Lichen planus is also known as lichen ruber planus. It is an inflammatory skin disease that can involve the skin, mucous membranes, nails and hair. The cause of this disease is unknown, and in recent years there have been more studies on its pathogenesis, and various theories have been proposed. The typical skin lesion is a purple-red or dark red cap pinhead to lentil-sized polygonal papule or plaque, which can fade on its own, mostly accompanied by obvious pruritus, with a certain predilection for sites, mostly in middle-aged people, and characteristic histopathological changes. There are some other skin lesions with different manifestations, which have histopathological changes of lichen planus, so they are classified as atypical lichen planus. The disease is similar to the “purpura” recorded in the literature of Chinese medicine.
Clinical manifestations
1, typical lichen planus This disease is mostly seen in adults, 30 to 60 years old is the age of prevalence, children and the elderly is rare, slightly more women than men. Typical lesions are purple-red or dark red, reddish-brown cap pinhead to lentil large polygonal flat papules, the border is clear, the surface is covered with a layer of thin, waxy luster of the adhesive scales (Figure 1, 2), sometimes can be seen in the center slightly concave, or there are small horn embolism, the surface of the papules have grayish-white spots and interlocking mesh streaks, called Wickham pattern, such as after wiping with liquid oil appears more clear. The lesions begin as red spots and form purplish papules after a few weeks. Sometimes they can develop and spread rapidly in a short period of time. The lesions may fuse with each other and appear as mossy patches of varying size and shape, surrounded by a scattered rash (Figures 3, 4), with a linear isomorphic reaction after scratching in the acute phase. The rash can occur all over the body, often symmetrically, with the flexors of the extremities, medial femur, N-fossa, buttocks and waist being the most common, and the neck is also frequently affected. Self-perceived pruritus varies in degree, even intense pruritus, and a few have no self-perceived symptoms. Mucous membranes can be involved, and about 60% to 70% of patients with lichen planus have oral lesions, which can occur at the same time as the lesions, or before or after the occurrence of the lesions, or some only have mucous membrane damage. Oral lesions may appear as creamy white spots, small isolated spots, arranged in rings, lines and irregular networks, or plaques, atrophy, papules, erosive ulcers and macules. Erosive ulcers are more common in older individuals and tend to cause pain and burning sensations. The buccal, gingival, and lingual mucosa are the most commonly affected areas. Damage occurring on the lips may have adhesive scales, very similar to the lip damage caused by lupus erythematosus. About 15% of male genitalia can be damaged, with the glans and penis being the most commonly affected areas, often showing ring-shaped damage. In women, the damage to the external genitalia resembles mucocutaneous leukoplakia and proliferative erythema, sometimes with erosions and occasionally manifesting as extensive desquamation vaginitis. Damage in lichen planus may have mucocutaneous leukoplakia, hyperkeratosis, fissures, and erosions. Nail involvement can account for 10-15% of lichen planus, with rare cases occurring only in the nail. Nail plate thinning, longitudinal ridges and distal fissures are the most common damages, and longitudinal nail fissures, hyperkeratosis under the nail and even loss of the nail plate are also seen. Disappearance of the nail can be caused by ulcerative lichen planus. Nail pterygium, an upward growth of the dorsal nail fold that fuses with the adjacent nail bed, is a characteristic manifestation of nail damage in lichen planus. Fingernails are more often involved than toenails, and lesions can occur simultaneously or sequentially. Scalp damage can also occur, as perifollicular erythema and hair follicle keratosis, one or more hair loss, or even permanent hair loss.
2, drug flat moss Drug-induced flat moss occurs after injection, contact and inhalation of a chemical substance. The lesions appear from a few months to a year after the drug, or longer, with the dose of the drug, individual sensitivity, exposure and the use of the drug. The time to resolution of the lesions varies, mostly from 3 to 4 months, and the resolution of mossy rash caused by gold agents may take up to 2 years after discontinuation of the drug. The rash can be typical or atypical for lichen planus, as localized or generalized eczema-like papules and plaques, irregularly polygonal, with post-inflammatory hyperpigmentation, alopecia and loss of the typical Wickham pattern, mostly on the trunk and extremities, with more symmetrical rashes. Mucosal involvement is less frequent.
The disease has a chronic course, lasting months to years, with most resolving spontaneously in 1 to 2 years. Oral damage can last for more than 20 years. After healing, temporary hyperpigmentation, hypopigmentation or atrophic scar remains.
3, atypical lichen planus The clinical manifestation of lichen planus varies, and there are many types according to its onset, rash form and different arrangements and other characteristics. List the common ones as follows.
(1) striped or linear flat moss (lichen planus liuearis): the lesions are arranged in lines of varying lengths, often distributed along the nerve segments or vascular paths, sometimes occurring at trauma or scratches, forming a homomorphic reaction. The lesions are mostly found on one side of the limbs, especially on the posterior side of the lower limbs, and sometimes extend up to the entire limb (Figure 5). It should be distinguished from linear moss, linear psoriasis and linear nevus.
(2) Lichen planus annularis: It accounts for about 10% of lichen planus. Most of the rashes are arranged in a ring shape, or the rashes are extended to the surrounding area, the edges are slightly elevated, the center is slightly depressed or atrophied, and the damage can be in a ring shape when there are many, commonly in the penis, glans (Figure 6), labia majora or oral mucosa. The damage that occurs on the trunk and extremities can be 2 to 3 cm in diameter, with an elevated periphery and hyperpigmentation, easily misdiagnosed as annular granuloma.
(3) warty flat moss (lichen planus verucosus): also known as hypertrophic flat moss (lichen planus hypretrophicus). The rash is wart-like in appearance, and can be mostly aggregated or hypertrophic plaques, similar to chronic hypertrophic psoriasis, the surface is covered with gray-black solid scales, surrounded by scattered polygonal flat papules, sweat holes and pores at the lesions are commonly covered with horn plugs, which are visible as depressions after removal. This type is mostly seen on the extensor side of the lower leg, but also on the extensor side of the upper limb, femur, wrist, neck, buttocks and trunk (Figure 7), and is more common in the elderly. After the damage fades, there is pigmentation and skin atrophy.
4, atrophic flat moss (lichen planus atrophicans) This type can be divided into primary and secondary types. The primary type is rare, the lesions are polygonal, with central atrophy, hair follicle mouth and sweat hole with horn bolus, hypopigmentation at the atrophy, forming pale white dots, which can be fused into large patches, commonly found on the extremities and trunk. This type should be distinguished from punctate leukoplakia (morphea guttate), atrophic sclerosing moss (lichen sclero-siset atrophicus). Secondary cases are most often seen during the regression of annular lichen planus or hypertrophic lichen planus. Histopathology shows that the epidermis and epidermal attachments are atrophied, cellular infiltration is small, and the infiltrative zone is not obvious.
5, flat moss (lichen planus bullous) This type is rare. It often appears small or large blisters on the primary papule, plaque or normal skin, and its size is consistent with the papule or plaque. The blisters may appear in the acute phase of lichen planus with moderate discomfort and may disappear within a few months. The lesions often occur on the lower extremities, and the oral mucosa may also be eroded with large blisters and be painful. There are typical histological changes of lichen planus. The clinical manifestations of blisters on normal skin are similar to those of pemphigus or herpes-like dermatitis, but have the typical histological appearance of lichen planus, with IgG, IgM, and C3 deposits in the basement membrane area by direct immunofluorescence examination at the blisters and circulating anti-basement membrane antibodies in serum. Most of them develop on the basis of acute generalized lichen planus. This type is rare and should be distinguished from aspergillosis.
6, follicular flat moss (lichen planus follcularis) is also called flat follicular moss (lichen planopilaris), mostly seen in adult women. Can be single in the hair follicle or with other flat moss skin and mucous membrane damage. The lesions are distinctive follicular papules and stud-like plaques, which may form atrophic scars with hair loss over time. In addition to the scalp, it is more common on the neck, scapula, chest and lateral extremities. Follicular lichen planus of the skin and/or scalp, scarring alopecia of the scalp and non-scarring alopecia of the axillae and pubic bone are known as the Graham-Little-Pic Cardi-Lassueur triad. In addition to the typical lichen planus histology, histopathology also reveals follicular keratosis with significant infiltration of the hair follicle roots. This type should be distinguished from follicular keratosis, tuberculous moss, and discoid lupus erythematosus.
7, photosensitive flat moss (lichen planus actinicus) also known as subtropical flat moss (lichen planussubsubtropicus). Tropical flat moss (lichen plinus tropicus), summertime actinic chenoid eruption, etc. This type is rare, mostly seen in children and young people, and is associated with sun exposure. It often occurs in Middle Eastern countries in the spring and summer. The lesions are found on the forehead, neck, arms, forearms, lower lip and upper chest, but also on mucous membranes and other parts of the body. In addition to the typical lichen planus lesions, pigmented or hypopigmented patches, or light brown and purple-blue round and oval patches with distinct boundaries, raised edges and depressed centers are also seen. Self-perceived symptoms are mild and may be slightly itchy in summer. It is thought to be a type of lichen planus, or the same disease as actinic granuloma. It should be distinguished from discoid lupus erythematosus and solar dermatitis.
8, palmoplantar flat moss (lichen planus of palms and soles) is less common. It occurs mostly on the edge of palmoplantar, asymmetric, and the lesions lack the characteristics of flat moss. It is a keratinized patch or plaque, hard, with significant surface keratinization and roughness, similar to callus or like punctate keratinization, without conscious symptoms. If there is lichen planus elsewhere on the body, it is easy to diagnose. If the disease occurs in the heel of the foot, large blisters can be formed, often due to frictional stimulation to form ulcers, called ulceratie lichen planus of the feet. Oral mucosa can also be involved at the same time, and finger (toe) nails can have permanent loss. It should be distinguished from callus, plantar warts, palmoplantar psoriasis.
9, acute or subacute lichen planus (acute or subacute lichen planus) This type of rapid onset, inflammation is obvious, the beginning of most red papules, and then the skin gradually changed to purple, fading can be gray-brown. It is often seen in batches and can involve a wide range of skin surfaces, the skin is red and swollen, and sometimes small or large blisters can appear. This type should be distinguished from lichen planus type drug rash.
10, other lichen planus Clinical manifestations of many forms, in addition to the above, there can also be rosacea (arranged like a rosary, mostly seen in the face, neck and other parts of the body); blunt head (rash large, few, flat or dome-shaped, mostly seen in the limbs); isolated (isolated, like pigmented nevus, mostly in the upper extremities) and so on.
Treatment methods
(I) Treatment
There are more treatment methods, but there is no particularly effective method yet. Except for the rare possibility of malignant transformation, it is basically benign and usually self-limiting, and most cases may heal themselves within 2 years. Therefore, when using a certain treatment, one should weigh the pros and cons and choose an appropriate method.
1.General treatment
Limit alcohol consumption and stimulating diet, regularize life, eliminate mental tension, treat chronic lesions, control scratching and avoid hot soap scalding, etc.
2.Internal treatment
(1) Corticosteroid: It is a more effective drug for the treatment of the disease, especially for acute generalized cases, which can make the lesions subside and reduce itching. The minimum effective dose applied is equivalent to 15-20mg/d of prednisone, and the dose is gradually reduced to stop after effective, and the duration of medication is about 3 months.
(2) Retinoic acid: It is reported that the treatment of lichen planus is effective with monoaromatic retinoic acid retinoic acid (etretinate) 75mg/d and the main metabolite of retinoic acid (etretinate) 20~50mg/d. Itchiness is generally reduced after 1 month of treatment, and the lesions are reduced in extent and infiltration is reduced after 2-3 months, and remission or effect is often seen after 4-6 months of treatment. The drug should be stopped when it is not effective for 1 month. The mechanism of action of retinoic acid in the treatment of lichen planus is not clear, but it may be related to its ability to inhibit epidermal hyperkeratosis and normalize atrophied or hyperkeratotic epithelial cells.
(3) Antihistamines: They can be applied to those who itch to reduce itchiness.
(4) Aminophenone: It is effective for skin and oral erosion type and herpetic lichen planus. The dosage is 50mg, taken orally, 2-3 times a day.
(5) Antibiotics: Isoniazid, penicillin, sulfamethoxazole, and sulfamethoxazole have been reported. azole/methoprene (cotrimoxazole) and metronidazole are effective in the treatment of lichen planus.
(6) ashwagandha: literature reports with ashwagandha for the treatment of lichen planus, the healing rate of 54.5% ~ 70%, the efficacy is related to the acute degree of lesions and the length of treatment. The dosage is 0.6~1.0g per day, the course of treatment is 2~3 months, and the course of treatment should be longer for those with nail damage, and the dosage can be reduced after 1 month or so. The mechanism of action is related to the anti mitotic effect of ashwagandha.
(7) Chloroquine or hydroxychloroquine: It is effective in the treatment of glossy lichen planus and lichen planus nail, and it is also effective in the treatment of herpetic lichen planus, red lichen planus, linear lichen planus and mucous membrane lichen planus. The dose is 250 mg twice daily, and after two weeks it is changed to 250 mg once daily for 1 to 3 months. Hydroxychloroquine, 200-400mg/d. Some authors observed the changes of serum interleukin 2 receptors before and after chloroquine treatment for oral lichen planus and the relationship with clinical symptom changes, and concluded that it is appropriate to treat oral lichen planus with chloroquine in a course of 30 days, and other methods can be used between 2 courses, which can control the symptoms of lichen planus and avoid the toxic side effects caused by long-term application of chloroquine.
(8) Immunomodulators: levamisole is effective in treating this disease, and it is more effective in treating generalized lichen planus and erythematous lichen planus, and transfer factor is effective in treating oral lichen planus.
(9) Phenytoin sodium: There are reports of treating 25 cases of lichen planus patients with phenytoin sodium 100-200mg per day, of which 15 cases were treated with the drug for 9-24 weeks and 10 cases were treated with the drug for 2-8 weeks, with the result that 14 cases were cured and 11 cases were effective. The mechanism of action may be related to its ability to inhibit cell-mediated immune abnormalities, reduce leukocyte wandering, anti-inflammatory, anti-collagenase and lysosomal enzyme activity.
(10) Immunosuppressants: For more severe and intractable lichen planus, azathioprine or cyclophosphamide 25-50mg twice a day can be tried. In recent years, there are some reports that the treatment of lichen planus with cyclosporine is effective, the dosage is 3-5mg/(kg?d), the course of treatment for 2 weeks, the lesions are obviously improved, but there are recurrences after stopping the drug. This drug is expensive, and can cause hypertension, renal insufficiency and other systemic side effects, so it should be used with caution.
3.Topical treatment
(1) The principle of topical medicine is to stop itching and anti-inflammation. A variety of corticosteroid emulsion or with 0.05% to 0.1% vitamin A acid cream, or a variety of tar preparations (such as black bean distillate, bran distillate, pine distillate, coal tar) and 5% salicylic acid, 1% to 2% carbolic acid, etc. formulated into ointment or mud paste for external use. For limited or hypertrophic people can be applied externally with 10%-20% salicylic acid fire cotton glue.
(2) In addition to gargling with hydrogen peroxide, compounded boric acid solution or chrysanthemum, double flower flush, external application of goose mouth dispersion, siping class dispersion, watermelon cream, Qing Dai dispersion, or compounded retinoic acid film can be used externally for oral erosion.
(3) A few isolated or hypertrophic and topical drugs are ineffective can be prednisolone acetate or dexamethasone plus an equal amount of 1% procaine hydrochloride injection subcutaneous injection at the lesion, 1 to 2 times a week, 4 times a course.
4.Physical therapy and surgical treatment
(1)Photochemotherapy (PUVA): It has been reported that the treatment of lichen planus with photochemotherapy is effective, clinical remission, histology also shows that the inflammatory cells in the lesions disappeared, and no recurrence was seen in those who were cured, so it is considered that there is no need to consolidate the efficacy with the maintenance amount after curing lichen planus with PUVA.
(2) laser: erythematous scaly damage can be used argon ion laser irradiation; warty proliferation, hypertrophic plaques and other damage can be used carbon dioxide laser cautery, oral erosion type lichen planus can also be used carbon dioxide laser treatment, but may recur.
(3) Surgical treatment: surgical excision is feasible for small-scale ulcerative damage or those with cancerous lesions.
Pathogenesis
So far there is no definite conclusion, there are autoimmune, infection, neuropsychiatric factors, the role of cytokines, family genetics and other theories. Drug factors, endocrine abnormalities, chronic lesions and other factors can also trigger the disease. It has been found that glucose-6-phosphate dehydrogenase (G-6-PD) may have structural abnormalities in the skin of patients with lichen planus, while others have the opposite opinion. In addition, there are changes in the activity of respiratory enzymes and coenzymes in the rash, and whether these abnormalities are the cause of lichen planus has not been determined.
Pathogenesis
In recent years, there have been more studies on the pathogenesis of the disease, and various theories have been proposed.
1, autoimmune lichen planus is accompanied by certain autoimmune diseases, and auxiliary cells such as Langerhans cells and keratinocytes are involved in these reactions, so that T cells activate, proliferate and move to the epidermis, and certain cytokines, lymphotoxins and cytotoxic T cells produced by them lead to the destruction and damage of basal cells, thus causing a series of pathological changes in lichen planus. Some experiments have shown the presence of elevated CD3 and CD8 cells and decreased CD4/CD8 in lichen planus, and a significant decrease in CD4/CD8 in pancytopenia. Some scholars have applied indirect immunofluorescence techniques to detect lichen planus-specific antigens (LPSA) in the epidermis of lesions of patients with oral lichen planus, and specific antibodies to LPSA have been detected in the blood. It has also been shown that patients with lichen planus have antinuclear antibodies specific for lichen planus, and the detection rate was found to vary depending on the substrate used, with the best substrate being rat esophageal epithelium, with a high detection rate in the mucosal erosion type.
In terms of humoral immunity, it was found that IgM values were low during the active phase of lichen planus or when the lesions had just faded, but normal in cases with old damage.
2, In recent years, it has been reported that the prevalence of hepatitis C virus (HCV) DNA in patients with lichen planus has increased, suggesting that HCV plays an important role in the pathogenesis of lichen planus. The presence of HCV and its replication in skin lesions still needs further study.
3.In some cases, the lesions improve or subside after the improvement or disappearance of psychoneurological symptoms, but some authors found no significant difference in the neuropsychiatric condition between patients and healthy individuals through controlled studies.
4.Many studies have shown that cytokines secreted by keratinocytes and activated T cells may play an important role in the formation of lichen planus, such as thymocyte activating factor (ETAF), T cell growth factor (KTGF), lymphocyte chemotactic factor (LCF) and IL-1, IL-3, etc. Activated T cells secrete IL-2, tumor necrosis factor (TNF)β and granulocyte-monocyte colony-stimulating factor (GMCSF), especially IFN-1, further promote lymphocytes to swim out and form infiltrates, and finally destroy basal cells and develop basal cell liquefaction degeneration. This process has the participation of multiple factors and forms a chain reaction, which finally causes the pathological changes of lichen planus.
5.There are reports of 10.7% of patients with a positive family history of lichen planus. Although the reports are not completely consistent, there are differences with normal controls, suggesting that the disease may be related to genetics.
6.The incubation period between the application of drugs and the onset of rash is long, averaging 1 year. There are two theories for the mechanism of occurrence: drug antigens bind to the epidermis and expose surface antigens on keratinocytes in the basal cell layer or induce their expression, thereby initiating an immune response; drugs may also directly affect immunoreactive cells and lead to the activation of T-lymphocyte clones.
Differential diagnosis
Atypical cases should be differentiated from the following diseases.
1, neurodermatitis Mostly located in the neck, significant mossiness, no polygonal umbilical fossa papules, often consistent with skin color, no Wickham lines, not complicated by oral and nail damage.
2, skin amyloidosis lesions mostly occur in the bilateral anterior shin, slightly flat papules dense moss-like changes, the surface is rough and lusterless, gray-brown or consistent with the skin color, no Wickham lines, Congo red test negative.
3, psoriasis Infiltration is significant, there are multiple layers of silvery-white scales, peeling the base can be seen dotted bleeding, no Wickham pattern.
4, drug rash Many drugs can cause lichen planus-like rash, but drug rash rapid onset, the site is extensive, there is a clear history of drug use, easy to cure after discontinuation of drugs.
5.Hair red furunculosis There are dry and hard cornified papules consistent with hair follicles, the back of the fingers (toes) and buttocks, etc. more prominent, often accompanied by palmoplantar hyperkeratosis, finger (toe) nails are often involved.
6.Other oral mucosal damage should be distinguished from mucosal white spots. The latter is a pre-cancerous lesion, the plaque is relatively hard, clear boundary, uniform surface color, often divided into most small pieces, interspersed with red fine lines, can be secondary to cancer. It may be related to smoking and is mostly seen in middle-aged men. Vesicular and maculopapular cases should be differentiated from common aspergillosis and erythema multiforme, and histopathological examination can confirm the diagnosis.
Examination methods
Histopathology: Typical pathological changes are: hyperkeratosis; focal thickening of the granular layer; irregular thickening of the spinous layer; liquefied degeneration of the basal cells; banded inflammatory cell infiltration in the superficial dermis. Moderate thickening of the stratum corneum and incomplete keratinization were rare. The granular layer was irregularly thickened, and the granulosa cells in the thickened areas were larger than normal and contained coarser, more abundant keratin. The spinous layer is irregularly thickened and the epidermal protrusions are irregularly prolonged, with some of the lower ends becoming pointed and serrated. The dense inflammatory cells in the superficial dermis infiltrate and infiltrate between the basal cells of the epidermis, causing liquefaction and degeneration of the basal cells, making the boundary between epidermis and dermis unclear. The infiltrating cells in the superficial layer of the dermis were distributed in a band, and the infiltrating band was clearly defined at the lower edge. The infiltrating cells were mainly lymphocytes, with a small number of histiocytes and pigmentophilic cells in between. In the lower part of the epidermis and upper part of the dermis, gelatinous vesicles were seen. Fissures were sometimes seen between the epidermis and dermis, and blisters could be formed when the fissures increased. Lymphocytes in the advanced infiltrate are reduced or even not banded, and histiocytes and fibroblasts are increased.
Complications
Acute or subacute lichen planus may develop secondary to erythrodermatitis.
Prognosis
The disease is chronic and lasts for months to years, with most resolving spontaneously in 1 to 2 years. Oral damage can last more than 20 years. After healing, temporary hyperpigmentation, hypopigmentation or atrophic scarring remains.