Classic LP is an idiopathic inflammatory dermatosis characterized by the onset of small, dullred to violaceous, flat-topped, usually pruritic papules (Fig. 1A). In typical cases, the single lesions show a tiny network of whitish striae on the surface (Wickham striae), which are easily observed by dermoscopic examination (Fig. 1B, C). In darkly pigmented skin the lesions appear brown–black in color rather than red-violaceous, and Wickham striae are less evident. Confluence of papules may give rise to flat, irregular plaques, and generalized confluence may result in suberythroderma in exceptional cases (Fig. 1J) [11–13]. In other cases, the lesions may be very tiny. The typical locations are the flexural site of the wrists and forearms, the dorsal hands, the shins, and the presacral area, but lesions may arise at any skin site and may be generalized. In some cases, confluence of lesions may result in large, infiltrated plaques (Fig. 2B–D, J). Palmoplantar involvement may present in the form of a partial or diffuse, usually hyperkeratotic involvement of volar skin (Fig. 2E–H).

The histopathological features of classic LP are characterized by a dense, band-like lymphoid infiltrate obscuring the dermo-epidermal junction (Fig. 6A, B). The epidermis shows variable acanthosis with wedge-shaped hypergranulosis and mild, compact orthohyperkeratosis, these last 2 findings being the histopathologic counterpart of the Wickham striae. Several apoptotic keratinocytes are present in the basal layer of the epidermis, and homogeneous eosinophilic globules (colloid bodies or Civatte bodies) are found in the subepidermal papillary dermis, representing clumps of degenerative material from the overlying keratinocytes [14]. The Civatte bodies are PAS-positive and diastase-resistant, and stain for IgM with direct immunofluorescence; in spite of their name, they were not described by Civatte but by Sabouraud in 1912 [15]. In rare cases, the infiltrate may be confined to the site of acrosyringia [16], and in other cases a prominent involvement of the eccrine glands (syringotropism) may mimic the histopathological features of adnexotropic mycosis fungoides (Fig. 6K) [17]. The dermal infiltrate is composed mainly of lymphocytes admixed with some histiocytes. Pigment incontinence may be present in the form of melanophages, but this is more common in resolving lesions, in individuals with dark skin, or in Middle-Eastern and Asian patients. Plasma cells are usually absent; even in cases arising at sites where plasma cells are prevalent, such as the mucosae, genital regions, face, posterior neck, and intertriginous areas, they are usually present only in small numbers. Although the presence of eosinophils is considered as a typical finding of drug-induced LP, they can be found, albeit uncommonly, in classic LP as well. In cases with pronounced damage of the dermoepidermal junction, small subepidermal clefts may form (so-called Caspary–Joseph or Max Joseph spaces) (Fig. 6C) [18, 19]. The histopathological evolution of LP is characterized by progressive increase in the density of the infiltrate, whereas in resolving lesions the infiltrate is less dense, and sometimes may show a minimal extension into the reticular dermis [20].

Figure 1. 

Clinical variations of lichen planus: A) “classic” lichen planus on the wrist; B) single large, flat papule of lichen planus with whitish striae (Wickham striae); C) better appreciated with dermoscopic examination; D) annular lichen planus in intertriginous area; E) inverse lichen planus in the groin; F) atrophic, pigmented lichen planus; G) linear lichen planus along the Blaschko lines on the thigh; H) exanthematic lichen planus; I) verrucous lichen planus with a linear distribution of confluent lesions; J) erythrodermic lichen planus with confluent, tiny papules covering most of the trunk; K) actinic lichen planus on the face of a Middle-East patient; L) lichen planus with Köbner phenomenon along a scratching site.

Figure 2. 

Unusual clinical presentations of lichen planus: A) waist-band lichen planus; B) confluent lichen planus on the left buttock and proximal thigh; C) large, verrucous plaques of lichen planus on the foot; note also small, typical papule near the site of biopsy (marked with ink) (inset); D) confluent lichen planus on the dorsum of the hands; E) palmar lichen planus with involvement of the entire palms and volar aspect of the fingers and with focal keratoses; F) palmar lichen planus with large, confluent, partly hyperkeratotic lesions; note more typical lesions on the wrists; G) plantar involvement with large, partly confluent papular lesions; H) plantar involvement with massive hyperkeratosis; I) perianal lichen planus with confluent, red-livid lesions; J) confluent lesions on the left arm and elbow giving rise to an infiltrated, hyperpigmented plaque; K) inverse lichen planus with large, flat, hyperpigmented lesions; L) submammary lesion of inverse lichen planus with linear distribution.

Exanthematic LP is characterized clinically by the rapid onset of generalized lesions with conventional morphologic features, but often of smaller dimensions (Fig. 1H); distinction from drug-induced LP may be both clinically and histopathologically impossible.

Histopathologically lesions of exanthematic LP resemble those of classic LP but both the hyperplasia of the epidermis and the hypergranulosis are less marked. The presence of numerous eosinophils should prompt to consider drug-induced LP.

Like inverse psoriasis, inverse LP is characterized by the presence of typical lesions at intertriginous sites such as the axillae, groins, and inframammary folds (Fig. 1E). Perianal lesions may present with a distribution similar to that seen in psoriasis and lichen simplex chronicus at the same site, but the lichenoid aspect is usually clinically obvious (Fig. 2I). Concomitant lesions at other sites may be present. Clinically, the lesions are usually flatter than those seen in classic LP and may be hyperpigmented, thus presenting overlapping features with LP pigmentosus and atrophic LP. In some cases large, hyperpigmented macules may be observed (Fig. 2K).

Histopathologically, inverse LP is similar to atrophic LP, showing a flattened epidermis, a less heavy infiltrate than classic LP, and often numerous melanophages.

Hypertrophic LP is characterized clinically by very itchy, verrucous lesions located mostly on the distal part of the lower extremities, often on the background of chronic stasis (Figs 1I, 2C) [21]. The lesions are usually larger than common papules of LP and show a keratotic surface. A linear distribution may be visible due to vigorous scratching. The clinical appearance may be similar to squamous cell carcinoma (SCC) and keratoacanthoma (KA) (Fig. 7J, K) [22], and the development of SCC in chronic lesions of verrucous LP can be observed. The development of KA in patients with hypertrophic LP has been described as well [23–25]; however, at least in some cases, a keratoacanthomatous architecture of the epidermis may represent an evolutionary stage of hypertrophic LP rather than a genuine KA.

Similar lesions have also been described associated with drugs [26].

Histopathologically, hypertrophic LP is characterized by variable, irregular, epidermal hyperplasia with hyperkeratosis (Fig. 6G, H). The inflammatory infiltrate is variable but usually less dense than in classic LP. Eosinophils may be observed within the infiltrate [27]. The epidermal hyperplasia may be pseudoepi­theliomatous, but clear-cut atypia is usually lacking, allowing distinction from SCC in most cases. In some cases, shave biopsy may show only an irregular, partly crateriform architecture of the epidermis, thus being virtually indistinguishable from the superficial part of a keratoacanthoma (Fig. 7l). The presence of perforating elastic fibers has been reported as a finding pointing to a diagnosis of keratoacanthoma [28]. Hypertrophic LP may be very difficult to distinguish histopathologically from hypertrophic lupus erythematosus (LE), as both diseases present with an interface/lichenoid inflammatory reaction and apoptotic keratinocytes. Clusters of CD123-positive plasmacytoid dendritic cells (PDCs) are a typical feature of verrucous LE [29]; in other variants of LP, the number of CD123+ PDCs was higher in LE than in LP [30], representing a potential clue in the differential diagnosis.

Atrophic LP is characterized clinically by flat papules, which are often confluent to form patches and thin plaques and are often located in the intertriginous areas (Fig. 1F). The lesions are frequently hyperpigmented (atrophic/pigmented LP). An annular configuration may be observed [31]. Although it is possible that atrophic LP represents a resolving stage of classic LP, the predilection sites are different and the lesions are usually hyperpigmented, suggesting that this variant may present with thin lesions from the outset.

Rarely, atrophic LP may present clinically with the picture of parakeratosis variegata [32].

Histopathologically, atrophic LP is characterized by a flat, thin epidermis with variable numbers of apoptotic keratinocytes (Fig. 6D, E). There is no hypergranulosis. The infiltrate is less dense than in classic LP and the melanophages are usually numerous.

We have observed a few cases of atrophic LP in which the density of the infiltrate was a reason for concern for a possible diagnosis of mycosis fungoides (Fig. 6F). The clinical presentation is typical of atrophic/pigmented LP, mostly in intertriginous areas, but in contrast to the sparse infiltrate usually found in this variant, very dense, band-like infiltrates with epidermotropic lymphocytes were observed. A predominant population of CD4+ T lymphocytes was found, but many CD8+ T cells were present as well, a pattern that is observed infrequently in mycosis fungoides.

Annular LP is characterized clinically by small annular lesions with a raised border and flat central portion. The raised border is composed of confluent papules with the typical morphology of LP, whereas the central part is characterized by normal or hyperpigmented skin (Figs 1D, 3L) [33]. Annular LP may be the sole manifestation of the disease or associated with more conventional lesions. Lesions are usually less pruritic than those of classic LP. Annular LP is often encountered in the genital area, but may arise at other body sites as well. Scales are minimal or absent; if present, the differential diagnosis is mainly with tinea corporis or, less commonly, porokeratosis; if absent, granuloma annulare represents the main differential diagnosis. Annular LP should also be distinguished from a rare disorder described by Annessi et al., namely, annular lichenoid dermatitis of youth (ALDY) [34]. The lesions in ALDY are larger and clinically resemble morphea or mycosis fungoides, and histopathologically are characterized by a typical finding consisting of „squaring“ of the rete ridges, that is, rete ridges with dense lymphoid infiltrates and apoptosis of the entire distal part resulting in a flattened aspect.

As already mentioned, annular lesions may also be observed in atrophic/pigmented LP.

Histopathologically, annular LP presents with features identical to those of classic LP.

Linear LP should be distinguished from short linear lesions arising as a Köbner phenomenon, for example after scratching or trauma, and is characterized by conventional papules of LP arranged along the lines of Blaschko (Fig. 1G). Besides Köbnerization along scratching lines, a linear arrangement of relatively small lesions may also be observed in cases of LP arising at the site of previous herpes zoster on the trunk or extremities, or in cases of various LP subtypes (particularly inverse and atrophic) (Fig. 2L), but true linear LP does not show a dermatomal distribution. The clinical morphology of single lesions in linear LP is similar to that in classic LP, and only the distribution allows one to recognize this variant. Linear LP should be distinguished from other linear dermatoses such as lichen striatus and linear psoriasis among others (Table 2). Genetic analyses by whole exome sequencing performed on one case from Thailand did not reveal clear cut pathogenetic alterations [35].

The histopathological features of linear LP are identical to those seen in classic LP with common pigment incontinence [36].

Figure 3. 

Clinical variations of lichen planus at oral and genital sites: A) discrete whitish network in the buccal mucosa; B) prominent, partly confluent reticulated, whitish network in the buccal mucosa; C) erosive cheilitis of the lower lip; note also hyperpigmented, flat lichenoid papules on the upper lip; D) partly erosive, mild involvement of the tongue; E) prominent whitish lesions, partly with reticular aspect, on the tongue; F) erosive glossitis; G) confluent papular lesions on the vagina and perigenital skin; H) partly confluent papules, some with an annular configuration, on the penis; I) dermoscopic image of (H); J) whitish, elevated network on the penis; K) papular lesions on the glans, some with a reticular pattern; L) annular lesions on the penis.

Figure 4. 

Clinical variations of lichen planus in dark skin and in patients from Asia and Middle-East: A) exanthematic lichen planus in a Middle-East patient; B) detail of the lesion with darker lesions than in Whites; C) papules of lichen planus on the breast of an African patient; D) detail of partly hyperpigmented papules; E) hyperpigmented papules on the thigh of an African woman; F) hyperpigmented, small plaque of lichen planus in an Asiatic patient.

Figure 5. 

Clinicopathological variations of lichen planopilaris and of lichen planus of the nails: A) lichen planopilaris of the scalp with erythematous lesions and focal scarring alopecia; B) detail of the lesion; C) histopathologic example of early lichen planopilaris of the scalp with dense perifollicular inflammation at the level of the infundibulum and isthmus; D) lichen planopilaris of the scalp with perifollicular scales and scarring alopecia; E) detail of the lesions; F) histopathologic example of late lichen planopilaris of the scalp with prominent dermal fibrosis and only sparse inflammation; G) lichen planopilaris of the back with papules partly centered around the hair follicles; H) detail of the lesions; I) histopathological features showing lichenoid inflammatory infiltrates involving the infundibular and isthmic areas of the hair follicle; J) lichen planus of the nail with early proximal nail involvement and still normal distal nail; K) lichen planus of the nail with several longitudinal streaks and a distal depression of the nail; L) lichen planus of the nail with longitudinal ridging.

Ulcerative lesions are observed mostly in the setting of mucosal LP, particularly oral LP, and can also be observed on the palms and soles in patients with classic LP with palmo-plantar involvement. Ulcerative LP should not be confused with perforating LP, characterized by the elimination of numerous hyaline bodies through the epidermis rather than by a true ulceration [37].

Histopathology shows ulceration and a typical lichenoid infiltrate at the margin of the ulcer. Specimens showing ulcerations without remnants of epithelium cannot be distinguished from ulcerations in other settings (e.g., in the mouth aphthae), thus biopsies should be taken from the margin of the ulcer.

Actinic LP is observed mainly in young adults or children from Middle-Eastern countries, and is characterized clinically by reddish-brown thin patches and plaques, often with an annular configuration, located on chronically sun-exposed areas such as the face and neck, the dorsal hands, and the lower arms (Fig. 1K) [38]. Lesions restricted to the face may resemble melasma in some cases. Actinic LP has also been referred to as LP actinicus, LP subtropicus, LP tropicus, and lichenoid melanodermatitis.

The histopathological features of actinic LP are similar to those of pigmented lesions in classic lichen planus; the infiltrate usually is less dense than that seen in classic LP, the epidermis is less acanthotic and may show parakeratosis, and numerous melanophages are present in the papillary dermis.

LP pigmentosus is not synonymous with atrophic/pigmented LP, and is characterized by pigmented macular lesions that arise on chronic sun-exposed skin of the face and neck, often evolving into diffuse or reticulated hyperpigmentation [39, 40]. This condition is observed mainly in patients from India [41] as well as from other countries in South Asia, Latin America, and the Middle-East. LP pigmentosus can be observed in intertriginous areas (inverse LP pigmentosus). Only a minority of patients with LP pigmentosus have other lesions of classic LP, or a history of it [39]. The features of LP pigmentosus and erythema dyschromicum perstans overlap, but the distribution of the lesions in erythema dyschromicum perstans is different (see below).

Histopathologically, the epidermis is flattened and the infiltrate is less dense than that seen in classic LP. Apoptotic keratinocytes are present, and there are numerous melanophages in the papillary dermis.

There have been many controversies concerning the exact classification of cases labeled as ashy dermatosis or erythema dyschromicum perstans, and a relationship to LP has often been suggested. In addition, ashy dermatosis and erythema dyschromicum perstans are commonly used synonymously, although a consensus conference proposed the presence of an erythematous border in erythema dyschromicum perstans as a feature distinguishing it from ashy dermatosis [39]. In our opinion, ashy dermatosis and erythema dyschromicum perstans represent the same condition, although the relationship to LP is unclear. Erythema dyschromicum perstans should be distinguished from post-inflammatory hyperpigmentation of a different etiology.

Clinically patients present with hyperpigmented macules located mostly on the trunk and extremities; concomitant lesions of LP may coexist in a minority of patients.

Histopathological examination of early lesions shows a mild lichenoid infiltrate with occasional apoptotic keratinocytes in the overlying epidermis. The infiltrate may extend into the reticular dermis with a perivascular pattern. A prominent feature is the presence of numerous melanophages in the papillary dermis. In late lesions, the lichenoid infiltrate is no longer present, and the presence of many melanophages is the only feature, sometimes together with occasional apoptotic keratinocytes (Fig. 6J). In general, the histopathological aspects are similar to those of LP pigmentosus, and it has been suggested that the two conditions cannot be reliably distinguished on a tissue biopsy [42].

Figure 6. 

Histopathological variations of lichen planus: A) classic lichen planus; lichenoid inflammatory infiltrate with (B) involvement of the dermo-epidermal junction, apoptotic keratinocytes, hypergranulosis and hyperkeratosis; C) typical Caspary–Joseph space; D) atrophic lichen planus characterized by atrophic epidermis with (E) apoptotic keratinocytes and pigment incontinence; F) pseudolymphomatous lichen planus with very dense inflammatory infiltrate; G) hypertrophic lichen planus characterized by epidermal hyperplasia with (H) lichenoid inflammatory infiltrates and some apoptotic keratinocytes; I) lichenoid drug eruption; note apoptotic keratinocytes in suprabasal layers; J) erythema dyschromicum perstans with only sparse inflammatory infiltrate and pigment incontinence; K) lichen planus of the trunk with involvement of one hair follicle and of the eccrine glands; L) oral lichen planus: the mucosa shows a pathologic hypergranulosis and compact hyperkeratosis corresponding to the whitish striae seen clinically.

Bullous LP is not synonymous with LP pemphigoides (see below) [43–45]. In bullous LP, the detachment of the epidermis from the dermis is due to the presence of dense inflammation with pronounced, confluent Caspari-Joseph spaces leading to the formation of broad dermoepidermal clefts (Fig. 7I). In contrast to LP pemphigoides, the formation of vesicles/bullae is not due to an immunological mechanism, but rather due to the increased apoptosis of the basal layer of the epidermis. Thus, direct immunofluorescence studies in bullous LP do not show any deposits along the basement membrane.

Clinically, vesiculation is visible on long-standing lesions, and particularly on larger ones. The vesicles/bullae are usually restricted to the site of some LP lesions and do not extend to the contiguous skin. Development of bullae can also be observed in nail LP.

More commonly, lesions that are „bullous“ histopathologically, i.e., characterized by large clefts separating the epidermis from the dermis, are not bullous clinically (Fig. 7G, H). In this context, bullous LP is a rare clinical, but not a rare histopathological finding. Besides the presence of subepidermal clefts, other histopathological features of bullous LP are similar to those of classic LP (Fig. 7I). In contrast to LP pemphigoides, eosinophils are absent in bullous LP.

Figure 7. 

Clinicopathological variations of lichen planus: A) lichen planus with the clinical presentation of parakeratosis variegata; B) detail of the lesions; C) histology shows an atrophic epidermis with a sparse, lichenoid inflammation; D) lichen planus evolving with milia on the ankle; E) detail of the lesions; F) histology shows a lichenoid infiltrate with two superficial milia; G) large, flat plaques of lichen planus on the dorsal aspect of both feet; H) detail of the lesions; I) histology shows a subepidermal cleft; a vesiculo-bullous pattern is often not visible in cases of lichen planus that are “bullous” histopathologically; J) keratoacanthomatous lichen planus; K) note flat papules of the disease near the keratoacanthoma-like one; L) histopathological features show a keratoacanthomatous architecture in one part of the biopsy, and lichenoid infiltrates in deeper levels.

LP pemphigoides represents the association of classic LP with classic bullous pemphigoid (BP), and patients have circulating autoantibodies directed against the 180 kDa BP antigen [44–46]. Direct immunofluorescence usually shows linear deposition of IgG and C3 at the basement membrane zone. Split-skin immunofluorescence shows binding to the roof of the split. However, the epitope of the BP180 antigen recognized by the autoantibodies of patients with LP pemphigoides (MCW-4) is different from those implicated in conventional bullous pemphigoid [47]. Thus, it has been suggested that, rather than a simple combination of LP and BP, LP pemphigoides may represent an entity on its own [48]. Patients are often younger than in those with classic BP, and the disease has been reported in children [49]. Lesions of BP may arise within, near, or at sites distant from those of LP [50]. Either disease may be the first to be diagnosed or they may rarely arise concomitantly, but the diagnosis of LP precedes that of BP in most cases (time varying from a few days to several years) [49].

The clinical features are characterized by a combination of aspects typical of LP and of BP, with overlapping features of the two disorders visible only in some areas (Fig. 8A, B).

Histopathologically, biopsies will show features of either LP or BP alone in many cases, and a subepidermal bulla is visible only rarely near an area with lichenoid infiltrates (Fig. 8C).

Eosinophils and neutrophils are commonly seen.

Figure 8. 

Lichen planus associated with other disorders: A) lichen planus pemphigoides characterized by (B) multiple bullae and confluent papular lesions of lichen planus; C) histology shows a subepidermal bulla and a lichenoid infiltrate at the site of the bulla; D) lichen planus / lupus erythematosus overlap syndrome characterized by (E) confluent lesions giving rise to irregular plaques; F) histology shows a superficial lichenoid infiltrate, typical of lichen planus, and also the presence of dense perivascular and periadnexal infiltrate in the reticular dermis, typical of lupus erythematosus.

LE/LP overlap syndrome is probably a potpourri of cases including those showing genuine features of both diseases in one and the same patient, and others representing one or the other of the two diseases with unusual cli­nicopathological features, leading to a misinterpretation of the findings. The existence of overlapping cases between the two diseases was already postulated in 1970 by Copeman and coworkers [51]. Recently, based on a review of published cases the distinction between „classic“ and „possible“ LE/LP overlap syndrome has been proposed [52]. In this paper, the „classic“ LE/LP overlap syndrome was defined as cases that show mixed clinical features of LE and LP, histologic features of LP (with or without features of LE), and any positive serologic markers of LE (positive ANA with titers ≥1:80 on HEp-2 cells, ENA antibodies, anti-double-stranded DNA antibodies, or antiphospholipid antibodies); the „possible“ LE/LP overlap syndrome was defined as cases with the same clinical and histologic features but with negative ANA (titers <1:80) and negative serologic tests.

Most patients with LE/LP overlap syndrome have the chronic discoid variant of LE (CDLE). Direct immunofluorescence studies may be characterized by mixed features, showing both cytoid bodies that stain for IgM and fibrin as in LP, and linear granular deposition of immunoglobulin and complement along the dermo–epidermal junction as in LE [53].

Clinically patients present with confluent lesions (Fig. 8D, E) that commonly involve the palms and soles. Nail dystrophy, mucosal membrane involvement, and scarring alopecia have also been reported. Histopathologically features of LP and of LE are present in the same lesion or in different lesions (Fig. 8F). In this context, it should be reminded that Civatte bodies may be numerous in cutaneous LE, and the inflammatory infiltrate may be superficial, thus mimicking LP.

In the context of the discussion about LE/LP overlap syndrome it should be mentioned that LP may be associated with dermatomyositis as well, albeit rarely, although this may be a chance association [54, 55].

Lichen planopilaris (LPP) is characterized by the prominent involvement of the hair follicles particularly on the scalp, and represents one of the most common causes of scarring alopecia. Frontal fibrosing alopecia (FFA) most likely represents a variant of LPP. Another rare variant is the Graham-Little (or Graham-Little–Piccardi–Lassueur) syndrome (GLPLS), characterized by the triad (not necessarily simultaneous) of scarring alopecia of the scalp, non-cicatricial loss of pubic and axillary hairs and disseminated spinous or acuminated follicular papules; and typical cutaneous or mucosal LP. A classification of LPP including these three subtypes (classic LPP, FFA and GLPLS) has been proposed by the North American Hair Research Society [56], and some authors proposed also adding fibrosing alopecia in a pattern distribution to this group [57].

It has been suggested that the damage of stem cells at the level of the bulge in LPP may explain why the hairs lose their potential for regrowth, resulting in scarring alopecia [58]. In fact, in alopecia areata, an inflammatory form of non-scarring alopecia, the infiltrate is located in the bulb region, sparing the stem cells of the bulge (the bulb represents the deepest part of the hair follicle, whereas the bulge is located at the lower end of the isthmus).

Clinically, active lesions of LPP are characterized by keratotic plugs surrounded by a livid rim (Fig. 5A, B); in advanced lesions, complete loss of hairs with scarring is usually observed, a feature indistinguishable from that observed in late stages of other types of scarring alopecia (Fig. 5D, E). Dermoscopic features („trichoscopy“) include follicular hyperkeratosis, perifollicular erythema and perifollicular tubular casts (perifollicular scales) in early, active lesions, as well as white dots, hair tufting (i.e., several hair shafts emerging from a single hair orifice), perifollicular blue-gray dots creating a targetoid pattern, and finally the absence of follicular openings in late stages. Lesions of classic LP coexist with those of LPP in approximately 50% of patients.

Histopathologically, LPP shows prominent, lichenoid follicular infiltrates confined mostly to the infundibulum and the isthmus of the hair follicles with variable perifollicular fibrosis (Fig. 5C) [59, 60]. Unlike alopecia in discoid lupus erythematosus, the infiltrate extends to the interfollicular epidermis only in a minority of cases (and not in lesions arising on the trunk and extremities), and usually there are no perivascular infiltrates in the mid and deep dermis [61]. In advanced stages scarring alopecia develops, with hair follicles replaced by linear tracts of fibrosis, which may completely disappear in very late stages (Fig. 5F).

In a minority (~10%) of patients with LP the nails show pathological signs due to damage to the epithelium of the matrix, including longitudinal ridging, fissuring, and lateral thinning (Fig. 5J–L) [62]. Several nails are usually affected, and some patients, particularly children, present with a 20-nail dystrophy as a manifestation of LP. Rarely, the nails are the only affected site (isolated nail LP) [63]. Like lichen planopilaris, prolonged lichenoid inflammation of the matrix may lead to scarring between the proximal nail fold and the nail matrix (pterygium) in late stages.

Histopathological features of nail LP are similar to those observed in classic LP. Plasma cells may be observed [64].

Oral LP is observed in approximately 75% of patients with LP, and may be the only manifestation of the disease. In patients with exclusive oral involvement, the subsequent development of cutaneous lesions of LP is uncommon, and observed in only a minority of cases. Patients with oral LP may also have involvement of the esophagus (esophageal LP), and female patients of the genital mucosa. Screening for chronic liver disease, particularly due to hepatitis C virus (HVC), should be performed in patients with oral LP, as the association has been demonstrated in several studies [65, 66]. SCC may arise on the background of long-standing oral LP.

Clinically, several presentations can be observed. The most common is characterized by the presence of slightly elevated, whitish lesions with a reticular pattern located bilaterally on the buccal mucosa (Fig. 3A, B). The tongue may be involved in the form of variably erosive glossitis (Fig. 3D–F). The gingivae are often involved, usually in the form of a desquamative gingivitis, and may be the only affected site at the oral mucosa. The presence of concomitant gingival and vulvovaginal involvement without other oral lesions has been referred to as vulvovaginal–gingival syndrome. Rare cases characterized by lesions located on the perianal and gingival regions are referred to as ano-gingival syndrome. Patients may also present with discomforting or painful bullous or erosive/ulcerative lesions, and still others with atrophic or papular lesions. These lesions may coexist with the more common reticular ones. Another uncommon presentation with plaque-like lesions is more frequently observed in patients with HCV infection [65]. The involvement of the lips is not uncommon, and erosive lesions are often seen (Fig. 3C). An uncommon pigmented presentation of oral LP should be distinguished from amalgam tattoos, keeping in mind that amalgam may sometimes elicit a lichenoid reaction. Pigmented oral LP represents a form of post-inflammatory hyperpigmentation occurring on the background of LP.

Histopathologically, oral LP shows features similar to cutaneous classic LP, but the number of apoptotic keratinocytes is usually lower. Plasma cells may be found, but are surprisingly few for a plasma cell-rich site such as the oral mucosa.

LP in the vulvovaginal region usually presents with erosive lesions involving the vulva and in most cases the vagina as well (Fig. 3G). As in oral LP, patients with vulvovaginal LP are at risk of developing SCC in long-standing lesions.

LP is not uncommon on the penis, and can present with different clinical features ranging from whitish networks similar to those observed in the oral mucosa, to annular, papular, hyperpigmented, and atrophic lesions (Fig. 3H–L).

The histopathological features of genital LP are similar to those of oral LP.

The last, and most controversial variant of LP (if it is a variant of the disease at all) that we will discuss is keratosis lichenoides chronica (KLC), a disease first described by Kaposi in 1895 as “lichen ruber acuminatus verrucosus et reticularis” [67]. In subsequent years many authors reported cases of what they perceived as the same entity, using various terms including „lichen ruber acuminatus verrucosus et reticularis“, „lichen verrucosus et reticularis“, „porokeratosis striata lichenoides“, „porokeratosis striata“, „morbus moniliformis lichenoides“, „dermatose papulo-hyperkératosique en stries“, „kératose lichenoide striée“, and „lichenoid trikeratosis“ (reviewed by Masouye and Saurat [68]). In their review of the literature, based on the clinical and histopathological features depicted in the original publications, Masouyè and Saurat attempted to re-classify the published cases, suggesting that some were examples of dystrophic epidermolysis bullosa, some of congenital ichthyosiform syndromes, and some were unclassifiable, while 40 out of 50 reported cases represented genuine examples of the condition as reported by Kaposi [68]. Patients with KLC were mostly adults of both sexes, presenting clinically with a progressive eruption of symmetrical, violaceous papules with pronounced hyperkeratosis, located predominantly on the dorsal aspects of the extremities and on the trunk, dysplaying a characteristic linear arrangement. The face was involved with lesions that were similar to those seen in seborrheic dermatitis or rosacea. Oral manifestations and nail lesions were observed in 50% and 30% of the cases, respectively. Histopathologically, KLC is characterized by a lichenoid tissue reaction very similar to that observed in classic, atrophic, or hyperkeratotic LP. Direct immunofluorescence studies usually show the presence of numerous IgM-containing colloid bodies.

Despite over one century of discussions, it is still unclear whether KLC represents a distinct disease or a variant of LP, and arguments both for and against its inclusion in the group of LP have been published [69–72]. Böer again reviewed the literature in 2006, suggesting that a small group of patients with KLC had an authentic, exceedingly rare disorder distinct from LP and LE, which was characterized clinically by the combination of seborrheic dermatitis-like features on the face and linear and reticulate, confluent papules on the trunk and limbs [73]. The histopathological findings showed a lichenoid-interface dermatitis with numerous apoptotic keratinocytes and with parakeratosis admixed with neutrophils [73].

Drug-induced LP may be caused by innumerable drugs including immunomodulatory ones, and is usually a reaction occurring after long-standing use of the responsible drug; in fact, the median latency between the introduction of the drug and the onset of the cutaneous reaction is several months and can be as long as some years, depending also on the dosage and frequency of administration [74]. In some cases, drug-induced LP may represent a genuine LP triggered by drugs.

Clinically, a generalized, symmetrical distribution sparing the predilection sites of LP and with presence of typical lesions of LP together with other ones with different morphological features (e.g., psoriasiform, pityriasis rosea-like) suggests a drug etiology. Wickham striae and mucosal involvement are uncommon in drug-induced LP.

Histopathologically, focal parakeratosis, focal interruption of the granular layer, and especially the presence of apoptotic keratinocytes in the upper layers of the epidermis favour the diagnosis of a drug-induced LP (Fig. 6I) [75]. When more than one biopsy is taken, different biopsies may show different features, supporting the diagnosis of drug reaction. In exceptional cases, we have observed different histopathological features in a single punch biopsy, where one part showed a pattern indicative of a hypersensitivity reaction, whereas the other part had features of a lichenoid reaction.

A peculiar histopathological pattern of lichenoid drug reaction is represented by lichenoid granulomatous dermatitis (LGD). In LGD a superficial granulomatous infiltrate is admixed with a lichenoid lymphocytic infiltrate. Besides drug eruptions, LGD as a histopathological pattern has also been described in different conditions such as rheumatoid arthritis, infections by different microorganisms, sarcoidosis, lichenoid keratosis, hepatobiliary disease, and tattoos among others [76, 77].

The authors have declared that no competing interests exist.

The authors declared that no clinical trials were used in the present study.

The authors declared that no experiments on humans or human tissues were performed for the present study.

The authors declared that no informed consent was obtained from the humans, donors or donors’ representatives participating in the study.

The authors declared that no experiments on animals were performed for the present study.

The authors declared that no commercially available immortalised human and animal cell lines were used in the present study.

No funding was reported.

Conceptualization: LC. Investigation: IF, LC, ES, AK. Writing – original draft: LC. Writing – review and editing: IF, AK, LC, ES.

Eva Schadelbauer https://orcid.org/0000-0001-6110-520X

Angelika Kogler https://orcid.org/0000-0002-8612-7234

All of the data that support the findings of this study are available in the main text.