Victoria P. Werth, M.D.

From Lupus News Summer 2002, Vol. 22, No. 2

Drug reactions that affect the skin
Descriptions of common rashes
Corticosteroids
Antimalarials
Dapsone
Non-steroidal anti-inflammatories
Immunosuppressives
DHEA
Summary
References
About the author

Drug reactions that affect the skin

There are many potential side effects from medications used for rheumatologic disorders, and the skin is one of the most common organs that can be affected. Nearly 15 percent of patients with rheumatoid arthritis have adverse drug reactions involving the skin.

Patients with lupus erythematosus also frequently get rashes from medications. There are many types of rashes caused by medications, and most are not very serious. Usually the important issue is to recognize that a rash is from a medication, and then to stop the drug if the rash is intolerable or serious. Stopping the drug usually will result in rapid improvement of rashes from medications, but the rate of improvement depends on the drug and the type of rash.

> back to the top

Descriptions of common rashes

Common types of drug rashes in lupus erythematosus include exanthems (red, usually flat, often widespread rashes that often involve the back, chest, or stomach areas), and hives. The hives are usually very itchy and a given spot will usually last about a day, although some hive-like rashes from drugs can persist longer. The other types of rashes from medicines are less common, and can often be diagnosed by the clinical appearance of the rash. At times, a skin biopsy is required to confirm the exact cause and type of a rash.

> Back to the top

Drugs known to cause skin rashes

Corticosteroids
Steroids such as prednisone or Medrol may cause a lot of side effects in the skin. Since these medications are frequently used in lupus erythematosus and have a high incidence of side effects, skin changes from steroids are fairly common. Shortly after starting to take moderate to high doses of steroids, it is common to develop acne on the face and sometimes the chest and back. This acne can be treated with acne creams such as retinoids or with anti-inflammatory antibiotics used on the skin or taken by mouth.

With longer use of steroids, the skin can become thin and easily bruised. Some people develop stretch marks on the skin. Sometimes healing from local cuts or with surgery can be a problem, particularly when patients are on higher doses of steroids. It is also easier to develop an infection on the skin, and infections may not be as obvious because of the anti-inflammatory effects of the steroids.

Thus, if a patient on steroids develops a skin infection, it is important to have it evaluated and treated. Infections can be due to bacteria, fungal, or unusual organisms that may not normally infect people if they weren't on the steroids. Other less common side effects from steroids include redness of the face, thinning of hair, development of fine small hairs, and even hives.

> Back to the top

Antimalarials
Antimalarials like hydroxychloroquine (Plaquenil), chloroquine, and Quinacrine are frequently used to treat both the skin and systemic symptoms of lupus erythematosus. These highly effective drugs cause skin reactions in about 10 percent of patients.

There are a number of different kinds of rashes that can occur, including exanthems, hive-like rashes, and itching, among others. Sometimes it can be hard to tell whether a rash is from the medication or from the lupus, and a skin biopsy can sometimes be helpful.

Pigmentary changes are quite common with all the antimalarials, and this can include a bluish discoloration that resembles a bruise. The skin, lining of the mouth, hair, and nails can be affected by these color changes.

Quinacrine, a drug that is commonly used in combination with either hydroxychloroquine or chloroquine, can also cause a yellow discoloration of the skin and even the eyes, so that sometimes there is concern that this could be from a liver problem. The yellow color is from deposition of the drug in the skin. Rarely, antimalarials can cause hair loss.

> Back to the top

Dapsone
Dapsone is an anti-inflammatory drug that is sometimes used to treat some forms of skin lupus erythematosus. Skin side effects from Dapsone are not common, but can include a variety of different rashes, including exanthems. There are some rare potentially life-threatening side effects with Dapsone, and if patients develop a rash shortly after beginning Dapsone, often after about three weeks, sometimes with a fever and flu-like symptoms, it is important to immediately stop taking the drug and call your physician.

> Back to the top

Non-steroidal anti-inflammatories
Non-steroidal anti-inflammatory drugs (NSAIDs) are very frequently used for arthritis related to lupus. There are many different non-steroidals, and they can cause a number of different skin reactions.

Bruising is very common because of the affects of NSAIDs on cells involved in blood clotting. More rarely they can cause an inflammation of blood vessels (vasculitis), often showing palpable non-blanching purple-red spots on the skin.

Another reaction to NSAIDs, called pseudoporphyria, causes formation of blisters, erosions, and scars on the skin in areas of sun exposure, often involving the face and backs of the hands. This reaction can continue for a number of months after stopping the medication, and is worse in sunny climates. Sunscreen and sun avoidance are beneficial should such a reaction occur.

One specific class of NSAIDs is most associated with this side effect, and the NSAIDs in the group include naproxen (Naprosyn, Aleve, and others), ibuprofen (Motrin, Advil], diflunisal (Dolobid), ketoprofen (Orudis), nabumetone (Relafen), and oxaprozin (Daypro).

Pseudoporphyria seems to be more common in children (although most of the literature on NSAIDs in children relates to juvenile rheumatoid arthritis), but the frequency of reported reactions may be related more to use patterns, since naproxen is so frequently used in children.

> Back to the top

Immunosuppressives
Patients with systemic lupus often require use of immunosuppressives such as Imuran or Cytoxan. When these drugs are used for long periods of time, they can cause an increase in the risk of skin cancers such as squamous cell carcinomas. These are spots that are usually located on sun-exposed skin, and they slowly enlarge and can bleed or form crusts on the skin.

The good news is that these skin cancers are treatable and normally don't spread internally. If they are diagnosed when the spots are fairly small, they are easy to treat and cure. Thus, it is good to examine the skin for new spots, and should they grow or change, have your medical doctor examine them.

Immunosuppressives can also cause some individuals to have thinning of their hair, although frequently people who require these medications also have active disease that can also cause hair thinning. Some people get sores in the mouth from these medications. It is known that folic acid can help prevent such mouth sores when they are caused by methotrexate.

Sometimes people are given cyclosporine, a different type of immunosuppressive. This medication can cause some unusual changes in the skin, including increased body hair, increased size of the gums in the mouth, and acne. The other thing to watch out for with cyclosporine is increased skin cancers, similar to the other immunosuppressives previously discussed.

> Back to the top

DHEA
Some newer agents are being used to treat lupus. One example, dehydroepiandrosterone (DHEA), is associated with a mild acne-like dermatitis that can usually be easily treated.

> Back to the top

Summary

Skin reactions to medications used to treat lupus erythematosus are not uncommon. The goal has been to review reactions caused by drugs used in lupus erythematosus. As new medications are developed, it is important to observe and characterize potential skin reactions. It is also important to know which drugs can be reintroduced or continued after a reaction occurs, and to determine alternative medications to minimize skin reactions.

> Back to the top

References

Al-Khenaizan, S., Schechter, J.F. and Sasseville, D. Pseudoporphyria induced by propionic acid derivatives. J.Cut.Med.Surg. 3:162-166, 1999.

Checketts, S.R. and Morgan, G.J.,Jr. Two cases of nabumetone-induced pseudoporphyria. J.Rheumatol. 26:2703-2705, 1999.

Checketts, S.R., Morrison, K.A. and Baughman, R.D. Nonsteroidal anti-inflammatory induced pseudoporphyria: is there an alternative drug?. Cutis 63:223-225, 1999.

Ingrish, G. and Rietschel, R.L Oxaprozin-induced pseudoporphyria. Arch.Dermatol. 132:1519-1520, 1996.

Krischer, J., Scolari, F., Kondo-Oestreicher, M., Vollenweider-Roten, S., Saurat, J.H. and Pechere, M. Pseudoporphyria induced by nabumetone. J.Am.Acad.Dermatol. 40:492-493, 1999.

Magro, C.M. and Crowson, A.N. Pseudoporphyria associated with Relafen therapy. J.Cut.Pathol. 26:42-47, 1999.

Meggitt, S.J. and Farr, P.M. Pseudoporphyria and propionic acid non-steroidal anti-inflammatory drugs. Br.J.Dermatol. 141:591-592, 1999.

> back to the top

About the Author

Dr. Victoria Werth is an internist and dermatologist with a practice that specializes in patients with autoimmune diseases that involve the skin. She attended medical school at Johns Hopkins, trained in internal medicine at Northwestern Memorial, followed by a residency in dermatology at New York University. She had research training during a fellowship in immunodermatology at NYU. She is now an Associate Professor of Dermatology and Medicine and the University of Pennsylvania and Chief of Dermatology at the Philadelphia V.A. Hospital. Her research relates to the photoimmunology of autoimmune skin diseases, and she recently identified a genetic abnormality that is associated with a particularly photosensitive form of skin lupus.

> back to the top

July 30, 2003