Method for prediction of deterioration probability of clinical course of psoriasis, progression into erythroderma considering immunological values, liver detoxification and metabolic functions

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to dermatology. To predict the deterioration probability of the clinical course of psoriasis, the progression into erythroderma, an integrated assessment of a pathoigenetic significance of the detected risk factors promoting the deterioration is made. What is determined is a prognostic coefficient (PC) for such criteria, as: sex; age; petrochemical workers; agricultural workers; construction workers; drivers; office staff; hyper insolation; adverse agricultural labour conditions (pesticide and fertiliser contact); petroleum contact; construction material contact; drug abuse; pockets of chronic bacterial and/or mycotic infections; frequent acute respiratory viral infections; chronic gastrointestinal and/or hepatic diseases; chronic pulmonary diseases; chronic respiratory infections; chronic otorhinolaryngological organs; disturbed liver detoxification; liver metabolic disturbance; circulating immune complex increase; immunoglobulin increase; immunoregulatory index decrease; stimulation index decrease; cytotoxic index decrease; antitissue autoantibody increase; blood skin antigen; leukocyte migration inhibition index increase. If a factor is absent, the related PC is considered to be zero. The derived PCs are summed up. If PC is 5.64-16.24, the low deterioration probability of the clinical course of psoriasis and the favourable prognosis; the PC value being 16.25-26.85 shows the medium deterioration probability and the relatively favourable prognosis; the value of 26.86-37.86 and more provides the high probability and the unfavourable prognosis, and the potential progression into erythroderma.

EFFECT: method enables predicting the deterioration probability of the clinical course of psoriasis, the progression into erythroderma.

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The invention relates to medicine, namely to dermatology, and can be used to predict the probability of worsening clinical course of psoriasis, crossing his erythroderma, to justify the choice of tactics and observation of patients, aiming to prevent adverse clinical course.

There is a method of diagnosing deterioration of the clinical course of psoriasis by examining the functional pathology of the liver, metabolism of bile acids by the method of ascending thin-layer chromatography [Baltabaev, M.K., Khamidov S.A., Jalalov CD method for the diagnosis of functional liver pathology of psoriasis. Patent for invention No. 2250. Rasmi Ahborotnoma (Official Gazette), Tashkent. - 1995. No. 1. - p.19-20]. The authors have analysed the state of the metabolism of bile acids in 50 patients with psoriasis and 30 patients with chronic hepatitis without concomitant cutaneous pathology, concluded that a violation of the initial mechanisms of production of bile acids by the liver psoriasis. In this way, the authors predict the likelihood of a worsening clinical course of psoriasis is the result of accumulation in the blood of excess of free bile acids, but do not take into account changes in immunological parameters, detoxification and metabolic functions of the liver, do not predict ve is aatest transition psoriasis erythroderma in contrast to the claimed method.

There is a method of predicting the course of psoriasis by examining the patient's blood based on the determination of the activity of the enzyme phospholipase A2 in the haemolysis of red blood cells and blood plasma, allowing to predict early relapse (within 4-8 months) with targets exceeded in two or more times the norm. When the value of the indices within the normal range predict disease remission (10 months or more) (RF patent 2009509, 1994). The disadvantages of this method are its complexity, length of study, disregard of immunological disorders, detoxification and metabolic functions of the liver, lack of forecasting the possibility of transition of psoriasis erythroderma in contrast to the claimed method.

The prototype of the invention, the closest technical solution is a method of predicting the course of psoriasis by examining the patient's blood, wherein determine the level of immunoglobulins A, G, T_TFF/T_TFCin the serum, and in excess of the indicators JgA level of 3.0 g/l, JgG level 18 g/l, the decrease in T_TFF/T_TFCbelow 2,0 predict the development of more severe clinical forms of psoriasis, mainly eritrodermii (RF patent No. 2134882, 1999). This method allows you to objectively assess the severity of psoriasis in some the eye immunological indicators to predict the transition of psoriasis erythroderma, but does not reflect the state of metabolic and detoxification functions of the liver, does not take into account the role of the autoimmune process, inducing an inflammatory response in the dermis of patients with psoriasis, i.e. does not take into account other pathogenesis of this disease in contrast to the claimed method.

The objective of the invention is to develop a method for predicting the likelihood of deterioration in the clinical course of psoriasis, crossing his erythroderma by conducting an integrated assessment of the pathogenetic significance of the identified risk factors contributing to the deterioration of the disease, taking into account the immunological parameters, detoxification and metabolic functions of the liver.

The technical result - getting individual criteria to predict the probability of worsening clinical course of psoriasis, crossing his erythroderma, to justify the choice of tactics and observation of patients, aiming to prevent adverse course of the disease, by eliminating the identified risk factors, the purpose of timely and adequate rational therapy.

The claimed method for predicting the likelihood of deterioration in the clinical course of psoriasis, move it to the erythroderma is as follows. Determine gender, age, profession bol is different, collect anamnesis of the disease, identify the presence or absence of factors that contribute to the deterioration of the disease, conduct clinical, immunological, and biochemical studies. Metabolic liver function assessed by biochemical studies performed on autoanalyzer firm "SINNOWA - 300", with reagent kits firms Chema Hospitex diagnostics. Patients determine total protein, albumin, urea, creatinine, total lipids and cholesterol, liver enzymes, alanineaminotransferase (ALT), aspartataminotransferaza (ACT), total bilirubin and its fractions, glucose. The activity of the monooxygenase system (MOS) of the liver is assessed through antivirusoveho test that indirectly indicates changes of liver detoxification function. The concentration of immunoglobulin classes a, M, G (IgA, IgM, IgG) in the blood sera calculated by the method of radial immunodiffusion according to Mancini. The functional activity of lymphocytes is determined in response to besttransport (rbtl) with PHA, the activity of natural killer cells (NK activity) analyze standard³N-uredinium cytotoxic test against target cells (KM) K 562 line cells, with a ratio of effector cells and KM (EK:KM) 1:25 on the cytotoxic index (QI). Lymphocyte proliferation appreciate the inclusion of³H thymidine. Detection of circulating immune complexe the (CEC) carried out by the method of precipitation by polyethylene glycol (PEG-6000). To characterize the autoimmune process (titer autoantibodies) put the Treponema pallidum haemagglutination assay (TPHA), blood levels of skin antigen was determined by response inhibition passive haemagglutination (RTPA), using capillary variant of response inhibition of migration of leukocytes (RTML). The obtained results are statistically processed using student's criterion and are in the form of a table (table 1). Integrated assessment of the pathogenetic significance of the obtained results revealed exogenous and endogenous factors that contribute to the deterioration of the disease, conduct Bayesian (1987). Calculate the frequency of the identified factors in 100 patients, normalized intensive index (NIP), the relative risk (ERP) deterioration in the clinical course, prognostic factor (PC), integrated risk ratio (IPR) of the transition psoriasis erythroderma. The results of these calculations are presented in table 2, which shows that the relative risk (ERP) deterioration in the clinical course of psoriasis in men 3.13 times more than women, persons in "the age of 51 years and older it is increased to 5.03. During the history taking every third patient was noted permanent residence during the work shift under the influence of chemical, toxic or other harm to the s factors of production. The relative risk of worsening clinical course of psoriasis in these socio-professional groups with long-term constant contact with the production of harm was 13,63.

Concomitant diseases of the gastrointestinal tract, the liver was 56.1% of patients, the lungs of 15.2%, ENT of 18.2%, frequent recurrent colds of 12.12%. The relative risk of worsening clinical course of psoriasis in individuals with comorbid chronic diseases barrier of lymphoepithelial masses of the bodies and undergoing viral, bacterial and/or fungal infection, reaches 16,07. Surveyed patients in 68,19% of the cases took more than 5 different drugs on average within 10 years prior to the worsening of the clinical course of psoriasis. In 65.4% of patients with psoriasis were identified violation detoxification functions of the liver, manifested by decreased activity monooxygenase system of the liver in the form of increased period of propitiatio of antipyrine on average 2 hours more than normal. In 72.3% of patients with psoriasis were identified violation of the metabolic functions of the liver, manifested by reduced levels aminotrasferase on average 2.5 times than normal, total protein and albumin on average 1.3 and more times than normal, the increase in the level of total lipids in average 1.5 or more times than normal, increasing the level cholesterin is in the blood in an average of 1.4 or more times, than normal. The overall predictive coefficient (PC) transition probabilities of psoriasis erythroderma when combined with the violation of detoxification (PC 29,41) and metabolic (PC - 32,62) of the liver is the most high - 62,03. The increase in the level of the CEC 1.4 and more times than normal found in 83.5% of the examined patients with psoriasis, the increase in the average level of immunoglobulins (a, M, G) is 1.5 or more times than normal, 78,8%, increase immunoregulatory index of 1.2 or more times than normal, 56,5%, a decrease of cytotoxic index of 1.4 or more times than normal, 40,0%, reducing the stimulation index of 2.5 or more times than normal, and the increase in the index of inhibition in 6.6 and more times than normal, all 100% of patients. In healthy people cutaneous antigen in our research is not detected in patients with psoriasis it is detected in 98.3% of patients. Level protivotankovyh autoantibodies was higher than the control value of 4.8 or more times at 72,5% of patients. The relative risk of worsening clinical course of psoriasis in individuals with immune disorders equal 27,32.

Thus, according to the results of our study relative risk factors for worsening clinical course of psoriasis are: the development of immune disorders in the body (LONG-27,32), the presence of concomitant chronic liver diseases, gastrointestinal tract, lungs, upper respiratory tract, re Esenia viral, bacterial and/or fungal infection (ERP 16,07), belonging to a particular socio-professional group (ERP 13,63), having contact with professional production impurities, allergens and antigens (ERP 11,25), age 50 years and older (ERP 5,03). Given the possibility of participation of the above-described various mechanisms in the pathogenesis of psoriasis was additionally conducted an integrated assessment of the results, calculated low-range risk of worsening clinical course of psoriasis with predictive coefficient from 5,64 to 16,24, which was typical for the limited plaque forms of psoriasis with a favorable prognosis; middle range of risk with predictive coefficient from 16,25 to 26,85 was typical for common patchy form of the disease with a relatively favourable prognosis; high range of risk prognostic factor of 26,86 to 37,86 was characterized by poor prognosis, the probability of psoriasis erythroderma (table 3). Prognosis the clinical course deteriorated by the combined action of several factors, for example, when the irrational use of drugs (PC 21,49) in combination with gastrointestinal diseases, liver (PC 25,23) in violation metabolic (PC 32,62), detoxification (PC 29,41) of the liver, was $ 108,75 and exceeded the maximum value of the claim worsening clinical course of psoriasis 2.9 times, predicting the likelihood of eritrodermii, then as a prognostic factor for each characteristic individually smaller than the maximum values of the risk of worsening clinical course of psoriasis.

The research of the authors was first proved the possibility of predicting the likelihood of deterioration in the clinical course of psoriasis, move it to the erythroderma of the claimed method. Therefore, the claimed invention meets the criterion of "inventive step". The authors in scientific medical and patent literature found no information on the integrated risk assessment of the probability of deterioration in the clinical course of psoriasis, crossing his erythroderma, taking into account the immunological parameters, detoxification and metabolic functions of the liver. Thus, the claimed invention meets the patentability criteria of "novelty".

The inventive method of predicting the likelihood of deterioration in the clinical course of psoriasis move it erythroderma with regard to immunological parameters, detoxification and metabolic functions of the liver is illustrated by the following examples.

Example 1. Sick S.A., 62 years old, have complained of rashes on the skin and scalp, the change of the nail plates, dryness and itching of the skin, a constant bitter taste in the mouth, wsdot the belly, heaviness in the right hypochondrium. Suffering from psoriasis for 20 years, during which simultaneously took more than 4 different medicines inside the regarding concomitant chronic colitis, cholicistitus. Worked on a construction site, laid concrete, was often sick with colds.

An objective examination of the pathological process has been limited, localized on the hands, scalp, back, chest, abdomen, upper and lower extremities. Psoriatic plaques were stagnant red, with clear boundaries of 4.5-6.5 cm in diameter, covered with silvery-white scales, easily removable by poskablivanii, the triad of symptoms of Auspitz-Luchetta, Cabrera were positive. The results of laboratory tests: ALT 0,35 mkat/l, AST 0,22 mkat/l, total bilirubin to 10.62 mmol/l, cholesterol 6,72 g/l, total protein 52,42 g/l, albumin 34,52 g/l, urea of 4.2 mmol/l, creatinine 99,41 mmol/l; preliminaly of antipyrine 15,13 hours. Immunoregulatory index of 1.44, rbtl with PHA 5.7%index braking 32.4 per cent, TPHA titer of 15.6, cytotoxic index 37,53%; IgA 192,54 ME; IgM 164,43 ME, IgG 196,21 ME; CEC 18,32 used On the basis of clinical data and the survey exhibited a primary diagnosis: limited plaque psoriasis; concomitant diagnoses: chronic colitis, chronic cholecystitis, hepatitis with impaired metabolic and detoxification functions the liver.

On the 5th day of treatment, in spite of the traditional standard hospital treatment, experienced a deterioration of the clinical course of psoriasis, which was manifested by the transition plaque limited psoriasis in common patchy form, then erythroderma. The General condition was characterized by a sudden increase in body temperature up to 40°C, weakness, malaise, chills, development of diffuse erythema and edema of the skin. The affected skin was hyperemic, infiltrated, hot, dense palpation. It was noted abundant peeling plate scales, hair loss, peeling of the nail plates. Subjectively, the patient felt a sense of pulling, burning, dryness, itching, General malaise, weakness. The patient spent in the intensive corticosteroid therapy, detoxification therapy in conjunction with medication, hepabene and hofitol 1 tablet 3 times a day, with a diuretic.

The regression process began on the 4th day of therapy in the form of a slight decrease infiltration and congestion, improve the General condition of the patient, edema dyspepsia, intestinal (decorated chair 1 time per day), pain syndromes. Pronounced clinical effect was observed on the 8th day from the beginning of treatment disappeared inflammatory response and decreased significantly in illitracy and dry skin. Observed inverse regression of the disease, manifested by the disappearance of eritrodermii, but remained in the presence of psoriatic plaques. After 4 weeks of therapy were observed flattening of the plaque elements, the disappearance of a bright color and peeling, the skin of the forehead and in the back began to appear secondary depigmented spots on the location of the regression of psoriatic plaques. Skin itching stopped. At week 6 showed a significant improvement of the skin and biochemical parameters. 8 weeks psoriatic lesions completely regressed in their place remained secondary depigmentation.

In this example, the sick man (PC 6,63), age 62 years (PC 4,07), Builder (PC 4,63), had constant contact with construction materials (PC 5,74), often relapsing, ARVI (PC 5,46), gastrointestinal diseases, liver (PC 25,23), metabolic disorders (PC 32,62), detoxification functions of the liver (PC 29,41), the overall predictive factor of deterioration in the clinical course of psoriasis was 113,79, table grades (table 3) exceeded the upper limit of the maximum value of risk transfer psoriasis erythroderma 3 times. Despite the fact that the patient was in hospital under medical supervision, received standard conventional therapy, have been deteriorating clinical course of psoriasis move it erythroderma, which was p what dorjderem our poor prognosis.

Example 2. Patient Century, 40 years, the driver of materials, have complained of rashes on the skin of the trunk, arms, legs and scalp, itching and tightening of the skin, sore throat. Suffering from psoriasis for 5 years. Often treated as an outpatient and inpatient, took more than 3 drugs inside about psoriasis and comorbidities. Diagnosis: limited plaque psoriasis. Concomitant diagnosis: chronic tonsillitis. The results of laboratory tests: ALT 0,7 mkat/l, AST of 0.75 mkat/l, total bilirubin 11,71 µmol/l, cholesterol 5.8 g/l, total protein of 72.3 g/l, albumin of 37.7 g/l, urea of 4.6 mmol/l, creatinine 90,1 mmol/l; preliminaly of antipyrine 13,02 hours. Immunoregulatory index 2,41, rbtl with PHA 14,1%, the index of inhibition 26,0%, TPHA titer 5,2, cytotoxic index 50,31%; IgA 120,44 ME; IgM 140,25 ME, IgG 159,84 ME, the CEC 14,13 used When carrying out biochemical studies have not found significant violations of metabolic and detoxification functions of the liver, immunological parameters were within the age limit, but there was an increase half-life of antipyrine for 2 hours. On the basis of clinical data and the survey exhibited a primary diagnosis: limited plaque psoriasis associated with chronic tonsillitis.

On day 10 of treatment, despite ongoing in the hospital the standard conventional therapy, deteriorated General condition of the patient, worsening clinical course of psoriasis, which can be explained by transition limited plaque psoriasis in widespread plaque. There was an increase of body temperature up to 39°C, weakness, malaise, fever. The skin in the area of plaques was hyperemic, infiltrated, swollen, hot, dense palpation. Subjectively, the patient felt a sense of pulling, burning, dryness, itching of the skin. Possible worsening of the clinical course of psoriasis, transition limited plaque forms in common patchy form was due to increased half-life of drugs from the body, which is implicitly testified antipiracy test. The regression of the distribution of the plaques came on the 6th day from the beginning of detoxification treatment and short-term corticosteroid therapy. Completely disappeared inflammatory response and significantly decreased infiltration, dry skin.

In this example, the sick man (PC 6,63), age 40 years (PC 1,71), driver (PC 1,1), had contact with construction materials (PC,74), diseases of ENT organs, (PC 2,09), the overall predictive factor of deterioration in the clinical course of psoriasis was 17,27 that included table grades (table 3) in the medium range of risk and predicted probability of deterioration of clincheck the th psoriasis, without the development of eritrodermii. Relatively favorable prognosis allowed to substantiate the choice of tactics detoxification and short-term corticosteroid therapy, which in a short time stopped the spread of plaques on the trunk and for 6 days led to a complete regression of the disease. In the patient summary prognostic factor (17,27) does not exceed the maximum value prognostic factor (26,85) medium range of risk probability of worsening clinical course of psoriasis, which corresponded to the clinical dynamics of the disease, rapid regression of psoriatic process without going erythroderma.

Example 3. Patient L., 22, clerk, filed a complaint for limited lesions on the skin of hands, feet and scalp, often recurrent colds, cough with phlegm. Objective: Pathological process is localized in the region of the extensor surfaces of the upper and lower extremities, presents a symmetric default plaque size of 4.5-6.5 cm in diameter, bright red, with clear boundaries, covered with silvery-white scales. Subjectively, the patient felt discomfort, a feeling of tightening, dryness, itching of the skin. After the examination, in which the pathology of internal organs is not detected, biochemical, immuno is logicheskie parameters were within normal limits, diagnosis: limited plaque psoriasis. Treatment the patient was carried out according to standard topical therapy in conjunction with antiviral drugs about SARS. The regression process is started on day 2 of therapy in the reduction of scaling, infiltration of plaques. Pronounced clinical effect was observed on the 5th day from the start of treatment, plaques partially regressed, leaving secondary depigmentation. Appointed external therapy ointment "Diprosalic" led to a complete regression of psoriatic plaques on the 7th day of the disease.

In this example, the sick woman (PC 2,13), clerk (PC 0,88), had often recurrent colds (PC 5,46), lung diseases (PC 6,91), the overall predictive coefficient of the probability of deterioration in the clinical course of psoriasis was 15,38 that included table grades (table 3) in the low risk range with favorable prognosis. This, in turn, helped to justify the choice of tactics of external therapy of psoriasis, which led to a complete regression of the disease. Our forecast coincided with clinical data, deterioration of the flow of psoriatic process was not observed, the transition limited plaque forms of psoriasis in common, and then erythroderma has not occurred.

As seen from the above examples, integrated risk assessment, the results of the count n is gnostichesky coefficients for each patient individually allow an individual to predict the likelihood of a worsening clinical course of psoriasis, move it to the erythroderma.

The claimed method was assessed probability of worsening clinical course of psoriasis, its shift of erythroderma in 42 patients with the limited form of plaque psoriasis, in 37 patients with widespread plaque form of psoriasis and in 21 patients with erythrodermia, and in all cases was achieved the specified technical result. Way reproduce in conditions of clinic of skin and venereal clinic, hospital, therefore, the claimed invention meets the patentability criterion of "industrial applicability".

Thus, compared with the prototype (table 4) claimed a method for predicting the likelihood of deterioration in the clinical course of psoriasis, crossing his erythroderma with regard to immunological parameters, detoxification and metabolic liver function allows you to:

a) to take into account different possible pathogenesis of psoriasis and eritrodermii;

b) individually to predict the likelihood of a worsening clinical course of psoriasis, crossing his erythroderma with the division of risk ranges for low, medium and high;

C) on the basis of the calculation of the prediction coefficients to justify the choice of tactics and observation of patients, aiming to prevent adverse course of the disease, which, in turn, allows p is ecotricity development of eritrodermii, by assigning adequate rational therapy.

A method for predicting what ereatest deterioration in the clinical course of psoriasis, move it erythroderma, by conducting an integrated assessment of the pathogenetic significance of the identified risk factors contributing to the worsening of the disease with regard to immunological parameters, detoxification and metabolic functions of the liver, including the collection of medical history, conducting biochemical, immunological studies of serum, wherein the patient determine gender, age, socio-professional identity, the presence of factors that contribute to the deterioration of the disease, immune, metabolic, detoxification of the liver, expect predictive coefficient (PC) of each trait and the male is estimated as 6,63, female as 2,13; age 18-30 years is estimated as 0,90, 31-40 - 1,71, 41-50 - as 2,97, 51-60 - as 4,48, 61 and older - as 4,07; workers of the petrochemical production are estimated as 15,67, selhozraboty as 6,95 construction as 4,63, drivers 1,1, employees - 0,88; heparinase is estimated as 6,46, adverse conditions selfhosted (contact with pesticides, fertilizers) assess how 12,94, contact with oil - as 16,76, contact with the materials as 5,74, irrational use of drugs as 21,49, the presence of foci of chronic bacterial and/or fungal infection - as 4.00, often recurrent ARVI 5,46, chronic diseases W is lubochna-intestinal tract and/or liver as 25,23, chronic lung disease as 6,91, chronic diseases of ENT-organs - as 2,09, disorders of liver detoxification function as 29,41, metabolic disorders of the liver as 32,62; increased levels of circulating immune complexes in 1.4 and more times than normal, estimated as 5,85, increased levels of immunoglobulins in 1.5, and more times than normal, as of 5.53, increase immunoregulatory index of 1.2 or more times than normal, estimated as 3,95, reducing the stimulation index of 2.5 or more times than normal, as of 7.0, a decrease of cytotoxic index of 1.4 or more times than normal, estimated as of 2.8, an increase in the level protivotankovyh autoantibodies 4.8 and more times than normal, estimated as 5,07, the presence of skin antigen in the blood is estimated as 4,78, in its complete absence in the rate of increase of the index of inhibition of migration of leukocytes in 6.6 and more times than normal, estimated as 17,0; in the absence of factor prognostic factor taken for zero; summarize the obtained predictive coefficients (PC), and when the sum value PC 5,64-16,24 forecast low probability of worsening clinical course of psoriasis and favorable prognosis of the disease, 16,25-26,85 - average probability and a relatively favorable prognosis, 26,86-37,86 and above - high probability and poor prognosis, the transition is of soriana erythroderma.