Atopy or atopic syndrome refers to the genetic predisposition to develop hypersensitivity reactions to allergens. Atopy is characterized by allergic rhinitis, asthma, and atopic dermatitis.
Presentation
Allergic shiners or dark circles under the eyes and nasal crease across the lower half of the bridge are very common features of patients with allergic rhinitis. Mucosa of the nasal cavity is often swollen, with a pale color. Erythema of mucosa may also be noted in some cases. Patients complain of thin, watery nasal secretions. Occasionally, thick, purulent, and colored mucus may be present. Chronic rhinitis is characterized by septal perforation.
Those with mild episodes of asthma may present with breathlessness after physical activity. They may have moderate wheezing with increased respiratory rate. In moderately severe forms of asthma, supraclavicular and intercostal retractions can be noted. Nasal flaring and abdominal breathing are also common. Wheezing may be loud and patients may feel breathless while talking. Affected individuals may feel breathless even while at rest when asthma is severe. Respiratory rate may be more than 30 per minute. Loud wheezing and hunched position is also characteristic of this condition.
Xerosis, lichenification, and eczematous lesions are the three manifestations of atopic dermatitis. Dermatitis is often seen immediately after birth. The eczematous changes may vary with age. The initial lesions may be seen affecting the creases, and this may gradually localize to cheeks, forehead and scalp. Lichenification is commonly seen in childhood dermatitis. In adults the lesions may become more diffuse in nature. Many patients present with a brown macular ring in the neck.
Workup
Testing for specific allergens, based on the history of exposure, is helpful in confirming the allergen triggers of atopy. Allergen immunotherapy may then be based on the type of allergen that causes hyperreaction. Allergy testing also helps to assess the degree of allergen sensitivity. This may be done with allergy skin test, and radioallegosorbent test (RAST). RAST is an in vitro diagnostic test to measure the extent of IgE response to a particular antigen. An elevated serum IgE and eosinophil levels may also refer to allergic reactions, particularly in case of asthma. Asthma is characterized by blood eosinophil level more than 300-400/μL. Serum IgE levels are usually more than 100 IU. Arterial blood gas measurement is used in the assessment of acute asthma. This helps to evaluate the level of hypoxemia, or the presence of respiratory alkalosis. There are no chemical markers for atopic dermatitis.
Treatment
Treatment of atopy has three major categories:
- Avoidance of allergens
- Pharmacological management
- Immunotherapy
Avoiding triggers of allergy including pollen, mites, molds, nonspecific triggers like smoke, and occupational allergens, goes a long way in controlling and preventing allergic rhinitis and asthma. Indoor allergens can be avoided by vacuum cleaning the carpets and rugs, washing bed linens in hot water, and dehumidification. In case of occupational allergens, a mask or a respirator might be of help. If any of the non-specific triggers like smoke, perfumes, or pollution, aggravate the symptoms, completely avoid the same.
High dose allergy shots may be helpful in alleviating symptoms in case of allergic rhinitis. Success rate of this method is found to be as high as 80%-90% with respect to some allergens. Immunotherapy for desensitization is usually continued for 3-5 years. For those affected by asthma, inhaled corticosteroids, long-acting bronchodilators, theophylline, leukotriene modifiers, and anti-immunoglobulin E antibodies are suggested. Short-acting bronchodilators and systemic corticosteroids may be used as relief medications. Rapid-acting beta 2 agonists are used for quick relief from symptoms.
Immunotherapy is used in asthma only when certain criteria are fulfilled. This include presence of symptoms all year round, a clear relationship between symptoms and exposure to allergen, and when pharmacologic management does not give relief. Monoclonal antibody therapy is suggested for patients with severe, persistent asthma, who show reactivity to aeroallergens.
Prognosis
Allergen avoidance, immunotherapy and treatment provide a good prognosis for allergic rhinitis. Failure to manage asthma, may lead to increased mortality, particularly among young patients. Smoking, age above 40 years, and blood eosinophilia may affect a good outcome for atopy. Poorly controlled asthma may lead to many long-term changes in the body. These patients may develop chronic symptoms. Appropriate treatment of atopic dermatitis also provides a good prognosis.
Etiology
The most common cause of the condition is localized hypersensitivity to an allergen. Study on familial inheritance shows that the risk of atopy increases with each family member having manifestations of atopy [2]. Allergic rhinitis, which can be classified as seasonal, sporadic, or perennial, may be caused by pollens, mold, pets, mites, cockroaches, or even rodents. Allergic rhinitis may also be caused by allergens at workplace.
Mutation of filaggrin gene is a strong genetic risk in the development of atopic dermatitis. The susceptible loci is found to be different in different populations. For European population, the susceptible region is 11q13.5, while for Chinese Han population it is 1q21.3. 20q13.33 is also implicated in the development of this condition in both Chinese Han and German population. Staphylococcus aureus infection may cause atopic dermatitis in some. Extremes of climate are known to cause flare up of atopic dermatitis.
Hyperreactivity of bronchi to allergens is caused by environmental allergens, viral infections, hyperventilation, gastroesophageal reflux disease (GERD), obesity, and use of certain medications like beta-adrenergic receptor blockers [3]. Risk of asthma is increased by exposure to acetaminophen in some patients [4]. About 10-15% of bronchial asthma is caused by occupational factors. Jobs like farming, painting, and plastic manufacturing have a high risk of developing atopy. Multiple mutations are also implicated in the development of bronchial hyperreactivity. Asthma may be caused by polymorphisms in certain genes like platelet-activating factor hydrolase [5].
Epidemiology
Atopy is a very common condition in the general population, and the incidence is found to be increasing. Family history is one of the most common risk factor in the development of atopy. About 60% of children with both parents affected by atopy, develop the condition. In those with one of the parents suffering from atopy, 40% of the children are affected. About 10% of the children with neither parents affected, may also develop this condition.
The cumulative prevalence rate of allergic rhinitis in United States is about 20% [6] and about 40 million people in US are affected by allergic rhinitis. The prevalence of the condition may vary with country. The difference arises from the variation in the type and severity of allergen in the region. It is found to affect people of all races, but prevalence may differ. Among children, allergic rhinitis is more common among boys when compared to girls. But the prevalence seem to be more or less equal among the two genders in adulthood. The mean age of onset of allergic rhinitis is around 8-11 years.
Atopic dermatitis affects about 2-10% of adults, and around 15-30% of children. The prevalence of this condition is increasing. In United States, the prevalence is reported around 10-12% in children, and around 0.9% in adults. This condition is also found in all races with a male to female ratio of 1:1.4. Atopic dermatitis has an early onset, often within the first year of life.
About 23.4 million people are reported to be affected by asthma [7]. In childhood, asthma is found to be more common among boys with a prevalence ratio of 2:1. In adulthood, the rate becomes more or less equal among men and women. The prevalence rate is higher among young persons and very old people.
Pathophysiology
Allergic rhinitis, one of the characteristic manifestations of atopy, is caused by inflammation of the membranes of nose, eyes, eustachian tube, middle ear, sinuses and pharynx. This inflammation delevops due to an IgE-mediated response directed towards a foreign protein. Upon inhalation, the allergens bind to IgE, leading to the release of a number of mediators. Typical features of rhinitis like nasal congestion, sneezing, tearing, ear pressure and postnasal drip. The mediators may also continue inflammation leading to late-phase response [8]. Inflammatory response results in fatigue, sleepiness, and malaise.
Pathophysiology of atopic dermatitis is not clearly understood. Inflammation is implicated in the development of the different conditions associated with atopic dermatitis. According to one theory, primary immune dysfunction lead to IgE sensitization causing a disturbance in epithelial barrier. Another theory proposes that a disruption in the epithelial barrier leads to dysregulation of immune function leading to atopic dermatitis. Epithelial barrier disruption is considered to increase the production of cytokines. Loss of filaggrin function due to mutation is reported to increase transepidermal penetration of environmental antigens, leading to atopy [9].
Viral respiratory infections and inflammation play a key role in the development of bronchial hypersensitivity. Airway inflammation, airflow obstruction and bronchial hyper-responsiveness are the three major components of this condition. T-lymphocytes, activated by the presence of antigen, release cytokines leading to airway inflammation. The cell mediators produced by the exposure to antigens bring structural changes in the airway that causes inflammation. Chronic inflammation of the airways is a precursor for bronchial hyper-responsiveness. This results in the typical features of asthma including wheezing, shortness of breath, and coughing. Changes like bronchoconstriction, airway edema, mucous plug formation and structural changes lead to airway obstruction. Airway obstruction is one of the most common cause of hyperinflation.
Prevention
Avoiding triggers that cause or exacerbate the symptoms is the best possible method for avoiding atopy. Using deterrents of triggers is helpful in case of occupational atopy.
Summary
Atopy or atopic syndrome refers to the genetic predisposition to develop hypersensitivity reactions to allergens. Atopy is often characterized by the triad of allergic rhinitis, bronchial asthma, and atopic dermatitis, usually referred to as an atopic triad. Food allergy is also commonly associated with this hypersensitivity. The immune responses are significantly heightened for allergens with increased production of IgE [1]. There is a strong family tendency to develop these allergic reactions. Eczema is often the first manifestation, developing at an early age. This increases the risk of developing other features, which have their onset at a later age. In children, atopy is often used to describe the presence of excessive IgE reaction. The incidence and prevalence of atopic dermatitis is increasing. Rhinitis is the inflammation of the nasal membranes and allergic rhinitis is the most common among the different types. Asthma is a very common chronic condition caused by bronchial hypersensitivity and responsiveness. In majority of cases, patients are sensitized to multiple allergens, though some are hypersensitive to just one or more.
Patient Information
Atopy is an inherited tendency to develop allergic conditions including allergic rhinitis, eczema, and asthma. It is characterized by an exaggerated immune response when exposed to allergens. Prevalence of this condition is increasing in the recent years. The most common cause of the disease is the hypersensitivity to allergens. It may be triggered by allergens like pollen, dust mites, cockroaches, molds and many occupational allergens. Mutations in genes are considered to be the reason behind the development of this hypersensitivity. The most common risk factor of this condition is the family history.
Different types of allergens are known to incite an exaggerated immune response in susceptible people. When exposed to the right trigger, the body responds by secreting a large number of immune mediators which launch an inflammatory response. These inflammatory responses are responsible for the various clinical manifestations of atopy. Appropriate treatment provide a good prognosis for the condition.
Rhinitis is characterized by dark circles under the eyes, crease over the lower half of the nasal bridge, and thin, watery nasal secretions. Breathlessness and wheezing are the symptoms of asthma. Eczema is characterized by the presence of reddish lesions on the body. Testing for specific allergens, based on the history of exposure is the most appropriate diagnostic test for atopy. The two most common tests used for diagnosis include skin allergy test and radioallergosorbent test. Blood eosinophil test is usually conducted for the diagnosis of asthma.
Treatment has three categories – avoiding allergens, medication and immunotherapy. Avoiding triggers is the best possible method for deterring atopy. Immunotherapy helps to densensitize the body towards allergens. Medications like corticosteroids, bronchodilators, and theophylline help in controlling the symptoms.
References
- Pawankar R, Holgate ST, Rosenwasser LJ. Allergy Frontiers: Classification and Pathomechanisms. Japan,Springer; 2009.
- Küster, W, Küster W, Petersen M, Christophers E, Goos M, Sterry W. A family study of atopic dermatitis. Archives of Dermatological Research. 2004;282: 98–102.
- Camargo CA Jr, Weiss ST, Zhang S, Willett WC, Speizer FE. Prospective study of body mass index, weight change, and risk of adult-onset asthma in women. Arch Intern Med. 1999;159(21):2582-2588.
- Beasley RW, Clayton TO, Crane J, Lai CK, Montefort SR, Mutius E, et al. Acetaminophen use and risk of asthma, rhinoconjunctivitis, and eczema in adolescents: international study of asthma and allergies in childhood phase three. Am J Respir Crit Care Med. 2011;183(2):171-178.
- Ito S, Noguchi E, Shibasaki M, Yamakawa-Kobayashi K, Watanabe H, Arinami T. Evidence for an association between plasma platelet-activating factor acetylhydrolase deficiency and increased risk of childhood atopic asthma. J Hum Genet. 2002;47(2):99-101.
- Settipane RA. Demographics and epidemiology of allergic and nonallergic rhinitis. Allergy Asthma Proc. 2001;22(4):185-189.
- Tarlo SM, Balmes J, Balkissoon R, Beach J, Beckett W, Bernstein D, et al. Diagnosis and management of work-related asthma: American College Of Chest Physicians Consensus Statement. Chest. 2008;(3 Suppl):1S-41S.
- Hansen I, Klimek L, Mosges R, Hormann K. Mediators of inflammation in the early and the late phase of allergic rhinitis. Curr Opin Allergy Clin Immunol. 2004;4(3):159-163.
- Kubo A, Nagao K, Amagai M. Epidermal barrier dysfunction and cutaneous sensitization in atopic diseases. J Clin Invest. 2012;122(2):440-447.