key: cord-0843406-aoz1pzau authors: Furiani, Nicla; Porcellato, Ilaria; Brachelente, Chiara title: Reversible and cachexia‐associated feline skin fragility syndrome in three cats date: 2017-05-31 journal: Vet Dermatol DOI: 10.1111/vde.12457 sha: 66867778cf02cd5f3599ccb86376794fbde4a2e9 doc_id: 843406 cord_uid: aoz1pzau 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. 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. 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. 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) 9 10 6 /lL; 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. 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. 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 The epidermis and dermis showed no significant differences compared to the control skin samples. 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 b c d 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. R esum e Contexte -Le syndrome d'hyper fragilit e cutan e f elin (FSFS) est une maladie acquise caract eris ee par une production anormale de collag ene r esultant en une peau extrêmement fine et fragile. Le FSFS est associ e a des maladies caract eris ees par un exc es d'hormones st ero€ ıdiennes qui peut inhiber la synth ese de collag ene. C'est egalement d ecrit concomitamment avec des atteintes n eoplasiques ou infectieuses, avec une inflammation s ev ere dont la pathog enie reste largement m econnue. Objectifs -D ecrire trois cas de FSFS chez des chats devenus cachectiques secondairement a diff erentes causes sans lien avec des cortico€ ıdes. D ecrire les donn ees histopathologiques des tissus conjonctifs a la fois pour la peau fragile et pour la peau apr es cicatrisation. Conclusions et importance clinique -A la connaissance des auteurs, ceci est la premi ere description d'un FSFS non induit par les cortico€ ıdes, r eversibles, associ es a une rapide cachexie chez les chats. Introducci on -El s ındrome felino de fragilidad de la piel (FSFS) es un trastorno adquirido caracterizado por la alteraci on de la producci on de col ageno, resultando en una piel extremadamente delgada y fr agil. FSFS se asocia con enfermedades caracterizadas por exceso de hormonas esteroides que pueden inhibir la s ıntesis de col ageno. Tambi en se describe asociados con enfermedades inflamatorias, infecciosas o neopl asicas severas en las que la patog enesis permanece ampliamente desconocida. Objetivos -Describir tres casos de FSFS en gatos que progresaron con caquexia secundario a causas diferentes sin presencia de glucocorticoides. Describir las caracter ısticas histopatol ogicas del tejido conectivo tanto para la piel fr agil como para la piel despu es de la cicatrizaci on. Resultados -Todos los gatos desarrollaron caquexia en menos de dos meses ( ındice de condici on corporal que oscilaba entre 1-1,5). Enfermedades concomitantes fueron diagnosticadas en el caso 1 (neumon ıa por aspiraci on por megaes ofago) y en el caso 2 (virus de la inmunodeficiencia felina (FIV)). En el caso 3, se sospechaba la malnutrici on como una causa primaria. La caracter ıstica histol ogica principal de la piel fr agil era una dermis atr ofica con fibras de col ageno eosinof ılicas p alidas, delgadas e irregulares con numerosos centros rojos observados con la tinci on de Masson. Las fibras el asticas eran normales. Los hallazgos histopatol ogicos tras su recuperaci on de la enfermedad a los 11 meses (caso 1) y los seis meses (caso 3) despu es del diagn ostico mostraron normalizaci on de la apariencia del col ageno y de la piel completa en comparaci on con los controles. Conclusiones e importancia cl ınica -Seg un conocimiento de los autores, este es el primer informe que describe una FSFS reversible no inducida por esteroides, asociada con caquexia de r apido desarrollo en gatos. Hintergrund -Das Hautfragilit€ atssyndrom der Katze (FSFS) ist eine angeborene Erkrankung, die durch eine ver€ anderte Kollagenproduktion charakterisiert ist, die in einer extrem d€ unnen und fragilen Haut resultiert. FSFS wird im Zusammenhang mit Erkrankungen gesehen, bei denen eine hohe Steroidproduktion vorkommt, die die Kollagensynthese inhibieren kann. Es wird ebenfalls gleichzeitig mit hochgradig entz€ undlichen, infekti€ osen oder neoplastischen Zust€ anden, bei denen die Pathogenese weitgehend unbekannt ist, beschrieben. e um dist urbio adquirido caracterizado pela produc ßão alterada de col ageno, resultando em uma pele extremamente fr agil e atrofiada. A SFCF est a associada a doenc ßas que cursam com excesso de hormônios esteroidais que podem inibir a s ıntese de col ageno. E tamb em descrita concomitantemente com doenc ßas inflamat orias, infecciosas e neopl asicas, e esta patogênese permanece desconhecida. Objetivos -Descrever três casos de SFCF em gatos que se tornaram caqu eticos secundariamente a diferentes causas, sem envolvimento de glicocorticoides. Descrever as caracter ısticas histopatol ogicas do tecido conectivo da pele fr agil e da pele ap os resoluc ßão do quadro. Resultados -Todos os gatos desenvolveram caquexia em menos de dois meses (escore de condic ßão corp orea variando de 1-1,5). No Caso 1, foram diagnosticadas concomitantemente pneumonia por aspirac ßão secund aria a megaesôfago. No Caso 2, foi diagnosticado o v ırus da imunodeficiência felina (FIV). No Caso 3, a causa prim aria suspeita para SFCF foi a malnutric ßão. O principal achado histopatol ogico da fragilidade cutânea foi atrofia d ermica com eosin ofilos p alidos, fibras col agenas finas e irregulares com numerosos grumos vermelhos corados com corante de Masson. As fibras el asticas estavam normais. Os achados histopatol ogicos p os recuperac ßão, 11 meses (Caso 1) e seis meses (Caso 3) ap os o diagn ostico, demonstraram normalizac ßão do col ageno e de toda a pele, quando comparados aos controles. Conclusões -De acordo com o conhecimento do autor, este e o primeiro relato descrevendo SFCF revers ıvel, não induzida por esteroides e associada ao desenvolvimento r apido de caquexia em felinos. Muller and Kirk's Small Animal Dermatology Skin Diseases of the Dog and Cat Staining abnormalities of dermal collagen in cats with cutaneous asthenia or acquired skin fragility as demonstrated with Masson's trichrome stain Abnormal skin fragility in a cat with cholangiocarcinoma Hyperadrenocorticism and hyperprogesteronemia in a cat with an adrenocortical adenocarcinoma Hyperaldesteronism and hyperprogesteronism in a cat Pituitary-dependent hyperadrenocorticism and generalised toxoplasmosis in a cat with neurological signs Feline pituitary-dependent hyperadrenocorticism and insulin resistance due to a plurihormonal adenoma Concurrent somatotroph and plurihormonal pituitary adenomas in a cat Feline skin fragility syndrome in a cat with hepatic lipidosis Skin fragility syndrome in a cat with feline infectious peritonitis and hepatic lipidosis Skin fragility syndrome in a cat with cholangiohepatitis and hepatic lipidosis Skin fragility syndrome in a cat with multicentric follicular lymphoma Reversible dermal atrophy in a cat treated with phenytoin AAHA nutritional assessment guidelines for dogs and cats Textbook of Veterinary Internal Medicine The authors are grateful to Veronica Greatti for providing the second skin biopsy in case 3.