1. General Considerations

   1. Cutaneous asthenia, also known as Ehlers-Danlos syndrome and dermatoparaxis, is a rare hereditary group of disorders characterized by abnormal collagen development.
   2. Several forms of cutaneous asthenia have been recognized in man, dogs, cats, cattle, horses, mink, and sheep based on clinical, genetic, and biochemical variations.
   3. The common basis for all these forms is that they are accompanied by connective tissue weakness due to abnormalities in biosynthesis or post-translational modifications of collagen.

2. Pathogenesis

   1. In dogs, cutaneous asthenia is a simple autosomal dominant condition associated with collagen packing defect characterized by focal or diffuse areas of severely disorganized fibers with many abnormally large fibrils. The disease is called “classical Ehlers-Danlos syndrome” and is associated with variants in COL5A1 and COL5A2 genes.
   2. Cats have two forms of cutaneous asthenia, a dominant form similar to the dog’s disease and a recessive form.
      1. The recessive form is characterized by decreased activity of N-procollagen peptidase enzyme, which results in the affected collagen forming twisted ribbons instead of cylindrical fibrils and fibers.
      2. The dominant form is similar to the dog’s condition and is associated with collagen packing defect. A COL5A1 variant was reported in a cat.
   3. The loss of rigidity and tensile strength associated with the collagen defect leads to skin fragility and ultimately tearing.

3. Clinical Signs

   1. Cutaneous asthenia has been reported in the beagle, boxer, dachshund, English setter, Irish setter, keeshond, toy poodle, English springer spaniel, German shepherd dog, Garafian shepherd, greyhound, Yorkshire terrier, Irish setter, Alaskan malamute, Welsh corgi, soft-coated wheaten terrier, red kelpie, Keeshond, Saint Bernard, Fila Brasileiro, and mixed breed dogs.
   2. In cats, it has been documented in the domestic shorthair or longhair, Himalayan, Persian and Burmese cats.
   3. Fragility of the skin since birth is the most characteristic clinical sign. However, it may not be recognized by the owner until lesions develop, which may only occur few weeks to months after birth.
   4. Clinically, animals will have multiple skin tears and scars. The skin lacerations are associated with minimal or no bleeding and healing occurs rapidly by the formation of a thin and irregular scar tissue. The skin tensile strength of affected dogs is reduced 40-fold and that of cats 10-fold.

1. 5. Some animals will also have hyperextensibility of the skin and/or joint laxity. The skin hyperextensibility may be the only presentation in some cases.
      1. Extensibility is determined by extending a dorsolumbar skin fold to the maximal distance above the spine. This distance and the body length from the occipital crest to the tail base are measured. These parameters are used in the formula below:
         1. Extensibility index = Vertical height of skin fold/body length X 100.
         2. In affected dogs the skin extensibility is >14.5% and in cats >19%.

1. 6. Hematomas, elbow hygromas, join laxity and umbilical or inguinal hernias may occur in some animals.
   7. Ocular problems such as microcornea, lens luxation, cataracts, and scleroderma may be part of the clinical signs in some cases.
   8. Cats may also develop fragile skin due to spontaneous or iatrogenic hyperadrenocorticism, diabetes mellitus, liver disease, or with excessive use of megestrol acetate. However, skin fragility is acquired in these cases and will only develop in middle age to old cats, which is an important differentiating factor.

4. Diagnosis

   1. The patient’s history (especially age of disease onset) and characteristic clinical signs are usually sufficient to make a diagnosis of cutaneous asthenia.
   2. Histopathological findings are variable. Using hematoxylin and eosin stain, collagen fibers in the affected skin are small and sparse compared with control sections. Some fibers can appear fragmented, shortened, disorganized and bundle sizes may be irregular. However, in some cases (mostly cats) dermal collagen appears normal. Masson’s trichrome stain is useful in identifying collagen abnormalities.
   3. Currently, whole genome sequencing analyses is done to identify the gene mutation associated with the collagen defect.
   4. Electron microscopic is sensitive to identify structural collagen abnormalities and biochemical analysis of the dermal collagen can be done to determine the specific abnormality in collagen synthesis.

5. Treatment

   1. There is no specific treatment for cutaneous asthenia.
   2. Lacerations can be sutured using tension patterns, but they often heal spontaneously and uneventfully.
   3. The animal should be protected from any minor or major trauma.
   4. Cats should be declawed to prevent wounding during grooming or scratching.
   5. Affected animals cannot be used for breeding and owners need to know that the disease cannot be cured.

References

Barnett KC, Cottrell BD. Ehlers-Danlos syndrome in a dog: Ocular, cutaneous and articular abnormalities. J Small Anim Pract 1987; 28:941.

Burton G, Stenzel D, Mason KV. Cutaneous asthenia in Burmese cats: a vasculopathy? Vet Dermatol 2000; 11:31.

Fernandez CJ, et al. Staining abnormalities of dermal collagen in cats with cutaneous asthenia or acquired skin fragility as demonstrated with Masson’s trichrome stain. Vet Dermatol 1998; 9:49-54.

McKeever PJ, Nuttall T, Harvey RG. A Color Handbook of Skin Diseases of the Dog and Cat. 2nd edn. London: Manson Publishing Ltd., 2009; 142-143.

Miller WH, Griffin GE, Campbell KL. Muller & Kirk Small Animal Dermatology. 7th edn. St Louis: Elsevier Inc., 2013; 602-604.

Paciello O, Lamagna F, Lamagna B, et al. Ehlers-Danlos-like syndrome in 2 dogs: clinical, histologic, and ultrastructural findings. Vet Clin Pathol 2003; 32:13-18.

Patterson DF, Minor RR. Hereditary fragility and hyperextensibility of the skin of cats. A defect in collagen fibrillogenesis. Lab Invest 1977; 37:170-179.

Spycher M, Bauer A, Jagannathan V et al. A frameshift variant in the COL5A1 gene in a cat with Ehlers-Danlos syndrome. Anim Genet doi: 10.1111/age.12727.