Before the era of corticosteroids, mortality of patients with vulgar ulcer disease was observed in 60-90% of cases. Therapy should be initiated at the dermatological hospital after a thorough clinical examination of the patient and verify the diagnosis (biopsy – n orazhennoy skin, immunological studies). It is especially important to find out the state of the gastrointestinal tract, the presence of chronic foci of infection and other associated diseases.
Therapeutic tactics and dose range is determined by the nature and activity of the pathological process. The basic principle is to achieve the maximum effect with minimum doses, given that the use of inadequate doses increases the duration of treatment and the likelihood of side effects.
Allocate substitution, pharmacodynamic and suppressive therapy. Pharmacodynamic therapy is divided into systemic and local. In general therapeutic practice, there are three types of pharmacodynamic therapy:
- Intensive, in some cases, “pulse therapy”, when ultra-high doses of HA are administered once or for several days (for prednisolone, more than 20–30 mg / kg per day).
- Limited – when average doses of corticosteroids are used for several weeks or months ( for prednisone – from 25 to 250 mg per day).
- Long – with the appointment for months or years of low doses of corticosteroids (for prednisone a – from 2.5 to 10 mg per day).
- The main form of therapy is long-term continuous, with the division of the daily dose into several doses.
In the treatment there are 3 stages:
1. Appointment of “shock” daily doses of corticosteroids at the beginning of treatment, which achieve optimal results usually within 3-6 weeks (cessation of the formation of new blisters, complete epithelialization of erosions on the skin. The initial dose of corticosteroids should be adequately high, most of which is administered orally. The purpose of the initial dose is mainly related to the experience of clinicians, since there are no objective criteria for their magnitude.
2. A gradual slow reduction of the daily dose of corticosteroids to maintenance (the duration of the stage is about 4 months ).
3. Prolonged (lifelong) outpatient treatment of a patient with maintenance doses of a glucocorticosteroid hormone with careful follow-up. The duration of treatment is determined individually (usually given lifelong therapy).
The duration of the use of shock doses of glucocorticosteroids and the tactics of their reduction are extremely important in the treatment of patients with pemphigus.
Most authors are unanimous that the initial adequate “shock” dose of corticosteroids should remain unchanged until complete epithelialization of erosion on the skin. Preservation of small erosions on the mucous membrane of the oral cavity is not an obstacle to the beginning of a decrease in the daily dose of the drug, since in this location epithelialization usually occurs much slower.
The most commonly used combination is the oral route of administration with parenteral administration of drugs. On average, treatment at stage I lasts from 3 to 6 weeks.
The decrease in the daily dose of corticosteroids begins on average by 13% from the initial “loading” dose in the first week of reduction, by 10% from the remaining daily dose – in the second week, by 8% – in the third week. Further reduction of corticosteroids is carried out very slowly (on average, 5 mg of prednisone in seven to ten days) to a maintenance dose. The maintenance dose of corticosteroids is considered the minimum dose that inhibits the formation of blisters in a particular patient.
This dose is “ regulated ” by the doctor according to specific clinical data – until a fresh bladder or erosion appears. In each patient, the maintenance dose of corticosteroids is individual and usually ranges from about 20 mg of prednisone per day. Unfortunately, there are no strict objective criteria to help determine this dose.
Only the amount of autoantibody titers to desmosomal proteins in the blood of patients allows, to some extent, to orient in the adequacy of therapy.
Stage II treatment of corticosteroids usually lasts about 4 months. Therefore, by lowering the daily dose of prednisone to below 50 mg, patients are usually transferred to a dispensary treatment, where they “ titrate ” a maintenance dose. On an outpatient basis, extremely slowly and carefully reduce the daily dose of prednisone (1/2 or even 1/4 tablet and 10-15 days).
The success of treatment depends on the daily dose of the drugs and the timing of the start of treatment. According to the unanimous opinion, treatment of patients with pemphigus should be started with shock doses of corticosteroids, better than prednisone or prednisone. The literature discusses the size of shock doses of corticosteroids. In the US, doses from 150 mg to 150 360 mg of prednisone.
According to the data of domestic dermatologists, these doses can lead to the development of side effects more quickly and significantly complicate the treatment of patients. The dose of corticosteroids is selected taking into account the prevalence of lesions, but it should not be less than 1 mg/kg/day. In case of serious condition of the patient, higher doses of corticosteroids are prescribed – up to 200 mg / day and higher.
Oral administration of high doses of corticosteroids can be partially replaced by parenteral administration or administration of prolonged forms of the drug ( no more than 1 time in 7-10 days). According to the results of a study of leading dermatological clinics in our country, the dose of prednisone 120 mg per day in most cases is an adequate loading dose, which allows you to stop the formation of blisters and speed up the epithelialization of erosion.
If during the week it is not possible to suppress the formation of blisters, the daily dose of prednisolone is increased by 1/3, and if necessary it can be doubled. Therapy should begin as early as possible in the development of the disease.
Currently, there is a large arsenal of tablets of synthetic corticosteroids (prednisolone, prednisone, metnlpredpizolon, ftors about – holding medications – triamcinolone and its analogues – kenakort, polkortolon;. Derivatives betamstazona (tseleston) They were more effective in the treatment of patients, than an equivalent dose of soluble, since it is longer but not excreted.
Prednisone is recognized by many scientists as a drug of choice. Prednisolone is more effective in patients with vulgar vesicular than seborrheic and exfoliative.
In appointing glucocorticoid therapy, it must be remembered that the effectiveness of treatment increases if the daily dose of the hormone is distributed in accordance with the physiological rhythm of secretion of hormones by the adrenal cortex. The use of CC in a continuous pattern should be carried out taking into account the circadian rhythms of corticosteroid secretion: 2/3 of the daily dose of the drug is prescribed in the morning, 1/3 in the afternoon.
The use of ” pulse therapy ” in the treatment of PAI is recommended in the case of an active generalized process, while the daily dose of prednisolone can reach 180-360 mg/day.
- Schaumburg-Lever reports on the experience of treating severe cases with high doses of prednisone in order to quickly suppress the disease.180-360 mg of prednisone was administered per day for 6-10 weeks. In the absence of the appearance of fresh lesions after 6-10 weeks started at a reduced dose 40mg daily in the first week, 30 mg of the second, on the 25 in the third.
When pemphigus seborrheic effective is a combination of HA derivatives chloroquinoline (delagil, rezohin, Plaquenil). One of these drugs is prescribed in 7-10-day cycles of 0.25 x 2 times a day with 3-5-day intervals against the background of the continued use of corticosteroids .
When a disease is first detected or when a pecococcal or candidal infection is attached, it is recommended that polyoxidonium, 6 mg, 2 times a week, be administered subcutaneously for 5 injections, in a total dose of 30 mg simultaneously with prednisone, in a complex therapy of an immunomodulator . Repeated courses polyoxidonium can be carried out in 3-6 months, 12 mg 1 time per week for 2 months.
In the case of recurrence of the disease, as well as a slow regression of lesions, it is recommended to administer 1 ml of 1% solution in combination with corticosteroids glutoxim and 1 injection of 1% solution. Repeated courses can be carried out according to the same scheme in 3 and then 6 months against the background of maintenance therapy of corticosteroids.
Supportive Therapy and Canceling Glucocorticoids
The longest in treating patients is Stage III . Maintenance therapy for corticosteroids has to be carried out permanently for years even with the development of complications caused by their use. Reducing the dose to maintenance stretches for many months. This process depends on many factors: the response to the drug, the development of side effects, tolerability, medical experience, etc. In connection with these m single dose reduction algorithm does not exist.
Sometimes it is outpatient, contrary to the recommendation of the doctor, patients voluntarily completely stop the treatment with supporting doses of GK (or quickly reduce the dose), believing that they are cured. In most of these cases, the disease recurs, which is even more malignant. In this situation must be re-hospitalization and treatment resumption shock doses HA, but the magnitude of the daily dose should be applied at a higher than 30-40%.
In such cases, combined therapy of corticosteroids and cytotoxic drugs is also possible ( azathioprine 2.5 mg / kg body weight per day or methotrexate 35-50 mg per day. The use of cytostatics is appropriate for the development of severe complications in patients with latent pemphigus therapyon the background of long-term maintenance of corticosteroids . Joining immunosuppressant possible at different stages of treatment.
The amount of the daily dose of corticosteroids and the possibility of its combination with immunosuppressants are determined by the doctor taking into account the clinical form of the pemphigus, its stage, the effectiveness of the previous treatment of corticosteroid, as well as the type and significance of associated diseases.
A long continuous treatment regimen, although it provides the greatest clinical effect, most often caused the development of complications. Considering this, various schemes have been proposed intermittent corticosteroids – that the alternating and of intermittent, which is, applied mainly in stage III treatment.
In case of alternating therapy, a 48-hour single dose of corticosteroids is administered once in the morning every other day. This method of dosing reduces the risk of atrophy of the adrenal cortex and maintains their response to stress. Also less pronounced, and other side effects N- medical Cushing’s syndrome, growth retardation in children.
With intermittent therapy – (3-4 day reception, 3-4 days I- break) the adverse effect on the adrenal glands is less than with continuous, but more than with alternating therapy.
And non-limiting therapy is almost never used.
The transition from a continuous treatment regimen to an alternating should take place gradually – 2-3 months, under more careful control of the patient.
With a decrease in the daily dose of prednisolone, it should be remembered that the full replacement effect of endogenous corticosteroids have doses of prednisolone more than 10 mg.
Therefore, a dose reduction from a higher dose up to 10–15 mg per day can occur quite quickly, especially when side effects occur.
Below this limit, the dose should be reduced slowly – in stages of 2.5-5 mg every 5-7 days, and, the slower the longer the treatment was carried out (in some cases, 1 mg per month). According to experts, the maintenance dose is 1-2 tablets . It is recommended totake up to a suppository dose of 1/2 pill, and preferably to ¼. Tablets in the maintenance dose is recommended to apply simultaneously after breakfast. In such dosages, steroid therapy does not affect the patient’s quality of life.
Adrenal insufficiency can persist for many months after the complete abolition of corticosteroids, which, in the face of stress, trauma, infection, surgical interventions, can lead to severe adrenal insufficiency, primarily with circulatory disorders.