Epidermolysis bullosa

From Dog
Footpad erosions due to sloughing of the superficial epithelium, associated with ectodermal dysplasia in a dog[1]

Epidermolysis bullosa syndrome is a group of immune-mediated sub-epidermal blistering skin diseases that result from defects in the dermal-epidermal attachment structures and characterized by flaccid bullae that soon rupture, leaving glistening, flat erosions[2].

Although recognized in dogs for many years, until recently, these diseases were group into a category of bullous pemphigoid. In recent years, advanced diagnostic methods have allowed categorization based on immunohistochemistry developments[3]. Epidermolysis bullosa is now categorized depending upon the level of intracutaneous cleavage[4] into three major subgroups: simplex, junctional, and dystrophic epidermolysis bullosa, which contain more than 20 genetically and clinically distinct subtypes.

In dogs, these include:

- Epidermolysis bullosa acquisita (junctional) - autosomal-recessive laminin 5 deficiency[5] - seen in the Chesapeake Bay Retriever, German Shorthaired Pointer[6], Great Dane
- Epidermolysis bullosa dystrophia (dystrophic) - autosomal recessive in the Golden Retriever[7] - caused by mutations in the gene encoding collagen VII and is characterized by a lack of this collagen and its polymers — the anchoring fibrils — in the skin and mucosa[8]
- Ectodermal dysplasia (skin fragility syndrome) - Mexican Hairless and Chinese Crested dogs[9]
- Type I bullous systemic lupus erythematosus[10]
- Vesicular cutaneous lupus erythematosus
- Linear immunoglobulin-A bullous disease[11]
- Mucous membrane pemphigoid[12]

These diseases are an immune-mediated disease directed against junctional basement-membrane laminin, triggered by autoantigens. Although the etiology of these diseases is unknown, a strong genetic predisposition in some breeds suggests a defect in autoantigen regulation.

Affected dogs usually present with crusting, ulcerated lesions, alopecia and pigmentation on the face, trunk and extremities, together with dystrophic nails[13]. Bilateral symmetrical erosions and ulcers are often seen affecting several mucous membranes in mucous membrane pemphigoid, the presence of characteristic eosinophil-rich sub-epidermal vesicles in bullous pemphigoid, and blisters and erosions affecting friction areas and footpads in epidermolysis bullosa acquisita.

Diagnosis is usually based on histological examination of skin biopsy samples.

A differential diagnosis would include dermatomyositis, cutaneous asthenia, ringworm and demodicosis[14].

Successful treatment has been reported with the use of prednisolone, azathioprine, colchicine, intravenous infusion of immunoglobulins[15] and doxycycline-niacinamide combinations[16].

References

  1. Olivry T et al (2012) Deficient plakophilin-1 expression due to a mutation in PKP1 causes ectodermal dysplasia-skin fragility syndrome in Chesapeake Bay retriever dogs. PLoS One 7(2):e32072
  2. Merck Veterinary Manual
  3. Olivry T & Jackson HA (2001) Diagnosing new autoimmune blistering skin diseases of dogs and cats. Clin Tech Small Anim Pract 16(4):225-229
  4. Fine JD et al (2008) The classification of inherited epidermolysis bullosa (EB): Report of the third international consensus meeting on diagnosis and classification of EB. J Am Acad Dermatol 58:931–950
  5. Capt A et al (2005) Inherited junctional epidermolysis bullosa in the German Pointer: establishment of a large animal model. J Invest Dermatol 124(3):530-535
  6. Pertica G et al (2010) Prevalence of inherited junctional epidermolysis bullosa in German shorthaired pointers bred in Italy. Vet Rec 167(19):751-752
  7. Magnol JP et al (2005) Characterization of a canine model of dystrophic bullous epidermolysis (DBE). Development of a gene therapy protocol. Bull Acad Natl Med 189(1):107-119
  8. Bruckner-Tuderman L et al (2010) Animal models of epidermolysis bullosa: update 2010. J Invest Dermatol 130(6):1485-1488
  9. Drögemüller C et al (2008) A mutation in hairless dogs implicates FOXI3 in ectodermal development. Science 321(5895):1462
  10. Olivry T et al (1999) Bullous systemic lupus erythematosus (type I) in a dog. Vet Rec 145:165–169
  11. Olivry T et al (2000) Autoantibodies against the processed ectodomain of collagen XVII (BPAG2, BP180) define a canine homologue of linear IgA disease of humans. Vet Pathol 37:302–309
  12. Olivry T et al (2001) A spontaneous canine model of mucous membrane (cicatricial) pemphigoid, an autoimmune blistering disease affecting mucosae and mucocutaneous junctions. J Autoimmun 16:411–421
  13. Nagata M et al (1997) Non-lethal junctional epidermolysis bullosa in a dog. Br J Dermatol 137(3):445-449
  14. Yoon JS et al (2010) Two dogs with juvenile-onset skin diseases with involvement of extremities. J Vet Med Sci 72(11):1513-1516
  15. Hill PB et al (2008) Epidermolysis bullosa acquisita in a Great Dane. J Small Anim Pract 49(2):89-94
  16. Olivry T (2004) Spontaneous canine model of epidermolysis bullosa acquisita. In: Animal Models of Human Inflammatory Skin Diseases, ed. Chan LS. pp:227–237. CRC Press, Boca Raton, FL