Course Content

Introduction

Colds, allergic rhinitis, and sinus infections are some of the most common conditions for which patients self-medicate and initiate access to the health care system. Many individuals have difficulty differentiating these conditions as they all have similar manifestations and incorporate the same symptoms. However, it is vital to be able to distinguish between these upper respiratory disorders in order to take the appropriate treatment approach.

Therefore, the purpose of this continued education program is to aid health care workers in appropriately identifying key differences between colds, allergic rhinitis, and acute bacterial rhinosinusitis and appropriately managing these conditions.

Colds Introduction

A cold, also known as the common cold, is a viral infection of the upper respiratory tract. Health experts estimate that Americans experience 500 million cases of the cold each year, which makes this illness one of the top five diagnoses in the United States. On average, children usually have 6-10 colds per year while adults younger than 60 typically have 2-3 colds per year. Adults older than 60 years of age usually have only one cold per year. People can develop a cold at any time throughout the year; however, in the United States, the cold season extends from late August through early April. During this time, people are more likely to develop a cold.

Colds are the leading cause of work and school absenteeism. Although colds are usually self-limiting, patients frequently self-medicate because the symptoms are bothersome. Health experts estimate that Americans annually spend $7 billion on nonprescription cold and cough products.

Pathophysiology of Colds

Limited to the upper respiratory tract, colds primarily affect the following respiratory structures: pharynx, nasopharynx, nose, cavernous sinusoids, and paranasal sinuses. The host defense system in the respiratory tract typically protects the body from infection and foreign particles, as it is well innervated and perfused, especially the nose. The nose contains sensory, cholinergic, and sympathetic nerves. When stimulated by an infectious process like a cold virus, these nerves play a role in the resulting symptoms and are also targets for nonprescription treatments. The stimulation of sensory fibers by mechanical and thermal stimuli or by mediators such as bradykinin and histamine results in a sneezing response. Cholinergic and sympathetic nerves are involved in congestion as they innervate glands and arteries in the upper respiratory system that supply the glands. Sympathetic stimulation often constricts arterial blood flow while cholinergic stimulation dilates arterial blood flow. These specific sensory nerves can also respond to a variety of neuropeptide neurotransmitters, which can cause or add to the bothersome symptoms.

Researchers have identified more than 200 viruses that cause colds. Rhinoviruses are the most common viruses that cause colds in children and adults. Other viruses known to cause colds include coronaviruses, respiratory syncytial virus, parainfluenza, adenoviruses, human metapneumovirus, and enteroviruses. A cold caused by a virus like the ones already mentioned can be accompanied by a bacterial co-infection (usually with group A beta-hemolytic streptococci) but is usually rare in occurrence. When a virus like rhinoviruses enters the upper respiratory tract, it binds to intercellular adhesion molecule-1 receptors on respiratory epithelial cells in the nose and nasopharynx. Once inside the epithelial cells, the virus starts to replicate and infection spreads to other cells. Peak viral concentrations are achieved two to four days after initial inoculation, and the virus can be present in the nasopharynx for up to 16-18 days. Once cells are infected by the virus, they release chemokine “distress signals” and cytokines then activate inflammatory mediators and neurogenic reflexes. Once these processes are activated, it results in the recruitment of additional inflammatory mediators, vasodilation, transudation of plasma, glandular secretion and stimulation of pain nerve fibers, and sneeze and cough reflexes. Inflammatory mediators and parasympathetic nervous system reflex mechanisms cause hypersecretion of watery nasal fluid. Viral infection ends once enough neutralizing antibody (secretory immunoglobulin A [IgA] or serum IgG) leaks into the mucosa to attack the virus and end viral replication.

Common cold viruses can be transmitted and spread by three mechanisms: hand contact (via direct contact with an infected person or via indirect contact with a contaminated environmental surface), small particle droplets (droplet nuclei or aerosols) that become airborne from sneezing or coughing, or large particle droplets (droplet transmission) that typically require close contact with an infected person. The most efficient mode of viral transmission is self-inoculation of the nasal mucosa or conjunctiva after contact with virus-laden secretions on animate or inanimate objects. Many of the viruses that cause colds may remain viable on human skin for up to two hours. The risk of person-to-person transfer is dependent upon the amount of time people spend together, the proximity of their contact with one another, and the amount of virus shed by the infected patient. Increased susceptibility to colds has been linked to higher exposure rates, allergic disorders affecting the nose or pharynx, less diverse social networks, and weakened immune systems due to smoking, sedentary lifestyles, chronic psychological stress, or sleep deprivation. Many researchers are conflicted about increased susceptibility due to cold environments, sudden chilling, or exposure to central heating (low humidity); however, these contributing factors have yet to be proven. Walking outside barefoot, teething, and suffering from enlarged tonsils or adenoids have also not been shown to increase susceptibility to viral upper respiratory infections such as the common cold.

Clinical Presentation of Colds

Symptoms from the common cold are typically due to the body’s immune response to infection, rather than direct viral damage to the respiratory tract. Moreover, symptoms usually begin 1-3 days after the initial infection. A sore throat is typically the first symptom to arise, followed by nasal symptoms. Cough develops in roughly 30% of patients by day 4 or 5. Other possible symptoms include malaise and conjunctivitis. Fever is uncommon in adults with a cold but may be present in children, although unlikely. A physical assessment of the patient suffering from a cold may include the following: slightly red pharynx with evidence of postnasal drip, nasal obstruction, and mildly to moderately tender sinuses on palpation. Host factors, such as age, underlying illnesses, and prior immunological experience, as well as the type of infecting virus play a major role in the intensity of symptoms and clinical signs of a cold.

Diagnosis of the Common Cold

The diagnosis of a cold is clinical, based upon reported symptoms and/or observed signs. Physical examination may reveal conjunctival injection, nasal mucosal swelling, nasal congestion, and pharyngeal erythema. Adenopathy is typically absent or minimal; in the absence of secondary bronchospasm, the lung examination is typically clear.

Several clinical scoring systems are available that help differentiate the common cold from other similar upper respiratory disorders. These include the Wisconsin Upper Respiratory Symptom Survey (WURSS) and the Jackson cold scale, but generally have inadequate sensitivity and specificity for use in clinical practice.

Differential diagnosis is extremely important when evaluating a patient for the common cold due to other conditions that mimic similar clinical signs and symptoms. The differential diagnosis should include allergic rhinitis, bacterial pharyngitis or tonsillitis, bacterial sinusitis, influenza, and pertussis. The common cold can be differentiated from simple rhinitis by the presence of a sore throat and cough and from bacterial tonsillitis by the presence of prominent rhinorrhea and nasal stuffiness. Patients with acute rhinosinusitis generally experience a level of facial pain in conjunction with purulent discharge. Patients with influenza typically have a high fever, headache, and myalgias. The main difference between pertussis and the common cold is that pertussis is associated with prolonged coughing, mostly paroxysmal, and with vomiting and sometimes apnea.

Non-Pharmacological Approach for the Common Cold

Although evidence of efficacy is lacking, popular nonpharmacological measures include increased fluid intake, adequate rest, increased humidification (steamy showers, vaporizers, humidifiers), and a nutrition diet as tolerated. Saline nasal sprays help moisten irritated mucosal membranes and aid in the loosening of encrusted mucus. Gargling salt water may ease a sore throat. Hot tea with lemon and honey, chicken soup, and vegetable and other broths may induce a soothing effect as well. Nondrug therapy for all patients, especially infants, should include upright positioning to enhance nasal drainage. Due to children not being able to blow their own noses until the approximate age of 4 years, careful clearing of the nasal passageways with a nasal aspirator is indicated with an accumulation of mucus interferes with sleeping or eating. Nasal aspirators may be mechanically or manually operated (e.g., bulb syringe). To use a bulb syringe and avoid harm to the child, the caregiver should squeeze the large end of the bulb before inserting it, continue to compress the bulb while gently inserting the tip into the infant’s nose, and then slowly release the squeezing pressure to draw out the fluid. After the pressure is completely released, the syringe is removed from the infant’s nose and the fluid is expelled from the syringe by again compressing the bulb.

Proper hygiene should be a top priority in patients suffering from the common cold as it reduces the transmission of cold viruses. The Centers for Disease Control and Prevention (CDC) encourages frequent hand cleansing with soap or soap substitutes, such as hand sanitizers, to limit virus exposure and spread. Disinfectant wipes should also be utilized on popularly used inanimate objects (doorknobs, countertops, toys, etc.) in order to further reduce the risk of transmission and spread.

Pharmacological Approach for the Common Cold

Currently, there is no known cure for colds; the goal of therapy is to reduce bothersome symptoms and prevent the transmission of cold viruses to other persons. Most colds are self-limiting, so symptoms usually resolve on their own in 7-14 days. For a majority of patients, targeted nonprescription therapy will relieve their cold symptoms. Antibiotics are ineffective against viral infections and the mainstay of therapy is nonpharmacological treatment, as mentioned above. If a patient does decide to self-treat, there are five main categories of drugs that target specific symptoms and are preferred over the use of combination products, because symptoms appear, peak, and resolve at different times throughout the course of the infection. Possible pharmacologic therapy options include decongestants, antihistamines, local anesthetics, systemic analgesics, antitussives and protussives (expectorants), and combination products.

Decongestants

These agents specifically treat sinus and nasal congestion. Decongestants are adrenergic agonists and stimulate alpha-adrenergic receptors, which constrict blood vessels and decrease sinusoid vessel engorgement and mucosal edema. These agents are indicated for the temporary relief of nasal and eustachian tube congestion and for cough associated with postnasal drip. These agents are not approved by the U.S Food and Drug Administration (FDA) to self-treat nasal congestion associated with sinusitis.

Three types of decongestants are available: direct-acting, indirect-acting, and mixed-acting. Direct-acting decongestants include phenylephrine, oxymetazoline, and tetrahydrozoline; they work by binding directing to adrenergic receptors. Indirect-acting decongestants, like ephedrine, displace norepinephrine from storage vesicles in prejunctional nerve terminals and tachyphylaxis can develop as stored neurotransmitters are depleted. Mixed-acting decongestants, like pseudoephedrine, have both direct and indirect activity.

Below are the common decongestants and their dosage forms:

Systemic Nasal Decongestants

• Phenylephrine HCL

• Phenylephrine bitartrate

• Pseudoephedrine

Topical Nasal Decongestants

• Ephedrine (0.5%)

• Levmetamfetamine (0.04-0.15 mg/800 mL of air)

• Naphazoline (0.025-0.05%)

• Oxymetazoline (0.025-0.05%)

• Phenylephrine (0.125-1.0%)

• Propylhexedrine (0.4-0.5 mg/800 mL of air

• Xylometazoline (0.05-0.1%)

Adverse effects associated with decongestants include cardiovascular stimulation (high blood pressure, tachycardia, palpitations, or arrhythmias) and CNS stimulation (restlessness, insomnia, anxiety, tremors, fear, or hallucinations). Children and older adults are more likely than persons in other age groups to experience the associated side effects. Additionally, systemic decongestants are more likely to cause adverse effects than topical dosage forms because topical agents are minimally absorbed in the body. However, accidental ingestion of nasal or ocular decongestants can cause adverse effects ranging from nausea, vomiting, and drooling to more serious effects including hypotension, hyperthermia, lethargy, sedation, and coma. Due to topical decongestants being minimally absorbed, more common side effects related to these agents include propellant- or vehicle-associated effects (burning, stinging, sneezing, or local dryness). Rhinitis medicamentosa (RM), also known as rebound congestion, has been associated with the use of topical decongestants. The exact cause of RM is unknown, but short-acting products, preservative agents (benzalkonium chloride), and a long duration of therapy are likely contributing factors. In order to avoid RM, therapy of 3-7 days is the accepted duration for topical decongestants.

Due to the associated side effects of decongestants, they have the potential to exacerbate diseases sensitive to adrenergic stimulation, such as hypertension, coronary heart disease, ischemic heart disease, diabetes mellitus, hyperthyroidism, elevated intraocular pressure, and prostatic hypertrophy. Patients that fall in these medical subgroups should use decongestants only with medical advice.

Antihistamines

Monotherapy with nonprescription antihistamines may provide benefits in adults if started early in the course of a cold (day 1 or 2 of symptom onset). These agents work by blocking histamine within the body, in this case the nose, which causes an itchy nose and swelling. Histamine is released during infectious processes as a host defense mechanism. Antihistamine efficacy in relieving cold symptoms is conflicting, although many patients seek these medications when suffering from the common cold. Apart from questions of efficacy, an important issue is whether the potential benefits of sedating antihistamines outweigh the known risks associated with these drugs. More information about antihistamines will be discussed in the allergic rhinitis section.

Local Anesthetics

A variety of products containing local anesthetics are available for temporary relief of sore throats. These products may be used every 2-4 hours. A thorough history of a patient’s allergies is warranted before using these agents due to many patients reporting allergic reactions to anesthetics and should not be used if allergic to benzocaine. Besides allergic reactions, benzocaine has also been associated with methemoglobinemia, especially in children younger than 2 years, and should be avoided in this age group. Some products contain local antiseptics (cetylpyridinium chloride, hexylresorcinol) and/or menthol or camphor. Local antiseptics are not effective for viral infections. Emerging evidence suggests that menthol and camphor may provide pain relief by stimulation of the TRPM8 or “menthol” receptor.

Below are common local anesthetics used for sore throat cold symptoms:

• Benzocaine

• Pectin

• Dyclonine HCl

• Menthol

• Phenol

Systemic Analgesics

Systemic analgesics, such as acetaminophen, ibuprofen, naproxen, and aspirin, are effective for aches and fever sometimes associated with colds. There has been concern that the use of aspirin and acetaminophen may increase viral shedding and prolong illness but has not been validated. Because of the risk of Reye’s syndrome, aspirin and aspirin-containing products should not be used in children or teenagers who have or are recovering from chickenpox or influenza-like symptoms. Non-steroidal anti-inflammatory drugs (ibuprofen, naproxen, and aspirin) should be used with extreme caution in patients with cardiovascular disease and GI disorders.

Antitussives and Protussives (Expectorants)

When present, cough associated with colds is usually nonproductive. Antitussive agents (codeine and dextromethorphan) have questionable efficacy in colds, and their use in this setting is not recommended. Guaifenesin is an expectorant and has not been proved effective in natural colds due to its lack of efficacy.

Allergic Rhinitis Introduction

Allergic rhinitis, also known as allergic rhinosinusitis, is a systemic disease with prominent nasal symptoms. It is a worldwide problem that affects both adults and children. It is estimated that 8% of adults and 10% of children in the United States are newly diagnosed with allergic rhinitis annually. Direct costs are estimated to be roughly $3.4 billion per year, which includes medications and office visits. When accounting for indirect costs, such as related work and school absenteeism, the annual costs rise to $11 billion.

People suffering from allergic rhinitis have the potential to have an impaired quality of life. Symptoms of the condition generally begin after the second year of life and continue to be prevalent in children and adults 18-64 years of age. After the age of 65 years, the number of cases tends to decrease. The prevalence of allergic rhinitis is higher in the southern United States than in any other region.

Pathophysiology of Allergic Rhinitis

Allergic rhinitis affects the upper respiratory system. The condition is triggered by indoor and outdoor environmental allergens. Upon exposure to an allergen, atopic individuals first undergo a sensitization phase. The allergen stimulates beta-lymphocyte-mediated IgE production. After the sensitization phase, the individual then undergoes the early phase, which occurs within minutes of subsequent allergen exposure. The early phase consists of a rapid release of preformed mast cell mediators (histamine, proteases, etc.) as well as the production of additional mediators, such as prostaglandins, kinins, leukotrienes, and neuropeptides. After the early phase, cellular recruitment occurs. Circulating leukocytes, especially eosinophils, are attracted to the nasal mucosa and release more inflammatory mediators. Lastly, the late phase begins 2-4 hours after allergen exposure and includes signs and symptoms of mucus hypersecretion secondary to submucosal gland hypertrophy and congestion. Continued persistent inflammation primes the tissue and results in a lower threshold for allergic- and non-allergic-mediated triggers (strong odors, cold air, etc.).

Common outdoor aeroallergens include pollen and mold spores. Other nonairborne pollens have also been identified as triggers. Pollutants like ozone, tobacco smoke, and diesel exhaust particles are considered environmental triggers and are becoming more of a concern in highly populated areas. Common indoor aeroallergens include those from house-dust mites and cockroaches, pet dander, and mold spores. Occupational aeroallergens include latex, biologic enzymes, wool dust, resins, organic dust (flour), and various chemicals (glutaraldehyde, isocyanate).

There are many proposed risk factors that contribute to the development and severity of allergic rhinitis. Potential risk factors are listed below:

• Family history of atopy (genetic predisposition to develop allergic diseases)

• Male sex

• Birth during the pollen season

• Firstborn status

• Early use of antibiotics

• Maternal smoking exposure in the first year of life

• Exposure to indoor allergens, such as dust mite allergen

• Serum immunoglobulin E (IgE) > 100 international units/mL before age 6

• Presence of allergen-specific IgE

• Filaggrin (skin barrier protein) gene mutation

• Higher socioeconomic level

• Eczema

• Positive reaction to allergy skin tests

• Poor diet in children and adolescents (consuming three or more fast-food meals per week)
  
  

Clinical Presentation of Allergic Rhinitis

Allergic rhinitis can be classified as intermittent, persistent, and episodic. The condition’s specific classification depends on the timing and duration of symptoms. The symptoms of allergic rhinitis can be further classified as mild or moderate/severe. Below describes the different classifications of allergic rhinitis:

Intermittent

• Symptoms occur < 4 days per week or < 4 weeks

• Mild severity

  • Symptoms do not impair sleep or daily activities, no troublesome symptoms

• Moderate/severe severity

  • One or more of the following occurs: impairment of sleep, impairment of daily activities, troublesome symptoms

Persistent

• Symptoms occur > 4 days per week and > 4 weeks

• Mild severity

  • Symptoms do not impair sleep or daily activities, no troublesome symptoms

• Moderate/severe severity

  • One or more of the following occurs: impairment of sleep, impairment of daily activities, troublesome symptoms

Episodic

• Symptoms occur if an individual is in contact with an exposure that is not normally part of the individual’s environment (i.e., a cat at a friend’s house)

• Severity can be mild, moderate, or severe (based on symptoms)

It is also important to know the key differences between allergic rhinitis from nonallergic rhinitis. The cause of allergic rhinitis is allergen-driven, while the causes of nonallergic rhinitis are broader. For example, nonallergic rhinitis can be caused by hormonal imbalances (pregnancy, puberty, thyroid disorders), structural damages (septal deviation, adenoid hypertrophy), drug-induced (cocaine, beta-blockers, ACEIs, chlorpromazine, clonidine, reserpine, hydralazine, oral contraceptives, aspirin or other NSAIDs, overuse of topical decongestants), systemic inflammatory disorders (eosinophilic nonallergic rhinitis), lesions (nasal polyps, neoplasms), traumatic experiences (recent facial or head trauma), and autonomic or vasomotor conditions (age-related, physical or chemical agent causing parasympathetic hyperactivity). The below table describes the differentiation between the two conditions.

Clinical manifestations of allergic rhinitis include paroxysms of sneezing, rhinorrhea, nasal obstruction, and nasal itching. Postnasal drip, cough, irritability, and fatigue are other common symptoms of the condition. Some patients experience itching of the palate and inner ear. Acute complications of allergic rhinitis include sinusitis and otitis media with effusion. Complications of a chronic nature include nasal polyps, sleep apnea, sinusitis, and hyposmia (diminished sense of smell). Allergic rhinitis and asthma share a common pathology, and allergic rhinitis has been implicated in the development of asthma and exacerbations of preexisting asthma in children and adults. Depression, anxiety, delayed speech development, and facial or dental abnormalities have also been linked to allergic rhinitis.

Diagnosis of Allergic Rhinitis

The diagnosis of allergic rhinitis is primarily made on clinical grounds based upon the presence of characteristic symptoms, such as paroxysms of sneezing, rhinorrhea, nasal obstruction, nasal itching, postnasal drip, cough, irritability, and fatigue. A clinical history, including the presence of patient-specific risk factors, and supportive findings on a physical exam is also useful in correctly identifying the condition. With a physical exam, the nose, oropharynx, tympanic membranes, and eyes should be examined as each of these structures may show findings of allergic rhinitis or associated disorders. Allergy skin testing confirms that the patient is sensitized to aeroallergens but is not necessary for the initial diagnosis. Imaging is not usually warranted in the diagnosis unless a concomitant condition such as chronic rhinosinusitis is suspected or there is a history of facial trauma or features to suggest anatomic abnormalities. Additionally, a positive response to a therapeutic trial of either topical nasal glucocorticoids or topical antihistamines does not conclusively establish a diagnosis of allergic rhinitis, due to these agents also being effective in the treatment of nonallergic rhinitis.

Non-Pharmacological Approach to Allergic Rhinitis

Allergen avoidance is the primary nonpharmacologic method for allergic rhinitis. Avoidance strategies ultimately depend on the specific allergen. House-dust mites (Dermatophagoides spp), found in all but the driest regions of the United States, thrive in warm, humid environments. The main allergen is a fecal glycoprotein, but other mite proteins and proteases are also allergenic. Avoidance strategies, targeted at reducing the mite population, include lowering the household humidity to less than 40%, applying acaricides, and reducing mite-harboring dust by removing carpets, upholstered furniture, stuffed animals, and bookshelves from the patient’s bedroom and other rooms if possible. Mite populations in bedding are reduced by encasing the mattress, box springs, and pillows with mite-impermeable materials. Bedding that cannot be encased should be washed at least weekly in hot (131oF) water; bedding that cannot be encased or laundered should be discarded.

Outdoor mold spores are prevalent in late summer and fall, especially on calm, clear, dry days. Alternaria and Cladosporium are common outdoor allergenic molds; Penicillium and Aspergillus are common indoor molds. Avoiding activities that disturb decaying plants (e.g., raking leaves) lessens exposure to outdoor mold. Indoor mold exposure is minimized by lowering household humidity, removing houseplants, venting food preparation areas and bathrooms, repairing damp basement or crawl spaces, and frequently applying fungicide to obviously moldy areas.

Cat-derived allergens (the Fel d1 family of proteins, secreted through sebaceous glands in the skin) are small and light, and they stay airborne for several hours. Cat allergens can be found in the home months after the cat is removed. Although unproven, weekly cat baths may reduce the allergen load.

Cockroaches are a major source of urban allergens; their saliva, feces, and body parts all have been implicated. To eliminate cockroaches, patients should be encouraged to keep kitchen areas clean, to keep stored food tightly sealed, and to treat infested areas with baits or pesticides.

Pollutants (e.g., ozone, diesel fumes) are an additional concern in urban environments. Pollutants such as diesel exhaust particles are especially irritating to the respiratory tract and have been shown to increase the severity of allergic rhinitis. Patients whose allergies are triggered by air pollutants should be aware of the air quality index (AQI) (a measure of five major air pollutants per 24 hours) and should plan outdoor activities when the AQI is low.

In general, trees produce pollen in spring, grasses in early summer, and ragweed from mid-August to the first fall frost. Knowledge of pollen counts (the number of pollen grains per cubic meter per 24 hours) helps patients plan outdoor activities. Most patients are symptomatic when pollen counts are very high, and only very sensitive patients have symptoms when pollen counts are low. Pollen counts are highest early in the morning and lowest after rainstorms clear the air. Avoiding outdoor activities when pollen counts are high and closing house and car windows reduce pollen exposure.

Ventilation systems with high-efficiency particulate air (HEPA) filters remove pollen, mold spores, and cat allergens from household air but not fecal particles from house-dust mites, which settle to the floor too quickly to be filtered. Filters need to be changed regularly to maintain effectiveness. The systems are expensive and not effective for all patients. HEPA filters are also found in some vacuum cleaners. Weekly vacuuming of carpets, drapes, and upholstery with a HEPA filter-equipped vacuum cleaner may help reduce household allergens, including those from house-dust mites.

Nasal wetting agents (e.g., saline, propylene, polyethylene glycol sprays, gels) or nasal irrigation with warm saline (isotonic or hypertonic) delivered using a syringe or Neti pot may relieve nasal mucosal irritation and dryness, thus decreasing nasal stuffiness, rhinorrhea, and sneezing. That process also aids in the removal of dried, encrusted, or thick mucus from the nose. No significant adverse effects have been noted with the use of nasal wetting agents. Mild stinging or burning has been noted with saline irrigation. Only distilled, sterile, or boiled tap water should be used to prepare nasal irrigation solutions because of the risk of rare but serious infections.

Pharmacological Approach to Allergic Rhinitis

Allergic rhinitis, unfortunately, cannot be cured. The goals of therapy are to reduce symptoms and improve a patient’s functioning status and sense of well-being. The condition is treated in three steps: allergen avoidance, pharmacotherapy, and immunotherapy. Treatment is individualized to provide optimal symptomatic relief and/or control. Since allergen avoidance alone is generally not sufficient to provide complete relief of allergic rhinitis, targeted therapy with single-entity drugs is typically initiated. As more medications become available without a prescription, patients can extensively self-treat. Medications commonly used in treating allergic rhinitis include intranasal corticosteroids, antihistamines, decongestants, and cromolyn sodium. The management of allergic rhinitis is influenced by the frequency and severity of symptoms, the age of the patient, and the presence of concurrent conditions.

Each type of medication will be discussed further below.

Intranasal Corticosteroids

Intranasal corticosteroids (INCS), also known as glucocorticoids, are extremely effective agents for the treatment of nasal symptoms associated with allergic rhinitis such as itching, rhinitis, sneezing, and congestion. These drugs inhibit multiple cell types and mediators, including histamine, and effectively stop the “allergic cascade.” They downregulate inflammatory responses by binding to intracellular glucocorticoid receptors in the cytoplasm of inflammatory cells and enhance anti-inflammatory genes, while also suppressing the transcription of most cytokine and chemokine genes. These agents are the most effective single maintenance therapy for allergic rhinitis and cause few side effects at recommended doses. Concerns with the long-term use of many glucocorticoid preparations include adrenal suppression, slowed growth in children, decrease in bone mineral density, glaucoma, and cataract formation. Due to the drug formulation being topical, the risk of these long-term complications appears to be small because of the limited systemic absorption and relatively low doses involved. More common side effects of these agents include local irritation and epistaxis. Septal perforation is another possible adverse effect but is rare on occasion. INCS can be divided into first- and second-generation preparations, with second-generation formulations carrying a lower risk of systemic effects because of markedly lower total bioavailability. First-generation products include beclomethasone, flunisolide, triamcinolone, and budesonide. Second-generation products include fluticasone propionate, mometasone furoate, ciclesonide, and fluticasone furoate.

Antihistamines

Antihistamines have been used to treat allergies since the 1940s. These agents can be classified as first-generation and second-generation products, where first-generation formulations are significantly more sedating than second-generation formulations. Sedating antihistamines are effective, readily available without a prescription, and relatively inexpensive. However, these antihistamines expose individuals to risks of anticholinergic effects and should be used with caution. Antihistamines work by competing with histamine at central and peripheral histamine-1 receptors that prevent the histamine receptor interaction and subsequent mediator release. In addition, second-generation antihistamines inhibit the release of mast cell mediators and may decrease cellular recruitment. Differences among antihistamines relate to the rapidity and degree to which they penetrate the blood–brain barrier as well as to their receptor specificity. Sedating antihistamines are highly lipophilic molecules that readily cross the blood–brain barrier. Nonsedating antihistamines, large protein-bound lipophobic molecules with charged side chains, do not readily cross the blood–brain barrier. Both types of antihistamines are highly selective for H1 receptors but have little effect on H2, H3, or H4 receptors. The sedating antihistamines have anticholinergic, antiserotonin, and anti–alpha-adrenergic effects.

These agents are indicated for relief of symptoms of allergic rhinitis including itching, sneezing, and rhinorrhea. The adverse effects of antihistamines ultimately depend on receptor activity, chemical structure, and lipophilicity of the drug. The primary adverse effects, CNS effects (depression and stimulation) and anticholinergic effects, are common with first-generation antihistamines but are rarely seen with second-generation agents. CNS-depressive effects include sedation and impaired performance (e.g., impaired driving performance, poor work performance, incoordination, reduced motor skills, and impaired information processing). CNS-stimulatory effects include anxiety, hallucinations, appetite stimulation, muscle dyskinesias, and activation of epileptogenic foci. Adverse effects related to cholinergic blockage include dryness of the eyes and mucous membranes, blurred vision, urinary hesitancy and retention, constipation, and reflex tachycardia. Sedating antihistamines are contraindicated in newborns or premature infants, lactating women, and patients with narrow-angle glaucoma. Additional contraindications include acute asthma exacerbation, stenosing peptic ulcer, symptomatic prostatic hypertrophy, bladder neck and pyloroduodenal obstruction, and concomitant use of MAOIs. Patients with lower respiratory tract diseases (e.g., emphysema, chronic bronchitis) should use sedating antihistamines with caution. People whose activities require mental alertness should not use sedating antihistamines and should use levocetirizine and cetirizine with caution. Patients should also be advised to use sunscreen and wear protective clothing when administering sedating antihistamines, due to these drugs being photosensitizing. Below are the common first- and second-generation antihistamines used in allergic rhinitis:

First-generation antihistamines

• Diphenhydramine

• Chlorpheniramine

• Hydroxyzine

• Brompheniramine

• Doxylamine

Second-generation antihistamines

• Cetirizine

• Levocetirizine

• Loratadine

• Desloratadine

• Fexofenadine

Antihistamines can also be used as topical agents through nasal preparations. These agents include azelastine and olopatadine. Below is a further classification of antihistamines in terms of their activity and adverse effect profile:

Decongestants

Congestion is a common allergic rhinitis symptom controllable with systemic decongestants or with short-term use of topical nasal decongestants. These agents were discussed earlier in the cold section.

Cromolyn Sodium

Cromolyn is a mast cell stabilizer indicated for preventing and treating the symptoms of allergic rhinitis. The agent is thought to work by blocking the influx of calcium into mast cells, which results in the prevention of mediator release. It is approved for use in patients 2 years of age or older and treatment is more effective if started before symptoms begin. It may take 3-7 days for the initial clinical benefit to become apparent and 2-4 weeks of continued therapy to achieve maximal therapeutic benefit. Sneezing is the most common adverse effect reported with intranasal cromolyn. Other possible side effects include nasal stinging and burning.

Clinical Approach to Specific Patient Groups with Allergic Rhinitis

Young Children (< 2 years of age)

• Minimally sedating antihistamines are available in liquid formulations. Cetirizine and fexofenadine are approved for children > 6 months of age

• Sedating antihistamines should be avoided in young children due to the paradoxical agitation risk

• Cromolyn sodium nasal spray is another great option as it is available without a prescription and has essentially no adverse effects because it is not absorbed systemically

• Severe symptoms

  • Changing to glucocorticoid nasal spray is the next step for children with severe symptoms not responsive to the above measures

  • Mometasone furoate, fluticasone furoate, and triamcinolone acetonide are approved by the FDA for use in children > 2 years

Older children and adults

• Mild or episodic symptoms

  • A second-generation oral antihistamine can be administered regularly or as needed (ideally two to five hours before exposure for cetirizine and fexofenadine, while loratadine peaks eight hours after administration)

  • An antihistamine nasal spray can be used effectively in older children. The FDA has approved the use of intranasal azelastine in children > 5 years of age and the use of intranasal olopatadine in children > 12 years of age

  • A glucocorticoid nasal spray is more effective than antihistamines when administered regularly or as needed. For predictable exposures, it is suggested to initiate therapy two days before, continuing through, and for two days after the end of exposure

  • A cromolyn sodium nasal spray is another option

• Persistent or moderate/severe symptoms

  • Glucocorticoid nasal sprays are the most effective pharmacologic therapy for allergic rhinitis and are recommended by guidelines as the best single therapy for patients with persistent or moderate/severe symptoms

  • Possible addition of an antihistamine (non-sedating)

• Moderate/severe asthma

  • Omalizumab and dupilumab are monoclonal antibodies that are available for moderate/severe asthma that is not controlled with high doses of inhaled glucocorticoids and also improves the symptoms of allergic rhinitis, although they are not FDA approved for allergic rhinitis

• Older adults

  • Glucocorticoid nasal sprays are the first-line agents for older adults with allergic rhinitis

Acute Bacterial Rhinosinusitis Introduction

Acute rhinosinusitis is defined as inflammation or infection of the mucosa of the nasal passage and at least one of the paranasal sinuses lasting up to 4 weeks. It is one of the ten most common conditions treated in ambulatory practices in the United States. In a national health survey conducted in 2008, nearly 1 in 7 of all non-institutionalized adults aged > 18 years were diagnosed with rhinosinusitis within the previous 12 months. Incidence rates among adults are higher for women than men, and adults between 45 and 74 years are most commonly affected.

Although most cases are caused by viruses and aeroallergens, as mentioned earlier, some cases can be caused by bacteria; these cases are known as acute bacterial rhinosinusitis. The signs and symptoms of acute bacterial rhinosinusitis and viral upper respiratory infections are similar, which makes accurate clinical diagnosis and appropriate management difficult. The prevalence of a bacterial infection during acute rhinosinusitis is estimated to be 2-10%, whereas viral causes, like the common cold, account for 90-98%. Despite this significant difference in prevalence rates, antibiotics are frequently prescribed for patients presenting with symptoms of acute rhinosinusitis, being the fifth leading indication for antimicrobial prescriptions by physicians in office practices.

Pathophysiology of Acute Bacterial Rhinosinusitis (ABRS)

The pathophysiology of acute bacterial rhinosinusitis is identical to the common cold and other upper respiratory viral infections and has already been discussed in previous sections. However, instead of a viral etiology, a bacterial pathogen is the culprit of the condition, with Streptococcus pneumoniae and Haemophilus influenzae being the two most common causing microbes. Other possible pathogens include Moraxella catarrhalis, Streptococcus pyogenes, Staphylococci, gram negative bacilli, and anaerobic bacteria. Patients with nosocomial infections are more likely to have gram negative organisms, while anaerobic sinus infections are often associated with dental infections or procedures.

Clinical Presentation of ABRS

The clinical presentation of ABRS is very similar to that of viral upper respiratory infections, as mentioned earlier. For example, patients with either condition can present with symptoms of nasal congestion, hyposmia/anosmia, postnasal drip, fever, cough, ear fullness, facial pain/pressure, and sore throat. However, the duration of symptoms is the key differentiating factor when assessing patients for acute bacterial vs. viral rhinosinusitis. The key differences between infectious vs. allergic rhinosinusitis were discussed in the allergic rhinosinusitis section in the table describing allergic rhinitis vs. nonallergic rhinitis. Typically, a viral illness will usually last about 2-7 days, whereas acute bacterial rhinosinusitis persists beyond that time frame causing increased purulent nasal drainage and fatigue. Worsening symptoms after 7 days may indicate that a bacterial infection is present.

Diagnosis of ABRS

The diagnosis of acute rhinosinusitis is based upon clinical signs and symptoms and is diagnosed when patients present with < 4 weeks of purulent nasal drainage and severe nasal obstruction, facial pain/pressure/fullness, or both. The diagnosis is further supported by the presence of secondary symptoms, including anosmia, ear fullness, cough, and headache. Patients are diagnosed with either viral or bacterial acute rhinosinusitis depending on the quality, duration, and progression of symptoms. According to IDSA clinical guidelines for acute bacterial rhinosinusitis, the following clinical presentations (any of 3) are recommended for identifying patients with acute bacterial vs. viral rhinosinusitis:

• Onset with persistent symptoms or signs compatible with acute rhinosinusitis, lasting for > 10 days without any evidence of clinical improvement

• Onset with severe symptoms or signs of high fever (> 39oC) and purulent nasal discharge or facial pain lasting for at least 3-4 consecutive days at the beginning of illness

• Onset with worsening symptoms or signs characterized by the new onset of fever, headache, or increase in nasal discharge following a typical viral upper respiratory infection that lasted 5-6 days and were initially improving (also known as double-sickening)
  
  

Pharmacological Approach to ABRS

Empiric antimicrobial therapy should be initiated as soon as the clinical diagnosis of ABRS is established as defined in the diagnosis section above. The type of antimicrobial therapy is based on age, penicillin allergies, and risk factors for resistance. Risk factors for resistance include age < 2 years or > 65 years, daycare exposure, prior antibiotic usage within the past month, prior hospitalization within the past 5 days, comorbidities, or immunocompromised hosts. Below are the specific IDSA recommendations in treating patients with ABRS:

Antibiotic Therapy of ABRS in Adults

• No risk factors for resistance

  • No penicillin allergy (one of the following)

    • Amoxicillin/Clavulanate 875 mg by mouth twice daily

    • Alternative = doxycycline 100 mg by mouth twice daily

    • Duration of therapy = 5-7 days

  • Penicillin allergy (one of the following)

    • Doxycycline 100 mg by mouth twice daily

    • Moxifloxacin 400 mg by mouth daily

    • Levofloxacin 500-750 mg by mouth daily

    • Duration of therapy = 5-7 days

  • Penicillin allergy (one of the following)

    • Doxycycline 100 mg by mouth twice daily

    • Moxifloxacin 400 mg by mouth daily

    • Levofloxacin 500-750 mg by mouth daily

    • Duration of therapy = 7-10 days

• Risk factors for resistance

  • No penicillin allergy (one of the following)

    • High dose amoxicillin/clavulanate (2 grams) by mouth twice daily

    • Alternative = doxycycline 100 mg by mouth twice daily

    • Duration of therapy = 7-10 days

Antibiotic Therapy for ABRS in Children

• No risk factors for resistance

  • No penicillin allergy

    • Amoxicillin/clavulanate 45 mg/kg/day by mouth divided into twice-daily administration

    • Duration of therapy = 5-7 days

  • Penicillin allergy (one of the following)

    • Levofloxacin 10-20 mg/kg/day by mouth divided into once or twice-daily administration

    • Clindamycin 30-40 mg/kg/day by mouth divided into three administrations daily plus cefixime or cefpodoxime 8-10 mg/kg/day by mouth divided into twice-daily administration

    • Duration of therapy = 5-7 days

  • Penicillin allergy (one of the following)

    • Levofloxacin 10-20 mg/kg/day by mouth divided into once or twice-daily administration

    • Clindamycin 30-40 mg/kg/day by mouth divided into three administrations daily plus cefixime or cefpodoxime 8-10 mg/kg/day by mouth divided into twice-daily administration

    • Duration of therapy = 7-10 days

• Risk factors for resistance

  • No penicillin allergy (one of the following)

    • High dose amoxicillin/clavulanate (90 mg/kg/day) by mouth divided into twice-daily administration

    • Levofloxacin 10-20 mg/kg/day by mouth divided into once or twice-daily administration

    • Clindamycin 30-40 mg/kg/day by mouth divided into three administrations daily plus cefixime or cefpodoxime 8-10 mg/kg/day by mouth divided into twice-daily administration

    • Duration of therapy = 7-10 days

Adjunctive therapies may be beneficial for symptom management in certain patients. Intranasal saline with either physiologic or hypertonic saline can be used to loosen encrusted mucus in the nose. Intranasal corticosteroids may pose a benefit for patients suffering from severe nasal congestion and nasal symptoms, particularly in patients with a history of allergic rhinitis.