Drug-Induced Autoimmune Diseases

JANUARY 20, 2016
Anyssa Garza, PharmD
Drug-Induced Subacute Cutaneous Lupus Erythematosus
There have also been reports of drugs inducing subacute cutaneous lupus erythematosus (SCLE). Medications that have been implicated in SCLE include antihypertensives (calcium channel blockers, angiotensin-converting enzyme inhibitors, beta-blockers), terbinafine, ticlopidine, and statins.1 Refer to Online Table 31 for a list of medications implicated in SCLE.1

Table 3: Drugs Associated with Subacute Cutaneous Lupus Erythematosus1
Antihypertensives  
Calcium channel blockers Diltiazem, verapamil, nifedipine
Angiotensin-converting enzyme inhibitors  
Thiazide diuretics Hydrochlorothiazide
Beta blockers Acebutolol
HMG-CoA reductase inhibitors (statins)  
Interferon alpha and beta  
Antifungals Terbinafine, griseofulvin
Antiplatelets Ticlopidine
Nonsteroidal anti-inflammatory drugs Piroxicam, naproxen
Antidepressants Bupropion
Others Lansoprazole, tamoxifen, leflunomide, docetaxel
Biologicals Efalizumab, etanercept, infliximab, interferon-beta
Adapted from reference 1.

Diagnosis
Because there are no set criteria for diagnosing DILE, diagnosis presents a challenge. When making a diagnosis, a clinician must be aware of the differential diagnosis, which includes drug hypersensitivity, eosinophilia- myalgia syndrome, serum sickness, toxic oil syndrome, hemolytic anemia, and other environment factors.1

In The Annals of the New York Academy of Sciences, Borchers et al suggested criteria for diagnosing DILE that included no previous SLE or autoimmune disease.5 This poses a challenge when diagnosing DILE in the case of TNF blockers or other biologic agents, as affected patients already have an autoimmune disease. In these cases, health care providers need to rule out an exacerbation of preexisting lupus and the possibility of unmasking a second autoimmune disease.1

Management
Once DILE is confirmed, stopping the offending agent is the first step in treatment. When treating musculoskeletal symptoms, nonsteroidal anti-inflammatory drugs can be prescribed.4 If symptoms are serious, more aggressive therapy can be prescribed. In these cases, corticosteroids are considered first-line treatment.3

Other Drug-Induced Autoimmune Diseases
In a review article published in Drug Safety, Chang and Gershwin reported, “Drugs have also been implicated in other autoimmune diseases, including rheumatoid arthritis, polymyositis, dermatomyositis, myasthenia gravis, pemphigus, pemphigoid, membranous glomerulonephritis, autoimmune hepatitis, autoimmune thyroiditis, autoimmune haemolytic anaemia, Sjögren’s syndrome, and scleroderma.”1

Conclusion
Although DILE has a more favorable prognosis than SLE, prompt diagnosis and discontinuation of the offending agent are critical. Once mainly associated with cardiovascular drugs, DILE is now associated with more drug classes, including TNF blockers and interferons. Because these agents are used to manage autoimmune disorders, diagnosing DILE can be challenging. The challenge is being able to differentiate a true drug-induced lupus from an exacerbation of preexisting lupus or the unmasking of a second autoimmune disease.1

As we gain a better understanding of pharmacogenetics, it is important that we use the available tools to identify patients who are at higher risk of developing DILE. In addition, research efforts need to focus on identifying susceptible genes to stand as biomarkers to help identify patients at risk for developing DILE.


Dr. Garza received her doctor of pharmacy degree from the University of Texas at Austin. She is currently working as the director of the Life Sciences Library at RxWiki, where she continues to build her practice on the fundamental belief that providing patients with medication information and medical knowledge contributes significantly to the quality of care they receive and improves quality of life and health outcomes. Her work focuses on educating patients and providing them with the resources needed to navigate the overwhelming and complex health system. Before RxWiki, she was director of pharmacy for a Central Texas Department of Aging and Disability facility.

References
  1. Chang C, Gershwin ME. Drug-induced lupus erythematosus: incidence, management and prevention. Drug Saf. 2011;34:357-374.
  2. Vasoo Sheila. Drug-induced lupus: an update. Lupus. 2006; 15:757-761.
  3. Araújo-Fernández S, Ahijón-Lana M, Isenberg DA. Drug-induced lupus: Including anti-tumor necrosis factor and interferon induced. Lupus. 2014; 23:545-553.
  4. DiPiro JT, Talbert RL, Yee GC, et al. Pharmacotherapy: A Pathophysiologic Approach. 7th ed. United States: The McGraw-Hill Companies, Inc; 2008: 1439-1440.
  5. Borchers AT, Keen CL, Gershwin ME. Drug-induced lupus. Ann N Y Acad Sci 2007 Jun; 1108; 166-82.