Human chronic inflammatory disease
Medical condition
Lichen planus (LP) is a chronic inflammatory and autoimmune disease that affects the skin, nails, hair, and mucous membranes. It is not an actual lichen, but is named for its appearance. It is characterized by polygonal, flat-topped, violaceous papules and plaques with overlying, reticulated, fine white scale (Wickham's striae), commonly affecting dorsal hands, flexural wrists and forearms, trunk, anterior lower legs and oral mucosa. The hue may be gray-brown in people with darker skin. Although there is a broad clinical range of LP manifestations, the skin and oral cavity remain as the major sites of involvement. The cause is unknown, but it is thought to be the result of an autoimmune process with an unknown initial trigger. There is no cure, but many different medications and procedures have been used in efforts to control the symptoms.
The term lichenoid reaction (lichenoid eruption or lichenoid lesion) refers to a lesion of similar or identical histopathologic and clinical appearance to lichen planus (i.e., an area which resembles lichen planus, both to the naked eye and under a microscope). Sometimes dental materials or certain medications can cause lichenoid reactions. They can also occur in association with graft versus host disease.
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Classification.
"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.
Pattern.
Lichen planus lesions can occur in many different forms or morphologies:
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.
'Ring-shaped' lesions that develop gradually from single small pigmented spots into circular groups of papules with clear, unaffected skin in the center. The ring-like lesions may very slowly enlarge, co-join and morph into larger irregular (serpentine) bands, sometimes accompanied by lines (See Linear, below). Annular CLP is uncommon and classically involves the male genitalia (glans penis and penile shaft), groin, axilla and also the extremities.
 Papules are arranged in a line (the "Blaschko line"). This pattern may develop secondary to trauma (koebnerization) or, uncommonly, as a spontaneous, isolated eruption, usually on the extremities, and rarely on the face.
 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. This form is also known as "lichen planus verrucosus".
 This morphology is characterized by the presence of a few well-demarcated, white-bluish papules or plaques with central superficial atrophy. Atrophic CLP is the clinical endpoint of chronic annular or hypertrophic LP with atrophic lesions. The use of potent topical corticosteroids for a long-term may predispose the patient to developing atrophic lesions.
 This morphology is characterized by the development of vesicles and bullae with the skin lesions. This is a rare variant of lichen planus, and also known as "vesiculobullous lichen planus".
 Rare form presenting as nummular patches or plaques with a hypopigmented halo surrounding a hyperpigmented center. Actinic CLP is more prevalent in African Americans, Indians, and Middle-Eastern individuals and commonly affects the sun-exposed areas.
 This morphology is characterized by chronic, painful bullae and ulceration of the feet, often with cicatricial sequelae evident. This is a rare variant of lichen planus.
 This morphology is characterized by hyperpigmented, dark-brown macules in sun-exposed areas and flexural folds. This is a rare variant of lichen planus.
 Characterized by follicular, flat, elevated or hemispherical erythematous papules with or without keratoses presenting in groups or disseminated. The Graham‐Little‐Piccardi‐Lasseur syndrome, seen in a familial pattern and also predominantly in women, is characterized by the appearance of follicular LP on the trunk with LP follicularis decalvans on the scalp. Follicular LP on the scalp is more likely to lead to scarring alopecia.
 Characterized by extensive erythematous lesions with poorly defined borders and in part with lichenification. Inverse LP typically affects the axillae, inguinal creases, limb flexures and submammary region. Pigmentation of the individual lesions at these inverse locations are typical. Additionally, keratotic papules and erosions with a bizarre configuration can occur.
Overlap syndromes.
Occasionally, lichen planus is known to occur with other conditions. For example:
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. This rash, after regressing, is likely to leave an area of hyperpigmentation that slowly fades. That said, a variety of other lesions can also occur.
Skin.
Variants of cutaneous lichen planus are distinguished based upon the appearance of the lesions and/or their distribution. Lesions can affect the:
Other variants may include:
Mucous membranes.
Lichen planus affecting mucosal surfaces may have one lesion or be multifocal. Examples of lichen planus affecting mucosal surfaces include:
Mouth.
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:
 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.
 The second most common form and the most advanced form of oral lichen planus, is characterised by oral ulcers presenting with persistent, irregular areas of redness, ulcerations and erosions covered with a yellow slough. This can occur in one or more areas of the mouth. In 25% of people with erosive oral lichen planus, the gums are involved, described as desquamative gingivitis (a condition not unique to lichen planus). This may be the initial or only sign of the condition. Involvement of the dorsum of the tongue might cause an altered sense of taste (dysgeusia).
 This form is characterized by small white pinpoint papules that are asymptomatic. Hence, they can be easily missed during a routine checkup. It is referred to as the initial and transient phase of OLP.
 Large, homogenous white patches are characteristic of this form which may resemble leukoplakia. This form is more prevalent in tobacco smokers.
 This form is a common presentation that has similarities to the erosive form. It has a more prominent atrophic lesion on a background of erythema with radiating white striae at the margins. Atrophic oral lichen planus may also manifest as desquamative gingivitis.
 Rare form of OLP characterized by fluid-filled vesicles ranging in size from 1 to 2 mm to several cm in diameter. The vesicles or bullae appear white or gray-purple in color and are fluctuant. The fluid in the vesicles are usually clear but may be hemorrhagic or purulent upon secondary infection. These rupture easily and they leave an ulcerated, painful surface.
These types often coexist in the same individual. Oral lichen planus (OLP) tends to present bilaterally as mostly white lesions on the inner cheek, although any mucosal site in the mouth may be involved. Other sites, in decreasing order of frequency, may include the tongue, lips, gingivae, floor of the mouth, and very rarely, the palate.
Generally, oral lichen planus tends not to cause any discomfort or pain, although some people may experience soreness when eating or drinking acidic or spicy foodstuffs or beverages. When symptoms arise, they are most commonly associated with the atrophic and ulcerative subtypes. These symptoms can include a burning sensation to severe pain. They may also experience mucosal bleeding in response to mild trauma, such as toothbrushing. Additionally, the Koebner phenomenon (the development of new lesions at sites of trauma) is not only present in cutaneous lichen planus (CLP) but can also occur in the setting of OLP.
Residual postinflammatory hyperpigmentation has been reported in association with OLP, manifesting as brown to black pigmentation on the oral mucosa and may most likely occur in dark-skinned individuals.
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 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 in support of autoimmunity by expanding in vitro T cells isolated from the skin lesions of two patients, followed by testing the ability of these T cells to kill autologous keratinocytes (cytotoxicity).
Several potential triggers of oral LP have been proposed over the years, mainly
Pathogenesis.
Oral LP is considered to be 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:
Antigens presented on MHC 1 molecules activates CD8+ T cells on keratinocytes or by encounters with activated CD4+ helper T cells or cytokines produced by activated CD4+ helper T cells
Activated CD8+ T cells induce keratinocyte apoptosis through various mechanisms such as secretion of tumor necrosis factor (TNF)-alpha, secretion of granzyme B, or Fas-Fas ligand interactions. Chemokines are produced by activated CD8+ T cells that attract additional inflammatory cells, thereby promoting continued inflammation.
Other mechanisms that have been proposed include:
Oral LP may also be caused by genetic factor which influence 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 need to be taken to diagnose lichen planus. Patients with suspected cutaneous lichen planus need to 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 entire cutaneous surface including the scalp, oral cavity and external genitalia need to be included. Wickham's striae often can be 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:
A full examination that includes the evaluation of the mucosal and cutaneous surfaces, including the vulva, vagina, penis, scalp, and nails should be performed. Thorough examination may lead to the detection of extraoral manifestations of LP that provide additional support for the diagnosis or the identification of clinical findings that suggest another diagnosis.
Tissue biopsies of oral LP help to confirm the diagnosis and are particularly of value for erythematous