibodies are detectable in the skin in lichen ruber bullosus. Furthermore, the blisters in bullous lichen ruber form only in pre-existing lichen planus lesions, whereas the blisters of lichen ruber pemphigoides occur both intralesionally and on previously unaffected skin.

The etiopathogenetic role of tumor necrosis factor in lichen ruber pemphigoides is currently unclear.

It is thought that a humoral autoimmune response against structural proteins of the basement membrane, especially BP180, is initiated by the chronic inflammatory reaction at the dermo-epidermal junction zone in the context of lichen planus.

In isolated cases, a coincident occurrence of lichen ruber pemphigoides and malignancies has been observed (Shimada H et al. 2015).

Drugs: In recent years, several cases of lichen ruber pemphigoides have been described as a cutaneous anti-PD-1 antibody-mediated side effect(pembrolizumab/nivolumabtherapy) in patients with metastatic malignant melanoma, among others (Schmidgen MI et al. 2017/Mueller KA et al. 2021).

Notes: Monoclonal antibodies to programmed cell death 1 (anti-PD-1) include maculopapular, psoriasiform, and lichenoid, and in rarer cases, autoimmune bullous exanthema and vitiligo.

Mostly occurring in adulthood, well before the 6th decade.

In contrast to the lichen planus bullosus, in this variant the blisters do not (only?) occur in the lichen planus lesions, but also on unmodified skin. It is described as lesional itching and burning.

Common detection of circulating autoantibodies against a 180 kDa BP antigen (BPAG2, type XVII collagen).

Perilesional skin shows linear deposits of IgG and_C3 along the dermoepidermal junction zone. Not infrequently, circulating AK against the 180kDa BP antigen (BPAG2), but not against the 230kDA BP antigen, can be detected in this bullous dermatosis.

Lichen planus bullosus: No detection of BP180AK in the perilesional skin. Lesions only in pre-existing lichen planus efflorescences.

Bullous pemphigoid: No clinical evidence of lichenoid efflorescences.

According to the bullous pemphigoid. In individual cases, good therapeutic effects with ustekinumab have been described (Knisley RR et al. 2017)

A 45-year-old patient presented with acute blistering with previously histologically confirmed lichen planus. The lichen planus consisted of generalized distribution (lichen planus exanthematicus) for about 10 months, with a relapsing course and a deterioration phase for about 5 months.

Clinical signs: Generalized papular exanthema with disseminated red, smooth papules of about 0.2-0.3 cm in size, which conflued to large plaques and showed the typical planus lichen morphology. On the lower extremities, 0.3-0.5 cm large, bulging blisters were found without an inflammatory environment.

Suspected diagnosis: Lichen planus pemphigoides / bullous Lichen ruber

Histology/immune fluorescence (perilesional): Linear deposition of C3 and IgG at the dermo-epidermal junction zone.

Laboratory: Serum detection of autoantibodies against BP180 NC16A.

Dg. Lichen planus pemphigoides

Therapy: Combination of acitretin, 20mg/day p.o. and prednisolone pulse therapy (200mg/day i.v.) and external prednicarbate cream. The blisters healed within a few weeks. After 3 months no AK was detectable. The lichen planus efflorescences also healed completely within one year.

Remark: The further course of the disease remains to be seen.

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2. Knisley RR et al (2017) Lichen planus pemphigoides treated with ustekinumab. Cutis 100:415-418.
3. Kolb-Maurer A et al (2003) Treatment of lichen planus pemphigoides with acitretin and pulsed corticosteroids. Dermatologist 54: 268-273
4. Mueller KA et al (2021) A case of severe nivolumab-induced lichen planus pemphigoides in a child with metastatic spitzoid melanoma. Pediatr Dermatol 40: 154-156.
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8. Shah RR et al (2022) Lichen planus pemphigoides: A unique form of bullous and lichenoid eruptions secondary to nivolumab. Dermatol Ther 35:e15432.
9. Shimada H et al. (2015) Lichen planus pemphigoides concomitant with rectal adenocarcinoma: fortuitous or a true association? Eur J Dermatol 25:501-503.
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11. Zillikens D et al (1999) Autoantibodies in lichen planus pemphigoides react with a novel epitope within the C-terminal NC16A domain of BP180. J Invest Dermatol 113:117-121.