Lichen planus

Lichen planus lesions are so called because of their "lichen-like" appearance and can be classified by the site they involve, or by their morphology. Site Lichen planus may be categorized as affecting mucosal or cutaneous surfaces. • Cutaneous forms are those affecting the skin, scalp, and nails. • Mucosal forms are those affecting the lining of the gastrointestinal tract (mouth, pharynx, esophagus, stomach, anus), larynx, and other mucosal surfaces including the genitals, peritoneum, ears, nose, bladder and conjunctiva of the eyes. Pattern Lichen planus lesions can occur in many different forms or morphologies: ;Papular :Papular form is the classic cutaneous lichen planus (CLP) lesion characterized by shiny, red or purple-colored, flat-topped papule. Lesions may have a thin, transparent, and adherent scale. Fine whitish points or lacy lines (Wickham's striae) may be seen on the surface of well-developed papules. This pattern may develop secondary to trauma (koebnerization) or, uncommonly, as a spontaneous, isolated eruption, usually on the extremities, and rarely on the face. ; Hypertrophic : This pattern is characterized by hyperkeratotic thick pruritic red-brown to purple-gray plaques with follicular accentuation. Hypertrophic CLP commonly involves the extremities, especially the interphalangeal joints and the anterior legs in a symmetrical distribution. • Lichen sclerosus overlap syndrome, sharing features of lichen planus and lichen sclerosus. ==Signs and symptoms==

Although lichen planus can present with a variety of lesions, the most common presentation is as a well-defined area of purple-coloured, itchy, flat-topped papules with interspersed lacy white lines (Wickham's striae). This description is known as the characteristic "6 Ps" of lichen planus: planar (flat-topped), purple, polygonal, pruritic, papules, and plaques. Lesions can affect the: • Extremities (face, dorsal hands, arms, and nape of neck). This is more common in Middle Eastern countries in spring and summer, where sunlight appears to have a precipitating effect. • Palms and soles • Intertriginous areas of the skin. This is also known as "inverse lichen planus". characterized by irregular longitudinal grooving and ridging of the nail plate, thinning of the nail plate, pterygium formation, shedding of the nail plate with atrophy of the nail bed, subungual keratosis, longitudinal erthronychia (red streaks), and subungual hyperpigmentation. A sand-papered appearance is present in around 10% of individuals with nail lichen planus. Other variants may include: • Lichen planus pemphigoides is characterized by the development of tense blisters atop lesions of lichen planus or the development of vesicles de novo on uninvolved skin. • Keratosis lichenoides chronica (also known as "Nekam's disease") is a rare dermatosis characterized by violaceous papular and nodular lesions, often arranged in a linear or reticulate pattern on the dorsal hands and feet, extremities, and buttock, and some cases manifest by seborrheic dermatitis-like eruption on the scalp and face; also, palmoplantar keratosis has been reported. • Lichenoid keratoses (also known as "benign lichenoid keratosis", and "Solitary lichen planus" Restated, this is a cutaneous condition usually characterized by a solitary dusky-red to violaceous papular skin lesion. • Lichenoid dermatitis represents a wide range of cutaneous disorders characterized by lichen planus-like skin lesions. Examples of lichen planus affecting mucosal surfaces include: • Genital lichen planus, which may cause lesions on the glans penis or skin of the scrotum in males, and the vulva or vagina in females. or vulva destruction. The corresponding syndrome in males, affecting the glans penis and gums, is the peno-gingival syndrome. Mouth of non-erosive lichen planus in the left buccal mucosa (left cheek) Oral lichen planus (also termed oral mucosal lichen planus), is a form of mucosal lichen planus, where lichen planus involves the oral mucosa, the lining of the mouth. This may occur in combination with other variants of lichen planus. Six clinical forms of oral lichen planus (OLP) are recognized: ; Reticular : The most common presentation of oral lichen planus (OLP) is characterised by the net-like or spider web-like appearance of lacy white lines, known as Wickham's striae. This is usually asymptomatic. Reticular OLP may progress to the more severe subtypes, such as the erosive form, if left untreated. Involvement of the dorsum of the tongue might cause an altered sense of taste (dysgeusia). OLP may occur as a sole manifestation of the disease or in conjunction with other clinical manifestations of LP, including cutaneous LP, genital LP, nail LP, and lichen planopilaris (scalp LP). ==Causes==

Cutaneous LP is a self-limiting condition. It usually resolves within 6 to 12 months. Oral LP is a non-infectious, chronic inflammatory condition that involves the oral mucosa and may be accompanied by skin lesions. The etiology of oral LP are unknown. It is not clear whether the mechanisms causing isolated oral LP are different from those causing oral LP with cutaneous LP. An immune-mediated mechanism where basal keratinocytes are being targeted as foreign antigens by activated T cells, especially CD8+ T cells, has been proposed. Upregulation of intercellular adhesion molecule-1 (ICAM-1) and cytokines associated with T-helper 1 immune response, may also play an important role in the pathogenesis of lichen planus. Stress is thought to play a role in the pathogenesis of oral LP. Patients with anxiety and depression are reported more commonly with oral LP if compared to normal healthy individuals. Some studies have indicated that stressful events can induce LP lesions in otherwise healthy individuals. However, a cause-and-effect relationship between stress and the onset of oral LP has not been demonstrated. Autoimmune response to epithelial self-antigens remains a possibility. A single study of cutaneous LP reported evidence supporting autoimmunity by expanding in vitro T cells isolated from the skin lesions of two patients, followed by testing the T cells' ability to kill autologous keratinocytes (cytotoxicity). Several potential triggers of oral LP have been proposed over the years, mainly • Hypersensitivity reaction • Restorative material (e.g., amalgam and composite) or drugs can cause hypersensitivity reaction and lead to oral LP. • Oral LP usually resolves upon removal of the trigger. This is characteristic of oral LP. • Viral infection == Pathogenesis ==

Oral LP is considered a T-cell-mediated chronic inflammatory tissue reaction that results in a cytotoxic reaction against epithelial basal cells. The inflammatory infiltrate in oral LP is primarily composed of CD8+ T cells. A potential pathway for CD8+ T cell-mediated cytotoxicity in oral LP is described as follows: Oral LP may also be caused by a genetic factor that influences the immune function. A separate study performed in China found an association between a polymorphism in the TNF-alpha gene and risk for oral LP in a subset of patients. An Italian study found a significant increase in a genetic polymorphism of the first intron of the interferon (IFN)-gamma promoter in patients with oral LP compared with controls. ==Diagnosis==

Skin Patient history and clinical presentation must be obtained to diagnose lichen planus. Patients with suspected cutaneous lichen planus must be evaluated clinically through patient interviews and physical examinations. Patients should be questioned about their medication history, any history of pruritus or genital pain, and history of dysphagia or odynophagia. Examination of the entire cutaneous surface, including the scalp, oral cavity, and external genitalia, must be included. Wickham's striae are often seen during microscopic examination of cutaneous lesions of lichen planus. To confirm the diagnosis of cutaneous lichen planus, a skin biopsy can be done. A punch biopsy of sufficient depth to the mid dermis is usually significant. Immunofluorescence studies are not always needed. Direct immunofluorescence (DIF) can be useful in patients with bullous lesions to differentiate the condition from an autoimmune vesiculobullous disease. Mouth A diagnosis of oral lichen planus (LP) is confirmed through review of the patient history, physical examination, and histologic findings. The clinical evaluation should include a patient history that assesses the following: • History of LP involving other body sites or other skin disorders that may present with similar findings (e.g., autoimmune blistering diseases) • Presence of associated symptoms (e.g., pain, burning) • Medication the patients are taking within the few weeks to months after drug initiation e.g. antihypertensives, antidepressants, diuretics, antidiabetics, NSAIDs, etc. to evaluate for the possibility of an oral lichenoid drug eruption • History of dental restorations, Differential diagnosis Skin • Lichenoid drug eruption • The cutaneous manifestations resemble idiopathic lichen planus. • Chronic graft-versus-host disease • The history of preceding hematopoietic cell transplant is helpful for diagnosis • Psoriasis • Atopic dermatitis • Cutaneous lupus erythematosus • Discoid lupus erythematosus Oral involvement in acute GVHD is less well characterized than chronic GVHD, but has been associated with erythematous, erosive, ulcerative, or lichenoid oral lesions. Leukoplakia Leukoplakia is a manifestation of squamous epithelial hyperplasia that may be a precursor to oral squamous cell carcinoma. White patches or plaques usually appear on the oral mucosa. To rule out malignancy, a biopsy of leukoplakia is indicated. Oral squamous cell carcinoma Oral squamous cell carcinoma (SCC) can present as erythematous or white patches, ulcers, or exophytic masses. The highest risk for oral SCC may occur in patients with erythematous or erosive oral LP. A biopsy is indicated. Leukoedema Leukoedema is a common, benign finding in the oral cavity that presents as white-gray, somewhat translucent plaques on the mucosa. The buccal mucosa is the most common site for involvement. Symptoms are absent, and no treatment is necessary. Oropharyngeal candidiasis Oropharyngeal candidiasis (also known as thrush) is a common infection that has a predilection for infants, older adults with dentures, immunosuppressed individuals, and individuals utilizing intraoral corticosteroid therapy. Patients present with white plaques or erythematous patches on the buccal mucosa, palate, tongue, or oropharynx that may be mistaken for reticular LP. Histopathology The histologic findings of oral LP can offer strong support for the diagnosis, but are not pathognomonic. Clinical correlation is required. Common histologic findings of oral LP include: ==Treatment==

There is no cure for lichen planus, When medical treatment is pursued, first-line treatment typically involves either topical or systemic corticosteroids, Without treatment, most lesions will spontaneously resolve within 6–9 months for cutaneous lesions, Skin Many treatments have been reported for cutaneous lichen planus; there is a general lack of evidence of efficacy for any treatment. The mainstay of localized skin lesions is topical steroids. Currently, there are no FDA-approved therapies specifically for OLP, representing a significant unmet medical need. Available treatments are palliative rather than curative and often provide inadequate symptom control. Current treatment limitations include: Poor drug delivery to oral mucosal surfaces due to saliva clearance; Limited contact time between topical medications and moist mucosal tissues; Systemic side effects with oral immunosuppressants; Treatment failures and symptom relapses; Secondary complications, including oral candidiasis from chronic corticosteroid use. The FDA's approval of expanded access programs for investigational OLP treatments underscores the regulatory recognition of this condition as a serious disease with substantial unmet therapeutic need. ==Prognosis==

Cutaneous lichen planus lesions typically resolve within six months to a year. However, some variants, such as the hypertrophic variant, might persist for years if left untreated or unmonitored. In contrast to cutaneous LP, which is self limited, lichen planus lesions in the mouth may persist for many years, Overall, it is found that patients with erythematous or erosive oral lichen planus have a higher risk of oral squamous cell carcinoma compared to patients diagnosed with other variants. Due to the possibility that oral LP may increase risk for oral cancer, patients with oral lichen planus are encouraged to avoid activities known to increase the risk for oral cancer, such as smoking and alcohol use. OLP carries a significant risk of malignant transformation to oral squamous cell carcinoma. The chronic inflammatory nature of OLP creates an environment that may predispose to dysplastic changes and eventual malignant transformation. Studies demonstrate that patients with erythematous or erosive oral lichen planus have a markedly higher risk of developing oral squamous cell carcinoma compared to patients with other variants or the general population. Cancer surveillance is critical, as dysplastic lesions may be inadvertently diagnosed as "lichenoid mucositis with mild reactive epithelial atypia" when they may actually represent dysplasia with malignant potential. Patients with oral lichen planus should be followed up at least every 6 to 12 months to assess the disease activity, changes in symptoms, or detect early signs of malignancy. ==Epidemiology==

The overall estimated prevalence of lichen planus in worldwide population is in the range of 0.2% to 5%. It occurs more commonly in females, with a 3:2 ratio, and most cases are diagnosed between the ages of 30 and 60, but it can occur at any age. ==History==

Lichen planus was first described in 1869 by Erasmus Wilson as an inflammatory disorder with unknown etiology. Initially, the characteristic surface markings or striae were described by Weyl in 1885. In 1895, Wickham further explained the characteristic of the lesion, now known as Wickham striae. Further on, Darier explained the presence of such characteristic markings by correlating with an increased thickness of the granular cell layer. Fritz Williger published the first documented clinical case of malignant transformation of oral lichen planus in 1924. The coexistence of oral, cervical, and stomach lichen planus lesions was described by Guogerot and Burnier in 1937. A similar variant of mucosal lichen planus, the vulvovaginal-gingival syndrome, with erosive lesions involving oral and vulvovaginal mucosa were introduced by Pelisse and colleagues in 1982. The origin of the word is believed to be from the Greek word λειχήν (leikhḗn), originally 'liverwort', and the Latin word planus, 'flat, even'. == Research ==

Apremilast is undergoing investigation as a potential treatment. == Explanatory notes ==