4-year-old female spayed domestic short hair cat, (Felis domestics).A 4-year-old spayed female domestic short-haired cat presented with weight loss of 3.5 lbs over the past several months. The cat lived indoors and had no major previous health problems, but recently the owners felt the cat had appeared agitated and possibly painful. On presentation the cat weighed 7.5 lbs and appeared quiet, alert, and responsive although was easily stressed and began to pant. Physical examination was unremarkable with the exception of a fractured tooth and a tooth with an enamel defect. A CBC with manual differential count was performed and the cat had a mature neutrophilic, lymphocytic, and monocytic leukocytosis. A chemistry panel revealed an elevated GGT and slightly elevated sodium. A urinary tract infection was noted on urinalysis. Heartworm testing, FeLV, and FIV were negative and total T4 was normal. The referring veterinarian recommended radiographs, ultrasound, and screening for a variety of infectious diseases, which the owner declined at the time. The cat was sent home on clindamycin 25 mg capsules, for treatment of the urinary tract infection, with the option for adding buprenorphine and high calorie diets with appetite stimulants. The cat returned to the clinic 6 weeks later for euthanasia due to further decline. While restraining the cat for euthanasia the cat was unruly and appeared to be in pain. After euthanasia a technician went to move the cat by its scruff, and the skin over the dorsal thorax tore forming a large flap. A section of skin and liver was collected and submitted for histological evaluation.
Skin: Two sections of haired skin are examined.Â The sections consist of epidermis and dermis, with normal appearing hair follicles.Â The epidermis is thin and ranges from 1-2 cell layers thick, and has diffuse mild orthokeratotic hyperkeratosis.Â The dermis is severely atrophied and there is loss of a majority of the dermal collagen.Â The remnant collagen is loosely packed and interspersed with small to moderate numbers of lymphocytes, plasma cells and mast cells.Â The erector pili muscles within the specimen are prominent.Â
Liver: The cytoplasm of nearly all of the hepatocytes is expanded by several small, distinct, clear cytoplasmic vacuoles (lipid).Â The swollen hepatocytes have compression of the associated sinusoids.Â Moderate numbers of hepatocytes, often within the periacinar region have intracytoplasmic green-brown pigment (hemosiderin).Â
1.Â Dermal atrophy, diffuse, chronic, severe.
2.Â Hepatic lipidosis, diffuse chronic, moderate to severe.
|Parameter||Value||Reference Range/ Units|
|Parameter||Value||Reference Range/ Units|
Urinalysis (collected off counter)
|pH||6.5 on strip, 7.4 on meter|
|Epithelial cells||occasional squamous|
|Casts||Waxy (one seen)|
|Crystals||triple phosphate 1-2+|
Feline skin fragility syndrome, hepatic lipidosis
Acquired skin fragility syndrome has long been recognized in the cat.(2) The gross and histologic lesions are consistent with the condition feline skin fragility syndrome (FSFS).Â The pathogenesis of the syndrome is unknown; however, it is typically associated with a hyperglucocorticoidism, diabetes mellitus, or excessive use of progestational compounds.(4) It has been seen in conjunction with severe liver disease, including hepatic lipidosis.(4,8) This cat did have hepatic lipidosis.Â However, it is unknown whether this was a primary condition or secondary to some other systemic illness that resulted in anorexia as has been reported previously.(8)
Ehlers-Danlos syndrome was considered to be one of the differential diagnoses by the submitting veterinarian.Â Ehlers-Danlos syndrome was ruled out due to the severe dermal atrophy, being more consistent with acquired skin fragility syndrome.Â Dermis is of normal thickness and lacks attenuation of dermal collagen seen in Ehlers-Danlos syndrome.(2,5) Another case of dermal atrophy in a cat reports the occurrence after treatment of the cat with phenytoin, but no mechanism was established.(1) It is important to note, phenytoin is metabolized in the liver.Â Not all cases of FSFS are related to endocrine or hepatic disease.Â There is a report of fragile skin due to cutaneous histoplasmosis.(7) In that case, the epidermis was attenuated and there was dermal edema.Â Fibrinoid necrosis of blood vessels in the subcutis with granulomatous inflammation was reported.
Skin fragility cases have been reported associated with a variety of concurrent diseases.Â However, the mechanism for this syndrome has yet to be determined.Â Clinical cases of FSFS should be an indication of concurrent disease and further evaluation of cases should be performed.
1.Â Haired skin: Epidermal, dermal, and follicular atrophy, diffuse, severe.
2.Â Liver, hepatocytes: Lipidosis, diffuse, severe.
As there was some difficulty in distinguishing glycogen from lipid type hepatocellular vacuolar change, initial conference discussion focused on the histological differences between these two processes.Â In general, lipid-type vacuolar degeneration produces hepatocytes with discrete globules which may coalesce into a single large vacuole that peripheralizes the nucleus, while glycogen-type vacuolar degeneration causes significant cell swelling with indistinct vacuolar boundaries and fine, feathery cytoplasm (see WSC 2013-2014 conference 13, case 1 for a more detailed summary as well as an example of glycogen-type change).Â Unlike dogs, steroid hepatopathy is uncommon in cats, even those with hyperadrenocorticism.Â Additionally, cats suffering from hepatic lipidosis typically exhibit micro- or macrovesicular hepatocellular vacuolation, rather than a single large vacuole that peripheralizes the nucleus.(6) Thus in this case, hepatic lipidosis is a more likely diagnosis than glycogen-type hepatocellular degeneration.Â There was also some debate regarding the origin of the golden-brown granular material noted multifocally within Kupffer cells.Â Initially, some participants speculated that this was bile pigment, lipofuscin or ceroid, but histochemical staining for iron identifies the material as hemosiderin.Â The significance of the iron is not evident in this case.
Conference participants went on to discuss the differential diagnosis for the histological skin lesions.Â Ehlers-Danlos syndrome is reported (albeit rarely) in cats, and results in hyperextensible skin; however, severe, diffuse attenuation of dermal collagen is not a characteristic feature.Â Additionally, acquired feline skin fragility syndrome (FSFS) typically presents in middle aged to older cats, while Ehlers-Danlos occurs in young animals.(4) Electron microscopy (not performed in this case) is also a useful tool in diagnosis of Ehlers-Danlos syndrome, which classically demonstrates enlarged, fragmented collagen fibrils.(3) Similarly, ultrastructural studies in cats with FSFS reveal disorganized, tangled, variably sized collagen fibrils, although fibrils are not generally fractured.(4) Paraneoplastic alopecia secondary to pancreatic/biliary carcinoma was also suggested as a possible rule-out.Â While this condition is associated with follicular atrophy, the dermis is unaffected and epidermal hyperplasia, rather than atrophy, is the most frequent microscopic characteristic; furthermore, the footpads are often involved and skin fragility is not reported, which aids in differentiating this condition from FSFS.(9)
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9.Â Turek MM.Â Cutaneous paraneoplastic syndromes n dogs and cats: a review of the literature.Â Vet Dermatol. 2003;14:279-296.