Allergic rhinitis
Highlights
Cough and Cold Products for Children
Decongestants, antihistamines, and other cough and cold products should not be used to treat infants and small children under the age of 2, according to recent recommendations by the Food and Drug Administration (FDA). These medicines can cause serious and potentially life-threatening side effects, including rapid heart rate, convulsions, loss of consciousness and death. The FDA is currently reviewing the safety of these over-the-counter products in children ages 2 - 11.
Breastfeeding for Allergic Rhinitis Prevention
Exclusive breastfeeding for a babys first 4 months can help prevent the development of allergic rhinitis and other types of allergies in high-risk infants, according to new guidelines from a committee of the American Academy of Pediatrics. Solid foods should not be introduced before the baby is 4 - 6 months old. The committee did not find that changes in a mothers eating habits affect a babys risk of developing allergies later in life.
Avoiding Allergy Triggers
People with allergies should try to avoid potential triggers such as:
- Pollen
- Dust mites
- Animal dander
- Mold
- Fungi
Introduction
The nose is separated into two passages by a wall of cartilage called the septum. The nasal passages are lined with a membrane that produces a clear liquid called mucus. Mucus is a one of the body's defense systems:
- The mucus traps small particles and bacteria, which may enter the nose as a person breathes.
- The trapped bacteria usually do not cause harm in healthy individuals.
- However, the bacteria can lead to a daily cycle of congestion and decongestion.
- When one side of the nose is congested, air passes through the open (decongested) side. The sides alternate between being wide-open and partly or completely blocked.
Rhinitis
If the congestion becomes severe or other changes occur that irritate the nasal passage, rhinitis develops. To be diagnosed with rhinitis, the patient must experience at least two of the following symptoms for an hour or more on most days:
- Runny nose
- Obstruction in the nasal passage
- Nasal itching
- Sneezing
Click the icon to see an image showing symptoms of allergic rhinitis.
These symptoms may occur as a result of colds or environmental irritants, such as allergens, cigarette smoke, chemicals, changes in temperature, stress, exercise, or other factors.
Infectious Rhinitis. If symptoms last fewer than 6 weeks, the condition is referred to as acute rhinitis and is usually caused by a cold or infection, or temporary overexposure to environmental chemicals or pollutants. [For more information, see In-Depth Report #94: Colds and the flu.]
Chronic Rhinitis. When rhinitis lasts for a longer period, the condition is called chronic rhinitis. Allergies are often the cause, but structural problems or chronic infections could also be to blame.
Causes
The allergic process, called atopy, and its connection to asthma is not completely understood. It involves various airborne allergens or other triggers that set off a cascade of events in the immune system, leading to inflammation and hyper-reactivity in the airways.
- The conductor in an orchestra of immune factors that contribute to allergies and asthma appears to be a category of white blood cells known as helper T cells, in particular a subgroup called Th2 cells.
- Th2 cells overproduce interleukins (ILs), immune factors that are molecular members of a family called cytokines, which are involved in the inflammatory process.
- Interleukins 4, 9, and 13 may be responsible for a first-phase asthma attack. These interleukins stimulate the production and release of antibody groups known as immunoglobulin E (IgE). People with both asthma and allergies appear to have a genetic predisposition for overproducing IgE.
- During an allergic attack, these IgE antibodies bind to special cells in the immune system called mast cells, which are generally concentrated in the lungs, skin, and mucous membranes. This bond triggers the release of a number of active chemicals, importantly potent molecules known as leukotrienes. These chemicals cause airway spasms, overproduce mucus, and activate nerve endings in the airway lining.
- Another cytokine, interleukin 5, appears to contribute to a late-phase inflammatory response. This interleukin attracts white blood cells known as eosinophils. These cells accumulate and remain in the airways after the first attack. They persist for weeks and mediate the release of other damaging particles that remain in the airways.
Better Hygiene, Fewer Childhood Infections
One theory blames the dramatic increase in asthma and allergies on the reductions in childhood infections that have occurred with modern hygiene and antibiotic use. The basic theory rests on the idea that infections that occur early in life stimulate production of specific immune factors called Th1 cells. As these cells build up, they replace other immune factors called Th2 cells, which react to allergens -- a less serious threat to the body. Without infections to stimulate the production of the Th1 infection fighters, the Th2 allergen fighters are not replaced, and they persist at high levels, making the growing child more susceptible to allergies and asthma.
The standard vaccinations against serious childhood infections, according to several important studies, pose no risk for developing allergic rhinitis or asthma. No one should stop giving their children vaccinations against childhood killers.
Triggers of Seasonal Allergic Rhinitis (Hay Fever or Rose Fever)
Seasonal allergic rhinitis occurs only during periods of intense airborne pollen or spores. It is commonly, although inaccurately, called hay fever or rose fever, depending on whether it occurs in the late summer or spring. No fever accompanies this condition, and the allergic response is not dependent on either hay or roses. In general, triggers of seasonal allergy in the U.S. include:
- Ragweed. Ragweed is the most dominant cause of allergic rhinitis in the U.S., affecting about 75% of allergy sufferers. One plant can release 1 million pollen grains a day. Ragweed occurs everywhere in the U.S., although it is less common in western coastal states, southern Florida, northern Maine, Alaska, and Hawaii. The effects of ragweed in the northern states are first felt in middle to late August and last until the first frost. Ragweed allergies tend to be most severe before midday.
- Grasses. Grasses affect people in mid-May to late June. Grass allergies are experienced more in the late afternoon.
- Tree Pollen. Small pollen grains from certain trees usually produce symptoms in late March and early April.
- Mold Spores. Mold spores that grow on dead leaves and release spores into the air are common allergens throughout the spring, summer and fall. Mold spores may peak on dry windy afternoons or on damp or rainy days in the early morning.
Click the icon to see an animation about allergies.
Major weather changes, such as El Nino, can affect the timing of allergy seasons. For example, in 1998, when the effects of El Nino were very strong, allergy attacks were markedly increased, and maximum tree pollen counts occurred 2 - 4 weeks earlier and mold counts 2 - 3 months earlier than the previous year.
Triggers of Perennial (Year-Round) Allergic Rhinitis
Allergens in the House. Allergens in the house can trigger attacks in people with year-long allergic rhinitis, called perennial rhinitis. Household allergens may include the following:
- House dust and mites. Dust mites, specifically mite feces, are coated with enzymes that contain a powerful allergen.
- Cockroaches
- Pet dander
- Molds growing on wallpaper, house plants, carpeting, and upholstery
However, some studies suggest that early exposure to some of these allergens, including dust mites and pets, may prevent allergies from developing in the first place in children.
Fossil Fuels. There may be an association between traffic-related air pollution and allergic rhinitis. Some experts believe that refined fossil fuels, such as diesel fuel and particularly kerosene, are important triggers for allergic rhinitis. In people who already have allergies or asthma, exposure to such fossil fuels may worsen symptoms.
Other Causes of Chronic Nasal Congestion
Aging Process. The elderly are at risk for chronic rhinitis as the mucous membranes become dry with age. In addition, the cartilage supporting the nasal passages weakens, causing changes in airflow. In such cases, therapy involves avoiding possible allergens and airborne irritants as well as measures to keep the nasal passages moist. Decongestants are not helpful.
Irritative Rhinitis. Irritative rhinitis is caused by an overreaction to irritants, such as cigarette smoke, dozens of other air pollutants, strong odors, alcoholic beverages, and exposure to cold. The nasal passages become red and engorged. This reaction is not the same as an allergic reaction, although both are associated with increased numbers of white blood cells called eosinophils.
Vasomotor Rhinitis. Vasomotor rhinitis, also sometimes called idiopathic or irritant rhinitis, is congestion and stuffy nose that is produced by the changes in blood vessels and nerve cells in the nasal passages. It occurs in response to irritants, including smoke, environmental toxins, changes in temperature and humidity, stress, and even sexual arousal. This over-reaction is not associated with any immune response. The biologic causes are unknown. Some research has found an association between vasomotor rhinitis and gastroesophageal reflux disorder (GERD, a common cause of heartburn), which some experts think may be due to a common defect in the nervous system that controls muscle action. Symptoms of vasomotor rhinitis are similar to most of those caused by allergies. Usually, however, they are more severe and occur predominantly on one side of the nose.
Blockage in the Nose from Polyps or Structural Abnormalities. A number of conditions may block the nasal passages. Surgery may be helpful for certain cases.
- Polyps. These are soft, gray, fluid-filled sacs that develop off stalk-like structures on the mucus membrane. They impede mucus drainage and restrict airflow. Polyps usually develop from sinus infections that cause overgrowth of the mucus membrane in the nose. They do not regress on their own and may multiply and cause considerable obstruction.
- Deviated Septum. A common structural abnormality that causes rhinitis is a deviated septum. The septum is the inner wall of cartilage and bone that separates the two sides of the nose. When deviated, it is not straight but shifted to one side, usually the left.
- Other Causes of Blockage. Rarely, cleft palates, overgrowth of bones in the nose, or tumors cause rhinitis.
Medications and Illegal Drugs. A number of drugs can cause rhinitis or worsen it in people with conditions such as deviated septum, allergies, or vasomotor rhinitis:
- Overuse of decongestant sprays used to treat nasal congestion can, over time (3 - 5 days) cause inflammation in the nasal passages and worsen rhinitis.
- Other medications that may cause rhinitis include oral contraceptives, hormone replacement therapy, anti-anxiety drugs (particularly alprazolam), some antidepressants, and some blood pressure medications, including beta-blockers and vasodilators.
- Sniffing cocaine damages nasal passages and can cause chronic rhinitis.
Estrogen in Women. Elevated levels of estrogen appear to increase mucus production and swelling in the nasal passages and can cause congestion. This effect is most apparent in women during pregnancy. In such cases the condition usually clears up after delivery. Oral contraceptives and hormone replacement therapies that contain estrogen have also been associated with nasal congestion in some women.
Symptoms
The general symptoms of rhinitis are congestion, runny nose, and postnasal drip, in which mucous drips into the throat from the back of the nasal passage, especially when lying on the back. Symptoms may vary depending on the cause of rhinitis. Symptoms of influenza and sinusitis must also be differentiated from allergies and colds.
Symptom Phases
Symptoms of allergic rhinitis occur in two phases, early and late.
Early Phase Symptoms. The early phase occurs within minutes of exposure to the allergens and includes:
- Runny nose
- Frequent or repetitive sneezing
- Itching in the nose, eyes, throat, or roof of the mouth
Late-Phase Symptoms. The late phase occurs 4 - 8 hours later and may include one or more of these symptoms:
- Nasal congestion and possibly plugged ears. Children may push their nose upward with the palm of their hand or twitch their nose rabbit-like to clear the obstruction.
- Fatigue.
- Mental changes can include irritability, a slight decrease in attention span, worsened memory, and slower thinking.
- Other common physical symptoms include a decreased sense of smell, plugged ears, sinus headache, postnasal drip or some combination. In severe allergies, dark circles may develop under the eye. The lower eyelid may be puffy and lined with creases.
Risk Factors
Allergic rhinitis affects 20 - 40 million Americans of all ages. As with asthma and many upper respiratory infections, the incidence in allergic rhinitis is increasing. Allergies most often appear first in childhood, and allergic rhinitis is the most common chronic condition in childhood, although it can develop at any age. About 20% of allergic rhinitis cases are due to seasonal allergies, 40% to perennial (chronic) rhinitis, and the rest are mixed.
Having Other Allergies
Having other allergies increases the risk for allergic rhinitis. Here are some examples:
- Young children who have eczema (an allergic skin reaction) have a later risk for allergic rhinitis and asthma. In fact, a family history of eczema increases the risk.
- Food allergies are associated with allergic rhinitis and asthma. (Early feeding patterns, time of weaning, and introduction of solid food do not appear to affect this risk.)
- Asthma, especially in patients who develop it as adults, may increase allergic sensitivity to ragweed and other allergens. Patients who have asthma and a genetic tendency towards allergies (atopy) are also at risk for rhinitis.
Breastfeeding and Nutritional Interventions
Exclusively breastfeeding for the first 4 months of life can help prevent or delay allergic rhinitis and other atopic (allergic) conditions in high-risk infants. Some types of infant formulas that are made without cows milk may possibly help prevent allergies. (There is no evidence that soy-based formulas are helpful.) Solid foods should not be introduced until an infant is 4 - 6 months old. Alterations in a mothers diet do not appear to affect her babys risk for developing allergies.
Prognosis
Seasonal allergic rhinitis tends to diminish as a person ages. The earlier the symptoms start, the greater the chances for improvement. People who develop hay fever in early childhood tend not to have the allergy in adulthood. In some cases, allergies go into remission for years and then return later in life. People who develop allergies after age 20, however, tend to continue to have hay fever at least into middle age.
People with allergic rhinitis may be at higher risk for other allergies, including potentially serious food or latex allergies.
Quality of Life
Although allergic rhinitis is not considered a serious condition, it nonetheless can interfere with many important aspects of life. Surveys of nasal allergy sufferers report that symptoms such as feeling tired (80%), miserable (65%), or irritable (62%) are present in one half to three quarters of patients. Interference with work performance is present in around 50% of allergy sufferers.
People with allergic rhinitis, particularly those with perennial allergic rhinitis, may experience sleep disorders and daytime fatigue. Often they attribute this to medication, but studies suggest congestion may be the culprit in these symptoms. Patients who have severe allergic rhinitis tend to have worse sleep problems than those with mild allergic rhinitis.
Higher Risk for Asthma, Eczema, Nasal Polyps
Asthma and allergies often coexist, and the allergic response plays a strong role in childhood asthma. About 70 - 85% of children with asthma also have allergies. Aggressive treatment of allergies in children with asthma can lower the risk for asthma attacks. Treating allergies in children may also help prevent the onset of asthma. Patients with allergies also have a higher risk for eczema and nasal polyps.
Chronic Swelling in the Nasal Passages (Turbinate Hypertrophy)
Any chronic rhinitis, whether allergic or nonallergic, can cause swelling in the turbinate, which may become persistent (turbinate hypertrophy). The turbinate is a tiny shelf-like bony structure that protrudes in the nasal passageways. It helps warm, humidify, and clean the air that passes over it. If turbinate hypertrophy develops, it causes persistent nasal congestion and, sometimes, pressure and headache in the middle of the face and forehead. This condition may require surgery.
Complications of Chronic Rhinitis in Children
- Children with severe allergies may have a higher risk for behavioral problems than those without allergies.
- Some research suggests that allergic rhinitis is responsible for 2 million missed school days each year.
- Chronic nasal obstruction from year-round allergies can affect a child's appearance. If a child can only breathe through the mouth, the continual force of air passing through the oral cavity can cause changes in facial development. Such changes may include an elongated face and an overbite from teeth coming in at an abnormal angle.
- Chronic rhinitis can cause headaches and also affect a child's sleep, concentration, hearing, appetite, and growth.
Associations with Other Disorders
Depression. During allergy season, patients with allergies are more likely to experience mood changes, including sadness, lethargy, and mental fatigue, than at other times. Some evidence suggests that specific immune factors in the allergic response can cause depressive symptoms. Other research indicates that both may have a common cause.
Diagnosis
To determine the cause of allergic rhinitis, the doctor will ask a number of questions about:
- Time of day and year of rhinitis episodes. Rhinitis that appears seasonally is typically due to pollens and outdoor allergens. If symptoms occur throughout the year, the doctor will suspect perennial allergic or non-allergic rhinitis.
- Family history of allergies.
- History of medical problems.
- In women, if they are pregnant or taking drugs that contain estrogen (oral contraceptives, hormone replacement therapy).
- Use of other medications including decongestants, which can cause a rebound effect.
- Pets.
- Any additional unusual symptoms. As examples, bloody nasal discharge and obstruction in only one nasal passage could suggest a tumor. Fatigue, sensitivity to cold, weight gain, and depression may be signs of hypothyroidism.
Physical Examination
The doctor will examine the inside of the nose with an instrument called a speculum. This is a painless examination allowing the doctor to check for redness and other signs of inflammation. The doctor will also usually check the eyes, ears, and chest.
Possible physical findings may include:
- Dark circles under the eyes
- Redness and swelling of the eyes
- Swollen mucous membranes in the nose
- Swollen nasal turbinates or nasal polyps
- Evidence of fluid behind eardrum
- Skin rashes
- Wheezing
Allergy Skin Tests
A skin test is a simple method for detecting common allergens. Patients are usually tested for a panel of common allergens. Skin tests are rarely needed to diagnose mild seasonal allergic rhinitis, since the cause is usually obvious. The skin test is not appropriate for children younger than age 3.
The procedure is as follows:
- Patients should not take antihistamines for at least 12 - 72 hours before the test. Otherwise an allergic reaction may not show up.
- Small amounts of suspected allergens are applied to the skin with a needle prick or scratch or are injected a few cells deep into the skin. The injection test may be more sensitive than the standard prick test.
- If an allergy is present, a hive (a swollen reddened area) forms within about 20 minutes.
The test is not completely accurate. In most situations, before testing occurs, patients will have tried to avoid any of thier known allergens, as well as tried medications, often including nasal corticosteroid sprays. However, patients with more severe symptoms, particularly those with asthma, significant eczema, or nasal polyps, may benefit from earlier skin testing.
Laboratory Tests
Nasal Smear. The doctor may take a nasal smear. The nasal secretion is examined microscopically for factors that might indicate a cause, such as increased numbers of white blood cells, indicating infection, or high counts of eosinophils. High eosinophil counts indicate an allergic condition, but low counts do not rule out allergic rhinitis.
Tests for IgE. Blood tests for IgE immunoglobulin production may also be performed. One test is called the radioallergosorbent Test (RAST), used to detect increased levels of allergen-specific IgE in response to particular allergens. Blood tests for IgE may be less accurate than skin tests. They should be performed only on patients who cannot undergo skin testing or when skin test results are uncertain.
Imaging Tests
In people with chronic rhinitis, the doctor may also check for sinusitis. Imaging tests may be useful if other tests are ambiguous. CT scans may be useful for some cases of suspected sinusitis or sinus polyps.
Click the icon to see an image of a CT scan.
Nasal Endoscopy
In certain cases of chronic or unresponsive seasonal rhinitis, a doctor may use endoscopy to examine for any irregularities in the nose structure. Endoscopy uses a tube inserted through the nose that contains a miniature camera to view the passageways.
Treatment
If rhinitis symptoms are caused by non-allergic conditions, particularly if there are accompanying symptoms indicating a serious problem, the doctor should treat any underlying disorders. If rhinitis is caused by medications, such as decongestants, the patient may need to stop taking them or find alternatives.
Overall Approaches to Treating Allergic Rhinitis
A variety of items must be considered in selecting a treatment approach. These include:
- Severity of the symptoms
- Frequency (seasonal versus all year, how often during the week)
- Age of patient
- Presence of other related illnesses, such as asthma, atopic eczema, sinusitis, and polyps
- Patient preference regarding types of treatment
- Association with allergens
- Potential and known side effects of medications
- In children, it is important for parents to determine if the child is actually under severe distress and that the parent is not simply responding to their own anxiety when they hear their child snorting or snoring.
Patients with allergic rhinitis have a variety of treatment options available to them:
- Environmental control measures
- Nasal washes may provide good symptomatic relief for some patients.
- Drugs that reduce the inflammatory response are important for preventing moderate or severe allergic rhinitis. Nasal corticosteroids (commonly called steroids) are now considered to be the most effective measure for preventing allergy attacks. Other anti-inflammatory drugs, including leukotriene-antagonists and nasal cromolyn, may be tried as second-line medications.
- Antihistamine tablets relieve sneezing and itching and can prevent nasal congestion before an allergy attack, or may be used to treat symptoms. Many brands are available by prescription and over-the-counter.
- Immunotherapy ("allergy shots") may be considered for patients with more severe seasonal allergies that do not respond to treatment. It may also prevent asthma and the development of new allergies in children. Many experts now recommend immunotherapy for people with both asthma and allergies. Newer immunotherapeutic approaches using specially designed antibodies and vaccines are also showing promise, but are not currently used in the treatment of most patients.
All drug treatments have side effects, some very unpleasant and, in rare cases, serious. Patients may need to try different drugs until they find one that relieves symptoms without producing excessively distressing side effects.
Treating Seasonal Allergies
Because seasonal allergies generally last only a few weeks, most doctors do not recommend the more potent prescription treatments for children.
- Prescription drugs are required only in severe cases. However, in children with both asthma and allergies, treatments for allergic rhinitis may also improve asthmatic symptoms.
- Patients with severe seasonal allergies should start medications a few weeks before the pollen season and continue taking them until the season is over.
- Immunotherapy ("allergy shots") may be considered for patients with severe seasonal allergies that do not respond to treatment.
Treating Mild Allergy Attacks. Treating mild allergy attacks usually involves little more than reducing exposure to allergens and using a nasal wash. Dozens of treatments are available for allergic rhinitis. Many are available over-the-counter, but some require a prescription. They include:
- Nasal washes
- Intermittent usage of second-generation, nonsedating antihistamines
- Decongestants that relieve nasal congestion and itchy eyes for children over the age of 2 and adults
- Decongestant/antihistamine combinations
Treating Moderate-to-Severe Allergic Rhinitis. Patients with chronic allergic rhinitis or those who have bothersome symptoms that active during most of the year (particularly if they also have asthma) may require daily medications. These drugs include:
- Anti-inflammatory drugs. Nasal corticosteroids are now considered to be the most effective measure for preventing allergy attacks. They are recommended for patients with moderate-to-severe allergies, either alone or in combination with second-generation antihistamines.
- Antihistamines. The second-generation, non-sedating antihistamines -- such as cetirizine (Zyrtec), loratadine (Claritin), fexofenadine (Allegra), or desloratadine (Clarinex) -- cause less drowsiness than older antihistamines, such as Benadryl. They are recommended alone or in combination with nasal corticosteroids for treatment of moderate-to-severe allergic rhinitis.
- Leukotriene-antagonists and nasal cromolyn may be beneficial in specific cases of allergies.
- Immunotherapy ("allergy shots") works well for many patients with severe allergies. It is also proving to reduce asthma symptoms and the use of asthma medications in patients with known allergies.
Nasal Washes
For mild allergic rhinitis, a nasal wash can be helpful for removing mucus from the nose. You can purchase a saline solution at a drug store or make one at home (one cup of warm water, half teaspoon salt, pinch of baking soda). Over-the-counter saline nasal sprays that contain benzalkonium chloride as a preservative may actually worsen symptoms and infection.
Simple method for administering a nasal wash:
- Lean over the sink head down.
- Pour some solution into the palm of the hand and inhale it through the nose, one nostril at a time.
- Spit the remaining solution out.
- Gently blow the nose.
The solution may also be inserted into the nose using a large rubber ear syringe, available at a pharmacy. In this case the process is:
- Lean over the sink head down.
- Insert only the tip of the syringe into one nostril.
- Gently squeeze the bulb several times to wash the nasal passage.
- Then press the bulb firmly enough so that the solution passes into the mouth.
- Repeat the process in the other nostril.
Other Treatments
Natural Remedies
Nearly half of asthma or allergy sufferers resort to alternative treatments. To date, however, little evidence supports treatments such as high-dose vitamins, homeopathic remedies, and most herbal remedies. Some relaxation methods, such as massage therapy, may help reduce stress related to allergy symptoms. According to research presented at a 2004 allergy conference, acupuncture is now the most popular alternative treatment among allergy sufferers.
Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.
Decongestants
For mild allergic rhinitis, a nasal wash can help remove mucus from the nose. Decongestants may help dry nasal congestion. They work by shrinking vessels in the nose. By reducing blockage, they decrease the risk of developing sinusitis caused by viruses or bacteria. Many over-the-counter decongestants are available, either in tablet form or as nasal or inhaled decongestants that are applied directly into the airways as sprays, drops, or vapors.
Nasal-Delivery Decongestants
Nasal-delivery decongestants are applied directly into the nasal passages with a spray, gel, drops, or vapors. Nasal decongestants come in long-acting or short-acting forms. The effects of short-acting decongestants last about 4 hours; long-acting decongestants last 6 - 12 hours. The active ingredients in nasal decongestants include oxymetazoline, xylometazoline, and phenylephrine. Nasal forms work faster than oral decongestants and may not cause as much drowsiness. However, they can cause dependency and rebound.
Dependency and Rebound. The major hazard with nasal-delivery decongestants, particularly long-acting forms, is a cycle of dependency and rebound effects. The 12-hour brands pose a particular risk for this effect.
- With prolonged use (more than 3 - 5 days), nasal decongestants lose effectiveness and can cause swelling in the nasal passages.
- The patient then increases the frequency of the dose. As the congestion worsens, the patient may respond with even more frequent doses.
- This causes dependency and increased nasal congestion.
Tips for Use. The following precautions are important for people taking nasal decongestants:
- When using a nasal spray, spray each nostril once. Wait a minute to allow absorption into the mucosal tissues, and then spray again.
- Do not share droppers and inhalers with other people.
- Discard sprayers, inhalers, or other decongestant delivery devices when the medication is no longer needed. Over time, these devices can become reservoirs for bacteria.
- Discard the medicine if it becomes cloudy or unclear.
Oral Decongestants
Oral decongestants also come in many brands, which have similar ingredients. The most common active ingredient is pseudoephedrine (Sudafed, Actifed, Drixoral), sometimes in combination with an antihistamine. Taking pseudoephedrine in the morning, as opposed to later in the day or before bedtime, can help patients avoid side effects such as insomnia and nervousness.
Side Effects of Decongestants
Decongestants have certain adverse effects, which are more apt to occur in oral than nasal decongestants. These side effects include:
- Agitation and nervousness
- Drowsiness (particularly with oral decongestants and in combination with alcohol)
- Changes in heart rate and blood pressure
- Avoid combinations of oral decongestants with alcohol or certain drugs, including monoamine oxidase inhibitors (MAOI) and sedatives.
Individuals at Risk for Complications from Decongestants. People who may be at higher risk for complications are those with certain medical conditions, including disorders that make blood vessels highly susceptible to contraction. Such conditions include:
- Heart disease
- High blood pressure
- Thyroid disease
- Diabetes
- Prostate problems that cause urinary difficulties
- Migraines
- Raynaud's phenomenon
- High sensitivity to cold
- Emphysema or chronic bronchitis. (Individuals with these conditions should particularly avoid high-potency, short-acting nasal decongestant.)
- Medications that increase serotonin levels, such as certain antidepressants, anti-migraine drugs, diet pills, St. John's wort, and methamphetamine. The combination of these medicines and decongestants can cause blood vessels in the brain to narrow suddenly, causing severe headaches and even stroke.
Anyone with these conditions should not use oral or nasal decongestants without a doctor's guidance. Other people who should not use decongestants without first consulting a doctor include:
- Pregnant women
- Children. Children appear to metabolize decongestants differently than adults. Decongestants should not be used at all in infants and children under the age of 2 years, and some doctors recommend not giving them to children under the age of 6. Children are at particular risk for central nervous system side effects, including convulsions, rapid heart rates, loss of consciousness, and death.
Antihistamines
Histamine is one of the chemicals released when antibodies overreact to allergens. It is the cause of many symptoms of allergic rhinitis. Antihistamines can help relieve:
- Itching, sneezing, and nasal discharge
- Other allergy symptoms unrelated to rhinitis, including hives and some rashes
- Nasal congestion, for some of the newer antihistamines, such as cetirizine (Zyrtec) and desloratadine (Clarinex)
If possible, patients should take antihistamines before an anticipated allergy attack.
Many antihistamines are available. They include short-acting and long-acting forms, and they come in form of tablets, nasal-inhalers, eye drops, and syrups. Antihistamines are generally categorized as first- and second-generation. First-generation antihistamines may cause more side effects than newer second-generation ones.
There are some notes of caution when taking any antihistamine:
- Antihistamines may thicken mucus secretions and can worsen bacterial rhinitis or sinusitis.
- Antihistamines can lose their effectiveness over time, and a different one may need to be tried.
First-Generation Antihistamines
First-Generation Antihistamine Ingredients and Brand Names. The older, so-called first generation antihistamines include:
- Diphenhydramine (Benadryl)
- Carbinoxamine (Clistin)
- Clemastine (Tavist)
- Chlorpheniramine (Chlor-Trimeton). Some health care providers recommend this drug if antihistamines are required during pregnancy. It may be as effective as the second generation antihistamines and much less expensive.
- Brompheniramine (Dimetane)
First-generation antihistamines contain compounds called anticholinergics, which tend to produce more side effects than second-generation antihistamines.
Side Effects.
- Drowsiness and impaired thinking
- Dry mouth
- Dizziness
- Agitation
- Insomnia or nightmares
- Sore throat
- Rapid heart beat and chest tightness (uncommon and should be reported)
- Men with enlarged prostate glands may experience difficulty urinating
Drowsiness and First-Generation Antihistamines. Drowsiness is the most distressing side effect reported from first-generation antihistamines, and is potentially serious. It may pose a higher than average risk for work-related and automobile accidents than alcohol, narcotics, or prescription sedatives. Although some studies have not found any strong differences in sedation between the first- and second-generation antihistamines, experts caution against first-generation antihistamines for people most at risk from sedative effects. To reduce risks, take the antihistamine at home a few hours before bedtime, and do not combine it with alcohol or tranquilizers. Do not drive or operate heavy machinery. In general, second-generation antihistamines are now recommended as first-line therapy when antihistamines are used.
Second-Generation (Nonsedating) Antihistamines
The newer second-generation antihistamines do not contain anticholinergics, so they do not usually cause drowsiness to the extent that the first generation antihistamines do. They are sometimes referred to collectively as nonsedating antihistamines. They are now generally recommended as first-line treatment when antihistamines are needed.
Brand Names. The second-generation drugs include:
- Loratadine (Claritin). Claritin is available over-the-counter and is approved for children ages 2 and older. Desloratadine (Clarinex) is similar to Claritin but stronger and longer-lasting. It is available only by prescription.
- Cetirizine (Zyrtec). Zyrtec is approved for both indoor and outdoor allergies. It is the only antihistamine to date approved for infants as young as 6 months. It is available over-the-counter.
- Fexofenadine (Allegra) is also available over-the-counter.
- Acrivastine (Semprex)
- Ebastine, norastemizole, levocetirizine, and mizolastine are other second-generation antihistamines under investigation in the U.S. and Europe. Some may prove to be useful for specific populations.
For nonprescription antihistamines, some studies suggest that cetirizine (Zyrtec) is more effective than Allegra or Claritin in improving symptoms, including those in children. However, cetirizine can cause drowsiness when taken at high doses.
Side Effects and Precautions.
- Common side effects include headache, dry mouth, and dry nose. (These are often only temporary and go away during treatment.)
- Drowsiness occurs in about 10% of adults and in 2 - 4% of children.
- Uncommon side effects include rapid heart beat and chest tightness. Tell your doctor if these effects occur.
- Extended-release forms of Claritin and Zyrtec have other ingredients that can cause other symptoms, including nervousness, restlessness, and insomnia. Some patients taking Claritin-D 24 Hour Extended Release tablets have reported obstruction in the upper gastrointestinal tract, including difficulty swallowing.
Nasal-Spray Antihistamines
Azelastine (Astelin) and levocabastine (Livostin) are available in nasal spray form. They can reduce nasal congestion as well as allergy symptoms. Both reduce symptoms, although azelastine may be more effective in some patients. Their disadvantages are a bitter taste, drowsiness, and expense. They are not as effective as steroid nasal sprays.
Combination Antihistamines and Decongestants
Many prescription and non-prescription products that combine antihistamines and decongestants are available. Combinations sold over-the-counter include Allerest, Sudafed Severe Cold Formula, Vicks DayQuil, Benadryl Allergy/Sinus, Contac Day/Night Allergy & Sinus, and Zyrtec-D. Prescription combinations include Claritin-D and Allegra D. Symptoms may improve within 60 minutes, with congestion clearing up first.
Treating Itchy Eyes
Itching and redness in the eyes sometimes respond to oral antihistamines. Eye drops, however, provide faster relief, and a combination of the two may be best. The following are eye drops for itchy eyes. Others are also available. Individual responses vary, and patients need to find which specific treatment works best for them.
- Antihistamine eye drops: azelastine (Optivar), olopatadine (Patanol), ketotifen (Zaditor), levocabastine (Livostin) for relief of both nasal symptoms and itchy red eyes
- Decongestant eye drops: phenylephrine (Allergan Relief), naphazoline (Naphcon, Opcon-A, VasoClear), tetrahydrozoline (Murine Plus, Visine)
- Combination decongestant/antihistamine: Visine A.
- Corticosteroids: loteprednol (Lotemax, Alrex), pemirolast (Alamast).
General Side Effects and Warning.
- All eye drops can cause stinging, and some may result in headache and congestion.
- No one should continue taking eye drops if they experience pain, changes in vision, worsened redness, or irritation, or if the condition lasts more than 3 days.
- Do not touch the tip of the device to the eye or touch other surfaces with it. Replace the cap after using. Discard any solution that changes color or becomes cloudy.
- People who have heart disease, high blood pressure, an enlarged prostate gland, or glaucoma should talk to their doctor before taking these types of eye drops.
Nasal Corticosteroids
A number of drugs are available for reducing the inflammatory response in allergies. These drugs can help prevent allergy attacks.
Corticosteroid Nasal Sprays
Nasal-spray corticosteroids (commonly called steroids) are considered the most effective drugs for treating moderate-to-severe allergic rhinitis. They are often used either alone or in combination with second-generation oral antihistamines. The benefits of nasal spray steroids include:
- Reducing inflammation and mucus production
- Improving night sleep and daytime alertness in patients with perennial allergic rhinitis
- Treating polyps in the nasal passages
Comparison studies report that nasal steroid sprays work better than second generation antihistamines, such as loratadine (Claritin) and cetirizine (Zyrtec), and are possibly even more effective than allergy shots. They have no effect on itchy eyes, however.
Nasal-Spray Brands. Corticosteroids available in nasal spray form include:
- Triamcinolone (Nasacort). Approved for children over age 6.
- Mometasone furoate (Nasonex). Approved for use in patients age 3 and older.
- Fluticasone (Flonase, Flounce, Veramyst, generic). Approved for children over age 2.
- Beclomethasone (Beconase, Vancenase), flunisolide (Nasalide), and budesonide (Rhinocort). Approved for children over age 6.
- Ciclesonide (Omnaris). Approved for patients age 12 and older.
Side Effects. Corticosteroids are powerful anti-inflammatory drugs. Although oral steroids can have many side effects, the nasal-spray form affects only local areas and has less risk for widespread side effects unless the drug is used excessively. Side effects of nasal steroids may include:
- Dryness, burning, stinging in the nasal passage
- Sneezing
- Headaches and nosebleed (uncommon but should be reported to your doctor immediately)
Possible Long-Term Complications. All corticosteroids suppress stress hormones. This effect is known to produce some serious long-term complications in people who take oral steroids. Researchers have found far fewer concerns with nasal administration or inhaled forms, but there may be certain problems:
- Effect on growth. The major concern for children is whether nasal steroids, like other forms of steroids, will adversely affect growth. Different nasal corticosteroid sprays may be absorbed differently or may stay longer in the body. Most children who take only recommended dosages of nasal sprays, and do not also take inhaled corticosteroids for asthma, will not have growth impairment.
- Effect on eyes. Glaucoma is a known side effect of oral steroids. Some ophthalmologists have observed higher pressure in the eye (a sign of glaucoma) in some patients taking nasal steroid sprays, particularly those taking higher dosages or those who also take inhaled corticosteroids for asthma. (Studies have found no increased risk with intranasal steroids). The eye pressure appears to return to normal after stopping the steroid, but periodic eye examinations are advised.
- Use during pregnancy. Steroids are most likely safe during pregnancy, but pregnant women should talk to their doctors before taking them.
- Nasal passage injury. Steroid sprays may injure the nasal septum (the bony area that separates the nasal passage) if the spray is directed onto it. This complication is very rare.
- Lower resistance to infection. People with any infectious disease or injury in the nose should not take these drugs until the disease or wound has been treated and cured.
Cromolyn
Cromolyn serves as both an anti-inflammatory drug and a specific blocker for allergens. The standard cromolyn nasal spray (Nasalcrom) is not as effective as steroid nasal sprays but does work well for many people with mild allergies. It is one of the preferred first-line therapies for pregnant women with mild allergic rhinitis. It may take up to 3 weeks to experience full benefit.
Side Effects. Cromolyn has no major side effects, but minor ones include nasal congestion, coughing, sneezing, wheezing, nausea, nosebleeds, and dry throat. The spray can cause burning or irritation.
Leukotriene-Antagonists
Leukotriene-antagonists are oral drugs that block leukotrienes, powerful immune system factors that are important in causing airway constriction and mucus production in allergy-related asthma. They appear to work as well as antihistamines for treatment of allergic rhinitis, but are not as effective as nasal corticosteroids. Leukotriene-antagonists include zafirlukast (Accolate), montelukast (Singulair), zileuton (Ziflo), and pranlukast (Ultair, Onon). These drugs are mainly used to treat asthma. Montelukast was approved in 2003 to treat seasonal allergies, and in 2005 to treat indoor allergies.
Immunotherapy
Immunotherapy (commonly referred to as "allergy shots") is a safe and effective treatment for patients with allergies. It is based on the premise that people who receive injections of a specific allergen will lose sensitivity to that allergen. The most common allergens for which shots are given are house dust, cat dander, grass pollen, and mold.
Immunotherapy benefits include:
- Targeting the specific allergen
- Reducing sensitivity in airways in the lungs as well as in the upper airways
- Preventing the development of new allergies in children
- Reducing asthma symptoms and the use of asthma medications in patients with known allergies. Research suggests it may also help prevent the development of asthma in children with allergies.
Candidates
Candidates for Immunotherapy. Immunotherapy may be given to anyone over age 7 with allergies and does not gett better with medication. Many experts agree that immunotherapy should be considered as soon as possible for children with asthma and allergies. Immunotherapy is safe for pregnant women who are already receiving it, although half-strength doses are generally recommended, and it should not be started during pregnancy.
Individuals at Risk for Complications. People who should probably avoid immunotherapy include those who have:
- An extreme response to skin tests (this may predict an allergic reaction).
- Wheezing.
- Uncontrolled severe asthma or lung disease.
- Patients taking certain medications (such as beta-blockers).
- The health status of anyone should be determined before starting treatment.
Administering Therapy
The major downside to immunotherapy is that it requires a prolonged course of weekly injections. The process generally includes:
- Injections of diluted extracts of the allergen are given on a regular schedule, usually twice a week to weekly at first, then in increasing doses until a maintenance dose has been reached. It usually takes several months and may take up to 3 years to reach a maintenance dose.
- At that time, intervals between shots can be 2 - 4 weeks, and the treatment is continued for another 3 - 5 years.
- Patients can experience some relief within 3 - 6 months. If there is no benefit within 12 - 18 months, discontinue the shots.
After stopping immunotherapy, about a third of allergy sufferers no longer have any symptoms, a third have improved symptoms, and a third relapse.
The use of an injection series is effective, but patients often fail to comply with the regimens. Some other schedules and delivery methods are being investigated that might make the program easier and less distressing.
Rush Immunotherapy. Investigators are studying "rush immunotherapy," in which patients achieve the full maintenance dose with several shots a day over a period of 3 - 5 days. Rush therapy uses modifications that reduce the risk of severe reactions to excessive doses. Studies suggest that it is effective and safe, but anaphylaxis and severe reactions can occur. Patients must be selected carefully and must be monitored closely during this period for severe reactions.
Oral Forms. Trials are underway to test forms of immunotherapy taken by mouth as an alternative to allergy shots. These methods include using a pill taken by mouth or a sublingual (under-the-tongue) tablet. Although oral and sublingual immunotherapy is prescribed in many countries in Europe and South America, it is not approved in the United States and is not considered accepted therapy at this time.
Side Effects and Complications of Immunotherapy
Injections for ragweed and, sometimes, dust mites have higher risks for side effects than other allergy shots. If complications or allergic reactions develop, they usually occur within 20 minutes, although some can develop up to 2 hours after the shot is given.
Side effects of immunotherapy include:
- General itching, swelling, red eyes, hives, soreness at the injection site.
- Less common side effects are low blood pressure, asthma worsening, or difficulty breathing. This is due to an extreme hypersensitivity response called anaphylaxis. It can also occur if excessive doses are given.
- In rare cases, particularly because of excessive doses or if a patient has a serious lung problem, severe reactions can occur, which can be life threatening.
- Premedicating patients with antihistamines and corticosteroids may help reduce the risk of reactions to immunotherapy, although this could mask early warning signs.
In a 10-year study, the incidence of any adverse effect was less than two-tenths of 1%, and the great majority of events were mild. The risk for a fatal response is estimated to be 1 in 63 million injections. (As a comparison, the risk for a fatal reaction to penicillin is much higher, 1 in 7.5 million injections.)
Investigational Immunotherapy Approaches
Vaccines. Of particular interest is the development of immunotherapeutic vaccines that use more specific targets to produce an insensitivity to allergens. One such vaccine uses a small protein from the allergen, which is injected into the patient. Other vaccines under investigation are those that use the allergen's genetic material (its DNA) to promote tolerance to the allergen. In a promising 2006 pilot study, patients who received 6 weekly injections of a DNA-based experimental ragweed vaccine had symptom reductions that lasted a year later into a second ragweed season. Researchers will be testing this vaccine in further clinical trials.
Monoclonal Antibodies. Monoclonal antibodies (MAb) are genetically-developed antibodies that are designed to target and attack very specific factors. A MAb known as omalizumab (Xolair) prevents the antibody immunoglobulin E (IgE) from triggering the inflammatory events that lead to allergies. The drug is currently approved for asthma that is associated with allergies. It is not yet well studied for treatment of allergic rhinitis in the absence of asthma. In 2007, the FDA warned that omalizumab may cause a life-threatening allergic reaction (anaphylaxis) in some patients.
Prevention
People with existing allergies should avoid irritants or allergens. These triggers include:
- Pollen. This is the primary cause of allergic rhinitis.
- Dust mites, specifically mite feces, which are coated with enzymes that contain a powerful allergen. These are the primary allergens inside the home.
- Animal dander (flakes of skin) and hair from cats, house mice, and dogs. House mice are proving to be significant sources of allergens, particularly in urban children.
- Molds.
- Fungi.
- Cockroaches are major asthma triggers and may reduce lung function even in people without a history of asthma.
- Some research suggests that alcohol intake may influence allergy severity. One study found that as little as one drink a day is enough to worsen dust mite allergies.
- Some studies suggest that early exposure to some of these allergens, including dust mites and pets, may actually prevent allergies from developing in children.
Indoor Protection against Allergens
Controlling Pets. People who already have pets and are not allergic to them are probably at low risk for developing such allergies later on. When children are exposed to more than one dog or cat during their first year, they have a much lower risk for not only pet allergies but also seasonal allergies and asthma. (Pet exposure does not protect them from other allergens, notably dust mites and cockroaches).
For children who have an existing allergy to pets:
- If possible, pets should be given away or kept outside.
- If this isn't possible, they should at least be confined to carpet-free areas outside the bedroom. Cats harbor significant allergens, which can even be carried on clothing. Dogs usually present fewer problems.
- Washing animals once a week can reduce allergens. Dry shampoos, such as Allerpet, that remove allergens from skin and fur and are now available for both cats and dogs and are easier to use than wet shampoos.
Preventing Exposure to Cigarette and Cooking Smoke. Parents who smoke should quit. Studies show that exposure to second-hand smoke in the home increases the risk for asthma and asthma-related emergency room visits in children. [For help in quitting, see In-Depth Report # 41: Smoking.]
Controlling Dust. Spray furniture polish is very effective for reducing both dust and allergens. Air cleaners, filters for air conditioners, and vacuum cleaners with High Efficiency Particulate Air (HEPA) filters can help remove particles and small allergens found indoors. Neither vacuuming nor the use of anti-mite carpet shampoo, however, is effective in removing mites in house dust. Vacuuming actually stirs up both mites and cat allergens. People with these types of allergies should avoid having carpets or rugs in their homes. For children with allergies, vacuuming should be performed when the child is not around.
Bedding and Curtains.
- Replace curtains with shades or blinds, and wash bedding using the highest temperature setting.
- Encase mattress and pillow in special dust mite proof covers (however, washing is very important since impermeable covers alone do not help prevent allergies).
- Wash pillow in water hotter than 150 F, or in cooler water with detergent and bleach.
- Wash sheets in blankets weekly and hot water.
- Avoid sleeping or lying on cushions or furniture that is cloth covered.
- Stuffed toys should be kept away from the bed and washed weekly as described above. Placing toys in a dryer or freezer may help but is not considered enough.
- Children should sleep as high off the floor as possible (avoid the bottom bunk of a bunk bed).
Reducing Humidity in the House. Living in a damp environment is counterproductive.
- Humidity levels should not exceed 30 - 50%.
- Fix all leaky faucets and pipes, and eliminate collections of water around the outside of the house.
- Dehumidify basements, but empty and clean humidifier daily with a vinegar solution.
- Clean often any moldy surfaces in basement or in other areas of the home.
Exterminating Pests (Cockroaches and Mice).
- Use professional exterminators to eliminate cockroaches. (One study reported that ridding a home of cockroaches and cleaning the house using standard housecleaning techniques failed to eliminate the cockroach allergens themselves.)
- Exterminate mice and attempt to remove all dust, which might contain mouse urine and dander.
- Keep food and garbage in closed containers.
- Keep food out of bedrooms.
Outdoor Protection
Avoiding Outdoor Allergens. The following are some recommendations for avoiding allergens outside:
- Start taking allergy medications 1 - 2 weeks before ragweed season begins. Be sure to take allergy medications before going outside. If regular medications do not work, ask your doctor about allergy shots.
- Camping and hiking trips should not be scheduled during times of high pollen count (May and June for grass pollen and September to October for ragweed).
- Patients who are allergic should avoid barns, hay, raking leaves, and mowing grass. (A mask can be worn during outdoor chores to help reduce pollen exposure.)
- Sunglasses can help prevent pollen from getting into eyes.
- After being outdoors, clean off pollen residue by bathing, washing hair and clothes, and using a nasal salt water rinse.
Dietary Factors
Some evidence suggests that people with allergic rhinitis and asthma may benefit from a diet rich in omega-3 fatty acids (found in fish, almonds, walnuts, pumpkin, and flax seeds) and fruits and vegetables (at least five servings a day). Some studies also suggest reducing sodium, trans fatty acids (hydrogenated fats found in commercial products and baked goods), and omega-6 fatty acids (found in most vegetable oils). Investigators are also studying probiotics -- so-called good bacteria, such as lactobacillus and bifidobacterium, which can be obtained in supplements.
Resources
- www.aaaai.org -- American Academy of Allergy, Asthma & Immunology
- www.acaai.org -- American College of Allergy, Asthma & Immunology
- www.niaid.nih.gov -- National Institute of Allergy and Infectious Diseases
- www.njc.org -- National Jewish Medical and Research Center
- www.lungusa.org -- The American Lung Association
References
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Bahls C. In the clinic. Allergic rhinitis. Ann Intern Med. 2007 Apr 3;146(7):ITC4-1-ITC4-16.
Bielory L. Ocular toxicity of systemic asthma and allergy treatments. Curr Allergy Asthma Rep. 2006 Jul;6(4):299-305.
Blaiss MS. Safety considerations of intranasal corticosteroids for the treatment of allergic rhinitis. Allergy Asthma Proc. 2007 Mar-Apr;28(2):145-52.
Calderon MA, Alves B, Jacobson M, Hurwitz B, Sheikh A, Durham S. Allergen injection immunotherapy for seasonal allergic rhinitis. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD001936.
Ernst P, Baltzan M, Deschnes J, Suissa S. Low-dose inhaled and nasal corticosteroid use and the risk of cataracts. Eur Respir J. 2006 Jun;27(6):1168-74. Epub 2006 Feb 15.
Greer FR, Sicherer SH, Burks AW; American Academy of Pediatrics Committee on Nutrition; American Academy of Pediatrics Section on Allergy and Immunology. Effects of early nutritional interventions on the development of atopic disease in infants and children: the role of maternal dietary restriction, breastfeeding, timing of introduction of complementary foods, and hydrolyzed formulas. Pediatrics. 2008 Jan;121(1):183-91.
Saleh HA, Durham SR. Perennial rhinitis. BMJ. 2007 Sep 8;335(7618):502-7.
Scow DT, Luttermoser GK, Dickerson KS. Leukotriene inhibitors in the treatment of allergy and asthma. Am Fam Physician. 2007 Jan 1;75(1):65-70.
Sheikh A, Hurwitz B, Shehata Y. House dust mite avoidance measures for perennial allergic rhinitis. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD001563.
Smits WL, Giese JK, Letz KL, Inglefield JT, Schlie AR. Safety of rush immunotherapy using a modified schedule: a cumulative experience of 893 patients receiving multiple aeroallergens. Allergy Asthma Proc. 2007 May-Jun;28(3):305-12.
Reviewed By: Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.
