Introduction
Almost every day, neonatologists and pediatricians are faced with the need to establish the genesis of fever in children.
It is well known that the state of temperature homeostasis is determined by the balance of two multidirectional processes: heat production and heat transfer. Most often, hyperthermia in children is associated with infections. It should be noted that the pathogenesis of fever does not depend on the etiology of infectious and inflammatory diseases. Non-infectious hyperthermia is much less common, the etiology and pathogenetic mechanisms of which are very diverse, which requires their detailed consideration.
One of the features of heat exchange in newborns and infants is a sharply limited ability to increase heat transfer during overheating or increase heat production during cooling [1], therefore, in newborns, fever may appear against the background of dehydration due to large loss of body weight due to the syndrome of regurgitation and vomiting, lack of food baby, overheating due to tight swaddling or high ambient temperatures. The reasons for the rise in body temperature can be toxic erythema, urticaria, allergic dermatitis, etc. Massive (widespread) hemorrhages in the skin, intracranial injuries, and cephalohematomas can have the same effect.
Hyperthermia can develop with metabolic disorders, for example, with ketoacidosis, characteristic of diabetes mellitus, or metabolic acidosis, characteristic of a crisis of adrenal insufficiency in adrenogenital syndrome, withdrawal syndrome, in the case of hemorrhages in the adrenal glands, and other endocrine pathologies.
In the work of a neonatologist and pediatrician, febrile patients may encounter a rare hereditary pathology caused by anatomical and physiological features of the skin structure, which lead to disturbances in the heat transfer process and, as a consequence, fever.
Stages of development of dysplasia
The dysplastic process is a continuation of hyperplasia - an increase in the number of cells caused by chronic inflammation and degeneration. Often hyperplasia and dysplasia are accompanied by tissue atrophy (death), since these processes have common genetic mechanisms.
To be precise, the term “dysplasia” is not used in medicine to characterize transient precancerous processes. With pathology in the vaginal sector of the cervix, the condition is designated CIN (cervical intraepithelial neoplasia), precancerous changes in the vagina are designated - VaIN, vulva - VIN.
There are three degrees of dysplasia:
- Mild, mild (D I)
– up to 1/3 of the thickness of the epithelial layer is affected; - Moderate, medium (D II)
- altered cells grow on 2/3 of the epithelial tissue; - Severe, pronounced (D III)
- the entire layer is changed. This degree of dysplasia is the initial stage of cervical and vaginal cancer.
The determining criterion for the degree of dysplasia is the severity of cellular atypia. The more severe the degree, the greater the size, hyperchromicity and polymorphism of the cell nuclei. Epithelial dysplasia can regress (reverse process), be stable or progress. How quickly the process of malignancy progresses depends on the severity and duration of the disease. The more significant the dysplasia, the lower the likelihood of regression.
Severe dysplasia is regarded by gynecologists as an obligate precancer that guarantees the development of cancer. Therefore, patients with obligate precancer are registered with an oncologist.
Clinical observation
Boy M. was born on October 12, 2017, from the 1st pregnancy, complicated by bronchitis at the 18th week. gestation, anemia in the third trimester; I spontaneous labor at 41 weeks. gestation in a 27-year-old woman with A (II) blood group, Rh-negative, suffering from chronic cystitis and being a carrier of cytomegalovirus infection, herpes simplex virus, and human papillomavirus. Labor is quick: I period - 6 hours, II - 30 minutes. The anhydrous interval is 7 hours. The amniotic fluid is light. Apgar score 8/8 points. Anthropometry at birth: weight - 3150.0 g, body length - 52 cm. At birth, the condition is satisfactory, but over time with deterioration due to neurological symptoms (excitation syndrome of the central nervous system (CNS)).
He was transferred to the neonatal pathology department on the 3rd day of life with a diagnosis of “Hypoxic-ischemic damage to the central nervous system, agitation syndrome.” Neonatal jaundice."
Upon admission, the severity of the condition was determined by neurological symptoms (excitement, hyporeflexia, muscular dystonia) and the course of conjunctivitis.
Phenotypically, craniofacial dysmorphia was noted: large forehead, lack of hair on the head, absence of eyebrows and eyelashes; periorbital pigmentation, hyperemia and swelling of the conjunctiva, mucous discharge from the eyes; micrognathia of the lower jaw. The skin is very dry, with peeling, the skin is thin, mobile, icterus of the I-II degree (transcutaneous bilirubin - 210 mmol/l). Heart sounds are rhythmic, loud, no murmurs are heard. Breathing is puerile. No wheezing. The abdomen is soft, painless on palpation. Liver +1.5 cm from under the edge of the costal arch. The spleen is not palpable.
General signs of infectious toxicosis were absent clinically (actively sucking, positive weight curve) and laboratory (immunogram without signs of inflammation, C-reactive protein less than 6 mg/l). Stool and urine output are normal.
X-ray revealed no focal infiltrative changes in the lungs. An ultrasound examination of the abdominal organs also did not reveal any pathology. Electrocardiogram and echocardiogram without abnormalities. According to neurosonography, the brain parenchyma is of medium echogenicity. The pattern of convolutions and grooves is pronounced. Dopplerography of cerebral vessels - without pathology.
Consultation with a neurologist: intrauterine hypoxia, degree 2 cerebral ischemia, acute period, depression syndrome with elements of excitation.
Consultation with a dermatologist: skin xerosis.
Consultation with an otorhinolaryngologist: there is no evidence of acute pathology.
Otoacoustic emission test: passed right and left.
Consultation with an ophthalmologist: subacute blepharoconjunctivitis on both sides. Dry eye syndrome.
On the 3rd day of hospital stay, episodes of increased body temperature to 39 0C appeared. There was a decrease in fever when the baby was unswaddled. When the temperature rose, he became lethargic. Sucking worse, nasal breathing was impaired.
Therapy included the antibiotic ampicillin 100 mg/kg/day (based on current blepharoconjunctivitis), correction of intestinal biocenosis with a drug containing bifidobacterium bifidum, 5 doses/day, fluconazole 5 mg once a day for 3 days.
After 3 days, taking into account the persistent hyperthermia, the presence of sluggish conjunctivitis and the lack of effect from the therapy, the antibiotic was changed to ceftriaxone 50 mg/kg/day. As prescribed by an ophthalmologist, solutions of furatsilin and tetracycline ointment were used locally for the treatment of conjunctivitis.
Through examination, the following were consistently excluded: neuroinfection, pneumonia, herpetic group infections, specific infections (mycoplasmosis, chlamydia), pathology of the urinary system. No foci of infection other than indolent conjunctivitis have been identified.
A clinical blood test over time during the hospital stay, despite disturbances in temperature homeostasis, only once showed leukocytosis of 19.5 × 109/l. The leukocyte formula did not have changes typical of an infectious-inflammatory process.
All parameters in the biochemical blood test were also within normal limits.
However, episodes of increased body temperature continued, especially against the background of restlessness and tight swaddling. It should be especially noted that hyperthermia was not accompanied by signs of infectious toxicosis. Temperature normalization occurred with the use of physical cooling methods.
Considering the phenotypic characteristics of the boy in the form of craniofacial dysmorphia (high forehead, lack of hair on the head, absence of eyebrows and eyelashes, micrognathia of the lower jaw, hyperpigmentation around the eyes, dryness, thinning and peeling of the skin), hyperthermia during swaddling, ineffectiveness of antibacterial therapy, the absence of all the above causes of fever, as well as the male gender of the patient, it was suspected that it was not an infectious, but a genetically determined nature of hyperthermia associated with impaired thermoregulation (heat transfer) against the background of congenital underdevelopment of the sweat and sebaceous glands, anhidrotic ectodermal dysplasia syndrome.
When examined by direct automatic sequencing at the Federal State Budgetary Institution MGSC, a mutation was identified in the coding sequence of the EDA
(EctoDysplasin A, ectodysplasin A), which is responsible for the development of anhidrotic ectodermal dysplasia. Thus, the diagnosis of “Anhidrotic ectodermal dysplasia” was confirmed by the molecular genetic method.
Antibiotics were discontinued in therapy. Nitrofural solution and tetracycline eye ointment were replaced with dexpanthenol eye gel and fusidic acid eye drops. The skin began to be treated with creams and ointments containing dexpanthenol, complex emollients, ethyl esters of linolenic and linoleic acids. Daily bathing and loose swaddling were prescribed.
Against the backdrop of a changed approach to therapy, the symptoms of conjunctivitis were stopped, the general condition improved, motor activity increased, the reflexes of newborns became more stable, appetite improved, the amount of food was expanded to normal, and body temperature returned to normal.
After 16 days in hospital, the boy was discharged in satisfactory condition for outpatient observation. In addition to traditional advice on caring for children of this age, recommendations were given for the mandatory continuation of skin treatment with special moisturizing and softening agents (dexpanthenol, complex emollients, ethyl esters of linolenic and linoleic acids). When clinical manifestations of conjunctivitis resumed, it was recommended to return to the use of eye gel with dexpanthenol and eye drops with fusidic acid. Particular attention was paid to the need for free swaddling, daily baths, mandatory walks in the fresh air and frequent ventilation of rooms. Parents were warned that if their child became very restless, they should have their body temperature taken.
Diagnostics
SM-Clinic specialists diagnose dysplasia based on complaints, general examination and additional research methods:
- in case of cervical dysplasia, the vaginal mucosa is examined with mirrors, colposcopy, biopsy followed by cytological examination;
- To establish hip dysplasia, X-ray examination, ultrasound diagnostics, and magnetic resonance imaging are prescribed;
- Connective tissue dysplasia is detected using ultrasound of internal organs, X-ray examination of the lungs and skeleton, ECG, Echo-CG, blood system examination.
Discussion
What formed the basis for verification of the diagnosis? Analysis of clinical data (absence of symptoms of infectious toxicosis, ineffectiveness of antibacterial therapy, rapid relief of fever when undressing the child, features of the condition of the skin and its appendages) and the absence of laboratory markers of infectious inflammation became arguments in favor of syndromic genetic pathology. The diagnosis was confirmed by molecular genetic method. Conjunctivitis was part of the syndrome.
Anhidrotic ectodermal dysplasia (Christ-Siemens-Touraine syndrome, OMIM305100) is a hereditary disease in which a genetically determined disruption of the development of the outer germ layer, the ectoderm, occurs [2, 3]. As a result, sentinel signs affect derivatives of the ectoderm: skin, hair, teeth, some cartilages, sweat, sebaceous, lacrimal and mammary glands. Key signs: decreased sweating, alopecia, hypodontia.
The accepted division into anhydrotic and hydrotic dysplasia is conditional depending on the preservation of sweating. The degree of underdevelopment of sweat glands and hair follicles varies widely.
The first description of anhidrotic ectodermal dysplasia was published in 1848 by J. Touraine. In 1929, A. Wiig identified the disease as an independent form. Independently of each other, dentist J. Christ in 1913 and dermatologist H. Siemens in 1929 also described the clinic of this (most common) form of ectodermal dysplasia (synonyms: Christ-Siemens syndrome, Siemens syndrome). Occurs with a frequency of 1:17,000 newborns. In 95% of cases, inheritance is X-linked. EDA gene
is located in the chromosome segment Xq12-Xq13 and encodes the protein ectodysplasin A, which is necessary for the normal development of ectoderm derivatives. There is a carrier test (Minor test), which allows identifying female carriers in 90% of cases. An alcohol solution of iodine is applied to the skin of the back, and an oil solution of starch is applied on top of it. In carriers, areas without sweat glands remain uncolored [4].
Phenotypic features:
skin: thin, with wrinkles and peeling in the first days of life;
hair: thin, dry, bleached, sparse, up to complete baldness; sweat glands are underdeveloped or completely absent, as are sebaceous glands;
mucous membranes: absence of glands on the mucous membrane of the mouth, nose, and sometimes the bronchi;
teeth: hypodontia or adontia; tenon-shaped incisors; underdevelopment of alveolar arches;
head: large forehead, massive brow ridges; hyperpigmentation around the eyes.
Rare signs include hypo- or aplasia of the mammary glands or nipples, underdevelopment of the nasal turbinates, nail dystrophy, mental retardation, bronchial asthma, and cataracts.
Prognosis: Hyperthermia can be fatal.
It is advisable for patients to live in a cool climate and douse themselves with water. They are predisposed to purulent conjunctivitis, rhinitis, otitis, and pulmonary infections. The mucous membrane of the esophagus and colon suffers.
In most observations, if the diagnosis is made at an early age of the child and preventive measures have been taken (fighting overheating, secondary infections), then the prognosis is generally favorable. In terms of intellectual development, the prognosis is ambiguous - both mental retardation and complete preservation of intelligence are equally likely to be recorded.
Treatment of cervical dysplasia
Treatment depends on the severity of dysplasia. If the mucous membrane is affected in the first degree, expectant management is used, especially in nulliparous women. A routine examination is carried out every six months, and if the disease does not progress, a preventive visit to the gynecologist is recommended.
In more severe cases, surgical treatment is used. The most effective methods:
- Excision of affected tissue - electroexcision (conization); Radio wave - the most modern method of treating dysplasia, recommended by European gynecologists.
- Amputation of the cervix is used in rare, especially severe cases, when there is no other way to help - this is done by oncologists.
To combat the papilloma virus (HPV), antiviral drugs and agents to stimulate the immune system are used. At the same time, treatment of concomitant pathologies is carried out.
Where is vaginal and cervical dysplasia treated in St. Petersburg?
Treatment of dysplasia requires a serious approach, since the disease is considered a dangerous precancerous condition. Gynecologists at the Diana Medical Center in St. Petersburg have many years of experience in treating epithelial dysplasia, which allowed us to develop an effective and safe approach to the treatment of this pathology.
We are happy to help every patient diagnosed with dysplasia, and we use only modern approaches to treatment and innovative hardware - the latest radio wave knife "Fotek".