Section 7. Medical science
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Sirazitdinova Victoriya Felixovna, Senior scientific assistant, applicant of the Department of Dermal and Venereal diseases, Tashkent Pediatric Medical Institute
E-mail: mbshakur@mail.ru
Characteristic peculiarities of virusologic values in children with herpes simplex combined with atopic dermatitis
Abstract: In the article we presented the data of checking of 61 children with clinical manifestations of Herpes simplex combined with atopic dermatitis. Characteristic types of Herpes Simplex DNA were revealed with the help of Real-time PCR, so in 26.0% we revealed EBV, in 16.3% — HSV-2, and CMV in 10.2%. In 49.2% we revealed its association. In 37.7% of the children with AD high titers of IgG antibodies to Herpes Simplex virus and in 47.4% cases diagnostically significant presence of specific IgM we determined using immune enzyme analysis.
Keywords: Herpes Simplex virus, atopic dermatitis, children
One of the most topical and complex problems of the modern medicine is infectious pathology in children, explained by the high level of morbidity, difficult diagnostics, and low efficiency of the therapy. Among great number of diseases caused by pathogenic microorganisms such as bacteria, fungi, protozoa, the most dangerous are viral infections, often processing without symptoms, non-pathognomically, in association with other diseases, and more often together with the background weak immunity.
Unfavorable epidemiological circumstances, and causes leading to the growth of manifest forms of infections and its relapses prove insufficient vigilance of doctors in relation to viral diseases, late laboratory diagnostics, absence of a common concept of therapy and prophylaxis — all these lead to increase of the number of patients with viral diseases [1].
Several researches, performed both in our country and foreign, show high level of Herpes virus infection (HSV, CMV, EBV) among children with somatic pathologies [2; 3; 5; 6].
Many studied performed recently showed that, from 3% to 15% children and from 2% to 10% adults suffer atopic dermatitis (AD) [2; 10]. In the present time significant rise ofAD morbidity is noted among children, and its manifestations are registered in 90% of the patients applying to a dermatologist [4]. These data prove that, AD becomes a significant problem of health care.
There is a hypothesis about a possible role persisting herpetic and cytomegaloviral infections play in the development of allergic pathologies, including AD in children [3].
In spite of the fact that clinical manifestations of various forms of the pathology are well known and described, for the confirmation of the diagnosis, definition of prognosis and prescription of adequate therapy of herpetic infection it is necessary to apply a complex of laboratory research methods.
Objective: to study characteristic peculiarities of viral values in children with Herpes Simplex associated with atopic dermatitis.
Characteristic peculiarities of virusologic values in children with herpes simplex combined with atopic dermatitis
Materials of methods of the research: we performed checking of 61 children with atopic dermatitis and clinical
manifestations of Herpes simplex in the age from 1 to 14 years old. Duration of AD progress in all patients corresponded to the age. Exacerbation stage was noted in 57 (93.4%) patients, while the rest had incomplete remission. From the anamnesis data we detected that, first clinical manifestations of AD on skin in the majority of the children (41 or 67.2%) appeared within the first year of life, less from one year to two years old (17 or 27.9%) and in few patients it appeared later (3 or 4.9%). Hereditary predisposition to AD was determined in 57.4% of the children. We also analyzed the prevalence of clinical manifestations of Herpes simplex virus among close relatives sick with AD, and it was equal to 36.1%.
Dermal manifestations of dermatitis were characterized by typical morphology and location of rash (face, neck, body, flexor surfaces of limbs). In clinics there was prevalence of symmetric erythematous-papulous rash tend for grouping, with small and middle plate peelings; foci of infiltration and lichenification; linear and spotty excoriations; and hemorrhagic crusts. White spread dermagraphism was defined in 44.3% (27) patients, mixed in 57.4% (35), and pink one in 16.4% (10).
The study of clinical progress peculiarities of AD associated with HSV in children was performed by means of analysis of clinical-epidemiological cards filled for each patient. We took into account severity degree of AD scaled with the help of SCORAD, type of the disease progressing (relapsing or continuous), activity degree, prevalence, clinical form ofAD, presence of complications, concomitant lymph adenopathy, etc.
The degree ofAD severity was average 57.5±7.1 points. In 33.3% children we registered maximal activity degree. Spread form of AD was registered in 64.8%, general form in 27.6%, and local one in 7.6% children.
The complex studies of the children included traditional research methods such as clinical blood, urine analysis, copro-gram, ultra sound checking of inner organs, and the patients were checked by other specialists, if necessary.
All children were also checked with the help of PCR-real time method for detection of genome DNA of the agent. Besides that we performed detection of markers of HSV1 and HSV2, cytomegalovirus (CMV) and Epstein-Barr virus (EBV). For the study of humoral immunity parameters by means of immune enzyme analysis (IEA) we performed serological test in 61 children for the detection of specific antibodies to HSV, CMV, EBV and other herpes viruses.
For the material we used peripheral blood, saliva, and urine.
Results of the research: with the PCR real time analysis data we determined the following characteristic rules: markers of HSV2 were detected in 16 (16.3%), CMV in 10 (10.2%), EBV in 26 (26.0%) patients, and the last groups were mostly children in the age from 1 to 3 years old; and HHV6 was detected in 9 (9.1%) patients. In relation to association with other herpes viruses in the children with AD,
we detected association of HSV-1+HSV-2 in 19 (19.3%) children, HSV-1+EBV in 6 (6.1%) and HHV-6+EBV in 5 (5.1%).
The highest percent values of the virus isolation were achieved in urine (96%) and saliva (91.3%).
The analysis of the results of antibodies titer (AT) definition showed that, it varied from 1:50 to 1:24800. In compliance with the accepted regulations for "Vector-Best" test system titers 1:200 and more are considered to be diagnosti-cally significant (DST). Titers below this value are not diag-nostically significant (DNST). We revealed high prevalence of the viruses (HSV and CMV) among children with AD, and this value was equal to 63.9%. In 18% we revealed CMV, less — combination of two infections HSV and CMV (8.1%). 2/3 of the children had high titers of antibodies IgG to HSV (37.7%). The obtained data testify reactivation of herpes viruses in AD.
Activity of infectious process was determined by the presence of specific IgM antibodies to viruses. Diagnostically significant titers (31:200) were revealed in 12 (19.6%) children with AD, high titers were determined in 17 (27.8%), and it was about half (47.4%) of the total number of the examined children with specific IgM.
Thus, markers of Herpes Simplex virus in children with AD were met in 63.9% cases. High titers of specific IgM in blood serum were revealed in 47.4%, and that proved persisting and reactivity of herpes viruses in children with atopic dermatitis.
In conclusion it should be noted that, for the establishment of reliable diagnosis, detection of intra-cellular location of the infectious agent and definition of quantitative viral load it is necessary to apply high sensitive, very specific and fast PCR-technologies, it is especially important in pediatric practice. In the checking of the direct markers of herpes viral infections in new-born babies and children of young age preference should be given to the urine test, as viral particles in it accumulate in great amounts and the material is obtained by means of non-invasive method.
Conclusions:
1. The types of Herpes simplex virus DNA were detected in children with Herpes Simplex virus associated with atopic dermatitis with the help of PCR method with hybrid-fluorescent detection of amplification products in real-time mode; thus in 26.0% we detected EBV, in 16.3% HSV-2, and CMV in 10.2%. In 49.2% we revealed association of these viruses such as HSV-1+HSV-2 in 19 (19.3%), HSV-1+EBV in 6 (6.1%) and HHV-6+EBV in 5 (5.1%) patients.
2. 2/3 of the children with AD had high titers of antibodies IgG to Herpes Simplex virus (37.7%). The obtained data testify reactivation of herpes viruses in AD.
3. Diagnostically significant titers to Herpes simplex (31:200) we detected in 19.6% of the children with AD, and high titers were revealed in 27.8%, it was equal to 47.4% of the total number of the examined children with specific IgM.