Defects of Structural Integrity in Animals

Defects of structural integrity include genetic defects in structural elements responsible for the integrity of the epidermis and dermal-epidermal junction as well as some dermal structural anomalies.

Cutaneous asthenia (dermatosparaxis, Ehlers-Danlos syndrome) is a group of syndromes characterized by defects in collagen production. Clinical signs include loose, hyperextensible, fragile skin; joint laxity; and other connective tissue dysfunctions (see images of cats with cutaneous asthenia and hyperextendable and torn skin).

Cutaneous asthenia, cat

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Courtesy of Dr. Stephen White.

Cutaneous asthenia, hyperextendable skin, cat

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Courtesy of Dr. Karen A. Moriello.

Cutaneous asthenia, torn skin, cat

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Courtesy of Dr. Karen A. Moriello.

Collagen defects have been described in numerous species:

• cattle (Belgian Blue and White, Charolais, Hereford, Holstein-Friesian, Simmental)

• mink

• goats

• sheep (Norwegian Dala, Border Leicester-Southdown, Finnish-Merino cross, Romney, White Dorper)

• pigs (Large White-Essex cross)

• horses (Quarter Horse, Arabian cross)

• rabbits (New Zealand white)

• cats (Himalayan-recessive gene and domestic shorthair–dominant gene)

• dogs (litter of Garafian Shepherds, sporadically in several breeds)

Clinical features of cutaneous asthenia include fragile skin from the time of birth, wounds that heal with thin scars, delayed wound healing, pendulous skin, and hematoma and hygroma formation. In lambs, rupture of the GI tract and arterial aneurysms are features, and the disease is fatal in lambs and calves. In horses, onset is later and lesions are well circumscribed, consisting of hyperextensible and somewhat fragile skin.

In dogs and cats, cutaneous asthenia is not fatal. Older animals develop hanging folds of skin and exhibit extensive scarring; some have joint laxity or ocular anomalies.

Diagnosis is based on clinical signs and histological studies of collagen structure, which require age- and breed-matched controls. For diagnosis in cats and dogs, a skin extensibility index has been developed. There are anecdotal reports of affected dogs improving with vitamin C supplementation. The major differential diagnosis in adult cats is feline hyperadrenocorticism with acquired skin fragility.

The epidermolysis bullosa syndromes are a group of congenital and hereditary diseases that result from defects in the dermal-epidermal attachment structures. These are known as mechanobullous diseases because minor cutaneous trauma results in dermal-epidermal separation with formation of flaccid bullae that soon rupture, leaving glistening, flat erosions.

Syndromes are classified according to the ultrastructural location of the epidermal-dermal defect:

• simplex, in the epidermal basal cell layer

• junctional, within the basement membrane (see junctional epidermolysis bullosa image)

• dystrophic, below the basement membrane in the subepidermal anchoring fibrils

Junctional epidermolysis bullosa, histopathological lesions, horse

Image

Courtesy of Dr. Robert Dunstan.

In large animals, lesions are most common on the gingivae, palate, lips, tongue, and feet. Some forms of epidermolysis bullosa are scarring, and most are fatal. In large animals, epidermolysis bullosa syndromes are known in calves (Simmental, Brangus), domestic buffalo, lambs (Suffolk, South Dorset Down, Scottish Blackface, Weisses Alpenschaf, Welsh Mountain), and Belgian foals (see epidermolysis bullosa necropsy image and oral lesion).

Epidermolysis bullosa, calf

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Courtesy of Dr. Aiden Foster.

Epidermolysis bullosa, oral lesion, calf

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Courtesy of Dr. Aiden Foster.

All three forms of epidermolysis bullosa have been characterized in dogs and cats. Epidermolysis bullosa simplex has been described in Collies and Shetland Sheepdogs. Junctional epidermolysis bullosa has been reported in a Toy Poodle, German Shorthaired Pointers, mixed-breed dogs, and Siamese cats and tentatively identified in Beaucerons. Dystrophic epidermolysis bullosa has been reported in a domestic shorthair cat, a Persian cat, and in Golden Retrievers and Akitas.

Lesions may be present at birth or develop within the first weeks of life. The most severe lesions are on the feet (with sloughing of hooves, claws, or footpads), oral mucous membranes, and facial and perigenital skin (erosions). Except for epidermolysis bullosa simplex, these diseases are fatal.

Canine benign familial chronic pemphigus is a mechanobullous disorder that is caused by a defect in cell-to-cell adhesion in the epidermis. This disorder has been described in a family of English Setters. It develops within a few weeks of birth and causes crusting alopecic lesions on pressure points of the skin that slowly enlarge as puppies grow. The disease is benign, and no treatment is reported.

Familial acantholysis, reported in New Zealand Angus calves, is a fatal genetic condition with an autosomal recessive mode of inheritance. Affected calves develop erosions, with collarettes and crusts, in areas subjected to trauma. Some show partial separation of the hooves. Diagnosis in both puppies and calves is established by skin biopsy of newly forming lesions.

Cutaneous mucinosis is thought to be familial in some lines of Chinese Shar-Pei. Normal Shar-Pei have more cutaneous mucin than other dogs; however, in some young dogs, cutaneous mucin formation in the dermis is so excessive that the skin exhibits pronounced folding and mucinous vesiculation.

Diagnosis of cutaneous mucinosis is by skin prick of the vesicles and observation of strings of mucus that have the same appearance as normal joint fluid or, alternatively, by skin biopsy. The syndrome is partially responsive to corticosteroids; however, they are contraindicated because of affected dogs' young age. As these dogs mature, the severity of the syndrome may abate; however, it can be exaggerated by the development of allergic skin disease, common in the breed. The major differential diagnosis is hypothyroidism.