CED

Clinical dermatology • Concise report

Clinical and Experimental Dermatology

Lichen planus pemphigoides associated with chronic hepatitis B virus infection S. H. Jang, S. J. Yun, S. C. Lee and J. B. Lee Department of Dermatology, Chonnam National University Medical School, Gwangju, Korea doi:10.1111/ced.12530

Summary

Lichen planus pemphigoides (LPP) is a rare autoimmune dermatosis with the features of both lichen planus (LP) and bullous pemphigoid (BP). Although in rare cases, LPP has been associated with several medications and conditions, it is generally considered an idiopathic disorder, and its pathogenesis remains uncertain. We report a 56-year-old woman who presented with a 2-year history of flat-topped, polygonal, violaceous-colored papules and some bullae. She was diagnosed with chronic hepatitis B virus (HBV) infection, which had been treated intermittently with entecavir. Histopathological examination showed the typical features of LP with subepidermal blisters, and with linear deposits of IgG along the basement membrane zone on direct immunofluorescence. Immunoblotting revealed antibodies directed at the BP180 and BP230 antigens. We diagnosed the patient with LPP, and treated the condition with systemic steroids and dapsone. To our knowledge, this is the first report of LPP in a patient with chronic HBV infection.

Lichen planus pemphigoides (LPP) is a rare immunobullous disorder characterized by the coexistence of lichen planus (LP) and bullous pemphigoid (BP). It presents clinically as tense blisters arising on both LP lesions and uninvolved skin. The diagnosis of LPP is made on clinical, histopathological and immunological grounds. Although LPP is usually idiopathic, it has been associated with a wide variety of conditions including malignancies,1 phototherapy,2 multiple drugs, and varicella.3 However, LPP associated with viral diseases such as chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection has rarely been described. We report a case of LPP development in a patient with chronic HBV infection, which is the first such case, to our knowledge.

Correspondence: Dr Jee-Bum Lee, Department of Dermatology, Chonnam National University Medical School, 42 Jebong-ro, Dong-gu, Gwangju 501-757, Korea E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 1 June 2014

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Report A 56-year-old woman presented with a 2-year history of pruritic scattered papules on her arms and abdomen. According to her medical history, the patient had developed HBV infection 20 years previously, and she had been treated with entecavir (guanosine analogue) and ursodesoxycholic acid for 6 years. On physical examination, flat-topped, polygonal, violaceous-colored papules were seen on the patient’s arms, and some papules were accompanied by small vesicles or had central crusting on the surface (Fig. 1). Bullous lesions developed several weeks after the papules, and were distributed both on the lichenoid lesions on the arms and normal skin of the trunk. Superficial ulcerations were present only on the oral mucosa. Laboratory investigations, including complete blood count, platelet count and chemical analyses were normal, except for raised IgE (606.0 IU/mL; normal range 0–100.0 IU/mL) and ALT (39 U/L; normal range 10– 37 U/L). Histopathological examination of a biopsy taken from a papule accompanied by a small vesicle on the arm identified a subepidermal blister with moderate

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LPP associated with chronic HBV infection  S. H. Jang et al.

(a)

(b)

Figure 1 Multiple violaceous, flat-topped, polygonal papules with

central crusting on the upper arms.

acanthosis, and a lichenoid lymphocytic inflammatory infiltrate in upper dermis (Fig. 2a). Direct immunofluorescence (DIF) of perilesional skin showed linear deposits of IgG along the basement membrane zone (BMZ) (Fig. 2b). Immunoblotting analysis was performed with normal human foreskin epidermal extract. It revealed antibodies directed against the 180 and 230 kDa BP polypeptides, which were compatible with the molecular weights of BP, which was used as a control serum (Fig. 3). Based on the concurrent clinical, histopathological and immunological features of both LP and BP, a diagnosis of LPP was made. Combination therapy with prednisolone 30 mg/day and dapsone 100 mg/day was started. The lichenoid lesions resolved gradually within the first month of treatment, and no new bullae developed. Prednisolone was subsequently tapered over the following 6 months, and dapsone was discontinued after 5 months. During the 3-year follow-up, remission of bullous formation was maintained, although mild itching due to LP occurred occasionally. LPP is a rare clinical variant of BP, which is characterized by bullae arising on LP papules and on clinically uninvolved skin, histological findings of subepidermal bullae, and DIF findings of linear deposits of IgG and/or C3 along the BMZ. Typically, a lichenoid

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Figure 2 (a) A subepidermal blister with band-like lymphocytic

infiltrate in the upper dermis (haematoxylin and eosin, original magnification 9 100). (b) Linear deposits of IgG along the basement membrane zone shown by direct immunofluorescence (original magnification 9 200).

eruption precedes the development of bullae by several weeks or months, and the bullae tend to be restricted to the limbs. Zaraa et al.4 reported that the average time from development of LP lesions to vesicobullous lesions of LPP was 8.3 months, and the bullae were predominant (95.4%) on both the upper and lower limbs. The pathogenesis of LPP is still unknown. Some studies have shown that LPP is associated with the major BP180 antigen, while others report that BP230 may also be specific to the condition. Zillikens et al.5 suggested that the primary inflammatory process in LP lesions might cause BMZ damage and expose BP180 antigens, which in turn induce the production of autoantibodies against the BMZ.

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LPP associated with chronic HBV infection  S. H. Jang et al.

Immune complexes and the viral antigens associated with chronic hepatitis may be involved in the development of LP. In our case, we believe that the lymphocytic inflammatory process in LP with chronic HBV infection led to the release of antigenic determinants, resulting in an autoimmune response against hemidesmosomal structures. Therefore, LP lesions might cause BMZ damage and bullous formation. LPP has been treated with systemic steroids, topical steroids, dapsone and immunosuppressive drugs, with variable success. Systemic steroids appear to be the most effective treatment in the extensive LPP. Our patient was successfully treated with a combination of systemic steroids and dapsone. To our knowledge, LPP associated with chronic HBV infection has not been reported previously. In endemic areas of chronic HBV and HCV, especially in Korea, the possibility of LPP in the patients with LP patients and chronic hepatitis virus should be considered.

Learning points Figure 3 Immunoblotting analysis using normal foreskin epider-

mal extract detected antibodies against both the bullous pemphigoid (BP)180 and BP230 kDa polypeptides, which were compatible with the molecular weights of BP, used as a control serum.

LPP has been reported to be induced by malignancies,1 phototherapy [ultraviolet (UV)B, psoralen UVA),2 and medications such as ramipril6 and cinnarizine.7 The interval between drug administration and occurrence of LPP usually ranged from 2 to 12 weeks in previous reports.6,7 Our patient was treated with entecavir and ursodesoxycholic acid for 6 years, and she took the drugs intermittently when her serum HBV DNA level and alanine aminotransferase level were raised. Consequently, we could not prove a cause-and-effect relationship between entecavir and LPP. There have been previous reports of LPP occurrences in a patient treated with interferon and ribavirin for HCV infection, 4 and in a child with acute HBV infection.8 There have also been many reports of an association with LP and chronic hepatitis. Rebora et al.9 reported that 13.5% of patients with chronic hepatitis had LP, and Korkij et al.10 reported that abnormal hepatic enzyme elevations were noted in 52% of patients with LP.

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 LPP is a rare skin disorder characterized by a

mixture of clinical, histological and immunological features of both LP and BP.  LPP is usually idiopathic, but there have been some reports of association with malignancies, various drugs and viral infection.  To our knowledge, this is the first report of LPP in a patient with chronic HBV infection.  Our patient was successfully treated with systemic steroids and dapsone.

References 1 Bouloc A, Vignon-Pennamen MD, Caux F et al. Lichen planus pemphigoides is a heterogeneous disease: a report of five cases studied by immunoelectron microscopy. Br J Dermatol 1998; 138: 972–80. 2 Kuramoto N, Kishimoto S, Shibagaki R et al. PUVAinduced lichen planus pemphigoides. Br J Dermatol 2000; 142: 509–12. 3 Ilknur T, Akarsu S, Uzun S et al. Heterogeneous disease: a child case of lichen planus pemphigoides triggered by varicella. J Dermatol 2011; 38: 707–10. 4 Zaraa I, Mahfoudh A, Sellami MK et al. Lichen planus pemphigoides: four new cases and a review of the literature. Int J Dermatol 2013; 52: 406–12.

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LPP associated with chronic HBV infection  S. H. Jang et al.

5 Zillikens D, Caux F, Mascaro JM et al. Autoantibodies in lichen planus pemphigoides react with a novel epitope within the C-terminal NC16A domain of BP180. J Invest Dermatol 1999; 113: 117–21. 6 Ogg GS, Bhogal BS, Hashimoto T et al. Ramiprilassociated lichen planus pemphigoides. Br J Dermatol 1997; 136: 412–14. 7 Miyagawa S, Ohi H, Muramatsu T et al. Lichen planus pemphigoides-like lesions induced by cinnarizine. Br J Dermatol 1985; 112: 607–13.

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8 Flageul B, Hassan F, Pinquier L et al. Lichen pemphigoid associated with developing hepatitis B in a child. Ann Dermatol Venereol 1999; 126: 604–7. 9 Rebora A, Rongioletti F, Canepa A. Chronic active hepatitis and lichen planus. Acta Derm Venereol 1982; 62: 351–2. 10 Korkij W, Chuang TY, Soltani K. Liver abnormalities in patients with lichen planus. A retrospective case-control study. J Am Acad Dermatol 1984; 11: 609–15.

Clinical and Experimental Dermatology (2015) 40, pp868–871

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Lichen planus pemphigoides associated with chronic hepatitis B virus infection.

Lichen planus pemphigoides (LPP) is a rare autoimmune dermatosis with the features of both lichen planus (LP) and bullous pemphigoid (BP). Although in...
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