History
A 4-year-old 7.0-kg (15.4-lb) sexually intact female Dachshund that had a history of self-inflicted wounds was evaluated at the Veterinary Teaching Hospital of Bologna University because of a skin wound on the ventral aspect of the thorax. The first episode had occurred 6 months prior and involved a cutaneous wound in the thoracic region; this was followed 2 months later by development of a cutaneous lesion in the right shoulder region. The owner had also noticed other minor skin lesions on the dog's flanks. During the few days preceding the evaluation, the dog had started to bite and lick the thoracic region continuously.
Clinical and Gross Findings
On physical examination, the dog was found to be in good body condition with lesions affecting only the skin. The dog had a large (4 Ă— 7-cm) skin wound on the ventral aspect of the thoracic region. The dog also had a large gaping wound (a so-called fish mouth wound)1 on the neck caused by a plastic collar applied by the owner in an attempt to prevent the dog from causing further damage to the injured tissues by the continuous licking. In addition, a depigmented shiny scar covered by thin epidermis (cigarette paper scar) was noted in the area of the reported previous wound on the right shoulder.
The skin was loose and hyperextensible predominantly over the neck, trunk, axillae, and feet (Figure 1) and characterized by increased fragility. The extensibility index (a percentage calculated by lifting a fold of skin over the lumbar portion of the vertebral column to its maximum distance, and dividing that distance by the dog's body length, multiplied by 100) was 23%.1 The only abnormality noted on the coat was mild generalized dandruff. Results of a CBC and serum biochemical profile were unremarkable. Full-thickness skin biopsy specimens were collected with a 5-mm-diameter punch from the head, between the ears, and from the back.
Photograph of a 4-year-old sexually intact female Dachshund with a history of self-inflicted wounds that was evaluated because of a skin wound on the ventral aspect of the thorax. Notice the hyperextensible skin.
Citation: Journal of the American Veterinary Medical Association 249, 2; 10.2460/javma.249.2.161
Surgical curettage and treatment with gauze impregnated with Triticum vulgare (phytostimuline) were performed on the sternal wound, and oral administration of cephalexin (30 mg/kg [13.6 mg/lb], q 12 h) was started. The dog was re-evaluated weekly for wound cleaning for 2 months, until complete secondary intention healing was achieved.
One year later, the dog was re-evaluated for another self-inflicted wound involving a large area of the skin surface on the abdomen, ventral aspect of the thorax, and left flank. The dog was euthanized by means of an IV injection of a euthanasia solution preceded by sedation and general anesthesia. Unfortunately, a complete postmortem examination was declined by the dog's owner.
Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page→
Histopathologic Findings and Ultrastructural Evaluation
Histologic evaluation of the skin biopsy specimens revealed mild disarray of collagen fibers (Figure 2). The adnexa and epidermis were morphologically normal, and no dermal inflammation was evident. In skin sections stained with Masson trichrome stain, collagen fibers stained deeply blue, indicative of normal tinctorial affinity. Part of each biopsy specimen was fixed in 2.5% glutaraldehyde (pH, 7.2) for 3 hours and then immersed in 1% OsO4 in 0.1M cacodylate buffer for 60 minutes. The specimens were routinely processed and embedded in epoxy resin for transmission electron microscopy. Dermal collagen fibers were characterized by variable diameter both among fibers and within the same fiber and irregular shape in transverse section (Figure 31). Parallel fiber arrangement was multifocally lost.
Photomicrograph of a section of skin from the dog in Figure 1. Mild disarray of the dermal collagen is evident. H&E stain; bar = 100 ÎĽm.
Citation: Journal of the American Veterinary Medical Association 249, 2; 10.2460/javma.249.2.161
Transmisssion electron micrographs of the collagen in the skin of the dog in Figure 1. A—Variation in diameter among collagen fibers (white arrow) and within a given fiber (black arrow) is noticeable. Uranyl acetate and lead citrate; bar = 500 nm. B—In addition to fiber diameter variation, many collagen fibers have an abnormal and irregular shape in transverse section (arrow). Uranyl acetate and lead citrate; bar = 500 nm.
Citation: Journal of the American Veterinary Medical Association 249, 2; 10.2460/javma.249.2.161
Morphologic Diagnosis and Case Summary
Morphologic diagnosis: cutaneous hyperextensibility and fragility with minimal dermal atrophy, mild collagen fiber disarray, and moderate collagen fiber size variation.
Case summary: Ehlers-Danlos syndrome (EDS, also known as cutaneous asthenia) in a dog.
Comments
For the dog of the present report, the cutaneous hyperextensibility and fragility were suggestive of EDS. The evidence of collagen fiber size variation and disarray at the ultrastructural level confirmed the suspected diagnosis. Ehlers-Danlos syndrome comprises a spectrum of inherited congenital defects in collagen formation with multisystemic and variable clinical abnormalities affecting primarily the skin, ligaments and joints, blood vessels, and internal organs.2 The disease is also known as cutaneous asthenia and dermatosparaxis without further distinction, but the newer Villefranche classification of EDS in humans recognizes 6 subtypes based on pheno-type, inheritance pattern, and underlying biochemical and molecular defects.3
In humans, most forms of EDS identified to date result from mutations in one of the genes encoding fibrillar collagen or enzymes involved in collagen biosynthesis.3,4 The disease is rare and has also been described in dogs, cats, mink, cattle, and sheep.2–5 Cats are more commonly affected than dogs, and no breed predisposition has been detected in dogs; however, young animals are more commonly affected in both species.5 The usual clinical signs include evidence of soft, hyperextensible, and usually fragile skin. A 40-fold decrease in tensile strength of the skin in affected dogs has been reported, predisposing them to cutaneous tears and wounds with minimal bleeding and rapid healing with the formation of scars covered by thin epidermis (cigarette paper scars).2,3–6,7 In the case described in the present report, such cutaneous anomalies were identified, including a cigarette paper scar in an area of previous laceration. The dog's skin had a high extensibility index; an index > 14.5% is considered diagnostic for cutaneous asthenia in a dog. We speculated that the self-inflicted wounds observed in the present case could be related to increased skin sensitivity associated with EDS, as reported in the veterinary medical literature.7
Other noncutaneous signs associated with EDS in dogs, including joint laxity or dislocations, hygromas, and ocular abnormalities (blue thin sclera, microcornea, lens luxation, and cataract formation),6 were absent in the dog of the present report. This finding was consistent with published data, which indicate that coexistence of all EDS-associated abnormalities in the same animal is rare and the cutaneous form is the most common.7 The diagnosis is easily suspected on the basis of the history and typical clinical signs that differentiate EDS from other acquired diseases. Additional information can also be derived from histologic examination of Masson trichrome–stained skin sections, in which affected collagen fibers have an abnormal tinctorial affinity; however, this finding is not always observed, as in the case described in the present report. Hence, transmission electron microscopic examination of skin is often pivotal in establishing the diagnosis.8 In the dog of the present report, transmission electron microscopy of skin samples revealed collagen alterations including collagen disarray and variation in fiber diameter (among different fibers and within the same fiber). Although the prognosis for dogs with EDS is unfavorable, steps can be taken to provide a protective environment to reduce injury and strict ectoparasite control to eliminate any pruritic insult to the skin. Cats should be declawed to prevent self-trauma. Supplemental vitamin C could be of some benefit (50 mg/kg [22.7 mg/lb]). Affected animals should not be bred because of the EDS inheritance pattern.5
References
1. Miller WH, Griffin CE, Campbell KL. Congenital and hereditary defects. In: Miller WH, Griffin CE, Campbell KL, eds. Muller & Kirk's small animal dermatology. 7th ed. St Louis: Elsevier Mosby, 2013; 602–604.
2. 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.
3. De Paepe A, Malfait F. The Ehlers-Danlos syndrome, a disorder with many faces. Clin Genet 2012; 82: 1–11.
4. Smith LT, Wertelecki W, Milstone LM, et al. Human dermatosparaxis: a form of Ehlers-Danlos syndrome that results from failure to remove the amino-terminal propeptide of type I procollagen. Am J Hum Genet 1992; 51: 235–244.
5. Paterson S. Congenital and hereditary skin diseases. In: Manual of skin diseases of the dog and cat. 2nd ed. Oxford, England: Blackwell Publishing, 2008; 251–252.
6. Barrera R, Mañe C, Duran E, et al. Ehlers-Danlos syndrome in a dog. Can Vet J 2004; 45: 355–366.
7. Matthews BR, Lewis GT. Ehlers-Danlos syndrome in a dog. Can Vet J 1990; 31: 389–390.
8. Gross TL, Ihrke PJ, Walder EJ, et al. Degenerative, dysplastic and depositional diseases of dermal connective tissue. In: Gross TL, Ihrke PJ, Walder EJ, eds. Skin diseases of the dog and cat. 2nd ed. Oxford, England: Blackwell Publishing, 2005;386–389.
