RU2630063C1 - Method of predicting degree of atopic dermatitis in children - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: in the blood serum of a child with atopic dermatitis, the concentration of neopterin is determined when entering the hospital, and at a neopterin concentration of 2.6 ng/ml to 4.0 ng/ml, a mild atopic dermatitis is predicted at a concentration of 4.1 ng/ml to 5.9 ng/ml predict an average degree, and at a concentration of 6.0 ng/ml and above predict a severe degree of atopic dermatitis.

EFFECT: improving the accuracy of the prognosis of atopic dermatitis in children.

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Description

The invention relates to medicine, namely to dermatology, pediatrics and allergology, and can be used to predict the severity of atopic dermatitis in children.

Atopic dermatitis is a chronic neurodermatosis with a pronounced genetic predisposition to sensitization by specific and nonspecific allergens and the ability to form allergen-specific IgE antibodies. Atopic dermatitis continues to be one of the urgent problems of modern dermatology due to an increase in the incidence, a fairly wide spread in the population and a chronic course. The problem is caused not only by its high prevalence, but also by the characteristics of the course of the disease, characterized by a chronic course, severe skin itching, increased sensitivity to one or more allergens and, in turn, leading to social maladaptation and disability of patients.

A known method for predicting the severity of atopic dermatitis, based on a comprehensive assessment of clinical indicators in the form of calculating the SCORAD index (Severity Scoring of Atopic Dermatitis) no formula SCORAD = A / 5 + 7⋅B / 2 + C, where A is the prevalence of skin lesions (area defeat in%); B - the intensity of clinical manifestations (erythema / hyperemia), edema / papule formation, weeping / crust, excoriation, lichenification, dryness); C - subjective symptoms (itching, sleep disturbances) (The SCORAD index. Consensus Report of the European Task Force on Atopic Dermatitis Dermatology. - 1993; 186 (1): 23-31).

However, this method has several disadvantages:

- it is quite subjective, since with this method a number of indicators (sleep disturbances, intensity of skin itching) are evaluated either by the parents or by the patient himself. In young children, this method is not applicable due to the lack of the ability to evaluate the listed subjective indicators;

- the method is not accurate enough, since an assessment of the severity and nature of the course of atopic dermatitis is carried out at the time of treatment of the patient during the exacerbation;

- the assessment of the intensity of skin manifestations included in the SCORAD index also has sufficient subjectivity, since it is based on the personal experience of the doctor or patient;

- the method is quite time-consuming and cannot be widely used in practical health care, as it involves the first stage of determining the affected skin areas with the calculation of the area of skin lesion and the intensity of clinical manifestations with their assessment on a point scale;

- the method does not allow to accurately assess the prognosis of the disease.

A known method for predicting the course of atopic dermatitis [Pat. RU 2310195], which consists in the fact that at the same time epithelial cells are isolated in brush biopsy samples of the oropharyngeal mucosa, a material for the integrated assessment of the resistance of a patient’s macroorganism according to indicators characterizing the microbiocenosis and morphofunctional state of the mucosa, determine the electrokinetic activity of buccal nuclei epithelial cells (Al), infection index (AI), adhesion index (IA) and the washings were taken from infected areas of the skin area of 2 cm ^2, which was determined dissolved number of colony forming units (CFU) S.aureus / cm ^2. When the value of the infection index> 70%, the adhesion index> 100-150 microbial cells of S.aureus per epithelial cell, CFU> 200 / cm ² and ElA <20% during the initial examination, severe course of atopic dermatitis is predicted, with values of the infection index <30%, adhesion index <50 microbial cells S.aureus / epithelial cell, CFU <50 / cm ² and ElA> 30% at the initial examination predict a mild course.

The disadvantages of the method: time-consuming, the calculation part is quite complicated, requires complex microbiological and laboratory equipment, and therefore cannot be widely used in practical health care.

There is also a method for assessing the severity of atopic dermatitis, based on a qualitative and quantitative assessment of the structural components of the lipid film from the affected areas of the skin: phospholipids (PL), cholesterol (cholesterol), fatty acids (FA), triacylglycerides (TAG), cholesterol esters (ECS) [Ogorodova L.M., Khodkevich L.V., Nagaeva T.A., Ryzhov SV. A method for assessing the severity of atopic dermatitis. Registration number of the application 2002122176/15, date of filing the application August 15, 2002, patent number 2239837].

However, this method has the following disadvantages:

- does not provide accuracy in predicting the underlying disease;

- time-consuming, since when it is carried out, a large number of technological operations are performed (extraction, centrifugation, evaporation, chromatography);

- requires high material costs due to the need to use expensive equipment and reagents to perform many laboratory tests.

The closest analogue - the prototype - is a method for predicting the severe course of atopic dermatitis by the level of specific IGG autoantibodies in children older than 3 years [application RU 2009130183, 08/08/2009], according to which, at the initial level of autoantibodies to keratin, more than 333.68 IU / ml predict severe persistent course of atopic dermatitis after 6 months.

The disadvantages of the prototype are the following:

- the method is based on taking into account an indicator reflecting the presence of autoimmune mechanisms in the pathogenesis of atopic dermatitis, while atopic (allergic) mechanisms are the predominant pathogenetic mechanism;

- this method is not used in children under three years of age, while it is in children of this group that the SCORAD scale is limited, and there is no objective assessment of the severity of atopic dermatitis;

- requires specific diagnostic equipment and expensive test systems, which limits the use in real clinical practice.

The main task solved by the invention is to improve the prediction of the severity of atopic dermatitis in children.

The invention is aimed at improving the accuracy of prediction of atopic dermatitis in children.

The specified technical result is achieved by the fact that in the blood serum of a child with atopic dermatitis upon admission to the hospital, the concentration of neopterin in the blood serum is determined and at a concentration of neopterin from 2.6 ng / ml to 4.0 ng / ml, a mild severity of atopic dermatitis is predicted, at a concentration of 4.1 ng / ml to 5.9 ng / ml, a moderate degree is predicted, and at a concentration of 6.0 ng / ml and above, a severe severity of atopic dermatitis is predicted.

The proposed method uses the determination of the concentration of neopterin [2-amino-4-hydroxy-6- (D-erythro-1 ', 2', 3'-trihydroxypropyl) -teridine], which is a low molecular weight compound derived from guanosine triphosphate (GTP).

The determination of the optical density and concentration of neopterin was carried out using a Neopterin ELISA kit from IBL International (Germany). The test was developed based on the following works: 1. Westermann J., Thiemann F., Gerstner L. et al. Evaluation of a New Simple and Rapid Enzyme-Linked Immunosorbent Assay Kit for Neopterin Determination / Clin Chem Lab Med 38 (4): 345-353 (2000), 2. Bayer M., Schmitz S., Westermann J et al / Evalution of a New-Linked Immunosorbent Assay for the Determination of Neopterin / Clin Lab / 51 (2005).

According to modern concepts, neopterin (NP) is a nonspecific highly sensitive marker of activation of the monocytic link of cellular immunity and biochemical changes induced by cytokines that determine the activity of inflammation of various etiologies [Shevchenko OP, Olefirenko GA, Orlova OV The use of neopterin to assess the activation of cellular immunity. // Laboratory. - 2004. - No. 48. - C.6]. A high level of neopterin is an indicator of the activity of the immunopathological process and, according to some researchers, precedes the clinical manifestations of the disease [Oldhafer K.J., Schafer O., Wonigeit K. et al. Monitoring of serum neopterin levels after liver transplantation.// Transplantation Proc. - 1988. - Vol. 20.1. - P.671-673, Werner-Fermayer G., Werner E.R., Fuchs D. et al. Tumor necrosis factor-alpha and lipopolysaccaride enhance interferon-induced tryptophan degradation and pteridine synthesis in human cells.// Biol. Chem. Hoppe-Seyler. - 1989. - Vol. 370. - P. 1 063-1069], which determines the high prognostic significance of the identified changes.

The determination of NP in biological fluids was previously used to diagnose, predict, and evaluate the effectiveness of the treatment of a number of diseases in adults [Fuchs D., Samsonov M.Yu., Weiss G. et al. Clinical significance of neopterin in human diseases, Fuchs D., Weiss G., Reibnegger G. et al. The role of neopterin as a monitor of cellular immune activation in transplantation, inflammatory, infection and malignant disease.//Crit.Rev.Clin.Lab.Sci. - 1992. - Vol. 29. - P. 307-341, Murr C., Bergant A., Widschwendter M. Neopterin is an independent prognostic variable in females with breast cancer.// Clin. Chem. - 2002. - Vol. 75. - P. 1999-2001].

From the patent technical literature and the practice of examining and treating children with atopic dermatitis, it is not known about a method for predicting the severity of atopic dermatitis in children using the determination of the level of NP.

Hence, the conclusion about the conformity of the proposed solution to the criterion of "novelty" is legitimate.

The above set of essential features is necessary and sufficient to obtain a technical result - a forecast of the severity of atopic dermatitis in children.

There is a causal relationship between the essential features and the problem to be solved, where each feature is necessary and influences the receipt of the technical result, and the combined features are sufficient to obtain it. The conclusion that the claimed technical solution meets the criterion of "inventive step" is legitimate.

The proposed method can be implemented repeatedly using the essential features inherent in it, and, therefore, the claimed technical solution meets the criterion of "industrial applicability".

The proposed method improves the objectivity and accuracy of predicting the course of atopic dermatitis, simple, does not require the cost of purchasing expensive equipment, is highly informative.

The invention was tested on 20 children in the allergology department of the GBUZ JSC Regional Children's Clinical Hospital named after N.N. Silishcheva ”, Astrakhan.

Below are the results of testing.

Clinical example 1. Child D., 5 years old.

Anamnesis of the disease: he was admitted to the hospital with complaints of skin rashes, itching of the skin, nasal congestion, scanty mucous discharge, dry cough, recurrent swelling of the eyes, frequent viral infections (monthly). The first rashes in the form of bright hyperemia of the cheeks while taking paracetamol syrup at 10 months of age, then soaking in the neck folds and axillary area for the use of strawberries, peaches, fish. For 3 months, nasal congestion, redness of the eyes after walking and contact with grass are worried.

A child from II pregnancy against the background of gestosis, edema, II urgent birth. Heredity is burdened: father has acrodermatitis, mother has drug allergy (ceftriaxone), and grandmother has hay fever (quinoa).

At admission: Moderate severity. The skin is pale, maculopapular rash in the elbow, on the ears, scratching. In the throat is unsharp hyperemia of the arches. Peripheral lymph nodes of elastic consistency, not soldered to each other and surrounding tissues, painless. Nasal breathing is slightly complicated by the mucous discharge. The conjunctiva of the eyes is hyperemic. In the lungs, harsh breathing, no wheezing. NPV 20 in 1 minute. Borders of relative cardiac dullness by age. Heart sounds are clear, rhythmic, systolic murmur at 5 point. Heart rate of 95 beats per minute. The abdomen is soft, painless. Liver +0.5 cm from under the rib, the edge is elastic, painless. The spleen is not palpable. Stool, diuresis are not broken.

A comprehensive laboratory examination was carried out. A blood test for total IgE is 523 IU / ml.

The concentration of neopterin in the blood serum is 3.83 ng / ml. A mild course of atopic dermatitis is predicted, although according to the SCORAD scale, indicators are between mild and moderate severity. Diagnosed with atopic dermatitis, infant form, limited, mild, exacerbation, mixed sensitization. Allergic rhinoconjunctivitis, persistent, moderate.

The treatment was prescribed without the use of topical corticosteroids, incl. emollients, antihistamines inside. After 3 months the dynamics is positive, persistent. Exacerbations of the underlying disease were not noted. In dynamics, the concentration of neopterin in the blood serum is 0.96 ng / ml, which is within normal values.

Clinical example 2. Child E., 7 years old.

Anamnesis of the disease: Girl from I pregnancy, I urgent delivery. The mother of the child did not follow a diet during pregnancy; she ate a lot of cow's milk and cottage cheese. Heredity is burdened: the mother has allergic diathesis in her childhood, her father has hives for insect bites and penicillin antibiotics.

The girl has been sick since 6 months of age, when hyperemia of the cheeks, legs, and then soaking in the neck and inguinal folds appeared against the background of the transfer to milk formulas (NAS, Nutrilon) and the introduction of complementary foods with buckwheat milk porridge. The diagnosis was established: Atopic dermatitis, infant form, moderate to severe course, with food sensitization to BCM. Transferred to highly hydrolyzed mixtures, hypoallergenic monocomponent complementary foods. Periodically, a deterioration was observed due to a violation of the diet, in connection with which the girl received antihistamines of the 1st and 2nd generation, Elidel, topical corticosteroids (Advantan, Eloc) with a positive effect.

Last deterioration after acute respiratory infections and the use of antibiotics.

Upon admission to the hospital, the girl complains of skin itching, rashes on the upper and lower extremities, hands. The state of moderate severity. The skin is dry, with patches of erythema, lichenification, excoriation, crust. Subcutaneous fat is moderately developed. Visible mucous membranes are clean. The pharynx is not hyperemic. Lymph nodes are not enlarged. NPV 20 in 1 min. Nasal breathing is free. In the lungs, vesicular breathing, no wheezing. Blood pressure 100/60 mm Hg Heart rate 88 beats / min. The pulse is satisfactory filling, the rhythm is correct, the tones are sonorous, rhythmic. The language is clean. The abdomen is soft, painless. The liver does not protrude from under the costal arch, painless. The gall bladder is not palpable. The spleen is not palpable. The genitourinary system is developed according to the female type. Stool, diuresis are not broken.

An additional examination in the blood serum revealed a moderately high concentration of neopterin 4.27 ng / ml. The medium-severe course of the disease, the period of exacerbation is predicted. Diagnosed with atopic dermatitis, infant form, moderate to severe, exacerbation, with food sensitization. The treatment was carried out taking into account international recommendations a course of topical corticosteroids for no more than 2 weeks, with a further transition to pimecrolimul (elidel), emollients (emolium, lipicar), antihistamines (Xisal). After 3 months, a slight increase in neopterin concentration of 2.86 ng / ml was determined in the dynamics during the examination in blood serum. A mild course of the disease is predicted. It is recommended to further limit the amount of therapy without using topical corticosteroids.

Clinical example 3. Seraphim K., 1 year 10 months.

Anamnesis of the disease: The child is sick from 3 weeks of age with the appearance of papular rashes on the skin of the trunk, extremities, then erythematous lesions, weeping, excoriation, crusts, severe itching, anxiety.

Anamnesis of life: A boy from 5 pregnancies (1 - spontaneous abortion, 2, 3 - term birth, 4 - ectopic), physiologically flowing, 3 term births on time, with a birth weight of 4100, height 50 cm. The early adaptation period went smoothly. Weight gain and psychomotor development at 1 year of age. A baby from birth on breastfeeding. The first manifestations of allergies are from 3 weeks in the form of papular rashes. Hypoallergenic diet of a nursing mother - no effect. From 8 months old, the child was transferred to feeding Nutrilon Pepti Allergy. He received long-term therapy with antihistamines and topical corticosteroids with a positive but short-term effect. There was a further spread of rashes, the appearance of foci of redness and wetness. At 1 year old, he was diagnosed with atopic dermatitis, an infant form, common, moderate, with food sensitization. According to the results of an allergic examination, an increased level of IgE (above 1080 IU / ml), a high level of specific IgE for cow's milk proteins, gluten, buckwheat, rice, and wheat were revealed. Repeatedly, the child received treatment inpatiently, where, against the background of parenteral and local use of hormonal preparations, a slight improvement in skin condition was noted. However, a few days after discharge from the hospital, widespread rashes appeared again, intensification of skin itching.

In the diet of the child: corn, buckwheat porridge, potatoes, beef, rabbit, turkey. Hypoallergenic life is observed.

At admission: the condition is medium-severe for the disease. The skin is pale pink, common erythematous-squamous rashes, dryness, scratching. In the ankle joints - foci of lichenification, erosion under hemorrhagic crusts. On the face - foci of weeping under serous-hemorrhagic crusts. Visible mucous membranes are clean. The pharynx is loosened, subcutaneous fat is moderately developed. Lymph nodes are not enlarged. NPV 25 in 1 min. Nasal breathing is free. In the lungs, puerile breathing, no wheezing. Blood pressure 90/60 mm Hg Heart rate = 115 bpm. The pulse is satisfactory filling, the rhythm is correct, the tones are sonorous, at the top a soft systolic murmur is heard. The language is clean. The stomach is moderately swollen, soft. The liver protrudes from under the costal arch by 1.5 cm, the edge is even. The gall bladder is not palpable. The spleen is not palpable. The genitourinary system is developed by the male type. Stool, diuresis are not broken.

An additional examination in the blood serum revealed a high concentration of neopterin 7.6 ng / ml. The conclusion was made about the need to review the diagnosis of atopic dermatitis in the direction of increasing the severity of the disease (to a severe degree), despite the fact that on the SCORAD scale for the totality of symptoms there was reason to determine the moderate severity.

The child was sent to provide high-tech medical care in the NCHA (Moscow), where the diagnosis was confirmed: Atopic dermatitis, a common form, severe continuous-recurrent course. Food allergy.

During hospitalization, the child underwent a comprehensive examination according to the protocol for the provision of high-tech medical care, including clinical, laboratory and instrumental research methods, multicomponent therapy was carried out using immunosuppressive and immunobiological preparations.

Given the severe, continuously recurring course of atopic dermatitis, the lack of a sustained effect from standard methods of therapy (topical corticosteroids, antihistamines), the immunosuppressive drug Sandimmun Neoral at the rate of 3.5 mg / kg / day, 0.2 ml × 2 each, was connected to the treatment times. However, due to the lack of a significant clinical effect, this drug was canceled from December 23, 2015, by the decision of a medical consultation, the Xolar immunobiological drug at a dose of 75 mg (0.6 ml) was connected once. Against the background of the treatment, the condition of the skin with significant positive dynamics, itching stopped. Remaining residual manifestations of atopic dermatitis, dry skin. Discharged home in satisfactory condition under the supervision of specialists in the community.

In dynamics, the concentration of neopterin in the blood serum decreased to 5.6 ng / ml, which corresponds to the moderate severity of the disease. The child is under “D” observation and treatment using topical corticosteroids with strong action.

The advantages of the proposed method for predicting the severity of atopic dermatitis:

- the method allows you to accurately assess the prognosis of the disease, as it is a reliable laboratory criterion that reflects the presence and severity of the inflammatory process;

- the method is based on taking into account an indicator that reflects the prevailing mechanisms of the inflammatory process in the pathogenesis of chronic atopic inflammatory disease (atopic dermatitis);

- the method is fairly objective, since when using it there is no need to take into account a number of subjective indicators, which cannot be evaluated either by parents or patients, including young children, not practicing physicians;

- can be used in patients of different ages, including early;

- it is possible to predict the further severity of the course in different periods of the disease with atopic dermatitis (exacerbations, remissions, etc.);

- the method is not time-consuming and can be widely used in practical health care, as it provides for laboratory studies by enzyme-linked immunosorbent assay, which is available even for outpatient care.

Claims (1)

A method for predicting the severity of atopic dermatitis in children on the basis of an immunochemical blood test, characterized in that in the blood serum of a child, upon admission to the hospital, the concentration of neopterin is determined and at a neopterin concentration of from 2.6 ng / ml to 4.0 ng / ml a mild severity of atopic dermatitis is predicted, with a mean severity of 4.1 ng / ml to 5.9 ng / ml, and a severe severity of atopic dermatitis in children is predicted at 6.0 ng / ml and higher.