Reversible and cachexia‐associated feline skin fragility syndrome in three cats

Abstract

Background

Feline skin fragility syndrome (FSFS) is an acquired disorder characterized by altered collagen production resulting in an extremely thin and fragile skin. FSFS is associated with diseases characterized by excessive steroidal hormones that can inhibit collagen synthesis. It is also described concomitantly with severe inflammatory, infectious or neoplastic conditions where the pathogenesis remains largely unknown.

Objectives

To describe three cases of FSFS in cats that become cachectic secondary to different causes without glucocorticoid involvement. To describe the histopathological features of connective tissue for both fragile skin and the skin after healing.

Results

All cats developed cachexia in less than two months (body condition score ranging from 1–1.5). Concomitant diseases were diagnosed in Case 1 (aspiration pneumonia due to mega‐oesophagus) and Case 2 (feline immunodeficiency virus (FIV)). In Case 3, malnutrition was suspected as a primary cause. The main histological feature of fragile skin was an atrophic dermis with pale eosinophilic, thin and irregular collagen fibres with numerous red cores observed with Masson's stain. Elastic fibres were normal. Postrecovery histopathological findings at 11 (Case 1) and six months (Case 3) after diagnosis, indicated normalization of the collagen and of the whole skin as compared with controls.

Conclusions and clinical importance

To the best of the authors’ knowledge, this is the first report describing a reversible, nonsteroid‐induced FSFS, associated with rapidly developing cachexia in cats.

Background – Feline skin fragility syndrome (FSFS) is an acquired disorder characterized by altered collagen production resulting in an extremely thin and fragile skin. FSFS is associated with diseases characterized by excessive steroidal hormones that can inhibit collagen synthesis. It is also described concomitantly with severe inflammatory, infectious or neoplastic conditions where the pathogenesis remains largely unknown. Objectives – To describe three cases of FSFS in cats that became cachectic secondary to different causes without glucocorticoid involvement. To describe the histopathological features for connective tissue for both fragile skin and the skin after healing. Conclusions and clinical importance – To the best of the authors’ knowledge, this is the first report describing a reversible, nonsteroid‐induced FSFS, associated with rapidly developing cachexia in cats.

Abbreviations

BCS

body condition score

FIV

feline immunodeficiency virus

FSFS

feline skin fragility syndrome

Introduction

Feline skin fragility syndrome (FSFS) is an acquired disorder characterized by markedly thin skin that easily tears following minimal trauma.1 Hyperextensibility is not observed. Skin wounds are usually associated with absent or poor bleeding and are difficult to manage. The main histological changes include a thin epidermis and a severely atrophic dermis with disorganized collagen fibres that are reduced in number and size.2 Hair follicle atrophy can be variable whereas arrector pili muscles appear relatively enlarged. Masson's trichrome stain can demonstrate tinctorial abnormalities of collagen fibres whereas elastic fibres are normal.2, 3 Electron microscopy reveals collagen bundles that are convoluted and arranged haphazardly with fibrils of different diameters, and loosely packed.4

This syndrome is described in cats suffering from diseases with well‐known negative effects on collagen synthesis including hypercortisolism (spontaneous or iatrogenic) or excessive use of progestational drugs.5, 6, 7, 8, 9 It also has been reported in association with different diseases where the pathogenesis is not clear including hepatic lipidosis, feline infectious peritonitis (FIP), cholangiohepatitis, cholangiocarcinoma and multicentric lymphoma.4, 10, 11, 12, 13 To the best of the authors’ knowledge, histopathological descriptions postrecovery are not available due to the fact that cats usually don't recover or are euthanized shortly after diagnosis. There is one case of a reversible defect in a cat experimentally receiving phenytoin.14

This case report describes three cases of FSFS associated with cachexia secondary to different causes without the implication of steroidal hormones.

Case reports

Case1

A 9‐year‐old, 2.6 kg, castrated male domestic short hair (DSH) cat was presented with a markedly thin skin observed after clipping for abdominal ultrasound and the appearance of a skin tear at the base of the tail. The cat had been examined two weeks before, with a three month history of regurgitation associated with the loss of 1.5 kg. Complete blood analysis was unremarkable, serology for feline immunodeficiency virus (FIV), feline leukaemia virus (FeLV) and feline coronavirus were negative; hyperthyroidism was excluded (TT4 1.06, reference interval (r.i.) 1.21–3.29; fT4 8.1, r.i. 8.1–16.9). The abdominal ultrasound was normal.

The cat appeared slightly depressed with significant muscle wasting and a body condition score (BCS) of 1.5 of 5 and with estimated dehydration of 5–6%.15, 16 Serous nasal discharge, dyspnoea and respiratory stridor were also present. Dermatological examination revealed a dull sparse hair coat and easily visible blood vessels in the region of clipping. One single, nonbleeding, irregular skin tear of about 3 cm was observed on the sacral region (Figure 1). Radiographs revealed the presence of mega oesophagus and an alveolar pattern in the cranial lung lobes consistent with aspiration pneumonia. Oral antibiotic therapy was started once daily with cefadroxil (Cefacure Tabs, MSD Animal Health; Milan, Italy; 25 mg/kg) and enrofloxacin (Baytril, Bayer; Milan, Italy; 5 mg/kg). Specific management of feeding to reduce the risk of regurgitation was introduced. Histopathological findings were consistent with FSFS. The owner declined any further investigation to determine the cause of mega oesophagus. Three months later, the cat was 3.2 kg and the respiratory and cutaneous problems were resolved. A second biopsy of macroscopically normal skin was taken 11 months after the first visit. There has been no recurrence three years after the condition was diagnosed.

Figure 1.

Acquired skin fragility syndrome in a cat. Case 1, skin tear observed on the sacral region. The lesion was 3 cm long and resembled an irregular “W”.

Case 2

A 13‐year‐old, 2.1 kg, male DSH feral cat was evaluated for a skin tear on the right shoulder that occurred during a restraint technique.

Ten weeks before, the cat had been hit by a car resulting in severe facial trauma with multiple fractures of the mandible and palate. The cat weighed 3 kg, was FIV positive, slightly anaemic (red blood cells (RBC) 4.70 (range 5–10) × 10⁶/μL; haematocrit (Hct) 23 (30–45)%) with mild hyperechoic liver parenchyma and renal cortex based on ultrasound examination. After stabilization, three reconstructive surgeries were performed but normal mastication was not achieved; the cat's skin was normal during the four week recovery period. Six weeks after discharge, the cat was presented with severe cachexia (BCS of 1 of 5), hypothermia and hypoglycaemia. Abdominal ultrasonic findings were unchanged whereas the anaemia had progressed (RBC 4.64, Hct 21.3%) and the albumin decreased (2.1 (2.5–4) g/dL). Two linear, nonbleeding, skin tears of about 2–3 cm were observed on the right scapula and flank together with fine dark material consistent with flea faeces. Cutaneous histopathological evaluation confirmed a diagnosis of FSFS. The cat died spontaneously after several days of hospitalization. Postmortem examination was not performed.

Case 3

A 3‐month‐old, 0.9 kg, female DSH cat living in an outdoor feral cat colony was presented due to poor body condition and lethargy. The physical examination revealed a markedly decreased body condition with a BCS of 1.5 of 5 and an estimated dehydration of 6–7%. The cat was hospitalized to receive intravenous fluids and nutritional support. Serological tests for FIV and FeLV were negative. During normal restraint for removing the needle‐cannula, the skin tore on the forelimb and dorsal neck. Examination revealed generalized thinning of the skin, no evidence of scarring and hyperextensibility. The skin lacerations were sutured and a skin biopsy was collected. Histopathological evaluation and special stains for connective tissue were suggestive of FSFS. Meanwhile, the cat was adopted by a family and fed with a balanced diet. Cutaneous wounds healed and the kitten grew normally. At nine months of age, two skin biopsies were taken during ovariohysterectomy. At the time of writing, the cat was clinically healthy three years after the condition was diagnosed.

Histological examination and special stains

Skin biopsy specimens were collected using a 6–8 mm skin biopsy punch under local anaesthesia (cases 1 and 2) or general anaesthesia (Case 3). Samples were obtained from the interscapular area in cases 1 and 2 and from the left dorsolumbar region in Case 3. Postrecovery samples were taken from the interscapular region (cases 1 and 3) and dorsolumbar sacral region (Case 3). Control tissue was obtained from two cats with normal appearing skin and without history of skin diseases. Samples were processed and stained with haematoxylin and eosin (H&E), Masson's trichrome stain and Mallory's trichrome stain; specimens were examined by one of the authors (CB). The thickness of the epidermis (from the basement membrane (BM) to the stratum corneum) and of the dermis (from the BM to the panniculus, perpendicularly to the epidermis) was recorded in 10 different points across each biopsies. The mean value was calculated for each biopsy.

Fragile skin (cases 1–3)

When compared with the control skin, the dermis appeared reduced in thickness (mean: 1 mm versus 1.7 mm). The arrector pili muscles were prominent. The collagen fibres were diffusely pale eosinophilic, thin and irregular in shape. Masson and Mallory's trichrome stains demonstrated a reduced staining intensity of collagen fibres whereas elastic fibres were normal. Furthermore, Masson's stain revealed an altered tinctorial affinity of collagen fibres (red fibres) in affected cats compared to nonaffected cats (Figure 2).

Figure 2.

Histopathological findings of acquired skin fragility syndrome. (a) Histological section of the fragile skin of a cachectic cat (Case 1). The dermis is severely reduced in thickness and collagen fibres are diffusely pale, thin and irregular in shape. Haematoxylin and eosin (H&E) stain, ×100 magnification. (b) Histological section of the fragile skin of the same cachectic cat as in (a), after healing (Case 1). The dermal thickness and collagen fibre appearance have returned to normal morphology. H&E, ×40 magnification. (c) Histological section of the skin of a cat with steroid‐induced, acquired feline skin fragility syndrome. The dermis is severely reduced in thickness and the arrector pili muscles are prominent. H&E, ×40 magnification. (d) Altered tinctorial affinity of collagen fibres (red fibres) observed in the skin of an affected cat (Case 3). Masson's trichrome stain, ×200 magnification.

Macroscopically normal skin (cases 1 and 3)

The epidermis and dermis showed no significant differences compared to the control skin samples.

Discussion

Feline skin fragility syndrome (FSFS) is an acquired disorder most commonly reported in association with diseases where there are high levels of steroid hormones.5, 6, 7, 8, 9 It is presumed that reduced collagen synthesis due to endogenous or exogenous glucocorticoids contributes to the aetiopathogenesis of this syndrome. Less commonly, FSFS has been described in cats affected by severe inflammatory, infectious or neoplastic diseases without glucocorticoids involvement.10, 11, 12, 13 In these latter cases none of the cats recovered, contrary to this report. Hepatic lipidosis, a condition frequently observed in FSFS, was excluded in cases 1 and 2 by abdominal ultrasound and in Case 3 because the history was not consistent with this disease. In the cats in this series, skin fragility was diagnosed after the development of a cachectic condition. A common element observed in cases 1 and 2 was the relatively abrupt reduction in food intake and the consequent rapid and marked weight loss. Undoubtedly, the presence of infectious diseases likely contributed to the development of cachexia. In Case 2, FIV was considered to have a chronic course but it could have further hampered the recovery of the cat exacerbating its already limited ability to feed itself. In the kitten (Case 3), malnutrition was the only suspected cause. In this cat, the high‐energy requirements due to the young age may have prompted the development of cachexia, even in the absence of a concurrent illness.

These case reports seem to reinforce the hypothesis that lack of nutrient intake and severe catabolic state, as happens during cachexia, can negatively influence collagen production in some predisposed cats, leading to skin fragility. As demonstrated by histological examination and special stains, the skin of these cats was indistinguishable from the controls once the animals recovered from the cachectic status. Because corticosteroids also induce a catabolic state, the steroid‐induced FSFS and the cachexia‐related FSFS could share, at least partially, similar pathogenic pathways. Cachexia per se, or in association with other specific diseases, could play a crucial role in the pathogenesis of FSFS, mainly in those cases where exogenous steroids are not involved.

This report demonstrates that not all the cats with FSFS have a poor prognosis and, depending on the cause, a complete recovery is possible.