Pediatric hereditary epidermolysis bullosa

Introduction to pediatric hereditary bullous epidermolysis Hereditary bullous epidermolysis (epidermolysisbullosahereditaria) is a group of more common hereditary diseases characterized by blisters after minor trauma to the skin and mucous membranes. The classification has not been unified so far. Since 1991, Fine et al. have classified the blister or fissure formation under electron microscopy into three categories, and are classified into several subtypes due to the characteristics of clinical manifestations. It is now clear that the three types of bullous epidermolysis are autosomal recessive or dominant inheritance. basic knowledge The proportion of illness: 0.003% Susceptible people: children Mode of infection: non-infectious Complications: muscular dystrophy, myasthenia gravis, sepsis, arrhythmia

Pediatric hereditary bullous epidermolysis

(1) Causes of the disease

The disease is autosomal recessive or dominant, and the causative genes are keratin K5 and K14 genes, but do not include rare mutations and subtypes, as new pathogenic genes are still under investigation.

(two) pathogenesis

Because it can form keratosis, this disease is considered to be a variation of follicular keratosis. Acantholytic and keratosis can occur in these two diseases. Two diseases may also occur in the same patient, electron microscopy Tension microfilaments and desmosome complex changes or intercellular substance formation disorders, this potential genetic defect plus external stimuli such as friction, heat, damage, cold and bacteria and fungi, especially Candida infection, can induce this disease.

Pediatric hereditary bullous epidermolysis prevention

According to genetic and epidemiological analysis, assess the risk of recurrence of genetic diseases, and do a good job in genetic counseling.

Pediatric hereditary bullous epidermolysis complications Complications muscular dystrophy myasthenia gravis arrhythmia arrhythmia

After the scar is formed, it affects function and even disabling, resulting in small mouth malformation and tongue tassel shortening, esophageal stricture, small intestine involvement, trachea, laryngeal lesions, accompanied by muscular dystrophy or congenital myasthenia gravis, often involving multiple organs. Severe anemia and intestinal abnormalities can cause growth retardation, arrhythmia caused by sepsis or electrolyte disturbance secondary to infection.

Pediatric hereditary bullous epidermolysis symptoms common symptoms herpes blister papules dystrophy scarring arrhythmia epithelial bleeding permanent alopecia muscle atrophy

Hereditary bullous epidermolysis is divided into three types and many subtypes, but has common clinical features, mostly after birth or within 2 years of age, friction parts such as hands, feet, knees, elbows, ankles, buttocks Rubbing is the appearance of blister blood blister of varying sizes, erosion, crusting, pigmentation, visible millet rash, atrophy, scar, nail dystrophy, alopecia and secondary infection, etc., after the nail toe scar affects function and even disabling.

The three types and subtypes are now briefly described as follows:

1. Epidermolysis bullosa simplex (EBS)

(1) Localized:

1 EBS of hands and feet: also known as Weber-Cockayne type, is the most common EBS subtype, blister mainly occurs in athlete's foot, followed by palm, mechanical friction is serious, Blisters can occur in any part of the body, in the neonatal or infancy, a few delays to adolescence or adulthood, heavy winter light and heavy summer, long walks and mechanical friction can make the condition worse, often forming limitations or extensive paralysis, with age Some patients have ameliorated their condition, and a small number of patients have malnutrition, bruises and scar formation, and no extracutaneous lesions.

2 teeth or dysplasia of simple bullous epidermolysis (EBS with anodontia / hypodontia): also known as Kallin syndrome, this type is rare, in addition to localized blister, accompanied by brittle hair, partial alopecia and teeth hypoplasia.

(2) generalized:

1Koebner type simple bullous epidermolysis (EBS, Koebner variant): the second common subtype of EBS, often at birth or shortly after birth, generalized blistering, obvious compression site, can have a Malnutrition, millet rash and/or scar, but the scar is superficial and limited, except for some patients with mild and limited blisters in the early mouth of the baby, no extracutaneous lesions.

2 herpes simple epidermolysis epilepsy (EBS herpetiformis): also known as Dowling-Meara type, is the third common subtype of EBS, the incidence of birth, extensive skin exfoliation, often lead to children after birth In the first year of death, the lesions of most patients were similar to the Koebner type. The occurrence of nail dystrophy, millet rash and/or scar was similar to that of the Koebner type. In prepuberty, most patients developed extensive or fused palmar horns. Chemical.

3 EBS with mottled pigmentation with/without keratoderma: rare in this type, irregular pigments in some parts of the skin Most of these pigmentation spots do not occur in areas where blisters have occurred. Some cases can be alleviated with age. The palmar keratosis is similar to Weber-Cockayne type, and there is no extracutaneous lesion.

4 superficial simple bullous epidermolysis (EBS superficialis): blister or fissure only occurs under the horny layer, similar to the peeling syndrome, because the lesion is very shallow, therefore, erosion and post-inflammatory hyperpigmentation or decline Spots are more common than intact blisters, and the difference from peeling syndrome is that there is no spontaneous peeling and no extracutaneous lesions.

5Ogna type simple bullous epidermolysis (EBS, Ogna variant): This type is rare and unique, no report in the country, the lesion is characterized by local intradermal hemorrhage, like the color of the contusion and the hook.

6 EBS with or without associated neuromuscular disease: This type is rare and severe, often accompanied by muscular dystrophy or congenital myasthenia gravis. Because of the high early childhood mortality rate, it is also known as fatal EBS. In some cases, there are atrophic scars, pigmentation and nail dystrophy. At this time, it is difficult to distinguish from JEB in clinical practice. There are often multiple organ involvement, such as severe bone marrow abnormalities. Moderate to severe growth retardation caused by anemia and intestinal abnormalities.

7Mendes da Costa type simple bullous epidermolysis (EBS, Mendes da Costa variant): is the most common type of systemic EBS.

2. Junctional bullous epidermolysis (junctional EB, JEB) All JEB are autosomal recessive, further divided into 6 subtypes according to the extent of skin lesions and other clinical and laboratory characteristics. type.

(1) Localized:

1 reverse borderline bullous epidermolysis (JEB, inverse): blisters, erosions and atrophic scars only occur in skin folds, such as the armpits, groin and neck, in addition to the Orrlitz type in the mouth and esophagus There are no external skin lesions other than the same serious blisters and scars.

2 acral borderline bullous epidermolysis (JEB, acral): also known as the lightest JEB (JEB, minimus), the lesion is limited to the extremity.

3 Progressive borderline bullous epidermolysis (JEB, progressive): also known as neuronal JEB (neurotropica), characterized by mid- or late childhood onset.

(2) generalized:

1 Heavy borderline bullous epidermolysis (JEB, gravis): also known as Herlitz type, also known as lethal JEB (EB lethalis) due to high infant mortality, clinical features of generalized blister, erosion And atrophic scars, when the skin lesions involve the scalp, can form part or complete alopecia, can form a symmetric highly proliferated granulation tissue around the nose and mouth, when the nostrils are involved, can form narrow nostrils, even occlusion, granulation tissue It can affect the back of the neck, the upper part of the back, the armpits and the nail folds of the nails. This type of skin is extremely fragile, and it is common for malnutrition, which can eventually cause nails to fall off. The nail bed is covered by scar tissue, which can cause contracture due to scar formation of the armpit. Extra-external skin involvement is widespread and severe. Common oral malformations and tongue tassel shortening, esophageal stricture, growth and development disorders caused by small bowel involvement, others may also affect the eye and genitourinary tract, iron caused by intestinal damage Loss of blood caused by malabsorption and chronic extensive skin lesions often causes multi-factor anemia, and a small number of patients can have severe trachea, laryngeal lesions and even Occlusion occurs. In NE-BR cases, at least 30% of these patients have tracheal and laryngeal lesions. Tracheostomy can save the lives of such patients, but eventually these patients often die early in the baby, although most The cause of death is unclear, but some may be due to arrhythmias caused by sepsis or electrolyte imbalance secondary to infection. 15% of patients with this type have pyloric atresia, accounting for only 3% of NEBR cases.

2 light borderline bullous epidermolysis (JEB, mitis): also known as non-Herlitz type or generalized atrophic EB (generalized atrophic EB), despite blistering, erosion, atrophic scar and post-inflammatory hypopigmentation or deepening Can occur, but proliferative granulation is lacking, and in addition to trachea, laryngeal lesions, other extracutaneous lesions are lacking, A, scalp lesions are similar to Herlitz type, but life expectancy, in addition to enamel dysplasia, in many ways this type Similar to systemic DDEB.

3 scar border junctional bullous epilepsy (cicatricial JEB): is a rare systemic JEB, characterized by pseudo and finger (toe) malformation, clinically difficult to identify with Hallopeau-Siemens type.

3. Malnutrition bullous epidermolysis (Dystrophic EB, DEB) Common features of this type are blisters, erosion, scarring, atrophic scars, millet rash and nail dystrophy or nail deficiency, according to the distribution of lesions The range and genetic pattern are different and are divided into 9 subtypes.

(1) Localized:

1 reverse dystrophic bullous epidermolysis (DEB, inverse): is a rare type, lesions are confined to the neck, armpits, groin and lumbosacral, extracutaneous lesions involving the mouth and esophagus, and sometimes esophagus The lesion is more severe than the skin lesion.

2 acral dystrophic bullous epidermolysis (DEB, acral): also known as the lightest DEB (minimus).

3 anterior malnutrition bullous epidermolysis (DEB, pretibial): is a special type of lesion, lesions are limited to the anterior iliac crest, recurrent small blisters and papule-like scars, sometimes purplish purple Red, similar to lichen planus, except for malnutrition, no extracutaneous lesions.

4 centripetal dystrophic bullous epidermolysis (DEB, centripetal).

(2) generalized:

1 autosomal dominant forms of eutrophic dystrophy (DEB): dominant hereditary white papules dystrophic bullous epidermolysis (DDEB, albopapuloidea) and dominant Hereditary proliferative dystrophic bullous epidermolysis (DDEB, hyperplasique), also known as Pasini type and Cockayne-Touraine type, these two types of lesions are similar, the only difference is that the former has white fibrotic papules, the pimples It is a localized scar, sometimes difficult to identify clinically. It needs to be genetically diagnosed. Extra-oral lesions may have mild oral erosion and scarring. Sometimes severe esophageal involvement may occur. Very few patients may develop squamous cell carcinoma, but have an impact on life. Not big.

Transient bullous dermolysis of the newborn, often at birth or shortly after birth, self-healing by 6 to 9 months, leaving a slight atrophic scar and localized nails Malnutrition.

2 autosomal recessive forms (DEB, autosomal recessive forms): recessive hereditary severe dystrophic bullous epidermolysis (RDEB, gravis), also known as Hallopeau- The Siemens type is one of the serious types of hereditary EB. It occurs at birth, the skin lesions gradually affect the whole body, and the early infant mortality rate is high. The surviving children often develop invasive squamous cell carcinoma on the surface of recurrent blisters and scars. Most squamous cell carcinomas have localized or systemic metastasis, leading to death. Commonly severe multiple organ involvement, the most common is small mouth malformation caused by oral involvement and shortness of the tongue strip. Extensive dental caries cause early tooth loss. Further nutritional difficulties, in addition to esophageal stricture, growth retardation, severe multi-factor anemia, rare corneal and conjunctival blister erosion and scarring, extensive genitourinary and lower gastrointestinal involvement, many patients in early childhood False and finger deformities can occur, similar to the claw type, resulting in muscle atrophy, partial finger (toe) bone absorption, and finally serious work Barriers, repeated secondary infection can also lead to sepsis.

Recessive hereditary mild dystrophic bullous epidermolysis (RDEB, mitis), this type of patient is clinically similar to the Cockayne-Touraine type, and the extracutaneous involvement is rare.

Under the light microscope, except for the superficial EBS, the blister or fissure of all EBS is close to the bottom of the epidermis under the epidermis, and the blisters or fissures of JEB and DEB are located under the epidermis, so the two can not be distinguished under the light microscope.

Transmission electron microscopy showed that the fissures of the superficial EBS occurred in the granular layer, while the cracks of all other EBS were in the basal layer or the basal layer; the blister of JEB occurred in the middle layer of the transparent plate, and the fissure of DEB was located in the dense plate below the boundary of the dermis epidermis. Anchor fibrils are usually absent in severe RDEB, reduced in most RDEB, and reduced or normal in DDEB. Recent studies have found that the severity of DEB is inversely related to the mean diameter of the anchor fibril cross section. From the limited type of DDEB to the whole body type and finally to RDEB, this diameter gradually becomes smaller.

Examination of pediatric hereditary bullous epidermolysis

When anemia occurs, the peripheral blood image shows a decrease in red blood cell count and hemoglobin; in concurrent infection, peripheral blood leukocyte count and neutrophil count are significantly increased; when severe infection is accompanied by water and electrolyte disorders, blood sodium, potassium, and chlorine should be used. pH and liver and kidney function tests.

Immunofluorescence antigen localization showed that in EBS, bullous pemphigoid serum, type IV collagen antibody and platein antibody were on the dermis side; in JEB, bullous pemphigoid serum was on the epidermal side, type IV The collagen antibody and the plate antibody are on the dermis side; in DEB, the bullous type pemphigoid serum, the type IV collagen antibody and the plate antibody are on the epidermis side.

In addition, electron microscopy also showed that in the upper part of the dermis of most DEB, there are different amounts of collagen dissolved. In neonatal transient bullous skin lysis, amorphous stellate bodies can be seen in the nucleus of the basal cells.

Severe cases should be chest X-ray, ECG, B-ultrasound and other examinations.

Diagnosis and differential diagnosis of hereditary bullous epidermolysis in children

According to the clinical manifestations of the disease before the age of 2, the clinical manifestations of blistering at the friction site combined with the medical history can make a preliminary diagnosis. The diagnosis must be confirmed by immunofluorescence antigen localization and projection electron microscopy, and subtype and variant diagnosis.

In the neonatal period, it is sometimes necessary to distinguish from herpes simplex, congenital porphyria, pigment incontinence, bullous mastocytosis, Staphylococcus aureus scalded skin syndrome and epidermolysis keratosis.

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