RU2828120C1 - Method for prediction of clinical effectiveness in atopic dermatitis in pregnant women using combination of emollient and topical antipruritic agent - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to allergology, immunology and dermatovenerology, and is intended to predict the effectiveness of treating aggravated atopic dermatitis during pregnancy with a combination of "emollient + topical antipruritic agent". Method for predicting the effectiveness of treating atopic dermatitis in pregnant women with a combination of an emollient and a topical antipruritic agent involves calculating a probability coefficient p=1/(1+e ^−y), where e is an exponent, and y is determined by the formula y=12.293−0.138x ₁ −0.468x ₂ −0.008x ₃ , where x ₁ is the severity of the disease, determined by the SCORAD index, measured in points; x ₂ is blood serum filaggrin level in pg/ml; x ₃ is the blood serum interleukin 31 level in pg/ml. If the probability coefficient p is more than 0.5, the treatment is considered to be effective, and if the value is less than 0.5, the treatment is considered to be ineffective.

EFFECT: method enables a personalized approach to the choice of therapy.

1 cl, 3 tbl, 4 ex

Description

The invention relates to medicine, namely to allergology, immunology and dermatovenereology, and is intended to predict the effectiveness of treating exacerbation of atopic dermatitis during pregnancy with a combination of "emollient + topical antipruritic agent".

Atopic dermatitis is a multifactorial inflammatory skin disease, the pathogenesis of which includes a predisposition to atopy, dysfunction of the skin and a cascade of immune reactions underlying allergic inflammation. The relevance of the problem of treating atopic dermatitis is due to its widespread prevalence and the growing number of patients among pregnant women, as well as the lack of a unified tactic for the management and treatment of exacerbation of atopic dermatitis during pregnancy.

Pregnant women with exacerbation of atopic dermatitis represent a special cohort, since during pregnancy it is impossible to use most of the medications necessary for treatment due to adverse pharmacological effects on the fetus.

Today, the immunopathogenesis of atopic dermatitis is actively studied. Atopic dermatitis is based on a set of complex pathways of interaction between the immune system, nervous system, and skin. One of the important links in pathogenesis is dysfunction of the immune system, which manifests itself in cytokine imbalance. Atopic dermatitis during pregnancy is characterized by an increased content of interleukin 31 in the blood serum. Another equally important link in the pathogenesis of atopic dermatitis is a violation of the skin barrier. One of the possible causes of dysfunction of the skin barrier is a violation of the metabolic processes of protective skin proteins. Filaggrin protein is currently considered a marker of dysfunction of the skin barrier.

We propose using additional markers of atopic dermatitis during pregnancy, such as the SCORAD index, interleukin 31, filaggrin, which allow for a personalized approach to the choice of therapy.

A method is known for predicting the course and assessing the effectiveness of treatment of atopic dermatitis based on determining the level of proteins - lactoferrin, alpha-1-antitrypsin, alpha-2-macroglobumin in the blood serum and calculating the coefficient K using a specific formula (RU Patent No. 2603463C1, IPC G01N 33/48, A61B 5/00).

The disadvantage of this method in relation to the treatment of pregnant women is the limited possibility of using standard therapy, as well as the peculiarities of protein metabolism during pregnancy.

Another method for assessing the effectiveness of treatment of atopic dermatitis is based on the assessment before and after treatment of the proportion of the total area of the skin occupied by the main element of the rash Sэ with the determination of the integral index. If the integral index of atopic dermatitis decreases after treatment by 50% or more, a conclusion is made about the high effectiveness of the treatment; if the said index decreases by 10-49% - about the moderate effectiveness of the treatment; if the index decreases by less than 10% - about the insufficient effectiveness of the treatment (RU Patent No. 2445921C1, IPC A61B 5/107).

The disadvantage of this method is the impossibility of predicting the effectiveness of treatment at the initial stages of therapy.

The objective of our invention is to create an accurate method for predicting the effectiveness of external therapy for atopic dermatitis during pregnancy using a combination of an emollient and a topical antipruritic agent.

The result is achieved by creating a mathematical model, including the determination of the SCORAD index, the level of cytokine - interleukin 31 and protective skin protein - filaggrin in the blood serum by the enzyme immunoassay method. It was revealed that these indicators are the most significant for determining the effectiveness of combined therapy with an emollient and a topical antipruritic agent. The method is implemented as follows.

A mathematical model that allows predicting the effectiveness of treating atopic dermatitis during pregnancy with a combination of emollient + topical antipruritic agent was constructed using statistical analysis of the data from the study as a result of multivariate analysis.

A mathematical model that allows predicting the effectiveness of treating atopic dermatitis during pregnancy with a combination of “emollient + topical antipruritic agent” was constructed using statistical analysis of the data from the study as a result of multivariate analysis. The first stage of the multivariate analysis was to evaluate the correlation between independent predictor factors and the effectiveness of the treatment. The most significant correlations are presented in Table 1.

Table 1. Results of correlation analysis

A pair of variables Spearman's rank correlations
The correlations noted are significant at the p<0.05 level. Number of observations Spearman R p – level Treatment Efficacy & SCORAD Index 76 0.725 0,001 Treatment Efficiency & Filaggrin 76 0.735 0,001 Treatment Efficiency & Interleukin 31 76 0.619 0,001

Correlation analysis showed the presence of a strong reliable dependence of the effectiveness criterion on the parameters of the SCORAD index (scores) (R = 0.725, p = 0.001, direct relationship), filaggrin (serum level, pg/ml) (R = 0.735, p = 0.001, direct relationship), interleukin 31 (serum level, pg/ml) (R = 0.619, p = 0.001).

The next step was to construct a model directly for predicting the effectiveness of treatment with the combination of "emollient + topical antipruritic agent" using the stepwise regression analysis method. The model coefficients (B) for the factors included in the model and their significance are given in Table 2.

Table 2. Results of regression analysis (Variables in the equation)

Parameter IN
(Regression coefficient B) (SE)
Standard error Wald (Wald) df Sig.
(Significance) Exp(B) SCORAD Index -0.138 0.064 4,658 1 0.031 0.871 FLG -0.468 0.197 5,659 1 0,017 0.626 IL-31 -0.008 0,007 1,330 1 0.149 0.992 Constant 12,293 3,259 14,229 1 0,011 218104,750

Thus, a mathematical model for predicting the effectiveness of treatment with a combination of an emollient and a topical antipruritic agent was obtained.

Y = 12.293 – 0.138x ₁ –0.468x ₂ – 0.008x ₃ ,

where y is the probability coefficient of effective treatment with the combination of “emollient + topical antipruritic agent”,

x ₁ – SCORAD index, points,

x ₂ – Serum filaggrin level, pg/ml,

x ₃ - Interleukin 31 level in blood serum, pg/ml,

probability of effectiveness

If the value of p<0.5, treatment with the combination of “emollient + topical antipruritic agent” for atopic dermatitis in pregnant women will be ineffective; if p>0.5, it will be effective.

Based on the calculated model, a classification table is provided (Table 3), in which the observed indicators of group membership are contrasted with the predicted ones.

Table 3. Classification table

Observed (Observed indicator) Predicted Group Percentage Correct Ineffective treatment Effective treatment Step 1 Group Ineffective treatment 15 3 83.3% Effective treatment 1 57 98.3% Overall Percentage 94.7%

From the table, it can be concluded that out of the total of 58 cases with effective treatment, only 57 were recognized as such by the test, and only 1 was determined as a “false negative” result. Out of the 18 cases with ineffective treatment, 15 were recognized as ineffective by the test, and 3 as false positives. In total, 72 out of 76 cases were correctly recognized, which is 94.7%.

Thus, the percentage of correct prediction reaches 94.7%, as a result of which this model can be used to predict the effectiveness of treating atopic dermatitis during pregnancy with a combination of an emollient and a topical antipruritic agent.

Clinical examples

Example 1

Pregnant woman M., 23 years old, 26 weeks pregnant, complains of skin rashes, skin itching of varying intensity, accompanied by insomnia.

From the anamnesis: the above complaints have been bothering since 12 weeks, the allergy history is burdened, the onset of AD is in childhood (2 years), notes up to 2 exacerbations per year, mainly in the spring and autumn periods. Pregnancy - 1, without any peculiarities.

Objectively: the condition is satisfactory. The skin is of normal color, erythematous rashes are noted in the area of the face, chest, abdomen, back, upper limbs, thighs.

SCORAD index = 52.9 points (severe severity).

Beck Anxiety Inventory = 18 points.

Itch scale 5 D=25 points.

DIKZh=25 points.

Diagnosis: Atopic dermatitis, severe, exacerbation.

An examination was conducted, as a result of which the following indicators were obtained: the level of FLG in the blood serum was 19.72 pg/ml, the level of SP in the blood serum was 121.64 pg/ml, the level of IL-31 in the blood serum was 254.88 pg/ml, and the level of IL-33 in the blood serum was 9.59 pg/ml.

y=12.293 – 0.138*52.9–0.468*19.72 – 0.008*254.88=-6.25

p=0.002.

An unfavorable prognosis for the effectiveness of treatment of this patient with a combination of emollient and topical antipruritic agent was revealed.

Example 2

Pregnant woman M., 24 years old, 19 weeks pregnant, complains of rashes on the skin of the back of the hands, forearms, shoulders, chest, abdomen, thighs, back, accompanied by itching.

From the anamnesis: the above complaints have been bothering since 15 weeks, the allergy history is not burdened, AD is diagnosed for the first time. Pregnancy - 1, without any peculiarities.

Objectively: the condition is satisfactory. The skin is of normal color, eczematous rashes are noted on the back of the palms, forearms, shoulders, abdomen, chest, back, thighs.

SCORAD index = 51.3 points (severe severity).

Beck Anxiety Scale = 10 points.

Itch scale 5 D=25 points.

DIKZh=20 points.

Diagnosis: Atopic dermatitis, severe, exacerbation.

An examination was conducted, as a result of which the following indicators were obtained: FLG level in blood serum - 7.3 pg/ml, SP level in blood serum - 122.83 pg/ml, IL-31 level in blood serum - 29.06 pg/ml, IL-33 level in blood serum - 9.5 pg/ml.

y=12.293 – 0.138*51.3 – 0.468*7.3 – 0.008*29.06=1.6

p=0.83.

A favorable prognosis for the effectiveness of treatment of this patient with a combination of emollient and topical antipruritic agent was revealed. The patient was recommended to use a combination of emollient and topical antipruritic agent.

Example 3

Pregnant woman K., 30 years old, 15 weeks pregnant, complains of rashes in the area of the forearms, shoulders, back of the hands, itchy skin.

From the anamnesis: the above complaints have been bothering since 14 weeks, the allergy history is burdened, the onset of AD in childhood, exacerbation of AD 1-2 times a year. Pregnancy - 2, without any special features.

Objectively: the condition is satisfactory. The skin is of normal color, lichenoid rashes are noted on the back of the palm, forearms, and shoulders.

SCORAD index = 26.2 points (moderate severity).

Beck Anxiety Inventory = 0 points.

Itch scale 5 D=20 points.

DIKZh=14 points.

Diagnosis: Atopic dermatitis, moderate severity, exacerbation.

An examination was conducted, as a result of which the following indicators were obtained: FLG level in blood serum - 9.34 pg/ml, SP level in blood serum - 134.50 pg/ml, IL-31 level in blood serum - 38.01 pg/ml, IL-33 level in blood serum - 7.42 pg/ml.

y=12.293 – 0.138*26.2 – 0.468*9.34 – 0.008*38.01=3.99

p=0.98.

A favorable prognosis for the effectiveness of treatment of this patient was revealed using a combination of emollient and topical antipruritic agent.

Example 4

Pregnant woman T., 36 years old, 35 weeks pregnant, complains of itching and rashes in the abdomen, chest, and face.

History: the above complaints have been bothering since 34 weeks, allergy history is not aggravated, AD is diagnosed for the first time. Pregnancy - 3, without any peculiarities.

Objectively: the condition is satisfactory. The skin is of normal color, rashes are noted in the area of the face, abdomen and chest.

SCORAD index = 40.1 points (moderate severity).

Beck Anxiety Inventory = 0 points.

Itch scale 5 D=18 points.

DIKZh=16 points.

Diagnosis: Atopic dermatitis, moderate severity, exacerbation.

An examination was conducted, as a result of which the following indicators were obtained: FLG level in blood serum - 19.2 pg/ml, SP level in blood serum - 136.75 pg/ml, IL-31 level in blood serum - 96.01 pg/ml, IL-33 level in blood serum - 12.55 pg/ml.

y=12.293 – 0.138*40.1 – 0.468*19.2 – 0.008*96.01=-2.99

p=0.05.

An unfavorable prognosis for the effectiveness of treatment with a combination of an emollient and a topical antipruritic agent was revealed.

Claims (1)

A method for predicting the effectiveness of treating atopic dermatitis in pregnant women with a combination of an emollient and a topical antipruritic agent, using an assessment of the severity according to the SCORAD index, an assessment of the filaggrin level in the blood serum, an assessment of the interleukin 31 level, characterized in that the probability coefficient p = 1/(1+ e ^{- y} ) is calculated, where e is the exponent, y is determined by the formula y = 12.293 - 0.138x ₁ - 0.468x ₂ - 0.008x ₃ , where x ₁ is the severity of the disease, determined by the SCORAD index, measured in points; x ₂ is the filaggrin level in the blood serum in pg/ml; x ₃ is the level of interleukin 31 in the blood serum in pg/ml, and if the probability coefficient p values are greater than 0.5, the treatment is considered effective; if the values are less than 0.5, the treatment is considered ineffective.