Hereditary equine regional dermal asthenia in three related Quarter horses in Brazil

Hereditary equine regional dermal asthenia belongs to a group of inherited, congenital connective tissue dysplasias usually described as hyperelastosis cutis, cutaneous asthenia, dermatosparaxis, or Ehlers-Danlos-like syndrome. This report presents the clinical and histological features of three related Quarter horses affected with regional dermal asthenia. These horses had bilateral asymmetric lesions of the trunk and lumbar regions, where the skin was hyperextensible. Handling of the skin elicited a painful response and superficial trauma led to skin wounds. The skin was thinner than normal in the affected areas, with thickened borders and harder fibrotic masses (pseudotumours). The histopathological findings included thinner and smaller collagen fibrils, and a loose arrangement of collagen fibres in the middle, adventitial and deep dermis. Masson's trichrome and Calleja stains did not reveal any abnormality of collagen and elastic fibres. Electron microscopy showed no abnormalities. As in human patients, pseudotumour histopathological findings included fibroplasia and neovascularization. The pedigree chart of these animals supports an autosomal recessive type of inheritance, which has been suggested by other studies. This is the first report of this disease in Brazil. Its clinical and histological features resemble those described in horses affected with this condition in the United States.     

Hereditary equine regional dermal asthenia (HERDA) in Quarter Horses: A review of clinical signs,genetics and research

Hereditary equine regional dermal asthenia (HERDA) results from a genetic mutation which affects the skin and other tissues of Quarter Horses and horses with Quarter Horse lineage. The disease HERDA has an autosomal recessive mode of inheritance and has become a significant concern in the Quarter Horse industry due to the high frequency of heterozygote carriers. Affected homozygous horses appear normal at birth; however, within the first 2 years of life they usually acquire loose, hyperextensible skin and wounds which result in disfiguring scars either spontaneously or from minor trauma. Some severely affected horses also develop haematomas and seromas. Consequently, most affected horses are subjected to euthanasia at an early age. No treatment options other than palliative therapy currently exist. As part of a five panel test ( http://www.aqha.com/News/News-Articles/2013/April/04292013-Genetic-Testing.aspx ) the American Quarter Horse Association presently requires DNA testing for HERDA on all breeding stallions. There are currently no restrictions on registration of horses heterozygous or homozygous for the HERDA mutation. Due to the autosomal recessive nature of the disease, Quarter Horse mares and horses of all breeds from HERDA‐associated bloodlines should also be tested.     

Ehlers-Danlos Syndrome in a Quarter Horse Gelding: A Case Report of PPIB-Independent Hereditary Equine Regional Dermal Asthenia

A Quarter Horse gelding presented with pathology consistent with hereditary equine regional dermal asthenia (HERDA) but without the familial association typically present with this disease. Grossly, lesions exhibited either a firm, scar-like appearance or a potential space between the superficial and deep dermis. Both lesioned and non-lesioned skin showed evidence of edema and collagen fragmentation, whereas lesions were also characterized by hemorrhage and inflammation. Genetic testing was performed by three independent laboratories, each using different methods to detect the mutation described in the PPIB gene, previously shown to be associated with HERDA. No mutations in the PPIB gene were revealed by genetic testing, either at the known location of the point mutation or at any other location in the coding sequence. These findings are suggestive of a diagnosis of HERDA or hyperelastosis cutis in the absence of the well-described, putatively causative mutation in the PPIB gene. We propose that, whereas HERDA refers specifically to a familial disease caused by a mutation in the PPIB gene, similar symptoms may in fact be caused by a syndrome resulting from either inherited or spontaneous mutations in any of a number of collagen-processing genes. We conclude that Ehlers-Danlos syndrome be diagnosed in horses of any breed with HERDA-like pathology without the causative mutation.     

Prevalence of the mutation in cyclophilin B (PPIB), a causal candidate gene for HERDA, among Quarter Horses in France

Hereditary equine regional dermal asthenia (HERDA) in Quarter Horses is an inherited degenerative skin disease. Initially reported as hyperelastosis cutis, HERDA has a phenotype of hyperextensible, fragile skin, with secondary seromas, haematomas, ulcers and scarring. It primarily affects the dorsal aspect of the body. An autosomal recessive mode of inheritance is considered likely, with affected horses more at risk to produce affected offspring. A mutation in cyclophilin B (PPIB) as a novel, causal candidate gene for HERDA has been described, and verified as segregating with carriers and affected horses. Screening of control Quarter Horses in the USA has indicated a 3.5% carrier frequency. The prevalence of this mutation among Quarter Horses in France was determined to be 1.6%.     

Clinical and pathological findings in a HERDA-affected foal for 1.5 years of life

A Quarter horse filly bred from two horses affected with HERDA (hereditary equine regional dermal asthenia) was observed clinically and its skin histologically for the 1.5 years of its life. Severe signs of the disease did not manifest until 1.5 years of age, and were not temporally related to saddling. Histological comparison to an age-, breed- and sex-matched control did not show any consistent diagnostic features. Monitoring of the proband substantiated previous reports of (i) the autosomal recessive nature of the disease, (ii) mares affected with HERDA being able to foal without damage to the skin or reproductive tract, (iii) HERDA foals appearing phenotypically normal throughout the first year of life, and (iv) demonstrated that histological interpretation of skin specimens from grossly normal skin may be insufficient to differentiate HERDA-affected horses from controls.     

Marjolin’s Ulcer in Two Horses with Hereditary Equine Regional Dermal Asthenia

Two Quarter Horse mares with hereditary equine regional dermal asthenia (HERDA) were diagnosed with metastatic squamous cell carcinoma (SCC) associated with chronic nonhealing wounds. The lesions were similar to the development of SCC from chronic nonhealing ulcers, known as Marjolin’s ulcers in humans. The horses showed recurrent skin wounds in the saddle and paralumbar regions and were confirmed by molecular techniques as having HERDA. Both horses were maintained as research animals for prolonged periods and received regular veterinary care and wound treatment. Both horses were ultimately euthanized because of their chronic progressive wounds, coupled with declining health. At necropsy, the nonhealing wounds were found to be complicated by infiltrative SCC; both horses had metastasis to lungs. Chronically inflamed, recurrent skin wounds that heal slowly and incompletely as a consequence of HERDA are proposed as a major pathogenetic factor in tumorigenesis. Consistent findings with respect to proliferation index (Ki-67) and mutations of p53 tumor suppressor gene were confirmed by immunohistochemistry in one horse. SCC consistent with Marjolin’s ulcer has been previously suggested in association with chronic ulcers or burn scars in horses, but this is the first report of an association with chronic poor healing wounds in HERDA horses.     

Industry Perceptions of HERDA in Performance Horses

Hereditary equine regional derma asthenia (HERDA), an autosomal-recessive trait, found in Quarter Horses, causes abnormal collagen structure. Owing to current breeding practices, 3.5% of registered quarter horses and 28.3% of the cow horse population are heterozygote carriers. Research demonstrated homozygote horses develop hyperextensible skin susceptible to injury and other abnormal tissues containing high fibrillar collagen content. No research exists determining the effects of the disease in heterozygote carriers. Currently, 30% of cutting sires are HERDA carriers, potentially increasing the number of heterozygous individuals when bred. The objective of the present study is to gauge knowledge of the disease, perception, and concerns of the diseases’ impact on horse performance and perceived value and breeding decisions. A Qualtrics link was distributed to horse owners via extension specialists and was available online on equine-related Facebook pages. Overall group means and standard deviations for constructs were reported. A total of 228 responses were collected. Most participants were involved in reining and cutting and 34.6% reported they were very familiar with the disease. Participants (78.5%) reported that HERDA status affects value of a breeding animal. Owners of HERDA carriers (62.5%) noticed no difference in performance or injury compared with noncarriers. Respondents (95.2%) believed that all breeding animals should have HERDA status available. Respondents are attempting to make informed breeding decisions based on HERDA status by pairing carriers with noncarriers; however, it remains to be seen if that is adequate to control the disease. Education regarding breeding practices and its impact on the genetic pool are warranted.     

Inheritance of hereditary equine regional dermal asthenia in Quarter Horses

OBJECTIVE: To assess heritability and mode of inheritance for hereditary equine regional dermal asthenia (HERDA) in Quarter Horses. ANIMALS: 1,295 horses with Quarter Horse bloodlines, including 58 horses affected with HERDA. PROCEDURE: Horses were classified as affected or unaffected or as undetermined when data were insufficient to assess phenotype. Pedigree data were analyzed to determine the probable mode of inheritance. Heritability was estimated by use of Bayesian statistical methods. RESULTS: Heritability (mean+/-SD) of HERDA was estimated to be 0.38+/-0.13, with both sexes having an equal probability of being affected. Results for evaluation of the pedigrees were consistent with a single Mendelian autosomal recessive mode of inheritance. CONCLUSIONS AND CLINICAL RELEVANCE: HERDA in Quarter Horses is an inherited disease, and affected horses are more likely to produce affected offspring. An autosomal recessive mode of inheritance should be considered by people making breeding decisions involving Quarter Horses when a first-degree relative has been confirmed with HERDA or has produced affected offspring. In addition, breeders whose horses have produced affected offspring can reduce the likelihood of producing affected horses in the future by avoiding inbreeding.     

Zonal dermal separation: a distinctive histopathological lesion associated with hyperelastosis cutis in a Quarter Horse

This case report describes a distinctive deep cutaneous lesion in a 1-year-old Quarter Horse filly with hyperelastosis cutis. The horse had a typical clinical presentation of hyperelastic skin associated with a 6-month history of cutaneous wounds that developed following minor cutaneous trauma. Punch biopsies of skin from the affected horse were thinner than similar biopsies from an age- and breed-matched control. Significant microscopic lesions were not seen in cutaneous punch biopsies stained with haematoxylin and eosin and Masson's trichrome stains, but the ultrastructure of the dermis from the affected horse was characterized by variation in collagen fibre diameter and loose packing of collagen fibres within bundles. The horse was euthanized and necropsied, and full-thickness sections of skin were collected and examined microscopically. Affected skin was of normal thickness; however, the deep dermis contained a distinctive horizontal linear zone in which separation of collagen bundles resulted in the formation of large empty cleft-like spaces between the upper and lower regions of the deep dermis. We suggest the term 'zonal dermal separation' for this microscopic lesion. Incisional full-thickness skin biopsies should be taken in suspected cases of equine hyperelastosis cutis because punch biopsies may not obtain enough deep dermis to adequately represent pathological change in the skin of horses with this disorder.     

Suspected wood poisoning caused by Simarouba amara (marupá/caixeta) shavings in two dogs with erosive stomatitis and dermatitis

Two male Labrador retrievers developed bleeding erosions/ulcerations involving the oral mucosa, mucocutaneous junctions of the lips, nose, prepuce and anus, ulcerated nodules on the chin, and crusting lesions on the elbows, hocks and scrotum. One of the dogs was anorexic and depressed, had haematological abnormalities consistent with damage to the liver and signs of neurological disease. As these dogs had recently been exposed to bedding containing Simarouba amara shavings and because of the striking similarities of clinical signs to those described for horses, a probable diagnosis of wood poisoning was made. This assumption was supported by the clinical course as healing of skin lesions occurred when the dogs were no longer exposed to the bedding.     

Renal tubular acidosis in two horses: diagnostic studies

An 11-year-old Quarter Horse mare and a 2-year-old Quarter Horse colt with clinical diagnoses of renal tubular acidosis (RTA) were donated to the University of California Veterinary Medical Teaching Hospital. A series of diagnostic tests was performed in an attempt to characterize the type and cause of RTA in these horses. Endogenous creatinine clearance and sodium sulfanilate clearance were within reference ranges; thus, no abnormality of glomerular function was detected. To assess renal tubular function in response to acid loading, each horse was given 0.1 g of NH4Cl/kg of body weight via nasogastric tube in 6 L of water. Urine acidification in response to the oral acid load was less than that observed in control horses. The urinary clearance ratio for sodium also was found to be greater for the principals than for the controls. These findings supported a diagnosis of RTA that closely resembled type 1 or distal RTA. In an attempt to determine the cause of RTA, renal ultrasonography, renal biopsy, and a mating study were performed. No abnormalities were identified, and the cause of RTA in these cases remained unknown.     

Staining abnormalities of dermal collagen in eosinophil- or neutrophil-rich inflammatory dermatoses of horses and cats as demonstrated with Masson's trichrome stain

A retrospective study was performed on skin biopsy specimens from horses and cats having eosinophilic granulomas with 'collagen degeneration', eosinophilic skin diseases without 'collagen degeneration' and pyogranulomas without 'collagen degeneration'. Neither the appearance of collagen fibres nor the dominant polymorphonuclear cells, as seen in H & E-stained sections, were predictive of Masson's trichrome findings. Hence, a Masson's trichrome staining abnormality of collagen fibres was no more likely to be present in lesions with 'collagen degeneration' than in those lesions without 'collagen degeneration'. In addition, evaluation of trichrome-stained specimens suggested that there is no collagen degeneration in equine and feline eosinophilic granulomas and that the areas previously referred to as collagen degeneration are more appropriately called flame figures.     

Inflammatory bowel disease characterized by multisystemic eosinophilic epitheliotropic disease (MEED) in a horse in Saskatchewan,Canada

A 3-year-old Quarter Horse gelding was evaluated for chronic weight loss, diarrhea, and pruritus. Physical examination revealed several ulcerative lesions on the skin and mucosal membranes. Diagnostic imaging findings were consistent with enteritis, typhlitis, and colitis. Multisystemic eosinophilic epitheliotropic disease (MEED) was diagnosed upon necropsy. This disease may be considered a form of equine inflammatory bowel disease complex which can be challenging to diagnose, requiring histological assessment, and in some cases, the use of immunohistochemical markers.Key clinical message:Multisystemic eosinophilic epitheliotropic disease is challenging to diagnose but should be considered in horses with chronic weight loss that fail to respond to conventional treatment for concurrent diarrhea and skin lesions.     

B-Mode Ultrasonographic Abnormalities and Power Doppler Signal in Suspensory Ligament Branches of Nonlame Working Quarter Horses

Information concerning B-mode ultrasonographic abnormalities and power Doppler (PD) signal in suspensory ligament branches of nonlame working Quarter Horses are not reported. The aims of this study were to investigate the prevalence of B-mode ultrasonographic abnormalities and PD signal in suspensory ligament branches in a group of nonlame working Quarter Horses and to compare B-mode findings with PD findings of horses in two different training (barrel racing and team roping). Twenty-one Quarter Horses in training, 14 barrel racing (Group B) and seven team roping horses (Group R), were assessed by ultrasound for screening purpose. A total of 168 suspensory ligament branches were examined (B-mode and PD examinations). B-mode lesions were seen more frequently in forelimbs (25 branches) than in hindlimbs (10 branches). Power Doppler signal was not detected in suspensory ligament branches that were normal at B-mode, whereas it was visible in 22 of the 35 branches abnormal at B-mode. Horses of Group R showed more B-mode abnormalities and more PD signal in branches abnormal in B-mode.     

Pathological aspects of Australian Stringhalt.

Nine horses with clinical signs of Australian Stringhalt were killed and tissues collected for a detailed pathological study. Lesions were limited to peripheral nerves and muscles. The most severely affected nerves were the superficial and deep peroneal, distal tibial, plantar digital, volar and recurrent laryngeal nerve with changes characterised by a selective loss of large diameter myelinated fibres with various degrees of demyelination, fibrosis, Schwann cell proliferation and onion-bulb formation. A routine evaluation of the brain and spinal cord by light microscopy failed to reveal any consistent abnormalities. Morphometric analysis of deep peroneal and recurrent laryngeal nerves confirmed the reduced number of large diameter myelinated axons. Teased fibre preparations of these nerves did not show any abnormalities in internodal distance. The most severe muscle lesions were in the long and lateral digital extensors, cranial tibial, dorsal cricoarytenoid, gracilis and lateral deep digital flexor with extensive atrophy of fibres and diffuse fibrosis. Histochemical evaluation of the long digital extensor from 3 affected horses showed an abnormally wide distribution in fibre size and a reduction in type II fibres compared with controls. These lesions are consistent with a distal axonopathy leading to neurogenic muscle atrophy. The distribution of neuromuscular lesions in Australian Stringhalt may be explained by the susceptibility of longer, larger myelinated nerve fibres to injury, but the cause for this distal axonopathy remains unknown.     

Effects of Topical Application of Sunflower-Seed Oil on Experimentally Induced Wounds in Horses

The objectives were to evaluate clinical and histopathological aspects of topical application of sunflower-seed oil (Helianthus annuus) on the healing process of experimentally induced wounds in lumbar and metacarpal areas of healthy horses. Six adult horses were used. Eight wounds were surgically produced on each horse: two 6.25-cm² wounds cranial to the sacrum on each side of the lumbar region and two 2.89-cm² wounds close to the proximal epiphysis of the metacarpus on the lateral aspect of each forelimb. Left side was used for macroscopic observations and right side for histopathological analysis. The experimental lesions were treated daily with sunflower-seed oil, whereas saline solution was used in control lesions. Macroscopic and histopathological analyses were performed on tissue harvested at 3, 7, 14, and 21 days. Complete healing time for all wounds was recorded. For lumbar region’s wounds, a contraction of 90.78% was recorded for those treated with oil and of 79.27% for control wounds after 21 days of treatment. For metacarpal region’s wounds, a contraction of 47.63% was recorded for wounds treated with oil and of 30.21% for control wounds. Wounds in the sunflower-seed oil treatment group had an elevation of polymorphonuclear cells, a newly formed vascular bed during the inflammatory phase, and a better alignment of collagen fibers during the remodeling phase. In conclusion, topical application of sunflower-seed oil was beneficial in the healing process of experimentally induced skin wounds in horses, with best results for treatment of lumbar wounds, making it a therapeutic option in equine wound healing.     

Antibodies to elastin peptides in sera of Belgian Draught horses with chronic progressive lymphoedema

REASONS FOR PERFORMING STUDY: Chronic progressive lymphoedema (CPL) is a recently recognised disease of the lymphatic system characterised by lesions in the skin of the lower legs in several draught horse breeds, including the Belgian Draught hourse. Clinical signs slowly progress and result in severe disfigurement of the limbs. Ideally, supportive treatment should be started early in the disease process. However early diagnosis and monitoring progression of CPL is still a challenge. HYPOTHESIS: Elastin changes, characterised by morphological alterations as well as increased desmosine levels, in the skin of the distal limbs of horses affected with CPL are probably associated with a marked release of elastin degradation products, which elicit production of circulating anti-elastin antibodies (AEAbs) in the serum. An enzyme-linked immunosorbent assay (ELISA) for detection of serum AEAbs may document elastin breakdown. METHODS: An ELISA technique was used to evaluate levels of AEAbs in sera of 97 affected Belgian Draught horses that were clinically healthy except for possible skin lesions, associated with CPL in their distal limbs. The horses were divided into 5 groups according to the severity of these skin lesions: normal horses (Group 1, n = 36), horses with mild lesions (Group 2, n = 43), horses with moderate lesions (Group 3, n = 8), horses with severe lesions (Group 4, n = 10) and, as a control, healthy Warmblood horses, unaffected by the disease (Group 5, n = 83). RESULTS: Horses with clinical signs of CPL had significantly higher AEAb levels compared to clinically normal Belgian Draught horses and to healthy Warmblood horses. These levels correlated with severity of lesions. CONCLUSIONS: CPL in draught horses is associated with an increase of serum AEAbs. POTENTIAL RELEVANCE: Evaluation of serum levels of AEAbs by ELISA might be a useful diagnostic aid for CPL. Pathological degradation of elastic fibres, resulting in deficient support of the distal lymphatics, is proposed as a contributing factor for CPL in Belgian Draught horses.     

Suspensory ligament degeneration associated with pituitary pars intermedia dysfunction in horses

In older horses, pituitary pars intermedia dysfunction (PPID) and suspensory ligament (SL) degeneration are common. The aim of the present study was to identify histopathological changes in the SL in horses with PPID. SLs of four horses with clinical signs of PPID (17–26 years of age) were compared with SLs from four old horses (18–31 years of age) and three young horses (4–9 years of age). In horses with PPID, there was reduced longitudinal arrangement of collagen fibres in SLs, along with inclusions of cartilage, extracellular matrix and haemorrhage, as well as significant proteoglycan accumulations between SL fibres. These changes are similar to the degeneration of connective tissues in Peruvian Paso horses with SL degeneration and in humans with Cushing's disease or after long term high dose corticosteroid treatments. These findings indicate an association between degeneration of the SL and PPID.     

Treatment of equine onchocerciasis with ivermectin paste

SUMMARY A single oral dose of ivermectin paste was administered to 12 horses with dermatitis and clinical signs typical of onchocerciasis. Two of the horses also had lesions of Queensland itch. Microfilarias of Onchocerca cervicalis were identified in fresh, macerated, skin biopsies from the neck, brisket or umbilical regions of all horses and microfilarias of O. gutturosa from the neck of 2. Eight of the horses developed skin reactions 4 to 24 h after the administration of the ivermectin, notably weals over the neck, shoulders and flanks and pitting oedema of the ventral midline and intermandibular space. Regression of the onchocerciasis lesions was evident within 7 days of treatment and affected skin had returned to normal within 3 months. The lesions of Queensland itch were not affected by the ivermectin treatment. Microfilarias were present in biopsies of skin, particularly in the superficial dermis, before treatment, but were absent from all skin biopsies taken one week after treatment. In some horses transient skin sensitivity reactions developed. Microfilarias began to reappear in the biopsies of some of the horses 2 months after treatment. It is concluded that the oral paste formulation of ivermectin, although not effective against adult onchocerca, is useful for the therapeutic control of microfilarias in the skin lesions of equine onchocerciasis.     

GROSS AND HISTOPATHOLOGIC CORRELATION OF LOW‐FIELD MAGNETIC RESONANCE IMAGING FINDINGS IN THE STIFLE OF ASYMPTOMATIC HORSES

With the recent introduction of a 0.25T rotating MRI system, clinical evaluation of the equine stifle joint is now possible in the average equine athlete. A recent publication described common abnormalities of horses with stifle lameness detected with a low‐field MRI system; however, postmortem corroboration of the lesions detected was not possible. Therefore, our objective was to compare postmortem findings with low‐field MRI findings in equine cadaver stifle joints. Ten fresh cadaver stifle joints from horses without clinical signs of stifle disease were evaluated using low‐field MRI, gross dissection, and histopathology. In eight stifles, either the lateral or medial cranial meniscotibial ligament had an irregular shape, fiber separation, or moderate abnormal signal intensity (SI) on all sequences. In five stifles, the medial femoral condyle had articular cartilage fibrillation with or without an osteochondral defect over the weight bearing surface of the medial femoral condyle. All stifles had abnormal SI on all sequences within the patellar ligaments that corresponded with adipose tissue infiltrating between the collagen bundles. Other abnormalities identified included articular cartilage fibrillation of the tibial condyles in three stifles, and articular cartilage fibrillation with chondral defects in the patella in three stifles. All abnormalities detected with low‐field MRI were corroborated by gross dissection. Findings from the current study supported the use of low‐field MRI for detection of stifle joint lesions in horses and demonstrated that some stifle joint pathologies may be subclinical in horses.