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DERMATOVENEREOLOGY

INVENTION
Patent of the Russian Federation RU2286570

A METHOD OF DIFFERENTIAL DIAGNOSTICS OF THE ERYTHRODERMAL FORM OF T-CELLULAR MALIGNANT LYMPHOMA OF SKIN AND OTHER ERYTHERODERMISM

A METHOD OF DIFFERENTIAL DIAGNOSTICS OF THE ERYTHRODERMAL FORM OF T-CELLULAR MALIGNANT LYMPHOMA OF SKIN AND OTHER ERYTHERODERMISM

The name of the inventor: Kungurov Nikolai Vasilyevich (RU); Kuklin Igor Aleksandrovich (RU); Kokhan Muza Mikhaylovna (RU); Kislyak Nadezhda Valeryevna
The name of the patent owner: Kungurov Nikolai Vasilyevich (RU); Kuklin Igor Aleksandrovich (RU); Kokhan Muza Mikhaylovna (RU); Kislyak Nadezhda Valeryevna
Address for correspondence: 620075, Yekaterinburg, ul. Lunacharskogo, 133, ap. 16, M.M. Cohan
Date of the beginning of the patent: 2004.08.30

The invention relates to medicine, namely, to dermatology, and concerns a method for differential diagnosis of the erythrodermal form of T-cell malignant skin lymphoma and erythrodermia in benign dermatoses. The method consists in the study of quantitative parameters of peripheral blood and clinical and anamnestic signs of the disease, such as intoxication syndrome, skin tooth, palmar-plantar hyperkeratosis, hair thinning, poly-lymphadenopathy, white dermographism, then calculate the indices using linear discriminant analysis using formulas to determine Values ​​of variables characterizing different types of erythrodermia (F1 and F2, F3, F4, F5), which are then compared among themselves and diagnose this or that type of disease. The method provides an increase in the efficiency of differential diagnostics of the erythrodermal form of T-cell malignant skin lymphoma and other erythrodermatomas and thereby contributes to the reduction of the pre-diagnostic period for patients with T-cell malignant skin lymphoma.

DESCRIPTION OF THE INVENTION

The invention relates to medicine, namely, to dermatology, and can be used for differential diagnosis of the state of erythrodermia in benign dermatoses and T-cell malignant skin lymphoma (T-ZLK, mushroom mycosis).

Erythroderma (E) is a condition characterized by a universal lesion of the skin, marked by inflammatory skin infiltration, fever, lymphadenopathy and endogenous intoxication. The development of the erythrodermal version of the course of dermatosis, regardless of its nosological affiliation, indicates a complicated condition of the patient (Differential diagnosis of skin diseases., Edited by Studnitsina AA - M .: Meditsina, 1983. - p.108).

This condition can develop with complicated or severe course of many dermatoses (secondary erythroderma), but the main causes of erythrodermia are psoriasis, eczema, toxicermy, atopic dermatitis, Devergie's disease, etc. (Kalamkaryan AA, Averbakh EV, Zabanova E Vs. Persina IS Clinical features of malignant skin lymphomas, Vestnik, Dermatology and Venerology, 1989. - No. 12.-C.8-12., Rodionov AN Erythrodermal lymphoma of the skin: Textbook - L., 1989, - 67. Lezvinskaya EM The method of television computer morphodensitometry of lymphocytes in the diagnosis of malignant lymphomas of the skin, proceeding according to the type of erythroderma, // Russian Journal of Skin and Venereal Diseases - 1998. - ą2 - Lezhvinskaya EM Cytological diagnosis of malignant lymphomas of the skin, proceeding according to the type of erythroderma: Dis .... Doctor of medical science, M., 1997. - 239 pp.). Erythroderma and may be primary, without previous typical manifestations of dermatosis, or be a manifestation of malignant lymphoproliferative skin disease (T-cell malignant skin lymphoma - fungal mycosis).

Definition (clarification, verification) of the diagnosis of erythrodermia in chronic benign dermatosis (secondary) or erythrodermal T-ZLK form (primary) should be carried out at the earliest possible stage of the disease development in order to determine the strategy and tactics of therapy, which differs significantly for these diseases; And the most important is the early detection of erythrodermia in malignant skin lymphoma (EFTLC), since this diagnosis indicates the presence of oncolympoproliferative lesions and has a progressive course that threatens death.

The established fact is the considerable complexity of the diagnosis of EFTRL, and the possibilities of clinical diagnostics are recognized as limited due to the lack of specificity of erythroderma and polymorphism of the clinical picture, which largely imitates other chronic skin diseases (Vavilov AM, Lezvinskaya EM Primary skin lymphomas: phenotypic characteristic The main clinical forms, classification. // Archive of pathology .- 1998. - № 2. - P.3-7; Lezvinskaya EM, Molochkov VA, Larina NK The incidence of malignant skin lymphomas in the Moscow region and Ways to improve medical and diagnostic care for patients. // Russian Journal of Skin and Venereal Diseases .- 2000. - No. 4. - P.12-17., Zackheim HS, Koh N.K., Weinstock MA. Assessing clinical outcomes in Cutaneous T-cell lymphoma, // Hematol, Oncol., Clinical North, Am., 1995.-Vol. 9 (5).-P.1021-1029; Burg G., Kempf W., Haeffher A., ​​Nestle F ., Dummer R. Cutaneous Lymphomas., Current Probl., Dermatol. - 1997. - Vol. 9 (5). - P.137-204).

Laboratory studies (histo-morphological, immunomorphological, immunological) in the early stages of the development of the disease may be poorly informative and insufficient for the final verification of the diagnosis (Kutasevich Ya.F. Features of pathogenesis, methods for early diagnosis and rational therapy of fungal mycosis: Doctor of medical sciences M., 1989. - 320 pp. Trofimova IB Modern concepts of diagnostics, classification and treatment of skin lymphomas // Russian Medical Journal .- 1997.-T.5, - No. 11 .- P.704-708. ). High-tech methods for the diagnosis of T-ZLK (including erythrodermic form), such as electron microscopy of the skin, molecular genetic studies (PCR), remain inaccessible under conditions of domestic dermatological institutions (Vavilov AM, Lezvinskaya EM Immunocompetent structures of the skin and their Role in the development of primary skin lymphomas // Archives of Pathology - 1996. - № 6, - C.7-11, Savvateeva MV et al., 2003).

The most weighted and reproducible approach to the diagnosis of ETETP is the comprehensive (performed by the doctor) assessment of all available history data, clinical manifestations and paraclinical studies, on the basis of which a preliminary diagnosis of the disease is formulated. The most authoritative researchers in the field of lymphology emphasize the necessary account of all these sections (Kalamkaryan AA, Berenbein BA, Potekaev NS Modern problems of the clinic, diagnosis, pathogenesis, treatment of malignant lymphomas of the skin and Kaposi's sarcoma. // Vestn. Dermatology and Venerology - 1991. - № 7. - P.18-26, Skin and venereal diseases / A guide for doctors in 4 volumes / edited by Academician Yu.K. Skripkina .- Moscow: Medicine, 1995. - 453 pp. Yastrebov VV, Raznatovsky IM Skin Lymphomas: Urogenital Herpesviral Infection - Edited by EV Sokolovsky, Sotis, St. Petersburg, 2000; Burg G., Dummer R. , Haefflier A., ​​Kempf W., Kadin M. From inflammation to Neoplasia // Arch., Dermatol .-- 2001. - Vol.137 .-- P.949-952).

In recent years, the active introduction into medicine of methods of mathematical modeling and the creation of automated systems, including computer systems, has significantly expanded the possibilities of diagnosis and therapy of diseases. One of the varieties of medical computer diagnostic systems is nosological diagnosis with the establishment (substantiation) of a specific diagnosis based on the available information (clinical and paraclinical) (Kobrinsky BA Systems of artificial intelligence in medicine: State, problems and prospects // News of the Art of Intelligence 1995 ; 2: 65-79). In the dermatology industry, such developments are few.

There are known developments where the authors proposed an automated expert diagnostic system for assessing the histological pattern of a skin biopsy that allows the diagnosis of the presence of the maximum possible number of morphological characters and their combinations to establish a diagnosis of mushroom mycosis and differentiate it from plaque parapsoriasis (Rodionov AN, Barbinov V VV, Kazakov DV Histological Diagnosis of Lymphoma of the Skin (Achievements and Problems) // Journal of Dermatovenereology and Cosmetology - 1997. №1 .- P.5-14; Samtsov AV, Barbinov VV, Kazakov DV Histological differential diagnostic features of early mushroom mycosis and small-pellet parapsoriasis established with the help of an expert system // Journal of Dermatovenereology and Cosmetology .- 1998. - №1 .- P.12-24, Kazakov DV New criteria Differential diagnostics of early forms of lymphomas of the skin and plaque parapsoriasis (Author's dissertation, Candidate of Medical Science, St. Petersburg, 1999, - 23 pp.).

By definition, this system has a limited range of applications (differential diagnosis of only 2 diseases), the approach to diagnosis does not take into account anamnesis, clinic and other manifestations of the disease.

The method of computerized (mathematical) evaluation of the quantitative characteristics of the chromatin structure of peripheral blood lymphocytes used for the diagnosis of T-ZLK and differential diagnosis of erythrodermia is closer to the nosological topic under consideration (EM Lezvinskaya, "Cytological Diagnosis of Malignant Lymphomas of the Skin Based on the Type of Erythroderma: Dys. ... Doctor of Medical Sciences, M., 1997. - 239. E. Lezvinskaya Method of television computer morphodensitometry of lymphocytes in the diagnosis of malignant lymphomas of the skin, proceeding according to the type of erythrodermia // Russian Journal of Skin and Venereal Diseases - 1998. - № 2. - С.23-27.). This method was developed using a mathematical apparatus, which is essentially the same as the one claimed, but is limited to an automated evaluation of only one of the diagnostic methods (cytomorphology), without taking into account the possibility of a mathematically assessed difference in anamnestic, clinical and paraclinical data.

The aim of the invention is to increase the efficiency of differential diagnosis of the erythrodermal form of T-cell malignant skin lymphoma and other erythrodermatomas by a standardized assessment of the complex of clinical and paraclinical data and mathematical modeling.

The goal is realized by calculating a standardized formula that allows one to determine the values ​​of variables characterizing different types of erythroderms (F1 and F2, F3, F4, F5), which then are compared among themselves and with high certainty diagnose this or that type of disease.

The method of diagnosis is used in the conditions of a specialized dermatological department or in a day hospital in the corresponding profile.

Stepwise development of standardized diagnostic formulas.

1. Ranking of reference clinical-anamnestic and laboratory features based on the construction of a mathematical model of differential diagnosis of EFTZLK.

The initial data are complaints, clinico-anamnestic and laboratory-instrumental results of the examination of patients. The actual data structured in the responses of the standardized maps were entered into an electronic database in the format of the Microsoft Excel 97 program tables.

2. Cluster analysis (the KVAZAR pattern recognition software package) identified atypical representatives ("releases") for each of the groups of patients studied, whose presence in the sample could significantly distort the results of the analysis (Fig. 1, 2). As follows from the presented drawings, among patients with EFTZLK atypical representatives or "emissions", distorting the results of the analysis, it was not revealed, which indicated the homogeneity of the group. At the same time, among the representatives of the group of patients with erythroderms in benign dermatoses (using the criterion of minimum distance in the space of 138 studied indices), a region of atypical "emissions" was identified, which was excluded from further calculations.

3. Calculation of correlation coefficients between patients with erythroderms for the identification of multidirectional vectors of patients belonging to the same group was carried out. The indicated multidirectional vectors were not revealed in patients.

4. Detection of differential diagnostic signs by methods of variance analysis using non-parametric criteria for comparing mean and multiple comparison of means, t-test for normal features and comparison of the shares of characteristics of different sets of patients was carried out.

To assess the degree of informative parameters, one-way analysis of variance was used, which allows one to assess the degree of influence of an individual trait on the diagnostic result, for which the zero hypothesis about the absence of such influence was put forward and evaluated. At the same time, an alternative hypothesis was put forward, stating that such an influence of the trait in question exists. To test the hypothesis, the Fisher test (F) was calculated, which depended on two parameters (N is the number of patients in the sample, n is the number of gradations of the trait).

The observed value of the Fisher test (Fn) was compared with the critical value of this criterion (Fcr), which depended on the significance level p ( Ј 0.05). If Fn> Fcr, an alternative hypothesis was adopted, which allowed us to affirm, with a probability of not less than 0.95, the effect of the test feature on the diagnostic result. Thus, the observed value of the Fisher test (Fn) served as a measure of the degree of influence of the trait on the result of the diagnosis: the greater the value, the higher the degree of its influence was estimated. However, it should be noted that even weakly informative signs by the Fisher criterion could exert a strong enough influence, interacting with other signs. Therefore, weakly informative features were excluded from further consideration with great caution, only after constructing a model of multiple linear regression.

5. Decisive rules for diagnosis are developed, taking into account and participation of all selected informative features. Using the procedure of step-by-step selection of variables, it was possible to reduce the dimension of the decision rule while maintaining the maximum correctness of pattern recognition.

6. As a result of the discriminant analysis, 11 statistically significant and uncorrelated signs were identified, allowing differential diagnosis of EFTLC and erythrodermia in benign dermatoses (Table 1). For EFTZLK such were the syndrome of intoxication, intolerable and intense itching of the skin, palmar-plantar hyperkeratosis, hair thinning, poly-lymphadenopathy, white dermographism, leukocytosis, eosinophilia, hyperIgE, reduction of gamma-interferon concentration and increase of IL-4 blood. These features were subsequently used as the basic ones in the construction of the "decisive rule" of the mathematical model of diagnosis.

For benign dermatoses, using discriminant analysis, we were able to identify 5 statistically significant features that distinguish erythroderma from each other, which were used to construct the "decisive rule" of the mathematical model of diagnosis (Table 2).

7. Expressions of linear discriminant functions F1 and F2 are developed in the following form:

Where

X 1 - the absolute value of eosinophils in peripheral blood,

X 2 - concentration of gamma-interferon serum,

X 3 is the serum IgE value,

X 4 - concentration of IL-4 serum,

X 5 - the number of leukocytes in the peripheral blood,

X 6 - palmar-plantar hyperkeratosis,

X 7 - hair thinning,

X 8 - poly-lymphadenopathy,

X 9 - white dermographism,

X 10 - a syndrome of intoxication,

X 11 - intolerable and intense itching of the skin.

Note: X 1 -X 5 are informative quantitative traits, and X 6 -X 11 are informative qualitative features.

8. Expressions of linear discriminant functions F3, F4 and F5 are developed in the following form:

Where

X 1 - the absolute value of eosinophils in peripheral blood,

X 2 - concentration of gamma-interferon serum,

X 3 is the serum IgE value,

X 4 - palmar-plantar hyperkeratosis,

X 5 - white dermographism,

Implementation of the diagnostic method:

- In order to carry out differential diagnostics of erythroderms, the value of the corresponding characteristic must be substituted in each equation, in the case of X 1 -X 5 - absolute (quantitative) values, in the case of X 6 -X 11 - the value equal to 1 (if the characteristic is present in the patient) or 0 (If the characteristic is absent).

The obtained values ​​of variables F1 and F2 are compared with each other and at F2> F1 the results of differential diagnostics with 97.6% accuracy can be interpreted in favor of EFTZLK, and at F1> F2 - in favor of benign erythroderma.

To perform differential diagnosis of erythrodermia in benign dermatoses, it is necessary to substitute the value of the corresponding attribute in each equation, in the case of X 1 -X 3 - absolute (quantitative) values, in the case of X 4 and X 5 - a value equal to 1 (if there is a characteristic for the patient ) Or 0 (if the characteristic is absent). After that, the obtained values ​​of variables F3, F4 and F5 are compared with each other. With F3> F4> F5, the results of differential diagnosis of erythrodermia can be interpreted in favor of erythrodermia in atopic dermatitis, with F4> F3> F5 - in favor of psoriatic erythroderma, and in the case of F5> F3> F4 - in favor of erythroderma with eczema.

To facilitate the calculation of variables (F1, F2, F3, F4, F5), formulas are created that function in the Microsoft Excel spreadsheet system, where the coefficients with their signs and the possibility of substituting arguments are taken into account.

Clinical and diagnostic approbation of the differential diagnosis model of EFTZLK

The described method was applied in the clinic of the Ural Institute of Internal Medicine and the Ministry of Health of the Russian Federation for diagnosis in 123 patients with different types of erythroderma. Tables 3 and 4 provide a comparison of the correctness of the diagnosis in patients with erythrodermia using the method of mathematical modeling with clinical and laboratory verification in the UrNIIDViI. As follows from the presented tables 3 and 4, the coincidence of the results of the tests conducted on the training sample with clinico-laboratory verification of the diagnosis in patients testifies to the specificity of the method developed by us to diagnose EFTRL. The reliability of such a separation of patients with EFTZLK and erythrodermia in benign dermatoses was 97.6%, and in the differentiation of benign erythroderms on the basis of the indicated signs, the average number of nasological forms was 87.8%.

Effectiveness of the method

To assess the overall effectiveness of the claimed method, we compared the duration of the pre-diagnostic period in patients with T-CLC (this cohort includes GM in a traditional clinical form and EFTLC), to which various diagnostic diagnostic complexes were used (all studies were performed in the clinic URNIIDVII of the Ministry of Health of the Russian Federation) in Consecutive time periods. The data in Table 5 indicate a reliable decrease in the pre-diagnostic period in patients who, in addition to routine methods, were subjected to the claimed differential diagnosis method, compared with those used in 1996-1999. At the same time, the claimed method of differential diagnosis contributed to the reduction of the pre-diagnostic period on average to 5.75 ± 0.8 years, which does not differ significantly from the data of Kokhan M.M. (2002), which used high-tech, expensive methods in the diagnosis of T-ZLK.

The use of the method is illustrated by the following clinical examples

Example 1 . The patient L., born in 1935, entered the dermatological department of the UrNIIDVI with complaints of reddening of the skin, accompanied by intense itching, constriction and flaking of the skin, increased hair loss on the scalp, general weakness, chills and fever, weight loss of 7 kg For the previous 12 months. She considers herself to be sick for 3 years, when for no apparent reason on the skin of her back appeared itchy elements that spread to other parts of the body within 1-2 months, there was skin hyperemia. With a significant increase in foci of skin damage and intensification of skin itching appealed to a dermatologist at the place of residence. Inpatient treatment was performed in the dermatological department with DS: Acute eczema, secondary erythroderma (antihistamine and desensitizing preparations, dyspropan 1.0 W / M No. 1, external ointment therapy with GCS ointments), discharged in a state of clinical improvement. Within 2 months of discharge from the hospital, the condition deteriorated sharply and in May 2001, in connection with the exacerbation, was again hospitalized in the dermatological department with DS: Erythrodermia of unknown origin (eczema eczema, toxicermia ?, T-cell malignant skin lymphoma? ). In the histological study of the skin data for T-ZLK was not detected, skin changes were nonspecific. Consulted by a hematologist - data for a systemic blood disease was not revealed. Against the background of the treatment (antihistamines and desensitizing drugs, external ointment therapy with glucocorticosteroids), improvement of the condition (decrease in the intensity of hyperemia and skin itching) was noted. Over the previous 2-3 months, she noted a sharp deterioration in the course of the disease - total skin damage, increased itching, and therefore was hospitalized in the dermatological department of UrNIIDViI to clarify the diagnosis.

Anamnesis of life, allergic anamnesis, professional route - without any special features. Heredity for skin diseases and oncopathology is not burdened. Postponed diseases - scarlet fever, measles, ARVI.

Objectively: a patient of medium height, regular physique, satisfactory nutrition. In the lungs, breath is vesicular, rales are not heard. Heart sounds are muffled, rhythmic, BP 150/90 mm Hg. V., Heart rate of 74 per minute. The abdomen is soft, painless on palpation, the liver and spleen are not enlarged. Palpable inguinal lymph nodes, up to 2 cm in diameter, are dense, painless and mobile during examination. Physiological administration is normal.

Local status: the skin process is generalized, occupying 85-90% of the skin. Skin in the state of erythroderma, brick-red in color, with pronounced infiltration, with fine and large-plate scaling, increased dryness, turgor is reduced. In the forearm area, linear excoriation, hemorrhagic scaly-crusts. Pronounced hyperkeratosis of the palms and soles, deep hemorrhagic cracks with large-scale scales. The nail plates are polished. Hair is brittle, dull, with a diffuse thinning on the skin of the scalp. Dermographism is white. (Fig. 3).

Based on clinical and anamnestic data, at the first stage of diagnosis, a clinical diagnosis was not established.

Laboratory data. The general analysis of a blood: Нb150 g / l, эр. 4.3 × 10 12 / l, color. Poc. 1.04, watering can. 14.0 × 10 9 / l, fell. 1%, seq. 23%, eosis. 1%, lymph. 71%, mon. 4%, ESR 5 mm / h. In the general analysis of urine and the biochemical hepatogram of deviations is not revealed. Complex serological reactions to syphilis negative

In the immunogram: pronounced lymphocytosis due to an increase in the content of T- and B-lymphocytes. Moderate increase in monocyte and eosinophil content. Increase in serum IgM and IgE (836.7 IU / ml). INF-gamma-4.9 (pkg / ml), IL-4 - 151.0 (pg / ml).

According to the X-ray study of the chest, no pathological changes were detected, ultrasound of the abdominal cavity organs - diffuse changes in the parenchyma of the pancreas, and ultrasound of the pelvic organs - no volume formations.

Against the backdrop of the treatment (detoxification, antibacterial therapy, antihistamines, glucocorticosteroids per os 40 mg / day, external ointment therapy), improvement was noted (decrease in the intensity of itching and the number of hemorrhagic excoriations).

To perform differential diagnostics in this way, the values ​​of the corresponding characteristics were substituted in each equation:

F 1 = -36.26 + 4.54 * 0.14 + 0.79 * 4.9 + 0.0009 * 836.7-0.06 * 151.0 + 0.52 * 14.0-8, 1 * 1-4.36 * 1 + 1.58 * 1 + 5.94 * 1 + 8.94 * 1 + 11.21 * 1

F 2 = -75.27 + 7.31 * 0.14-0.55 * 4.9 + 0.0011 * 836.7 + 0.1 * 151.0 + 0.5 * 14.0 + 12 * 1 + 5.96 * 1 + 1.74 * 1 + 7.54 * 1 + 11.72 * 1 + 19.15 * 1

Comparing the values ​​of the variables F1 (-17.5) and F2 (4.05), with F2> F1, the results of differential diagnosis meant a high probability of the patient having EFTLC.

In order to further refine the diagnosis (stage 2), a repeated histological examination of the skin biopsy, immunophenotyping of the skin sample was performed. At histological examination: in all departments of the dermis a dense diffuse epidermotrophic polymorphic infiltrate was found, represented by tumor lymphoid cells of predominantly large size with a well-expressed cytoplasm, nuclei of different shapes and structures. Immunomorphologically: the infiltrate is represented by T-limocytes with the phenotype CD4 +; High positivity of MCA Ki67 and moderate CD95 +.

After carrying out immunomorfologic studies (2 stages of diagnosis), taking into account clinical and immunomorfologic data, the patient was diagnosed with the final nosological diagnosis of EFTLC, after which she was hospitalized in the regional scientific and practical center "Oncology" for specific therapy.

Example 2 . Patient M., born in 1955, in October 2000 entered the dermatological department of UrNIIDVI with complaints of intense itching, dryness, tightening and flaking of the skin, redness of the skin; Pain in the muscles of the upper and lower extremities, increase in temperature to 37.0-37.2 ° C; General weakness, poor sleep; Pain in the region of the heart of a crushing nature, arising from physical and emotional overloads and being stopped by the ingestion of nitroglycerin.

He considers himself to be sick from childhood, when, for no apparent reason, during the winter period, skin peeling and itching appeared in the area of ​​the flexural surfaces of the elbow and knee joints. Until the age of 18, he was treated as an outpatient by his place of residence with DS: Neurodermatitis. After serving in the ranks of the SA and until 1997, he noted short-term exacerbations during the course of the illness, mainly in spring and autumn. Treatment was carried out by traditional methods in district KVD.

In 1997, after closed traumatic brain injury and treatment in the neurological department, erythrodermia developed for the first time, which was not resolved despite the ongoing therapy of GCS (30 mg / day of prednisolone per os) in the dermatological department of the Pervouralsk HPC. For the period from 1997 to 2000, The patient was repeatedly on inpatient treatment, where antihistamines, desensitizing therapy, dyspropan 1.0 v / m, external - topical steroids were prescribed, as a result of which a short-term improvement was achieved. Previous hospital treatment without significant improvement in the skin process, was prescribed at a dose of prednisolone 15 mg / day. With a preliminary diagnosis of erythroderma of unknown origin (atopic dermatitis ?, malignant skin lymphoma?), The patient was hospitalized in the dermatological department of the URIIRI.

Anamnesis of life and a professional route - without any special features. Allergic anamnesis - in 1998, an episode of the development of Quincke's edema to use an unidentified drug. Heredity for skin diseases and oncopathology is not burdened. Postponed diseases in childhood do not remember. In the anamnesis: 1999 - myocardial infarction, III group of disability; IHD, postinfarction cardiosclerosis, stenocardia II f. Class.

Objectively on admission: the general condition is satisfactory. Patient with a regular physique, medium height, normal nutrition. In the lungs vesicular breathing, wheezing is not heard. Cardiac rhythm sounds, muffled, blood pressure 120/80 mm Hg, heart rate 66 per minute. The abdomen is soft and painless in palpation, the liver and spleen are not enlarged. Palpable inguinal lymph nodes, diameter up to 1 cm, densely elastic consistency, painless and mobile in the study. Physiological administration is normal.

Local status: the skin process is universal. The cutaneous pattern is underlined, the turgor is reduced. Skin covers in the state of erythroderma, increased dryness, bright red color, with infiltration, are covered with small-plate scales on the face and mid-plate on the limbs. Peeling is particularly pronounced in the upper and lower extremities, where there are numerous linear excoriations and hemorrhagic crusts. Lichenification of the skin is uneven: from moderate on the body to pronounced on the limbs. Nail plates are polished, physiological color, the usual form. Hair thin, dull. Hair growth on the scalp, pubis and in the armpits is preserved. There is no hyperkeratosis of the palms and soles. Dermography is white, fast (Fig. 4).

Laboratory data. The general analysis of a blood: Нb140 g / l, эр. 4.2 × 10 12 / l, color. Poc. 1.0, watering can. 8.9 × 10 9 / l, fell. 5%, seq. 56%, eosis. 6%, lymph. 24%, mon. 9%, ESR 19 mm / h. In the general analysis of urine and the biochemical hepatogram of deviations is not revealed. Complex serological reactions to syphilis negative

In the immunogram: a mild imbalance of the T-lymphocyte. Increase in serum IgE (267.3 IU / ml). INF-gamma-5.0 (pkg / ml), IL-4 - 27.0 (pg / ml).

According to the X-ray study of the chest, no pathological changes were detected, according to the ultrasound of the abdominal cavity organs - diffuse changes in the pancreatic parenchyma.

With histological examination, skin changes were of a non-specific nature, not permitting a final diagnosis. Taking into account the anamnestic data and the clinical and histological picture, a preliminary diagnosis was determined at the first stage of differential diagnosis: T-cell malignant skin lymphoma (mushroom-like mycosis), erythrodermic form? Atopic dermatitis, erythroderma?

To carry out the second stage of differential diagnostics, the method developed by us was applied where in each equation the values ​​of the corresponding clinical and anamnestic signs and laboratory data were substituted:

F 1 = -36.26 + 4.54 * 0.53 + 0.79 * 5.0 + 0.0009 * 267.3-0.06 * 27.0 + 0.52 * 8.9-8, 1 * 0-4.36 * 0 + 1.58 * 0 + 5.94 * 1 + 8.94 * 0 + 11.21 * 1

F 2 = -75.27 + 7.31 * 0.53-0.55 * 5.0 + 0.0011 * 267.3 + 0.1 * 27.0 + 0.5 * 8.9 + 12 * 0 + 5.96 * 0 + 1.74 * 0 + 7.54 * 1 + 11.72 * 0 + 19.15 * 1

Comparing the obtained values ​​of the variables F1 (-9,512) and F2 (-37,37) with F1> F2, the results of differential diagnostics with a high probability showed the absence of the patient with EFTLC.

На фоне проводимого лечения (дезинтоксикационная, антибактериальная терапия, антигистаминные препараты, гепаринотерапия п/к по схеме, преднизолон per os 15 мг/сутки с постепенным снижением, наружная мазевая терапия) отмечалось улучшение состояния: снижение интенсивности кожного зуда и инфильтрации кожи, разрешение эритродермии. Пациент был выписан в удовлетворительном состоянии, с улучшением, с диагнозом атопический дерматит, эритродермия.

Через 5 месяцев в УрНИИДВиИ при проведении повторной биопсии кожи у пациента диагноз атопического дерматита был гистологически верифицирован.

Таким образом, заявляемый способ дифференциальной диагностики эритродермий, позволяющий с высокой долей вероятности выявить у больных ЭФТЗЛК или другие формы эритродермий при доброкачественных дерматозах, является воспроизводимым инструментом в арсенале специалиста дерматолога.

Его основной целью является обеспечение при минимально достаточной полноте обследования пациента (анамнез, клинические проявления, рутинные параклинические методы) с высокой степенью достоверности предположить наличие у больного ЭФТЗЛК и/или эритродермий иного генеза, в соответствии с этим научно обосновать применение высокотехнологичных диагностических исследований, необходимых для окончательной верификации диагноза.

Table 1

Коэффициенты линейных дискриминантных функций для дифференциальной диагностики ЭФТЗЛК и эритродермий при доброкачественных дерматозах.
Переменные Коэффициенты дискриминантных функций
Эритродермии при доброкачественных дерматозах ЭФТЗЛК
Свободный коэффициент -36,26 -75,27
X 1 4,54 7,01
X 2 0,79 -0,55
X 3 0,0009 0,0011
X 4 -0,06 0.1
X 5 0,52 0.5
X 6 -8,1 12,54
X 7 -4,36 5,96
X 8 1,58 1,74
X 9 5,94 7,54
Х 10 8,94 11,72
X 11 11,21 19,15

table 2

Коэффициенты линейных дискриминантных функций для дифференциальной диагностики эритродермий при доброкачественных дерматозах.
Переменные Коэффициенты дискриминантных функций
АДЭ PE ЭЭ
Свободный коэффициент -17,87 -10,94 -13,51
X 1 0,68 -0,63 0,14
X 2 0.63 0.57 0,37
X 3 0.003 0,001 0.002
X 4 4,38 5,91 7,53
X 5 10,14 6.12 6,75

Table 3

Сопоставление правильности постановки диагноза у больных эритродермиями методом математического моделирования с клинико-лабораторной верификацией в УрНИИДВиИ
Группы больных № гр-пы Отнесены к группе I Отнесены к группе II % правильной диагностики % диагностических ошибок
Обучающая выборка больных I 47 1 97,92 2,08
II 2 73 97,3 2.7
Контрольная оценка I 48 0 100 0
II 0 75 100 0
Примечание: Группа I - больные ЭФТЗЛК, группа II - больные эритродермиями при атопическом дерматите, экземе и псориазе.

Table 4

Сопоставление правильности постановки диагноза у больных доброкачественными эритродермиями методом математического моделирования с клинико-лабораторной верификацией в УрНИИДВиИ
Группы больных № группы Отнесены к группе I Отнесены к группе II Отнесены к группе III % правильной диагностики % диагностических ошибок
Обучающая выборка больных эритродермиями I 22 0 2 91,66 8,33
II 1 25 2 89,28 10,72
III 2 2 19 82,6 17.4
Контрольная оценка I 24 0 0 100 0
II 0 28 0 100 0
III 0 0 23 100 0
Note: Group I - ADE patients, group II - patients with psoriatic erythroderma, group III - patients with eczematous erythroderma.

Table 5

The comparative duration of the pre-diagnostic period with the use of various technologies (the overall effectiveness of the new method)
Analyzed period Applied approaches to diagnostics Duration of pre-diagnostic period Data source
1996-1999 Routine comprehensive diagnosis of T-ZLK 8.4 ± 1.0 years Kungurov NV, Kokhan MM, Sazonov SV, Kuklin IA Principles and algorithms of clinical and laboratory diagnosis of malignant skin lymphomas. A manual for doctors. - Ekaterinburg. - 2000. - 24 C.
2000-2002 Complex diagnosis of T-ZLK, supplemented with morphometry, study of immune status, immunomorphology of the skin 6.15 ± 0.8 years Kokhan M.M. T-cell malignant skin lymphomas: clinical and immunological aspects of diagnosis, staging and therapy. Diss .... dokt. honey. Sciences., 2002
2002-2004 Comprehensive diagnostics of EFTAWC carried out using the claimed method 5.75 ± 0.8 * years The description and actual data on the results obtained will be presented in the thesis
* - reliability of differences in the index p <0.05

CLAIM

A method for differential diagnosis of the erythrodermal form of T-cell malignant skin lymphoma and erythrodermia in benign dermatoses, which consists in examining the parameters of peripheral blood with the subsequent calculation of indices using linear discriminant analysis, characterized by the inclusion of clinical and anamnestic signs of the disease, for calculating the linear discriminant Analysis of the syndrome of intoxication, intolerable and intense itching of the skin, palmar-plantar hyperkeratosis, hair thinning, poly-lymphadenopathy, white dermographism, leukocyte count, eosinophil, IgE, gamma-interferon and interleukin-4 by the formulas:

F 1 = -36.26 + 4.54 · X 1 + 0.79 · X 2 + 0.0009 · X 3 -0.06 · X 4 + 0.52 · X 5 -8.1 · X 6 - 4.36 · X 7 + 1.58 · X 8 + 5.94 · X 9 + 8.94 · X 10 + 11.21 · X 11 ;

F 2 = -75.27 + 7.31 · X 1 -0.55 · X 2 + 0.0011 · X 3 + 0.1 · X 4 + 0.5 · X 5 + 12 · X 6 +5, 96 · X 7 + 1.74 · X 8 + 7.54 · X 9 + 11.72 · X 10 + 19.15 · X 11 ,

Where X 1 is the absolute value of eosinophils in the periodic blood, X 2 is the concentration of gamma interferon in the blood serum, X 3 is the IgE value in the blood serum, X 4 is the concentration of IL-4 in serum, X 5 is the number of leukocytes in the peripheral blood , X 6 - palmar-plantar hyperkeratosis, X 7 - hair thinning, X 8 - poly-lymphadenopathy, X 9 - white dermographism, X 10 - intoxication syndrome, X 11 - intolerable and intense itching of the skin, while in X 1 -X 5 substitute Quantitative values, and in X 6 -X 11 - value equal to 1, if the characteristic is present in the patient, or 0, if the characteristic is absent;

By the formulas:

F 3 = -17.87 + 0.68 · X 1 + 0.63 · X 2 + 0.003 · X 3 + 4.38 · X 4 + 10.14 · X 5 ;

F 4 = -10.94 + 0.63 · X 1 + 0.57 · X 2 + 0.001 · X 3 + 5.91 · X 4 + 6.12 · X 5 ;

F 5 = -13.51 + 0.14 · X 1 + 0.37 · X 2 + 0.002 · X 3 + 7.53 · X 4 + 6.75 · X 5 ,

Where X 1 is the absolute value of eosinophils in the peripheral blood, X 2 is the concentration of gamma interferon in the serum, X 3 is the IgE value in the blood serum, X 4 is the palmar-plantar hyperkeratosis, X 5 is white dermographism, while in X 1 -X 3 substitute quantitative values, in X 4 -X 5 - a value equal to 1, if the characteristic is present in the patient, or 0 if the symptom is absent; The obtained values ​​of F 1 , F 2 , F 3 , F 4 and F 5 are compared among themselves, at F 2 > F 1, the erythrodermal form of T-cell malignant skin lymphoma is diagnosed, and for 3 3 > F 4 > F 5 erythroderma is diagnosed in atopic dermatitis , At F 4 > F 3 > F 5 - psoriatic erythroderma is diagnosed, and in the case of F 5 > F 3 > F 4 - eczematous erythroderma is diagnosed.

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Date of publication 01.04.2007гг