Lichenoid and interface dermatitis

Clinical features

Lichen planus (Gr. leichen , tree moss) is a common, usually intensely pruritic, symmetrical, papulosquamous dermatosis. Its prevalence in the general population is approximately 1%, and it most often presents in the fourth to sixth decades with a slight female predominance. It is uncommon in childhood. Occasional familial cases have been reported.

The disease is characterized by small, smooth, shiny, flat-topped polygonal papules measuring several millimeters to 1 cm in diameter and often having a violaceous color ( Fig. 7.1 ). Delicate white lines known as Wickham striae typically cross the slightly scaly surface ( Fig. 7.2 ). The lesions are found most commonly on the flexor aspect of the wrists, the forearms, the extensor aspect of the hands and ankles, the lumbar area, and the glans penis ( Fig. 7.3 ). Rare cases may also have associated palmoplantar keratoderma. Annular lesions may be seen. Lichen planus is associated with a positive Koebner phenomenon. It is a usually self-limiting although sometimes protracted disorder, patients clearing of lesions within weeks to 1 or 2 years.

Oral involvement, which is very common (affecting up to 60% of patients with cutaneous disease), shows a marked female preponderance and presents most often in the seventh decade. It may sometimes be the sole manifestation (an estimated 15–35% of patients with oral lichen planus never develop skin lesions). The buccal mucosa, vestibule, tongue, gingivae, hard palate, fornix, lip, and soft palate may be affected, in decreasing order of frequency. Patients frequently present with a white lacelike pattern, but papules, plaques and erosions, ulcerated, atrophic, and bullous variants may also be found ( Figs 7.4–7.6 ). Lesions are usually asymptomatic, although erosions and bullae are sometimes tender and painful. Chronic ulcerated oral lichen planus is of particular importance because it has been related to an increased risk, albeit low, of developing squamous cell carcinoma ( Fig. 7.7 ). The risk of developing malignancy is debated, with current literature suggesting that 0–12.5% of affected patients will develop an oral malignancy. Oral involvement in lichen planus and its relationship to cutaneous squamous cell carcinoma is discussed in greater depth elsewhere (see Chapter 11 ). Involvement of the gums may present as desquamative gingivitis. Other mucous membranes that may be involved include those of the pharynx, larynx, esophagus, nose, anus, and genitalia. Familial cases of lichen planus limited to oral involvement are noted.

Ocular involvement is rare and may include eyelid lesions, blepharitis, conjunctivitis, keratitis, punctate corneal opacities, iridocyclitis, and chorioretinitis.

Esophageal involvement, although rare, is an important potential cause of morbidity and is the most frequently involved gastrointestinal site. Concomitant oral lesions are typically present, but in rare cases esophageal involvement is the initial presentation. To date, middle-aged or elderly females are typically affected. Complications include chronic dysphagia and stricture formation affecting the mid or upper esophagus. Patients with esophageal lichen planus may have a risk of developing squamous cell carcinoma. Some patients may develop squamous cell carcinoma associated with esophageal lichen planus in the absence of oral or cutaneous manifestations. The role of surveillance is uncertain.

Genital lesions in lichen planus are common (particularly in males), being present in up to 25% of patients, and sometimes adopting an annular configuration ( Fig. 7.8 ). Similar annular lichen planus may be found elsewhere on the body, including intertriginous areas. Occasionally, penile lesions are the sole expression of the disease, and there is an association in uncircumcised men. Vulval lesions may be found in up to 51% of females with cutaneous involvement. Sometimes gingival and female genital lesions may coexist as a variant of erosive lichen planus, the so-called vulvovaginal-gingival syndrome. Patients present with dyspareunia and intense burning vulval pain. The vulva appears congested, and there may be erosions, which are often surrounded by a white reticulate border. Vaginal involvement similarly presents as dyspareunia and often postcoital bleeding due to inflammatory, desquamative, and erosive changes. More typical features of lichen planus may be encountered elsewhere on the body. Squamous carcinoma is an important complication, albeit rare, of chronic vulval lichen planus and appears to be more common in nonhair-bearing mucosa. The development of penile cancer is rare. Genital involvement in lichen planus is discussed elsewhere (see Chapter 12 ).

The nails are affected in about 10% of patients with lichen planus; manifestations include thinning of the nail plate, longitudinal ridging, striations, pterygium formation, subungual hyperkeratosis, and, very rarely, complete destruction of the nail ( Fig. 7.9 ). Although nail involvement in children is said to be rare, some authors regard twenty-nail dystrophy of childhood as a variant of localized lichen planus, although not all accept this hypothesis.

Most lesions heal within 6–18 months of onset. However, oral and hypertrophic variants and lichen planopilaris tend to have a chronic course. Postinflammatory hyperpigmentation is not uncommon, particularly in darker-skinned people ( Fig. 7.10 ).

A number of variants of lichen planus merit specific mention:

• Lichen planopilaris (follicular lichen planus) presents as single or multiple plaques of scarring alopecia associated with a spectrum of lesions including typical lichenoid papules involving the scalp to brown or violaceous keratotic follicular papules affecting the trunk and extremities ( Figs 7.11–7.13 ). Nonscarring plaques with prominent follicular papules may also be present. Linear lesions have rarely been described. Some authors suggest that scalp lichen planus results in some cases of pseudopélade of Brocq, although that entity likely represents the end stage of a variety of scarring alopecias. Children can also be affected. The Graham-Little-Picardi-Lasseur syndrome refers to a variant of lichen planopilaris characterized by the following triad: 1. multifocal scarring alopecia of the scalp; 2. nonscarring alopecia of the axilla and groin; 3. follicular lichen planus of other areas of the body, scalp, or both.

  
  
  

• Atrophic lichen planus, the clinical features of which merely reflect resolution of the more typical active phase.

• Lichen planus actinicus [lichen planus subtropicus, summertime actinic lichenoid eruption (SALE)] develops in patients with prolonged exposure to sunlight and, therefore, usually manifests in spring or summer, with improvement or remission in the autumn or winter. It occurs particularly in the Middle East (especially Egypt) and the Far East and affects younger people, with a maximum incidence in the second and third decades and a slight female predominance ( Fig. 7.14 ). Affected sites include the lateral aspects of the forehead, the dorsum of the hands, the forearms, face, and neck. The eruption can include a mixture of lichen planus-like and lichen nitidus-like lesions, whereas in others, the lesions appear as purely one or the other (see actinic lichen nitidus , below). Typically, the lichen planus lesions have an annular configuration with a bluish-brown, rather atrophic center and slightly raised border. They may sometimes coalesce to form circinate plaques. Occasionally, a melasma-like appearance has been documented. There is usually little pruritus, and Koebner phenomenon is commonly absent. The nails are often unaffected.

  

• Lichen planus pigmentosus, most commonly encountered in the tropics in dark-skinned patients, is characterized by the development of variably pruritic pigmented dark brown macules predominantly affecting exposed skin and the flexures ( Figs 7.15 and 7.16 ). The most common affected sites include the face and neck, but intertriginous areas may also be affected (lichen planus pigmentosus inversus). There is no sex predilection. The disorder is characterized by periods of exacerbation and remission. Exceptionally, involvement of the oral mucosa has been documented.

  
  

• Hypertrophic lichen planus, which represents superimposed lichen simplex chronicus, commonly affects the lower limbs, particularly the shins, and manifests as highly pigmented warty plaques ( Fig. 7.17 ). Often, involvement is restricted to the shins with no other lesions elsewhere. Familial lichen planus shows an increased incidence of this variant. The lesions are intensely itchy and very persistent. There is an attendant (albeit very slight) risk of neoplastic transformation.

  

• Ulcerative lichen planus, a chronic variant affecting the fingers, hands, soles, and toes, is often associated with permanent loss of nails ( Figs 7.18 and 7.19 ). Squamous cell carcinoma may complicate this variant of lichen planus.

  
  

Other variants include lichen planus linearis, which occurs predominantly in children, and the rare vesicular or bullous variants, which must be distinguished from lichen planus pemphigoides. Bullous lichen planus implies the development of vesicles or bullae on preexistent lichenoid lesions as a consequence of severe basal cell hydropic degeneration. It is more often a histologic finding rather than a clinical observation. In contrast, lichen planus pemphigoides is characterized by the development of large tense bullae arising on normal or erythematous skin in a patient with typical lichen planus elsewhere. It represents the combined expression of lichen planus and bullous pemphigoid.

Childhood lichen planus shows a modest male predominance (2 : 1). Although mucosal involvement is said to be rare, recent series report a frequency of 14–39%. Hypertrophic lesions may be seen in up to 26% of cases.

Pathogenesis and histologic features

The etiology of lichen planus is unknown. Theories of infectious (bacterial and viral), autoimmune, metabolic, psychosomatic, and genetic causes have all had their proponents. Currently, however, it is thought that lichen planus represents an abnormal delayed hypersensitivity reaction to an as yet undetermined epidermal neoantigen, possibly to a combination of an external antigen coupled with an internal self-antigen. The association of lichen planus with a number of viral infections including hepatitis B and C and human immunodeficiency virus (HIV), combined with the well-recognized relationship to numerous drugs, adds support to this hypothesis.

Lichen planus is associated with a variety of liver cell abnormalities including aberrant liver function tests and serology. An increased incidence of chronic active hepatitis, primary sclerosing cholangitis and primary biliary cirrhosis has also been recorded. Not all documented series, however, have confirmed these observations, suggesting that the reported relationship may be dependent on the background level of hepatitis B virus infection. Lichen planus has also followed vaccination, most commonly hepatitis B vaccination but also influenza, rabies, and Tdap vaccination. More recently, lichen planus (particularly oral disease) has been linked to hepatitis C virus and chronic liver disease. The incidence of hepatitis C virus in patients with lichen planus is, however, very variable, ranging from effectively zero in some countries, including the United Kingdom, India, Germany, and Slovenia, to as high as 100% in Japan.

Evidence of other disorders including thyroid disease, dyslipidemia, and impaired carbohydrate metabolism including overt diabetes mellitus, has also been documented in lichen planus, particularly the oral variant. A recent study from Japan suggests a possible association of hepatitis C infection with both diabetes and lichen planus. Other studies have cast doubt on some of these associations.

A significant association between lichen planus and human leukocyte antigen (HLA)-DR1, HLA-DQ1, and HLA-DQB1 has been noted by a number of authors. This association pertains to patients with or without mucosal lesions but does not extend to patients with the drug-induced variant. It is suggested that this association relates to antigen presentation by HLA-DR1+ cells to T-helper cells with the resultant development of an autoimmune response.

Although it is generally accepted that the pathogenesis of the basal cell damage in lichen planus primarily involves the cellular immune response, likely through the action of type I interferons increasing the expression of IP10/CXCR10 and recruiting CD8+ T cells via CXCR3 and CCR5, the precise mechanism(s) require further elucidation. It is unlikely that autoantibody and immune complex-mediated damage have a significant role in the lichenoid tissue reaction.

The initial event in the evolution of the lichen planus papule is destruction of the basal epidermal layer (keratinocytes and melanocytes). In the earliest stage of development, increased numbers of Langerhans cells are present within the epidermis, and it is believed that these cells process modified epidermal antigens for presentation to T lymphocytes. Keratinocytes express HLA-DR, and this is likely to be of pathogenetic importance. Subsequent migration with resultant CD8+ T-cell activation results in basal keratinocyte death due to the combined effects of interferon-gamma (IFN-γ), interleukin (IL)-6, granulocyte-macrophage colony stimulating factor (GM-CSF), and tumor necrosis factor alpha (TNF-α). The expression of FasR/FasL by the basal keratinocytes suggests that apoptosis is an important mode of cell death in lichen planus. The dermal infiltrate consists predominantly of Ia+, CD4+ lymphocytes. CD8+ lymphocytes are also present in close apposition to the dermal–epidermal junction adjacent to foci of basal keratinocyte necrosis and are said to predominate in early lesions. B lymphocytes are scarce and plasma cells are characteristically absent in cutaneous lesions, except in the hypertrophic variant.

Development of the typical papule appears to be due to a combination of continued keratinocyte destruction and regenerative activity, with the latter depending upon the migration of epithelium from the edge of the lesion and from adjacent eccrine ducts, rather than from increased mitotic activity. There is little uptake of tritiated thymidine at the site of basal cell damage, but conspicuous uptake at the edges of the lesion and, as a reflection of regeneration, keratin 17 expression is also upregulated in the suprabasal epithelium. The typical features of lichen planus therefore depend upon a variable interplay between basal cell liquefactive degeneration and irregular epidermal regeneration.

The earliest identifiable change in lichen planus is the presence of cytoid bodies and associated pigmentary incontinence. Cytoid bodies (colloid or Civatte bodies) are round or oval, homogeneous, eosinophilic bodies identifiable within the basal epithelium and the papillary dermis ( Fig. 7.20 ). They display diastase-resistant periodic acid-Schiff (PAS) positivity, and may be identified within papules, perilesional skin, and even apparently uninvolved skin. Although they may be seen in a variety of dermatoses (including lupus erythematosus, graft-versus-host disease, and poikiloderma) and seemingly normal skin, where their presence, if either in large numbers or in a cluster, suggests lichen planus.

Ultrastructurally, cytoid bodies are composed of tightly arranged aggregates of filaments 6–8 nm in diameter; immunocytochemically they are composed of keratin.

Characteristic histologic features of an established papule can usually be recognized at scanning magnification ( Fig. 7.21 ). They comprise hyperkeratosis, typically wedge-shaped hypergranulosis (clinically presenting as Wickham striae) related to the intraepidermal components of sweat ducts and hair follicles, and irregular acanthosis ( Figs 7.22 and 7.23 ). The acanthosis often has a sawtooth appearance ( Figs 7.24 and 7.25 ). The presence of prominent parakeratosis argues strongly against a diagnosis of cutaneous lichen planus. Lymphocytes and histiocytes may sometimes be seen in the epidermis and occasionally satellite cell necrosis is a feature. Liquefactive degeneration of the basal layer of the epithelium is characteristic and often subepidermal clefts are present (Max Joseph spaces). Pigmentary incontinence is common ( Fig. 7.26 ). A lymphohistiocytic bandlike infiltrate occupies the upper dermis and obscures the dermal–epidermal junction. Occasional eosinophils may be present. Hyperkeratosis persists in resolving lichen planus, but the acanthosis regresses, leaving a flattened epidermis ( Fig. 7.27 ); there may be focal scarring and the dermal infiltrate is less conspicuous ( Fig. 7.28 ).

Lesions may become completely atrophic and histologically there is flattening of the epidermis, variable number of colloid bodies, and pigment incontinence with almost no inflammation. If colloid bodies are rare, distinction from poikiloderma may be very difficult.

In lesions of annular lichen planus, the typical histologic features are only seen in the periphery at the advancing edge of the lesion.

In micropapular lichen planus, the changes are so focal that the diagnosis may be missed if serial sections are not examined.

Lichen planopilaris in its early stages shows an infiltrate surrounding the lower hair follicle and papilla, follicular dilatation, and keratin plugging ( Fig. 7.29 ). The adjacent interfollicular epithelium may or may not show a typical lichenoid infiltrate ( Fig. 7.30 ). Basal cell hydropic degeneration, cytoid body formation, and pigmentary incontinence are also sometimes evident. In advanced scalp lesions, the hair follicles are destroyed and replaced by vertically orientated fibrous scars, reminiscent of the fibrous streamers seen in pseudopélade of Brocq.

Lichen planoporitis represents a rare variant in which lichenoid/interface changes are centered on the acrosyringium and eccrine sweat duct as it enters the epidermis. Squamous metaplasia of the ductal lining epithelium may be a feature.

In lichen planus actinicus, the annular borders of the macules show typical features of lichen planus. In the center of the lesions, however, the epithelium is atrophic, thin, and flattened, although the lymphohistiocytic infiltrate remains. Foci of parakeratosis and eczematization within the follicular epithelium have also been described. Lichen nitidus-like lesions may sometimes be seen (see below).

Lichen planus pigmentosus is characterized by epidermal thinning accompanied by basal cell vacuolization, pigmentary incontinence, and a superficial dermal lichenoid lymphohistiocytic infiltrate.

Hypertrophic lichen planus is characterized by more marked hyperkeratosis and acanthosis, with the epithelium sometimes showing pseudoepitheliomatous hyperplasia such that misdiagnosis as squamous cell carcinoma is a distinct possibility, particularly in small biopsies and if clinical information is not available ( Figs 7.31–7.33 ). A number of changes not seen in ordinary lichen planus may be observed and include parakeratosis, spongiosis, necrotic keratinocytes above the basal cell layer, more frequent eosinophils, and plasma cells in the dermal infiltrate. These changes may raise the possibility of a lichenoid drug eruption. The differential diagnosis is not difficult, as lichenoid drug eruptions tend to be more generalized and are not usually associated with hypertrophic changes.

The oral lesions of lichen planus, although often displaying the classical features, usually show parakeratosis; occasionally, alternate foci of both are evident. In contrast to the cutaneous lesions, the epithelium is sometimes rather thin and the sawtooth pattern indistinct ( Fig. 7.34 ). There is typically basal cell hydropic degeneration. Basement membrane thickening due to the deposition of fibrin-rich eosinophilic amorphous material is commonly present. The cellular infiltrate, in addition to lymphocytes and histiocytes, frequently contains plasma cells. Dysplasia may be seen.

Unlike skin involvement, esophageal lesions show parakeratosis. Variable epithelial atrophy and/or mild thickening are usually seen, and the sawtooth pattern of acanthosis is not a feature. As with oral lesions, plasma cells often accompany the lymphocytic infiltrate.

Vesicular or bullous lesions are subepidermal and occur due to excessive edema developing in association with the basement membrane zone damage complicating basal cell hydropic degeneration ( Fig. 7.35 ).

Direct immunofluorescence studies from patients with lichen planus usually reveal a linear fibrillar band of fibrin at the dermal–epidermal junction ( Fig. 7.36 ). The cytoid bodies may be highlighted non-specifically, mainly to IgM, but also to IgG, IgA, and C3 ( Fig. 7.37 ). A lichen planus ‘specific antigen’, which is present in the prickle cell and granular cell layers, has been demonstrated by indirect immunofluorescence of patients' serum with fetal skin. The pathogenetic significance of this is unknown. Direct immunofluorescence of lichen planopilaris reveals follicular, linear basement membrane zone labeling with immunoglobulin (primarily IgG or IgA). Fibrin may also be present. The nosological implications of this observation are uncertain. Indirect immunofluorescence for circulating antibasement membrane zone antibodies is negative.

Differential diagnosis

Lichen planus should be differentiated from other diseases showing a lichenoid infiltrate and hydropic degeneration of the basal layer of the epithelium. Thus, lichen planus may be indistinguishable from lichenoid keratosis and their distinction is entirely dependent on clinicopathological correlation. In many cases of lichenoid keratoses, there are other associated changes including focal spongiosis and parakeratosis. Atrophic lesions may be confused with poikiloderma and chronic discoid lupus erythematosus. A lichen planus-like morphology is typical of the early stages of chronic graft-versus-host disease (GVHD), but the density of the infiltrate is typically less in this entity.

Poikiloderma shows epidermal atrophy, with loss of the ridge pattern and no tendency to a sawtooth appearance. In those examples associated with mycosis fungoides, the lichenoid infiltrate contains variable numbers of atypical lymphocytes.

Chronic discoid lupus erythematosus is associated with epidermal atrophy and follicular plugging. The inflammatory cell infiltrate is patchy with a tendency to periappendageal location with associated dermal mucin deposition. A positive lupus band test can be helpful.

Lichen planus may easily be mistaken for a lichenoid drug reaction, particularly in the absence of clinical information. Histologic features favoring the latter include high-level cytoid bodies and frequent eosinophils within the dermal infiltrate.

Clinical features

Lichen nitidus is a rare but distinctive dermatosis, which shows an equal sex incidence. Children and young adults are predominantly affected. It presents clinically as an eruption of pinhead-sized, flesh-colored, shiny, flat-topped or dome-shaped papules and shows a predilection for the arms, chest, abdomen, and genitalia ( Figs 7.38 and 7.39 ). A positive Koebner phenomenon is typically present. The condition is usually localized and asymptomatic, although occasionally there may be mild or even intense pruritus. Rarely, generalized lesions have been described. An association with generalized lesions and Down syndrome has been documented, as has been a case after interferon-alpha therapy. Occasionally, papules may be encountered on the palms and soles. Familial cases have been rarely described. Lichen nitidus can spontaneously resolve within a few months or persist indefinitely.

Mucosal involvement presenting as grayish-yellow papules has also been described. Nail involvement, which is rare, presents as thickening with ridges, rippling, terminal splitting, striations, and pits.

Keratodermic, vesicular, hemorrhagic, purpuric, and perforating variants may rarely be encountered. Perforating lichen nitidus shows a predilection for the forearms and fingers, and may be trauma related.

Actinic lichen nitidus refers to the development of lichen nitidus on sun-exposed sites, usually during the summer months. In some cases, involvement is predominantly facial and it may present in black patients. It shows considerable overlap with actinic lichen planus (see above).

Histologic features

Lichen nitidus is recognizable by a characteristic histology in many cases. The classic papule is sharply circumscribed and occupies the space of only four or five dermal papillae. It is often depressed in the center and composed of atrophic epidermis, frequently covered by a parakeratotic tier and overlying a cellular infiltrate ( Figs 7.40–7.43 ). Clawlike extensions of epidermal ridges mark the lateral boundaries of the lesion. The epithelium shows basal cell hydropic degeneration, and cytoid bodies may be a feature. The inflammatory component consists of lymphocytes, histiocytes, and variable numbers of epithelioid cells. Giant cells are sometimes a feature and true granulomata may occasionally be found, although caseation is never present. A plasma cell-rich variant is exceptional. In addition to red blood cell extravasation, purpuric variants may show increased vascularity with vessel wall thickening and hyalinization. In rare cases, a prominent lymphocytic inflammatory infiltrate can extend down the hair follicle and eccrine glands, making the distinction from lichen striatus challenging. A follicular variant of lichen nitidus may be seen and mimics lichen spinulosus histologically. However, rarely, lichen nitidus and lichen spinulosus may coexist clinically.

Palmar lesions may be identical to those seen elsewhere or show a more diffuse bandlike upper dermal lymphohistiocytic infiltrate with associated giant cells and focal parakeratosis.

Fibrin can be detected at the basement membrane zone by immunofluorescent techniques, but immunoglobulin deposition is not a feature. Immunophenotypic studies show that there is a marked excess of CD4+ cells (helper/inducer T cells) over CD8+ cells (cytotoxic/suppressor T cells). Langerhans cells are conspicuous. These findings are similar to those described for lichen planus.

Ultrastructural examination reveals rather non-specific findings including epidermal intercellular edema, subepidermal edema, colloid bodies, decreased numbers of desmosomes, and disruption or reduplication of the lamina densa. Perivascular electron-dense deposits (the nature of which is unknown) have been described in purpuric variants.

Comment

Lichen nitidus may coexist with lichen planus or predate it and lichen nitidus-like lesions may be found in patients with typical lichen planus, but it is unlikely that the conditions are closely related. Wickham striae are not a feature of lichen nitidus, and mucosal involvement is exceptional. Lichen nitidus is associated with parakeratosis and epidermal atrophy, in contrast to the orthohyperkeratosis and acanthosis seen in lichen planus. The sawtooth appearance of the lower border of the epidermis seen in lichen planus is not a feature of lichen nitidus, and immunofluorescence for immunogloblins is negative. Epithelioid cells and giant cells are characteristic of lichen nitidus and are not typically a feature of lichen planus. Four patients with Crohn disease were reported to develop lichen niditus; however, it remains to be seen if lichen nitidus is truly an extragastrointestinal finding of this disease. Another patient developed lichen nitidus after hepatitis B vaccine injection. The significance of this is uncertain.

Clinical features

Lichenoid keratosis (benign lichenoid keratosis, lichen planus-like keratosis, solitary lichen planus) is not uncommon and usually presents as a solitary, 0.3–2-cm diameter, sharply demarcated, erythematous, violaceous, tan or brown papule or plaque ( Fig. 7.44 ). Occasionally, multiple lesions may be present. It is usually of short duration and shows a predilection for the face (particularly the cheeks and nose), neck, upper trunk (especially the presternal area), forearm, and dorsum of the hand. The surface is often scaly. Lesions are commonly asymptomatic, but mild pruritus has sometimes been documented. Patients are frequently Caucasian, but occasionally blacks are affected. Females develop these lesions more commonly than males, usually in their fourth to seventh decades.

Lichenoid keratosis is often clinically misdiagnosed as a seborrheic keratosis, superficial basal cell carcinoma, squamous cell carcinoma, actinic keratosis, or Bowen disease.

Pathogenesis and histologic features

The precise nature of lichenoid keratosis is uncertain. In the past, it was regarded as a solitary lesion of lichen planus or thought to have an actinic pathogenesis. It was also proposed to represent an immunological or regressive response to a preexistent epidermal lesion similar to the phenomenon encountered with a ‘halo’ nevus. The frequent association of solar lentigines or, less commonly, seborrheic keratoses in the adjacent epithelium has been cited as evidence in favor of this hypothesis. Recent studies have shown the lymphocytic infiltrate in lichenoid keratosis to be immunophenotypically distinct from lichen planus. The lymphocytes in lichenoid keratosis are predominantly CD8-reactive in contrast to lichen planus. More CD20-positive B cells are usually seen in lichenoid keratosis. Furthermore, the lymphocyte infiltrate in lichenoid keratosis lacks the cutaneous lymphocyte antigen (CLA) expression, suggesting the absence of localized antigenic stimulation as seen in lichen planus. These studies suggest that lichenoid keratosis is distinct from lichen planus despite the similarities in histology.

Histologically, as its name suggests, the features are often very similar or even identical to those of lichen planus. There is hyperkeratosis, wedge-shaped hypergranulosis, variable acanthosis, and basal cell liquefactive degeneration sometimes accompanied by lymphocytic exocytosis ( Figs 7.45 and 7.46 ). Foci of parakeratosis are also frequently seen. Although the sawtooth acanthosis of lichen planus is sometimes evident, more often the epithelium merely shows broadened, widened, and irregular epidermal ridges. The basal epidermal layers may sometimes show very minor degrees of cytological atypia, including cellular and nuclear enlargement with conspicuous nucleoli, but these changes represent regenerative phenomena. Dysplasia as seen in lichenoid actinic keratosis is not a feature of a lichenoid keratosis. Colloid bodies are usually conspicuous in both the epidermis and dermis, and pigmentary incontinence is often marked ( Figs 7.47–7.49 ). Apoptotic keratinocytes can be prominent and may be associated with inatraepidermal blister formation with subepidermal vesiculation. In such cases, the histology can mimic conditions such as subacute cutaneous lupus erythematosus and even erythema multiforme. Epidermal pallor and dermal edema can be seen in cases with only slight or no acanthosis and an interface population of lymphocytes along the junction with vacuolar degeneration. Foci of atrophy can be occasionally encountered. In some cases, a combination of lichenoid and spongiotic changes may be seen.

A dense chronic inflammatory cell infiltrate is typically present in the superficial dermis. Although this characteristically has a lichenoid distribution, on some occasions it may be more discrete and predominantly perivascular in location. The infiltrate consists largely of lymphocytes and histiocytes, but small numbers of plasma cells and eosinophils are occasionally present. Exceptionally, atypical large T lymphocytes (enlarged with hyperchromatic, irregular, contoured nuclei) which are activated CD30 positive cells can be also seen. The adjacent dermis sometimes shows lentigo and solar elastosis. Features suggestive of mycoses fungoides such as Pautrier abscesses, dermal–epidermal tagging, and mild lymphocytic atypia have been exceptionally noted in benign lichenoid keratosis (lymphomatoid lichenoid keratosis). Clinicopathological correlation and careful follow-up are essential in such cases to avoid misdiagnosis.

Immunofluorescence findings, which are similar to those of lichen planus, comprise deposits of IgM and, less commonly, IgG outlining cytoid bodies.

Differential diagnosis

Many conditions show lichenoid histology and therefore come into the differential diagnosis. Most prominently, these include lichen planus and lichenoid drug reactions.

If clinical information is available, differentiation from lichen planus should present little difficulty. Lichen planus is characterized by large numbers of lesions in contradistinction to the single papule or plaque of lichenoid keratosis. In addition, lichen planus is usually itchy. Parakeratosis and dermal plasma cells are not usually a feature of lichen planus, but are more common of lichenoid keratosis.

Both actinic keratoses and squamous cell carcinoma in situ may sometimes show a lichenoid inflammatory cell reaction. Dysplasia by definition is not a feature of lichenoid keratosis. Inflamed seborrheic keratosis and porokeratosis can have a prominent lichenoid reaction. The absence of horn cyst formation, squamous eddies, and laminated stratum corneum keratin helps distinguish these lesions from seborrheic keratosis, whereas the absence of cornoid lamella excludes porokeratosis. Melanocytic lesions with halo phenomenon can become a diagnostic consideration and require examination of the dermis and dermal–epidermal junction for melanocytic nests. In difficult cases, additional step sections or immunohistochemical studies can prove useful. Finally, the presence of scattered CD30-positive lymphocytes in some cases of lichenoid keratosis may raise the histologic differential diagnosis of lymphomatoid papulosis. However, the paucity of these enlarged CD30-positive cells, the absence of a deep infiltrate, and the clinically history of a solitary lesion is reassuring for lichenoid keratosis.

Clinical features

Lichen striatus [Blaschko linear acquired inflammatory skin eruption (BLAISE)] is an uncommon, usually asymptomatic, dermatosis of unknown etiology, affecting the limbs or neck in which lesions typically follow Blaschko lines. Infrequently, the condition is pruritic. It is self-limiting, normally disappearing within months to a year of onset. It shows a female predominance (2–3 : 1) and, although it may occur at any age, it most often presents in children aged 5–15 years. Rarely, lichen striatus has been described in adults ( adult Blaschkitis , see below). Occurrence during pregnancy is very rare. A family history is rarely encountered, suggesting a genetic predisposition and/or a common environmental etiology in such cases. It is associated with seasonal variation with most series reporting the majority of patients presenting in spring and summer, with the exception of one large series where the majority of patients presented in the winter Case clustering has been documented.

Lesions, usually solitary and unilateral, present as erythematous or flesh-colored lichenoid or sometimes psoriasiform scaly papules, which coalesce into a continuous or interrupted linear or curved band, 1–3 cm wide and often covering the whole length of a limb, either lower or upper extremities ( Figs 7.50 and 7.51 ). Occasionally, multiple lesions have been recorded, as has bilaterality. Presentation at two different sites and at multiple sites may exceptionally occur. Nail changes, which may affect a single nail, include onycholysis, longitudinal ridging, splitting, and nail loss. Exceptionally, lichen striatus with bilateral nail dystrophy has been described. Lichen striatus is not associated with Koebner phenomenon. Hypo- or hyperpigmentation sometimes follows resolution, which may be marked in people with pigmented skin. Lichen striatus is associated with atopy in up to 60% of patients.

Pathogenesis and histologic features

The etiology of this condition is unknown although case clustering and seasonality raises the possibility of an environmental or infective basis in conjunction with an abnormal host response. The development of lesions along Blaschko lines also raises the possibility of a cell-mediated autoimmune reaction to an abnormal clone of cells. Blaschko lines are believed to represent the direction along which epidermal growth centers expand during early skin development. It has been suggested that the distribution of lesions in lichen striatus may reflect a postzygotic abnormality such as somatic mutation affecting localized stem cells. An intriguing case following trauma in an adult has been reported. Further exceptional cases associated with solarium use, varicella and influenza infection, hepatitis B and BCG vaccine, interferon and etancercept therapy, and bee stings have been described.

The histologic features of lichen striatus may be non-specific and show changes of mild chronic non-specific dermatitis. In an established lesion, however, the changes often consist of an admixture of spongiotic dermatitis with lichenoid and interface features ( Fig. 7.52 ). Thus, there is often parakeratosis with a normal or slightly acanthotic epidermis accompanied by intercellular edema, lymphocytic exocytosis, and keratinocyte necrosis ( Figs 7.53–7.55 ). Satellite cell necrosis may sometimes be a feature, and transepidermal elimination of keratinocyte debris (perforating lichen striatus) has occasionally been documented. Intraepidermal Langerhans cell vesicles have exceptionally been described. A heavy lymphohistiocytic infiltrate is present in the superficial dermis and also surrounds the vessels of the superficial and deep vascular plexuses and sometimes also the cutaneous adnexae ( Figs 7.56 and 7.57 ) . Eosinophils and plasma cells are uncommon.

Some biopsies may be indistinguishable from lichen planus. In those cases where there is follicular involvement, the features can resemble those of lichen planopilaris, and old lesions sometimes simulate lichen nitidus.

By immunohistochemistry, the majority of the intraepidermal lymphocytes are of a CD8+ cytotoxic phenotype. The dermal lymphocytes consist of an admixture of CD4+ and CD8+ subtypes. CD7 is typically conserved. Intraepidermal Langerhans cells may be normal, increased, or decreased.

Nail changes include slight spongiosis with exocytosis, focal hypergranulosis, dyskeratosis, and a bandlike lymphohistiocytic infiltrate affecting the proximal nail fold, nail bed, and nail matrix dermis.

Clinical features

Adult Blaschkitis (acquired relapsing self-healing Blaschko dermatitis) is a rare, relapsing linear eruption with a mean age of onset of 40 years, predominantly affecting males. Lesions, which are pruritic papules and vesicles, affect multiple sites, particularly the trunk, following Blaschko lines and typically resolve in days or weeks. The condition, which may be unilateral or more commonly bilateral, recurs over the ensuing months or years.

Pathogenesis and histologic features

The etiology is unknown. Abnormalities in chromosome 18 in cells from involved skin in comparison to normal-appearing skin has been described in a female patient with adult Blaschkitis, supporting a link with cutaneous genetic mosaicism. Association with drugs and emotional stress has been reported.

Histologically, adult Blaschkitis is characterized by spongiotic changes often combined with focal interface inflammation; lichenoid features are rare, and deep involvement of adnexal structures is not often a feature.

Differential diagnosis

It resembles lichen striatus, and it has been suggested that there is no justification for separating the two entities. However, it differs clinically by the presence of vesicles, its truncal distribution, and relatively rapid resolution. Relapsing courses are typical. Pruritus is rare in lichen striatus. Lichen striatus predominantly affects young children although rare cases similar to adult Blaschkitis but affecting children have been described.

Clinical features

Keratosis lichenoides chronica (Nekam disease, lichen ruber verrucosus et reticularis) is a rare, chronic inflammatory dermatosis that combines the features of a seborrheic dermatitis-like eruption of the scalp and face with a progressive often reticular, lichenoid papulonodular dermatosis affecting the trunk, buttocks, and limbs. Patients usually present in the third to fifth decades although exceptionally reports of pediatric involvement have been documented, some with possible familial association. It may be persistent, but improvement can be seen in summer months and with phototherapy and/or systemic retinoids.

Facial and scalp lesions are erythematous, greasy and scaly, and bear no resemblance to those found on the trunk and extremities, which are erythematous or violaceous lichenoid scaly papules in a confluent, reticulate, or linear distribution. The latter may suggest Koebner phenomenon ( Fig 7.58 ). Papulonodular and infiltrated plaques are sometimes also present. Lesions are typically bilateral, symmetrical, and usually asymptomatic although rarely pruritus may be intense. Scarring is not a feature. Associated features include oral papules and ulceration, ocular lesions (blepharitis, conjunctivitis, anterior uveitis, and iridocyclitis), laryngeal nodules, palmoplantar keratoderma, and nail changes including yellow discoloration and dystrophy (longitudinal ridging, nail plate thickening, onycholysis, and paronychia) ( Fig. 7.60 ). Genital involvement including penile and scrotal papules, chronic balanitis, and phimosis has been documented.

Keratosis lichenoides chronica has been described in association with a number of systemic diseases including chronic infections (toxoplasmosis, tuberculosis, and viral hepatitis), kidney disease, and lymphoma.

Pathogenesis and histologic features

The precise nature of keratosis lichenoides chronica is uncertain. Although some authors regard it as a variant of hypertrophic lichen planus, this is unlikely.

Histologically, the lichenoid eruption is characterized by hyperkeratosis and parakeratosis, variable acanthosis, and epidermal atrophy associated with a bandlike lymphohistiocytic infiltrate in the superficial dermis, often with conspicuous melanophages. Neutrophils may be prominent in the stratum corneum. Perifollicular/acrosyringotropic and perivascular chronic inflammation may also be evident. Epidermal basal keratinocytes show hydropic degeneration, and cytoid body formation has been described. Many necrotic keratinocytes are present. Exceptionally, amyloid deposition has been documented.

The dermal infiltrate consists of lymphocytes, histiocytes, and variable plasma cells and eosinophils.

Direct immunofluorescence highlights the cytoid bodies.

The scalp and facial lesions show the features of a chronic dermatitis, namely, spongiosis with exocytosis and patchy parakeratosis. A perivascular chronic inflammatory cell infiltrate of lymphocytes, histiocytes, and plasma cells may be present in the upper dermis.

Clinical features

Erythema dyschromicum perstans (dermatosis cenicienta, ashy dermatosis) is an acquired, usually asymptomatic, disfiguring dermatosis which occurs particularly in Latin American (especially Mexican) populations and in Asians. It was originally named dermatosis cenicienta after the clinical appearance of affected patients – los cenicientos (the ash-colored ones). However, white-skinned races may rarely be affected. It is of unknown etiology, shows a female predilection, and can develop at any age, although the majority of patients are in their first three decades. Presentation in infancy has been documented.

Patients develop oval, irregular or polycyclic, gray macules with erythematous, indurated, inflammatory borders of 1–2 mm. The lesions extend peripherally, show a tendency to coalesce, and often affect large areas of the integument ( Figs 7.59–7.61 ). With progression, the eruption develops a gray-blue color and loses the erythematous border, which is sometimes replaced by a hypopigmented periphery. It is usually symmetrical, and particularly affects the trunk, proximal extremities, and, to a lesser extent, the face and neck. The palms and soles, scalp, nails, and mucous membranes do not appear to be involved.

Pathogenesis and histologic features

The etiology is unknown. Cases have followed HIV infection, and there is a report of simultaneous development of vitiligo and erythema dyschromicum perstans. The significance of these observations is doubtful. Increased susceptibility with HLA-DRB1*0407 in Mexican patients has been reported.

Sections from the inflammatory border show hyperkeratosis and an epidermis of normal thickness or somewhat atrophic, accompanied by basal cell hydropic degeneration and cytoid body formation ( Fig. 7.62 ). Pigmentary incontinence is marked, and a mild perivascular or lichenoid inflammatory cell infiltrate is present in the superficial dermis ( Fig. 7.63 ). Sections from the central gray area show epidermal atrophy, follicular hyperkeratosis, and pigmentary incontinence. Often, biopsies are obtained from late lesions, with the only feature noted that of prominent pigment incontinence. The dermal inflammatory infiltrate is composed of both CD4 and CD8 T cells, usually with CD8 forms slightly predominating.

Direct immunofluorescence reveals a pattern similar to lichen planus, with non-specific staining of the cytoid bodies with IgG, IgM, and C3, and fibrinogen deposition at the dermal–epidermal junction. The epidermal keratinocytes express Ia antigen, and the lymphocytic population comprises both helper/inducer and suppressor/cytotoxic phenotypes similar to lichen planus.

Ultrastructural findings are non-specific, comprising intra- and interepidermal edema with cytoplasmic vacuolation, separation of keratinocytes, retraction of desmosomes, cytoid body formation, focal gaps in the keratinocyte basal lamina, and pigment-laden histiocytes in the papillary dermis.

Differential diagnosis

The precise relationship of erythema dyschromicum perstans to lichen planus is uncertain. The histologic, immunological, and ultrastructural findings certainly suggests a relationship. Typical lichen planus may precede the development of erythema dyschromicum perstans and sometimes the two conditions have presented simultaneously, although some of the documented cases may have represented lichen planus pigmentosus.

Clinical features

These lesions were described in 2000 by Magro and Crowson to have features of both lichenoid and granulomatous dermatitis. There is a slight female predominance (21 : 15) affecting a broad range of ages (5–86 years old). The extremities and trunk are most often involved, followed by the head and neck region. Clinically, the lesions present as lichenoid papules. The absence of further reports since its original description casts doubts as to whether it represents a distinctive entity.

Pathogenesis and histology

Various etiologic agents including drug, coexisting medical illnesses, and infections have been implicated. Similar to any lichenoid disorder, there is a bandlike infiltrate of lymphocytes and histiocytes. The histiocytes are variably described as loosely aggregated and superficially located, cohesive granulomata, diffuse interstitial granulomatous inflammation, scattered solitary giant cells, and granulomatous vasculitis. Cases associated with drugs also may display parakeratosis, keratinocyte necrosis, acrosyrinogeal accentuation, red cell extravasation, granulomatous vasculitis, eosinophils, and a plasma cell infiltrate sparing the deep dermis. Lymphocyte atypia may also be a feature in examples associated with cutaneous lymphoma or lymphomatous drug reactions.