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Topic:Inflammation

Inflammation is a biological response of the horse's body to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a complex process that involves the activation of immune cells, the release of inflammatory mediators, and changes in blood flow. In horses, inflammation can manifest in various forms, affecting different tissues and organs, including the joints, respiratory system, and skin. The inflammatory response is an essential component of the horse's immune system, aiming to eliminate the initial cause of cell injury, clear out damaged cells and tissues, and establish tissue repair. This topic page gathers peer-reviewed research studies and scholarly articles that explore the mechanisms, effects, and management of inflammation in equine health.
Comparison of tensile strength and early healing of acute repeat celiotomy through a ventral median or a right ventral paramedian approach.
Veterinary surgery : VS    January 27, 2014   Volume 43, Issue 6 741-749 doi: 10.1111/j.1532-950X.2014.12139.x
Boone LH, Epstein K, Cremer J, Rogers A, Foutz T, Quandt J, Howerth E, Mueller PO.To compare tensile strength, failure location, and histologic features after acute repeat celiotomy through a ventral median (RVM) or a right ventral paramedian (RVP) celiotomy in horses. Methods: Ex vivo experimental study. Methods: Adult horses (N = 18). Methods: Twelve adult horses had original ventral median (OVM) celiotomy. Repeat celiotomy was performed 72 hours postoperatively through the original ventral median (RVM, N = 6) or a RVP (N = 6) celiotomy. Celiotomies were scored daily for edema, drainage, and dehiscence. Fourteen days after repeat celiotomy, horses were eutha...
Peritoneal response to abdominal surgery: the role of equine abdominal adhesions and current prophylactic strategies.
Veterinary medicine international    January 20, 2014   Volume 2014 279730 doi: 10.1155/2014/279730
Alonso Jde M, Alves AL, Watanabe MJ, Rodrigues CA, Hussni CA.Intra-abdominal adhesions constitute a significant clinical and surgical problem that can lead to complications such as pain and bowel occlusion or subocclusion. These adhesions are frustrating and potentially fatal, representing a major postoperative complication in abdominal surgery. It is estimated that 32% of horses undergoing laparotomy will present clinical symptoms due to adhesions, but the true prevalence is not known because a large proportion of animals with postoperative recurrent colics are medically treated or submitted to euthanasia without necropsy. Adhesions are highly cellular...
Analyses of lipid rafts, Toll-like receptors 2 and 4, and cytokines in foals vaccinated with Virulence Associated Protein A/CpG oligonucleotide vaccine against Rhodococcus equi.
Veterinary immunology and immunopathology    January 15, 2014   Volume 156, Issue 3-4 182-189 doi: 10.1016/j.vetimm.2013.09.021
Kaur N, Townsend H, Lohmann K, Marques F, Singh B.Rhodococcus equi establishes long-term pulmonary infection, survives in phagolysosomes of alveolar macrophages and causes pneumonia in foals. The failure of the foal to clear R. equi bacteria is believed to be due to its inability to produce IFN-γ and defects in Toll-like receptor(TLR) signaling. Lipid rafts sequester immune receptors such as TLRs and facilitate efficient cell signaling and therefore, a deficiency in accumulation of receptors in lipid rafts may result in failure to activate. We tested whether a Virulence Associated Protein A (VapA)/CpG vaccine against R. equi would impact the...
Processionary caterpillar setae and equine fetal loss: 2. Histopathology of the fetal-placental unit from experimentally exposed mares.
Veterinary pathology    January 14, 2014   Volume 51, Issue 6 1131-1142 doi: 10.1177/0300985813516639
Todhunter KH, Cawdell-Smith AJ, Bryden WL, Perkins NR, Begg AP.Pregnant mares were experimentally exposed to whole caterpillar or exoskeleton of the Processionary caterpillar (Ochrogaster lunifer) via gavage. Tissues were collected from resulting abortions and near or full-term pregnancies consisting of 13 aborted fetuses, 3 fetuses from treated euthanized mares, membranes of 5 foals, and organs from 3 foals. Three control membranes and 1 control fetus and membranes were examined. Caterpillar setal fragments were present in the allantochorion of the 3 fetuses from the euthanized mares and 11 of 12 aborted fetuses (92%) embedded in the chorion (villi or st...
Membrane culture and reduced oxygen tension enhances cartilage matrix formation from equine cord blood mesenchymal stromal cells in vitro.
Osteoarthritis and cartilage    January 11, 2014   Volume 22, Issue 3 472-480 doi: 10.1016/j.joca.2013.12.021
Co C, Vickaryous MK, Koch TG.Ongoing research is aimed at increasing cartilage tissue yield and quality from multipotent mesenchymal stromal cells (MSC) for the purpose of treating cartilage damage in horses. Low oxygen culture has been shown to enhance chondrogenesis, and novel membrane culture has been proposed to increase tissue yield and homogeneity. The objective of this study was to evaluate and compare the effect of reduced oxygen and membrane culture during in vitro chondrogenesis of equine cord blood (CB) MSC. Methods: CB-MSC (n = 5 foals) were expanded at 21% oxygen prior to 3-week differentiation in membrane or...
Relevance of synovial fluid chondroitin sulphate as a biomarker to monitor polo pony joints. Baccarin RY, Rasera L, Machado TS, Michelacci YM.Osteoarthritis (OA) of the metacarpophalangeal joint is the most common articular disease in polo ponies leading to early retirement. A biomarker that would discriminate between pathological and physiological changes secondary to exercise could be helpful in OA prevention. The aim of this study was to investigate the effects of polo training on synovial fluid biomarkers of inflammation and cartilage turnover in polo ponies of different skill levels. Synovial fluid samples were collected from metacarpophalangeal joints of polo ponies before and during the polo season (320 d). Nucleated cells, s...
Participation of T regulatory cells in equine recurrent airway obstruction.
Veterinary immunology and immunopathology    January 7, 2014   Volume 158, Issue 3-4 128-134 doi: 10.1016/j.vetimm.2013.12.005
Henríquez C, Perez B, Morales N, Sarmiento J, Carrasco C, Morán G, Folch H.Recurrent airway obstruction (RAO) is an equine immune-mediated disease with a high incidence worldwide. The aim of this work was to contribute to the understanding of RAO pathogenesis by studying T cells bearing regulatory markers in peripheral blood (PB) and in bronchoalveolar lavage fluid (BALF) recovered from the same group of susceptible horses before and after exposure to moldy hay, which has been shown to induce RAO signology in our horse herd. With this purpose, mononuclear cells were obtained from the BALF and PB from horses before and after antigenic challenge and were stained with f...
Recurrent airway obstruction: a review.
Equine veterinary journal    January 7, 2014   Volume 46, Issue 3 276-288 doi: 10.1111/evj.12204
Pirie RS.Recurrent airway obstruction is a widely recognised airway disorder, characterised by hypersensitivity-mediated neutrophilic airway inflammation and lower airway obstruction in a subpopulation of horses when exposed to suboptimal environments high in airborne organic dust. Over the past decade, numerous studies have further advanced our understanding of different aspects of the disease. These include clarification of the important inhaled airborne agents responsible for disease induction, improving our understanding of the underlying genetic basis of disease susceptibility and unveiling the fu...
Proteomic analysis of tendon extracellular matrix reveals disease stage-specific fragmentation and differential cleavage of COMP (cartilage oligomeric matrix protein).
The Journal of biological chemistry    January 7, 2014   Volume 289, Issue 8 4919-4927 doi: 10.1074/jbc.M113.511972
Dakin SG, Smith RK, Heinegård D, Önnerfjord P, Khabut A, Dudhia J.During inflammatory processes the extracellular matrix (ECM) is extensively remodeled, and many of the constituent components are released as proteolytically cleaved fragments. These degradative processes are better documented for inflammatory joint diseases than tendinopathy even though the pathogenesis has many similarities. The aims of this study were to investigate the proteomic composition of injured tendons during early and late disease stages to identify disease-specific cleavage patterns of the ECM protein cartilage oligomeric matrix protein (COMP). In addition to characterizing fragme...
Treatment of six cases of equine corneal stromal abscessation with intracorneal injection of 5% voriconazole solution.
Veterinary ophthalmology    January 6, 2014   Volume 17 Suppl 1 179-185 doi: 10.1111/vop.12136
Smith KM, Pucket JD, Gilmour MA.To describe a reproducible technique for intrastromal injection in the standing horse for treatment of corneal stromal abscessation. Methods: A retrospective clinical study addressing the history, treatment, and outcome of six equids (six eyes) that received intrastromal voriconazole injection. Methods: Equids having a deep stromal abscess suspected to be of fungal origin were administered intrastromal injection of 5% voriconazole solution under standing sedation in an effort to bring about enhanced resolution of clinical disease. Results: Intracorneal administration of 5% voriconazole solutio...
Carprofen inhibits the release of matrix metalloproteinases 1, 3, and 13 in the secretome of an explant model of articular cartilage stimulated with interleukin 1β.
Arthritis research & therapy    January 1, 2014   Volume 15, Issue 6 R223 doi: 10.1186/ar4424
Williams A, Smith JR, Allaway D, Harris P, Liddell S, Mobasheri A.Arthritic diseases are characterized by the degradation of collagenous and noncollagenous extracellular matrix (ECM) components in articular cartilage. The increased expression and activity of matrix metalloproteinases (MMPs) is partly responsible for cartilage degradation. This study used proteomics to identify inflammatory proteins and catabolic enzymes released in a serum-free explant model of articular cartilage stimulated with the pro-inflammatory cytokine interleukin 1β (IL-1β). Western blotting was used to quantify the release of selected proteins in the presence or absence of the cyc...
RNA sequencing of the exercise transcriptome in equine athletes.
PloS one    December 31, 2013   Volume 8, Issue 12 e83504 doi: 10.1371/journal.pone.0083504
Capomaccio S, Vitulo N, Verini-Supplizi A, Barcaccia G, Albiero A, D'Angelo M, Campagna D, Valle G, Felicetti M, Silvestrelli M, Cappelli K.The horse is an optimal model organism for studying the genomic response to exercise-induced stress, due to its natural aptitude for athletic performance and the relative homogeneity of its genetic and environmental backgrounds. Here, we applied RNA-sequencing analysis through the use of SOLiD technology in an experimental framework centered on exercise-induced stress during endurance races in equine athletes. We monitored the transcriptional landscape by comparing gene expression levels between animals at rest and after competition. Overall, we observed a shift from coding to non-coding regio...
Processionary caterpillar setae and equine fetal loss: 1. Histopathology of experimentally exposed pregnant mares.
Veterinary pathology    December 30, 2013   Volume 51, Issue 6 1117-1130 doi: 10.1177/0300985813516638
Todhunter KH, Cawdell-Smith AJ, Bryden WL, Perkins NR, Begg AP.Six pregnant Standardbred mares aged between 6 and 14 years were gavaged with 50 g or 100 g of suspended emulsified whole Processionary caterpillars (Ochrogaster lunifer) for 5 days during 2 experiments undertaken to study the etiology of equine amnionitis and fetal loss (EAFL). The 6 treated mares and 1 untreated mare were between 128 and 252 days gestation. Mare 1 (untreated) was euthanized on day 5 of the treatment period, while the treated mares were euthanized on days 2, 4, 8, 10, 12, and 24 days from their first treatment. Caterpillar setae were not found in the untreated mare. Setal fra...
Characterization of arginase expression by equine neutrophils.
Veterinary immunology and immunopathology    December 30, 2013   Volume 157, Issue 3-4 206-213 doi: 10.1016/j.vetimm.2013.12.007
Lavoie-Lamoureux A, Martin JG, Lavoie JP.Neutrophils are the predominant cells recruited in the airways of horses suffering from heaves. These cells have been shown to express arginase in some species. The metabolism of l-arginine is thought to be involved in chronic inflammation, and airway obstruction and remodeling. The aim of this study was to assess the expression, regulation, activity, and functional role of arginase isoforms in equine neutrophils. Arginase I, arginase II, ornithine decarboxylase (ODC) and ornithine aminotransferase (OAT) expression were assessed in resting and stimulated (IL-4, LPS/fMLP, PMA; 5 and 18 h) blood...
Comparison between palpation and ultrasonography for evaluation of experimentally induced effusion in the distal interphalangeal joint of horses.
American journal of veterinary research    December 29, 2013   Volume 75, Issue 1 34-40 doi: 10.2460/ajvr.75.1.34
Olive J, Lambert N, Bubeck KA, Beauchamp G, Laverty S.To ultrasonographically quantify experimentally induced effusion of the distal interphalangeal (DIP) joint of horses and compare results with those obtained with palpation. Methods: 8 forelimbs from equine cadavers and forelimbs of 5 mares. Methods: Preliminary ex vivo experiments were performed to validate the methods. Then, the DIP joints of the forelimbs of standing horses were serially distended with saline (0.9% NaCl) solution (1, 4, and 10 mL) by injection through an intra-articular catheter. Two ultrasonographers measured distension of the dorsal recess of the DIP joint, and 2 surgeons,...
Effect of anesthetizing individual compartments of the stifle joint in horses with experimentally induced stifle joint lameness.
American journal of veterinary research    December 29, 2013   Volume 75, Issue 1 19-25 doi: 10.2460/ajvr.75.1.19
Tóth F, Schumacher J, Schramme MC, Hecht S.To evaluate the effects of sequential anesthesia of the individual compartments of the equine stifle joint on lameness induced by intra-articular deposition of interleukin (IL)-1β. Methods: 6 horses. Methods: For each horse, baseline hind limb lameness was first evaluated. A randomly selected compartment of 1 stifle joint was then injected with IL-1β to induce synovitis and lameness; subsequently, the same compartment was anesthetized with 2% mepivacaine hydrochloride, and lameness was reevaluated. Two weeks later, baseline lameness was evaluated, and lameness was similarly induced; thereaft...
Plasma cortisol concentration increases within 6 hours of stabling in RAO-affected horses.
Equine veterinary journal    December 19, 2013   Volume 46, Issue 5 642-644 doi: 10.1111/evj.12201
Shaba JJ, Behan Braman A, Robinson NE.In many inflammatory diseases plasma cortisol concentration (CORT) increases at the onset of acute inflammation, but the situation in recurrent airway obstruction (RAO) of horses is unknown. Methods: Split-plot repeated measures design with one grouping factor (disease) and two repeated factors (day and 3-hour intervals). Objective: To test the hypothesis that CORT increases as acute exacerbations of RAO develop. Methods: Four RAO-susceptible and 4 control horses were placed in a low dust environment (LDEnv) for 2 days followed by 2 days in a high dust environment (HDEnv). Exacerbations of RAO...
Advances in the understanding of tendinopathies: a report on the Second Havemeyer Workshop on equine tendon disease.
Equine veterinary journal    December 18, 2013   Volume 46, Issue 1 4-9 doi: 10.1111/evj.12128
Smith R, McIlwraith W, Schweitzer R, Kadler K, Cook J, Caterson B, Dakin S, Heinegård D, Screen H, Stover S, Crevier-Denoix N, Clegg P, Collins M....No abstract available
Assessment of the safety and immunogenicity of Rhodococcus equi-secreted proteins combined with either a liquid nanoparticle (IMS 3012) or a polymeric (PET GEL A) water-based adjuvant in adult horses and foals–identification of promising new candidate antigens.
Veterinary immunology and immunopathology    December 17, 2013   Volume 157, Issue 3-4 164-174 doi: 10.1016/j.vetimm.2013.12.003
Cauchard S, Bertrand F, Barrier-Battut I, Jacquet S, Laurentie M, Barbey C, Laugier C, Deville S, Cauchard J.Rhodococcus equi is the most common infectious cause of mortality in foals between 1 and 6 months of age. Because of an increase in the number of antibiotic-resistant strains, the optimization of a prophylactic strategy is a key factor in the comprehensive management of R. equi pneumonia. The objectives of this study were to assess the safety and immunogenicity of R. equi-secreted proteins (ReSP) co-administered with either the nanoparticular adjuvant Montanide™ IMS 3012 VG, or a new polymeric adjuvant Montanide™ PET GEL A, and to further investigate the most immunogenic proteins for subse...
Evaluation of mesenchymal stem cell migration after equine tendonitis therapy.
Equine veterinary journal    December 17, 2013   Volume 46, Issue 5 635-638 doi: 10.1111/evj.12173
Carvalho AM, Yamada AL, Golim MA, Álvarez LE, Hussni CA, Alves AL.Mesenchymal stem cells (MSCs) have been used to treat equine tendonitis with promising results; however, little is known about the potential migration of these cells. Objective: To assess the possible migration of MSCs from an implantation site in the superficial digital flexor tendon (SDFT) to a lesion in the SDFT of the contralateral limb. Methods: In vivo experimental study. Methods: Adipose-derived MSCs were isolated from 4 healthy horses. Lesions were induced in the SDFTs of both forelimbs, followed by intralesional implantation of autologous adipose-derived MSCs labelled with nanocrystal...
Cutaneous leishmaniosis in a horse from northern Portugal.
Veterinary parasitology    December 14, 2013   Volume 200, Issue 1-2 189-192 doi: 10.1016/j.vetpar.2013.12.005
Gama A, Elias J, Ribeiro AJ, Alegria N, Schallig HD, Silva F, Santarém N, Cardoso L, Cotovio M.The first case of cutaneous leishmaniosis in a horse from the north of Portugal, with a 1.5 cm in diameter ulcerated nodular lesion on the left face, is reported. The skin nodule was surgically excised and assessed by histopathology, including an immunohistochemistry method applied for the first time to equine tissues which clearly demonstrated leishmanial amastigote forms. Two serological determinations with the direct agglutination test performed 13 months apart showed seroconversion specific for Leishmania from a <25 to a 200 antibody titre. Polymerase chain reaction followed by kinetopl...
The effects of three-month oral supplementation with a nutraceutical and exercise on the locomotor pattern of aged horses.
Equine veterinary journal    December 10, 2013   Volume 46, Issue 5 611-617 doi: 10.1111/evj.12182
Higler MH, Brommer H, L'Ami JJ, de Grauw JC, Nielen M, van Weeren PR, Laverty S, Barneveld A, Back W.Multiple in vitro studies assessing articular tissues have indicated that glucosamine and chondroitin sulphate may possess anti-inflammatory effects, but little is known of their clinical effects in vivo. Many old horses have stiff joints, which is likely to be attributable to inflammation and therapy with these nutraceutical compounds could improve joint function. Objective: To assess the clinical effects of a mixed supplement on the improvement of stiff gait in aged horses. Methods: Randomised, blinded, placebo-controlled study. Methods: A group of 24 geriatric equids (age 29 ± 4 years; mea...
Musculoskeletal scintigraphy of the equine athlete.
Seminars in nuclear medicine    December 10, 2013   Volume 44, Issue 1 4-14 doi: 10.1053/j.semnuclmed.2013.08.003
Dyson S.Nuclear scintigraphic examination of equine athletes has a potentially important role in the diagnosis of lameness or poor performance, but increased radiopharmaceutical uptake (IRU) is not necessarily synonymous with pain causing lameness. Nuclear scintigraphy is highly sensitive to changes in bone turnover that may be induced by loading and knowledge of normal patterns of RU is crucial for accurate diagnosis. Blood pool images can be useful for identification of some soft tissue injuries, although acute bone injuries may also have intense IRU in blood pool images. Some muscle injuries may be...
Prophylactic digital cryotherapy is associated with decreased incidence of laminitis in horses diagnosed with colitis.
Equine veterinary journal    December 5, 2013   Volume 46, Issue 5 554-559 doi: 10.1111/evj.12156
Kullmann A, Holcombe SJ, Hurcombe SD, Roessner HA, Hauptman JG, Geor RJ, Belknap J.Recent research suggested that prophylactic digital cryotherapy (ICE) improved lameness scores, diminished histological changes and early laminar inflammatory signalling in horses following oligofructose administration. In clinical practice, horses at risk for sepsis-associated laminitis receive ICE. Evidence to support this practice is lacking. Objective: To determine factors associated with development of laminitis in horses diagnosed with colitis, including ICE. Methods: Multicentre retrospective case series. Methods: Medical records for horses admitted to 2 university hospitals diagnosed w...
Expression of cyclo-oxygenases-1 and -2, and microsomal prostaglandin E synthase-1 in penile and preputial papillomas and squamous cell carcinomas in the horse.
Equine veterinary journal    December 5, 2013   Volume 46, Issue 5 618-624 doi: 10.1111/evj.12144
van den Top JG, Harkema L, Ensink JM, Barneveld A, Martens A, van de Lest CH, van Weeren PR, Gröne A.Penile and preputial papilloma and squamous cell carcinoma (SCC) are commonly diagnosed in horses. Papillomas have the potential to progress to potentially lethal SCC. Knowledge of pathogenetic mechanisms may help in prevention and definition of treatment targets. Methods: Retrospective study using archived material. Objective: To determine the expression of cyclo-oxygenase 1 (COX-1), cyclo-oxygenase 2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) in penile and preputial normal tissue, papilloma and SCC in horses, and whether expression of these enzymes is influenced by degree of...
Expression of inflammation-related genes is associated with adipose tissue location in horses.
BMC veterinary research    December 2, 2013   Volume 9 240 doi: 10.1186/1746-6148-9-240
Bruynsteen L, Erkens T, Peelman LJ, Ducatelle R, Janssens GP, Harris PA, Hesta M.In humans, adipose tissue (AT) originating from different depots shows varying gene expression profiles. In horses, the risk of certain metabolic disorders may also be influenced by the impact of specific AT depots. Macrophage infiltration in human and rat AT is considered to be a source of inflammatory changes. In horses, this relationship has not been extensively studied yet. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR), a useful method to evaluate differences in mRNA expression across different tissues, can be used to evaluate differences between equine A...
Systemic and respiratory oxidative stress in the pathogenesis and diagnosis of Rhodococcus equi pneumonia.
Equine veterinary journal. Supplement    December 1, 2013   Issue 45 20-25 doi: 10.1111/evj.12166
Crowley J, Po E, Celi P, Muscatello G.Oxidative stress (OS) is most simply defined as an imbalance between oxidants and antioxidants. Oxidative stress has been suggested to play roles in various equine respiratory diseases and the significance of OS in the pathogenesis of Rhodococcus equi pneumonia is unknown. Objective: To measure and relate biomarkers of OS to lesions consistent with R. equi pneumonia. Methods: Case-control study. Methods: Various OS biomarkers were measured from blood and exhaled breath condensate (EBC) samples collected from 26 foals between 1 and 2 months of age (n = 12 cases and n = 14 controls) on 2 Thoro...
Interstitial lung disease associated with Equine Infectious Anemia Virus infection in horses.
Veterinary research    December 1, 2013   Volume 44, Issue 1 113 doi: 10.1186/1297-9716-44-113
Bolfa P, Nolf M, Cadoré JL, Catoi C, Archer F, Dolmazon C, Mornex JF, Leroux C.EIA (Equine Infectious Anemia) is a blood-borne disease primarily transmitted by haematophagous insects or needle punctures. Other routes of transmission have been poorly explored. We evaluated the potential of EIAV (Equine Infectious Anemia Virus) to induce pulmonary lesions in naturally infected equids. Lungs from 77 EIAV seropositive horses have been collected in Romania and France. Three types of lesions have been scored on paraffin-embedded lungs: lymphocyte infiltration, bronchiolar inflammation, and thickness of the alveolar septa. Expression of the p26 EIAV capsid (CA) protein has been...
Equine Pastern Dermatitis.
The Veterinary clinics of North America. Equine practice    November 26, 2013   Volume 29, Issue 3 577-588 doi: 10.1016/j.cveq.2013.09.003
Yu AA.Equine Pastern Dermatitis (EPD) is not a single disease, but a cutaneous reaction pattern of the horse. EPD should be considered a syndrome, rather than a diagnosis. Uncovering the underlying etiology prior to treatment is key to minimizing treatment failures and frustration. To achieve a positive therapeutic outcome, treating the predisposing and perpetuating factors is just as important as addressing the primary cause of EPD. This article reviews clinical signs, differential diagnoses, diagnosis, and treatment of EPD.
Immune-mediated dermatoses.
The Veterinary clinics of North America. Equine practice    November 26, 2013   Volume 29, Issue 3 607-613 doi: 10.1016/j.cveq.2013.08.001
Rosenkrantz W.Pemphigus foliaceus is the most common autoimmune skin disease in horses and is associated with the production of autoantibodies directed against surface proteins of the keratinocyte. Pemphigus vulgaris is a rare autoimmune skin disease in horses. Systemic lupus erythematosus and cutaneous lupus erythematosus are recognized in horses and both are rare. Bullous pemphigoid is a rare autoimmune disease in horses caused by immunologic attack of the basement membrane zone by autoantibodies. Erythema muliforme is an immunologic reaction in the skin in which keratinocyte cell death is the prominent c...
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