Medicament Allergies

Medicament allergies, thus, are infrequent. But like food allergies, they can be quite severe, even fatal, when they do occur. The most notorious allergen among medicaments is penicillin, which accounts for about 75 percent of deaths from anaphylaxis in the United States. Ironically, penicillin is also the greatest lifesaver of the past sixty years. Many other medicaments, especially other antibiotics, are occasionally allergenic.

Adverse reactions

Medicaments, like foods, can cause various kinds of adverse reactions: allergies, intolerances, toxic reactions, and so on. An adverse reaction to a medicament is any untoward reaction or nontherapeutic effect of that medicament. Technically, the broad category of adverse reactions includes effects of an overdose. Side effects, too, are numbered among adverse reactions; they are not as universal and predictable as overdose effects, but they tend to affect significant numbers of those who take any given medicament. Many antihistamines, for example, have the side effect of making most people drowsy. Theophylline, often used to treat asthma, may make your heart race. Antibiotics often cause diarrhea. A side effect that is categorized as common may appear almost invariably or may affect only 1 in 20 people. A side effect that is rare may affect 1 in 10,000, or occur with even less frequency than that.

A medicament intolerance is an exaggerated response to a medicament. For example, people who are extremely sensitive to aspirin may get a ringing in the ears and feel nauseated after taking just one tablet. The average person would experience these unpleasant effects only after taking many aspirin.

There are also so-called idiosyncratic reactions to medicaments. These vary according to the individual, and often are not well understood. It is believed that in some cases enzyme deficiencies may be involved. (An example of an idiosyncratic reaction is the bone marrow failure that occurs, rarely, after use of chloramphenicol, an antibiotic. This occurs in approximately 1 in 30,000 uses.)

Finally, of course, there are allergic reactions to medicaments. About 15 percent of patients treated with medicaments experience adverse reactions, and very often these people wrongly say that they are "allergic" to the medicament that caused the problem. But only a fraction of such adverse reactions are due to allergy.

It is important to know the difference between an allergy and intolerance, because if you mistakenly report having an allergy to a medicament, a doctor may be forced to give you a less effective medication to avoid setting off an allergic reaction. Often patients think that if a medicament gives them diarrhea, they are allergic to it. But diarrhea is a common side effect of antibiotics and other medicaments, caused by changes in the bacterial environment in the intestines. On the other hand, if you are truly allergic to a medicament, the doctor must know this, because that medicament or another in its family could cause you life-threatening difficulty.

True medicament allergies

The key to identifying a medicament allergy is that it resembles other kinds of allergy. For instance, you will not get an allergic reaction the first time you take that medicament. A sensitivity must build up. But that buildup can occur quickly, with the result that allergy symptoms can appear during the initial course of therapy, even though everything went well for the first couple of doses. Moreover, some people are exposed to medicaments inadvertently or without realizing it because some medicaments are present in food we eat. A baby may be exposed to penicillin through breast milk. Penicillin and other medicaments may also be present in cow's milk or in meat from farm animals. In these cases, someone will have built up a sensitivity to the medicament without realizing it.

Assuming a normal exposure to medicaments, medicament allergies often appear in early adulthood, but there are no age limits. Some children have allergic reactions to medicaments. Some elderly people develop medicament allergies even after having taken a medicament many times.

Occurrence

Frequently, an allergic reaction to a medicament occurs within minutes to one hour after taking the medicament. If you are very allergic, even a minuscule dose will produce symptoms. There are also delayed reactions that take hours to two to three days to appear. Rarely, there are reactions that are even more delayed. For example, hives resulting from a sensitivity to ampicillin can occur several weeks after taking the medicament and last up to four months.

As a rule, the more rapidly the symptoms appear, the more dangerous the reaction. Symptoms arising within an hour of taking the medicament are potentially life-threatening. The delayed symptoms are normally less serious, but still require evaluation by a physician.

Major adverse reactions to medicaments

A medicament reaction in the first hour or first few minutes after exposure that includes the following symptoms requires immediate, expert medical attention: swelling (sometimes with hives); difficulty breathing or swallowing; vomiting or stomach cramps; itching; choking; weakness; and a sense of impending doom. These are signs of a dangerous reaction-anaphylaxis. Choking and difficulty breathing are caused by swelling in the throat that is closing off the windpipe. This sounds serious, and it is. That sense of impending doom is appropriate. You might die. If you experience any swelling of the lips, tongue, eyes, fingers, or hands-even without choking or wheezing-call your doctor or an ambulance immediately. Do not take the next dose of the medicament.

Typical symptoms of a medicament allergy are itching associated with hives or a rash, angioedema (swelling), and sometimes a fever. If you are taking a medicament and develop hives or itching, do not take another dose. Contact your doctor immediately. Your doctor will have to assess whether to try to continue the medicament or use another.

Another occasional sign of an allergy reaction is a cyanotic, or bluish, tinge to the skin; in dark-skinned people, this can be seen in the lips, nail beds, palms of the hands, and soles of the feet. Joint aches and fever may also occur. If you develop rash or any of the symptoms mentioned above, report this promptly to your doctor.

Incidentally, one sign of medicament allergy is that the symptoms usually clear up or begin to improve within several days after the medicament is discontinued.

Hives and rashes

Acute hives can be a sign of a dangerous medicament allergy and should be treated as a medical emergency, especially following an injection of a medicament.

A sensitivity to nonsteroidal anti-inflammatory medicaments may cause hives and in some cases be associated with chronic hives, as well as with asthma attacks. This sensitivity is sometimes linked to a sensitivity to the food additive tartrazine, a yellow dye. Unfortunately, the anti-inflammatories involved include some of the most widely used medicines for aches and pains: aspirin and ibuprofen. If you are sensitive to these medicines, your doctor may recommend a substitute, such as choline magnesium trisalicylate (Trilisate).

Rashes are a frequent manifestation of medicament allergy. Commonly they are morbilliform, that is, they resemble a measles rash, with multiple tiny red dots allover the body. The rash is itchy but not severely so.

A morbilliform rash can be the result of a medicament allergy or of a number of viral diseases. There is a distinguishing sign between the two, however; an allergic rash may cover your body, but it will not affect your palms and soles. A viral rash usually does not spare the palms or soles. Sometimes an allergic rash progresses to become thick and very red and itchy. Occasionally, when it is difficult to determine whether a rash is caused by the illness being treated or by the medicament used to treat the illness, diagnosis requires a biopsy of the rash.

Most rashes are relatively harmless, but they may develop into exfoliative dermatitis. This is a condition in which the rash spreads over the entire body and the skin begins to shed. This is similar to what happens as the result of a burn, and, as with burn victims, there is great danger of infection. Some patients afflicted with exfoliative dermatitis, chiefly among the elderly, do not survive. Exfoliative dermatitis can also result as a complication of eczema (atopic dermatitis) or psoriasis.

Almost any medicament can cause a rash, but the medicaments that most commonly do so include sulfa medicaments, amoxicillin, synthetic penicillin (such as dicloxacillin sodium and methicillin sodium), penicillin, cephalosporins (which are chemical cousins of penicillin), and hydantoin.

Patients with mononucleosis have an amazing 9 in 10 chance of developing a measles like rash from ampicillin. Certain leukemias also tend to make one susceptible to developing a rash when taking ampicillin. By and large this kind of allergy is not terribly serious, which is a small favor when one is so sick already. The rashes that follow treatment with penicillin and the cephalosporins are notable for their longevity. They may last up to four months after treatment is stopped.

Photosensitivity

Photosensitivity reactions occur when a medicament that is present in skin reacts with light. Usually the light must be sunlight, but artificial light is sometimes sufficient. Diagnosis is usually simplified by the fact that the reaction is limited to areas of skin exposed to light.

Photoallergic reactions resemble contact dermatitis but can recur months after the medicament is stopped, if the skin is exposed to light. Among many medicaments that can cause these reactions, the most commonly implicated are sulfa medicaments and salicylamides (used in medicated soaps and acne medications).

Phototoxic reactions, which are not allergic in nature, may be caused by coal-tar derivatives and other substances, including the antibiotics doxycycline and ciprofloxacin. A phototoxic reaction may give rise to an exaggerated sunburn like rash that can blister.

Serum sickness

Serum sickness is caused most commonly by penicillin but also by many other types of medicaments, including cephalosporins, sulfa medicaments and other antibiotics, phenytoin (used for epilepsy), and propylthiouracil (used to treat hyperthyroid conditions). Serum sickness is so named because it was originally associated with vaccines made from animal serums.

Typically, when this reaction occurs on first exposure to a medicament, it appears one to three weeks after starting the medicament. If the person has taken the medicament previously, an accelerated reaction may occur within several. days. The symptoms include itching (from hives or a rash), swelling, fever, headache, fatigue, pain and swelling in joints, swollen lymph glands, nausea, and diarrhea.

These symptoms may be mild or severe and last several days to several weeks. Usually recovery is complete, but in rare cases there is permanent neurological damage or involvement of internal organs, including the heart, kidney, liver, pancreas, and adrenal glands. Treatment includes stopping the offending medicament and taking antihistamines and oral cortisone, depending on the severity of the symptoms.

Medicament fever

Most medicaments are able to cause fever in susceptible persons. Certain anticancer medicaments, for example, ordinarily result in fever. Also, the injection of a medicament can cause local inflammation in the area where the shot was given, and the inflammation can cause a rise in temperature. But in some cases the fever is part of an allergic reaction. Fever associated with allergy can be confusing to both physician and patient, especially when an antibiotic is being used to treat an infection that produces fever. If there are accompanying signs of allergy, such as a rash, the answer may be obvious. But sometimes such signs are missing. To reach a diagnosis, the physician should try to find out if there has been a history of medicament allergy in the patient's past. One can also try stopping the medicament, and if allergy is the cause of the problem, the fever will usually subside quickly.

The medicaments most commonly implicated in medicament fever are penicillin and the cephalosporins, sulfa medicaments, certain medicaments used to treat high blood pressure (typically, methyldopa), and procainamide and quinidine used to treat heart-rhythm irregularities.

It is important to identify and treat the cause of the fever because more serious manifestations may follow, including hepatitis (liver inflammation), vasculitis (inflammation of the blood vessels), and severe rashes.

Medicament-induced lupus

Lupus (systemic lupus erythematosus) is a disease in which the body makes antibodies against its own tissues. These antibodies (autoantibodies) can seriously damage the kidneys, brain, blood vessels, liver, and heart. Certain medicaments can produce similar effects, causing the production of antibodies, although no underlying disease is present.

The most commonly implicated medicaments are hydralazine (used to treat high blood pressure), procainamide (for heart-rhythm irregularities), and isoniazid (an antituberculosis medicament). Other medicaments that may cause lupus are methyldopa (for high blood pressure), phenytoin (for epilepsy), and even birth-control pills.

In medicament-induced lupus, the patient is likely to develop fevers, joint pains, and rashes-and these may occur months to years after the patient has started to take the offending medicament. Usually the symptoms fade rapidly when the medicament is stopped, but the autoantibodies may remain in the body for years.

Vasculitis

Vasculitis, or inflammation of the blood vessels, caused by medicaments is usually associated with rashes, as the blood vessels of the skin are involved. But often the vasculitis shows itself in black-and-blue marks, especially on the legs. Other parts of the body, including the kidneys and joints, can be involved. The medicaments that most commonly cause allergic vasculitis are penicillin, sulfa medicaments, hydantoin (used to treat seizures), and allopurinol (used for gout). A rare form of vasculitis may very occasionally be associated with the asthma medications Accolate and Singulaire.

Respiratory manifestations

Asthma can be exacerbated by a number of medicaments, especially aspirin and beta blockers, the latter even when applied topically, as in the case of eye drops for glaucoma.

About 1 in 10 asthma patients is sensitive to aspirin, ibuprofen (Motrin, Nuprin), indomethacin, and related nonsteroidal anti-inflammatory medicaments. You may be able to substitute Trilisate. Acetaminophen (Tylenol) is not usually a problem. In rare cases, the asthmatic with nasal polyps who takes aspirin or another nonsteroidal anti-inflammatory medicament may experience a life-threatening asthma attack. This sensitivity is not a true allergy, but it can aggravate asthma. It is rather difficult to diagnose and does not show up with skin testing.

People who are sensitive to the yellow dye tartrazine (FD&C #5) or to sulfites should read labels on over-the-counter medicines and question their pharmacists about prescription medicaments.

The lungs can be affected by reactions to medicaments. Among the problem medications are penicillin, sulfa medicaments, and even, although rarely, cromolyn, which is used to prevent asthma symptoms. In cases involving the lungs, patients develop a cough seven to ten days after starting the medicament treatment. A chest X ray shows a picture that resembles that of pneumonia. The blood count reveals increased numbers of eosinophils, a type of white blood cell often involved in allergic reactions.

Nitrofurantoin, an antibiotic used to treat bladder infections, has a number of side effects to watch out for, including fever, chills, coughing, and chest pain. These symptoms appear in approximately 1 of 500 patients who take the medicament, and they usually disappear one or two days after the treatment is stopped.

Methotrexate can cause similar problems. It is an anticancer medicament; it is prescribed for some kinds of arthritis; recently it has been used as a steroid-sparing agent (to reduce the need for steroids) in severe asthma.

Coughing is a common side effect of a class of medicaments called angiotensin-converting enzyme inhibitors (such as captopril), which are used to treat high blood pressure. Coughing clears up after the medicament is stopped.

Blood, liver, and kidney reactions

Allergic and toxic reactions to medicaments can cause changes in the blood, including a reduction in platelets and a risk of abnormal bleeding; a decrease in the number of red blood cells (anemia); and a decrease in the number of white blood cells. These disorders are generally noticed only when a blood count is done, either routinely or because the patient is feeling sick.

Because the liver metabolizes medicaments, it may become involved in adverse medicament reactions. The symptoms of liver damage are often subtle or nonexistent. They may include stomachaches, nausea, or yellowing of the skin (jaundice). But in blood testing one can run various tests for liver function. The medicaments most often associated with liver damage include isoniazid (used for tuberculosis), certain antidepressants and other mood-altering medicaments, birth-control pills, and some antibiotics.

The kidneys, because of their general excretory function, also may be affected by medicaments in the bloodstream, including penicillin and the related cephalosporins, sulfa medicaments, diuretics (water pills), hydantoin medicaments (used for seizures), and nonsteroidal anti-inflammatory medicaments.

Penicillin

The age group most at risk is adults twenty to forty-nine years old. The more seriously ill the patient, the greater the risk of a serious reaction. Penicillin makes no distinction between male and female or among ethnic groups; all are equally liable to become allergic.

Over a period of years, one may mature out of a penicillin allergy. If you have experienced only a rash, especially a delayed rash, the chances are that, if it were necessary, you could use penicillin again if your skin tests to penicillin were negative. If you have developed, hives and other signs of an anaphylactic reaction, you may never be able to use penicillin. Future tests for penicillin sensitivity should probably be done only in the well-equipped allergist's office or hospital. Desensitization is even more tricky, although it can be attempted in critical cases.

Variants of penicillin taken orally, such as amoxicillin and ampicillin, almost always cause reactions in people sensitive to penicillin. The symptoms may be delayed days or even weeks.

Cephalosporins, which are chemically related to penicillin, contain allergenic factors similar to those in the penicillin molecule. But cephalosporins are not usually as potently allergenic as penicillin itself. The oral cephalosporins include Ceclor, Keflex, Ceftin, Suprax, and Velosef.

People who are truly allergic to penicillin have about a 5 percent to 16 percent chance of reacting to a cephalosporin. Typically, if penicillin causes a delayed, mild reaction, such as a rash, then it would be medically acceptable to try treating the patient with a cephalosporin in a case in which the medicament is needed and there are no good alternatives. The best procedure is to give the first dose in the doctor's office a little at a time over several hours.

Anesthetics and insulin

Painkillers and various anesthetics cause allergic and toxic reactions fairly frequently. Some opiates, for example, may cause direct histamine release. If you have ever developed a rash or any kind of adverse reaction to a painkiller, sedative, or anesthetic, you should report this to your doctor. Possibly you should avoid medicaments of the same type that caused you a problem. Often another class of medicaments can be substituted.

Symptoms such as weakness, changes in heartbeat, and fainting when local anesthetics are injected are not usually due to allergy but rather to the stress of the experience. But if there is doubt as to the cause, and you want to know if you are in any danger using local anesthetics, skin testing can indicate whether an allergy exists. If the skin tests are negative, then gradually increasing doses of the medicament are injected to be certain that tolerance is good.

Anaphylaxis and other severe allergic reactions can occur during the administration of general anesthesia. This is manifested during surgery by a sudden calamitous drop in blood pressure and even cardiac arrest. Other allergic stigmata such as hives and rash are not always present. This type of reaction can be confused with many other nonallergic reactions during surgery. It is essential to establish when an allergic reaction has occurred because it will occur again and can be prevented by appropriate premedication. This is a very important point, and patients who have had this type of reaction during general anesthesia should discuss it with their own physicians. In some cases, the reaction may be due to latex allergy, and it is important to identify the cause.

Insulin allergy can be highly problematic to diabetic patients who need this substance to maintain health. There are various methods of coping, which should be reviewed with a physician specializing in diabetes.

Chymopapain and streptokinase

Papain and chymopapain, derived from the papaya tree, are enzymes used in a variety of products from meat tenderizer to toothpaste. Chymopapain is useful in treating herniated disks. Unfortunately, it also causes anaphylaxis in about 1 of every 100 persons treated. It is believed that exposure to meat tenderizer and certain grass pollen may predispose people to react badly to chymopapain.

Typically, patients are tested for chymopapain sensitivity by both an in vitro (laboratory) blood test and a skin test before the chymopapain is injected into the disk, but these tests are not always reliable.

Streptokinase, another enzyme, dissolves blood clots and is used to treat circulatory-system disorders, such as heart attacks and phlebitis. Unfortunately, many people are allergic to it and develop anaphylaxis.

X-ray dyes

X-ray dyes, also called radiographic contrast media, are often used prior to certain CAT scans, myelograms, angiography, kidney X rays, and so on. The dye helps the radiologist see the organ being studied. But the intravenous injection results in allergy like reactions in 1 of 15 cases, in dangerous reactions in 1 of 50 cases, and in death in 1 in 40,000.

If you have ever had an allergy like reaction to an X-ray dye, this must be noted in your medical records. Be sure to mention the reaction to any doctor contemplating such diagnostic testing. There are new dyes to which you may be less sensitive but which are not used routinely because they are expensive. One of these newer dyes, however, should be used if you have had any previous reaction, no matter how mild, to X-ray contrast media. Also, pretreatment with antihistamines and corticosteroids is very helpful in preventing or damping a reaction. Severe reactions are less common when, as in a myelogram or barium enema, the dye is not injected into a vein.

It was formerly thought that a history of shellfish allergy was a predictor of reactivity to these dyes, but this is not so. However, a history of hay fever or asthma does increase the risk slightly.

Prevention of dangerous medicament reactions

Other antibiotics and painkillers, too, may cause anaphylactic reactions. Chymopapain can be dangerous. The single most important thing that you can do to prevent an overwhelming anaphylactic medicament reaction is to stay within reach of medical help for a half hour to forty-five minutes after having an injection of a medicament, especially penicillin.

Oral doses of a medicament are much less likely to cause a severe reaction than injected doses. Delayed reactions are usually milder than those that arise in the first half hour or so. But this does not mean that you should ignore symptoms associated with an oral dose of medicine, whether they occur soon after the medicine is ingested or are delayed.

If you have found that you have a medicament allergy, it is important that you mention this to your doctor before trying a new medication. It is wise to learn which other common medicaments belong to the family of medicaments to which you are allergic. You should avoid that whole family of medicaments.

When a doctor prescribes a new medicament, always remind her or him of your allergy. Unfortunately a doctor may have forgotten your allergy or, worse, failed to have taken your earlier report seriously. Another prudent safeguard is to check with your pharmacist as to whether a prescribed medicament is related to the medicament or class of medicament that previously caused you difficulty.

To avoid delayed but nevertheless serious manifestations of medicament allergy, it is important to notice and remember any and all reactions that you may have had to a medicament in the past. A remembered rash or fever that cleared up suddenly when you stopped taking the medicament may be helpful in diagnosing a troublesome reaction in the present. Alert your doctor to any possible sensitivity before starting a course of treatment. Ask that the information be included in your medical records.

Diagnosis and treatment of medicament allergy

Diagnosis of medicament allergy is often uncertain, and treatment is usually simple avoidance. This avoidance, by the way, can also be helpful in the diagnosis. If the medicament is withdrawn and the symptoms disappear relatively promptly, the chances are that the cause of the trouble was some sort of allergy. Elevated levels of eosinophils in the blood, together with other signs of allergy, such as a rash, indicate that an allergic process is present. But an increased number of eosinophils by itself is rarely enough reason to diagnose medicament allergy.

Skin tests for medicament allergy are imprecise and can be dangerous. Nevertheless, they may be undertaken, always under a physician's supervision, when it is important to determine whether an allergy really is present. This situation arises most often in the case of patients who need treatment for certain infections, such as staph infections, or for a herniated disk, or for some other condition for which there is really only one medicament of choice.

Skin testing for penicillin sensitivity, while risky, is of value in that it reveals the sensitivity in most (but not all) instances in which a sensitivity does exist. Skin testing is also fairly reliable for sensitivity to insulin, chymopapain, and local anesthetics.

If a medicament-sensitive patient must have the medicament in question, a program of desensitization may be undertaken under controlled conditions (preferably in an intensive care unit). Penicillin and insulin are the medicaments for which desensitization is most often attempted, frequently with good results.

The treatment of symptoms of medicament allergy is usually with antihistamines and corticosteroids, if necessary. Often just stopping the medicament is sufficient.