What is epidermolysis bullosa pruriginosa?
Epidermolysis bullosa pruriginosa (OMIM 604129) is a rare and clinically heterogeneous form of dystrophic epidermolysis bullosa (dystrophic EB), resulting from a mutation in the type VII collagen gene.
First described in 1994, there have been fewer than 100 cases documented in the literature, and as such, little is known about the condition or its treatment.
Epidermolysis bullosa pruriginosa: pretibial
Who gets epidermolysis bullosa pruriginosa?
Epidermolysis bullosa (EB) pruriginosa can either present shortly after birth, or in adulthood.
- In neonates, EB pruriginosa usually presents as blistering on the peripheral limbs. The blistering may either continue or temporarily resolve in infancy.
- During adolescence or early adulthood, patients with EB pruriginosa develop pruritic lichenified plaques that persist long term. The initial presentation may be delayed until the second or third decade of life.
What causes epidermolysis bullosa pruriginosa?
As with other forms of dystrophic EB, the clinical findings of EB pruriginosa are attributed to mutations in the COL7A1 gene on chromosome 3p21.3, which encodes type VII collagen. Case reports of epidermolysis bullosa pruriginosa reveal many different alterations to this gene, including missense, nonsense, frame shift, and splice-site mutations.
Type VII collagen is a major skin structural component of the anchoring fibrils at the dermo-epidermal junction (DEJ). Mutations in the coding gene hamper the function of the anchoring fibrils and lead to a split in the DEJ below the level of the lamina densa. Clinically, this manifests as trauma-induced blisters, which heal leaving a scar.
Inheritance is variable; autosomal dominant and autosomal recessive patterns of inheritance have been reported. Most cases however have been found to be sporadic.
The characteristic pruritic component of the condition is poorly understood. A raised serum IgE level has been found in 7 of 9 examined patients with epidermolysis bullosa pruriginosa, and in some cases was found to be over 3 times the upper limit of normal. However, a personal or family history of atopy was a confounding factor in three of these patients, and so the results are far from conclusive.
What are the clinical features of epidermolysis bullosa pruriginosa?
EB pruriginosa is characterised by intensely itchy (pruritic) hypertrophic papules, nodules, and plaques usually on the lower extremities.
- Violaceous lichenified lesions
- Usually linear pattern
- Prurigo-like lesion with scarring and milia
- Pretibial (shin) involvement is typical; can involve forearms and trunk
- Face, neck, and flexures are spared
- Nail dystrophy is common
Epidermolysis bullosa pruriginosa
What are the complications of epidermolysis bullosa pruriginosa?
- Impact of intense itch on quality of life
- Lichenification and scarring
- Cutaneous squamous cell carcinoma (rare)
What is the differential diagnosis of epidermolysis bullosa pruriginosa?
- Nodular prurigo
- Lichen simplex chronicus
- Hypertrophic lichen planus
- Cutaneous and lichen amyloidosis
How is epidermolysis bullosa pruriginosa diagnosed?
Epidermolysis bullosa pruriginosa should be considered clinically based on family history, clinical features, and a positive mechanobullous history, and confirmed with investigations.
- Light microscopy of skin biopsy
- hyperkeratosis, acanthosis, disruption of the dermo-epidermal junction forming a subepidermal blister, milia, prominent dermal and perivascular lymphohistiocytic infiltrate
- Direct immunofluorescence on skin biopsy - negative
- useful to exclude other blistering conditions
- Electron microscopy
- confirms the level of the split
- diminished or absent anchoring fibrils in the sub-lamina densa
- Genetic testing
- COL7A1 mutations
What is the treatment of epidermolysis bullosa pruriginosa?
- Avoid trauma
- Protective clothing
- Wound care
Topical treatment of itch
- Off-label use of dapsone, ciclosporin, and other systemic agents
- Dupilumab (off-label)
Success has been varied and many treatments have been reported for a single case. Sustained responses has been recently reported with dupilimab.
What is the outlook for patients with EB pruriginosa?
Little is known about the long-term outcome for patients with EB pruriginosa. It is lifelong and often refractory to treatment.
No long term data exists with regards to the sustainability of medication-induced remission.