What is Drug-Induced Lupus Erythematosus?
Drug-induced lupus (DIL) is a condition triggered by certain medications, causing symptoms similar to a disease called systemic lupus erythematosus (SLE). Essentially, it’s a type of autoimmune reaction that occurs when a person with a genetic predisposition to lupus takes certain drugs. The first drug linked to this was Hydralazine, which was discovered in 1954 to cause lupus-like symptoms. Since then, over 100 drugs have been found to potentially cause DIL, and this number grows each year as new drugs are developed. Typically, DIL is milder than SLE and its symptoms often go away once the person stops taking the problematic drug.
What Causes Drug-Induced Lupus Erythematosus?
There are hundreds of drugs that may potentially cause Drug-Induced Lupus (DIL). While there’s strong evidence linking certain drugs to DIL, there are also individual reports that suggest many other drugs could potentially cause it. Some herbal remedies have also been said to bring on a condition that resembles lupus.
Drugs like Procainamide and Hydralazine have the highest rates of causing DIL – up to 30% with Procainamide and between 5% to 10% with Hydralazine. Drugs designed to reduce the body’s immune response, like etanercept and infliximab, have been connected to DIL, with etanercept and infliximab having a higher associated risk. Other drugs that have a confirmed link with DIL include interferon-alpha, minocycline, isoniazid, rifampin, phenytoin, penicillamine, quinidine, methyldopa, chlorpromazine, carbamazepine, ethosuximide, propylthiouracil, and sulfasalazine.
Additionally, there are several other drugs suspected to cause DIL based on individual case reports. These include cholesterol-lowering medications, heart rhythm regulating drugs, ACE inhibitors, stomach acid reducers, gold salts, anti-inflammatory drugs, birth control pills, and others.
Finally, certain herbal remedies, such as alfalfa sprouts, echinacea, and melatonin, have reportedly led to more lupus flare-ups.
Risk Factors and Frequency for Drug-Induced Lupus Erythematosus
Drug-induced lupus forms around 6% to 12% of total lupus diagnoses, with an annual figure of between 15,000 and 30,000 new cases each year in the United States alone. This condition’s occurrence is directly linked to the group of people who are prescribed the drugs that can cause it. For example, younger females are more likely to develop lupus triggered by minocycline, while older people are more commonly affected by lupus caused by procainamide or hydralazine.
Signs and Symptoms of Drug-Induced Lupus Erythematosus
Drug-induced lupus (DIL) is a condition that can occur a few weeks to several months after beginning medication. It may be hard to distinguish between DIL and Systemic Lupus Erythematosus (SLE), another form of lupus, based only on clinical signs. However, DIL is usually less severe and complications like kidney involvement, nerve system involvement, inflammation of blood vessels, low white blood cell count, and inflammation of the heart sac are rare.
Symptoms of drug-induced lupus commonly include:
- Joint pain, which is often the first symptom and occurs in up to 90% of patients
- General symptoms like muscle pain, fever, and weight loss
- Skin symptoms such as sensitivity to sunlight, purpura (purple spots), erythema nodosum (skin inflammation), malar rash (butterfly-shaped rash across cheeks and nose), and subacute cutaneous lupus erythematosus (SCLE) rash
- Inflammation of the lining of the lungs
Unlike SLE, drug-induced lupus less commonly results in hair loss, disc-shaped skin sores, mouth ulcers, and inflammation of the heart sac. Hydralazine, a medication for high blood pressure, can trigger DIL with symptoms that mirror those of SLE. Symptoms of DIL usually go away a few weeks to months after stopping the drug, although lupus-associated antibodies may remain in the blood for several years.
SCLE is a form of lupus that primarily affects the skin, and about one-third of cases are drug-induced. The rash usually follows the areas of the skin that have been exposed to the sun. The rash may resemble psoriasis, have ring-like patches with a clear center, or may present other features. Positive tests for lupus-associated antibodies are common with SCLE.
Testing for Drug-Induced Lupus Erythematosus
When you experience symptoms similar to Lupus, but other autoimmune conditions have been ruled out, the issue may be Drug-Induced Lupus (DIL). This is often suggested if symptoms clear up when you stop taking certain medications.
Blood tests are really important in diagnosing DIL, but they may not always clearly differentiate between this condition and Systemic Lupus Erythematosus (SLE). Fewer people with DIL have low blood cell counts, and these are usually mild. Some medications, like methyldopa, have been linked to a type of blood disorder known as hemolytic anemia, while other drugs like methyldopa, procainamide, and carbamazepine can sometimes cause a positive result on the Coombs test, which checks for certain antibodies in your blood.
When lupus-related tests are run, people with DIL often have a positive result for a test called ANA. Anti-histone antibodies (specific proteins associated with DNA) are found in about 75% of people with DIL, but they can’t be relied upon as a definitive indicator because they can also be present in about the same proportion of people with SLE.
The presence of anti-dsDNA antibodies (another type of specific protein associated with DNA) is more common in SLE compared to DIL, with more than half of SLE patients testing positive for them compared to less than 5% of DIL cases. Nevertheless, certain medications have been found to cause these antibodies to appear in DIL patients.
Anti-Ro/SSA antibodies can be found in cases of a type of lupus that mainly affects your skin, whether it’s caused by medications or it’s the spontaneous type. Additionally, antiphospholipid antibodies, which are associated with an increased risk of blood clots, have been reported in some DIL cases linked to medications like chlorpromazine, procainamide, quinidine, and interferon-alpha.
Furthermore, there are some antibodies called antineutrophil cytoplasmic antibodies (or ANCA) that have been seen in DIL cases linked to medications like minocycline, hydralazine, propylthiouracil, methimazole, and anti-TNF medications. However, as many as 20% of people with SLE can also test positive for ANCA.
Other less frequent antibodies can help differentiate between DIL and other autoimmune conditions. In addition to these, blood tests for kidney and liver function, as well as proteins in the urine, are part of the regular check-ups. If there are any suspicious skin spots, a skin biopsy might be performed, however, it often doesn’t look different from a biopsy of an SLE patient.
Treatment Options for Drug-Induced Lupus Erythematosus
The most important part of treating drug-induced lupus (DIL) is identifying and stopping the use of the medication causing the symptoms. Even if a drug causes positive Antinuclear Antibodies (ANA) test results, it’s not always necessary to stop taking it, but close monitoring is essential to watch for DIL’s development.
Typically, DIL symptoms fade within a few weeks after stopping the medication, although in some rare cases, they can persist for several months. For less severe symptoms, over-the-counter painkillers, like NSAIDs, or low dose steroid medications might be suggested. More severe symptoms, like fluid around the heart (pericardial effusion), might warrant higher doses of steroid medication.
It’s important to remember even though physical symptoms usually disappear a few weeks after discontinuing the drug, the antibodies stimulated by drug exposure can stick around for several months or even years. Their continued presence isn’t a cause for alarm on its own, but they might necessitate the use of anti-inflammatory or immune-suppressing therapy.
What else can Drug-Induced Lupus Erythematosus be?
When diagnosing Drug-Induced Lupus (DIL), one main condition that doctors also need to consider is Idiopathic Systemic Lupus Erythematosus (SLE). Both illnesses have strikingly similar symptoms and immune responses. Still, if patients show severe symptoms like kidney or neurological issues, inflammation of blood vessels, and serious blood disorders, there’s a chance they might have SLE instead of DIL.
Considering the drug-induced Subacute Cutaneous Lupus Erythematosus (SCLE), there’s another condition that can present with the same symptoms: Idiopathic SCLE. However, if the rash is spread widely over the body and disappears after stopping medication, it’s more likely to be drug-induced SCLE rather than idiopathic SCLE.
If patients on anti-TNF drugs (medication that targets inflammation) have symptoms like fever, skin rash, and joint pain, it’s crucial to first check if these symptoms are due to an infection. This is because these drugs lower the body’s ability to fight infections, leaving the patient more prone to them.
What to expect with Drug-Induced Lupus Erythematosus
Drug-induced lupus typically has a better outlook and less complications compared to Systemic Lupus Erythematosus (SLE). In most situations, once the medication causing the issue is stopped, drug-induced lupus tends to clear up within a few weeks. However, a few patients may need treatment for several months. It’s uncommon for this type of lupus to become life-threatening.
However, it’s important to diagnose it early to prevent long hospital stays or multiple visits to the doctor because of uncertainty about the condition.
Possible Complications When Diagnosed with Drug-Induced Lupus Erythematosus
Generally, severe complications from drug-induced lupus are rare. However, in some exceptional cases, people may develop a kidney condition called glomerulonephritis. This can require treatment with steroids and medications that reduce the body’s immune response. Still, the progression to long-term kidney damage is not common.
