The bullous form of red squamous lichen planus as causes of alopecia areata

Vesicular form of lichen planus (Lichen ruber pemphigoides, Kaposi M. 1892; lichen bullosus haemorrhagicus, Straus W.1933)

Vesicular form of lichen planus (VFL) is a rare form of dermatosis (2-4% of all cases of this disease). Women over 50 are most often affected; blisters usually occur during a violent exacerbation of lichen planus, are accompanied by increased itching and are a stage of varying duration in the development of this dermatosis.

Symptoms

On the surface of typical papules and plaques, less often - next to them, tense small and large blisters with serous or serous-bloody contents appear. More often they appear in small quantities; a thick cover allows the blisters not to open for a long time. Along the periphery of bullous elements that have arisen on papules and plaques, there is an infiltrate zone, which is characteristic of papular elements of lichen planus. Usually the rash is polymorphic, widespread and resembles vesicular elements of different sizes, typical papules of lichen planus are visible on the skin, oral mucosa, and sometimes on the genitals. In the process of evolution of cystic elements on the skin, erosive and ulcerative lesions, serous and hemorrhagic crusts sometimes form. In some cases, pigmented areas of atrophy or foci resembling anetoderma remain in them. Quite rarely, bullous rashes occur isolated on the shins, feet, oral mucosa, scalp, etc. Sometimes they predominate in clinical manifestations, which significantly complicates the diagnosis of this rare form of lichen planus. When bullous elements are localized on the scalp, foci of atrophic alopecia, or pseudopelade, develop. According to some authors, more than 40 patients with the manifestation of bullous or erosive forms of lichen planus have scalp lesions. We believe this percentage to be clearly overstated. The combination of bullous rashes, typical papules of lichen planus and pseudopelade is, as a rule, a manifestation of the same disease. The bullous form of lichen planus can be observed in toxicodermia or paraneoplasia.

Some foreign dermatologists distinguish between bullous and pemphigoid forms of this dermatosis. Until recently, they were distinguished clinically and histologically, and in recent years - also using immunoelectron microscopy and immunofluorescence. In the bullous form of lichen planus, the rash is usually short-term, the appearance of blisters on typical lesions or near them is due to pronounced vacuolar degeneration of basal layer cells. Subepidermal blisters are combined with changes characteristic of lichen planus. Direct and indirect immunofluorescence are negative.

In the pemphigoid form of lichen planus, there is a tendency for the typical rash to develop acutely and quickly generalize, followed by large blisters suddenly appearing on the affected and healthy skin. Sometimes blisters may appear only on the typical lichen planus lesions. In the pemphigoid form of this dermatosis, a subepidermal blister is found histologically, but without the characteristic signs of lichen planus.

Immunological studies

Direct immunofluorescence on cryostat sections of the affected skin and the skin surrounding the lesion reveals linear deposition of immunoglobulin G and complement fraction C3 in the basement membrane zone. This leads to the formation of a large blister, as in bullous pemphigoid. Immunoelectromicroscopy reveals deposition of the same immunoglobulin G and complement fraction C3 at the base of the blister, but not in its cap, as in bullous pemphigoid. This occurs because the basement membrane does not split in the pemphigoid form of lichen planus, and therefore deposition of immunoglobulin G and complement fraction C3 is only seen at the base of the blister, which is not typical for bullous pemphigoid.

Immunoblotting revealed antigens with a molecular weight of 180 kD and 200 kD, which are similar to the basement membrane antigens in bullous pemphigoid. Based on this, some dermatologists suggest a possible combination of lichen planus and bullous pemphigoid in patients with the pemphigoid form of lichen planus. According to other studies, the basement membrane antigens in the pemphigoid form of this dermatosis and bullous pemphigoid differ. Thus, a unified opinion on this issue has not yet been formed; additional research is required.

Histopathology

The bullous form of lichen planus is characterized by the formation of subepidermal cracks or a fairly large cavity and pronounced vacuolar degeneration of the cells of the basal layer. In the dermis, there are changes characteristic of the typical or atrophic form of lichen planus: a strip-like, more often perivascular infiltrate of lymphocytes with an admixture of a large number of histiocytes. The cellular infiltrate is closely adjacent to the epidermis and has a sharp strip-like lower border. In old rashes, atrophic manifestations are expressed in the epidermis, its outgrowths are smoothed out, although hyperkeratosis and granulosis are almost always present. The infiltrate in the dermis is less dense, the number of histiocytes and fibroblasts increases, the connective tissue becomes sclerotic.

Diagnostics

The vesicular form of lichen planus is differentiated from dermatoses in which the rash element is a blister: vulgar pemphigus, bullous pemphigoid, multiform exudative erythema, pemphigoid form of lichen sclerosus, herpetiform dermatosis, bullous toxicoderma. The presence, along with large and small blisters, of typical polygonal papules, an inflammatory zone of infiltration along the periphery of individual blisters, the absence of symptoms of marginal epidermal detachment, the absence of acantholytic pemphigus cells in smears-imprints and histological changes typical of lichen planus usually allow establishing the correct diagnosis. Diagnostic difficulties may arise in rare isolated bullous manifestations that are not accompanied by typical elements of lichen planus.

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Treatment

Atrophic forms of lichen planus are rare varieties of dermatosis and usually occur chronically, recurring over a number of years. When localized on the scalp, foci of atrophic alopecia, or pseudopelade, occur. These forms are often resistant to therapy, so repeated courses of treatment are often required.

A patient with developing atrophic alopecia should be examined to verify the diagnosis. It is important to carefully study the anamnesis of the disease, pay attention to the possible connection of the onset or exacerbation of the dermatosis with the intake of medications. In recent years, numerous data have accumulated that confirm the possibility of the appearance of rashes resembling or identical to lichen planus, caused by the intake of a number of medications. These include beta-blockers, furosemide, acyclovir, tetracyclines, isoniazid, chlorpropamide and many others, including antimalarial drugs, which are often prescribed to patients for the treatment of lichen planus. Therefore, it is advisable to first of all exclude drugs that cause an exacerbation of the dermatosis - increased itching, the appearance of fresh lichenoid, and sometimes bullous rashes. The effectiveness of many drugs recommended for the treatment of patients with lichen planus has not been critically assessed and has not been proven in comparative studies. This applies primarily to broad-spectrum antibiotics, griseofulvin, phthivazid, vitamins of groups A, B, D, E, PP, immunomodulators, etc. The difficulty in assessing and assessing the effectiveness is that in most cases the common form of lichen planus regresses on its own within the next one to two years. The influence of suggestion on the involution of the dermatosis cannot be ruled out either. In widespread, atypical, long-term forms of lichen planus, which include its follicular and atrophic varieties, the above-mentioned drugs usually do not have a clear therapeutic effect. More often than others, the use of 4-aminoquinoline derivatives (hingamine, delagyl, resoquine or plaquenil), glucocorticosteroid hormones, retinoids (neotigazone or roaccutane) and PUVA therapy with simultaneous oral administration of a photosensitizer justifies expectations. In individual patients with significant prevalence of lichen planus manifestations and resistance to the above-mentioned drugs, cyclophosphamide or cyclosporin-A (sandimmune-neoral), which have an immunosuppressive effect, can be used. These drugs can cause long-term remission of the disease in cases where glucocorticosteroid hormone therapy was ineffective or impossible to administer. Courses of antihistamines with anticholinergic action (hydroxycin or atarax) or blocking adrenergic receptors (promethazine or diprazine) are also used as adjuvant treatment.

In the treatment of patients with the follicular form of lichen planus, preference is given to derivatives of 4-aminoquinoline, combined therapy with chloroquine and low doses of glucocorticosteroid hormone (usually prednisolone or methylprednisolone) and retinoids. Patients with the atrophic form of lichen planus are prescribed a derivative of 4-aminoquinoline, low doses of steroid hormone or their combination. In the bullous form of dermatosis, medium doses of glucocorticosteroid hormone usually have a rapid therapeutic effect.

When choosing a method of treating a patient with a certain form of lichen planus, the doctor must carefully weigh the real benefit and possible harm of the upcoming therapy. The prescription of aminoquinoline derivatives is based on their moderate immunosuppressive effect, the ability to inhibit the synthesis of nucleic acids, prostaglandins and leukocyte chemotaxis, and stabilize lysosome membranes.

Contraindications for prescribing aminoquinoline preparations are: impaired liver or kidney function, pregnancy and lactation, cardiovascular disease with heart rhythm disturbances, blood system disease and leukopenia, severe diabetes mellitus, hypersensitivity to the drug. Before treatment with aminoquinoline derivatives, it is necessary to examine a clinical blood and urine test, determine liver enzymes (aspartate aminotransferase-AST and alanine aminotransferase-ALT), make sure that the patient's blood urea, creatinine and bilirubin levels are normal. An initial examination by an ophthalmologist is also important. During treatment, a hemogram should be monitored monthly, liver enzymes once every three months, and the condition of the organ of vision once every 4-6 months.

There are different schemes for the use of aminoquinoline derivatives. They use course or continuous treatment. Thus, chloroquine diphosphate (hingamin, delagyl, resoquin) or hydroxychloroquine sulfate (plaquenil) are often prescribed in courses of 7-10 days, 1 tablet (0.25 or 0.2) 2 times a day after meals with breaks between them of 3-5 days. If necessary, 3-5 courses of therapy (60-100 tablets) are carried out. With continuous treatment, one of the aminoquinoline derivatives is prescribed daily at 1 (or 2) tablets for 1-2 months. The doctor must take into account possible undesirable consequences that arise during treatment with amino, quinoline drugs from the nervous system, gastrointestinal tract, peripheral blood composition, heart muscle, visual organ and skin. Sleep disorders, tinnitus, headache, dizziness, seizures, psychosis are possible, manifestations resembling malignant myasthenia are rarely observed, but with less severe muscle weakness. Long-term use of aminoquinoline preparations may cause liver dysfunction, nausea, vomiting, and abdominal pain. Ophthalmologic disorders may include decreased visual acuity, double vision, and irreversible retinopathy. Leukopenia most often develops during the first 3 months of treatment. Dystrophic changes in the myocardium with abnormal heart rhythms (changes in ECG, T-waves) are possible. Photosensitivity of the skin, bluish pigmentation of the face, palate, anterior surfaces of the shins, and nail beds are possible. Redheads may sometimes develop a grayish coloration of the hair on the head, chin, and eyebrows. Rarely, toxicoderma may develop, manifested by lichenoid or urticarial rashes, and even more rarely, toxic epidermal necrolysis; exacerbation of psoriasis is also possible.

Atrophic forms of lichen planus do not pose a danger to the life of patients. The developing condition of pseudopelade is only a cosmetic defect. In this regard, in the spectrum of therapeutic effects, glucocorticosteroids, despite their high efficiency, should not be used as first-choice drugs. Yes, with a significant spread of rashes, in addition to pseudopelade, the importance of medium and high doses of GCS for patients is unjustified. Their long-term use brings more harm to patients than good. In some cases, in the absence of contraindications, low doses of steroid hormones can be prescribed for 4-6 weeks with their gradual withdrawal. Glucocorticosteroid hormones have an anti-inflammatory immunosuppressive and antiproliferative effect on the skin. They have a pronounced vasoconstrictive effect, reduce the synthesis of prostaglandins, inhibit the migration of neutrophils to the site of inflammation and their ability to phagocytosis, suppress the activity of fibroblasts, which can lead to the limitation of sclerotic processes in the skin. Their immunosuppressive effect is manifested by: suppression of T-lymphocytes responsible for cellular reactions, a decrease in their number and the number of circulating monocytes, inhibition of the function of T-lymphocytes and macrophages, suppression of the formation of immune complexes and complement. Corticosteroids suppress the synthesis of deoxyribonucleic acid in the skin, have an antianabolic and atrophogenic effect.

Contraindications to the use of steroid hormones are: gastric ulcer and duodenal ulcer, esophagitis, hyperacid gastritis, diabetes mellitus, acute psychosis, Itsenko-Cushing syndrome, infectious lesions of the skin or internal organs (pyoderma, abscesses, osteomyelitis, thrombophlebitis, herpes simplex and herpes zoster, fungal diseases, tuberculosis, cholecystitis, pyelonephritis, etc.), hypertension, dysmenorrhea, cataracts, pancreatitis, obesity, severe degenerative changes in the heart and the condition after myocardial infarction, osteoporosis. With prolonged use of corticosteroids in children, growth disorders, ossification processes, and delayed puberty are possible.

In the 1980s, Presocil became widespread in dermatological practice. Each tablet contains 0.04 g of delagil, 0.75 mg of prednisolone, and 0.2 g of acetylsalicylic acid. The combination of an antimalarial drug with small doses of glucocorticosteroid hormone is well tolerated by patients with lichen planus and enhances the therapeutic effect of each drug. The combination of corticosteroids with acetylsalicylic acid turned out to be unnecessary, since their simultaneous use lowers the level of acetylsalicylic acid in the blood so much that its concentration is below the therapeutic one. If necessary and in the absence of contraindications, it is advisable to carry out combined treatment with chloroquine diphosphate (or hydroxychloroquine sulfate) and prednisolone (or methylprednisolone) according to the following scheme. Prescribe 1 tablet of chloroquine diphosphate (hingamin, delagyl, resoquin) daily for 5-6 weeks with 1 tablet of prednisolone (0.005 g) in the morning after meals for 2 weeks, then 1/2 tablet of prednisolone in the morning for 2 weeks and 1/4 tablet for another 2 weeks. The proposed dosage of chloroquine diphosphate and prednisolone corresponds to 6 tablets of Presocil. Usually, such a regimen of taking the drugs does not cause complications. An even more gentle scheme of combined treatment is also possible, when chloroquine diphosphate is prescribed in courses of 1 tablet daily for 7-10 days with breaks between cycles of 3-5 days against the background of continuous intake of prednisolone at a dosage of 0.005 (1 tablet), which is gradually reduced by half every 2 weeks (1/2-1/4-0). After discontinuing such combined treatment, it is advisable to prescribe glycyram 2 tablets 3-4 times a day 30 minutes before meals for 2-4 weeks (1 tablet contains 0.05 g of monosubstituted ammonium salt of glycyrrhizic acid, isolated from the roots of naked licorice). Glycyram has a moderate stimulating effect on the adrenal cortex and therefore has some anti-inflammatory action. Glycyram is contraindicated in organic heart disease, liver and kidney dysfunction.

Synthetic derivatives of vitamin A (aromatic retinoids) are used for widespread follicular lichen ruber with lesions of the scalp. Acitretin (neotigazone), isotretinoin (roaccutane, 13-cis-retinoic acid) and etretinate (tigazone) have an antikeratotic effect, most noticeable in severe hyperkeratosis as one of the manifestations of dermatosis. This is due to a decrease in the adhesion between the horny cells. Retinoids also inhibit cell proliferation, especially in the spinous layer of the epidermis, delay tumor growth, stimulate collagen synthesis and increase the production of glycosaminoglycans, and have an anti-inflammatory effect. Unlike other retinoids, isotretinoin (roaccutane) reduces the size of the sebaceous glands and suppresses their secretion, suppresses hyperkeratosis mainly inside the hair follicle and chemotaxis neutrophils. Contraindications to the use of retinoids are pregnancy, lactation, impaired liver or kidney function, elevated levels of triglycerides and cholesterol in the blood, inflammatory diseases of the gastrointestinal tract (gastritis, peptic ulcer, cholecystitis, colitis, etc.), obesity, severe diabetes mellitus, hypervitaminosis A, concomitant use of tetracyclines, nizoral or methotrexate, hypersensitivity to the drug. Retinoids have a teratogenic (non-mutagenic) effect, so they can be prescribed to young women only for strictly defined indications after explaining to the patient the consequences of the effect on the fetus (dysmorphia syndrome) and the need to prevent pregnancy during and after treatment.

Treatment begins on the 2nd-3rd day of the next menstruation and continues for the next 4 weeks of the cycle. In addition to contraception, a pregnancy test is performed. When treating with etretinate (tigazone) or acitretin (neotigazone), it is necessary to protect yourself from pregnancy for at least 2 years after their withdrawal. This is due to the fact that when treating with acitretin, there is a risk of the appearance of not only acitretin, but also etretinate in the blood serum. Therefore, the duration of the necessary contraception should be the same as when treating with etretinate. After discontinuing isotretinoin (roaccutane), it is necessary to protect yourself from pregnancy for at least 1-2 months.

Acitretin (neotigazone) is an active metabolite of etretinate (tigazone) and has the same indications and contraindications. In recent years, it has replaced etretinate in clinical practice, as it is excreted from the body much faster and does not accumulate in tissues. The initial dose of acitretin in adults is 20-30 mg (in capsules of 10 and 20 mg) for 2-4 weeks, then, if necessary, the dose can be gradually increased by adding 10 mg per week to the maximum - 50-75 mg per day.

The initial dose of isotretinoin (Roaccutane) is determined at a rate of 0.5 mg of the drug per 1 kg of body weight. Treatment usually begins with a small dose (20 mg; 10 mg × 2 times a day during meals), then it is gradually increased until a pronounced clinical effect is achieved (with a maximum daily dose of 40-60-70 mg of the drug). After 4 weeks of treatment, the patient is transferred to a maintenance dose of isotretinoin, calculated at 0.1-0.3 mg of the drug per 1 kg of body weight. The total duration of treatment usually does not exceed 12-16 weeks. After discontinuation, the effect of the drug continues for another 4-5 months.

Etretinate (tigazone) is the first drug from the aromatic retinoid group, introduced into clinical practice in 1975; it is currently rarely used due to the synthesis of its active metabolite, acitretin (neotigazone), which does not accumulate in tissues and less often leads to undesirable effects. Treatment with etretinate begins with 10-25 mg daily in capsules and is gradually increased weekly to the maximum, based on the calculation of 1 mg of the drug per kg of body weight, but not more than 75 mg per day. After achieving a clinical effect, it is recommended to reduce the daily dose of etretinate by about half (based on 0.3-0.5 mg / kg of body weight). It is also possible to immediately begin treatment with low daily doses of the drug (0.5 mg / kg).

During treatment with retinoids, it is necessary to check the blood levels of total cholesterol and triglycerides, alanine aminotransferase (GALT) and aspartate aminotransferase (AST), alkaline phosphatase, and examine the hemogram every month. If any of these biochemical parameters increase above the norm or if neutropenia, thrombocytopenia, anemia, or increased ESR occur, a break in treatment should be taken until these parameters return to normal. Patients with diseases that are a risk factor for treatment with retinoids should have their daily dose reduced, be advised an appropriate diet (in case of obesity), and be prohibited from drinking alcohol (make the patient understand the need to give up alcohol!). Vitamin A and tetracyclines should not be prescribed simultaneously with retinoids. If signs of increased intracranial pressure appear (headaches, visual impairment, numbness of the extremities, etc.), retinoids should be discontinued.

Contact lenses should not be used when treating with retinoids. Taking isotretinoin for many weeks can sometimes lead to hirsutism and thinning hair. The undesirable effects of retinoids are very diverse and essentially correspond to the manifestations of hypovitaminosis A. Vasculitis and dryness of the mucous membrane of the mouth, nose, and eyes appear first in almost every patient. Scarlet fever-like exfoliation of the stratum corneum on the palms and soles, peeling, thinning of the skin and its increased vulnerability are possible, sometimes - itching, paronychia, blepharoconjunctivitis, nosebleeds. When treatment is stopped, these phenomena quickly pass.

After long-term use of retinoids, increased hair loss, changes in the growth and structure of the nail plates (dystrophy, onycholysis) are possible. Rarely, changes in skin pigmentation, hair growth rate, and cracks may also occur. Muscle and joint pain has often been observed. After long-term use of high doses of retinoids, hyperostosis, osteoporosis, thinning of bones, calcification of tendons and ligaments (calcifications in tendons) have been described. These similar effects of retinoids develop rarely, are unpredictable, and slowly disappear after interruption of treatment. Premature ossification of the epiphyseal bones has been observed in children. Therefore, X-ray monitoring of the spinal column, long tubular bones, and joints of the hands and feet is advisable. Changes in the hemogram are possible: anemia, neutropenia, thrombocytopenia, increased ESR. The risk of complications during treatment with retinoids depends on the dose of the drug, the duration of its use, and the type of concomitant pathology. In patients with risk factors (obesity, diabetes, alcoholism, liver damage, lipid metabolism disorders, etc.), the possibility of complications is significantly higher. It is necessary to try to prescribe not so low doses of retinoid as clinical results allow.

Many authors report high efficiency of PUVA therapy in patients with widespread manifestations of lichen planus resistant to other treatment methods. However, photochemotherapy is not safe and has a number of contraindications. The main ones are serious liver and kidney dysfunction, pregnancy, diabetes mellitus, thyrotoxicosis, hypertension, tuberculosis, epilepsy, photodermatoses, suspected tumor disease (excluding skin lymphomas), etc. Treatment is carried out in courses during the period of exacerbation of dermatosis, a combination with topical glucocorticosteroids increases the efficiency of photochemotherapy.

Glucocorticosteroids in the form of ointments, creams or intralesional injection of a crystalline suspension (e.g. Kenalog-40 diluted in 3-5 ml of lidocaine solution once every 15-30 days) can be applied externally to limited lesions. The best effect is achieved with topical steroids of medium and high activity. It should be taken into account that the amount of steroid absorbed from the scalp is 4 times greater than from the forearm. Steroid ointments should not be applied to areas where atrophic alopecia has already formed. It is advisable to apply them to the peripheral zone of lesions where there are active manifestations of dermatosis. The increase in the pseudopelade area can be stopped by combining general and external treatment.