Signalment:  

2-year-old female neutered Siamese cat, feline, Felis catusThe cat was presented to the clinician with a 9 month history of prednisolone treatment due to a diagnosis of food hypersensitivity. The skin of the dorsum resembled wet tissue paper and was sensitive to touch. From the left and right thigh, blood vessels were directed towards the lesion (figures). The practitioner excised a 13 x 4 x 0.3 cm skin sample, which showed several tears and detachment of the dermis from the panniculus. The sample was fixed in formalin and routinely processed for histopathological evaluation.

Histopathologic Description:

Haired skin: The main lesion is a complete lack of subcutaneous adipose tissue which is replaced by a large clear cleft, extending throughout the whole tissue sample and leading to dermo-hypodermal separation. Collagen fibres in this area have a torn and stretched appearance. The epidermis consists of only one or two layers of partly flattened keratinocytes, interpreted as severe epidermal atrophy, and is covered by a layer of lamellar eosinophilic material (lamellar orthokeratotic hyperkeratosis). Superficial and periadnexal dermis show a perivascular to interstitial infiltrate composed of moderate numbers of lymphocytes, less macrophages, neutrophils and mast cells, and a few eosinophils and plasma cells. Around vessels of the superficial vascular plexus there are moderate numbers of extravasated erythrocytes (haemorrhage). Dermal collagen is extremely attenuated and shows a pale staining in H&E stained sections. Adnexal structures demonstrate a complete lack of anagen hair follicles, and the perifollicular fibrous sheaths of many telogen follicles are thickened. Sebaceous glands are decreased in size and number, interpreted as atrophy. Follicular infundibula are extended and filled with large amounts of an eosinophilic lamellar material (infundibular hyperkeratosis).

Morphologic Diagnosis:  

1. Skin and subcutis: Severe atrophy of epidermis and the subcutaneous panniculus with cleft formation, consistent with feline acquired skin fragility syndrome, Siamese cat, feline
2. Skin: Subacute suppurative dermatitis, superficial and perivascular, mild

Condition:  

Skin fragility syndrome

Contributor Comment:  

Different disease entities are described in man and animal species with an obvious fragility of the skin. Ehlers-Danlos syndrome (syn. collagen dysplasia, dermatosparaxia, cutaneous asthenia, cutis hyperelastica) as a congenital disease with abnormal collagen synthesis has been described in man, cattle, sheep, dogs, cats, mink and rabbits.(4) In man, six main types of the disease are defined due to biochemical, clinical and molecular studies.(7) In addition to skin lesions abnormal collagen synthesis leads to alterations in ligaments, joints, blood vessels and cardiac valves. In cats with Ehlers-Danlos syndrome skin lesions occur predominantly as cutaneous asthenia or dermatosparaxia. In contrast to other species a remarkable joint laxity is not typical in cats.(4)

Recently in man the usage of the term dermatoporosis has been presumed for skin lesions in aged people. In this syndrome an increased fragility of the skin is attributed to age-related alterations of the extracellular matrix metabolism.(6) A primary form due to aging or unprotected sun exposure and an iatrogenic form (after corticosteroid administration) are distinguished.

An ectodermal dysplasia with a congenital skin fragility syndrome due to a mutation in the desmosomal protein plakophilin 1 has been reported in man.(2)

Feline acquired skin fragility syndrome is a rare disease with marked skin lesions of multiple etiologies but without a genetic background. The syndrome has been reported only in cats. It has been noted in combination with several other diseases, such as diabetes mellitus, cholangiocarcinoma or hepatic lipidosis, and administration of different drugs.(4,5,8). Most commonly the syndrome is associated with iatrogenic or naturally occurring hyperglucocorticism.(5). There is one report of acquired skin fragility syndrome associated with phenytoin treatment. Since phenytoin inhibits collagen synthesis in vitro the authors assume that cats could acquire collagen disorders during treatment with phenytoin.(1)

Clinical features of acquired skin fragility syndrome are striking. Affected cats show markedly thin skin which tears with minor trauma and commonly leaves great flaps of loose skin. The lesions are most commonly seen at the back. Partial alopecia occurs in most affected regions.(5)

Differential diagnosis is not problematic since the lesions are typical. The patients normally are middle-aged or older and compared to Ehlers-Danlos syndrome the skin is abnormally thin but without evidence of hyperextensibility.(5) Histologically the lesions in Ehlers-Danlos syndrome and feline acquired skin fragility syndrome are similar or indistinguishable.(4)

To confirm the histopathologic diagnosis, Massons trichrome stain was performed due to described staining abnormalities (abnormal collagen fibers, presence of segmental red staining defects, birefringence of polarized light).(3) Unfortunately fiber abnormalities are not limited to acquired skin fragility syndrome. Similar alterations can also be seen in cutaneous asthenia.(3) In our case no staining abnormalities were detectable.

JPC Diagnosis:  

Skin: Epidermal and dermal atrophy, diffuse, marked with follicular atrophy and loss, dermal clefting, and mild subacute dermatitis

Conference Comment:  

Dr. Goldschmidt concentrated on the gross and histologic features of this disease during the discussion and described ways to differentiate feline acquired skin fragility syndrome from Ehlers-Danlos syndrome (EDS) both grossly and via histologic evaluation.

Cats with feline acquired skin fragility syndrome have extremely thin skin resembling tissue paper that tears very easily and is not hyperextensible. In contrast to feline acquired skin fragility syndrome, EDS is characterized clinically by the ability to stretch the skin to great lengths without tearing. The skin does not appear to be attached to the underlying subcutis. EDS is also a heritable disease, whereas feline acquired skin fragility syndrome is normally secondary to endocrine disorders, neoplasia, or improper drug administration.(5)

As the contributor stated these two entities are histologically similar. However, Dr. Goldschmidt pointed out features that allow them to be differentiated histologically in most cases. In feline acquired skin fragility syndrome, the epidermis is thin and there is also severe dermal atrophy with marked thinning of collagen fibers. Adnexal structures may also be atrophic. In contrast, the epidermis in EDS is generally unaffected, and the dermis may be of normal thickness or partially reduced in total thickness. The dermal collagen is abnormally arranged with affected fibers having red cores when stained with Massons trichrome stain.(5)

References:

1. Barthold SW, Kaplan BJ, Schwartz A: Reversible dermal atrophy in a cat treated with phenytoin. Vet Pathol 17:469-476, 1980

2. Ersoy-Evans S, Erkin G, Fassihi H, Chan I, Paller AS, S+�-+r+�-+c+�-+ S, McGrath JA: Ectodermal dysplasia-skin fragility syndrome resulting from a new homozygous mutation, 888delC, in the desmosomal protein plakophilin 1. J Am Acad Dermatol 55:157-161, 2006
3. Fernandez CJ, Scott DW, Erb HN, Minor RR: Staining abnormalities of dermal collagen in cats with cutaneous asthenia or acquired skin fragility as demonstrated with Masson's trichrome stain. Vet Dermatol 9:49-54, 1998
4. Ginn PE, Mansell JEKL, Rakich PM: Skin and appendages. In: Jubb, Kennedy and Palmer's Pathology of Domestic Animals, ed. Maxie GM, 5th ed., vol 1, pp 389-391, Saunders, Edinburgh, 2007
5. Gross TL, Ihrke PJ, Walder EJ, Affolter VK: Skin diseases of the dog and cat, 2nd ed., pp 386-391. Blackwell, Oxford, UK, 2005
6. Kaya G, Saurat JH: Dermatoporosis: a chronic cutaneous insufficiency/fragility syndrome. Clinicopathological features, mechanisms, prevention and potential treatments. Dermatol 215:284-294, 2007
7. Parapia LA, Jackson C: Ehlers-Danlos syndrome-a historical review. Br J Haematol 141:32-35, 2008
8. Trotman TK, Mauldin E, Hoffmann V, Del Piero F, Hess RS: Skin fragility syndrome in a cat with feline infectious peritonitis and hepatic lipidosis. Vet Dermatol 18:365-369, 2007

Click the slide to view.

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1-1. Haired skin, cat.

1-2. Haired skin, cat.

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