IL-17-positive mast cell infiltration in the lesional skin of lichen planopilaris: Possible role of mast cells in inducing inflammation and dermal fibrosis in cicatricial alopecia

Lichen planopilaris (LPP) is a primary cicatricial alopecia characterized by the infiltration of lymphocytes in the upper portion of hair follicles. Inflammation around the bulge region of hair follicles induces destruction of hair follicle stem cells and tissue fibrosis, resulting in permanent hair loss. Treatment is still challenging, and the precise pathophysiology of this disorder is unknown. To clarify the pathogenesis of LPP, we performed histological and immunohistochemical analysis on specimens obtained from LPP patients. Formalin-fixed and paraffin-embedded samples were evaluated by staining with haematoxylin and eosin (HE), toluidine blue stain, immunohistochemistry and immunofluorescence. The immunohistochemical analysis demonstrated that CD4-positive T cells preferentially infiltrated into the follicular infundibulum in the LPP lesions. Toluidine blue stain detected a large number of mast cells in the inflammatory lesions of LPP. Interestingly, immunohistochemical analysis demonstrated that the mast cells harboured IL-17A- and IL-23-producing activity and expressed the IL-23 receptor. The number of IL-17A-positive mast cells was significantly higher in the LPP lesions than in normal scalp. Moreover, the IL-17 receptor was expressed exclusively in the follicular epithelial cells in the LPP lesions. These results suggested that mast cells infiltrating hair follicles might play a role in the pathogenesis of LPP via the IL-23/IL-17 axis.     

A retrospective study of lichen planus pigmentosus with focus on palmoplantar involvement

Lichen planus pigmentosus (LPP) is a rare disease characterized by persistent and asymptomatic slate‐grey pigmentation, which mostly affects patients with skin types IV–VI. The face and neck are the most commonly involved sites, followed by the trunk and extremities. LPP is believed to spare the palms, soles and nails. In this report, we describe palmoplantar involvement in 10 (4.65%, 10/215) patients with LPP, and compare its clinicodemographic features with those of classic LPP. LPP lesions on the palms and soles present as asymptomatic, well‐circumscribed, hyperpigmented, brown–black patches without any history of prior lichen planus lesions. They are mostly observed in young patients with rapidly spreading active disease, who often require systemic treatment to control the disease activity. Strikingly, palmoplantar involvement is frequently associated with other atypical LPP variants. It is important to identify palmoplantar involvement in LPP, as it has a different clinical course and associations compared with classic LPP.     

A Case of Linear Lichen Planus Pigmentosus

Lichen planus pigmentosus (LPP) is chronic pigmentary disorder that shows diffuse or reticulated hyperpigmented, dark brown macules on the sun-exposed areas such as the face, neck and other flexural folds. Clinically, it is different from classical lichen planus because LPP has a longer clinical course and it manifests with dark brown macules. In case of LPP, involvement of the scalp, nail or mucosal area is rare. The histopathological findings of the lesions show an atrophic epidermis, the presence of melanophages and a vacuolar alteration of the basal cell layer with a sparse lymphohistiocytic lichenoid infiltration. Although there have been a few reports of LPP, there have only 3 cases of linear LPP along the lines of Blaschko in the Korean dermatologic literature. Our patient had lesions on the neck and chin with a linear pattern. In this report, we describe a very rare case of LPP with a linear distribution related to Blaschko''s lines on the neck and chin areas.     

Lichen planus pemphigoides: four new cases and a review of the literature

Lichen planus pemphigoides (LPP) is a rare autoimmune blistering disease. It appears to be combination of lichen planus and bullous pemphigoid. We describe four new cases of LPP and discuss the epidemiological, clinical, pathological, and therapeutic features of this singular association through a review of the 74 published cases within the English literature. We report four cases of LPP (three women aged respectively 47, 51, and 53 years old, and a 53‐year‐old man). All patients presented with bullae on lichenoid and normal skin, predominately on the extremities. The diagnosis was confirmed by immunohistological findings. Our patients were treated with oral corticosteroids with a good response. Our review of the literature of 78 cases of LPP (65 adults and 13 children) showed that it involved adults (mean age: 54 years), with a slight female preponderance. A mean lag time between LP and the development of LPP was 8.3 months. LPP is characterized by developing blisters on lichenoid lesions and on uninvolved skin with more acral distribution of bullous lesions. Involvement of palms and soles was more frequent in children. The diagnosis is based on pathological and immunological confrontation. LPP is usually idiopathic, but some cases were reported in association with various drugs. There have also been reports of association with internal malignancy. Most cases of LPP are successfully treated with systemic corticosteroids. In most cases, the prognosis was good.     

经典和色素性扁平苔藓常见皮肤镜特征的比较

目的：比较经典扁平苔藓与色素性扁平苔藓常见皮肤镜的特征。方法：选取13例经典扁平苔藓和6例色素性扁平苔藓患者共99处皮损进行皮肤镜检查并对其特征进行比较。结果：经典扁平苔藓常见的皮肤镜特征有Wickham纹,以片状模式为主的黄棕色色素结构和点状、线状及球状等血管;色素性扁平苔藓常见的皮肤镜特征有以点状、球状模式为主的蓝灰色、黄棕色色素结构和毛囊角栓。结论：皮肤镜可用于经典扁平苔癣和色素性扁平苔藓的辅助诊断。     

Frontal fibrosing alopecia versus lichen planopilaris: a clinicopathological study

BACKGROUND: Frontal fibrosing alopecia (FFA) is an acquired scarring alopecia currently considered a clinical variant of lichen planopilaris (LPP). Our purpose was to examine the clinicopathological features of FFA. In addition, we investigated the similarities and differences between FFA and LPP. METHODS: Biopsies from the scalp lesions of eight patients with FFA and eight patients with LPP were microscopically analyzed. Two cases of FFA and four cases of LPP were studied using direct immunofluorescence. RESULTS: In spite of the completely different clinical characteristics of FFA and LPP patients, the histopathological findings for the two entities were similar. Common microscopic findings for both FFA and LPP included an inflammatory lymphocytic infiltrate involving the isthmus and infundibulum of the hair follicles, the presence of apoptotic cells in the external root sheath, and a concentric fibrosis surrounding the hair follicles that resulted in their destruction with subsequent scarring alopecia. Biopsies taken from FFA patients showed less follicular inflammation and more apoptotic cells than those from LPP patients. In some cases of LPP, the inflammatory infiltrate involved the interfollicular epidermis, a finding never present in our FFA cases. Direct immunofluorescence was negative in the two cases of FFA studied and showed deposits of immunoglobulins and/or complement in two of the four LPP cases examined. CONCLUSIONS: The characteristic findings for FFA were more prominent apoptosis and less inflammation than found in LPP, along with spared interfollicular epidermis. FFA cases showed a rather characteristic histopathological pattern, although we could not find any clear-cut histological differences between FFA and LPP.     

A case of lichen planus pemphigoides with autoantibodies to the NC16a and C‐terminal domains of BP180 and to desmoglein‐1

Lichen planus pemphigoides (LPP) is a rare autoimmune blistering disease that occurs in association with lichen planus (LP). This report describes a 59‐year‐old Japanese female patient with LPP. The patient first showed LP lesions on her hands, and subsequently developed bullae on her extremities and erosions of the oral mucosa. The patient's serum was positive for IgG autoantibodies against the BP180 NC16a domain, the BP180 C‐terminal domain and desmoglein‐1. However, a serum sampled one and a half years before the diagnosis of LPP was negative for autoantibodies against BP180 NC16a and BP180 C‐terminal domains. These findings strongly suggest that the damage to the basal cells in the LP lesions exposed a sequestered antigen or formed neoantigens, leading to the production of pathogenic autoantibodies for LPP. Most of the previous cases of LPP have produced autoantibodies to the NC16a domain of BP180. This is the first case in which autoantibodies to the C‐terminal domain of BP180 were detected. The oral mucosal symptoms in this case may have been caused by autoantibodies to the BP180 C‐terminal domain.     

Lichen planus pigmentosus–inversus

We examined seven patients with lichen planus pigmentosus (LPP) clinically and microscopically. Clinically, all patients had a striking predominance of lesions in an intertriginous location, with most of them in the axillae. Microscopically, two biopsies were of significance. Except for the regressive lichen planus, which is usual in LPP, the active inflammatory phase was also present. In these biopsies the very intensive hydropic degeneration of basal keratinocytes was combined with the absence of compensatory increased proliferation of keratinocytes, i.e. without acanthosis. The short duration of this process probably led to the quick transformation into a long noninflammatory regressive phase with incontinence of the pigment. These specific morphogenetic dynamics are possibly why most of the morphs of LPP present as brown, non-pruritic, small inflammatory macules. Because of the highly characteristic inverse location of the lesions in our patients we propose the designation LPP-inversus for this variant of the disease.     

Evidence for neurogenic inflammation in lichen planopilaris and frontal fibrosing alopecia pathogenic mechanism

Lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) are lymphocytic scarring alopecias affecting primarily the scalp. Although both diseases may share some clinical and histopathological features, in the last decade, FFA has become an “epidemic” particularly in Europe, North and South America with unique clinical manifestations compared to LPP, thus, raising the idea that this disease may have a different pathogenesis. Symptoms such as scalp burning, pruritus or pain are usually present in both diseases, suggesting a possible role for nerves and neuropeptides in the pathogenesis of both diseases. Based on some previous studies, neuropeptides, such as substance P (SP) and calcitonin gene-related peptide (CGRP), have been associated with lipid metabolism and many chronic inflammatory disorders. In this study, we asked if these neuropeptides are associated with LPP and FFA scalp lesions. Alteration in the expression of SP and CGRP in affected and unaffected scalp skin from patients with both diseases was found with examination of sections using immunohistochemical techniques and confocal microscopy. We then quantitatively assessed and compared SP and CGRP expression from control, LPP and FFA scalp biopsies. Although LPP and FFA share similar histopathologic findings, opposite results were found in affected and unaffected scalp in the ELISA tests, suggesting that these diseases may have different pathogenic mechanisms. We also found presence of histopathological inflammation irrespective of evident clinical lesions, which raises the possibility that both diseases may be more generalized processes affecting the scalp.     

Basement membrane changes in lichen planopilaris

Background  Lichen planopilaris (LPP) is an inflammatory disease that affects the scalp and tends to produce cicatricial alopecia. The inflammatory process frequently results in the disruption of the basal cell of the external root sheath of the hair follicle.
Objectives  To investigate the alterations in the basement membrane zone (BMZ) in LPP by immunohistochemistry.
Methods  Skin biopsies from six patients with LPP plus six normal controls were studied by immunohistochemistry with antibodies to the following BMZ components: cytokeratin 5, cytokeratin 14, BP230 (bullous pemphigoid), BP180, plectin, laminin 5, collagen IV and collagen VII.
Results  The localization and staining of the hemidesmosome, laminin and collagen components were strikingly different in the inflamed follicular epithelium when compared to the uninvolved follicles or interfollicular epithelium in active LPP lesions. The hemidesmosome-associated complexes were weakly expressed and discontinuous in involved hair follicles. The expression of laminin-5, type IV collagen and type VII collagen was disrupted and not linear along the BMZ with finger-like projections of the staining protruding into the dermis. The expression of the intermediate filaments was normal.
Conclusion  These alterations in the BMZ in LPP may explain the abnormal healing at follicular level which leads to irreversible hair loss and scarring in this condition.     

Lichen planopilaris

Background

Lichen planopilaris (LPP) is an inflammatory condition of unknown etiology that affects pilosebaceous units, mainly of the scalp, and results in scaring alopecia.

Objective

A 51-year-old male presented with a pruritic eruption on the cheek consisting of atrophic macules and erythematous folliculocentric papules.

Results

Biopsy revealed a perifollicular lymphocytic infiltrate and vacuolar degeneration of the dermoepidermal junction consistent with LPP. Many treatment modalities have been utilized, with varying degrees of success. Our patient responded poorly to topical steroids. After nine months of topical tacrolimus therapy, his lesions resolved entirely.

Conclusion

The treatment of our patient demonstrates tacrolimus as a novel topical therapeutic option for patients with LPP.     

Lichen planopilaris: report of 30 cases and review of the literature

BACKGROUND: Lichen planopilaris (LPP) affects primarily the scalp, resulting in scaling, atrophy, and alopecia with scarring. The purpose of our study was to obtain original data on LPP and to evaluate the efficacy of topical therapy in comparison with systemic therapies. METHODS: We examined 30 patients affected by LPP between 1996 and 2001, performing clinical, laboratory, histopathologic and direct immunofluorescence examinations. Twenty-one of the patients (70%) were women and nine (30%) were men. The average age at presentation was 51.5 years. The average duration of the disease was 13 months at the time of the diagnosis. All patients received topical steroids for a total of 12 weeks. RESULTS: Resolution of the inflammatory process and blocking of the cicatricial progression were observed in 66% of cases, a mild reduction of fibrosis and cicatrization in 20% of patients, and no response in 13%. CONCLUSIONS: We concluded that topical therapy may be a valid alternative to systemic therapies, especially in patients with lesions in the early phase.     

“Normal-appearing” scalp areas are also affected in lichen planopilaris and frontal fibrosing alopecia: An observational histopathologic study of 40 patients

Lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) are lymphocyte-mediated scarring alopecias which clinically affect primarily the anterior and mid-scalp. However, unaffected scalp areas have not yet been investigated in a systemic manner. In this study, we assessed histopathologic changes in affected and unaffected scalp in both diseases and healthy control subjects and compared these findings with clinical signs and scalp symptoms. We have demonstrated that “normal-appearing” scalp that is devoid of clinical lesions of LPP and FFA showed lymphocytic perifollicular inflammation around the isthmus/infundibulum areas in 65% of biopsy specimens, perifollicular fibrosis in 15% and mucin deposits in 7.5% of the cases. None of these findings were found in control samples. No direct correlation was found between the degree of histopathological inflammation, scalp symptoms and clinical lesions in the corresponding affected scalp areas. This preliminary study suggests that both diseases may be more generalized processes which affect the scalp and therefore need systemic or total scalp therapy.     

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.     

Lichen planus pemphigoides associated with Chinese herbs

We report a 62-year-old Chinese woman with a 2-year history of lichen planus presenting with extensive violaceous maculopapules and plaques 1 week after taking an oral preparation of Chinese herbs. The patient developed vesiculobullous skin lesions 7 weeks later. Histopathological examination showed subepidermal blisters and adjacent bandlike lymphocytic infiltration. Direct immunofluorescence revealed linear deposits of IgG and C3 along the basement membrane zone. Indirect immunofluorescence showed IgG antibody deposition along the epidermal side of salt-split human skin. Circulating anti-bullous pemphigoid 180 antibodies were detected by ELISA. Lichen planus pemphigoides (LPP) was diagnosed. To our knowledge, this is the first report of LPP associated with oral Chinese herbs.     

Large plaque parapsoriasis: clinical and genotypic correlations

Twelve patients with large plaque parapsoriasis (LPP) were investigated for the presence of predominant T-cell clones, analyzing the T-cell receptor (TCR) gamma-chain gene. The diagnostic and prognostic significance of TCR gene rearrangement status was assessed by a correlation with the long-term clinical follow-up. Six out of 12 patients showed a clonal T-cell population. Clinically, among the patients with clonal disease one developed clearcut mycosis fungoides (MF) after a follow-up of 8 years, in the other 5 patients no such diagnosis could be made after follow-up of 2-21 years (median: 9 years). In patients with polyclonal infiltrates the lesions remained virtually unchanged. These findings indicate that in LPP TCR gene rearrangement status has no prognostic significance and does not allow distinction of LPP and early MF. Both conditions show a clonal T-cell infiltrate with similar frequency, are very similar in clinical and histologic presentation and according to recent studies share the same low risk to develop overt MF. Therefore both terms refer to the identical clinical situation. This should be designated as early MF and efforts should concentrate on identifying those patients that are at risk to develop aggressive disease.     

PUVA-induced lichen planus pemphigoides

A 72-year-old woman had suffered from parapsoriasis en plaque (large plaque type) controlled by topically applied psoralen ultraviolet A (PUVA) therapy. The parapsoriasis lesions gradually disappeared, but numerous tiny red papules with pruritus appeared over the forearms and lower legs 120 days after starting PUVA therapy. These papules developed to form violaceous plaques. Histological findings demonstrated the characteristics of lichen planus. Two months later, tense bullae developed on the plaques and on uninvolved skin of the limbs. These were subepidermal, with linear deposits of IgG and C3 along the basement membrane zone (BMZ) in immunofluorescence of peribullous skin, and immunodeposits of type IV collagen along the floor of the bullae. We therefore, diagnosed lichen planus pemphigoides (LPP). Using systemic and topical steroid therapy, the lesions rapidly resolved and there has been no recurrence. This case suggests that the combination of basal cell injuries caused by chronic inflammation and PUVA therapy could expose BMZ components to autoreactive lymphocytes and induce LPP.     

Genotypic analysis of cutaneous T-cell lymphoma: a comparative study of Southern blot analysis with polymerase chain reaction amplification of the T-cell receptor-γ gene

Summary The diagnosis of early cutaneous T-cell lymphoma (CTCL) is a difficult point in dermatology. Recently, Southern blot analysis (SBA) and polymerase chain reaction (PCR) have been used to detect clonality in initial lesions in which clinical and histological findings are unspecific. Forty-one, samples from 25 patients with CTCL were investigated for the presence of T-cell receptor-γ gene rearrangement using a nested PCR technique and analysed by polyacrylamide gel electrophoresis (PAGE). Conventional SBA was also performed on 28 samples from 20 of these patients. In addition, 20 samples corresponding to patients with large plaque parapsoriasis (LPP), cutaneous B-cell lymphoma (CBCL) and eczema were analysed by PCR in the same way as were the CTCL specimens. Most of the CTCL specimens (81%) showed clonality on PCR analysis. Among patients with mycosis fungoides, 71% of initial patch lesions and 100% of plaques and tumours showed clonal disease. Clonality could be detected in three of four histologically negative post-treatment lesions. Clonal rearrangement was detected in one of three patients with LPP and in three of 10 patients with CBCL. None of the samples corresponding to patients with eczema showed positive results. SBA was significantly less sensitive than PCR in detecting clonality in CTCL patients (42% among early disease and 60% among advanced cases). The results indicate that this PCR/PAGE technique is a reliable and useful method for the detection of clonality in early skin lesions of CTCL patients and probably in the identification of silent extracutaneous involvement.     

Linear lichen planopilaris of the trunk: first report of a case

BACKGROUND: Lichen planopilaris (LPP) is believed to be a follicular variant of lichen planus that affects pilosebaceous units, mainly of the scalp. An extremely rare variant of LPP is a linear form, which follows the lines of Blaschko. Of the five previously documented cases of linear LPP, all were limited to the face. OBJECTIVE: We report the case of a 34-year-old male who presented with a nonpruritic eruption on the trunk consisting of erythematous, keratotic, folliculocentric papules following Blaschko's lines. RESULTS: Biopsy revealed lichenoid and interface dermatitis involving the basilar epidermis and hair follicles, as well as apoptotic keratinocytes, consistent with LPP. CONCLUSION: This represents the first documented case of LPP, following the Blaschko's lines, in a nonfacial distribution.     

Lichen planus pemphigoides: its relationship to bullous pemphigoid

Clinical and immunopathological studies of three patients with lichen planus pemphigoides (LPP) were carried out to investigate the relationship between LPP and bullous pemphigoid (BP) and to determine whether the antigen in LPP is the classical BP antigen. LPP is usually considered to be the coexistence of lichen planus with BP. The bullae in LPP were subepidermal and indistinguishable from BP. Indirect immunofluorescence demonstrated antibody binding to the epidermal surface of 1 M NaCl-split skin and mucosae, as in BP. The tissue distribution of the LPP antigen mirrored the distribution of BP in stratified squamous epithelia but was absent from transitional epithelia (pig bladder). Immunoelectron microscopy, both direct (two cases) and indirect (one case), showed binding to the lamina lucida as with BP antigen. Western blotting of epidermal extracts using the patients' sera showed that instead of reacting with the classical bullous pemphigoid antigen (220 kDa in our series), the antisera reacted with a unique band of 200 kDa in addition to the band of 180 kDa found as a minor antigen in bullous pemphigoid, but more commonly in pemphigoid gestationis. The relationship between these antigens awaits molecular characterization. These findings suggest that the target antigen in LPP may be unique.