Bullous ichthyosis is an extremely rare form of genodermatosis, which is characterized by excessive keratinization processes, the formation of numerous blisters, yellow—brown scales. The disease is caused by an autosomal dominant type of inheritance. Skin changes include bullae, weeping erosions, foci of hyperkeratosis, palmar-plantar keratodermia. Diagnosis of the disease involves the examination of skin biopsies, molecular genetic tests. Methods of treatment of bullous ichthyosis are symptomatic: taking systemic retinoids, external desquamative therapy, pharmacy cosmetics for home care.
Q80.3 Congenital bullous ichthyoform erythroderma
Bullous ichthyosis in the medical literature has many synonyms: epidermolytic ichthyosis, epidermolytic hyperkeratosis, bullous congenital ichthyosiform Broca’s erythroderma. The disease was first described by the Russian dermatologist Nikolsky in 1897, and the French scientist L. Brock was engaged in a detailed study of the clinical picture of pathology in the early twentieth century. Bullous form of ichthyosis occurs with a frequency of 1 case per 200-300 thousand population, sexual and racial differences in the incidence were not found.
Ichthyosis with bullae can occur with several types of gene mutations, the most common are in the genes KRT–1 (locus 12q13.3), KRT-10 (locus 17q21.2). Inheritance of gene defects occurs according to the autosomal dominant type with full penetrance, however, in 50% of patients mutations occur sporadically with unencumbered familial anamnesis. In modern genetics, research is underway to establish the provoking factors of spontaneous mutations in genodermatoses.
The development of bullous ichthyosis is associated with damage to the genes encoding the formation of keratin type 1 (KRT-1) and type 10 (KRT-10). These types of collagen fibers are normally involved in maintaining the structural integrity of suprabasal keratinocytes. They are responsible for the stability of the barrier function of the skin, the formation of strong intercellular contacts, the preservation of moisture in the dermis.
In addition to the typical skin symptoms, the disease is characterized by multiple metabolic disorders: changes in lipidogram, proteinogram, hypovitaminosis. The work of the skin glands is also disrupted. Unlike X-linked recessive ichthyosis, the exchange of sterol proteases is not disrupted in the bullous form, therefore the connections between keratinized cells are weak, which causes fluid transudation and the appearance of blisters on the skin.
Dermatological manifestations of the disease are observed from the birth of an infant. The skin of a newborn has a bright pink or red color, they are covered with bubbles of different sizes filled with a transparent or cloudy liquid. A characteristic feature of this variant of ichthyosis is that areas of unchanged skin look natural, which distinguishes the condition from the “colloidal fetus” syndrome, when the child’s body is covered with a shiny stretched film.
Under pressure and friction, new bubbles are easily formed. With careless touches, the bulls are opened, exposing bright red erosive wetness. Erosions with bullous ichthyosis heal very slowly, stagnant red spots and flaking foci form in their place. Due to the alternation of superficial wounds, remnants of detached epidermis, large blisters, the child’s skin resembles a burnt one.
Starting from the age of 2-3, active symptoms of hyperkeratosis are noted. Numerous yellow or brown scales appear on the body, which are usually surrounded by inflamed reddened skin. The typical localization of dermatological elements in patients with bullous ichthyosis is the flexor surfaces of the extremities, armpits. A characteristic feature of the disease is palmar-plantar keratodermia.
Bullous ichthyosis is characterized by a severe course, lethal forms are not excluded: abortions in early stages, late miscarriages, stillbirth. Often, children are born prematurely, as a result of which they develop respiratory distress syndrome (“hyaline membrane disease”), intracerebral hemorrhages, retinopathy of prematurity. Prematurity can cause necrotic enterocolitis, severe hypoglycemia, and eating disorders.
Against the background of extensive lesions, all skin functions that are of paramount importance in the newborn period are disrupted — respiratory, excretory, thermoregulatory. Due to the massive loss of fluid during the opening of the bull, dehydration occurs in infants. Multiple open wounds become the entrance gate for infection, which in conditions of insufficient functioning of the newborn’s immunity is fraught with septic complications.
Bullous ichthyosis is characterized by typical skin manifestations, so a preliminary diagnosis is made during a consultation with a pediatric dermatologist in the first weeks of an infant’s life. For differential diagnosis of different types of genodermatoses, exclusion of other variants of dermatological pathologies accompanied by the formation of bull, patients are prescribed such research methods as:
- Study of the skin structure. Electron microscopy of biopsies of the affected areas reveals changes in the basal plate of the epidermis, loss of contacts between cells, lipid-like vacuoles in the cells of the horny and granular layers.
- Blood tests. To clarify the severity of the child’s condition, a clinical and biochemical blood test is performed. To exclude allergic epidermolysis bullosa, which has similar skin symptoms, an immunogram is recommended.
- Genetic testing. To confirm the presence of bullous ichthyosis, genome sequencing is performed to search for pathognomonic mutations at loci 17q21.2, 12q13.3.
- Prenatal diagnosis. In families where there are patients with bullous ichthyosis, it is advisable to conduct medical and genetic counseling of pregnant women. For early detection of pathology according to indications, amniocentesis or biopsy of chorionic villi is used.
During the period of active bull formation, medical care for the patient is similar to the protocol for managing burn patients. Adequate rehydration therapy is provided to correct the lost fluid, parenteral or probe nutrition is used to fill the nutritional needs of the child. Massive antibiotic therapy is necessarily used to prevent complications of an infectious nature.
At the bull stage, careful care of the child is necessary, the exclusion of traumatization of the skin, wearing clothes and underwear made of the softest possible fabrics. To reduce fluid loss, bandages with white vaseline are applied, with extensive lesions, gel compresses made of hydrolyzed polymer are effective. After the appearance of signs of keratinization, the therapy scheme changes, several groups of drugs are prescribed:
- Keratolytics. External formulations with urea, propylene glycol are necessary for softening the foci of hyperkeratosis, removing keratinized masses from the skin surface.
- Retinoids. External and systemic drugs are recommended for adult patients for effective control of hyperkeratosis, stabilization of skin regeneration processes.
- Fruit acids. Therapeutic cosmetics with acids are selected for routine home care in order to reduce the activity of keratinization, exfoliate the horny masses in time.
- Nourishing creams. To prevent roughening of the skin, eliminate dryness and discomfort, cosmetics are applied, which include glycerin, lanolin, vegetable oils.
- Funds with SPF. Sunscreens are prescribed for regular use to prevent excessive pigmentation. SPF-products are a mandatory component of care in the treatment of active substances (acids, retinoids).
Prognosis and prevention
Bullous ichthyosis is the most unfavorable option among the entire group of keratinization disorders, since it is associated with a high level of antenatal and infant mortality. The prognosis largely depends on the volume of bullous skin lesions, the presence of infectious complications, the timeliness and completeness of medical care. Taking into account the genetic prerequisites of pathology and the high frequency of spontaneous mutations, preventive measures have not been developed.