At a Glance

Why Get Tested?

To help in the diagnosis and monitoring of drug-induced lupus

When To Get Tested?

When you have symptoms associated with lupus that may be due to a drug that you are taking

Sample Required?

A blood sample drawn from a vein in your arm

Test Preparation Needed?


What is being tested?

Histone antibodies are autoantibodies. These are antibodies produced by a person’s own immune system that target his or her own histones. Histones are proteins that are a part of chromatin, the genetic material present in the nucleus of almost all cells within the body. Because histones are found inside cells, this attack on “self” can cause symptoms throughout the body. This test detects the presence of histone antibodies in the blood.

Histone autoantibodies are one of several types of antinuclear antibodies (ANA). ANA are associated with a variety of autoimmune disorders. The presence or absence of specific antinuclear antibodies is used to help determine which disorder a person may have.

Drugs can stimulate the production of histone antibodies in some people and can cause a type of lupus called drug-induced lupus erythematosus. Up to 95% of those with drug-induced lupus will have histone antibodies. The autoantibodies may also develop in up to 50% of those with non-drug-induced lupus and in 20% of those with other connective tissue diseases.

Many drugs have been associated with drug-induced lupus in some people. Some of the more common examples include:

  • Hydralazine
  • Isoniazid
  • Minocycline
  • Penicillamine
  • Procainamide
  • Quinidine

Other types of medications associated with drug-induced lupus include:

  • Antibiotics
  • Anti-seizure medications
  • Anti-tumor necrosis factor (anti-TNF) agents
  • Interferon-alpha
  • Blood pressure medications
  • Methyldopa
  • Thyroid medications

Common Questions

How is the test used?

Histone antibody testing is primarily used to support a diagnosis of drug-induced lupus, particularly in a person who is taking one of the medications mentioned above in the “What is being tested?” section.

Testing is used to distinguish drug-induced lupus from other forms of lupus such as systemic lupus erythematosus (SLE), from another autoimmune disorder, or from another cause of a person’s symptoms. While it is not diagnostic of drug-induced lupus, its presence is consistent with this diagnosis.

The test is typically ordered with or following a positive ANA test and may be ordered along with a test for anti-double-stranded DNA (anti-dsDNA) to help establish a diagnosis.

If a person is diagnosed with drug-induced lupus, the identified drug may be discontinued upon the recommendation of the healthcare practitioner. One or more histone antibody tests may be used as follow up to monitor antibody levels (titers), if present.

When is it ordered?

A histone antibody test is ordered when a person has been taking a drug for several weeks to a couple of years and develops signs and symptoms that could be due to drug-induced lupus. This is especially true when the person affected did not have a prior personal or family history of an autoimmune disorder. Symptoms may include:

  • Arthritis-like pain in one or more joints (but no or little joint inflammation)
  • Fatigue
  • Fever
  • Muscle pain (myalgia)
  • Red rash that frequently resembles a butterfly across the nose and cheek areas (malar rash)
  • Sensitivity to sunlight
  • Weight loss

Symptoms and complications involving the central nervous system (CNS) and kidneys occur with SLE but are much rarer with drug-induced lupus.

The histone antibody test may be repeated at intervals after the drug has been discontinued to monitor for decreases in histone antibody levels.

What does the test result mean?

Results of histone antibody testing consider several factors. A positive result means that a person likely has drug-induced lupus if the person also has:

  • Symptoms associated with lupus
  • Been taking a drug, especially one associated with the condition, for several weeks to a couple of years
  • No identified autoimmune disorder prior to taking the drug
  • Positive ANA test
  • Low or negative anti-dsDNA and other autoantibodies
  • Signs and symptoms that resolve when the drug is discontinued
  • Histone antibody levels that begin to decrease when the drug is discontinued

A positive histone antibody result by itself does not establish a diagnosis. About 50% of those with SLE will have histone antibodies, though generally not induced by a specific drug. In these cases, the anti-dsDNA test will be positive and significantly elevated.

A negative result means that the individual’s signs and symptoms may be due to a condition other than drug-induced lupus, such as a drug allergy. However, a negative result does not rule out drug-induced lupus. A small portion of individuals may have drug-induced lupus even if they do not have histone antibodies.

Is there anything else I should know?

An individual with SLE may have a flare-up that is caused or exacerbated by drug therapy without having drug-induced lupus.

SLE tends to affect more women than men and tends to occur in people in their 20s to 40s. Drug-induced lupus affects both sexes equally and can affect anyone but occurs most frequently in those who are older.

What can I do to change my histone antibody level?

Talk to your health care practitioner about discontinuing the potentially offending drug. When this is done, the histone antibody level should drop over time. Histone antibody levels do not respond to lifestyle changes.

If the level of my histone antibodies decreases, can I take my drug again?

No. The antibodies may drop to very low or undetectable levels, but a small amount will still exist. If you resume taking your drug, your symptoms and increased antibody levels may reemerge.

Should I tell all my health care providers about being diagnosed with drug-induced lupus?

Yes, this is an important part of your medical history and needs to be shared as it will need to be taken into account by your health care practitioners whenever you are given medications.

How long will it take for my results?

It may take several days before your results are available. This is not a routine test and your sample will frequently need to be sent to a regional reference laboratory for testing.


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