wikidoc - User contributions [en]

Drug-induced lupus erythematosus history and symptoms

2021-11-18T06:26:05Z

Khalafallah Mohammed: /* History */

__NOTOC__
{{Drug-induced lupus erythematosus}}
{{CMG}}; {{AE}} {{CZ}}

==Overview==

Drug-induced lupus may develop a few weeks to several months after starting the drug, which may make the diagnosis difficult. Further, it is not possible to differentiate DIL from SLE based on clinical features alone, although DIL tends to be milder and renal or CNS involvement, vasculitis, leukopenia, and pericarditis are rare.

1-https://www.ncbi.nlm.nih.gov/books/NBK441889/

==History==
Drug-induced lupus erythematosus manifests in three clinical syndromes:

*systemic drug-induced lupus erythematosus.
*subacute cutaneous lupus erythematosus.
*chronic cutaneous lupus erythematosus.

==Common Symptoms ==
Symptoms of drug-induced lupus erythematosus include:
* [[Arthralgia|Joint pain]]/[[arthritis]]
* [[Fever]]
* [[Inflammation]] of the heart and lungs
* [[Hypertension|Elevated blood pressure]]
* Skin rashes
*[[Fatigue]] and [[weakness]]
*Muscle pain
*[[Loss of appetite]]
*Facial [[butterfly rash]]
*Sensitivity to sunlight
*[[Chest pain]]
*[[Swollen]] [[lymph node]]s

These signs and symptoms are not side effects of the drugs taken which occur during short term use. DIL occurs over long-term and chronic use of the medications listed above. While these symptoms are similar to those of systemic lupus erythematosus, they are generally not as severe unless they are ignored which leads to more harsh symptoms, and in some reported cases, death.
==Less Common Symptoms==
==References==
{{Reflist|2}}
[[Category:Needs Overview]]
[[Category:Needs content]]
[[Category:Disease]]
[[Category:Autoimmune diseases]]
[[Category:Rheumatology]]
[[Category:Mature chapter]]

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

Drug-induced lupus erythematosus history and symptoms

2021-11-17T06:50:31Z

Khalafallah Mohammed: /* Overview */

__NOTOC__
{{Drug-induced lupus erythematosus}}
{{CMG}}; {{AE}} {{CZ}}

==Overview==

Drug-induced lupus may develop a few weeks to several months after starting the drug, which may make the diagnosis difficult. Further, it is not possible to differentiate DIL from SLE based on clinical features alone, although DIL tends to be milder and renal or CNS involvement, vasculitis, leukopenia, and pericarditis are rare.

1-https://www.ncbi.nlm.nih.gov/books/NBK441889/

==History==

==Common Symptoms ==
Symptoms of drug-induced lupus erythematosus include:
* [[Arthralgia|Joint pain]]/[[arthritis]]
* [[Fever]]
* [[Inflammation]] of the heart and lungs
* [[Hypertension|Elevated blood pressure]]
* Skin rashes
*[[Fatigue]] and [[weakness]]
*Muscle pain
*[[Loss of appetite]]
*Facial [[butterfly rash]]
*Sensitivity to sunlight
*[[Chest pain]]
*[[Swollen]] [[lymph node]]s

These signs and symptoms are not side effects of the drugs taken which occur during short term use. DIL occurs over long-term and chronic use of the medications listed above. While these symptoms are similar to those of systemic lupus erythematosus, they are generally not as severe unless they are ignored which leads to more harsh symptoms, and in some reported cases, death.
==Less Common Symptoms==
==References==
{{Reflist|2}}
[[Category:Needs Overview]]
[[Category:Needs content]]
[[Category:Disease]]
[[Category:Autoimmune diseases]]
[[Category:Rheumatology]]
[[Category:Mature chapter]]

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

Differentiating drug-induced lupus erythematosus from other diseases

2021-11-17T06:42:11Z

Khalafallah Mohammed: /* Differentiating Drug-Induced Lupus Erythematosus from other Diseases */

__NOTOC__
{{Drug-induced lupus erythematosus}}
{{CMG}}

==Overview==

==Differentiating Drug-Induced Lupus Erythematosus from other Diseases==
As a reminder, rheumatologic conditions tend to declare themselves over time, as opposed to immediately displaying all the classic clinical manifestations of the disease.

There is an inherited difficulty in distinguishing true drug-induced autoimmunity from an exacerbation of pre-existing autoimmunity or unmasking of a second autoimmune disease. It
will become even more important to recognize medication-induced lupus syndromes given the expanding list of medications associated with DIL.

Here are possible differentials to DIL:
*Idiopathic systemic lupus erythematosus
*Systemic sclerosis (scleroderma)
*Rheumatoid arthritis
*Connective tissue diseases
*Granulomatosis with polyangiitis
*Fibromyalgia
*Lichen planus
*Chronic radiation dermatitis
*Rosacea
*Psoriasis
*Dermatomyositis
*Granuloma annulare
*Actinic keratosis

https://www.visualdx.com/visualdx/diagnosis/drug-induced+lupus+erythematosus?diagnosisId=51883&moduleId=101
https://www.thepermanentejournal.org/issues/43-the-permanente-journal/original-research-and-contributions/7458-drug-induced-lupus,-a-one-time-hit-or-a-harbinger-of-future-autoimmunity-a-case-report.html

==References==
{{Reflist|2}}
[[Category:Needs Overview]]
[[Category:Disease]]
[[Category:Autoimmune diseases]]
[[Category:Rheumatology]]
[[Category:Mature chapter]]
[[Category:Needs content]]
{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

Differentiating drug-induced lupus erythematosus from other diseases

2021-11-16T11:02:13Z

Khalafallah Mohammed: /* Differentiating Drug-Induced Lupus Erythematosus from other Diseases */

__NOTOC__
{{Drug-induced lupus erythematosus}}
{{CMG}}

==Overview==

==Differentiating Drug-Induced Lupus Erythematosus from other Diseases==
Idiopathic systemic lupus erythematosus
Systemic sclerosis (scleroderma)
Rheumatoid arthritis
Connective tissue diseases
Granulomatosis with polyangiitis
Fibromyalgia
Lichen planus
Chronic radiation dermatitis
Rosacea
Psoriasis
Dermatomyositis
Granuloma annulare
Actinic keratosis

https://www.visualdx.com/visualdx/diagnosis/drug-induced+lupus+erythematosus?diagnosisId=51883&moduleId=101

==References==
{{Reflist|2}}
[[Category:Needs Overview]]
[[Category:Disease]]
[[Category:Autoimmune diseases]]
[[Category:Rheumatology]]
[[Category:Mature chapter]]
[[Category:Needs content]]
{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

Differentiating drug-induced lupus erythematosus from other diseases

2021-11-16T10:36:53Z

Khalafallah Mohammed: /* Differentiating Drug-Induced Lupus Erythematosus from other Diseases */

__NOTOC__
{{Drug-induced lupus erythematosus}}
{{CMG}}

==Overview==

==Differentiating Drug-Induced Lupus Erythematosus from other Diseases==
Idiopathic systemic lupus erythematosus
Systemic sclerosis (scleroderma)
Rheumatoid arthritis
Connective tissue diseases
Granulomatosis with polyangiitis
Fibromyalgia
Lichen planus
Chronic radiation dermatitis
Rosacea
Psoriasis
Dermatomyositis
Granuloma annulare
Actinic keratosis

==References==
{{Reflist|2}}
[[Category:Needs Overview]]
[[Category:Disease]]
[[Category:Autoimmune diseases]]
[[Category:Rheumatology]]
[[Category:Mature chapter]]
[[Category:Needs content]]
{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

Drug-induced lupus erythematosus causes

2021-11-16T10:19:24Z

Khalafallah Mohammed: /* Overview */

__NOTOC__
{{Drug-induced lupus erythematosus}}
{{CMG}}; {{AE}} {{CZ}}

==Overview==
Hundreds of drugs have been reported to cause DIL. They are classified as high, moderate, low, or very low risk. While some drugs have good evidence of association with DIL, there are case reports implicating several other drugs as a possible cause of DIL. In addition, Several herbal medications have also been reported to cause a lupus-like syndrome. Procainamide and hydralazine have the highest incidence of causing DIL, with risks reported as high as 30% with procainamide and 5% to 10% with hydralazine. All anti-TNF agents have been associated with DIL, with the risk being higher with etanercept and infliximab.
https://www.medsafe.govt.nz/profs/PUArticles/March2017/DrugInducedLupus.htm
https://www.ncbi.nlm.nih.gov/books/NBK441889/

== Causes ==
The processes that lead to drug-induced lupus erythematosus are not entirely understood. The exact processes that occur are not known even after 50 years since its discovery, but many studies present theories on the mechanisms of DIL.

A predisposing factor to developing DIL is N-acetylation speed, or the rate at which the body can metabolize the drug. [[Acetylation]] speed is generally a genetic factor. A study showed that 29 of 30 patients with DIL were slow acetylators. In addition, these patients had more hydralazine [[metabolites]] in their urine than fast acetylators.<ref name=Lahita>{{cite book
| last = Lahita
| first = Robert G.
| title = Systemic Lupus Erythematosus
| publisher = John Wiley & Sons
| year = 1987
| location = New York
| pages = p. 859
| id = ISBN 0-471-87388-8}}</ref> These metabolites (byproducts of the interactions between the drug and constituents in the body) of hydralazine are said to have been created when [[leukocyte]]s (white blood cells) have been activated, meaning they are stimulated to produce a [[respiratory burst]].<ref name=Uetrecht>{{cite journal
| author = Uetrecht J, Zahid N, Rubin R
| title = Metabolism of procainamide to a hydroxylamine by human neutrophils and mononuclear leukocytes
| journal = Chem Res Toxicol
| volume = 1
| issue = 1
| pages = 74–8
| year = 1988
| id = PMID 2979715
}}</ref> Respiratory burst in white blood cells induces an increased production of free radicals and oxidants such as [[hydrogen peroxide]].<ref name=Stites>{{cite book
| author = Stites, Daniel P.
| coauthors = Terr, Abba I., Parslow, Tristram G. (eds.)
| title = Basic & Clinical Immunology
| publisher = Appleton & Lange
| location = Norwalk, CT
| pages = 373
| year = 1994
| id = ISBN 0-8385-0561-9
}}</ref> These oxidants have been found to react with hydralazine to produce a reactive species that is able to bond to protein.<ref name=Hofstra1991>{{cite journal
| author = Hofstra A, Matassa L, Uetrecht J
| title = Metabolism of hydralazine by activated leukocytes: implications for hydralazine induced lupus
| journal = J Rheumatol
| volume = 18
| issue = 11
| pages = 1673–80
| year = 1991
| id = PMID 1664857
}}</ref> [[Monocytes]], one type of leukocyte, detect the antigen and relay the recognition to [[T helper cell]]s, creating [[antinuclear antibodies]] leading to an immune response.<ref name=Hoftra1994>{{cite journal
| author = Hofstra A
| title = Metabolism of hydralazine: relevance to drug-induced lupus
| journal = Drug Metab Rev
| volume = 26
| issue = 3
| pages = 485-505
| year = 1994
| id = PMID 7924901
}}</ref> Further studies on the interactions between oxidants and hydralazine are necessary to understand the processes involved in DIL.

Of the drugs that cause DIL, [[hydralazine]] has been found to cause a higher incidence. Hydralazine is a medication used to treat high blood pressure. Approximately 12% of the patients who have taken hydralazine over long periods of time and in high doses have shown DIL-like symptoms.<ref name=Schur223>Schur, Peter H. ''et al.'' (1983), p. 223.</ref> Many of the other drugs have a low to very low risk to develop DIL. The following table shows the risk of development of DIL of some of these drugs on a very to high scale.

* High risk:
** [[Procainamide]] ([[antiarrhythmic]])
** [[Hydralazine]] ([[antihypertensive]])
** [[Isoniazid]] ([[antibiotic]])

* Moderate to low risk:
** [[Infliximab]] anti ([[TNF-α]])
** [[Etanercept]] anti ([[TNF-α]])
** [[Minocycline]] ([[antibiotic]])
** [[Pyrazinamide]] ([[antibiotic]])
** [[Quinidine]] ([[antiarrhythmic]])
** [[D-Penicillamine]] ([[anti-inflammatory]])
** [[Carbamazepine]] ([[anticonvulsant]])
** [[Oxcarbazepine]] ([[anticonvulsant]])
** [[Phenytoin]] ([[anticonvulsant]])
** [[Propafenone]] ([[antiarrhythmic]])
* Herbal medications have also been linked to more lupus flares. These include:
**alfalfa sprouts.
**echinacea.
**melatonin.
https://www.ncbi.nlm.nih.gov/books/NBK441889/

==References==
{{Reflist|2}}
[[Category:Needs Overview]]
[[Category:Disease]]
[[Category:Autoimmune diseases]]
[[Category:Rheumatology]]
[[Category:Mature chapter]]

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

Drug-induced lupus erythematosus historical perspective

2021-11-16T10:05:44Z

Khalafallah Mohammed: /* Historical Perspective */

__NOTOC__
{{Drug-induced lupus erythematosus}}
{{CMG}}

==Overview==

==Historical Perspective==

Hydralazine was the first agent to be associated with the development of lupus-like symptoms in 1954. Since then, more than 100 drugs have been identified as the cause of drug-induced lupus, with the list expanding with the development of newer biologic agents each year. https://www.ncbi.nlm.nih.gov/books/NBK441889/

==References==
{{Reflist|2}}
[[Category:Needs Overview]]
[[Category:Disease]]
[[Category:Autoimmune diseases]]
[[Category:Rheumatology]]
[[Category:Mature chapter]]
[[Category:Needs content]]
{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

Drug-induced lupus erythematosus causes

2021-11-16T10:05:01Z

Khalafallah Mohammed: /* Causes */

__NOTOC__
{{Drug-induced lupus erythematosus}}
{{CMG}}; {{AE}} {{CZ}}

==Overview==

== Causes ==
The processes that lead to drug-induced lupus erythematosus are not entirely understood. The exact processes that occur are not known even after 50 years since its discovery, but many studies present theories on the mechanisms of DIL.

A predisposing factor to developing DIL is N-acetylation speed, or the rate at which the body can metabolize the drug. [[Acetylation]] speed is generally a genetic factor. A study showed that 29 of 30 patients with DIL were slow acetylators. In addition, these patients had more hydralazine [[metabolites]] in their urine than fast acetylators.<ref name=Lahita>{{cite book
| last = Lahita
| first = Robert G.
| title = Systemic Lupus Erythematosus
| publisher = John Wiley & Sons
| year = 1987
| location = New York
| pages = p. 859
| id = ISBN 0-471-87388-8}}</ref> These metabolites (byproducts of the interactions between the drug and constituents in the body) of hydralazine are said to have been created when [[leukocyte]]s (white blood cells) have been activated, meaning they are stimulated to produce a [[respiratory burst]].<ref name=Uetrecht>{{cite journal
| author = Uetrecht J, Zahid N, Rubin R
| title = Metabolism of procainamide to a hydroxylamine by human neutrophils and mononuclear leukocytes
| journal = Chem Res Toxicol
| volume = 1
| issue = 1
| pages = 74–8
| year = 1988
| id = PMID 2979715
}}</ref> Respiratory burst in white blood cells induces an increased production of free radicals and oxidants such as [[hydrogen peroxide]].<ref name=Stites>{{cite book
| author = Stites, Daniel P.
| coauthors = Terr, Abba I., Parslow, Tristram G. (eds.)
| title = Basic & Clinical Immunology
| publisher = Appleton & Lange
| location = Norwalk, CT
| pages = 373
| year = 1994
| id = ISBN 0-8385-0561-9
}}</ref> These oxidants have been found to react with hydralazine to produce a reactive species that is able to bond to protein.<ref name=Hofstra1991>{{cite journal
| author = Hofstra A, Matassa L, Uetrecht J
| title = Metabolism of hydralazine by activated leukocytes: implications for hydralazine induced lupus
| journal = J Rheumatol
| volume = 18
| issue = 11
| pages = 1673–80
| year = 1991
| id = PMID 1664857
}}</ref> [[Monocytes]], one type of leukocyte, detect the antigen and relay the recognition to [[T helper cell]]s, creating [[antinuclear antibodies]] leading to an immune response.<ref name=Hoftra1994>{{cite journal
| author = Hofstra A
| title = Metabolism of hydralazine: relevance to drug-induced lupus
| journal = Drug Metab Rev
| volume = 26
| issue = 3
| pages = 485-505
| year = 1994
| id = PMID 7924901
}}</ref> Further studies on the interactions between oxidants and hydralazine are necessary to understand the processes involved in DIL.

Of the drugs that cause DIL, [[hydralazine]] has been found to cause a higher incidence. Hydralazine is a medication used to treat high blood pressure. Approximately 12% of the patients who have taken hydralazine over long periods of time and in high doses have shown DIL-like symptoms.<ref name=Schur223>Schur, Peter H. ''et al.'' (1983), p. 223.</ref> Many of the other drugs have a low to very low risk to develop DIL. The following table shows the risk of development of DIL of some of these drugs on a very to high scale.

* High risk:
** [[Procainamide]] ([[antiarrhythmic]])
** [[Hydralazine]] ([[antihypertensive]])
** [[Isoniazid]] ([[antibiotic]])

* Moderate to low risk:
** [[Infliximab]] anti ([[TNF-α]])
** [[Etanercept]] anti ([[TNF-α]])
** [[Minocycline]] ([[antibiotic]])
** [[Pyrazinamide]] ([[antibiotic]])
** [[Quinidine]] ([[antiarrhythmic]])
** [[D-Penicillamine]] ([[anti-inflammatory]])
** [[Carbamazepine]] ([[anticonvulsant]])
** [[Oxcarbazepine]] ([[anticonvulsant]])
** [[Phenytoin]] ([[anticonvulsant]])
** [[Propafenone]] ([[antiarrhythmic]])
* Herbal medications have also been linked to more lupus flares. These include:
**alfalfa sprouts.
**echinacea.
**melatonin.
https://www.ncbi.nlm.nih.gov/books/NBK441889/

==References==
{{Reflist|2}}
[[Category:Needs Overview]]
[[Category:Disease]]
[[Category:Autoimmune diseases]]
[[Category:Rheumatology]]
[[Category:Mature chapter]]

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

Drug-induced lupus erythematosus historical perspective

2021-11-16T08:35:51Z

Khalafallah Mohammed: /* Historical Perspective */

__NOTOC__
{{Drug-induced lupus erythematosus}}
{{CMG}}

==Overview==

==Historical Perspective==

Hydralazine was the first agent to be associated with the development of lupus-like symptoms in 1954. Since then, more than 100 drugs have been identified as the cause of drug-induced lupus, with the list expanding with the development of newer biologic agents each year.

==References==
{{Reflist|2}}
[[Category:Needs Overview]]
[[Category:Disease]]
[[Category:Autoimmune diseases]]
[[Category:Rheumatology]]
[[Category:Mature chapter]]
[[Category:Needs content]]
{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

Drug-induced lupus erythematosus causes

2021-11-16T07:57:32Z

Khalafallah Mohammed: /* Causes */

__NOTOC__
{{Drug-induced lupus erythematosus}}
{{CMG}}; {{AE}} {{CZ}}

==Overview==

== Causes ==
The processes that lead to drug-induced lupus erythematosus are not entirely understood. The exact processes that occur are not known even after 50 years since its discovery, but many studies present theories on the mechanisms of DIL.

A predisposing factor to developing DIL is N-acetylation speed, or the rate at which the body can metabolize the drug. [[Acetylation]] speed is generally a genetic factor. A study showed that 29 of 30 patients with DIL were slow acetylators. In addition, these patients had more hydralazine [[metabolites]] in their urine than fast acetylators.<ref name=Lahita>{{cite book
| last = Lahita
| first = Robert G.
| title = Systemic Lupus Erythematosus
| publisher = John Wiley & Sons
| year = 1987
| location = New York
| pages = p. 859
| id = ISBN 0-471-87388-8}}</ref> These metabolites (byproducts of the interactions between the drug and constituents in the body) of hydralazine are said to have been created when [[leukocyte]]s (white blood cells) have been activated, meaning they are stimulated to produce a [[respiratory burst]].<ref name=Uetrecht>{{cite journal
| author = Uetrecht J, Zahid N, Rubin R
| title = Metabolism of procainamide to a hydroxylamine by human neutrophils and mononuclear leukocytes
| journal = Chem Res Toxicol
| volume = 1
| issue = 1
| pages = 74–8
| year = 1988
| id = PMID 2979715
}}</ref> Respiratory burst in white blood cells induces an increased production of free radicals and oxidants such as [[hydrogen peroxide]].<ref name=Stites>{{cite book
| author = Stites, Daniel P.
| coauthors = Terr, Abba I., Parslow, Tristram G. (eds.)
| title = Basic & Clinical Immunology
| publisher = Appleton & Lange
| location = Norwalk, CT
| pages = 373
| year = 1994
| id = ISBN 0-8385-0561-9
}}</ref> These oxidants have been found to react with hydralazine to produce a reactive species that is able to bond to protein.<ref name=Hofstra1991>{{cite journal
| author = Hofstra A, Matassa L, Uetrecht J
| title = Metabolism of hydralazine by activated leukocytes: implications for hydralazine induced lupus
| journal = J Rheumatol
| volume = 18
| issue = 11
| pages = 1673–80
| year = 1991
| id = PMID 1664857
}}</ref> [[Monocytes]], one type of leukocyte, detect the antigen and relay the recognition to [[T helper cell]]s, creating [[antinuclear antibodies]] leading to an immune response.<ref name=Hoftra1994>{{cite journal
| author = Hofstra A
| title = Metabolism of hydralazine: relevance to drug-induced lupus
| journal = Drug Metab Rev
| volume = 26
| issue = 3
| pages = 485-505
| year = 1994
| id = PMID 7924901
}}</ref> Further studies on the interactions between oxidants and hydralazine are necessary to understand the processes involved in DIL.

Of the drugs that cause DIL, [[hydralazine]] has been found to cause a higher incidence. Hydralazine is a medication used to treat high blood pressure. Approximately 12% of the patients who have taken hydralazine over long periods of time and in high doses have shown DIL-like symptoms.<ref name=Schur223>Schur, Peter H. ''et al.'' (1983), p. 223.</ref> Many of the other drugs have a low to very low risk to develop DIL. The following table shows the risk of development of DIL of some of these drugs on a very to high scale.

* High risk:
** [[Procainamide]] ([[antiarrhythmic]])
** [[Hydralazine]] ([[antihypertensive]])
** [[Isoniazid]] ([[antibiotic]])

* Moderate to low risk:
** [[Infliximab]] anti ([[TNF-α]])
** [[Etanercept]] anti ([[TNF-α]])
** [[Minocycline]] ([[antibiotic]])
** [[Pyrazinamide]] ([[antibiotic]])
** [[Quinidine]] ([[antiarrhythmic]])
** [[D-Penicillamine]] ([[anti-inflammatory]])
** [[Carbamazepine]] ([[anticonvulsant]])
** [[Oxcarbazepine]] ([[anticonvulsant]])
** [[Phenytoin]] ([[anticonvulsant]])
** [[Propafenone]] ([[antiarrhythmic]])
* Herbal medications have also been liked to more lupus flares. These include:
**alfalfa sprouts.
**echinacea.
**melatonin.
https://www.ncbi.nlm.nih.gov/books/NBK441889/

==References==
{{Reflist|2}}
[[Category:Needs Overview]]
[[Category:Disease]]
[[Category:Autoimmune diseases]]
[[Category:Rheumatology]]
[[Category:Mature chapter]]

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

Drug-induced lupus erythematosus pathophysiology

2021-11-16T06:38:55Z

Khalafallah Mohammed: /* Pathophysiology */

__NOTOC__
{{Drug-induced lupus erythematosus}}
{{CMG}}

==Overview==
* the exact pathophysiology of drug-induced lupus erythematosus is not fully understood.
* some genetic risk factors include HLA-DR4, HLA-DR0301, and complement C4 null allele.
* Drug-induced lupus is probably mediated by reactive drug metabolites, not the ingested medications, and susceptibility to neutrophil-mediated oxidative transformation is a property of ten lupus-inducing drugs reported so far.

==Pathophysiology==
* Three mechanisms are implicated in the causation of drug-induced lupus erythematosus:

# Slow acetylation with genetic deficiency of N-acetyltransferase.
# Inhibition of DNA methylation of CD4+ T-cells.
# The metabolites of the offending drug are subjected to oxidative metabolism and serve as a substrate for myeloperoxidase; which is activated in polymorphonuclear neutrophils.

==Pathophysiology==
Three mechanisms are implicated in the causation of drug-induced lupus erythematosus:

*Slow acetylation with genetic deficiency of N-acetyltransferase. It is found that slow acetylators with genetic deficiency of N-acetyltransferase are at higher risk of DIL, especially from procainamide and hydralazine.

*Inhibition of DNA methylation of CD4+ T-cells. the demethylation of CD4+ T-cells makes them auto-reactive by over-expression of the LFA-1 adhesion molecule. These auto-reactive T-cells can then overstimulate autoantibody production by interaction with self class II MHC molecules on B-cells and induce apoptosis of macrophages by interacting with self class II MHC molecules on macrophages which release the highly antigenic apoptotic chromatin from the dying macrophages. This autoantibody production and release of antigenic macrophages chromatin is thought to contribute to the development of lupus-like autoimmunity.

*The metabolites of the offending drug are subjected to oxidative metabolism and serve as a substrate for myeloperoxidase; which is activated in polymorphonuclear neutrophils. This interaction results in the formation of reactive metabolites that directly affect lymphocyte function in the thymus making them auto-reactive. Virtually all lupus-inducing drugs undergo oxidative metabolism, whereas analogous non-lupus-inducing drugs do not. Also, both mouse and human studies implicate thymic activity in the pathophysiology of DILE.

==References==
{{Reflist|2}}
[[Category:Needs Overview]]
[[Category:Disease]]
[[Category:Autoimmune diseases]]
[[Category:Rheumatology]]
[[Category:Mature chapter]]
[[Category:Needs content]]
{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

Drug-induced lupus erythematosus pathophysiology

2021-11-16T06:30:08Z

Khalafallah Mohammed: /* Pathophysiology */

__NOTOC__
{{Drug-induced lupus erythematosus}}
{{CMG}}

==Overview==
* the exact pathophysiology of drug-induced lupus erythematosus is not fully understood.
* some genetic risk factors include HLA-DR4, HLA-DR0301, and complement C4 null allele.
* Drug-induced lupus is probably mediated by reactive drug metabolites, not the ingested medications, and susceptibility to neutrophil-mediated oxidative transformation is a property of ten lupus-inducing drugs reported so far.

==Pathophysiology==
* Three mechanisms are implicated in the causation of drug-induced lupus erythematosus:
# Slow acetylation with genetic deficiency of N-acetyltransferase. It is found that slow acetylators with genetic deficiency of N-acetyltransferase are at higher risk of DIL, especially from procainamide and hydralazine.

## Inhibition of DNA methylation of CD4+ T-cells. the demethylation of CD4+ T-cells makes them auto-reactive by over-expression of the LFA-1 adhesion molecule. These auto-reactive T-cells can then overstimulate autoantibody production by interaction with self class II MHC molecules on B-cells and induce apoptosis of macrophages by interacting with self class II MHC molecules on macrophages which release the highly antigenic apoptotic chromatin from the dying macrophages. This autoantibody production and release of antigenic macrophages chromatin is thought to contribute to the development of lupus-like autoimmunity.

### The metabolites of the offending drug are subjected to oxidative metabolism and serve as a substrate for myeloperoxidase; which is activated in polymorphonuclear neutrophils. This interaction results in the formation of reactive metabolites that directly affect lymphocyte function in the thymus making them auto-reactive. Virtually all lupus-inducing drugs undergo oxidative metabolism, whereas analogous non-lupus-inducing drugs do not. Also, both mouse and human studies implicate thymic activity in the pathophysiology of DILE.

==Pathophysiology==
Three mechanisms are implicated in the causation of drug-induced lupus erythematosus:

*Slow acetylation with genetic deficiency of N-acetyltransferase. It is found that slow acetylators with genetic deficiency of N-acetyltransferase are at higher risk of DIL, especially from procainamide and hydralazine.

*Inhibition of DNA methylation of CD4+ T-cells. the demethylation of CD4+ T-cells makes them auto-reactive by over-expression of the LFA-1 adhesion molecule. These auto-reactive T-cells can then overstimulate autoantibody production by interaction with self class II MHC molecules on B-cells and induce apoptosis of macrophages by interacting with self class II MHC molecules on macrophages which release the highly antigenic apoptotic chromatin from the dying macrophages. This autoantibody production and release of antigenic macrophages chromatin is thought to contribute to the development of lupus-like autoimmunity.

*The metabolites of the offending drug are subjected to oxidative metabolism and serve as a substrate for myeloperoxidase; which is activated in polymorphonuclear neutrophils. This interaction results in the formation of reactive metabolites that directly affect lymphocyte function in the thymus making them auto-reactive. Virtually all lupus-inducing drugs undergo oxidative metabolism, whereas analogous non-lupus-inducing drugs do not. Also, both mouse and human studies implicate thymic activity in the pathophysiology of DILE.

==References==
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Drug-induced lupus erythematosus pathophysiology

2021-10-31T17:26:56Z

Khalafallah Mohammed: /* Overview */

Drug-induced lupus erythematosus pathophysiology

2021-10-31T17:19:42Z

Khalafallah Mohammed: /* Overview */