Epidermolysis bullosa dystrophica recessive, severe generalized Q81.2

Hallopeau, 1896; Siemens, 1921

Congenital, autosomal recessive inherited, generalized, severe blistering dermatosis with spontaneous and post-traumatic blistering and severe mutating scarring.

Autosomal recessive inheritance. A homozygous or compound heterozygous mutation of the COL7A1 gene mapped on chromosome 3p21.3. The mutation leads to reduced or absent synthesis of collagen type VII.

In this classic severe form of RDEB, the blisters are present at birth or occur in the neonatal period.

Integument:

• Large-surface blisters (100%) with serous or hemorrhagic contents and irregularly configured large-surface erosions (100%) that heal with scarring, reepithelialize hesitantly, and may cause severe disability due to mutilations and synechiae. They may affect the entire body.
• Clinically significant is the tendency to spontaneous or post-traumatic blistering (the acting trauma defines the localization of the lesions) with positive Nikolski phenomenon I, onychodystrophy (100%)
• Milia in healed lesions (100%).
• Many affected individuals develop large irregular brown patches that histologically consist of collections of melanocytes and are referred to as EB (melanocytic) nevi (Lanschuetzer et al 2010). To date, no cases of melanoma have been observed reported arising in these nevi.

Extracutaneous manifestations:

• Marked involvement of conjunctival, oral, pharyngeal, esophageal, and genital mucosa.
• Enamel defects and caries involvement (10-25%), skeletal hypoplasia, brain damage, speech disorders, severe contractures.
• Oral involvement can lead to fusion of the tongue with the floor of the mouth (ankyloglossia) and progressive reduction of the oral cavity and mouth opening (microstomia).

• Esophageal blisters and erosions, as well as webs and strictures, can cause severe dysphagia with resulting poor feeding (Mortell AE et al 2010). In rare cases, affected individuals may have esophageal disease with few or no skin manifestations. Gastroesophageal reflux disease is also common.

• Anal erosions, inadequate fluid and fiber intake, and use of opioid analgesics contribute to frequent severe constipation.

• Growth retardation (100%): Height and weight are often below peers.

• Eyes: Corneal erosions can lead to scarring and loss of vision.

• Heart: Dilated cardiomyopathy, sometimes associated with selenium and carnitine deficiency, has been reported in RDEB and may be fatal in some cases.

• Urologic/renal. Urethral erosions, strictures, bladder dysfunction, and glomerulonephritis may occur, sometimes leading to renal failure.

• Orthopedic. People with REBD tend to have contractures and pseudosyndactyly of the fingers, resulting in a "mitten" or "cocoon" hand and thus impaired function and decreased quality of life. Although fusion of the toes does not affect function, painful blistering and progressive contractures of the foot and ankle, as well as the larger joints (knee, hip, neck), can impair walking and function.

• Symptomatic. Antiseptic and wound-healing externals (see Epidermolysis bullosa group below). Prevention and treatment of secondary infections.
• Experimental vitamin E therapy (e.g. Evit Kps.) Infants: 25 mg/kg bw/day, adults: 600-1200 mg/kg bw/day, or collagenase inhibitors such as phenytoin (e.g. Zentropil, Epanutin) initially 2-3 mg/kg bw/day in 2 doses over 10-14 days, followed by a gradual dose increase up to a blood level of at least 8 μg/ml. Effectiveness can only be assessed after 6 months.
• Limited success has been described for DADPS, retinoids, chloroquine or Ciclosporin A.

See also Epidermolysis bullosa dystrophica (overview).

Avoidance of mechanical irritation and pressure points on the skin. Diet rich in vitamins and minerals.

Mucosal defects (20% of pat.) may lead to restricted food intake! Continuous and early dental care (malformation, caries).

Lifelong control for spinocellular carcinoma.

Surgical measures in case of synechiae and contractures.

Early physiotherapy to prevent contractures.

Unfavorable: risk of sepsis, esophageal stenosis, possible development of carcinoma (as early as 20-30 years of age) in the area of tight scar tracts. Lifetime risk of aggressive squamous cell carcinoma (SCC) is over 90% with significant metastatic potential. SCC usually occurs in the third decade, but can occur as early as the second decade. Affected individuals usually succumb to aggressive metastatic SCC (Mellerio et al 2016).

Diagnosis: clinic, histology, immunofluorescence, electron microscopy, molecular genetic testing, prenatal diagnosis if necessary.

See also Epidermolysis bullosa dystrophica (overview).

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15. Siemens HW (1921) Introduction to the general and special hereditary pathology of man. (Berlin) 2nd edition.
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