13 Allergy and Autonomic Dizziness

The prevalence of allergic diseases has been on the increase in the industrialized world for more than 60 years, affecting 10 to 30% of the population1 and more than 1 billion people worldwide. This is expected to reach 4 billion by the 2050s.² The increase in allergic rhinitis, asthma, and atopic eczema is defined as the “allergic epidemic.”¹ Food allergy is becoming more prevalent in the westernized world and has doubled in the last decade, with a sevenfold increase in hospital admissions for severe reactions (anaphylaxis) in Europe. This is known as the “second wave” of the allergic epidemic.³ Sensitization rates to one or more common allergens among school children are currently approaching 40 to 50%.⁴

The terminology used to describe allergic and allergy-like reactions is confusing. Therefore, the World Allergy Organization Nomenclature Review Committee⁵ revised the nomenclature, which now states that the term hypersensitivity should be used for “all reactions” that result in objectively reproducible symptoms and signs initiated by exposure to a defined stimulus that is tolerated by normal persons. Allergy is a hypersensitivity reaction initiated by immunologic mechanisms and can be antibodyor cell-mediated. It can be either IgE-mediated (IgE antibodies) or non-IgE-mediated (IgG antibodies, immune complexes, allergen-specific lymphocytes). Atopy is a genetic (inherited) tendency to produce IgE antibodies, usually to protein allergens in childhood or adolescence, and can produce typical symptoms of eczema, rhinoconjunctivitis, or asthma. Allergy symptoms in a typical atopic individual can be referred to as atopic, as in atopic asthma. Nonallergic hypersensitivity describes hypersensitivity reactions in which immunologic mechanisms cannot be proven (e.g., aspirin hypersenistivity). Sensitivity is an alternative term for special circumstances within the field of environmental medicine (e.g., total drug sensitivity, multiple chemical sensitivity, and symptomatic reactions attributed to amalgam in tooth fillings and electrical waves) that do not fill the criteria to be called hypersensitivity. An allergen is an antigen causing allergic disease.

The allergic diseases are one of the most chronic diseases and involve many organs, such as the eyes, respiratory tract, gastrointestinal tract, and skin. The diseases include rhinoconjunctivitis, asthma, eczema, urticaria, and angioedema, as well as drug and food allergies and anaphylaxis, and they vary in severity and clinical course.¹ Allergic conjunctivitis (AC—acute or perennial) is the most common allergic eye disorder and affects ~ 25% of the population.⁶ Allergic rhinitis (AR) is the most chronic noncommunicable disease, affects 10 to 20% of the total population, and may be a predisposing factor for development of disease in the adjacent structures, such as the paranasal sinuses, middle ear, nasopharynx, and larynx. Failing to diagnose sensitization to inhalant allergens could result in inadequate management of rhinosinusitis, tubal dysfunction, middle ear problems, laryngopharyngeal disorders, and dysphonia. The upper and lower airways are viewed as one entity and AR and allergic asthma are considered part of the airway allergy syndrome.6 Asthma is a global and chronic inflammatory disease affecting 1 to 18% of the population, depending on the country.⁶ The global prevalence of asthma ranges from 4.5% in young adults to 14% in children.⁷ In the industrialized countries, atopic eczema has increased twoto threefold and now affects up to 20% of children and 2 to 10% of adults. This increase in prevalence may be linked to the Western lifestyle.⁶ Food allergy (FA) is an adverse reaction to food, caused by an overreaction of the immune system, and affects ~ 3 to 8% of children and 1 to 5% of adults. These responses can be mediated by IgE antibodies, by immune cells, or by a combination of both.⁸ Drug allergy affects 7% of the general population and has doubled in the last decade.⁶

The inhalant allergens mainly involved are grass pollens, house dust mites, tree pollen, animal dander, and molds and vary according to geographic region. The most common food allergens in children are milk, hen’s eggs, peanuts, tree nuts, soya, and wheat. In adults, the most common food allergens are fish, shellfish, peanuts, tree nuts, fruits, and vegetables. Usually, peanuts, tree nuts, and seafood allergies are seldom outgrown. Other foods may be more prevalent in certain countries. Allergic reactions can be triggered by food, sometimes in very small amounts or even by inhalation and skin contact.⁸ The most common cause of anaphylaxis in children is food; in adults, drugs and Hymenoptera venom. In drug allergy, the most common allergen in children is penicillin; in adults, nonsteroidal anti-inflammatory drugs (NSAIDs), penicillin and related antibiotics, and sulfonamides.

The atopic (allergic) march is defined as the progression of atopic diseases, generally during childhood, and the first steps are usually atopic eczema and food allergies, followed later by respiratory allergies, including asthma and AR.⁶ With early onset of eczema in the first few weeks or months of life, ~ 30% of children will suffer from AR and/or asthma, and if the eczema is more severe, this increases to 50%. In infancy, FA is often seen with eczema, especially in boys, and children with multiple FAs have a higher risk of developing asthma.⁸ Milk, egg, and peanut allergens account for 80 to 90% of all eczema in the infant in the first year of life. Milk protein is the first allergen the infant encounters and milk allergy is the most common FA in infants (2–5%), inducing a larger spectrum of allergic diseases (eczema, asthma, and AR) and possibly heralding the start of a long-lasting atopic disease. Associated hypersensitivity reactions to other foods develop in ~ 50% and allergy to inhalants in 50 to 80% before puberty. Egg-specific IgE, with a positive family history (FH) of atopy, is a highly specific and predictive marker for sensitization to inhalant allergens at 3 to 4 years of age, and the child will develop either upper airway (AR) or lower airway disease (asthma).⁶ Clinical FA and IgE sensitization to food often precede the development of asthma.⁸ About 80% of asthma patients have associated AR and/or rhinosinusitis and 40% of AR patients develop asthma later.⁹

The head and neck are the most commonly affected areas in an allergic response. Lasisi and Abdullahi found ear symptoms in 66% of patients with nasal allergy.¹⁰ Vertigo was found in 13% and peripheral vestibular signs of imbalance were seen in 9%. The scientific basis for the involvement of the inner ear is poorly understood. The endolymphatic sac and duct are considered to be the immunoactive parts of the inner ear that secrete immunoglobulins and immunocompetent cells, and they may be the target of mediators released from the systemic inhalant or food reactions.¹¹ Furthermore, the deposition of circulating immune complex can produce inflammation and interference with the sac’s filtering capability, and a predisposing viral infection may interact with allergies in adulthood and cause the endolymphatic sac to decompensate, resulting in endolymphatic hydrops.¹²

In 1923, Duke was the first to report on a suspected allergic etiology for Meniere’s disease (MD). Derebery has suggested that 30% of patients with MD have food allergy.¹² The prevalence of allergy in patients with MD was established as ~ 41.6% for inhalants and 26.6% for food. The prevalence of type I hypersensitivity reactions to inhalants and food in the MD population evaluated was greater than in the general population. Allergy is believed to be one of the possible extrinsic factors that combine with underlying intrinsic factors to lead to MD.¹³

Electrocochleography (ECoG) has been shown to document changes in inner ear function objectively after intranasal challenge of patients with inhalant allergy (with no prior immunotherapy) and MD, using antigen to which they were most sensitive.¹⁴ Whether immunotherapy is able to reduce symptoms in patients with MD needs further clarification. Although some authors question the role of the sac and hydrops in the development of MD, a significant proportion of patients with cochlear hydrops showed improvement in their symptoms following treatment of inhalant and food allergy.¹² Eustachian tube (ET) dysfunction with blockage may be due to underlying inhalant or food allergies.¹⁵ With or without a middle-ear effusion, ET dysfunction has been considered one of the most common causes of balance disturbances in young children. Balance problems are found in 50% of children with chronic serous otitis media (CSOM) and serous otitis media (SOM) may be associated with both hearing loss and vertigo.16 Mostafa and coworkers found that in adults with CSOM, 54% complained of vertigo. Rotatory chair abnormalities were found in 70% of the cases, caloric hypofunction in 61.6%, and abnormal vestibular evoked myogenic potentials in 25%.¹⁷ These findings implied the involvement of both the semicircular canals and the saccule. Possible mechanisms of inner ear involvement may include pressure changes with restricted movement at the oval and round windows and the spread of toxins, inflammation, and immunocompetent particles to the inner ear.

Alternobaric vertigo is a condition that occurs in scuba divers. Up to 25% of divers may experience it at some time.¹⁸ The dizziness results from unequal pressure changes being exerted between the ears during especially ascent, descent, or immediately after surfacing. It is believed to happen when the two ETs do not function in tandem, with one opening slower or later than the other. Perilymph fistula (PLF) of the oval and round windows is a more serious cause of audiovestibular symptoms and occurs due to rapid pressure changes, especially with underlying ET dysfunction. Since the function of the ET may be influenced by allergy, allergy can therefore contribute to a higher incidence of alternobaric vertigo and PLF.

The existing medical literature supports a correlation between allergy and migraine.¹⁹ Allergy occurs more often in migraine patients with vertigo and motion sickness than in those without. In general, food allergy presents more specifically with migraine headaches, gastrointestinal upset, or chronic colitis. Headaches are otherwise not associated with MD. It is possible that the success of dietary control in the management of migraine with or without vestibular symptoms may be related to the avoidance of an underlying food allergen. Nonallergic (nonimmunological) mechanisms may also be involved for food-related migraine. Additives and chemicals have all been implicated, for example ethanol, sodium nitrate, caffeine, monosodium glutamate, sodium metabisulfite, theobromine, and benzoic acid. This may also depend on the direct effect of the vasoactive amines naturally found in foods, for example histamine, tyramine, phenylethylamine, and serotonin. The largest amount of histamine and tyramine are found in fermented foods such as cheese, alcoholic beverages, canned fish, tuna, sauerkraut, and also in chocolate, peanuts, tree nuts, and coffee, for example. The latter are called “trigger foods,” but milk and wheat have also been implicated. Some patients have symptoms after eating a very small amount of food containing one or more amines, while others react after an accumulative effect of a few days.

Allergy is a major contributor in the development and management of asthma. Individuals with asthma demonstrated a greater area for the center of pressure (CoP) displacement under somatosensory perturbations and a higher velocity in the forward-backward direction on a mobile balance platform when vestibular information only was made available, in comparison to a control group.²⁰ The relationship between asthma and anxiety has consistently been described in the literature. Up to a third of patients with anxiety may experience dizziness and balance disorders.²¹ The strong correlation between anxiety-asthma and anxiety-balance disorders suggests that balance abnormalities may also be present in asthmatic patients.

Balance disorders and ataxia are common with cerebellar disease. Acute cerebellar ataxia has been reported after administration of the human papilloma virus (HPV)-16/18 vaccine, with the short temporal association strongly suggesting an allergic reaction to the vaccine.²² Some patients with celiac disease, the classic form of wheat allergy, develop cerebellar ataxia. This is believed to be due to an immune reaction of the human body to gluten, the protein responsible for wheat allergy, causing damage to the cerebellum.²³ A detailed history should be taken of the indoor and outdoor allergens, the food ingested, environmental factors, and a personal and family history of atopy, to help determine the possible association with the symptom of dizziness. Allergy should be considered in all dizzy patients, especially with bilateral ear involvement, with a history of seasonal or weather-related symptoms, other allergic symptoms, atopic eczema, asthma, and allergic rhinosinusitis, or in patients refractory to usual medical therapy. Lightheadedness and dizziness are common symptoms of food allergies. It can occur immediately after eating the offending food but also hours later, often disguising the relationship between trigger and symptoms. In young children who present with balance problems, unsteady gait, pulling at the ear(s), banging the head against the cot, trouble hearing (especially when spoken to from behind), and restless sleep, CSOM should be considered and the child should be investigated for food allergies. Older children and adults may complain of a “popping” sensation in the ear, earache, or deafness.

Although the bedside neurotologic examination may be normal, the clinician is more likely to observe some symptoms and signs of the specific disease(s) involved. Allergic rhinoconjunctivitis presents with the classical symptoms of rhinorrhea, sneezing, itchy nose and eyes, and watery, red, bloodshot eyes. There is a marked “allergic facies”; twitching of the nose and mouth to relieve itching; a broad nasal bridge together with a nasal crease (Darrier’s line) due to the “allergic salute,” when the patient rubs the nose upward to relieve itching and nasal congestion; mouth breathing due to the blocked nose; and lower lid eye creases (Denne-Morgan lines) together with periorbital edema and bluish-black discoloration under the lower eyelids (“allergic shiners”).9 The comorbid condition of rhinosinusitis presents with blocked nose, with or without polyps, a chronic postnasal drip, enlarged lymphoid tissue of the pharynx (cobblestone appearance), and a cough that is often mistaken for asthma. Evidence of wheezing and eczema may be found. However, eczema lesions around the mouth are an indication that a culprit food or drink has been ingested, as eczema is sparing of the perioral region in the young child. In children with SOM, pneumatic otoscopy and immitance of the middle ear may support the diagnosis.

Allergy diagnosis depends mainly on the clinical history and physical examination and is supported by some tests. Two tests commonly used to determine IgE antibodies are skin prick tests (SPTs) and allergen-specific IgE in the serum (ImmunoCAP). For food allergen SPTs, standardized commercial extracts and fresh extracts can be used. Positive SPTs and allergen-specific serum IgE results for specific food and inhalant allergens indicate sensitization to the allergen, but not necessarily clinical symptoms. Negative results do not indicate that the patient is not allergic, because the reaction may be by other immunologic pathways; for example, milk allergy may be either IgE-mediated or non-IgE-mediated. Elimination of the suspected food(s) or oral food challenges may be necessary to confirm the diagnosis of FA. Generally, the stronger the positive reaction, the more likely the patient is allergic to the allergen. CAST testing (cellular allergen stimulation test) is indicated in certain food allergies, reactions to additives (colorants, flavorants, preservatives), and drug allergies, because these allergens have a small molecular structure and reactions are mainly non-IgE-mediated. CAST testing sensitivity is ~ 80%. Iron-deficiency anemia is common in children with food allergies and recurrent upper respiratory tract infections. Therefore, a full blood count and iron studies should always be done.

Imaging, such as chest X-rays in asthma or computed tomography (CT) of the nose and paranasal sinuses, may support target organ involvement in general allergic disease, but it is usually not helpful in assessing the involvement of the inner ear and vestibular system. In small children with imbalance that persists after management of SOM, magnetic resonance imaging (MRI) with gadolinium is indicated to rule out a posterior fossa tumor. A vestibular test is only requested to support a specific diagnosis, but should not be requested to prove the presence of an allergy. In cases where allergies have been identified as the root cause, the specific treatment can improve the dizziness. However, it is important to first determine the reason for the dizziness and then to treat accordingly, before assuming allergy is the cause. Based on a strong history and clinical findings, treatment can be started empirically for the dizziness.

Allergic rhinoconjunctivitis is mainly a clinical diagnosis and the management is mainly threefold:

1. Environmental control: Avoiding known triggers, such as foods and indoor and outdoor inhalants, as far as possible, together with avoiding the adjuvant triggers, such as cold air, tobacco, and wood smoke.

2. Pharmacotherapy: Second-generation nonsedating antihistamines should be used, such as cetirizine, levoceterizine, fexofenadine, loratidine, and desloratidine, because they have greater selectivity for the peripheral H₁ receptors. Intranasal steroids (INS) are first-line drugs to reduce the inflammation and congestion in the nose and for moderate to severe AR. The main INS are budesinide, beclomethasone, fluticosone propionate, and mometasone. They are often combined with antihistamines. Leukotriene antagonists (e.g., montelukast) are indicated in seasonal AR, in preschool children with AR, and in comorbid asthma and AC. Combination with antihistamines appears to be beneficial.⁹ Topical nasal and ocular antihistamines, together with mast cell stabilizers, are also very effective.

3. Allergen immunotherapy (AIT) is the only disease-modifying treatment with long-lasting effects. The two most common routes are subcutaneous injections (SCIT) and sublingual drops or tablets (SLIT). However, as AIT is given as a treatment for 3 to 5 years, compliance is poor, especially with SLIT, as it requires a daily maintenance dose. Unlike pharmacotherapy, the effects of AIT persists once discontinued and can prevent new allergen sensitizations or progression to asthma. Oral immunotherapy is being investigated for food allergy at present and may prove to be useful in the future.⁶

Although the timing of drainage and placement of ventilation tubes is still debated, it should be seriously considered if a child has SOM or CSOM with balance problems. Peripherally acting histamines, such as loratidine, fexofenadine, and cetirizine, should be used in patients taking betahistine for MD.²⁴ Betahistine is a histamine analogue that has a central effect and is neutralized by centrally acting antihistamines and antidepressants with antihistaminergic properties, such as amitriptyline.

Autonomic Dizziness

Autonomic dizziness is any form of dizziness that follows or is caused by dysfunction of the autonomic nervous system. The attacks in Meniere’s disease (MD) are often accompanied by autonomic manifestations, such as increased heart rate, vomiting, sweating, hyperventilation, and even diarrhea. In this section, however, the focus is on vertigo and disequilibrium caused by autonomic dysfunction.

The incidence of autonomic dysfunction is unknown. Pappas found that 5% of patients presenting with vertigo in his series had autonomic dysfunction.25 Females predominated, with a 15:1 ratio, similar to figures found in other autonomic dysfunction studies. In a series of 1,291 patients presenting with complaints of vertigo, dizziness, or disequilibrium, Ohashi and coworkers found a 10% incidence of orthostatic hypotension (OH).²⁶ Although dysautonomia and OH are well described in the literature, autonomic vertigo is seldom mentioned. Vertigo associated with autonomic dysfunction, OH, or mitral valve prolapse may represent one of several forms of dizziness experienced by the dysautonomic individual. True vertigo may be more common than previously anticipated. OH is defined as dizziness and lightheadedness due to a prolonged drop in blood pressure after standing up and has many potential causes, including heart conditions, dehydration, certain drugs, and heat exposure. Diabetes causes microangiopathy, affecting nerve function, and is an example of a metabolic cause for dysautonomia and OH. Underlying diseases of the brain, spinal cord, or nervous system, such as Parkinson’s disease, multiple system atrophy, pure autonomic failure, and certain neuropathies, cause neurogenic dysautonomia and neurogenic OH. An iatrogenic form of dysautonomia leading to OH is often seen in elderly patients, in whom chronic use of certain medications impairs the reflexive normal autonomic response to changes in body position.²⁷

Patients with autonomic vertigo can present with symptoms similar to those of MD. Autonomic dysfunction has been postulated to play a role in the pathophysiology of MD. In his study of 113 patients with autonomic and vestibular dysfunction, Pappas found that half of the patients presented with spontaneous attacks of rotational vertigo.²⁵ Many had nausea, and in the majority of patients, the attacks occurred daily and lasted for hours. Nearly all the patients had at least one associated otologic symptom. There were also important distinctions from MD in his study. Light-headedness was almost universal (97%), and an additional postural component to the dizziness was present in 50% of patients. Unlike in MD, vertigo worsened with a low-sodium diet or diuretic usage. From the time of onset, a large number had bilateral symptoms, which are not consistent with MD, and although 41% complained of hearing loss, it could actually be shown in only 4%.

It is not known whether autonomically induced vertigo is mediated centrally or peripherally. Impaired cerebral autoregulation is believed to be the mechanism behind central mediation. The peripheral mechanisms include possible autonomic influence of labyrinthine microcirculation or direct modulation of the vestibular neuroepithelium. Pappas supports a peripheral mechanism and believes that the symptom complex of episodic, spontaneous vertigo, ringing or roaring tinnitus, and aural fullness is generally the result of peripheral end-organ involvement. Although hearing loss was rarely measured in his study, electrocochleography (ECoG) findings were consistent with endolymphatic hydrops in 40% of those tested. The long-term improvement in 88% of patients and achievement of high-level function in 74% would not be expected with vertigo of central origin. Another theory is that hyporesponsiveness of the sympathetic nervous system to stress and asymmetric activity of the sympathetic system induce asymmetric blood flow in the vertebral arteries. This may lead to asymmetric activity in the inner ear and/or vestibular nuclei, resulting in the development of vertigo.²⁸

Lightheadedness and postural dizziness are common complaints in addition to vertigo. Any previous episode of syncope is highly suspect. Patients may complain of exertional dizziness (Video 13.1).²⁹ Residual dizziness after successful management of benign paroxysmal positional vertigo (BPPV) has been linked to autonomic dysfunction.³⁰ Otologic symptoms occur bilaterally but unilateral involvement is possible, with one ear being more susceptible or reacting independently from the other.

The neurotologic examination, which is often unrevealing, should include testing for OH. After the resting blood pressure (which may be low) is obtained in the seated position, the patient is requested to stand up. A positive result is defined as a drop of 20 mm Hg in the systolic blood pressure or 10 mm Hg in the diastolic blood pressure within 2 to 5 minutes. If the change in position causes symptoms, it is also considered positive and the onset may be delayed. With a drop in blood pressure, the heart rate usually increases; if it does not, a neurologic cause should be expected. Postural orthostatic tachycardia syndrome (POTS) is characterized by an abnormally long increase in heart rate on getting up. Auscultation of the chest may reveal an abnormal rhythm or a heart murmur suggestive of mitral valve prolapse. Anemia and hypoglycemia should be ruled out. In cases of abnormal findings or if an autonomic disorder is still suspected, a cardiologist who specializes in autonomic dysfunction should be consulted. The test battery will likely include a resting and stress electrocardiogram (ECG), ultrasound of the heart, and 24-hour ambulatory blood pressure and rhythm assessment. The tilt-table test is a reliable test to demonstrate orthostatic intolerance and may be combined with hyperventilation.31 The Valsalva maneuver may help to distinguish between adrenergic and hypervagal autonomic dysfunction. The baroreflex arc mediates both. The handgrip test assesses parasympathetic tone and the echo stress test assesses central and efferent sympathetic function. Depending on the findings, a neurologist’s opinion may be warranted if a neurogenic cause is suspected.

The treatment of autonomic related vertigo is aimed at improving overall autonomic function. Explanation helps to relieve anxiety and postural education may help to reduce symptoms. Hypovolemia caused by anemia, fluid loss, and diuretic use should be addressed. The effects of chronic medication should be critically assessed, especially in the elderly, and if there is uncertainty, the help of a physician should be sought. Intravascular volume expansion for hypotensive patients can be accomplished with increased fluid intake and added salt in the diet. Fludrocortisone causes renal sodium retention and increases the sensitivity of arterioles to norepinephrine. Factors that can aggravate volume depletion and should best be avoided include alcohol, excessive heat exposure, sweating, dehydration, and vasoactive medication, such as certain cold remedies and diet pills. Regular moderate exercise increases the blood-pumping effect of skeletal muscles that could increase venous return and possibly improve vascular tone. Compression stockings improve venous return but are uncomfortable to wear. Peripheral- and central-acting medications that elevate blood pressure include sympathomimetics, β-blockers with negative inotropic effects, dopamine antagonists, prostaglandin inhibitors, and selective serotonin reuptake inhibitors. Anticholinergic drugs can be used to treat unstable autonomic regulation or hypervagal responsiveness. Depending on the condition, caffeine intake can either help or worsen symptoms. Insertion of a pacemaker may help regulate heart rate in some patients. A correct diet and eating regularly helps to avoid insulin spikes and fluctuations in blood glucose. This prevents fatigue and avoids triggering additional autonomic symptoms.

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