X-linked ichthyosis is a common genodermatosis, which is manifested by excessive keratinization of the skin, the formation of scales. The disease is caused by a mutation of the sterol sulfatase gene in the female sex chromosome. The main symptoms are dense dark scales on the skin, lesions of the neck, trunk, extensor surfaces of the limbs, the onset of the disease in infancy. Diagnostics is based on dermatological examination and collection of family history, biochemical, molecular genetic, instrumental methods are carried out to clarify. Patients are prescribed special skin care with the use of keratolytics, emollient components, AHA / BHA acids.
ICD 10
Q80.1 X-linked ichthyosis
General information
Recessive X-linked ichthyosis (RXLI) belongs to the group of mendelian (inherited according to Mendelian laws) keratinization disorders. The disease was isolated in a separate form in 1960, occupies the second place in the structure of all types of ichthyosis, second only to ichthyosis vulgaris, and is registered with a frequency of 1:2000-1:6000. Given the type of inheritance, mostly men are ill, and most women are asymptomatic carriers of the affected gene. Pathology is not dangerous or fatal, but it is highly common, requires proper supportive treatment, which determines its relevance in modern dermatology.
Causes
The disease is caused by a point mutation in the steroid sulfatase (STS) gene, which is located on the short arm of the X chromosome at the Xp22 locus.3. A monogenic anomaly is inherited using an X-linked recessive transmission mechanism: in a marriage of a mother who is a healthy carrier of a mutant gene with a healthy man, in accordance with Mendel’s laws, 25% of sons are likely to be born sick, 25% are healthy, 25% of daughters are likely to be healthy, 25% are carriers of a mutant gene.
Children from the marriage of a healthy woman with a sick man will be clinically healthy, but all daughters will be carriers of a linked hereditary disease. All the sons of a woman with hereditary hyperkeratosis and a healthy man will be born sick, and the daughters will be carriers of the disease. And finally, in extremely rare cases when both parents suffer from ichthyosis linked to the X chromosome, all children will also be sick.
Pathogenesis
Pathological skin changes are caused by disorders of lipid metabolism in the epidermal layer. Normally, the enzyme hydrolase (sterol sulfatase) is present in the stratum corneum, which controls the production of steroid sulfates – cholesterol sulfate CSO4, sulfated steroid hormones. A sufficient level of these substances is necessary for regular exfoliation of keratinized cells, self-renewal of the skin.
Ichthyosis of the X-linked monogenic type is characterized by the insufficiency of this enzyme, as a result of which the level of CSO4 in the epidermis increases, the activity of epidermal sterol proteases is inhibited. Such changes provoke retention hyperkeratosis: connections between keratinized cells are strengthened, the normal process of desquamation of keratinocytes is disrupted. However, the proliferation of keratinocytes is not impaired.
Symptoms
Clinical manifestations of ichthyosis occur in the first months of a child’s life. On the child’s body, thin, non-pigmented scales of irregular shape become noticeable, which slightly adhere to the skin, are quite easily removed by mechanical action. After 3-4 months, they acquire a grayish or brown color, becoming similar to dirt. At the same time, the scales are firmly bound to the skin, they cannot be removed during hygienic procedures.
Typical localization of hyperkeratosis: the posterior surface of the neck (a symptom of a “dirty neck”), elbow joints, the outer surface of the forearms. Less often, elements of genodermatosis are observed on the trunk, in the popliteal pits. Palms, soles, face remain intact. The skin resembles a snake’s coat due to cracks, uneven coloring of scales. The activity of X-linked ichthyosis depends on the season: the disease worsens in the cold season, with high humidity.
Complications
Isolated skin manifestations of hyperkeratosis give negative consequences in the form of a cosmetic defect. A number of patients experience psychological discomfort, difficulties with socialization. More serious are the extracutaneous complications of X-linked ichthyosis: corneal opacity, ADHD – attention deficit hyperactivity disorder (40% of patients), autism spectrum disorders (25%), cryptorchidism (20%). Rarely pathology is accompanied by anosmia, unilateral aplasia of the kidneys.
Diagnostics
Examination of the patient by a dermatologist begins with a standard examination of the skin surface to detect typical elements of retention hyperkeratosis. You can suspect the disease by the presence of “dirty neck skin”, the clean surface of the skin of the soles and palms, the identification of similar changes in other family members. Laboratory and instrumental techniques are used to confirm the diagnosis:
- Blood test. In order to differentiate the X-linked variant from vulgar ichthyosis, serum protein electrophoresis is performed, the activity of STS in leukocytes or skin cells is studied.
- Genetic testing. In case of difficulties in diagnosis, a PCR study, fluorescent hybridization is recommended to detect a gene mutation on the X chromosome.
- Visualization of the skin structure. Histology and electron microscopy of the affected areas of the skin are necessary for the differential diagnosis of hereditary dermatoses.
In families with burdened heredity, prenatal examination is possible to exclude X-linked ichthyosis. It is possible to suspect pathology by reducing the level of maternal estradiol. Invasive diagnostic methods (amniocentesis, chorionic villus biopsy) are prescribed to verify the diagnosis. The resulting biomaterial is examined in the laboratory to confirm the insufficiency of sterol sulfatase.
Treatment
Etiotropic therapy of X-linked hyperkeratosis is absent. The main task is to select the right skin care products that reduce the intensity of subjective symptoms, inhibit the processes of keratinization, improve the appearance of the skin. In the complex therapy of ichthyosis , agents with the following active components are used:
- Keratolytics. Propylene glycol and urea are often prescribed in different dosage forms, which remove excess keratinized scales, make the skin smoother.
- AHA and BHA acids. Care cosmetics with acids (salicylic, lactic, glycolic) regulates the level of keratinization, enhances the exfoliation of keratinized particles, maintains a normal level of hydration of the skin.
- Glycerin. The component should be constantly present in cosmetics for patients with ichthyosis, as it softens the skin after keratolytics and acidic agents, eliminates dryness and discomfort.
- Retinoids. External drugs are recommended according to the indications for adult patients in the winter months to prevent the exacerbation of ichthyosis, normalize the processes of skin regeneration.
- Products containing SPF. Filters that block UV rays are mandatory components when using acids, retinoids. Sunscreens prevent the appearance of hyperpigmentation, prevent photoaging of the skin.
Prognosis and prevention
The X-linked type of disease is characterized by a benign course, although with age, unlike simple ichthyosis, the number of elements of dermatosis does not decrease. The prognosis is favorable with the correct selection of care, compliance with all the recommendations of the dermatologist. In the presence of extracutaneous symptoms of the disease, the prognosis is determined by their severity. The basis for the prevention of hyperkeratosis linked to the female sex chromosome is provided by medical and genetic counseling of couples in whose family history there have been cases of ichthyosis.
Literature
- Majmundar V. D., Baxi K. Hereditary And Acquired Ichthyosis Vulgaris // StatPearls Publishing. — 2021.
- Oji V., Tadini G., Akiyama M. et al. Revised nomenclature and classification of inherited ichthyoses: results of the First Ichthyosis Consensus Conference in Soreze 2009 // J Am Acad Dermatol. — 2010. — № 63. — Р. 607–641.
- Ahmed H., O’Toole E. A. Recent advances in the genetics and management of harlequin ichthyosis // Pediatr Dermatol. — 2014. — Vol. 31, № 5. — Р. 539–546.
- Almendra N. V., Duran L. A. Hereditary ichthyosis: A diagnostic and therapeutic challenge // Rev. chil. Pediatr. — 2016. — Vol. 87, № 3. — P. 213–223
- Millsop J. W., Sivamani R. K., Lee D. C. A Case of Bullous Congenital Ichthyosiform Erythroderma, a Rare Pediatric Genodermatosis, in a Newborn // Austin J Dermatolog. — 2014. — Vol. 1, № 4. — Р. 1016.
- Ichthyosis vulgaris // Mayo Clinic. — 2021.