A Case Report of Isolated Pigmentosus Atrophic Lichen Planus on the Supramaxillary Area: A New Variant (cid:0)

Background: Lichen planus pigmentosus (LPP) and atrophic lichen planus (ALP) are two rare subtypes of Lichen Planus (cid:0) LP (cid:0) , the former is characterized by epidermal atrophy and the latter by over pigmentation. LP with both of the above manifestations has few reports and there is a lack of treatment experience. Case presentation: We herein reported a 22-year old girl with a complaint of a sharply edged brown plaque on the supramaxillary area with pain and itchy for 6 months. The skin biopsy sample from the forehead revealed thinning of epidermal ridges, liquefaction degeneration of basal cells, loss of cuticular process, lichenoid lymphocytic inltration and incontinence of pigment as well as numerous melanophages. It was diagnosed as atrophic Lichen planus pigmentosus (ALPP), and the plaque was completely cleared after 10 months of Alternating topical corticosteroids or calcineurin inhibitors. Discussion and Conclusions: ALPP might be an independent variant of LP or LPP that causes signicant epidermal atrophy in the degenerative phase. This case revealed the special type of LP and provided a clinical reference for the treatment.


Background
Lichen planus (LP) is a chronic in ammatory and self-limiting skin condition with phenotypic heterogeneity. Lichen planus pigmentosus (LPP) and atrophic lichen planus (ALP) are two different subtypes of LP, the former is characterized by epidermal atrophy and the latter by over pigmentation. In addition, some cases with LPP have mild epidermal atrophy, and some ALP have slight pigmentation. We report a special case with the characteristics of both subtypes signi cantly which was diagnose as atrophic Lichen planus pigmentosus (ALPP) and successfully treated with topical glucocorticoids and calcineurin inhibitors.

Case Presentation
A 22-year-old girl with a history of brown plaque on her face and occasional pain and itching for 6 months presented to our hospital. The brown plaque has been slowly progressed to a 2 cm × 1 cm black-brown atrophic patch. She denied any history of preceding rash, fevers, chills, trauma,medical application and long time exposure to sunlight. There was no relevant past medical, family, drug or allergy history. On examination the lesion appeared as black-brown with middle atrophy and sharply raised border, and was presented on the right supramaxillary area of the girl (Fig. 1 A). Laboratory tests were negative for hepatitis B, syphilis, hepatitis C and HIV.
The patient was initially diagnoses as LP and differential diagnosis showed drug eruption and granuloma annulare. Interestingly, pathological section of the lesion showed a mixture of LPP and ALP, which are characterized by epidermal basket -like keratinization, hyperkeratosis, wedge-shaped hypergranulosis, thinning of epidermal ridges, liquefaction degeneration of basal cells, loss of cuticular process, lichenoid lymphocytic in ltration and incontinence of pigment as well as numerous melanophages within the papillary and super cial and middle of the dermis. ( Figure.2) The patient was given 1% pimecrolimus cream for topical application for 1 month at the beginning, and her itching was relieved, but the skin lesions showed no signi cant improvement. So, she was switched to 0.03% tacrolimus ointment for 1 month and the skin lesions became lighter in color and slightly reduced in area by 10%, and successively switched to 1% mometasone furfurate cream, desonide cream, chlorobetasol ointment, halometasone cream, triamcinolone acetonide and econazole nitrate cream every 2 weeks for 6 months, than changing to mucopolysaccharide polysulfonate cream, and calcitriol ointment for topical application 2 months. During this period, pigmentation and epidermal atrophy showed continuous improvement (Fig. 1B, C), and the patient's skin lesions were completely resolved after follow-up at 10 months (Fig. 1D).

Discussion And Conclusions
This case challenges our diagnosis and treatment because ALP and plaque-type LPP have similarities. According to our literature review, pigmentation is seen in nearly half of the ALP cases, while mild epidermal atrophy is seen in LPP cases. There are also signi cant differences between the two: the plaque boundary of LPP is unclear, while that of ALP plaque is depressed in the middle, elevated around and the boundary is clear; in LPP, more melanophages or pigment cells can be present, and the degree of epidermal atrophy remains mild; ALP has signi cant epidermal process disappearance, while pigment incontinence is mild. Both epidermal atrophy and pigmentary incontinence were evident in this patient, and so it was diagnosed as ALPP, which might be an independent variant of LP or LPP with signi cant epidermal atrophy in the degenerative phase.
LPP is a rare LP variant that is more commonly seen in the sun-exposed areas such as face, neck, and arms and can also be seen in exed sites. The disease mainly affects the patients with skin types III to IV, and is more commonly seen in India, Latin America, Asia, and Africa, and is rare in Caucasians. It is caused by hepatitis C virus, endocrine diseases and autoimmune diseases, cosmetics and environmental pollution stimuli. LPP is characterized by symmetrically distributed dark brown to gray or grayish blue-gray color round and oval spots with irregular and ill-de ned borders that eventually enlarges and coalesces, asymptomatic or mildly pruritic, and have a chronic course of 6 months to 3 years. According to pigmentation ndings, it can be divided into diffuse, reticular, blotchy, and perifollicular patterns [1][2][3]. The main characteristic pathological ndings of LPP are basal cell liquefaction and lichenoid in ltration. Moreover, perivascular lymphocytic in ltrate and pigment incontinence in the super cial dermis also could be seen in some cases. Epidermal hyperkeratosis and mild epidermal atrophy are also seen in some cases [4]. The in ltration pattern of LPP changes over time, with new lesions showing zonal in ltration and old lesions are characterized by perivascular in ltration [5].
Compared with LPP, ALP is even rarer, with few reports, unclear prevalence and unclear etiology [6]. It might be an independent subtype of LP or a regressive end stage of other LP types, and is seen to coexist with other types of LP damage [7]. Relevant literature was searched in the "Chinese Journal Full-text Database" and PubMed using the term "atrophic lichen planus," and analyzed 12 cases with de nite diagnosis and complete clinical information, with regard to age, gender, lesion site, lesion manifestation Table 1 , and histopathological characteristics ( Table 2) The mechanism of LP pathogenesis is related to immune dysregulation. Cytotoxic T cells, mainly CD8+ cells, promote Th1 cells to secrete cytokines with the aid of CD4 + T cells and initiate the attack on basal keratinocytes, resulting in epidermal basal layer destruction. At the same time, more CD8+ T cells are recruited to the basal layer, resulting in persistent damage and leading to the chronic course of LP. The generation and differentiation of dendritic cells, regulatory T cells, and multifunctional T cells triggered by toll-like receptors-related innate immune responses are also involved. Upregulation of interleukin (IL)-1a, IL-6, IL-8, TNF-α, TGF-β, intercellular adhesion molecule 1 (ICAM-1), and vascular endothelial growth factor might increase microvessel density at the dermal-epidermal junction by recruiting the lymphocytes [18].
Basal cell degeneration, pigment incontinence and epidermal atrophy appear simultaneously in both LPP and ALP, and so we speculated that there is an association between the three in the pathogenesis. Epidermal atrophy mainly occurs due to retraction of epidermal processes and reduced resistance of the epidermis to shear forces, leading to reduced nutrient supply to the epidermis and might inhibit the proliferation of keratinocytes. Decreased epidermal thickness and loss of cuticular process might be related to abnormal melanocyte function, affecting the proliferation and differentiation functioning of the keratinocytes. It has been shown that senescent melanocytes induce telomere dysfunction in a paracrine manner and limit the proliferation of surrounding cells by activating mitochondrial oxidative stress. A 3D model was used to culture melanocytes with keratinocytes in vitro, in which senescent melanocytes impair the proliferation of basal keratinocytes, leading to epidermal atrophy in vitro. Studies have shown that the expression of p16, which negatively regulates cell proliferation, is signi cantly increased in melanocytes present in the epidermis of the elderly. A highly signi cant correlation between the increase of telomere-associated foci (TAF) in melanocytes and attening of the epidermal-dermal junction is observed [19].
The patient was a young woman who denied other chronic diseases and did not use cosmetics or had no long-term sun exposure before disease onset. Starting from the pathogenesis of LPP and ALP, this case might be triggered by unknown external stimuli T lymphocyte-mediated immunity, resulting in interface in ammation, keratinocyte death triggered pigment incontinence, melanin granules and increased pigmented cells in the super cial dermis, and gradual appearance of epidermal atrophy with disease progression and keratinocytes were destroyed and increased.
The treatment of LP can be divided into three categories: oral drugs (acitretin, sulfapyridine, hydroxychloroquine, griseofulvin), topical creams (vitamin D analogues, corticosteroids), and phototherapy (narrow-band ultraviolet B) [20]. The classical therapeutic aim of LP is to accelerate the resolution while relieving from the pruritic symptoms. Moderate-to-high potency topical corticosteroids (TCS) are considered as the standard rst-line treatment option for this. The mode of action of corticosteroid therapy is non-speci c and exerted immunosuppressive and immunosuppressive effects by regulating the proin ammatory mediators at genetic, cytokine, and cellular levels. However, long-term topical corticosteroids might cause local pigmentation, epidermal atrophy, etc., while calcineurin inhibitors tacrolimus and pimecrolimus do not cause epidermal atrophy and pigmentation while inhibiting the in ammatory response [21].How to weigh the advantages and disadvantages and reasonable dressing change remains the key to successful treatment in this case. This is the rst report to date with marked pigmented and atrophic lichen planus, which we call this as pigmented atrophic lichen planus, the etiology and mechanism of it are unclear, and it might be an independent subtype of LP or catagen phase of LPP.

Declarations
Ethics approval and consent to participate: Not applicable.

Consent for publication:
Written informed consent for publication was obtained from all participants.
Availability of data and materials: Not applicable.