Drug-induced lupus erythematosus

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Drug-induced lupus erythematosus
Other namesDIL or DILE
Hydralazine.svg
Hydralazine, a medication associated with drug-induced lupus erythematosus
Specialty Immunology, rheumatology   OOjs UI icon edit-ltr-progressive.svg

Drug-induced lupus erythematosus is an autoimmune disorder caused by chronic use of certain drugs. These drugs cause an autoimmune response (the body attacks its own cells) producing symptoms similar to those of systemic lupus erythematosus (SLE). There are 38 known medications to cause DIL but there are three that report the highest number of cases: hydralazine, procainamide, and quinidine. [1] While the criteria for diagnosing DIL has not been thoroughly established, symptoms of DIL typically present as muscle pain and joint pain. Generally, the symptoms recede after discontinuing use of the drugs. [2]

Contents

Signs and symptoms

Signs and symptoms of drug-induced lupus erythematosus include the following:[ citation needed ]

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 below. 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.[ citation needed ]

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.[ citation needed ]

A predisposing factor to developing DIL is N-acetylation speed, or the rate at which the body can metabolize the drug. This is greatly decreased in patients with a genetic deficiency of the enzyme N-acetyltransferase. 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. [3] These metabolites (byproducts of the interactions between the drug and constituents in the body) of hydralazine are said to have been created when white blood cells have been activated, meaning they are stimulated to produce a respiratory burst. [4] Respiratory burst in white blood cells induces an increased production of free radicals and oxidants such as hydrogen peroxide. [5] These oxidants have been found to react with hydralazine to produce a reactive species that is able to bond to protein. [6] Monocytes, one type of white blood cell, detect the antigen and relay the recognition to T helper cells, creating antinuclear antibodies leading to an immune response. [7] Further studies on the interactions between oxidants and hydralazine are necessary to understand the processes involved in DIL.[ citation needed ]

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 5% of the patients who have taken hydralazine over long periods of time and in high doses have shown DIL-like symptoms. [8] 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 high to very low scale. [1]

Diagnosis

Antinuclear antibodies are usually positive in drug-induced Lupus. Anti-Neutrophil Cytoplasmic antibodies (ANCA) can also be positive in association with certain drugs. Furthermore, anti-histone antibodies can also be positive in drug-induced lupus.[ citation needed ]

Anti-Histone antibodies are positive in up to 95% of patients with drug induced lupus. The most common medications associated with drug induced lupus are hydralazine, procainamide, isoniazid, methyldopa, chlorpromazine, quinidine, and minocycline. [9]

Treatment

It is important to recognize early that these drugs are causing DIL like symptoms and discontinue use of the drug. Symptoms of drug-induced lupus erythematosus generally disappear days to weeks after medication use is discontinued. Non-steroidal anti-inflammatory drugs (NSAIDs) will quicken the healing process. Corticosteroids may be used if more severe symptoms of DIL are present.[ citation needed ]

See also

Related Research Articles

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<span class="mw-page-title-main">Antinuclear antibody</span> Autoantibody that binds to contents of the cell nucleus

Antinuclear antibodies are autoantibodies that bind to contents of the cell nucleus. In normal individuals, the immune system produces antibodies to foreign proteins (antigens) but not to human proteins (autoantigens). In some cases, antibodies to human antigens are produced.

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<span class="mw-page-title-main">Procainamide</span> Medication to treat cardiac arrhythmias

Procainamide (PCA) is a medication of the antiarrhythmic class used for the treatment of cardiac arrhythmias. It is a sodium channel blocker of cardiomyocytes; thus it is classified by the Vaughan Williams classification system as class Ia. In addition to blocking the INa current, it inhibits the IKr rectifier K+ current. Procainamide is also known to induce a voltage-dependent open channel block on the batrachotoxin (BTX)-activated sodium channels in cardiomyocytes.

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<span class="mw-page-title-main">Discoid lupus erythematosus</span> Autoimmune skin condition

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Drug rash with eosinophilia and systemic symptoms or drug reaction with eosinophilia and systemic symptoms (DRESS), also termed drug-induced hypersensitivity syndrome (DIHS), is a rare reaction to certain medications. It involves primarily a widespread skin rash, fever, swollen lymph nodes, and characteristic blood abnormalities such as an abnormally high level of eosinophils, low number of platelets, and increased number of atypical white blood cells (lymphocytes). However, DRESS is often complicated by potentially life-threatening inflammation of internal organs and the syndrome has about a 10% mortality rate. Treatment consists of stopping the offending medication and providing supportive care. Systemic corticosteroids are commonly used as well but no controlled clinical trials have assessed the efficacy of this treatment.

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Subacute cutaneous lupus erythematosus is a clinically distinct subset of cases of lupus erythematosus that is most often present in white women aged 15 to 40, consisting of skin lesions that are scaly and evolve as poly-cyclic annular lesions or plaques similar to those of plaque psoriasis.

<span class="mw-page-title-main">Lupus</span> Human autoimmune disease

Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Common symptoms include painful and swollen joints, fever, chest pain, hair loss, mouth ulcers, swollen lymph nodes, feeling tired, and a red rash which is most commonly on the face. Often there are periods of illness, called flares, and periods of remission during which there are few symptoms.

One of the most prevalent forms of adverse drug reactions is cutaneous reactions, with drug-induced urticaria ranking as the second most common type, preceded by drug-induced exanthems. Urticaria, commonly known as hives, manifests as weals, itching, burning, redness, swelling, and angioedema—a rapid swelling of lower skin layers, often more painful than pruritic. These symptoms may occur concurrently, successively, or independently. Typically, when a drug triggers urticaria, symptoms manifest within 24 hours of ingestion, aiding in the identification of the causative agent. Urticaria symptoms usually subside within 1–24 hours, while angioedema may take up to 72 hours to resolve completely.

Drug-Induced Aseptic Meningitis (DIAM) is a type of aseptic meningitis related to the use of medications such as nonsteroidal anti-inflammatory drugs (NSAIDs) or biologic drugs such as intravenous immunoglobulin (IVIG). Additionally, this condition generally shows clinical improvement after cessation of the medication, as well as a tendency to relapse with resumption of the medication.

Anti-histone antibodies are autoantibodies that are a subset of the anti-nuclear antibody family, which specifically target histone protein subunits or histone complexes. They were first reported by Henry Kunkel, H.R. Holman, and H.R.G. Dreicher in their studies of cellular causes of lupus erythematosus in 1959–60. Today, anti-histone antibodies are still used as a marker for systemic lupus erythematosus, but are also implicated in other autoimmune diseases like Sjögren syndrome, dermatomyositis, or rheumatoid arthritis. Anti-histone antibodies can be used as a marker for drug-induced lupus.

<span class="mw-page-title-main">Anti-SSA/Ro autoantibodies</span> Type of anti-nuclear autoantibodies

Anti-SSA autoantibodies are a type of anti-nuclear autoantibodies that are associated with many autoimmune diseases, such as systemic lupus erythematosus (SLE), SS/SLE overlap syndrome, subacute cutaneous lupus erythematosus (SCLE), neonatal lupus and primary biliary cirrhosis. They are often present in Sjögren's syndrome (SS). Additionally, Anti-Ro/SSA can be found in other autoimmune diseases such as systemic sclerosis (SSc), polymyositis/dermatomyositis (PM/DM), rheumatoid arthritis (RA), and mixed connective tissue disease (MCTD), and are also associated with heart arrhythmia.

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QT prolongation is a measure of delayed ventricular repolarisation, which means the heart muscle takes longer than normal to recharge between beats. It is an electrical disturbance which can be seen on an electrocardiogram (ECG). Excessive QT prolongation can trigger tachycardias such as torsades de pointes (TdP). QT prolongation is an established side effect of antiarrhythmics, but can also be caused by a wide range of non-cardiac medicines, including antibiotics, antidepressants, antihistamines, opioids, and complementary medicines. On an ECG, the QT interval represents the summation of action potentials in cardiac muscle cells, which can be caused by an increase in inward current through sodium or calcium channels, or a decrease in outward current through potassium channels. By binding to and inhibiting the “rapid” delayed rectifier potassium current protein, certain drugs are able to decrease the outward flow of potassium ions and extend the length of phase 3 myocardial repolarization, resulting in QT prolongation.

References

  1. 1 2 Rubin, Robert L. (2005-02-04). "Drug-Induced Lupus Erythematosus". Lupus Foundation of America. Archived from the original on 2006-10-13. Retrieved 2006-11-03.
  2. Schur, Peter H., ed. (July 1983). The Clinical Management of Systemic Lupus Erythematosus. New York: Grune & Stratton. p.  221. ISBN   978-0-8089-1543-0.
  3. Lahita, Robert G. (1987). Systemic Lupus Erythematosus. New York: John Wiley & Sons. p. 859. ISBN   978-0-471-87388-4.
  4. Uetrecht J, Zahid N, Rubin R (1988). "Metabolism of procainamide to a hydroxylamine by human neutrophils and mononuclear leukocytes". Chem Res Toxicol. 1 (1): 74–8. doi:10.1021/tx00001a013. PMID   2979715.
  5. Stites, Daniel P. (1994). Terr, Abba I.; Parslow, Tristram G. (eds.). Basic & Clinical Immunology. Norwalk, CT: Appleton & Lange. p.  373. ISBN   978-0-8385-0561-8.
  6. Hofstra A, Matassa L, Uetrecht J (1991). "Metabolism of hydralazine by activated leukocytes: implications for hydralazine induced lupus". J Rheumatol. 18 (11): 1673–80. PMID   1664857.
  7. Hofstra A (1994). "Metabolism of hydralazine: relevance to drug-induced lupus". Drug Metab Rev. 26 (3): 485–505. doi:10.3109/03602539408998315. PMID   7924901.
  8. Schur, Peter H. et al. (1983), p. 223.
  9. Chang, Christopher; Gershwin, M. Eric (2010). "Drugs and autoimmunity – A contemporary review and mechanistic approach". Journal of Autoimmunity. 34 (3): J266–J275. doi:10.1016/j.jaut.2009.11.012. PMID   20015613.