Lichen Planus

Etiology

Lichen planus is an idiopathic disease whose pathogenesis is not fully understood; however, it appears to represent a T-cell–mediated autoimmune disease. The prevailing theory is that exposure to an exogenous agent such as a virus, drug, or contact allergen alters epidermal self-antigens, leading to the activation of cytotoxic T cells. The altered self-antigens cross-react with normal self-antigens on basal keratinocytes, resulting in T-cell targeting and apoptosis.[6]

Various agents have been linked to the development of lichen planus, with particular emphasis on the association with viruses, especially the hepatitis C virus (HCV). Patients with lichen planus are 5 times more likely to test positive for HCV compared to the general population, and those with HCV seropositivity are 2.5 to 4.5 times more likely to develop lichen planus.[7][8] Recently, lichen planus has also been linked with the COVID-19 virus and its vaccine.[9]

Oral lichen planus is correlated with contact allergies to various metals found in dental restorations, including mercury, copper, and gold. Removal of the sensitizing metal has been reported to lead to the clearance of lichen planus lesions.[10][11]

A large number of drugs are associated with lichen planus; however, the recurrence of lesions after re-exposure to the drug is rare. More commonly associated drugs include antimalarials, angiotensin-converting enzyme inhibitors, thiazide diuretics, nonsteroidal anti-inflammatory drugs, quinidine, beta-blockers, tumor necrosis factor-α inhibitors, and gold.[5][12]

Epidemiology

The prevalence of cutaneous lichen planus is approximately 0.2% to 1% among adults worldwide.[13] Oral lichen planus is more common and reported in 1% to 4% of the population. Overall, women are more frequently affected compared to men at a ratio of 1.5:1, and most cases develop between the ages of 30 and 60. The condition is rare in children, representing less than 5% of all affected patients.[7] Although lichen planus is not generally considered to have an ethnic predilection, recent studies suggest a higher incidence of the disease in African Americans and individuals of Indian and Arabian descent.[14][15] There appears to be a familial component, as up to 10% of first-degree relatives of patients may also develop the disease.[16]

Pathophysiology

Multiple mechanisms explain the pathophysiology of lichen planus. Current understanding suggests that the immunopathogenesis of lichen planus is caused by cell-mediated cytotoxicity, particularly cytotoxic T lymphocytes, whose activity is further influenced by T_H1 and the interleukin 23/T_H17 axis. Other immunocytes and inflammatory pathways complement these mechanisms.[17]

Histopathology

Skin biopsy and microscopic analysis are valuable in confirming the diagnosis in atypical and severe cases, as the histopathologic features are generally the same regardless of the distribution or subtype. Principal findings include thickening of the stratum corneum without nuclei (hyperkeratosis without parakeratosis), irregular thickening of the stratum granulosum, destruction of the stratum basale, alteration or loss of rete ridges resulting in a sawtooth appearance, and a dense band of lymphocytes infiltrating the dermis along the dermo-epidermal junction (interface dermatitis). In addition, idiopathic lichen planus rarely demonstrates eosinophils, whereas drug-induced lichen planus may show eosinophils.

Apoptotic keratinocytes are often observed near the basal layer and are termed colloid or Civatte bodies. Direct immunofluorescence staining may display colloid bodies with irregular deposits of immunoglobulin A (IgA), IgM, IgG, or C3.[18][19]

History and Physical

Lichen planus can display various lesion types, but the most common presentation is an area of polygon-shaped, itchy, violaceous, flat-topped papules a few millimeters wide. This classic presentation is known as the 6 Ps of lichen planus—purple, polygonal, planar, pruritic, papules, and plaques (see Image. Lichen Planus). The lesions have a shiny surface covered in fine white lines known as Wickham striae and are firm on palpation. These lesions may appear as a few individual lesions, scattered widely, grouped in plaques, or arranged in annular, linear, or actinic (sun-exposed) patterns. The isomorphic response, known as the Koebner phenomenon, can occur in lichen planus, wherein new lesions arise in lines where scratching occurs, similar to what is observed in psoriasis. The most common areas of involvement include the flexor wrists, dorsal hands, lower back, ankles, and shins. Frequently, grayish-brown hyperpigmentation can be found after lesions resolve due to the deposition of melanin in the superficial dermis.[7][13]

Various subtypes of lichen planus exist that display patterns different from the classic presentation. Hypertrophic lichen planus is often found on the shins and ankles and is characterized by red, red-brown, or yellow-grey papules and plaques that coalesce with a thickened or verrucous surface. Ulcerative lichen planus is found on the soles of the feet or between the toes, with painful, erosive lesions that complicate walking (see Image. Lichen Planus, Palms). Bullous lichen planus often appears on the legs as small to large tense blisters filled with clear or pale-yellow fluid. Lichen planus pemphigoids display features of lichen planus with the development of bullae both on top of lichen planus lesions and on unaltered skin. Lichen planus pigmentosus is characterized by the development of macular or papular pigmented lesions often arranged in a linear, follicular, or Blashkoid pattern. Inverse lichen planus is similar to inverse psoriasis as it is found in skin folds and loses its typical appearance. Extensive erythematous lesions with lichenification and without distinct borders are observed in the axillae, limb flexures, inguinal creases, and beneath the breasts.[20]

Mucosal involvement affects over half of all patients with lichen planus and frequently is the sole presenting sign, most commonly observed in the mouth, but it can also be found on the lips, esophagus, glans penis, vulva, or vagina. Six subtypes of oral lichen planus exist—reticular, erosive, papular, plaque-like, atrophic, and bullous. Reticular is the most common form and presents as asymptomatic white, lacy lines often observed on the bilateral buccal mucosa (see Image. Oral Lichen Planus). The erosive and atrophic forms are commonly associated with a burning pain exacerbated by hot or spicy foods. Lesions can easily be mistaken for leukoplakia or candidiasis on the tongue or buccal mucosa. Esophageal lichen planus predominantly affects women and can give rise to dysphagia, strictures, and possibly squamous cell carcinoma.[10][21][22]

When lichen planus affects the glans penis, it commonly displays an annular configuration (see Image. Lichen Planus, Penis). In contrast, an erosive variant is most frequently found in women when lichen planus involves the vulva or vagina, and scarring and strictures are troublesome sequelae that may occur. Lichen planus found simultaneously on the female genital and oral mucosa is termed vulvovaginal-gingival syndrome. This severe, desquamative subtype has been associated with the HLA-DQB1*02:01 gene in 80% of patients, suggesting a genetic predilection for its development.[23][24]

Lichen planus of the nails occurs in approximately 10% of patients, typically affecting multiple nails without necessarily involving the surrounding skin.[25] Early signs include thinning of the nail plate and longitudinal ridging. Continued involvement leads to scarring of the nail matrix, dorsal pterygium formation, sandpaper nails (trachonychia), and possibly complete loss of the nail plate. Some patients may exhibit a variant of lichen planus called 20-nail dystrophy, where these findings are the only presenting sign of disease on all 20 nails. This subtype is much more common in children compared to adults.[26][27]

Lichen planus of the scalp and other hair-bearing regions is called lichen planopilaris (LPP). Small red follicular papules and macules appear at the site of inflammation, leading to progressive scarring alopecia. LPP may appear alone or with typical lichen planus lesions elsewhere on the body. When LPP occurs principally on the anterior scalp and eyebrows in older women, it is known as frontal fibrosing alopecia. A familial variant of LPP known as Graham-Little-Piccardi-Lasseur syndrome is characterized by scarring alopecia of the scalp, typical cutaneous or mucosal lichen planus, and nonscarring loss of pubic and axillary hairs with follicular papules.[28][29]

Lichenoid drug eruptions often appear in sun-exposed areas rather than appearing in the classic lichen planus sites. These eruptions are typically symmetric and are more generalized in distribution. Lesions may resemble eczematous or psoriasiform conditions, and Wickham striae are not commonly observed. There is typically a latent period of several months to a year from the initiation of a drug to an eruption of lesions. Hence, a thorough review of medication history is crucial for diagnosing drug-induced lichen planus.[5]

Evaluation

Evaluating lichen planus involves a comprehensive clinical assessment to accurately diagnose the condition and distinguish it from similar dermatological disorders. While in the clinic, dermoscopy allows visualization of Wickham striae in most cases. The classic finding is a network of white lines with red globules along the periphery.[30] Oral lichen planus lesions located near dental restorations should prompt patch testing to determine whether an allergy to one of the associated metals exists.[31]

A biopsy with microscopic analysis is the most effective tool for confirming the presence of lichen planus. The lesions display distinct features, as noted previously, that typically facilitate a definitive diagnosis. Incorporating direct immunofluorescence into histology can help differentiate lichen planus from other similar conditions, such as lupus erythematosus.[32]

Treatment / Management

Cutaneous lichen planus typically resolves spontaneously within 1 to 2 years; therefore, treatment is aimed at reducing pruritus and allowing time for resolution. For limited lichen planus, the recommended first-line treatment is superpotent topical steroids (clobetasol 0.05%) twice daily for 2 to 4 weeks. Inadequate response to topical steroids may be augmented with intralesional steroid injections (triamcinolone 5 to 10 mg/mL). For diffuse lichen planus, the first-line treatment is daily oral corticosteroids (prednisone 30 to 60 mg) tapered over 2 to 6 weeks.

If no change is observed, second-line therapy should be considered. Second-line therapy may include metronidazole (500 mg twice daily for 3 to 8 weeks), sulfasalazine (500 mg twice daily increased in 500 mg increments every 3 days until 2.5 g daily is reached, for 3 to 6 weeks), isotretinoin (10 mg twice daily for 2 months), acitretin (30 mg daily for 8 weeks), psoralen and ultraviolet A, ultraviolet B, topical calcineurin inhibitors, or methotrexate (15 mg per week for adults, 0.25 mg/kg per week for children). Third-line treatment may include trimethoprim-sulfamethoxazole, griseofulvin, terbinafine, antimalarials, tetracyclines, ciclosporin, mycophenolate mofetil, azathioprine, etanercept, adalimumab, or low-molecular-weight heparin.[7][33](A1)

Oral lichen planus may spontaneously resolve within 5 years, but many cases are chronic and do not resolve. Treatment-induced remission is typically followed by relapse. Thus, asymptomatic oral lichen planus should not be treated due to the high burden of adverse effects associated with treatment. The goal of treating symptomatic oral lichen planus is to heal erosive lesions, reduce pain, and allow normal food intake. Patients should be instructed to avoid spicy or acidic foods, alcohol, and tobacco, as these exacerbate symptoms. First-line treatment involves applying a very high-potency topical steroid 3 times daily until remission. If there is no improvement after 6 weeks, treatment should be escalated. The second-line treatment includes oral corticosteroids or the application of topical calcineurin inhibitors. Third-line treatment may include cyclosporine, azathioprine, mycophenolate mofetil, or methotrexate.[10][34](A1)

Consideration of drug-induced lichen planus must always be explored before starting therapy. Withdrawal of the suspected drug leading to the gradual disappearance of lesions confirms the diagnosis, although it may take some time for lesions to resolve fully.[35](B3)

Differential Diagnosis

Given that lichen planus may result from various exogenous agents such as viruses, drugs, or contact allergens, care should be taken to identify and treat any underlying causes before diagnosing idiopathic lichen planus. Various diseases that may resemble lichen planus include lupus erythematosus, erythema dyschromicum perstans, psoriasis, secondary syphilis, pityriasis rosea, lichen nitidus, graft-versus-host disease, and keratosis lichenoides chronica. Hypertrophic lichen planus can appear very similar to lichen simplex chronicus. Vulvar lichen planus can be difficult to distinguish from lichen sclerosis.

Differentiating between lichen planus and lupus erythematosus is challenging when lesions are only present on the scalp or in the mouth; therefore, biopsy with direct immunofluorescence is especially useful in these cases. The simultaneous presence of both diseases has been described in many reports, possibly related to the use of antimalarials in treating lupus erythematosus.[32][36]

Prognosis

Cutaneous lichen planus often resolves spontaneously within 1 to 2 years, but residual hyperpigmentation is common. Oral lichen planus may resolve spontaneously within 5 years, but typically, it is a chronic disease with a remitting and relapsing course. Hair loss from LPP is permanent. Drug-induced lichen planus lesions resolve slowly after the causative medication is withdrawn.

Complications

Lichen planus can lead to several complications, especially when it becomes chronic or involves mucosal surfaces. The condition can cause painful erosive lesions in the oral cavity, increasing the risk of secondary infections and possibly malignant transformation into oral squamous cell carcinoma. Genital involvement may result in scarring and strictures, whereas skin lesions can cause post-inflammatory hyperpigmentation. Nail involvement can lead to permanent nail loss or dystrophy. In severe cases, patients may experience significant discomfort, affecting their quality of life. Long-term care should include careful monitoring for malignant transformation and effective symptom management.[37]