Materiały źródłowe

• #1 Achalasia: Pathogenesis, clinical manifestations, and diagnosis – UpToDate

  https://www.uptodate.com/contents/achalasia-pathogenesis-clinical-manifestations-and-diagnosis

  Achalasia results from progressive degeneration of ganglion cells in the myenteric plexus in the esophageal wall, leading to failure of relaxation of the lower esophageal sphincter (LES), accompanied by a loss of peristalsis in the distal esophagus. […] The etiology of primary or idiopathic achalasia is unknown. Secondary achalasia is due to diseases that cause esophageal motor abnormalities similar or identical to those of primary achalasia. […] In Chagas disease, which occurs predominantly in Central and South America, esophageal infection with the protozoan parasite Trypanosoma cruzi can result in loss of intramural ganglion cells, leading to aperistalsis and incomplete lower esophageal sphincter (LES) relaxation. […] Achalasia has been assumed to result from inflammation and degeneration of neurons in the esophageal wall. The cause of the inflammatory degeneration of neurons in primary achalasia is not known.

• #2 Achalasia: Pathogenesis, clinical manifestations, and diagnosis – UpToDate

  https://www.uptodate.com/contents/achalasia-pathogenesis-clinical-manifestations-and-diagnosis/print

  Achalasia results from progressive degeneration of ganglion cells in the myenteric plexus in the esophageal wall, leading to failure of relaxation of the lower esophageal sphincter (LES), accompanied by a loss of peristalsis in the distal esophagus. […] The etiology of primary or idiopathic achalasia is unknown. Secondary achalasia is due to diseases that cause esophageal motor abnormalities similar or identical to those of primary achalasia. […] The cause of the inflammatory degeneration of neurons in primary achalasia is not known. The observations that achalasia is associated with variants in the HLA-DQ region and that affected patients often have circulating antibodies to enteric neurons suggest that achalasia is an autoimmune disorder. […] Some investigators have proposed that the inflammatory attack on esophageal neurons in achalasia is triggered by an antibody response to viral infections (eg, herpes zoster, measles viruses), but data have been inconclusive. […] A genetic predisposition to the inflammatory degeneration of ganglion cells in achalasia is suggested by its association with variants in the HLA-DQ region and by its occurrence in genetic syndromes such as Allgrove syndrome.

• #3 Pathophysiology of achalasia – Rogers – Annals of Esophagus

  https://aoe.amegroups.org/article/view/5440/html

  Achalasia is a rare esophageal motor disorder characterized by selective loss of esophageal inhibitory neuronal function, particularly at the lower esophageal sphincter (LES), where unopposed contractile tone leads to incomplete LES relaxation following swallows. […] The pathophysiologic basis is hypothesized to be initiated by an environmental trigger, probably a viral infection, in genetically predisposed individuals. […] Given similar antigenic structure and an associated mimicry, antibodies formed against the environmental trigger cause inflammation and damage to esophageal neurons and ganglia. […] If this process results in neuronal death, classic achalasia features develop, with esophageal body aperistalsis and loss of LES relaxation. […] Alternatively, if inflammation is profound without neuronal death, an imbalance of esophageal excitation and inhibition ensues, and esophageal body contraction may be maintained, albeit exaggerated and/or premature, producing non-classic achalasia subtypes.

• #4 Achalasia: Pathogenesis, clinical manifestations, and diagnosis – UpToDate

  https://www.uptodate.com/contents/achalasia-pathogenesis-clinical-manifestations-and-diagnosis

  Achalasia results from progressive degeneration of ganglion cells in the myenteric plexus in the esophageal wall, leading to failure of relaxation of the lower esophageal sphincter (LES), accompanied by a loss of peristalsis in the distal esophagus. […] The etiology of primary or idiopathic achalasia is unknown. Secondary achalasia is due to diseases that cause esophageal motor abnormalities similar or identical to those of primary achalasia. […] In Chagas disease, which occurs predominantly in Central and South America, esophageal infection with the protozoan parasite Trypanosoma cruzi can result in loss of intramural ganglion cells, leading to aperistalsis and incomplete lower esophageal sphincter (LES) relaxation. […] Achalasia has been assumed to result from inflammation and degeneration of neurons in the esophageal wall. The cause of the inflammatory degeneration of neurons in primary achalasia is not known.

• #5 Achalasia – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/achalasia/symptoms-causes/syc-20352850

  The exact cause of achalasia is poorly understood. Researchers suspect that it may be caused by a loss of nerve cells in the esophagus. There are theories about what causes this, but viral infection or autoimmune responses are possibilities. Very rarely, achalasia may be caused by an inherited genetic disorder or infection.

• #6 Achalasia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK519515/

  Achalasia is thought to occur from the degeneration of the myenteric plexus and vagus nerve fibers of the lower esophageal sphincter. […] The exact etiology of this degeneration is unclear though many theories have been proposed. These theories include an autoimmune phenomenon, viral infection, and genetic predisposition. […] Most cases seen in the United States are primary idiopathic achalasia; however, secondary achalasia may be seen in Chagas disease caused by Trypanosoma cruzi, esophageal infiltration by gastric carcinoma, eosinophilic gastroenteritis, lymphoma, certain viral infections, and neurodegenerative disorders.

• #7 Achalasia: Pathogenesis, clinical manifestations, and diagnosis – UpToDate

  https://www.uptodate.com/contents/achalasia-pathogenesis-clinical-manifestations-and-diagnosis

  The observations that achalasia is associated with variants in the HLA-DQ region and that affected patients often have circulating antibodies to enteric neurons suggest that achalasia is an autoimmune disorder. […] Some investigators have proposed that the inflammatory attack on esophageal neurons in achalasia is triggered by an antibody response to viral infections (eg, herpes zoster, measles viruses), but data have been inconclusive. […] A study evaluating T cells in patients with achalasia found reactivity to HSV-1, suggesting that achalasia may be triggered by HSV-1 infection. […] A genetic predisposition to the inflammatory degeneration of ganglion cells in achalasia is suggested by its association with variants in the HLA-DQ region and by its occurrence in genetic syndromes such as Allgrove syndrome. […] It has also been suggested that there may be an allergy-driven form of achalasia.

• #8 Achalasia: Pathogenesis, clinical manifestations, and diagnosis – UpToDate

  https://www.uptodate.com/contents/achalasia-pathogenesis-clinical-manifestations-and-diagnosis/print

  Achalasia results from progressive degeneration of ganglion cells in the myenteric plexus in the esophageal wall, leading to failure of relaxation of the lower esophageal sphincter (LES), accompanied by a loss of peristalsis in the distal esophagus. […] The etiology of primary or idiopathic achalasia is unknown. Secondary achalasia is due to diseases that cause esophageal motor abnormalities similar or identical to those of primary achalasia. […] The cause of the inflammatory degeneration of neurons in primary achalasia is not known. The observations that achalasia is associated with variants in the HLA-DQ region and that affected patients often have circulating antibodies to enteric neurons suggest that achalasia is an autoimmune disorder. […] Some investigators have proposed that the inflammatory attack on esophageal neurons in achalasia is triggered by an antibody response to viral infections (eg, herpes zoster, measles viruses), but data have been inconclusive. […] A genetic predisposition to the inflammatory degeneration of ganglion cells in achalasia is suggested by its association with variants in the HLA-DQ region and by its occurrence in genetic syndromes such as Allgrove syndrome.

• #9 Achalasia: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/169974-overview

  Achalasia is a primary esophageal motility disorder characterized by the absence of esophageal peristalsis and impaired relaxation of the lower esophageal sphincter (LES) in response to swallowing. The LES is hypertensive in about 50% of patients. These abnormalities cause a functional obstruction at the gastroesophageal junction (GEJ). […] Although much is known about the factors that contribute to achalasia, the exact pathogenesis remains unclear. […] There is some evidence that achalasia is an autoimmune disease. […] A European study compared immune-related deoxyribonucleic acid (DNA) in persons with achalasia with that of controls and found 33 single-nucleotide polymorphisms (SNPs) associated with achalasia. All of the were found in the major histocompatability complex region of chromosome 6, a location associated with autoimmune disorders such as multiple sclerosis, lupus, and type 1 diabetes.

• #10 Pathogenesis, clinical manifestations, diagnosis, and treatment progress of achalasia of cardia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10037292/

  Autoimmune attack of esophageal myenteric nerves through cell-mediated and possibly antibody-mediated mechanisms may lead to the inhibition of esophageal smooth muscles, resulting in loss of nerve function and nerve fiber degeneration. […] In addition, several pathological mechanisms have been proposed as possible triggers for this immune disruption process, including underlying viral infections, idiopathic autoimmune triggers, and genetic predisposition. […] According to a case-control study by Naik et al, 80% of patients with achalasia had varicella-zoster virus DNA present in their saliva. […] Sara et al found a two-fold increase in the prevalence of autoimmune diseases in patients with achalasia cardia, which is often associated with type I diabetes and thyroid diseases. […] In addition, patients with Sjogrens syndrome, psoriasis, autoimmune uveitis, rheumatoid arthritis, and Crohns disease are more prone to achalasia. […] Familial achalasia, achalasia with hereditary disease, and achalasia with autoimmune disease were present in 0.63%, 0.99%, and 2.40% of cases, respectively.

• #11 Pathogenesis, clinical manifestations, diagnosis, and treatment progress of achalasia of cardia

  https://www.wjgnet.com/2307-8960/full/v11/i8/1741.htm

  In addition, several pathological mechanisms have been proposed as possible triggers for this immune disruption process, including underlying viral infections, idiopathic autoimmune triggers, and genetic predisposition. […] According to a case-control study by Naik et al, 80% of patients with achalasia had varicella-zoster virus DNA present in their saliva. […] Sara et al found a two-fold increase in the prevalence of autoimmune diseases in patients with achalasia cardia, which is often associated with type I diabetes and thyroid diseases. […] In addition, patients with Sjogrens syndrome, psoriasis, autoimmune uveitis, rheumatoid arthritis, and Crohns disease are more prone to achalasia.

• #12 Achalasia: Pathogenesis, clinical manifestations, and diagnosis – UpToDate

  https://www.uptodate.com/contents/achalasia-pathogenesis-clinical-manifestations-and-diagnosis

  The observations that achalasia is associated with variants in the HLA-DQ region and that affected patients often have circulating antibodies to enteric neurons suggest that achalasia is an autoimmune disorder. […] Some investigators have proposed that the inflammatory attack on esophageal neurons in achalasia is triggered by an antibody response to viral infections (eg, herpes zoster, measles viruses), but data have been inconclusive. […] A study evaluating T cells in patients with achalasia found reactivity to HSV-1, suggesting that achalasia may be triggered by HSV-1 infection. […] A genetic predisposition to the inflammatory degeneration of ganglion cells in achalasia is suggested by its association with variants in the HLA-DQ region and by its occurrence in genetic syndromes such as Allgrove syndrome. […] It has also been suggested that there may be an allergy-driven form of achalasia.

• #13 Achalasia: Pathogenesis, clinical manifestations, and diagnosis – UpToDate

  https://www.uptodate.com/contents/achalasia-pathogenesis-clinical-manifestations-and-diagnosis/print

  Achalasia results from progressive degeneration of ganglion cells in the myenteric plexus in the esophageal wall, leading to failure of relaxation of the lower esophageal sphincter (LES), accompanied by a loss of peristalsis in the distal esophagus. […] The etiology of primary or idiopathic achalasia is unknown. Secondary achalasia is due to diseases that cause esophageal motor abnormalities similar or identical to those of primary achalasia. […] The cause of the inflammatory degeneration of neurons in primary achalasia is not known. The observations that achalasia is associated with variants in the HLA-DQ region and that affected patients often have circulating antibodies to enteric neurons suggest that achalasia is an autoimmune disorder. […] Some investigators have proposed that the inflammatory attack on esophageal neurons in achalasia is triggered by an antibody response to viral infections (eg, herpes zoster, measles viruses), but data have been inconclusive. […] A genetic predisposition to the inflammatory degeneration of ganglion cells in achalasia is suggested by its association with variants in the HLA-DQ region and by its occurrence in genetic syndromes such as Allgrove syndrome.

• #14 Achalasia: Pathogenesis, clinical manifestations, and diagnosis – UpToDate

  https://www.uptodate.com/contents/achalasia-pathogenesis-clinical-manifestations-and-diagnosis

  The observations that achalasia is associated with variants in the HLA-DQ region and that affected patients often have circulating antibodies to enteric neurons suggest that achalasia is an autoimmune disorder. […] Some investigators have proposed that the inflammatory attack on esophageal neurons in achalasia is triggered by an antibody response to viral infections (eg, herpes zoster, measles viruses), but data have been inconclusive. […] A study evaluating T cells in patients with achalasia found reactivity to HSV-1, suggesting that achalasia may be triggered by HSV-1 infection. […] A genetic predisposition to the inflammatory degeneration of ganglion cells in achalasia is suggested by its association with variants in the HLA-DQ region and by its occurrence in genetic syndromes such as Allgrove syndrome. […] It has also been suggested that there may be an allergy-driven form of achalasia.

• #15 Pathogenesis, clinical manifestations, diagnosis, and treatment progress of achalasia of cardia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10037292/

  Autoimmune attack of esophageal myenteric nerves through cell-mediated and possibly antibody-mediated mechanisms may lead to the inhibition of esophageal smooth muscles, resulting in loss of nerve function and nerve fiber degeneration. […] In addition, several pathological mechanisms have been proposed as possible triggers for this immune disruption process, including underlying viral infections, idiopathic autoimmune triggers, and genetic predisposition. […] According to a case-control study by Naik et al, 80% of patients with achalasia had varicella-zoster virus DNA present in their saliva. […] Sara et al found a two-fold increase in the prevalence of autoimmune diseases in patients with achalasia cardia, which is often associated with type I diabetes and thyroid diseases. […] In addition, patients with Sjogrens syndrome, psoriasis, autoimmune uveitis, rheumatoid arthritis, and Crohns disease are more prone to achalasia. […] Familial achalasia, achalasia with hereditary disease, and achalasia with autoimmune disease were present in 0.63%, 0.99%, and 2.40% of cases, respectively.

• #16 Achalasia: Pathogenesis, clinical manifestations, and diagnosis – UpToDate

  https://www.uptodate.com/contents/achalasia-pathogenesis-clinical-manifestations-and-diagnosis

  The observations that achalasia is associated with variants in the HLA-DQ region and that affected patients often have circulating antibodies to enteric neurons suggest that achalasia is an autoimmune disorder. […] Some investigators have proposed that the inflammatory attack on esophageal neurons in achalasia is triggered by an antibody response to viral infections (eg, herpes zoster, measles viruses), but data have been inconclusive. […] A study evaluating T cells in patients with achalasia found reactivity to HSV-1, suggesting that achalasia may be triggered by HSV-1 infection. […] A genetic predisposition to the inflammatory degeneration of ganglion cells in achalasia is suggested by its association with variants in the HLA-DQ region and by its occurrence in genetic syndromes such as Allgrove syndrome. […] It has also been suggested that there may be an allergy-driven form of achalasia.

• #17 Achalasia alters physiological networks depending on sex | Scientific Reports

  https://www.nature.com/articles/s41598-024-52273-3

  Achalasia is a rare esophageal motility disorder for which the etiology is not fully understood. Evidence suggests that autoimmune inflammatory infiltrates, possibly triggered by a viral infection, may lead to a degeneration of neurons within the myenteric plexus. […] Some studies have proposed that achalasia may be an autoimmune disease, wherein the potential causal agent could be a neurotropic virus that chronically infects the myenteric plexus of the esophagus in genetically susceptible hosts, leading to the breakdown of immunological tolerance. Proposed infectious agents include herpes simplex virus type 1 (HSV-1, a neurotropic virus with a preference for mucosal squamous epithelium, which persists in a latent state in neurons and induces a strong humoral and cellular immune response), varicella-zoster, measles, human papillomavirus, mumps, John Cunningham virus (commonly known as JC, a member of the polyomavirus family), and bornavirus (a related disease of psittacine birds that shows many similarities to achalasia).

• #18 Achalasia alters physiological networks depending on sex | Scientific Reports

  https://www.nature.com/articles/s41598-024-52273-3

  Achalasia is a rare esophageal motility disorder for which the etiology is not fully understood. Evidence suggests that autoimmune inflammatory infiltrates, possibly triggered by a viral infection, may lead to a degeneration of neurons within the myenteric plexus. […] Some studies have proposed that achalasia may be an autoimmune disease, wherein the potential causal agent could be a neurotropic virus that chronically infects the myenteric plexus of the esophagus in genetically susceptible hosts, leading to the breakdown of immunological tolerance. Proposed infectious agents include herpes simplex virus type 1 (HSV-1, a neurotropic virus with a preference for mucosal squamous epithelium, which persists in a latent state in neurons and induces a strong humoral and cellular immune response), varicella-zoster, measles, human papillomavirus, mumps, John Cunningham virus (commonly known as JC, a member of the polyomavirus family), and bornavirus (a related disease of psittacine birds that shows many similarities to achalasia).

• #19 Achalasia alters physiological networks depending on sex | Scientific Reports

  https://www.nature.com/articles/s41598-024-52273-3

  Achalasia is a rare esophageal motility disorder for which the etiology is not fully understood. Evidence suggests that autoimmune inflammatory infiltrates, possibly triggered by a viral infection, may lead to a degeneration of neurons within the myenteric plexus. […] Some studies have proposed that achalasia may be an autoimmune disease, wherein the potential causal agent could be a neurotropic virus that chronically infects the myenteric plexus of the esophagus in genetically susceptible hosts, leading to the breakdown of immunological tolerance. Proposed infectious agents include herpes simplex virus type 1 (HSV-1, a neurotropic virus with a preference for mucosal squamous epithelium, which persists in a latent state in neurons and induces a strong humoral and cellular immune response), varicella-zoster, measles, human papillomavirus, mumps, John Cunningham virus (commonly known as JC, a member of the polyomavirus family), and bornavirus (a related disease of psittacine birds that shows many similarities to achalasia).

• #20 Achalasia alters physiological networks depending on sex | Scientific Reports

  https://www.nature.com/articles/s41598-024-52273-3

  Achalasia is a rare esophageal motility disorder for which the etiology is not fully understood. Evidence suggests that autoimmune inflammatory infiltrates, possibly triggered by a viral infection, may lead to a degeneration of neurons within the myenteric plexus. […] Some studies have proposed that achalasia may be an autoimmune disease, wherein the potential causal agent could be a neurotropic virus that chronically infects the myenteric plexus of the esophagus in genetically susceptible hosts, leading to the breakdown of immunological tolerance. Proposed infectious agents include herpes simplex virus type 1 (HSV-1, a neurotropic virus with a preference for mucosal squamous epithelium, which persists in a latent state in neurons and induces a strong humoral and cellular immune response), varicella-zoster, measles, human papillomavirus, mumps, John Cunningham virus (commonly known as JC, a member of the polyomavirus family), and bornavirus (a related disease of psittacine birds that shows many similarities to achalasia).

• #21 Achalasia: The Current Clinical Dilemma and Possible Pathogenesis

  https://www.jnmjournal.org/journal/view.html?uid=1836&vmd=Full

  Taking account of all the established evidence involved in achalasia, we proposed a hypothesis on the pathogenesis which was plotted in the Figure, where susceptible individuals with genetic background, are affected by viruses or other environmental factors, which subsequently triggers an autoimmune response that involves many mediators such as cytokines, chemokines, autoantibodies, complements, and extracellular proteolytic enzymes. […] Although the degeneration of inhibitory neurons in patients with achalasia appears evident, the causes are still unknown. Many factors might contribute to the neurodegeneration of achalasia: (1) genetic abnormality, (2) viral infection, and (3) inflammation and immunity. […] The occurrence of achalasia in siblings and even in identical twins has been reported by previous studies, suggesting a background of genetic abnormality.

• #22 Achalasia: The Current Clinical Dilemma and Possible Pathogenesis

  https://www.jnmjournal.org/view.html?uid=1836&vmd=Full

  Achalasia: The current clinical dilemma of achalasia is mainly due to its unclear pathogenesis. […] The proposed hypothesis on the pathogenesis of achalasia is that genetically susceptible populations potentially have a higher risk of infection with viruses, triggering autoimmune and inflammation responses to inhibitory neurons in lower esophageal sphincter. […] Numerous heterogeneous studies on the pathogenesis of achalasia have proved that achalasia is caused by the neurodegeneration in the LES. […] Various contributing factors could lead to the neurodegeneration, including susceptible individuals with genetic background and the environmental factors which evoke a series of inflammation and immune response. […] The occurrence of achalasia in siblings and even in identical twins has been reported by previous studies, suggesting a background of genetic abnormality.

• #23 Achalasia: Pathogenesis, clinical manifestations, and diagnosis – UpToDate

  https://www.uptodate.com/contents/achalasia-pathogenesis-clinical-manifestations-and-diagnosis

  The observations that achalasia is associated with variants in the HLA-DQ region and that affected patients often have circulating antibodies to enteric neurons suggest that achalasia is an autoimmune disorder. […] Some investigators have proposed that the inflammatory attack on esophageal neurons in achalasia is triggered by an antibody response to viral infections (eg, herpes zoster, measles viruses), but data have been inconclusive. […] A study evaluating T cells in patients with achalasia found reactivity to HSV-1, suggesting that achalasia may be triggered by HSV-1 infection. […] A genetic predisposition to the inflammatory degeneration of ganglion cells in achalasia is suggested by its association with variants in the HLA-DQ region and by its occurrence in genetic syndromes such as Allgrove syndrome. […] It has also been suggested that there may be an allergy-driven form of achalasia.

• #24 Achalasia: Pathogenesis, clinical manifestations, and diagnosis – UpToDate

  https://www.uptodate.com/contents/achalasia-pathogenesis-clinical-manifestations-and-diagnosis/print

  Achalasia results from progressive degeneration of ganglion cells in the myenteric plexus in the esophageal wall, leading to failure of relaxation of the lower esophageal sphincter (LES), accompanied by a loss of peristalsis in the distal esophagus. […] The etiology of primary or idiopathic achalasia is unknown. Secondary achalasia is due to diseases that cause esophageal motor abnormalities similar or identical to those of primary achalasia. […] The cause of the inflammatory degeneration of neurons in primary achalasia is not known. The observations that achalasia is associated with variants in the HLA-DQ region and that affected patients often have circulating antibodies to enteric neurons suggest that achalasia is an autoimmune disorder. […] Some investigators have proposed that the inflammatory attack on esophageal neurons in achalasia is triggered by an antibody response to viral infections (eg, herpes zoster, measles viruses), but data have been inconclusive. […] A genetic predisposition to the inflammatory degeneration of ganglion cells in achalasia is suggested by its association with variants in the HLA-DQ region and by its occurrence in genetic syndromes such as Allgrove syndrome.

• #25 Achalasia: The Current Clinical Dilemma and Possible Pathogenesis

  https://www.jnmjournal.org/journal/view.html?uid=1836&vmd=Full

  Taking account of all the established evidence involved in achalasia, we proposed a hypothesis on the pathogenesis which was plotted in the Figure, where susceptible individuals with genetic background, are affected by viruses or other environmental factors, which subsequently triggers an autoimmune response that involves many mediators such as cytokines, chemokines, autoantibodies, complements, and extracellular proteolytic enzymes. […] Although the degeneration of inhibitory neurons in patients with achalasia appears evident, the causes are still unknown. Many factors might contribute to the neurodegeneration of achalasia: (1) genetic abnormality, (2) viral infection, and (3) inflammation and immunity. […] The occurrence of achalasia in siblings and even in identical twins has been reported by previous studies, suggesting a background of genetic abnormality.

• #26 Achalasia: The Current Clinical Dilemma and Possible Pathogenesis

  https://www.jnmjournal.org/view.html?uid=1836&vmd=Full

  Therefore, genetic factors are involved in the occurrence and development of achalasia. […] The presence of viral infection in achalasia has been confirmed by multiple studies. […] When viral infection occurs in susceptible populations, inflammation and immunity might be activated and cause sustained damage to myenteric neurons of the distal esophagus. […] Studies have demonstrated the elevation of cytokines and chemokines in achalasia, suggesting that inflammation is an indispensable part of the pathogenesis of achalasia. […] A matched case-control study including 6769 patients with achalasia and 27 076 controls found that the incidence of autoimmune diseases in patients with achalasia was significantly higher than that in controls, supporting the hypothesis that achalasia has an autoimmune component.

• #27 Pathogenesis, clinical manifestations, diagnosis, and treatment progress of achalasia of cardia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10037292/

  Autoimmune attack of esophageal myenteric nerves through cell-mediated and possibly antibody-mediated mechanisms may lead to the inhibition of esophageal smooth muscles, resulting in loss of nerve function and nerve fiber degeneration. […] In addition, several pathological mechanisms have been proposed as possible triggers for this immune disruption process, including underlying viral infections, idiopathic autoimmune triggers, and genetic predisposition. […] According to a case-control study by Naik et al, 80% of patients with achalasia had varicella-zoster virus DNA present in their saliva. […] Sara et al found a two-fold increase in the prevalence of autoimmune diseases in patients with achalasia cardia, which is often associated with type I diabetes and thyroid diseases. […] In addition, patients with Sjogrens syndrome, psoriasis, autoimmune uveitis, rheumatoid arthritis, and Crohns disease are more prone to achalasia. […] Familial achalasia, achalasia with hereditary disease, and achalasia with autoimmune disease were present in 0.63%, 0.99%, and 2.40% of cases, respectively.

• #28 Achalasia alters physiological networks depending on sex | Scientific Reports

  https://www.nature.com/articles/s41598-024-52273-3

  The susceptibility to develop achalasia has been associated with the HLA-DQβ1 alleles (HLA-DQβ1*03:04, HLA-DQβ1*05:03, HLA-DQβ1*06:01, and DQβ1*0602), HLA-DQα1 (HLA-DQα1*01:03), and HLA-DRβ*127-9. […] In achalasia, mast cell infiltration is associated with nitrergic nerves, S-100 positive cells, interstitial cells of Cajal, and neuronal degeneration. […] An essential feature includes a reduction in the count of ganglion cells and Cajal cells, accompanied by fibrosis, which can account for as much as 21% of the overall tissue composition. […] It is not preposterous to propose a viral etiology in achalasia because previous studies have established a link between viral infection and the trigger of the disease. […] This suggests that, although no single viral infection may be responsible for achalasia, vaccination against preventable diseases is a priority for women.

• #29 Achalasia: Pathogenesis, clinical manifestations, and diagnosis – UpToDate

  https://www.uptodate.com/contents/achalasia-pathogenesis-clinical-manifestations-and-diagnosis

  Achalasia results from progressive degeneration of ganglion cells in the myenteric plexus in the esophageal wall, leading to failure of relaxation of the lower esophageal sphincter (LES), accompanied by a loss of peristalsis in the distal esophagus. […] The etiology of primary or idiopathic achalasia is unknown. Secondary achalasia is due to diseases that cause esophageal motor abnormalities similar or identical to those of primary achalasia. […] In Chagas disease, which occurs predominantly in Central and South America, esophageal infection with the protozoan parasite Trypanosoma cruzi can result in loss of intramural ganglion cells, leading to aperistalsis and incomplete lower esophageal sphincter (LES) relaxation. […] Achalasia has been assumed to result from inflammation and degeneration of neurons in the esophageal wall. The cause of the inflammatory degeneration of neurons in primary achalasia is not known.

• #30 Achalasia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK519515/

  Achalasia is thought to occur from the degeneration of the myenteric plexus and vagus nerve fibers of the lower esophageal sphincter. […] The exact etiology of this degeneration is unclear though many theories have been proposed. These theories include an autoimmune phenomenon, viral infection, and genetic predisposition. […] Most cases seen in the United States are primary idiopathic achalasia; however, secondary achalasia may be seen in Chagas disease caused by Trypanosoma cruzi, esophageal infiltration by gastric carcinoma, eosinophilic gastroenteritis, lymphoma, certain viral infections, and neurodegenerative disorders.

• #31 Achalasia: Pathogenesis, clinical manifestations, and diagnosis – UpToDate

  https://www.uptodate.com/contents/achalasia-pathogenesis-clinical-manifestations-and-diagnosis

  Achalasia results from progressive degeneration of ganglion cells in the myenteric plexus in the esophageal wall, leading to failure of relaxation of the lower esophageal sphincter (LES), accompanied by a loss of peristalsis in the distal esophagus. […] The etiology of primary or idiopathic achalasia is unknown. Secondary achalasia is due to diseases that cause esophageal motor abnormalities similar or identical to those of primary achalasia. […] In Chagas disease, which occurs predominantly in Central and South America, esophageal infection with the protozoan parasite Trypanosoma cruzi can result in loss of intramural ganglion cells, leading to aperistalsis and incomplete lower esophageal sphincter (LES) relaxation. […] Achalasia has been assumed to result from inflammation and degeneration of neurons in the esophageal wall. The cause of the inflammatory degeneration of neurons in primary achalasia is not known.

• #32 Achalasia: Symptoms & Causes | NewYork-Presbyterian

  https://www.nyp.org/digestive/esophageal-diseases/achalasia

  Chagas disease may be linked to secondary achalasia. Chagas disease is an infection caused by a parasite passed to people through the bite of an insect. It is mainly found in rural areas of Mexico and Central and South America. […] Certain cancers can cause secondary achalasia, but this only accounts for 2-4% of all achalasia.

• #33 Pathophysiology of achalasia – Rogers – Annals of Esophagus

  https://aoe.amegroups.org/article/view/5440/html

  Chagas disease, also called trypanosomiasis, is an infectious disease prevalent in South America. […] It is caused by trypanosome cruzi, a parasite that is transmitted by an infected triatomine bug or the kissing bug. […] Chronic persistence of the infection is a prerequisite to esophageal involvement, which raises the possibility of a similar antigen mimicry mechanism as idiopathic achalasia.

• #34 Achalasia: Symptoms & Causes | NewYork-Presbyterian

  https://www.nyp.org/digestive/esophageal-diseases/achalasia

  Chagas disease may be linked to secondary achalasia. Chagas disease is an infection caused by a parasite passed to people through the bite of an insect. It is mainly found in rural areas of Mexico and Central and South America. […] Certain cancers can cause secondary achalasia, but this only accounts for 2-4% of all achalasia.

• #35 Achalasia causes – wikidoc

  https://www.wikidoc.org/index.php/Achalasia_causes

  Achalasia is chronic esophageal motility disorder. The most common form is primary achalasia, which has no known underlying cause. It is due to the failure of distal esophageal inhibitory neurons. However, a small proportion occurs secondary to other conditions, such as esophageal cancer or Chagas disease. […] Common causes include idiopathic and Chagas disease. […] Less common causes include gastric carcinoma, herpes zoster, HSV-1, measles virus, paraneoplastic syndrome, and sarcoidosis. […] Causes by organ system include gastroenterologic causes such as eosinophilic gastroenteritis, esophageal cancer, gastric carcinoma, idiopathic intestinal pseudo-obstruction, myenteric plexus degeneration, and pancreatic cancer. […] Infectious disease causes include Chagas disease, HSV-1, herpes zoster, and measles. […] Oncologic causes include esophageal cancer, lung carcinoma, lymphoma, pancreatic cancer, and paraneoplastic syndrome.

• #36

  https://step2.medbullets.com/gastrointestinal/120140/achalasia

  The etiology of primary/idiopathic achalasia is unknown […] Secondary achalasia occurs due to diseases that cause esophageal motor abnormalities […] Chagas disease […] protozoan parasite Trypanosoma cruzi destroys intramural ganglion cells […] other diseases include amyloidosis, scleroderma, sarcoidosis, neurofibromatosis, Fabry disease, and eosinophilic esophagitis. […] the cause of the degeneration is unknown but may be autoimmune as suggested by the association with variants in the HLA-DQ regions in affected patients and the presence of antibodies to enteric neurons.

• #37

  https://step1.medbullets.com/gastrointestinal/110034/achalasia

  the etiology of primary/idiopathic achalasia is unknown […] secondary achalasia occurs due to diseases that cause esophageal motor abnormalities […] Chagas disease: protozoan parasite Trypanosoma cruzi destroys intramural ganglion cells […] other diseases include amyloidosis, sarcoidosis, scleroderma, neurofibromatosis, Fabry disease, and eosinophilic esophagitis. […] the cause of the degeneration is unknown but may be autoimmune as suggested by the association with variants in the HLA-DQ regions in affected patients and the presence of antibodies to enteric neurons.

• #38 Esophageal achalasia – Wikipedia

  https://en.wikipedia.org/wiki/Esophageal_achalasia

  Autopsy and myotomy specimens have, on histological examination, shown an inflammatory response consisting of CD3/CD8-positive cytotoxic T lymphocytes, variable numbers of eosinophils and mast cells, loss of ganglion cells, and neurofibrosis; these events appear to occur early in achalasia. Thus, it seems there is an autoimmune context to achalasia, most likely caused by viral triggers. Other studies suggest hereditary, neurodegenerative, genetic and infective contributions.

• #39 Achalasia alters physiological networks depending on sex | Scientific Reports

  https://www.nature.com/articles/s41598-024-52273-3

  The susceptibility to develop achalasia has been associated with the HLA-DQβ1 alleles (HLA-DQβ1*03:04, HLA-DQβ1*05:03, HLA-DQβ1*06:01, and DQβ1*0602), HLA-DQα1 (HLA-DQα1*01:03), and HLA-DRβ*127-9. […] In achalasia, mast cell infiltration is associated with nitrergic nerves, S-100 positive cells, interstitial cells of Cajal, and neuronal degeneration. […] An essential feature includes a reduction in the count of ganglion cells and Cajal cells, accompanied by fibrosis, which can account for as much as 21% of the overall tissue composition. […] It is not preposterous to propose a viral etiology in achalasia because previous studies have established a link between viral infection and the trigger of the disease. […] This suggests that, although no single viral infection may be responsible for achalasia, vaccination against preventable diseases is a priority for women.

• #40 Pathophysiology of achalasia – Rogers – Annals of Esophagus

  https://aoe.amegroups.org/article/view/5440/html

  The higher magnitude of aganglionosis in type 1 achalasia compared to type 2 achalasia has led to speculation that type 1 achalasia is a later stage in the progression of the disease; however, it remains possible that the gradient of ganglion cell death differentiates type 1 from type 2 achalasia. […] In contrast, an imbalance between excitatory and inhibitory influence from inflammation of the myenteric plexus, but without profound ganglion cell death is likely in type 3 achalasia. […] In addition to traditional inflammatory pathways, eosinophilic inflammation has been identified in esophageal smooth muscle in some phenotypes of type 3 achalasia and EGJOO. […] This raises the question as to whether an allergic or hypersensitivity based mechanism underlies the pathophysiology of some achalasia phenotypes.

• #41 Pathophysiology of achalasia – Rogers – Annals of Esophagus

  https://aoe.amegroups.org/article/view/5440/html

  The higher magnitude of aganglionosis in type 1 achalasia compared to type 2 achalasia has led to speculation that type 1 achalasia is a later stage in the progression of the disease; however, it remains possible that the gradient of ganglion cell death differentiates type 1 from type 2 achalasia. […] In contrast, an imbalance between excitatory and inhibitory influence from inflammation of the myenteric plexus, but without profound ganglion cell death is likely in type 3 achalasia. […] In addition to traditional inflammatory pathways, eosinophilic inflammation has been identified in esophageal smooth muscle in some phenotypes of type 3 achalasia and EGJOO. […] This raises the question as to whether an allergic or hypersensitivity based mechanism underlies the pathophysiology of some achalasia phenotypes.

• #42 Achalasia: The Current Clinical Dilemma and Possible Pathogenesis

  https://www.jnmjournal.org/journal/view.html?uid=1836&vmd=Full

  Taking account of all the established evidence involved in achalasia, we proposed a hypothesis on the pathogenesis which was plotted in the Figure, where susceptible individuals with genetic background, are affected by viruses or other environmental factors, which subsequently triggers an autoimmune response that involves many mediators such as cytokines, chemokines, autoantibodies, complements, and extracellular proteolytic enzymes. […] Although the degeneration of inhibitory neurons in patients with achalasia appears evident, the causes are still unknown. Many factors might contribute to the neurodegeneration of achalasia: (1) genetic abnormality, (2) viral infection, and (3) inflammation and immunity. […] The occurrence of achalasia in siblings and even in identical twins has been reported by previous studies, suggesting a background of genetic abnormality.

• #43 Achalasia: The Current Clinical Dilemma and Possible Pathogenesis

  https://www.jnmjournal.org/view.html?uid=1836&vmd=Full

  Achalasia: The current clinical dilemma of achalasia is mainly due to its unclear pathogenesis. […] The proposed hypothesis on the pathogenesis of achalasia is that genetically susceptible populations potentially have a higher risk of infection with viruses, triggering autoimmune and inflammation responses to inhibitory neurons in lower esophageal sphincter. […] Numerous heterogeneous studies on the pathogenesis of achalasia have proved that achalasia is caused by the neurodegeneration in the LES. […] Various contributing factors could lead to the neurodegeneration, including susceptible individuals with genetic background and the environmental factors which evoke a series of inflammation and immune response. […] The occurrence of achalasia in siblings and even in identical twins has been reported by previous studies, suggesting a background of genetic abnormality.

• #44 Achalasia: The Current Clinical Dilemma and Possible Pathogenesis

  https://www.jnmjournal.org/journal/view.html?uid=1836&vmd=Full

  Achalasia is a primary esophageal motility disorder with unclear epidemiology, complicated diagnosis and no radical treatment. The difficulties in the diagnosis and treatment of achalasia are largely due to its unclear pathogenesis. One possible hypothesis is that genetically susceptible populations potentially have a higher risk of infection with viruses, triggering autoimmune and inflammation responses to inhibitory neurons in LES.

• #45 Idiopathic (primary) achalasia: a review | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-015-0302-1

  In contrast, intrinsic loss of inhibitory myenteric neurons in both the esophagus and LES has been reported as the most likely contributory factor in the pathophysiology of achalasia. […] The existence of familial cases suggest that achalasia is an inherited disease. […] Mutation of the ALADIN 12q13 gene is a commonly reported cause of achalasia in children. […] Several studies have suggested a possible association between viral infections and achalasia. […] Thus, although the infectious etiology of achalasia remains an unclear matter, there is mounting evidence suggesting an immune-mediated inflammatory disease in which latent HSV-1 infection leads to persistent immune activation and eventual self-destruction of esophageal neurons in genetically susceptible patients. […] Increased prevalence of circulating antibodies against myenteric plexus in some patients with achalasia led to the suggestion of a role for auto-antibodies in the pathogenesis of this disease; however, a recent study suggested that these circulatory antibodies are most likely the result of a nonspecific reaction to the disease process instead of being the cause of the disease. […] Overall, etiology behind the development of achalasia is likely multifactorial and continues to be highly investigated.

• #46 Achalasia: The Current Clinical Dilemma and Possible Pathogenesis

  https://www.jnmjournal.org/journal/view.html?uid=1836&vmd=Full

  Achalasia: The Current Clinical Dilemma and Possible Pathogenesis […] The proposed hypothesis on the pathogenesis of achalasia is that genetically susceptible populations potentially have a higher risk of infection with viruses, triggering autoimmune and inflammation responses to inhibitory neurons in lower esophageal sphincter. […] The current clinical dilemma of achalasia is mainly due to its unclear pathogenesis. Therefore, further clarification of the pathogenesis of achalasia is essential. Numerous heterogeneous studies on the pathogenesis of achalasia have proved that achalasia is caused by the neurodegeneration in the LES. Neurodegeneration is defined as the selective loss of inhibitory neurons in the myenteric plexus of the distal esophagus. […] Various contributing factors could lead to the neurodegeneration, including susceptible individuals with genetic background and the environmental factors which evoke a series of inflammation and immune response.

• #47 Achalasia – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/achalasia/symptoms-causes/syc-20352850

  The exact cause of achalasia is poorly understood. Researchers suspect that it may be caused by a loss of nerve cells in the esophagus. There are theories about what causes this, but viral infection or autoimmune responses are possibilities. Very rarely, achalasia may be caused by an inherited genetic disorder or infection.

• #48 Achalasia: The Current Clinical Dilemma and Possible Pathogenesis

  https://www.jnmjournal.org/view.html?uid=1836&vmd=Full

  Achalasia: The current clinical dilemma of achalasia is mainly due to its unclear pathogenesis. […] The proposed hypothesis on the pathogenesis of achalasia is that genetically susceptible populations potentially have a higher risk of infection with viruses, triggering autoimmune and inflammation responses to inhibitory neurons in lower esophageal sphincter. […] Numerous heterogeneous studies on the pathogenesis of achalasia have proved that achalasia is caused by the neurodegeneration in the LES. […] Various contributing factors could lead to the neurodegeneration, including susceptible individuals with genetic background and the environmental factors which evoke a series of inflammation and immune response. […] The occurrence of achalasia in siblings and even in identical twins has been reported by previous studies, suggesting a background of genetic abnormality.

• #49 Achalasia: The Current Clinical Dilemma and Possible Pathogenesis

  https://www.jnmjournal.org/journal/view.html?uid=1836&vmd=Full

  Achalasia is a primary esophageal motility disorder with unclear epidemiology, complicated diagnosis and no radical treatment. The difficulties in the diagnosis and treatment of achalasia are largely due to its unclear pathogenesis. One possible hypothesis is that genetically susceptible populations potentially have a higher risk of infection with viruses, triggering autoimmune and inflammation responses to inhibitory neurons in LES.

• #50 Idiopathic (primary) achalasia: a review | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-015-0302-1

  In contrast, intrinsic loss of inhibitory myenteric neurons in both the esophagus and LES has been reported as the most likely contributory factor in the pathophysiology of achalasia. […] The existence of familial cases suggest that achalasia is an inherited disease. […] Mutation of the ALADIN 12q13 gene is a commonly reported cause of achalasia in children. […] Several studies have suggested a possible association between viral infections and achalasia. […] Thus, although the infectious etiology of achalasia remains an unclear matter, there is mounting evidence suggesting an immune-mediated inflammatory disease in which latent HSV-1 infection leads to persistent immune activation and eventual self-destruction of esophageal neurons in genetically susceptible patients. […] Increased prevalence of circulating antibodies against myenteric plexus in some patients with achalasia led to the suggestion of a role for auto-antibodies in the pathogenesis of this disease; however, a recent study suggested that these circulatory antibodies are most likely the result of a nonspecific reaction to the disease process instead of being the cause of the disease. […] Overall, etiology behind the development of achalasia is likely multifactorial and continues to be highly investigated.

• #51 Achalasia: The Current Clinical Dilemma and Possible Pathogenesis

  https://www.jnmjournal.org/journal/view.html?uid=1836&vmd=Full

  Achalasia is a primary esophageal motility disorder with unclear epidemiology, complicated diagnosis and no radical treatment. The difficulties in the diagnosis and treatment of achalasia are largely due to its unclear pathogenesis. One possible hypothesis is that genetically susceptible populations potentially have a higher risk of infection with viruses, triggering autoimmune and inflammation responses to inhibitory neurons in LES.

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