Chronic graft versus host disease presenting as lichen planus pigmentosus

Chronic graft-versus-host-disease (cGVHD) is a frequent and severe complication of allogeneic hematopoietic stem cell transplantation (AHSCT). According to the National Institutes of Health, diagnostic clinical features of cGVHD include poikiloderma, lichen planus-like eruption, deep sclerotic features, morphea-like superficial sclerotic features and lichen sclerosus-like lesions [1].

Lichen planus pigmentosus (LPP) is an uncommon variant of lichen planus, mainly described in India and the Middle East. This cosmetically distressing pigmentary disorder is characterised by large hyperpigmented patches in sun-exposed areas or in the folds. Histological features of LPP include vacuolar degeneration of the basal cell layer and pigment incontinence in the dermis [2, 3]. Therapeutic options of LPP include topical corticosteroids, topical tacrolimus, depigmenting creams, isotretinoin and dapsone [4, 5].

Several types of lichenoid dermatitis have been described in skin cGVHD namely lichen planus, bullous lichen and lichen sclerosus and atrophicus [1, 4, 5]. We describe a new type of lichenoid skin cGVHD mimicking LPP.

We performed a retrospective monocentric study (Saint Louis Hospital, Paris, France) on 11 patients with LPP lesions seen at a dedicated dermatological post-transplant consultation between 2011 and 2016. Inclusion criteria for LPP were clinical +/− histological signs of LPP appearing after AHSCT and other definite symptoms of cGVHD (according to NIH criteria [6]) involving the skin or other organs. Clinical features and response to topical and systemic treatments were recorded retrospectively. Clinical pictures were performed routinely after informed consent of the patient. The response of LPP to treatments was assessed by the physician and classified as « complete response », « partial response », « stability» or « worsening » [7,8,9].

Main characteristics of the 11 LPP patients are summarised in Supplemental Table 1. Nine patients had extra-cutaneous cGVHD: GI tract n = 2; liver n = 4; bronchiolitis obliterans n = 3; opthalmologic n = 6; muscular involvement n = 1 and articular involvement n = 1. Seven patients had classical cGVHD skin symptoms: lichen planus n = 4, morphea n = 3, deep sclerotic features n = 1 and poikiloderma n = 3. Associated lichen planus was often present: oral (eight patients), genital (three patients) and ungueal lesions (one patient). Median time from AHSCT to LPP onset was 8 months (range 3–22). Patients presented with dark brown or slate grey patches or papules preferentially on sun-exposed areas (see examples in Fig. 1). There was no previous 'inflammatory' skin stage, as opposed to the red/violaceous lesions that are typically seen in lichen planus. A skin biopsy was performed in five cases showing lichenoid histological features (basal layer vacuolisation and pigmentary incontinence). All patients were advised to use a moisturising cream and sunscreen on a daily basis. Specific topical treatments were used in all patients, nine patients were receiving a stable dose of systemic immunosuppressive treatment and two patients were not receiving any systemic treatment. Systemic immunosuppressive treatments used for extra cutaneous cGVHD were prednisolone n = 9/9, cyclosporin n = 4/9, sirolimus n = 1/9, mycophenolate mofetil n = 1/9, mycophenolic acid n = 1/9 and extracorporeal photopheresis n = 5/9. Topical corticosteroids were used alone in three patients, along with tacrolimus (0.1%) in three, and with depigmenting cream 5% (hydroquinone 5% + hydrocortisone 1%) in two. Depigmenting cream 5% was used alone in one patient and along with topical tacrolimus 0.1% in another one. Topical steroids + topical tacrolimus 0.1% + depigmenting cream 10% (hydroquinone 10% + hydrocortisone 1%) were used in 1 patient. Median follow-up duration was 35 months (8–63 months). LPP skin lesions improved in 9 of 11 patients (Table 1). Median time to maximal skin response was 6 months (3–11months). As soon as a 'good' therapeutic response was obtained according to the patient and the clinician, topical treatments were progressively tapered. Local treatment failure was observed in three patients. One patient had spontaneous improvement of LPP without any local or systemic treatment after 36 months of follow-up. No adverse event of skin targeted therapies was reported but there were six cases of a possible side-effect of the immunosuppressive treatments used for cutaneous and extracutaneous cGVHD: recurrent systemic infections (n = 2), aseptic osteonecrosis (n = 2) and death (n = 2). LPP was the only cGVHD manifestation in two patients. In one patient, LPP appeared 10 months after AHSCT and a complete remission was observed after 6 months of topical corticosteroids use. In the other one, the diagnosis of LPP was made 7 months after AHSCT and complete remission was achieved without any treatment. The clinical courses of LPP and extra-skin cGVHD symptoms were strictly parallel for five patients (worsening and improvement of symptoms). LPP and extra skin cGVHD symptoms appeared at the same time for four patients. Although the retrospective nature of the study did not allow us to draw firm conclusions, LPP and other cGVHD skin and mucous membrane symptoms evolved in parallel in most of the patients.

Fig. 1
figure1

Lichen planus pigmentosus in two patients. Grey macules on the face without the previous inflammatory stage seen in 'classical' lichen planus

Table 1 Lichen planus pigmentosus topical treatment response under stable dose of immunosuppressive systemic treatment

This study describes the first cohort of LPP patients after AHSCT. Other hyperpigmented dermatoses such as erythema dyschromicum perstans (EDP), ashy dermatosis or idiopathic eruptive macular pigmentation may look like LPP [10, 11]. Some authors consider them part of the same nosological spectrum, while others argue that they are different diseases. EDP has classically an elevated erythematous border in its early stage whereas LPP does not present with an initial inflammatory stage. Histopathological studies did not show significant differences between LPP and EDP [12,13,14]. Other classical cGVHD skin symptoms such as morphea and lichen planus may induce hyperpigmented scars in the late stage [15] but the initial presentation (skin sclerosis with inflammatory borders for morphea and red-violacaeous patches for lichen planus) allows a clear distinction with LPP. Topical treatments in addition to stable doses of immunosuppressive agents resulted in an improvement in 9 of 11 patients (median time to maximal response = 6 months). Topical treatments of LPP occurring after AHSCT include topical steroids, topical tacrolimus and depigmenting creams used alone or in combination. LPP in the setting of cGVHD may induce important aesthetic discomfort and should be well known by the clinician to allow proper post-transplant patient management.

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Correspondence to Jean-David Bouaziz.

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Gérard Socié and Jean-David Bouaziz contributed equally to this work.

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Tétu, P., Jachiet, M., de Masson, A. et al. Chronic graft versus host disease presenting as lichen planus pigmentosus. Bone Marrow Transplant 53, 1048–1050 (2018). https://doi.org/10.1038/s41409-018-0110-z

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