Connective Tissue Diseases (CTDs) : Causes and Diagnosing

by Food and Drug Administration (FDA)

(Page 2 of 3)

What Causes CTDs?

The causes of CTDs are unknown, although scientists are investigating factors that may play a role in triggering the disorders. Suspected culprits are defective genes, overproduction of hormones, and faulty clearing from the body of antibodies and the substances with which they react.

"There appears to be a combination of some environmental agents acting on certain genetic backgrounds in these diseases," says Fred Miller, M.D., Ph.D., medical officer in FDA's Center for Biological Evaluation and Research, molecular immunology laboratory. He notes that occupational exposure to silica dust and polyvinyl chlorides have been associated with scleroderma. Drug-induced lupus, a variant of SLE, can be traced to the use of drugs such as hydralazine (a high blood pressure medication), procainamide (a treatment for irregular heartbeats), and isoniazid (a tuberculosis drug). When a patient stops the suspected drug, lupus symptoms may clear up. But why some people become ill after exposure to these agents remains unclear.

The idea that an environmental agent can trigger a CTD in susceptible people has led to conjecture about a possible link between silicone, collagen injections, and CTDs. Yet the data offered to support a connection are "very sparse and weak," says FDA's Miller.

Because FDA feels further study of silicone breast implants is warranted, the agency has restricted the use of these implants to women undergoing breast reconstruction following mastectomy and a limited number of women choosing the devices for augmentation.

Many physicians are urging caution with collagen injections. "It [the procedure] worries me a lot," says Judith Anderson, M.D., a hematologist and associate professor of internal medicine in the Division of Hematology/Oncology, Wayne State University School of Medicine. She points out that there is no standardization of the type of collagen used for injection. Most physicians use collagen products made from bovine (cow) collagen. Such products are likely to be properly purified and free of contaminants because they are prepared in large quantities for commercial use.

However, "unethical practitioners" may use collagen from cadavers, which may not be subject to the same high standards of quality control, Anderson says. Cadaver collagen may be contaminated with white cells that can cause an autoimmune reaction in a person who receives collagen injections. There is also potential for viral contamination of cadaver collagen. "If I were a young woman with a cleft chin or wrinkles, I would think 100 times before having collagen injections," she says.

Although patients are given a preliminary injection to test for allergic reaction before undergoing treatment, "that doesn't mean you won't develop problems several years down the road," adds Sara Kramer, M.D., a rheumatologist and instructor of clinical medicine at New York University Medical Center. "My feeling is, if you don't need the procedure for medical reasons, you're better off not having it done."

FDA holds that evidence is insufficient to show that collagen injections cause CTDs in people without a history of these diseases. Even so, this does not mean there is no risk of developing CTDs from these injections. The agency has mandated that collagen products' labels carry a warning about the possible association between collagen injections and PM/DM. People considering undergoing the procedure should ask their physicians for the patient information brochure, which lists the possible adverse effects of the products, and discuss these risks with their doctors.

Diagnosing CTDs

One reason it's so difficult to determine if silicone, collagen injections, or anything else triggers CTDs is that the illnesses themselves are not easily diagnosed. No single test can definitively determine whether a person has a CTD, and symptoms are very often vague, mimicking those of other diseases. As Shulman says about scleroderma, "It's like the snowflake of diseases — no two cases are alike."

A CTD is usually diagnosed by the patient's symptoms, medical history, and the results of a number of tests that assess the status of the immune system and tissues in the body.

Blood Tests: Several blood tests are used to help determine whether a patient has a CTD and, if so, what type. A physician may first order a complete blood count and other standard blood tests. Depending on results, the doctor may also order an anti-nuclear antibody test (ANA). This is a nonspecific test that determines if a patient has auto-antibodies that react with parts of the cell nuclei. However, results may be positive for conditions other than a CTD, such as infectious diseases or endocrine disease.

Disease-specific antibody tests may also be done. These tests indicate the presence of antibodies for specific CTDs. For example, the anti-DNA and anti-Sm antibody tests are specific to SLE. There are also specific antibody tests for scleroderma and PM/DM. However, many people with CTDs have negative antibody tests. These tests can help confirm a diagnosis in a patient with symptoms or a family history, but can't be used alone to make diagnoses.

Electromyography: This test assesses the electrical activity in muscles and is used in the diagnosis of PM/DM.

Biopsy: The removal of a small piece of tissue for inspection under a microscope can be a useful diagnostic tool. A biopsy of muscle tissue can help diagnose PM/DM. A biopsy of kidney tissue can give evidence that SLE has affected that organ.

About the Author

www.fda.gov
FDA is A United States government body that oversees medical devices, including contact lenses, intraocular lenses, excimer lasers and eyedrops. In the US, these products must be approved by the FDA before they can be marketed.