Dystrophic epidermolysis bullosa is a rare and clinically heterogeneous mechanobullous disorder. One unusual clinical variant is epidermolysis bullosa pruriginosa (EBP), in which the combination of pruritus and skin fragility can lead to hypertrophic, lichenified nodules and plaques. Here we report a case of epidermolysis bullosa pruriginosa in a 21-yearold male patient who presented with albopapuloid and prurigo-like lesions over body including scalp, causing alopecia, since five years of age and was successfully treated with topical tacrolimus for both body and scalp lesions.
Key Words: :
Epidermolysis Bullosa, Preriginosa; Alopecia; Tacrolimus
Epidermolysis bullosa pruriginosa (EBP) presents either at birth with mild acral blistering and erosions, or during infancy or childhood. It is characterized by extremely pruritic, lichenified or nodular lesions predominantly over legs, milia formation and albopapuloid lesions on the trunk. Most cases are sporadic; however, both autosomal recessive and dominant inheritances are recognized. The study of the molecular basis of dominant dystrophic EB (classical) and EB pruriginosa shows that both diseases are caused by a missense glycine substitution mutation by different amino acids in the same codon of COL 7A (G2028R and G2028A). This form of inherited epidermolysis bullosa may not clinically develop until adult life, leading to confusion regarding it's inherited nature.
Case Report :
A 21-year-old male patient presented to our outpatient department with complaint of blisters all over body since the age of five years. The blisters first appeared on the scalp, progressed to involve back, chest, arms, thighs and legs, and healed with pruritic papules or scars. Prior to his visit to us, he had been treated for the skin disease with various modalities, including topical and systemic steroids, with no long-lasting benefit. No family members of the patient had any similar skin disease. Cutaneous examination demonstrated whitish papules (the so-called albopapuloid lesions), as well as prurigo-like lesions over back [Figure 1] and chest [Figure 2]. There were pruriginous papules in linear distribution over both the shins. There were irregular patches of alopecia mostly on the temporal region of the scalp above both the ears, with crusting, scaling, and prurigious papules scattered over the hairless areas. Mucosae, nails, palms and soles were free from any lesion and teeth were normal. Systemic examination was unremarkable. Complete blood count, routine blood biochemistry and urine examination were within normal limits. Immunoglobulin E level was elevated (880 IU/ml). Histology of a lesion on the back showed sub-epidermal separation with mixed inflammatory cell infiltrate in upper dermis [Figure 3]. Histology from scalp lesion showed sub-epidermal separation. Direct immunefluorescence (DIF) of the lesional and perilesional skin was negative for IgA, IgG, IgM and C3 in both the areas. We diagnosed it as a case of epidermolysis bullosa pruriginosa on the basis of long history, albopapuloid lesions, pruritus, histopathological finding of dermoepidermal separation and negative DIF. The patient was advised topical tacrolimus ointment (0.1%) and lotion (0.03%), to be applied twice daily, for body and scalp lesions respectively. When the patient came for follow-up after 6 weeks, he had significant relief from itching, and reduction of both body and scalp lesions [Figure 4], [Figure 5], [Figure 6].
Fig. 1. Prurigo like lesion over back.
Fig. 2. Albopapuloid and prurigo like lesion overchest.
Fig. 3. Histopathology of body lesion. (H&E, X10). Sub-epidermal separation with variable mixed inflammatory cell infiltrate in the upper dermis.
Fig. 4. Post treatment after 6 weeks demonstrated reduction in lichenified plaques over back.
Fig. 5. Post treatment after 6 weeks demonstrated reduction in lichenified plaques and scarring overchest.
Fig. 6. Post treatment of scalp lesion after 6 weeks showed reduction in scaling.
EBP is a type of dystrophic epidermolysis bullosa (EB) described by McGrath in 1994. In the one original series of eight cases reported by McGrath, three had family history of similar skin disease, with two showing an autosomal dominant and the other an autosomal recessive pattern of inheritance. In our case there was no family history of similar complaints, indicating the likelihood of its being a sporadic case. However, our case is remarkable as involvement of the scalp is rare in EBP.
The exact cause of pruritus in this condition is unknown. Possibly, the exposure of type VII collagen triggers the activation of the kinin cascade. Bradykinin, possibly interacting with other mediators, might be responsible for the severe pruritus.
Ultrastructurally, there is blister formation below the level of the lamina densa, and quantitative or qualitative changes in anchoring fibrils at the dermoepidermal junction. Reduction in anchoring fibril numbers is found in lesional, perilesional and non-lesional skin of patients with EB pruriginosa. However, we could not perform electron microscopy (EM) or antigen mapping (as alternative to EM to determine the level of blister formation) in our case as we do not have facility for the same.
Treatment is aimed at controlling pruritus and halting the progression of cutaneous lesions. Potent topical steroids and intralesional triamcinolone have been reported to reduce the pruritus in some cases, but don't produce sustained improvement. Other helpful interventions include topical tacrolimus, systemic cyclosporine, cryotherapy. Tacrolimus is a macrolide immunosuppressant produced by the soil fungus streptomyces tsukubaensis. We believe that topical tacrolimus has potential benefits over topical corticosteroids when treating epidermolysis bullosa pruriginosa. There are currently no reports of systemic adverse effects after topical tacrolimus application.
To the best of our knowledge, this is the first reported case of epidermolysis bullosa pruriginosa from India successfully treated with topical tacrolimus. With its steroid sparing effect and lack of documented systemic adverse reactions, we consider topical tacrolimus to be of significant benefit in treating EB pruriginosa.