CLINICAL HISTORY:

Signs and symptoms:  Fragility of skin and slowly healing, scarring erosions and ulcers, difficulty swallowing, decreased appetite and weight loss

Previous Treatment:  Oral Antibiotics, pureed diet, high calorie diet, wound care including Vaseline gauze and Bactroban ointment, TAC 0.1% ointment, mineral oil, senicot, Iron

Other information:  12 year old sister has a similar presentation. Neither the parents nor another sibling are affected.

PHYSICAL EXAM:

Thin cachectic appearing 11 year old female appears younger than her stated age. Erosions, ulcerations and scarring of the neck, posterior shoulders, axilla, lower abdomen and scalp. Pseudosyndactyly of the 1st and 2nd digits of bilateral feet with anonychia. Scarring of the palms, soles and scarring alopecia of the temporal scalp. Oral mucosa with small linear erythematous erosions on the soft palate.

LABORATORY TESTS:

Iron Deficiency Anemia on CBC and Iron Studies.
Positive Electron Microscopy showing absent anchoring fibrils.
Blood Leukocyte DNA analysis positive for COL7A1 gene mutations.

DERMATOHISTOPATHOLOGY:

Microscopic description: Monoclonal antibody against Collagen 7 demonstrates absence of Collagen type 7 in the lesional, near perilesion, and distant perilesional skin. Cleavage plane of blistering is below the lamina densa by staining for BP230 and Collagen type IV which both localize to blister roof.

DIFFERENTIAL DIAGNOSIS:

1.   Epidermolysis Bullosa Simplex
2.   Junctional Epidermolysis Bullosa
3.   Recessive Dystrophic Epidermolysis Bullosa
4.   Dominant Dystrophic Epidermolysis Bullosa
5.  

SCROLL DOWN FOR ANSWER AND DISCUSSION.

CORRECT DIAGNOSIS:

Recessive Dystrophic Epidermolysis Bullosa

DISCUSSION:

Hallopeau-Siemens Recessive Dystrophic Epidermolysis Bullosa is a genetic mechano-bullous dermatosis which is often incapacitating for the 1-2 cases per million births annually. Incidence is higher in Norway and lower in Japan & Croatia. It affects both sexes equally and is characterized by autosomal recessive inheritance of COL7A1 gene mutations in which premature termination codons lead to the absence of anchoring fibrils within the Dermal Epidermal Junction (DEJ). Diagnosis is made by demonstration of a separation in the DEJ below the lamina densa in skin and extracutaneous mucosa, in addition to clinical signs of marked growth retardation, and wide spread scarring. The gold standard of diagnosis is the electron microscopic findings of absent anchoring fibrils or genetic evaluation of COL7A1 mutation.

Patients have progressive, scarring disease. Blistering is generalized at birth and while life expectancy is normal, early death from overwhelming infection, metastatic scar associated squamous cell carcinoma, or malnutrition associated complications is typical. Skin findings include: blisters, milia, atrophic scarring, dystrophic or absent nails, scalp abnormalities, and scar associated squamous cell carcinomas. Extracutaneous involvement includes: Anemia, malnutrition/ growth retardation, oral cavity soft tissue abnormalities, periodontitis, enamel hypoplasia leading to caries, gastrointestinal scarring/ stenosis, genitourinary scarring, ocular scarring, pseudosyndactyly (mitten hand deformity), and flexion contractures.

The most serious complication of RDEB is squamous cell carcinoma arising in chronic non-healing ulcers which are difficult to distinguish from the chronic ulceration, scarring and crusting typical of RDEB. These invasive SCC’s are typically well to moderately differentiated and occur mostly on the limbs. The incidence of these SCC’s are around the ages of 15-35,1 and 50% are affected by age 20-35. These SCC’s have a high metastatic potential.2

Diminished food intake and increased nutritional requirements leads to malnourishment which commonly results in a mixed anemia from iron deficiency or failure to thrive. Compounding this malnutrition is the mucosal scarring that leads to strictures and webs of the esophagus, urethral and anal stenosis, and phimosis. RDEB patients have increased caloric and protein requirements, and hemodynamic and metabolic responses typical of burn patents. This disequalibirum leads to an inability to overcome infection and inadequate wound healing. Impediments to the intake of adequate nutrition include: oral, pharyngeal, and gastrointestinal lesions, abnormal esophageal motility/ dysphagia, strictures, malabsorptive diarrhea, and dental problems. Nutritional deficits may lead to fatal cardiomyopathies. Fatal systemic amyloidosis has also been reported.

Ophthalmic complications affect 51% of RDEB patients including: corneal scarring, lid ectropions, lid blisters and symblepharon. These complications can be devastating for these patients and are treated with vigilant use of lubricants3

TREATMENT:

Most treatment is supportive nutrition, wound care and prevention of trauma.

Wound healing is treated by removal of necrotic tissue or foreign body, prevention of infection by liberal usage of antibiotic ointments and nutritional support to maintain an adequate immune status. Common pathogens are Staphyloccus aureus, Streptococcus pyogenes, and Gram-negative organisms like Pseudomonas aeruginosa. Treatment regimens may include whirlpool debridement and semiocclusive, non-adherent dressings like Vaseline gauze.

Tumor surveillance is important since multiple primary squamous cell carcinomas may arise as early as 15-20 years of age.1

Gastrointestinal evaluation of scarring and strictures is important, since nutritional requirements are high in these chronically wounded patients. Dysphagia may be managed by use of phyenytoin or oral steroid elixirs. It is also important to treat oral pharyngeal Candidiasis.

Ocular lesions (as above) may include cicatrical conjunctivitis, chronic blepharitis and corneal ulceration, erosion, and scarring. These may be treated with topical antibactierial ointments or cycloplegic agents to reduce ciliary spasm.

Oral care is important to maintain nutritional intake. Aggressive preventive interventions including gentle dental hygiene is the primary treatment to prevent dental caries, which are common due to enamel hypoplasia. Water pulsation devices and very soft gentle tooth brushing are critical. Oral mucosal blisters can be treated with saline rinses and avoidance of alcohol containing mouth washes. Avoidance of sharp edged food such as chips and hard candy in addition to more aggressive blenderized foods are important to maintain mucosal integrity.6

Gene therapy is the only definitive treatment but is still not a part of our armamentarium.

Surgical Care may include correction of esophageal strictures by balloon dilatation or colonic interposition. Aggressive active nutritional support includes starting at an early age and consideration of nasogastric or gastrostomy feeding tubes at earlier stages.7 Surgical correction of pseudosyndactyly followed by long term night splinting is associated with a typical recurrence in 5 years.8 Use of Apligraft to cover acute wounds has led to faster healing of ulcers, less pain, and better quality of life by preventing acute wounds from becoming chronic wounds. Apligraft skin is not lasting and is eventually replaced by the patient’s normal diseased skin over time. Reblistering occurs in about 20% of Apligrafted skin lesions.9

REFERENCES:

1 McGrath JA, Schofield OM, Mayou BJ, et al: Epidermolysis bullosa complicated by squamous cell carcinoma: report of 10 cases. J Cutan Pathol 1992 Apr; 19(2): 116-23

2 Terrill PJ, Mayou BJ, McKee PH, Eady RA: The surgical management of dystrophic epidermolysis bullosa (excluding the hand). Br J Plast Surg 1992 Aug-Sep; 45(6): 426-34

3 Tong L, Hodgkins PR, Denyer J, et al: The eye in epidermolysis bullosa. Br J Ophthalmol 1999 Mar; 83(3): 323-6

4 Pulkkinen L, Uitto J: Mutation analysis and molecular genetics of epidermolysis bullosa. Matrix Biol 1999 Feb; 18(1): 29-42

5 Fine JD, Eady RA, Bauer EA, et al: Revised classification system for inherited epidermolysis bullosa: Report of the Second International Consensus Meeting on diagnosis and classification of epidermolysis bullosa. J Am Acad Dermatol 2000 Jun; 42(6): 1051-66

6 Wright JT, Fine JD, Johnson L: Hereditary epidermolysis bullosa: oral manifestations and dental management. Pediatr Dent 1993 Jul-Aug; 15(4): 242-8

7 Allman S, Haynes L, MacKinnon P, Atherton DJ: Nutrition in dystrophic epidermolysis bullosa. Pediatr Dermatol 1992 Sep; 9(3): 231-8

8 Terrill PJ, Mayou BJ, Pemberton J: Experience in the surgical management of the hand in dystrophic epidermolysis bullosa. Br J Plast Surg 1992 Aug-Sep; 45(6): 435-42

9 Falabella AF, Valencia IC, Eaglstein WH, Schachner LA: Tissue-engineered skin (Apligraf) in the healing of patients with epidermolysis bullosa wounds. Arch Dermatol 2000 Oct; 136(10): 1225-30

10 Marinkovich MP, Herron, GS, Khavari, PA: Hereditary epidermolysis bullosa. In: Fitzpatrick's Dermatology in General Medicine, 5th ed. McGraw-Hill; 1999: 690-700.

Additional Comment:

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