Mechanobullous Disorders in Pediatrics

Overview

Mechanobullous disorders, also known as epidermolysis bullosa (EB), comprise a group of inherited disorders characterized by mechanical fragility of skin and mucous membranes, resulting in blistering with minimal trauma.

Key Points

• Incidence: 1:50,000 live births
• Inheritance patterns: Autosomal dominant or recessive
• Onset: Usually at birth or early infancy
• Affects both genders equally

Pathophysiology

• Genetic mutations affecting structural proteins in skin
• Disrupted protein function leads to skin fragility
• Different subtypes based on level of tissue separation
• Affects basement membrane zone components

Classification of Epidermolysis Bullosa

1. EB Simplex (EBS)

• Level of separation: Intraepidermal
• Affected proteins:
  • Keratin 5 and 14
  • Plectin
  • BPAG1-e
• Subtypes:
  • Localized (Weber-Cockayne)
  • Generalized intermediate (Köbner)
  • Generalized severe (Dowling-Meara)
  • EBS with muscular dystrophy

2. Junctional EB (JEB)

• Level of separation: Lamina lucida
• Affected proteins:
  • Laminin-332
  • Type XVII collagen
  • α6β4 integrin
• Subtypes:
  • Generalized severe (Herlitz)
  • Generalized intermediate
  • Localized

3. Dystrophic EB (DEB)

• Level of separation: Sub-lamina densa
• Affected protein: Type VII collagen
• Subtypes:
  • Dominant dystrophic EB
  • Recessive dystrophic EB (severe generalized)
  • Recessive dystrophic EB (generalized intermediate)

4. Kindler Syndrome

• Multiple levels of separation
• Affected protein: Kindlin-1
• Features: Photosensitivity and poikiloderma

Clinical Features

General Manifestations

• Skin fragility and blistering
• Erosions and wounds
• Scarring (varies by type)
• Nail dystrophy or absence
• Mucosal involvement

Type-Specific Features

EB Simplex

• Primarily affects palms and soles in localized form
• Herpetiform clustering in Dowling-Meara
• Usually improves with age
• Minimal scarring

Junctional EB

• Generalized blistering
• Granulation tissue
• Characteristic periorificial involvement
• Dental enamel defects
• Nail dystrophy or absence

Dystrophic EB

• Extensive scarring
• Milia formation
• Flexural contractures
• Esophageal strictures
• Pseudosyndactyly ("mitten deformities")

Diagnostic Approach

Initial Evaluation

• Detailed family history
• Pattern of inheritance
• Age of onset
• Distribution of lesions
• Associated features

Diagnostic Methods

• Skin Biopsy
  • Transmission electron microscopy
  • Immunofluorescence mapping
  • Level of separation determination
• Genetic Testing
  • Next-generation sequencing
  • Single-gene testing
  • EB-specific gene panels
• Prenatal Diagnosis
  • Chorionic villus sampling
  • Amniocentesis
  • Preimplantation genetic testing

Treatment and Management Strategies

Wound Care Principles

• Gentle handling of skin
• Non-adherent dressings
• Regular wound assessment
• Prevention of secondary infections
• Pain management during dressing changes

Multidisciplinary Care

1. Dermatological Care
   • Wound management protocols
   • Infection prevention
   • Topical therapies
2. Pain Management
   • Regular assessment
   • Multimodal analgesia
   • Procedural pain control
3. Nutritional Support
   • High protein diet
   • Micronutrient supplementation
   • Feeding strategies
4. Physical/Occupational Therapy
   • Contracture prevention
   • Activity modification
   • Assistive devices

Emerging Therapies

• Gene therapy approaches
• Protein replacement therapy
• Cell-based therapies
• Bone marrow transplantation

Complications and Prognosis

Systemic Complications

• Growth retardation
• Nutritional deficiencies
• Anemia
• Squamous cell carcinoma risk
• Cardiomyopathy (in some types)

Organ-Specific Complications

• Gastrointestinal
  • Esophageal strictures
  • Dysphagia
  • Malnutrition
  • Constipation
• Musculoskeletal
  • Contractures
  • Osteoporosis
  • Muscular dystrophy
• Dental
  • Enamel defects
  • Caries
  • Microstomia

Prognosis

• Varies significantly by subtype
• EBS: Generally good prognosis
• JEB: Poor prognosis in severe forms
• RDEB: Significant morbidity and reduced life expectancy