Chapter 5 5 Allergic Diseases (and Differential Diagnoses) 5.1 Diseases with Possible IgE Involve- tions (combination of type I and type IVb reac- ment (“Immediate-Type Allergies”) tions). Atopic eczema will be discussed in a separate section (see Sect. 5.5.3). There are many allergic diseases manifesting in The maximal manifestation of IgE-mediated different organs and on the basis of different immediate-type allergic reaction is anaphylax- pathomechanisms (see Sect. 1.3). The most is. In the development of clinical symptoms, common allergies develop via IgE antibodies different organs may be involved and symp- and manifest within minutes to hours after al- toms of well-known allergic diseases of skin lergen contact (“immediate-type reactions”). and mucous membranes [also called “shock Not infrequently, there are biphasic (dual) re- fragments” (Karl Hansen)] may occur accord- action patterns when after a strong immediate ing to the severity (see Sect. 5.1.4). reactioninthecourseof6–12harenewedhy- persensitivity reaction (late-phase reaction, LPR) occurs which is triggered by IgE, but am- 5.1.1 Allergic Rhinitis plified by recruitment of additional cells and 5.1.1.1 Introduction mediators.TheseLPRshavetobedistin- guished from classic delayed-type hypersensi- Apart from being an aesthetic organ, the nose tivity (DTH) reactions (type IV reactions) (see has several very interesting functions (Ta- Sect. 5.5). ble 5.1). It is true that people can live without What may be confusing for the inexperi- breathing through the nose, but disturbance of enced physician is familiar to the allergist: The this function can lead to disease. Here we are same symptoms of immediate-type reactions interested mostly in defense functions against are observed without immune phenomena particles and irritants (physical or chemical) (skin tests or IgE antibodies) being detectable. with clinical symptoms occurring physiologi- These reactions are called “pseudo-allergic re- cally under certain conditions (e.g., secretion, actions”(PARs),theterm“pseudo”onlyre- sneezing, obstruction) and which can take on flecting the not detectable participation of the thecharacteristicsofdiseaseinintenseor immune system and not implying “psychologi- chronic expression [10, 12]. For these com- cal” phenomena. People can die from pseudo- plaints, the term “rhinitis” has been accepted allergic reactions! The term is negatively de- internationally, although the demonstration of fined; with better techniques allowing the de- tection of antibodies or sensitized cells, PAR may turn into true allergy. IgE-mediated drug Table 5.1. Functions of the nose allergies will be covered together with other ) Airway ) Warming of air adverse drug reactions (see Sect. 5.7). ) Olfactory sensory ) Air-conditioner In atopic eczema, IgE antibodies play a role organ ) Body of voice resonance ) Filter organ ) Killing of microbes in many patients in the eliciting phase, albeit in ) closeconnectionwithT-cell-mediatedreac- Humidifier 5.1 Diseases with Possible IgE Involvement 77 inflammation cannot be done in each case. The following mechanisms contribute to the Therefore, “rhinopathy” would be a more logical development of nasal hyperreactivity: term, although it is not often used [3, 4, 10]. Nor- ) Increase in permeability mal findings and disease conditions overlap in ) Increase in sensitivity of irritant receptors rhinitis much more often than in asthma. Often ) Increase in number of receptors per cell the conjunctiva is also affected (“rhinoconjunc- surface tivitis”)(seeSect.5.1.7on“AllergyandEye”). ) Change of nerval impulses in the CNS The most common form of allergic rhinitis ) Increase in number of inflammatory cells and the most frequent atopic disease is pollino- ) Increase in function of effector cells (in- sis (pollen rhinitis, pollen conjunctivitis, pol- creased releasability) len asthma, hay fever, hay asthma, hay rhinitis) ) Hormonal influences (estrogens?) [19]. The disease was known in Arabic medicine Increased mast cells and basophil leukocytes and in the late middle ages it was known as rose (especially during late phase reactions) have fever. The first scientific description dates back been found in the nasal smear in allergic rhini- to 1819 when John Bostock described his own tis [9]. symptoms.Hesawthehighsummertempera- Clinical stigmata of patients with allergic ture as being the cause although many people rhinitis comprise: calledthedisease“hayfever.”Itwasnotuntil ) “Adenoid face” 1873 that Charles Blackley, using a skin and ) Permanent mouth breathing provocation test, proved the disease was caused ) Periorbital halo (“allergic shiners”) by pollen. Wolff-Eisner classified the disease in ) Lower lid edema 1906 as being hypersensitivity against pollen ) “Allergic greeting” (frequent wiping of the protein (the term “allergy” had only just been nose tip) (Fig. 5.1) introduced) (for literature see Chap. 1). ) Lateral fold in the lower nasal part 5.1.1.2 Symptoms and Pathophysiology In industrialized countries, 10–20% of the population suffer from pollinosis [21]. As first symptoms of allergic rhinitis, sneezing (1–2 min after allergen contact) and early se- cretion (5 min) develop triggered by a reflex mechanism. In parallel, edema (obstruction) of the mucosa occurs, reaching a maximum af- ter 30 min with itch, a “nasal voice,” distur- bance of olfactory and gustatory sensation, si- nus complaints, and formation of polyps in the chroniccourseasproductsofhyperplasticrhi- nosinusitis [4, 7, 10, 12]. Aqueous rhinorrhea is due to a cholinergic reflex (possibly via tachykinins) while the symptom of a “blocked nose” is due to vascular dilatation and edema formation. Among the numerous mediators of allergic reactions, histamine plays the most important role in nasal symptoms, but also other media- tors have been found in nasal secretions after allergen provocation such as kinins, eicosa- Fig. 5.1. “Allergic salutation” seen typically in children noids, and proteases [1]. with allergic rhinitis (H. Behrendt) 78 5 Allergic Diseases (and Differential Diagnoses) required. Normally, the diagnosis is done ac- 5.1.1.3 Classification of Different Forms cording to the type of secretion (putrid, milky) of Rhinitis and the rhinoscopic finding. With unilateral In patients with symptoms of rhinitis (itch, symptoms, hemorrhagic secretion and pain- sneezing, secretion, obstruction), other causes fulness, rhinoscopy is obligatory. If the secre- of impaired nasal ventilation have to be exclud- tion is clear or aqueous, further classification ed such as mechanical obstruction, structural into “allergic” and “non-allergic” (also called abnormalities, septum deviation, tumors, for- “vasomotor”) rhinitis is done (Fig. 5.2). eign bodies, atresia, as well as other severe or- While previously allergic rhinitis was clas- gan diseases (cystic fibrosis, Wegener’s granu- sified into seasonal (hay fever) in the spring lomatosis, lepra, or infectious diseases) [6, 19] and summer months and perennial (all year), (Table 5.2). the new WHO classification in the document For the diagnosis of “infectious rhinitis,” Allergic Rhinitis and Its Impact on Asthma usually no detection of an infectious agent is (ARIA) recommends a new classification into “intermittent” (duration of symptoms of less Table 5.2. Classification of rhinitis (according to WHO) than 4 weeks) and “persistent” (symptoms longer than 4 weeks). This new classification, Infectious however, does not replace the practically im- ) Viral ) Bacterial portant distinction between seasonal and pe- ) Others rennial. Allergic Furthermore, the classification of the severi- ) Intermittent ty of allergic rhinitis into “mild,” “moderate,” ) Persistent and “severe” is important. Symptoms like Occupational (allergic, non-allergic) “sleep disturbance,” “impairment of daily ac- ) Intermittent tivities,” “impairment in school or working ) Persistent place,” as well as other impairments in the Drug-induced quality of life are important. ) Acetylsalicylic acid ) Regarding therapy of allergic rhinitis, it is Others important to know that some symptoms such Hormonal as itching, secretion, and sneezing respond Others quite well to antihistamines, while nasal ob- ) NARES (non-allergic rhinitis eosinophilia struction is best treated with corticosteroids. syndrome) This is reflected in the guidelines for therapy of ) Irritants ) Gustatorial rhinitis allergic rhinitis [6]. ) Emotional factors While seasonal allergic rhinitis can mostly ) Atrophic rhinitis be diagnosed with classical allergy diagnosis, ) Gastrointestinal reflux ) in perennial rhinitis sometimes overlaps be- Idiopathic tween allergic (housedust mite allergy) and Rhinitis (Secretion: clear/aqueous) (Secretion: putrid/milky) allergic non allergic infectious (vasomotor) Hyperreactivity eosinophil Fig. 5.2. Breakdown of without inflammation inflammation rhinitis into its various forms 5.1 Diseases with Possible IgE Involvement 79 non-allergic mechanisms are observed. All too mechanistic, although of didactic value forms of rhinitis have in common a hyperreac- [10]. We know that pollen fragments may also tivity of the nasal mucosa similar to bronchial reach the bronchi. hyperreactivity in asthma. In the group of non-allergic vasomotor rhi- 5.1.1.4 Therapy nitis, two forms may be distinguished accord- ing to nasal cytology: an inflammatory form The general therapy of allergic rhinitis is cov- with increased eosinophil granulocytes and the ered in the sections on “Immunotherapy” non-inflammatory form. The form of vasomo-