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Lupus and Sulfasalazine

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By A. G. Moore 2/16/2013

DNA Sequencing
National Cancer Institute
Public Domain

While this essay specifically addresses the connection between sulfasalazine and lupus, the principles involved in the discussion have wider application. As an article in Pharmacological Review explains, “Individual variability in drug efficacy and drug safety is a major challenge in current clinical practice, drug development, and drug regulation” (Pharmacogenetics, Pharmacogenomics, and Individualized Medicine ). In other words, drug effectiveness varies according to the individual. The challenge is to find the most effective drug for each patient.

In the past, an appropriate patient/drug match was achieved through trial and error. Increasingly, though, science has improved the process of prescribing appropriate drugs for patients; often, a doctor can know in advance physical characteristics of patients which might make them more receptive to a drug or more likely to experience side effects.

Targeting medication to enhance effectiveness and avoid side effects is a gift to everyone: patients don’t lose precious, sometimes irreplaceable time with a therapy that doesn’t work; and dangerous, even lethal, side effects may be avoided.

Sulfasalazine is a drug therapy which can be administered today with greater confidence because of advances in genotyping–that is, identifying genetic elements which influence the way a patient processes medication. The history of this drug and its associated risks has been well-documented. In 1965 a physician from the Mayo Clinic reported that a patient he had been treating for inflammatory bowel disease went on to develop lupus. The doctor, Donato Alarcón-Segovia, attributed this development to the drug the patient had been taking: sulfasalazine. Since the 1965 case, sulfasalazine has been recognized as a drug which can induce lupus; the phenomenon is known as drug-induced lupus, or DIL. Sulfasalazine also may exacerbate disease in established lupus.

While doctors have known for a long time that drugs can induce lupus (first case was reported in 1945 in response to Sulfadiazine), this manifestation of lupus, known as drug-induced lupus or DIL, is usually described as being “mild”. However, “mild” lupus is not always the experience of a DIL patient. For example, an article which appears in Postgraduate Medical Journal (Postgrad Med J. 1982 February; 58(676): 98–99) describes a comatose 19-year old girl with “sulphasalazine-induced cerebral lupus erythematosus”.

Sulfasalazine has its uses: among other applications, some doctors find it a good alternative for controlling inflammatory bowel disease, rheumatoid arthritis, and, ironically, discoid lupus (see: Treatment of discoid lupus erythematosus with sulfasalazine: 11 cases ). According to the Lupus Foundation, sulfasalazine may even be prescribed to someone who has lupus if symptoms of rhuematoid arthritis are evident (see Lupus and Overlap).

So, what is a patient to do with this information? Whether sulfasalazine induces a “mild” or severe case of lupus, the development is obviously one a patient would like to avoid. As it turns out, this may be possible–without completely eliminating sulfasalazine from the physician’s list of viable treatment options. There is a way for doctors to profile individual patients and approximately assess their risk for developing sulfasalazine-induced lupus. Research has shown that almost all people who develop lupus after taking sulfasalazine fall in a group known as “slow acetylators” (see my blog: Medication Alert ). Those at high risk for developing sulfasalazine-induced lupus also tend to have specific genetic markers: HLA A1, HLA B8, and HLA DR3. If a patient does not have these markers and is not a “slow acetylator”, then the risk of developing drug-induced lupus may be greatly reduced.

Of course, it‘s impossible to tell how someone will respond to a drug. A serious discussion with the physician is in order before the decision is made to take sulfasalazine, or any medication. Risk and benefits need to be assessed.

Every drug has associated risks–not taking a drug also has associated risks. The more information a patient and doctor have about a proposed course of treatment, the more confidently can they assess the relative risk. In the case of sulfasalazine, it seems patients and doctors have the opportunity to weigh the medication’s benefits with more confidence than was available in the past.

Some articles helpful in learning about sulfasalazine and sulfasalazine-induced lupus:

Predisposing factors in sulphasalazine-induced lupus erythematosus from Rheumatology

Sulfasalazine-induced Lupus and Hypersensitivity, by Qingping Yao, and Bevra Hahn UCLA School of Medicine

Drug-induced lupus erythematosus on DermNet NZ

Update on the Management of Cutaneous Lupus Erythematosus, from the British Journal of Dermatology



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