Bubble form of red flat lichen as a cause of alopecia

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

The bubbly form of red flat lichen (PFCF) refers to rare forms of dermatosis (2-4% of all cases of this disease). Women are more often affected after the age of 50; Bubbles usually occur with rapid exacerbation of red flat lichen, accompanied by increased itching and are a stage of different duration in the development of this dermatosis.

Symptoms

On the surface of typical papules and plaques, less often - near them, tense small and large bubbles appear with serous or serous-bloody contents. More often they arise in a small amount; A thick tire allows the bubbles to not be opened for a long time. On the periphery of the bullous elements that appeared on the papules and plaques, there is an infiltration zone, which is characteristic for the papular elements of the red lichen planus. Usually, the rashes polymorphic, widespread and resemble the bubble elements of different sizes, you can see typical papules of red flat lichen on the skin, the mucous membrane of the mouth, sometimes on the genitals. In the course of the evolution of the cavitary elements, sometimes erosive and ulcerative lesions are formed on the skin, serous and hemorrhagic crusts. In some cases, they remain pigmented atrophy sites or foci resembling an antedoderm. Rarely, the bladder rashes occur isolated on the shins, feet, mucous membranes of the mouth, scalp, etc. Sometimes they prevail in clinical manifestations, which greatly complicates the diagnosis of this rare form of red flat lichen. When localized bullous elements on the scalp develop foci of atrophic alopecia, or the condition of the pseudo-phelala. According to some authors, more than 40 patients with manifestation of a vesicidal or erosive form of red flat lichen are affected by the scalp. We seem to be overestimating this percentage. The combination of bullous eruptions, typical papules of red flat lichen and pseudo-pelvis is, as a rule, the manifestation of the same disease. The blistering form of the red flattened diarrhea can be observed with toxemia 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 by immunoelectron microscopy and immunofluorescence. With the bullous form of the red flat lichen rash usually short-term, the appearance of blisters on typical lesions or next to them is due to the pronounced vacuolar degeneration of the basal layer cells. Subepidermal blisters are combined with changes characteristic of red flat lichen. Direct and indirect immunofluorescence is negative.

With the pemphigoid form of red flat lichen, there is a tendency to acute emergence and rapid generalization of typical rashes, followed by sudden large bubbles on the affected and healthy skin. Sometimes blisters can appear only on the foci of a typical red flat lichen. When the pemphigoid form of this dermatosis is histologically detected subepidermal bladder, but without the characteristic signs of red flat lichen.

Immunological research

With direct immunofluorescence on the cryostat sections of the affected and surrounding skin of the skin, a linear deposition in the region of the basement membrane of immunoglobulin G and C3 of the complement fraction is observed. This leads to the formation of a large bladder, as with a bullous pemphigoid. In immuno-electronomycroscopy, the same immunoglobulin G and C-3 complement are deposited at the base of the bladder, but not in its cover, as in the bullous pemphigoid. This is due to the fact that with the pemphigoid form of the red flat lichen the basal membrane is not cleaved and therefore the deposition of the immunoglobulin G and C-3 complement is traced only at the base of the bladder, which is not characteristic for the bullous pemphigoid.

With immunoblotting, antigens with a molecular weight of 180 kD and 200 kD were found, which are analogous to basal membrane antigens with a bullous pemphigoid. Based on this, individual dermatologists suggest a possible combination of red flat lichen and bullous pemphigoid in patients with pemphigoid form of red flat lichen. According to other studies, the basal membrane antigens with pemphigoid form of this dermatosis and bullous pemphigoid are different. Thus, a single opinion on this issue has not yet been formed; additional research is required.

Histopathology

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

Diagnostics

The bubbly form of the red flat lichen is differentiated from dermatoses, in which the vesicle is a bladder: vulgar pemphigus, bullous pemphigoid, multiforme exudative erythema, pemphigoid form of sclerotrophic lichen, herpetiform dermatosis, bullous toxemia. The presence, along with large and small bubbles, of typical polygonal papules, the inflammatory zone of the infiltrate around the periphery of individual blisters, the absence of symptoms of the marginal detachment of the epidermis, the absence of pemphigus acantholytic cells in smear-prints and the typical histological changes in red flat lichen usually make it possible to establish the correct diagnosis. Diagnostic difficulties can occur with rare isolated bullous manifestations, not accompanied by typical elements of red flat lichen.

[1], [2], [3]

Treatment

Atrophic forms of red flat lichen are rare species of dermatosis and usually occur chronically, recurring for a number of years. When localization on the scalp, there are foci of atrophic alopecia, or the condition of the pseudo-phelala. These forms often prove to be resistant to therapy, therefore, 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 history of the disease, pay attention to the possible connection of the beginning or exacerbated dermatosis with medication. In recent years, numerous data have accumulated, which confirm the possibility of rashes, resembling red lichen planus or identical to it, caused by taking 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 red flat lichen. Therefore, it is advisable first of all to exclude drugs, after which there is an exacerbation of dermatosis - an increase in itching, the appearance of fresh lichenoid, and sometimes bulezed rashes. The efficacy of many drugs recommended for the treatment of patients with red planus is not critically evaluated and not proven in comparative studies. This is especially true for antibiotics with a wide spectrum of action, griseofulvin, ftivazidu, vitamins of groups A, B, D, E, PP, immunomodulators, etc. The difficulty of evaluation and effectiveness lies in the fact that in most cases the usual form of red lichen regresses independently in the next one or two years. You can not also exclude the influence of suggestion on the involution of dermatosis. With common, atypical, long-lasting forms of red flat lichen, which include follicular and atrophic varieties, the drugs listed above usually do not have a distinct therapeutic effect. More often than not, the use of 4-aminoquinoline derivatives (hingamine, deligil, rheochin or plakvenil), glucocorticosteroid hormones, retinoids (neotigazone or roaccutane) and PUVA therapy with simultaneous administration of the photosensitizer is justified. In some patients with a significant prevalence of manifestations of red flat lichen and resistance to the above drugs can be applied cyclophosphamide or cyclosporin-A (sandimmun-neoral), providing immunosuppressive effect. These drugs can cause a prolonged remission of the disease in those cases when the therapy with glucocorticosteroid hormones was ineffective or it was impossible to conduct it. As an auxiliary means of treatment, courses of antihistaminic drugs with anticholinergic action (hydroxycin, or atarax) or blocking adrenergic receptors (promethazine, or diprazine) are also used.

In the treatment of patients with follicular form of red flat lichen, 4-aminoquinoline derivatives, combined therapy with chloroquine with small doses of glucocorticosteroid hormone (usually prednisolone or methylprednisolone) and retinoids are preferred. Patients with an atrophic form of red flat lichen are assigned a derivative of 4-aminoquinoline, small doses of a steroid hormone or a combination thereof. With the bullous form of dermatosis, the fastest therapeutic effect is usually given by the average doses of glucocorticosteroid hormone.

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

Contraindications for the administration of aminoquinoline drugs are. Impaired liver or kidney function, pregnancy and lactation period, cardiovascular damage with heart rhythm disturbance, blood system disease and leukopenia, severe diabetes mellitus, hypersensitivity to the drug. Before the treatment with aminoquinoline derivatives, the clinical analysis of blood and urine should be examined, the liver enzymes (aspartate aminotransferase-AST and alanine aminotransferase-ALT) determined, the urea, creatinine and bilirubin levels in the patient's blood should be normal. The initial examination of the ophthalmologist is also important. During treatment, the hemogram should be monitored monthly, once every three months - liver enzymes, once in 4-6 months - the state of the organ of vision.

There are different schemes for the use of aminoquinoline derivatives. Use course or continuous treatment. Thus, chloroquine diphosphate (hingamin, delagil, resohin) or hydroxychloroquine sulfate (plaquenyl is often prescribed courses of 7-10 days for 1 tablet (0.25 or 0.2) 2 times a day after meals with intermissions between them in 3-5 days, if necessary, 3-5 courses of therapy (60-100 tablets) .In continuous treatment, one of the aminoquinoline derivatives is prescribed daily for 1 (or 2) tablets for 1-2 months. During treatment with drugs of amino, quinoline from the side of the nervous system, the gastrointestinal tract peripheral blood, heart muscle, eyesight and skin, sleep disturbances, tinnitus, headache, dizziness, convulsive seizures, psychoses, there are rarely manifestations resembling malignant myasthenia gravis but with less pronounced muscular weakness. The administration of aminoquinoline drugs may impair liver function, nausea, vomiting, abdominal pain.Ophthalmic disorders may manifest as a decrease in visual acuity, doubling of objects, irreversible retinopathy. More often in the first 3 months of treatment, leukopenia develops. Dystrophic changes in the myocardium with a violation of the heart rhythm (changes in the ECG, T-wave) are possible. Possible photosensitivity of the skin, bluish pigmentation of the face, palate, front surfaces of the legs, nail bed. Redheads sometimes have a grayish hair color on the head, in the chin and eyebrows. Rarely, the development of toxicermidia, manifested by lichenoid or urticaria rashes, is even more rare - toxic epidermal necrolysis; possibly exacerbation of psoriasis.

Atrophic forms of red flat lichen do not pose a danger to the life of patients. The developing state of the pseudo-pancake is only a cosmetic defect. In this regard, in the spectrum of therapeutic effects, glucocorticosteroids, despite high efficiency, should not be used as first-choice drugs. Yes, with a significant spread of rashes, in addition to pseudo-phelps, the importance of patients with medium and high doses of GKSG is unjustified. Prolonged use of them 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 gradual cancellation. Glucocorticosteroid hormones exert anti-inflammatory immunosuppressive and antiproliferative action on the skin. They have a pronounced vasoconstrictor effect, reduce the synthesis of prostaglandins, inhibit the migration of neutrophils to the focus of inflammation and their ability to phagocytosis, inhibit 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 number of circulating monocytes, inhibition of T-lymphocyte and macrophage function, inhibition of the formation of immune complexes and complement. Corticosteroids inhibit the synthesis of deoxyribonucleic acid in the skin, have an anti-anabolic and atrophogenic effect.

Contraindication to the appointment of steroid hormones are: peptic ulcer and duodenal ulcer, esophagitis, hyperacid gastritis, diabetes mellitus, acute psychosis, Itzenko-Cushing syndrome, infectious lesions of the skin or internal organs (pyoderma, abscesses, osteomyelitis, thrombophlebitis, herpes simplex and zoster, fungal diseases, tuberculosis, cholecystitis, pyelonephritis, etc.), hypertension, dysmenorrhea, the presence of cataracts, pancreatitis, obesity, severe dystrophic changes in the heart and condition after myocardial infarction rda, osteoporosis. With prolonged use of corticosteroids by children, growth, ossification, and delay in puberty can be disturbed.

In the 1980s, "Presocil" was widely used in dermatological practice, one tablet containing 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 a glucocorticosteroid hormone is well tolerated by patients with red lichen planus and enhances the therapeutic effect of each of the drugs. The combination of corticosteroids with acetylsalicylic acid was superfluous, since their simultaneous use so lowers the level of acetylsalicylic acid in the blood that its concentration is lower than 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. Assign 1 tablet of chloroquine diphosphate (hingamine, deligil, resoquine) daily for 5-6 weeks with 1 tablet of prednisolone (0.005 g) in the morning after eating for 2 weeks, then 1/2 tablets of prednisolone in the morning also 2 weeks and 1/4 tablets - 2 more weeks. The suggested dosage of chloroquine Diphosphate and prednisolone corresponds to 6 Presocil tablets. Usually, this mode of taking medications does not cause complications. An even more sparing scheme of combined treatment is also possible, when chloroquine diphosphate is prescribed by courses of 1 tablet daily for 7-10 days with interruptions between cycles of 3-5 days on the background of continuous intake of prednisolone at a dosage of 0.005 (1 table), which is gradually reduced half every 2 weeks (1 / 2-1 / 4-0). After the abolition of this combination treatment, it is advisable to prescribe glycyram 2 tablets 3-4 times a day for 30 minutes before meals for 2-4 weeks (1 tablet contains 0.05 g of monosubstituted ammonium salt of glycyrrhizinic acid isolated from licorice nude roots). Glitsiram has a moderate stimulating effect on the adrenal cortex and therefore has some anti-inflammatory effect. Glitsira is contraindicated in cases of organic damage to the heart, impaired liver and kidney function.

Synthetic derivatives of vitamin A (aromatic retinoids are used in a common follicular red lachrymus with scalp lesions.) Acitretin (neotigazone), isotretino (roaccutane, 13-cis retinoic acid) and etretinate (tigazone) have an antiseratotic effect, most pronounced in severe hyperkeratosis as one of the manifestations of dermatosis.This is associated with a decrease in the adhesion between the horn cells.Retinoids also inhibit the proliferation of cells, especially in the thorny layer of the epidermis, delay growth tumors, stimulate the synthesis of collagen and increase the production of glycosoaminoglycans, have an anti-inflammatory effect.In contrast to other retinoids, isotretinoin (roacutane) reduces the size of the sebaceous gland and suppresses their secretion, suppresses hyperkeratosis mainly inside the hair follicle and chemotaxis of neutrophils.Preferred to the use of retinoids are pregnancy , lactation, impaired liver or kidney function, elevated levels of triglycerides and cholesterol in the blood, inflammatory diseases udochno tract (gastritis, peptic ulcer disease, cholecystitis, colitis, etc.), obesity, diabetes, heavy, hypervitaminosis A, the simultaneous use of tetracyclines, Nizoral or methotrexate, hypersensitivity to the drug. Retinoids have a teratogenic (not mutagenic) effect, so young women can be prescribed only according to strictly defined indications after explaining to the patient the effects on the fetus (dysmorphic syndrome) and the need to prevent pregnancy during and after treatment.

Treatment is started on the 2nd-3rd day of the next menstruation and spend the next 4 weeks of the cycle. In addition to contraception, a pregnancy test is conducted. When treatment with etretinate (tigazone) or acitretin (neotigazone), it is necessary to prevent pregnancy from at least 2 years after their withdrawal. This is due to the fact that in the treatment of acitretin, there is a danger of the appearance in the blood serum of not only acitretin, but also etretinate. Therefore, the duration of the necessary contraception should be the same as in the treatment with etretinate. The cancellation of isotretinoin (roaccutane) should be prevented from pregnancy at least 1-2 months.

Acitretin (neotigazone) is an active metabolite of etretinate (tigazone) and has the same indications and contraindications. In recent years, he has ousted from the clinical practice of etretinate, since it is significantly more rapidly excreted from the body and not cumulated 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, adding 10 mg per week to a maximum of 50-75 mg in day.

The initial dose of isotretinoin (roacutane) is determined from the calculation of 0.5 mg of the drug per 1 kg of body weight. Initiate treatment usually with a small dose (20 mg, 10 mg × 2 times a day during meals), then it is gradually increased to obtain a pronounced clinical effect (with a maximum amount of the drug per day 40-60-70 mg). After 4 weeks of treatment, the patient is transferred to a maintenance dose of isotretinoin, calculated on 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 cancellation, the drug continues for 4-5 months.

Etretinat (tigazon) - the first drug from the group of aromatic retinoids, introduced into clinical practice in 1975; Currently, it is rarely used in connection with the synthesis of its active metabolite - acitretin (neotigazone), which is not cumulated in tissues and less often leads to undesirable phenomena. Treatment with etretinate begins with 10-25 mg daily in capsules and gradually weekly dose increases 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 approximately twice (from the calculation of 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 the treatment with retinoids, it is necessary to check the blood levels of total cholesterol and triglycerides, alanine aminotransferase GALT and aspartate aminotransferase (ACT), alkaline phosphatase, and examine the hemogram. With an increase in excess of the norm of any of these biochemical parameters, or with the appearance of neutropenia, thrombocytopenia, anemia, an increase in ESR, a break in treatment should be made until these parameters are normalized. Patients with diseases that are a risk factor in the treatment with retinoids, it is necessary to reduce the daily dose, recommend the appropriate diet (for obesity), prohibit the use of alcohol (to make the patients understand the necessity of refusing alcohol!). Along with retinoids, vitamin A and tetracyclines should not be administered. When there are signs of increased intracranial pressure (headaches, visual impairment, numbness of the extremities, etc.), retinoids should be discarded.

When treating retinoids, contact lenses should not be used. Taking for many weeks isotretinoin can sometimes lead to hirsutism and thinning of the hair. The undesirable effect of retinas is very diverse and essentially corresponds to the manifestations of hypovitaminosis A. In the past, almost every patient has vasculitis and dry mucous membranes of the mouth, nose, and eyes. Possible scarlatine-like detachment of the stratum corneum on the palms and soles, scaling, thinning of the skin and its increased vulnerability, sometimes - itching, paronychia, blepharoconjunctivitis, nosebleeds. With the cessation of treatment, these phenomena quickly pass.

After a long reception of retinoids, hair loss can be increased, the growth and structure of the nails of the plates may change (dystrophy, onycholysis). Rarely, skin pigmentation, hair growth, and cracking can also occur. Often observed pain in the muscles and joints. After long-term administration of large doses of retinoids, hyperostosis, osteoporosis, bone thinning, calcification of tendons and ligaments (calcifications in the tendons) are described. These similar actions of retinoids develop rarely, are unpredictable and after the interruption of treatment slowly disappear. In children, premature ossification of the epiphyseal bones was observed. Therefore, radiologic control of the spinal column, long tubular bones, joints of the hands and feet is advisable. There are changes in the hemogram: anemia, neutropenia, thrombocytopenia, increased ESR. The risk of complications in the treatment with retinoids depends on the dose of the drug, the duration of its administration and the type of concomitant pathology. In patients who have risk factors (obesity, diabetes, alcoholism, liver damage, lipid metabolism disorder, etc.), the possibility of complications is much higher. It should strive to appoint not so much low doses of retinoids, as far as clinical results permit.

Many authors report a high effectiveness of PUVA therapy in patients with common manifestations of red flat lichen, resistant to other methods of treatment. However, photochemotherapy is not safe and has a number of contraindications. The main of them are serious violations of liver and kidney function, pregnancy, diabetes, thyrotoxicosis, hypertension, tuberculosis, epilepsy, photodermatosis, suspected tumor disease (excluding skin lymphoma), etc. Treatment is carried out by courses during the exacerbation of dermatosis, a combination with topical glucocorticosteroids increases the effectiveness of photochemotherapy.

For limited lesions, glucocorticosteroids can be applied topically in the form of an ointment, cream, or intramuscular administration of a crystalline suspension (eg, Kenalog-40 diluted in 3-5 ml of lidocaine solution, once every 15-30 days). The best effect is obtained from topical steroids with medium and high activity. It should be noted that the amount of steroid absorbed from the surface of the scalp is 4 times greater than from the surface of 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 the foci, where there are active manifestations of dermatosis. To achieve the cessation of an increase in the area of the pseudo-peloid can be a combination of general and external treatment.