Lately, watching the evening news includes watching a myriad of drug commercials and hearing a litany of side effects, which often seem worse than the illnesses the medications are supposed to treat. Who knew that some of these drugs might even induce lupus?

• Introduction
• What medications cause DIL?
• What are the symptoms of DIL?
• How is DIL treated? Will the symptoms eventually go away?
• In Conclusion

Introduction

Drug-induced lupus (DIL) is a condition that is thought to occur in 15,000 to 30,000 individuals each year in the U.S. This broad estimate reflects the many factors that may be involved in the development of DIL – population demographics, differences in medication dosages, how a particular medication metabolizes at different strengths, etc.

According to a seminal article published in 2018 in the journal, Annals of the Rheumatic Diseases, the factors of why and how DIL develops in an individual who does not already have SLE differ greatly from the why and how an individual develops SLE itself. While many of the symptoms of DIL may mimic SLE, their origin is quite different and, therefore, need to be treated differently.

It is also estimated that approximately 10% of SLE diagnoses are actually drug-induced lupus!

The demographics of those who may develop DIL is somewhat different than that of those who typically develop SLE. While more women than men will develop DIL just like with SLE, this is where the similarities end. Researchers of the 2018 Annals of the Rheumatic Diseases article note that the median age for the onset of DIL is 49, well beyond the childbearing years when an individual most likely will develop SLE.  Additionally, researchers in a 2018 article in the journal Autoimmunity Reviews noted that the age group mostly affected by DIL may include the elderly.

What medications cause DIL?

In the 2018 Annals of the Rheumatic Diseases article, researchers Laurent Arnaud and others used the World Health Organization’s (WHO) VigiBase, their “global individual case safety reports (ICSRs) database” that draws on drug data from more than 130 countries (mostly the U.S. and in Europe) to glean which medications may impact the development of DIL. Out of 8,163 ICSRs, the researchers were able to identify 118 suspected drugs that may be responsible for DIL – 42 more drugs than had been previously identified.

Researchers identified five main classifications of drugs that have the greatest potential for causing DIL. These classifications include:

• Antiarrhythmic drugs: These include procainamide and quinidine, most frequently prescribed for cardiac and ventricular arrhythmia.
• Antihypertensive drugs: These include hydralazine, captopril and acebutolol, commonly prescribed for high blood pressure.
• Antimicrobial drugs: Such as minocycline and isoniazid, which treat microbial infections.
• Anticonvulsants: These include carbamazepine and phenytoin which treat hyperactivity in the brain which can in turn cause migraines, epilepsy or other brain disorders.
• Immunomodulators: These include interferon alpha and antitumor necrosis factor (anti-TNF), and are often used to treat autoimmune diseases such as rheumatoid arthritis by decreasing inflammation. They may also be used during organ transplants.

Out of all of the medications, the immunomodulator anti-TNF was the most frequently reported as possibly causing DIL (32%). The antiarrhythmic drugs procainamide (6%) and hydralazine (5%) were next on the list.

Most of the drugs that were once the most linked to DIL such as sulfadiazine (used to treat infections) and hydralazine (used to lower blood pressure) are rarely prescribed these days as newer and better drugs have been developed – including a full spectrum of antibiotics – over the last 70 years.

After conducting a literature review, Arnaud et al. concluded that the following nine drugs definitely have a relationship to DIL:

• Procainamide, hydralazine, methyldopa and dihydralazine – used to treat high blood pressure.
• Minocycline – treats microbial infections,
• Quinidine – treats irregular heartbeat,
• Isoniazid – an antibiotic used to treat tuberculosis,
• Terbinafine – an antifungal used to treat fingernail and toenail fungal infections,
• Chlorpromazine – used to treat psychotic disorders, nausea, vomiting and even chronic hiccups.

The researchers also determined that another 19 individual drugs probably have a relationship to DIL and an additional 45 individual drugs that may possibly have a relationship.

It is important to note the drugs typically used to treat SLE – prednisone, corticosteroids, belimumab, mycophenolic acid, azathioprine, rituximab and hydroxychloroquine – were not considered in drug-by-drug analysis because the researchers suspected they were probably “co-reported.”

What are the symptoms of DIL?

Arnaud surmised that it typically takes about 170 days (approximately four months) for symptoms of DIL to develop after an individual has started a course of medication that may cause DIL. In a 2012 article published in the journal U.S. Pharmacist, Janene Marshall, PharmD, of the Chicago State University College of Pharmacy notes the following most common symptoms or expressions of DIL:

• Arthralgia: joint pain,
• Arthritis: joint inflammation,
• Myalgia: muscle pain,
• Serositis: inflammation of the lining of the chest or abdomen.

Marshall notes that arthralgia is the most common symptom and may occur up to 90% of the time.  It is often the only symptom an individual with DIL may experience.

Individuals may also present with these less common symptoms of DIL:

• Malar rash – the “butterfly” rash often associated with lupus,
• Alopecia – patches of hair loss,
• Photosensitivity – sensitivity to sunlight that can result in fever, pain, rash, and fatigue.

Drug-induced subacute cutaneous lupus erythematosus (SCLE) may also manifest in some individuals. According to Marshall, drugs such as terbinafine, hydrochlorothiazide, etanercept, and calcium channel blockers may trigger this condition. Drug-induced chronic cutaneous lupus erythematosus (CCLE) is quite rare, but can occur as a result of taking infliximab, etanercept or fluorouracil. These are medications used to treat scaly overgrowths of skin and sometimes basal cell carcinoma.

Major organ involvement rarely occurs with DIL.

It is interesting to note that in the 2018 Annals of the Rheumatic Diseases article, researchers discovered that approximately “90% of DIL cases have positive anti-nuclear antibodies (ANAs) … but, antihistone antibodies are positive in more than 75% of patients with DIL versus approximately 20%-83% in SLE,” and that “fewer develop clinically overt autoimmune disease” as a direct result from developing DIL.

How is DIL diagnosed?

Marshall notes that in order for an individual to be diagnosed with DIL, they must meet the following criteria:

• The individual has not been previously diagnosed with SLE or lupus.
• Laboratory tests that confirm that there is now a rheumatologic syndrome when there previously was not one.
• The individual has been exposed to the offending drug or agent for some time.
• There is a quick improvement of symptoms once the individual stops taking the drug.

Augusto Vaglio et al. of the 2018 Autoimmunity Reviews article note that an individual does not need to meet the American College of Rheumatology criteria for lupus in order to be diagnosed with DIL.

How is DIL treated? Will the symptoms eventually go away?

Drug-induced lupus is typically treated by stopping the use of whatever medication was causing the symptoms in the first place. Though rare, if there is organ involvement present, immunosuppressive therapies may be added to treatment while the individual is taken off of the offending medication. If the symptoms of DIL are mild enough, however, and do not cause too much discomfort, the healthcare practitioner may decide to just stick to the original treatment plan and be vigilant about monitoring the individual for any worsening of symptoms.

Once someone is taken off of the drug that was causing the DIL, they may see relief from symptoms in as quickly as several days to several weeks. It is always important, however, for an individual to report any worsening, persistent or new symptoms to a healthcare practitioner right away. It is also important to mention that even if an individual feels fine and the symptoms of DIL have subsided, they may still show elevated levels of antibodies, as these take longer to come down. Marshall states that an individual who is suffering from conditions like arthritis may still be given pain medications and anti-inflammatories (such as NSAIDs or low-dose corticosteroids) so that they will get some relief while they are being taken off the drug that caused the arthritis in the first place.

If a symptom proves irreversible, it is most likely because it is either an indication of an underlying disease or even undiagnosed SLE itself.  It is important to note that DIL does not cause SLE.

In Conclusion

While the development of DIL may be frightening, in most cases it should resolve fairly quickly once appropriate action is taken. Keeping the lines of communication open with a trusted healthcare practitioner during any treatment plan will ensure that the proper medication is prescribed an adjusted as needed depending on how an individual’s body responds and reacts.

 

References

Arnaud, L., Mertz, P., Gavand, P., Martin, T., Chasset, F., Tebacher-Alt, M., …Salem, J. (2018). Drug-induced systemic lupus: Revisiting the ever-changing spectrum of the disease using the WHO pharmacovigilance database. Annals of Rheumatic Diseases. Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/30793701

Marshall, J. (2012). Identifying drug-induced lupus. U.S. Pharmacist. Retrieved from: https://www.uspharmacist.com/article/identifying-drug-induced-lupus

Vaglio, A., Grayson, P., Fenaroli, P., Glanfreda, D., Boccaletti, V., Ghiggeri, G., & Morni, G. (2018). Drug-induced lupus: Traditional and new concepts. Autoimmunity Reviews, 17(2018), 912-918. doi.org/10.1016/j.autrev.2018.03.016

 

 

Author: Liz Heintz

Liz Heintz is a technical and creative writer who received her BA in Communications, Advocacy, and Relational Communications from Marylhurst University in Lake Oswego, Oregon. She most recently worked for several years in the healthcare industry. A native of San Francisco, California, Liz now calls the beautiful Pacific Northwest home.

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