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[[Autoimmune skin diseases]] occur when the [[immune system]] of an infected animal attacks its own skin.<ref>{{cite journal |last1=Gershwin |first1=Laurel J. |title=Current and Newly Emerging Autoimmune Diseases |journal=Veterinary Clinics of North America: Small Animal Practice |date=March 2018 |volume=48 |issue=2 |pages=323–338 |doi=10.1016/j.cvsm.2017.10.010 |pmid=29248206 }}</ref> In [[dog]]s, autoimmune skin diseases are usually not detected until visible symptoms appear, which differs from detection in humans who are able to verbally express their concerns.<ref name=":32">{{cite journal |last1=Tham |first1=Heng L. |last2=Linder |first2=Keith E. |last3=Olivry |first3=Thierry |title=Autoimmune diseases affecting skin melanocytes in dogs, cats and horses: vitiligo and the uveodermatological syndrome: a comprehensive review |journal=BMC Veterinary Research |date=December 2019 |volume=15 |issue=1 |page=251 |doi=10.1186/s12917-019-2003-9 |doi-access=free |pmc=6639964 |pmid=31324191}}</ref> [[Genetics]], nutrition, and external environmental factors all collectively contribute to increasing the probability an autoimmune skin disease occurring.<ref name=":42">{{cite journal |last1=Gershwin |first1=Laurel J. |title=Autoimmune Diseases in Small Animals |journal=Veterinary Clinics of North America: Small Animal Practice |date=May 2010 |volume=40 |issue=3 |pages=439–457 |doi=10.1016/j.cvsm.2010.02.003 |pmid=20471527 }}</ref> The severity of symptoms varies based on the specific disease present and how far it has progressed. Diagnosis often requires the onset of visible symptoms and for a [[biopsy]] to be performed. For many diseases, the condition itself cannot be cured, but a veterinarian can prescribe medications and other forms of treatment to help manage the symptoms of the dog.<ref name=":18">{{Cite journal |last=Fukushima |first=K. |date=April 1982 |title=Pathogenesis of pemphigus vulgaris in dog and man - a review |journal=The Canadian Veterinary Journal |volume=23 |issue=4 |pages=135–137 |pmc=1790145 |pmid=17422133 }}</ref>
{{Orphan|date=November 2019}}

'''Autoimmune skin diseases in dogs''' are [[disease]]s occurring in [[dogs]] in which the immune system targets itself, with [[white blood cell]]s or [[antibodies]] in the body attacking its own [[Tissue (biology)|tissues]] or the extracellular [[protein]] of the skin.<ref>{{Cite web|url=http://vcahospitals.com/know-your-pet/autoimmune-skin-disease-in-dogs|title=Autoimmune Skin Disease in Dogs|website=vca_corporate|language=en|access-date=2019-11-09}}</ref> When autoimmune diseases occur in dogs, detection is not noted until visible, compared to humans who can verbally express their concerns. Genetics, nutrition, and external environmental factors collectively contribute to increasing the probability of an autoimmune disease developing. For dogs diagnosed with an autoimmune disease, a veterinarian's care is necessary to manage the condition. The severity varies on the type of disease the dog has and the specific symptoms. Unfortunately, there is not always a guaranteed cure, but treatments can be offered to provide comfort.


== Overview ==
== Overview ==
{{see also|Autoimmunity}}
{{see also|Autoimmunity}}


The immune system has the ability to differentiate between the body's own [[Cell (biology)|cells]] and foreign cells.<ref>{{Citation|title=Immune system|date=2019-10-30|url=https://en.wikipedia.org/enwiki/w/index.php?title=Immune_system&oldid=923814247|work=Wikipedia|language=en|access-date=2019-11-09}}</ref> However, in the dogs affected by auto-immune disease, the immune system loses the ability to distinguish between body's own cells and foreign cells, causing their immune system to attack the body's own cells.<ref name="Autoimun">{{Cite web |url=http://www.thepetcheckup.com/works/screen/auto-immune_disease.html |title=Auto-immune Diseases |access-date=2019-10-27 |archive-date=2019-10-30 |archive-url=https://web.archive.org/web/20191030030740/http://www.thepetcheckup.com/works/screen/auto-immune_disease.html |url-status=dead }}</ref> Autoimmune diseases in the base layer of the [[epidermis]] are characterized by damage to the connective tissue and vesicle formation located below the epidermis layer and the dermis layer below it.<ref name="Papado">Papadogiannakis EI. 2005. Contemporary aspects of the immunopathogenesis of autoimmune diseases of the epidermal basement membrane in the dog. The Journal of the Hellenic Veterinary Medical Society 56(1) p 27-31.</ref><ref>{{Cite web|url=https://www.merckvetmanual.com/dog-owners/skin-disorders-of-dogs/structure-of-the-skin-in-dogs|title=Structure of the Skin in Dogs - Dog Owners|website=Merck Veterinary Manual|language=en-US|access-date=2019-11-09}}</ref>
The immune system has the ability to differentiate between the [[Cell (biology)|cells]] of the body and foreign cells. However, in dogs affected by an [[autoimmune disease]], the immune system loses the ability to make this distinction, causing the immune system to attack the body.<ref name="Autoimun">{{Cite web |url=http://www.thepetcheckup.com/works/screen/auto-immune_disease.html |title=Auto-immune Diseases |access-date=2019-10-27 |archive-date=2019-10-30 |archive-url=https://web.archive.org/web/20191030030740/http://www.thepetcheckup.com/works/screen/auto-immune_disease.html |url-status=dead }}</ref> Autoimmune diseases in the base layer of the [[epidermis]] are characterized by damage to the connective tissue and vesicle formation located below the [[epidermis]] layer and the [[dermis]] layer below it.<ref name="Papado">{{cite journal |last1=Papadogiannakis (E. ι. παπαδογιαννακης) |first1=E. I. |title=Contemporary aspects on the immunopathogenesis of autoimmune diseases of the epidermal basement membrane in the dog |journal=Journal of the Hellenic Veterinary Medical Society |date=29 November 2017 |volume=56 |issue=1 |pages=27 |doi=10.12681/jhvms.15066 }}</ref><ref name=":5">{{Cite web|url=https://www.merckvetmanual.com/dog-owners/skin-disorders-of-dogs/structure-of-the-skin-in-dogs|title=Structure of the Skin in Dogs - Dog Owners|website=Merck Veterinary Manual|access-date=2019-11-09}}</ref> There are many autoimmune diseases, and they all vary in impact to the dog and progress at their own rates.<ref>{{Cite journal |last=Pedersen |first=Niels C |date=August 1999 |title=A review of immunologic diseases of the dog |journal=Veterinary Immunology and Immunopathology|volume=69 |issue=2–4 |pages=251–342 |doi=10.1016/S0165-2427(99)00059-8 |pmc=7119806 |pmid=10507310}}</ref>


== Clinical symptoms ==
== Clinical symptoms ==
[[File:Canine pemphigus foliaceus 3.jpg|thumb|250px|'''Pemphigus foliaceus''' in [[dogs]]: hair loss occurs, skin becomes red, and itchy.]]
[[File:Canine pemphigus foliaceus 3.jpg|thumb|250px|'''Pemphigus foliaceus''' in [[dogs]]: hair loss occurs, skin becomes red, and itchy.]]
Dogs suffering from autoimmune diseases of the [[skin]] may experience a variety of symptoms, including persistent [[itching]] and scratching, lesions, wounds, blisters, and other skin damage, as well as loss of skin [[pigment]].<ref name="Autoimun" /> Two cases of autoimmune diseases that are often found include ''[[Discoid lupus erythematosus]]'' (DLE) and ''[[Pemphigus]]''. DLE can develop into [[Systemic lupus erythematosus|Systemic Lupus Erythematosus]] (SLE).<ref name="Mueller">[http://www.ivis.org/proceedings/scivac/2005/Mueller1_en.pdf?LA=1 Immune-mediated Skin Diseases. Rimini: 50th Congresso Nazionale Multisala SCIVAC]</ref> The initial stage of DLE is marked by a loss of skin [[pigment]]. The skin becomes red and [[Ulcer (dermatology)|sore]]s appear on the [[nose]]. The [[palate]] can undergo [[erosion]], ulceration, and injury to the nasal palate, as well as damage to the nostrils and the tissue around the eyes and ears. In [[chronic condition|chronic]] and severe cases, visual scar tissue often occurs.<ref name="Mueller" /> Most symptoms occur after the outer epidermis and inner dermis of the skin are affected by the disease. When this happens, the layers of the skin begin to separate, leading to painful lesions and pustules. The compromised integrity of the skin barrier not only exacerbates the discomfort experienced by the dog, but also heightens the risk of secondary bacterial infections. The weakening of the skin’s protective layers forms an environment susceptible to microbial infiltration, which could lead to severe complications. Intervening within an earlier time frame and targeted management strategies are essential to minimize further adverse effects.<ref>{{cite journal | doi=10.1186/s12917-019-2003-9 | doi-access=free | title=Autoimmune diseases affecting skin melanocytes in dogs, cats and horses: Vitiligo and the uveodermatological syndrome: A comprehensive review | date=2019 | last1=Tham | first1=Heng L. | last2=Linder | first2=Keith E. | last3=Olivry | first3=Thierry | journal=BMC Veterinary Research | volume=15 | issue=1 | page=251 | pmid=31324191 | pmc=6639964 }}</ref> Another autoimmune skin disease which can occur in dogs is vitiligo. The exact prevalence of this disease in dogs is currently unknown, as it is likely under-reported.'''<ref>{{Cite journal |last1=Tham |first1=Heng L. |last2=Linder |first2=Keith E. |last3=Olivry |first3=Thierry |date=2019-07-19 |title=Autoimmune diseases affecting skin melanocytes in dogs, cats and horses: vitiligo and the uveodermatological syndrome: a comprehensive review |journal=BMC Veterinary Research |volume=15 |issue=1 |pages=251 |doi=10.1186/s12917-019-2003-9 |issn=1746-6148 |pmc=6639964 |pmid=31324191 |doi-access=free}}</ref>''' Vitiligo can be found in humans and a variety of animals, including cats, horses, and dogs. Vitiligo is a type of autoimmune disease that damages melanocytes in the skin, lips, and oral cavity. Melanocytes are cells that contain pigments such as melanin. These pigments give rise to an organism's phenotype, which determines skin and hair color.'''<ref>{{Cite journal |last1=Yamaguchi |first1=Yuji |last2=Hearing |first2=Vincent J. |date=May 2014 |title=Melanocytes and Their Diseases |journal=Cold Spring Harbor Perspectives in Medicine |volume=4 |issue=5 |pages=a017046 |doi=10.1101/cshperspect.a017046 |issn=2157-1422 |pmc=3996377 |pmid=24789876}}</ref>''' Melanocytes are also found in other parts of the body, such as the oral mucosa, eye, cochlea, and the meninges. Certain breeds of dogs have a higher chance of developing Vitiligo based on their genetics. These breeds include Rottweilers, German Shepherds, Old English Sheepdogs, Doberman Pinchers, Dachshunds, and German Shorthaired Pointers.<ref>{{Cite web |title=ScienceDirect.com {{!}} Science, health and medical journals, full text articles and books. |url=https://www.sciencedirect.com/?ref=pdf_download&fr=RR-11&rr=85b34e9bf99b394c |access-date=2024-02-25 |website=www.sciencedirect.com}}</ref> In addition to Vitiligo, there are other autoimmune diseases that target melanocytes, such as Vogt-Koyanagi-Harada (VKH) syndrome, and Uveodermatological (UDS) syndrome.'''<ref>{{Cite journal |last1=Tham |first1=Heng L. |last2=Linder |first2=Keith E. |last3=Olivry |first3=Thierry |date=2019-07-19 |title=Autoimmune diseases affecting skin melanocytes in dogs, cats and horses: vitiligo and the uveodermatological syndrome: a comprehensive review |journal=BMC Veterinary Research |volume=15 |issue=1 |pages=251 |doi=10.1186/s12917-019-2003-9 |doi-access=free |pmid=31324191 |pmc=6639964 |issn=1746-6148}}</ref>'''
Dogs suffering from autoimmune diseases of the [[skin]] may experience a variety of symptoms, including persistent [[itching]] and scratching, lesions, wounds, blisters, and other skin damage, as well as loss of skin [[pigment]].<ref name="Autoimun" /> Two cases of autoimmune diseases that are often found include ''[[Discoid lupus erythematosus]]'' (DLE) and ''[[Pemphigus]]''. DLE can develop into [[Systemic lupus erythematosus|Systemic Lupus Erythematosus]] (SLE).<ref name="Mueller22">[http://www.ivis.org/proceedings/scivac/2005/Mueller1_en.pdf?LA=1 Immune-mediated Skin Diseases. Rimini: 50th Congresso Nazionale Multisala SCIVAC]</ref> The initial stage of DLE is marked by a loss of skin [[pigment]]. The skin becomes red and [[Ulcer (dermatology)|sore]]s appear on the [[nose]]. The [[palate]] can undergo [[erosion]], ulceration, and injury to the nasal palate, as well as damage to the nostrils and the tissue around the eyes and ears. In [[chronic condition|chronic]] and severe cases, visual scar tissue often occurs.<ref name="Mueller22"/>


Most symptoms occur after the outer epidermis and inner dermis of the skin are affected by the disease. When this happens, the layers of the skin begin to separate, leading to painful lesions and pustules.<ref name=":32"/> The compromised integrity of the skin barrier not only exacerbates the discomfort experienced by the dog, but also heightens the risk of secondary [[bacteria]]l infections. The weakening of the skin's protective layers forms an environment susceptible to [[Microorganism|microbial]] infiltration, which could lead to severe complications. Intervening within an earlier time frame and targeted management strategies are essential to minimize further adverse effects.<ref>{{cite journal | doi=10.1186/s12917-019-2003-9 | doi-access=free | title=Autoimmune diseases affecting skin melanocytes in dogs, cats and horses: Vitiligo and the uveodermatological syndrome: A comprehensive review | date=2019 | last1=Tham | first1=Heng L. | last2=Linder | first2=Keith E. | last3=Olivry | first3=Thierry | journal=BMC Veterinary Research | volume=15 | issue=1 | page=251 | pmid=31324191 | pmc=6639964 }}</ref>
When pemphigus occurs in humans, the skin will begin to blister due to antibodies attacking the adhesive proteins in epidermal cells, which causes them to separate. Different types of pemphigus can be identified based on the depth of separation present in the skin. Many forms of pemphigus can be identified in dogs using methods similar to those employed for humans.<ref>{{Cite journal |last=Olivry |first=Thierry |date=2006-09-04 |title=A review of autoimmune skin diseases in domestic animals: I – Superficial pemphigus |url=https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-3164.2006.00540.x |journal=Veterinary Dermatology |volume=17 |issue=5 |pages=291–305 |doi=10.1111/j.1365-3164.2006.00540.x |pmid=16961814 |issn=0959-4493}}</ref> In infections caused by ''[[Pemphigus vulgaris]],'' lesions are usually evident in the oral cavity of the dog.<ref name="Mueller" /> Sometimes symptoms are characterized by [[lymphadenopathy]], which is characterized by loss of appetite, weakness, [[fever]], and in rare cases, [[sepsis]].<ref name="Mueller" /> ''[[Pemphigus foliaceus]]'' is the most common autoimmune skin disease in dogs, making up around one-third of all canine autoimmune disorders.<ref name=":02">{{Cite web |date=2022-05-16 |title=Canine skin autoimmune diseases |url=https://www.vet.cornell.edu/departments-centers-and-institutes/riney-canine-health-center/health-info/canine-skin-autoimmune-diseases |access-date=2024-03-03 |website=Cornell University College of Veterinary Medicine |language=en}}</ref> This disease usually affects areas of the ears and face.<ref name="Mueller2">[http://www.ivis.org/proceedings/scivac/2005/Mueller1_en.pdf?LA=1 Immune-mediated Skin Diseases. Rimini: 50th Congresso Nazionale Multisala SCIVAC]</ref> Early symptoms are characterized by [[depigmentation]] of the nasal palate, dorsal cleft in the [[mouth]], the [[ear]], and the periocular area around the eye. Itching, pain, and weakness of the body have been observed in some cases. Other symptoms of ''Pemphigus foliaceus'' include hair loss, formation of pustules, and erosions with ulcers. These symptoms can appear on the dog's feet, groin area, and trunk if left untreated.<ref name=":0">{{Cite web |date=2022-05-16 |title=Canine skin autoimmune diseases |url=https://www.vet.cornell.edu/departments-centers-and-institutes/riney-canine-health-center/health-info/canine-skin-autoimmune-diseases |access-date=2024-03-03 |website=Cornell University College of Veterinary Medicine |language=en}}</ref>

Another autoimmune skin disease which can occur in dogs is [[vitiligo]]. In addition to humans, vitiligo can be found in a variety of animals, including [[cat]]s, [[horse]]s, and [[dog]]s. Vitiligo is a type of autoimmune disease that damages [[melanocyte]]s in the skin, lips, and [[oral cavity]]. Melanocytes are cells that contain pigments such as [[melanin]]. These pigments give rise to an organism's [[phenotype]], which determines skin and hair color.<ref>{{Cite journal |last1=Yamaguchi |first1=Yuji |last2=Hearing |first2=Vincent J. |date=May 2014 |title=Melanocytes and Their Diseases |journal=Cold Spring Harbor Perspectives in Medicine |volume=4 |issue=5 |pages=a017046 |doi=10.1101/cshperspect.a017046 |pmc=3996377 |pmid=24789876 }}</ref> Melanocytes are also found in other parts of the body, such as the oral [[Mucous membrane|mucosa]], eye, [[cochlea]], and the [[meninges]]. In addition to vitiligo, there are other autoimmune diseases that target melanocytes, such as [[Vogt–Koyanagi–Harada disease|Vogt-Koyanagi-Harada]] (VKH) syndrome, and [[Vogt–Koyanagi–Harada disease|Uveodermatological]] (UDS) syndrome.<ref>{{cite journal |last1=Tham |first1=Heng L. |last2=Linder |first2=Keith E. |last3=Olivry |first3=Thierry |title=Autoimmune diseases affecting skin melanocytes in dogs, cats and horses: vitiligo and the uveodermatological syndrome: a comprehensive review |journal=BMC Veterinary Research |date=December 2019 |volume=15 |issue=1 |page=251 |doi=10.1186/s12917-019-2003-9 |doi-access=free |pmid=31324191 |pmc=6639964 }}</ref> Vogt-Koyanagi-Harada syndrome is an autoimmune disease that affects the eyes. In addition to depigmentation of the skin, the disease is characterized by a combination of conditions, including uveitis, acute iridocyclitis, choroiditis, and retinal detachment.<ref name=":62">{{cite book |doi=10.1016/B978-012546401-7/50009-3 |chapter=Immunology of the Dog |title=Handbook of Vertebrate Immunology |date=1998 |pages=261–288 |isbn=978-0-12-546401-7 }}</ref>

When [[pemphigus]] occurs in humans, the skin will begin to blister due to [[Antibody|antibodies]] attacking the adhesive proteins in epidermal cells, which causes them to separate. Different types of pemphigus can be identified based on the depth of separation present in the skin. Many forms of pemphigus can be identified in dogs using methods similar to those employed for humans.<ref>{{cite journal |last1=Olivry |first1=Thierry |title=A review of autoimmune skin diseases in domestic animals: I – Superficial pemphigus |journal=Veterinary Dermatology |date=October 2006 |volume=17 |issue=5 |pages=291–305 |doi=10.1111/j.1365-3164.2006.00540.x |pmid=16961814 }}</ref>

[[Pemphigus vulgaris]] is rare in humans and animals, but is often fatal if left untreated. In dogs, the disease presents itself so similarly to the way it occurs in humans that dogs can be used as models for the disease in humans.<ref name=":18"/> When the disease first begins to manifest itself, lesions are usually evident in the oral cavity of the dog.<ref name="Mueller22"/> Aside from these blisters, the dog may be mostly [[asymptomatic]] before the disease progresses further.<ref name=":18"/> The blisters are easily ruptured and become painful upon doing so,<ref name=":18"/> which can cause the dog to have difficulty eating.<ref name=":53">{{cite journal |last1=Tham |first1=Heng L. |last2=Linder |first2=Keith E. |last3=Olivry |first3=Thierry |title=Deep pemphigus (pemphigus vulgaris, pemphigus vegetans and paraneoplastic pemphigus) in dogs, cats and horses: a comprehensive review |journal=BMC Veterinary Research |date=December 2020 |volume=16 |issue=1 |page=457 |doi=10.1186/s12917-020-02677-w |doi-access=free |pmc=7686683 |pmid=33228633}}</ref> As the disease progresses, the infected dog can become severely infirm, and may succumb to further [[infection]].<ref name=":18"/> Sometimes symptoms are characterized by [[lymphadenopathy]], which involves loss of appetite, weakness, [[fever]], and in rare cases, [[sepsis]].<ref name="Mueller22"/>

''[[Pemphigus foliaceus]]'' is the most common autoimmune skin disease in dogs, making up around one-third of all canine autoimmune disorders.<ref name=":02">{{Cite web |date=2022-05-16 |title=Canine skin autoimmune diseases |url=https://www.vet.cornell.edu/departments-centers-and-institutes/riney-canine-health-center/health-info/canine-skin-autoimmune-diseases |access-date=2024-03-03 |website=Cornell University College of Veterinary Medicine}}</ref> This disease usually affects areas of the ears and face.<ref name="Mueller22"/> Early symptoms are characterized by [[depigmentation]] of the nasal [[palate]], dorsal cleft in the [[mouth]], the [[ear]], and the periocular area around the eye. Itching, pain, and weakness of the body have been observed in some cases. Other symptoms of ''Pemphigus foliaceus'' include hair loss, formation of pustules, and erosions with ulcers. These symptoms can appear on the dog's feet, groin area, and trunk if left untreated.<ref name=":02"/>


== Disease incidence process ==
== Disease incidence process ==
The immune system functions in many ways to eliminate foreign substances and particles introduced to the body. This revolves around T-cell differentiation, where mature T-cells with receptors for non-self cells target foreign antigens and act with other cells to dispose of them.<ref>{{cite journal | doi=10.1098/rstb.2001.0846 | title=The thymus and central tolerance | date=2001 | last1=Sprent | first1=Jonathan | last2=Kishimoto | first2=Hidehiro | journal=Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences | volume=356 | issue=1409 | pages=609–616 | pmid=11375064 | pmc=1088448 }}</ref> There are two mechanisms of tolerance found in the immune system.<ref name="Papado" /> The first mechanism is positive selection by the [[thymus]], where only [[T cell]]s are selected. T cells recognize peptides in the [[Major histocompatibility complex|Histocompatibility Complex]] (MHC).<ref name="Papado" /> The second mechanism is negative selection, where T cells that recognize self-antigens with too high an affinity are removed through the process of [[apoptosis]] and are not allowed to enter the body's circulation.
The immune system functions in many ways to eliminate foreign substances and particles introduced to the body. This revolves around [[T cell|T-cell]] differentiation, where mature T-cells with receptors for non-self cells target foreign [[antigen]]s and act with other cells to dispose of them.<ref>{{cite journal |last1=Sprent |first1=Jonathan |last2=Kishimoto |first2=Hidehiro |title=The thymus and central tolerance |journal=Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences |date=29 May 2001 |volume=356 |issue=1409 |pages=609–616 |doi=10.1098/rstb.2001.0846 |pmid=11375064 |pmc=1088448 }}</ref> There are two mechanisms of tolerance found in the immune system.<ref name="Papado" /> The first mechanism is positive selection by the [[thymus]], where only [[T cell|T-cell]]s are selected. T-cells recognize [[peptide]]s in the [[Major histocompatibility complex|Histocompatibility Complex]] (MHC).<ref name="Papado" /> The second mechanism is negative selection, where T-cells that recognize self-antigens with too high an affinity are removed through the process of [[apoptosis]] and are not allowed to enter the body's circulation.

Incidences of autoimmune skin diseases can vary based on several factors. Some of these factors include the [[breed]], age, and sex of the dog, along with individual genetics and environmental factors.<ref name=":42"/>

In terms of vitiligo, certain breeds of dogs have a higher chance of developing the disease based on their genetics. These breeds include [[Rottweiler]]s, [[German Shepherd]]s, [[Old English Sheepdog]]s, [[Dobermann|Doberman Pinchers]], [[Dachshund]]s, and [[German Shorthaired Pointer]]s.{{fact|date=August 2024}} However, the exact prevalence of this disease in dogs is currently unknown, as it is likely under-reported.<ref name=":32"/> Certain dog breeds that have been documented with Vogt-Koyanagi-Harada (VKH) syndrome include Akitas, Samoyeds, Irish Setters, Golden Retrievers, Saint Bernards, Australian Sheepdogs, and Shetland Sheepdogs.<ref name=":62"/>

Pemphigus vulgaris can occur in any breed of dog irrespective of its sex or age.<ref name=":18"/> However, it appears to occur more often in male dogs than females, which differs slightly from its occurrence in humans. In humans, women are more likely to be affected than men. In terms of age, the disease usually begins when the dog is at least five to seven years old. This correlates to the typical age in which it begins in humans as well, generally occurring in [[middle age]].<ref name=":53"/>

== Diagnosis ==
Since many autoimmune skin diseases have similar symptoms and usually affect the oral cavity, a biopsy must often be performed in order to correctly diagnose the disease.<ref name=":23">{{cite journal |last1=Bizikova |first1=Petra |last2=Linder |first2=Keith E. |last3=Anderson |first3=Jamie G. |title=Erosive and ulcerative stomatitis in dogs and cats: which immune-mediated diseases to consider? |journal=Journal of the American Veterinary Medical Association |date=17 April 2023 |volume=261 |issue=S1 |pages=S48–S57 |doi=10.2460/javma.22.12.0573 |pmid=37059419 }}</ref> Due to the wide scale of clinical symptoms that can be present, along with the diverse variations of skin autoimmune dermatoses, a single symptom will more than likely not lead to a diagnosis. Instead, the results of the biopsy combined with the canine's history and other clinical signs can help in confirming the diagnosis of the disease. Breed predisposition and the age of the dog can also be indications of the various possibilities of autoimmune skin diseases.<ref name=":7">{{Cite web |title=Canine cutaneous autoimmune disease {{!}} Vet Focus |url=https://vetfocus.royalcanin.com/en/scientific/canine-cutaneous-autoimmune-disease |access-date=2024-04-16 |website=vetfocus.royalcanin.com}}</ref> Some common symptoms that can be used to lead to a confirmed diagnosis include alopecia, crusting, ulcerations, vasculitis, and many more.<ref name=":7" />

Histopathology evaluations can be done by extracting areas of the skin that show indications of being affected, such as taking biopsies of lesions, pustules, and sites of crustation. These tissue samples would then be typically examined under a microscope, where a clinician will form a conclusive diagnosis based on the observed cellular structures and abnormalities.<ref name=":7" /> Additionally, other tests such as antinuclear antibody tests (ANA) and complete blood count with white blood cell differential tests can be used to gather more information.<ref>{{Cite web |title=Autoimmune disorders Information {{!}} Mount Sinai - New York |url=https://www.mountsinai.org/health-library/diseases-conditions/autoimmune-disorders |access-date=2024-04-16 |website=Mount Sinai Health System}}</ref>

For Pemphigus vulgaris, after the skin begins to separate, [[Nikolsky's sign]] can be useful to help diagnose the disease. This involves placing pressure along the edge of a blister and observing if the skin separates further and if the blister increases in size.<ref>{{cite journal |last1=Maity |first1=Subhadeep |last2=Banerjee |first2=Ishita |last3=Sinha |first3=Rupam |last4=Jha |first4=Harshvardhan |last5=Ghosh |first5=Pritha |last6=Mustafi |first6=Subhasish |title=Nikolsky's sign: A pathognomic boon |journal=Journal of Family Medicine and Primary Care |date=2020 |volume=9 |issue=2 |pages=526–530 |doi=10.4103/jfmpc.jfmpc_889_19 |doi-access=free |pmid=32318376 |pmc=7114071 }}</ref> However, to diagnose the disease with complete certainty, biopsies must be taken from the edge of the blisters. The tissue sample must then be analyzed using a direct [[immunofluorescence]] technique and analyzed [[Microscopy|microscopically]]. The direct immunofluorescence technique should be used instead of indirect, as the results may be inaccurate before the disease has progressed to a certain point.<ref name=":18"/>

== Treatment ==
For most autoimmune skin diseases, it is imperative to begin treatment as early as possible, as the progression of the disease can lead to severe complications and even death.<ref name=":18"/> Treatment for many diseases usually involves the use of [[Immunosuppressive drug|immunosuppressants]] such as [[glucocorticoid]]s.<ref name=":23"/> The immunosuppressants aid in suppressing the reaction of the immune system fighting against the body's healthy cells and tissues.<ref>{{Cite web |title=Autoimmune Skin Disease in Dogs {{!}} VCA Animal Hospital {{!}} VCA Animal Hospitals |url=https://vcahospitals.com/know-your-pet/autoimmune-skin-disease-in-dogs |access-date=2024-04-16 |website=Vca}}</ref> This is done by the inhibition of calcineurin, an enzyme that controls and activates T-cell production. Without the consistent production of T-cells, a decrease of autoimmune activity can be observed, leading to less severe symptoms and potential remission of autoimmune diseases.<ref>{{Cite web |title=How Do Immunosuppressants Work? - Uses, Side Effects, Drug Names |url=https://www.rxlist.com/how_do_immunosuppressants_work/drug-class.htm |access-date=2024-04-16 |website=RxList}}</ref>

When treatment is first started for Pemphigus vulgaris, the dog will usually be given the [[corticosteroid]] [[prednisone]] for a limited time. This will be administered orally, and the amount given can vary between 1.5 and 13.3 [[milligrams]] for every [[kilogram]] of the dog's weight. This amount will continue until symptoms begin to subside. Afterward the dose will be lowered, and other medications will be used. The condition cannot be cured, so the dog will require immunosuppressants and [[steroid]]s for the duration of its lifespan. The specific immunosuppressants used generally include [[cyclophosphamide]], [[methotrexate]], or [[azathioprine]]. [[Antibiotic]]s may also be used to help reduce the risk of infection.<ref name=":18"/>


==See also==
==See also==

Latest revision as of 13:19, 3 August 2024

Autoimmune skin diseases occur when the immune system of an infected animal attacks its own skin.[1] In dogs, autoimmune skin diseases are usually not detected until visible symptoms appear, which differs from detection in humans who are able to verbally express their concerns.[2] Genetics, nutrition, and external environmental factors all collectively contribute to increasing the probability an autoimmune skin disease occurring.[3] The severity of symptoms varies based on the specific disease present and how far it has progressed. Diagnosis often requires the onset of visible symptoms and for a biopsy to be performed. For many diseases, the condition itself cannot be cured, but a veterinarian can prescribe medications and other forms of treatment to help manage the symptoms of the dog.[4]

Overview

[edit]

The immune system has the ability to differentiate between the cells of the body and foreign cells. However, in dogs affected by an autoimmune disease, the immune system loses the ability to make this distinction, causing the immune system to attack the body.[5] Autoimmune diseases in the base layer of the epidermis are characterized by damage to the connective tissue and vesicle formation located below the epidermis layer and the dermis layer below it.[6][7] There are many autoimmune diseases, and they all vary in impact to the dog and progress at their own rates.[8]

Clinical symptoms

[edit]
Pemphigus foliaceus in dogs: hair loss occurs, skin becomes red, and itchy.

Dogs suffering from autoimmune diseases of the skin may experience a variety of symptoms, including persistent itching and scratching, lesions, wounds, blisters, and other skin damage, as well as loss of skin pigment.[5] Two cases of autoimmune diseases that are often found include Discoid lupus erythematosus (DLE) and Pemphigus. DLE can develop into Systemic Lupus Erythematosus (SLE).[9] The initial stage of DLE is marked by a loss of skin pigment. The skin becomes red and sores appear on the nose. The palate can undergo erosion, ulceration, and injury to the nasal palate, as well as damage to the nostrils and the tissue around the eyes and ears. In chronic and severe cases, visual scar tissue often occurs.[9]

Most symptoms occur after the outer epidermis and inner dermis of the skin are affected by the disease. When this happens, the layers of the skin begin to separate, leading to painful lesions and pustules.[2] The compromised integrity of the skin barrier not only exacerbates the discomfort experienced by the dog, but also heightens the risk of secondary bacterial infections. The weakening of the skin's protective layers forms an environment susceptible to microbial infiltration, which could lead to severe complications. Intervening within an earlier time frame and targeted management strategies are essential to minimize further adverse effects.[10]

Another autoimmune skin disease which can occur in dogs is vitiligo. In addition to humans, vitiligo can be found in a variety of animals, including cats, horses, and dogs. Vitiligo is a type of autoimmune disease that damages melanocytes in the skin, lips, and oral cavity. Melanocytes are cells that contain pigments such as melanin. These pigments give rise to an organism's phenotype, which determines skin and hair color.[11] Melanocytes are also found in other parts of the body, such as the oral mucosa, eye, cochlea, and the meninges. In addition to vitiligo, there are other autoimmune diseases that target melanocytes, such as Vogt-Koyanagi-Harada (VKH) syndrome, and Uveodermatological (UDS) syndrome.[12] Vogt-Koyanagi-Harada syndrome is an autoimmune disease that affects the eyes. In addition to depigmentation of the skin, the disease is characterized by a combination of conditions, including uveitis, acute iridocyclitis, choroiditis, and retinal detachment.[13]

When pemphigus occurs in humans, the skin will begin to blister due to antibodies attacking the adhesive proteins in epidermal cells, which causes them to separate. Different types of pemphigus can be identified based on the depth of separation present in the skin. Many forms of pemphigus can be identified in dogs using methods similar to those employed for humans.[14]

Pemphigus vulgaris is rare in humans and animals, but is often fatal if left untreated. In dogs, the disease presents itself so similarly to the way it occurs in humans that dogs can be used as models for the disease in humans.[4] When the disease first begins to manifest itself, lesions are usually evident in the oral cavity of the dog.[9] Aside from these blisters, the dog may be mostly asymptomatic before the disease progresses further.[4] The blisters are easily ruptured and become painful upon doing so,[4] which can cause the dog to have difficulty eating.[15] As the disease progresses, the infected dog can become severely infirm, and may succumb to further infection.[4] Sometimes symptoms are characterized by lymphadenopathy, which involves loss of appetite, weakness, fever, and in rare cases, sepsis.[9]

Pemphigus foliaceus is the most common autoimmune skin disease in dogs, making up around one-third of all canine autoimmune disorders.[16] This disease usually affects areas of the ears and face.[9] Early symptoms are characterized by depigmentation of the nasal palate, dorsal cleft in the mouth, the ear, and the periocular area around the eye. Itching, pain, and weakness of the body have been observed in some cases. Other symptoms of Pemphigus foliaceus include hair loss, formation of pustules, and erosions with ulcers. These symptoms can appear on the dog's feet, groin area, and trunk if left untreated.[16]

Disease incidence process

[edit]

The immune system functions in many ways to eliminate foreign substances and particles introduced to the body. This revolves around T-cell differentiation, where mature T-cells with receptors for non-self cells target foreign antigens and act with other cells to dispose of them.[17] There are two mechanisms of tolerance found in the immune system.[6] The first mechanism is positive selection by the thymus, where only T-cells are selected. T-cells recognize peptides in the Histocompatibility Complex (MHC).[6] The second mechanism is negative selection, where T-cells that recognize self-antigens with too high an affinity are removed through the process of apoptosis and are not allowed to enter the body's circulation.

Incidences of autoimmune skin diseases can vary based on several factors. Some of these factors include the breed, age, and sex of the dog, along with individual genetics and environmental factors.[3]

In terms of vitiligo, certain breeds of dogs have a higher chance of developing the disease based on their genetics. These breeds include Rottweilers, German Shepherds, Old English Sheepdogs, Doberman Pinchers, Dachshunds, and German Shorthaired Pointers.[citation needed] However, the exact prevalence of this disease in dogs is currently unknown, as it is likely under-reported.[2] Certain dog breeds that have been documented with Vogt-Koyanagi-Harada (VKH) syndrome include Akitas, Samoyeds, Irish Setters, Golden Retrievers, Saint Bernards, Australian Sheepdogs, and Shetland Sheepdogs.[13]

Pemphigus vulgaris can occur in any breed of dog irrespective of its sex or age.[4] However, it appears to occur more often in male dogs than females, which differs slightly from its occurrence in humans. In humans, women are more likely to be affected than men. In terms of age, the disease usually begins when the dog is at least five to seven years old. This correlates to the typical age in which it begins in humans as well, generally occurring in middle age.[15]

Diagnosis

[edit]

Since many autoimmune skin diseases have similar symptoms and usually affect the oral cavity, a biopsy must often be performed in order to correctly diagnose the disease.[18] Due to the wide scale of clinical symptoms that can be present, along with the diverse variations of skin autoimmune dermatoses, a single symptom will more than likely not lead to a diagnosis. Instead, the results of the biopsy combined with the canine's history and other clinical signs can help in confirming the diagnosis of the disease. Breed predisposition and the age of the dog can also be indications of the various possibilities of autoimmune skin diseases.[19] Some common symptoms that can be used to lead to a confirmed diagnosis include alopecia, crusting, ulcerations, vasculitis, and many more.[19]

Histopathology evaluations can be done by extracting areas of the skin that show indications of being affected, such as taking biopsies of lesions, pustules, and sites of crustation. These tissue samples would then be typically examined under a microscope, where a clinician will form a conclusive diagnosis based on the observed cellular structures and abnormalities.[19] Additionally, other tests such as antinuclear antibody tests (ANA) and complete blood count with white blood cell differential tests can be used to gather more information.[20]

For Pemphigus vulgaris, after the skin begins to separate, Nikolsky's sign can be useful to help diagnose the disease. This involves placing pressure along the edge of a blister and observing if the skin separates further and if the blister increases in size.[21] However, to diagnose the disease with complete certainty, biopsies must be taken from the edge of the blisters. The tissue sample must then be analyzed using a direct immunofluorescence technique and analyzed microscopically. The direct immunofluorescence technique should be used instead of indirect, as the results may be inaccurate before the disease has progressed to a certain point.[4]

Treatment

[edit]

For most autoimmune skin diseases, it is imperative to begin treatment as early as possible, as the progression of the disease can lead to severe complications and even death.[4] Treatment for many diseases usually involves the use of immunosuppressants such as glucocorticoids.[18] The immunosuppressants aid in suppressing the reaction of the immune system fighting against the body's healthy cells and tissues.[22] This is done by the inhibition of calcineurin, an enzyme that controls and activates T-cell production. Without the consistent production of T-cells, a decrease of autoimmune activity can be observed, leading to less severe symptoms and potential remission of autoimmune diseases.[23]

When treatment is first started for Pemphigus vulgaris, the dog will usually be given the corticosteroid prednisone for a limited time. This will be administered orally, and the amount given can vary between 1.5 and 13.3 milligrams for every kilogram of the dog's weight. This amount will continue until symptoms begin to subside. Afterward the dose will be lowered, and other medications will be used. The condition cannot be cured, so the dog will require immunosuppressants and steroids for the duration of its lifespan. The specific immunosuppressants used generally include cyclophosphamide, methotrexate, or azathioprine. Antibiotics may also be used to help reduce the risk of infection.[4]

See also

[edit]

References

[edit]
  1. ^ Gershwin, Laurel J. (March 2018). "Current and Newly Emerging Autoimmune Diseases". Veterinary Clinics of North America: Small Animal Practice. 48 (2): 323–338. doi:10.1016/j.cvsm.2017.10.010. PMID 29248206.
  2. ^ a b c Tham, Heng L.; Linder, Keith E.; Olivry, Thierry (December 2019). "Autoimmune diseases affecting skin melanocytes in dogs, cats and horses: vitiligo and the uveodermatological syndrome: a comprehensive review". BMC Veterinary Research. 15 (1): 251. doi:10.1186/s12917-019-2003-9. PMC 6639964. PMID 31324191.
  3. ^ a b Gershwin, Laurel J. (May 2010). "Autoimmune Diseases in Small Animals". Veterinary Clinics of North America: Small Animal Practice. 40 (3): 439–457. doi:10.1016/j.cvsm.2010.02.003. PMID 20471527.
  4. ^ a b c d e f g h i Fukushima, K. (April 1982). "Pathogenesis of pemphigus vulgaris in dog and man - a review". The Canadian Veterinary Journal. 23 (4): 135–137. PMC 1790145. PMID 17422133.
  5. ^ a b "Auto-immune Diseases". Archived from the original on 2019-10-30. Retrieved 2019-10-27.
  6. ^ a b c Papadogiannakis (E. ι. παπαδογιαννακης), E. I. (29 November 2017). "Contemporary aspects on the immunopathogenesis of autoimmune diseases of the epidermal basement membrane in the dog". Journal of the Hellenic Veterinary Medical Society. 56 (1): 27. doi:10.12681/jhvms.15066.
  7. ^ "Structure of the Skin in Dogs - Dog Owners". Merck Veterinary Manual. Retrieved 2019-11-09.
  8. ^ Pedersen, Niels C (August 1999). "A review of immunologic diseases of the dog". Veterinary Immunology and Immunopathology. 69 (2–4): 251–342. doi:10.1016/S0165-2427(99)00059-8. PMC 7119806. PMID 10507310.
  9. ^ a b c d e Immune-mediated Skin Diseases. Rimini: 50th Congresso Nazionale Multisala SCIVAC
  10. ^ Tham, Heng L.; Linder, Keith E.; Olivry, Thierry (2019). "Autoimmune diseases affecting skin melanocytes in dogs, cats and horses: Vitiligo and the uveodermatological syndrome: A comprehensive review". BMC Veterinary Research. 15 (1): 251. doi:10.1186/s12917-019-2003-9. PMC 6639964. PMID 31324191.
  11. ^ Yamaguchi, Yuji; Hearing, Vincent J. (May 2014). "Melanocytes and Their Diseases". Cold Spring Harbor Perspectives in Medicine. 4 (5): a017046. doi:10.1101/cshperspect.a017046. PMC 3996377. PMID 24789876.
  12. ^ Tham, Heng L.; Linder, Keith E.; Olivry, Thierry (December 2019). "Autoimmune diseases affecting skin melanocytes in dogs, cats and horses: vitiligo and the uveodermatological syndrome: a comprehensive review". BMC Veterinary Research. 15 (1): 251. doi:10.1186/s12917-019-2003-9. PMC 6639964. PMID 31324191.
  13. ^ a b "Immunology of the Dog". Handbook of Vertebrate Immunology. 1998. pp. 261–288. doi:10.1016/B978-012546401-7/50009-3. ISBN 978-0-12-546401-7.
  14. ^ Olivry, Thierry (October 2006). "A review of autoimmune skin diseases in domestic animals: I – Superficial pemphigus". Veterinary Dermatology. 17 (5): 291–305. doi:10.1111/j.1365-3164.2006.00540.x. PMID 16961814.
  15. ^ a b Tham, Heng L.; Linder, Keith E.; Olivry, Thierry (December 2020). "Deep pemphigus (pemphigus vulgaris, pemphigus vegetans and paraneoplastic pemphigus) in dogs, cats and horses: a comprehensive review". BMC Veterinary Research. 16 (1): 457. doi:10.1186/s12917-020-02677-w. PMC 7686683. PMID 33228633.
  16. ^ a b "Canine skin autoimmune diseases". Cornell University College of Veterinary Medicine. 2022-05-16. Retrieved 2024-03-03.
  17. ^ Sprent, Jonathan; Kishimoto, Hidehiro (29 May 2001). "The thymus and central tolerance". Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences. 356 (1409): 609–616. doi:10.1098/rstb.2001.0846. PMC 1088448. PMID 11375064.
  18. ^ a b Bizikova, Petra; Linder, Keith E.; Anderson, Jamie G. (17 April 2023). "Erosive and ulcerative stomatitis in dogs and cats: which immune-mediated diseases to consider?". Journal of the American Veterinary Medical Association. 261 (S1): S48–S57. doi:10.2460/javma.22.12.0573. PMID 37059419.
  19. ^ a b c "Canine cutaneous autoimmune disease | Vet Focus". vetfocus.royalcanin.com. Retrieved 2024-04-16.
  20. ^ "Autoimmune disorders Information | Mount Sinai - New York". Mount Sinai Health System. Retrieved 2024-04-16.
  21. ^ Maity, Subhadeep; Banerjee, Ishita; Sinha, Rupam; Jha, Harshvardhan; Ghosh, Pritha; Mustafi, Subhasish (2020). "Nikolsky's sign: A pathognomic boon". Journal of Family Medicine and Primary Care. 9 (2): 526–530. doi:10.4103/jfmpc.jfmpc_889_19. PMC 7114071. PMID 32318376.
  22. ^ "Autoimmune Skin Disease in Dogs | VCA Animal Hospital | VCA Animal Hospitals". Vca. Retrieved 2024-04-16.
  23. ^ "How Do Immunosuppressants Work? - Uses, Side Effects, Drug Names". RxList. Retrieved 2024-04-16.