Angioedema/Anaphylaxis
This last chapter on sports-related inflammatory reactions discusses proba- bly one of the only potential sports dermatology-related emergencies. Athletes with a predisposition for exercise-induced angioedema/anaphylaxis (EIA) must be extremely cautious because their participation in exercise may lead to res- piratory or vascular collapse. It is important to remember that the term exercise- induced “anaphylaxis” is found throughout the literature, but its nomenclature is a bit misleading. This condition represents a spectrum of disease, and many authors draw parallels with cholinergic urticaria discussed in Chapter 10. Not all athletes with this disease present with vascular or respiratory collapse.
Exercise-Induced Angioedema/Anaphylaxis Epidemiology
Runners seem particularly prone to develop EIA. One study of 278 athletes with the disease noted that 78% experienced outbreaks while running (Shadick et al., 1999). A wide variety of athletes with the condition are reported, includ- ing cyclists, downhill skiers, and basketball, handball, racquetball, and tennis players (Adams, 2004; Nichols, 1992; Shadick et al., 1999; Sheffer and Austen, 1980). It is possible that runners have disproportionately developed EIA because there are a greater numbers of runners. Although most runners exhibit symp- toms after at least moderate activity, some runners develop signs and symptoms with even mild exertion. The mean age of onset of the disease was between 4 and 74 years (mean age 25 years). Females are more likely than males to develop EIA (ratio 2 : 1).
The cause of EIA is unclear. The symptoms of EIA are believed to result from histaminemia after mast cell degranulation (Nichols, 1992;
Sheffer and Austen, 1984). The cause of this degranulation is debatable. The list of possible degranulating promoters includes creatinine phosphokinase, immunoglobulin E, and lactate (Nichols, 1992; Sheffer and Austen, 1980).
Activation of the alternative complement pathway also may be a factor (Stephansson et al., 1991).
Clinical Presentation
Several authors noted a range of signs and symptoms in EIA (Adams, 2002, 2004; Shadick et al., 1999). More than 90% of patients complain of pruritus.
Urticaria is present in 86% of athletes. Angioedema occurs in 70% to 80% of cases and typically is located on the face, palms, and hands (Figure 11-1). Res- piratory symptoms are found in nearly half of the athletes with evanescent wheezing. One third of athletes develop chest tightness and syncope. Less com- monly (25%), athletes experience nausea, diarrhea, and hoarseness. Headache and flushing are seen.
Symptoms can begin within the first 5 minutes of exercise but also can start after exercise is completed. Typical angioedema usually persists, but the angioedema related to EIA resolves in 30 minutes to 4 hours. EIA-related headaches might persist for days.
Diagnosis
The diagnosis of EIA is based on a constellation of clinical findings, includ- ing angioedema and pruritus, with or without respiratory or vascular collapse.
No serologic test can confirm EIA. Patients with angioedema and at least mental status changes, laryngeal edema or hypotension should rapidly be recognized as having EIA and emergently referred for appropriate care.
The differential diagnosis primarily includes cholinergic urticaria (Table 11-1). Athletes with cholinergic urticaria may, like those with EIA, present with respiratory distress. The two conditions differ in two major ways.
Figure 11-1. Athletes with exercise-induced angioedema/anaphylaxis may demonstrate diffuse angioedema on the hands.
EIA exhibits angioedema, whereas cholinergic urticaria produces smaller (few mm to 1 cm), discrete, erythematous papules that may or may not coalesce into larger plaques. Second, although both conditions may present with respiratory distress, the reason for dyspnea in cholinergic urticaria stems from bron- chospasm (Adams, 2004), whereas laryngeal edema causes shortness of breath in EIA. Hypotension occurs only in EIA. It is important to distinguish vascular and respiratory difficulties related to EIA from those related to participation in the sport itself, such as overexertion in hot and humid conditions during a marathon. Another slightly more subtle way to distinguish the two conditions is the fact that sweating seems to exacerbate cholinergic urticaria but has little effect on EIA (Sayama et al., 2002). Furthermore, simple passive warming will not induce EIA but may induce cholinergic urticaria. Provocative tests may be necessary to confirm the diagnosis. Some authors have used a test of cold stimulation before and after exercise to confirm the diagnosis of cold-dependent exercise-induced anaphylaxis in athletes (Sayama et al., 2002).
A condition called vibratory angioedema should be included in the differ- ential diagnosis of EIA. Vibratory angioedema, reported in runners, presents with angioedema alone on the thighs and no associated systemic manifestations (Adams, 2002; Lawlor et al., 1989; Patterson et al., 1972). Like EIA, the angioedema in this sports-related variant does not persist and is caused by the constant vibration experienced during running.
Treatment
The primary treatment for EIA must resolve any respiratory or cardiovas- cular collapse. Athletes may require oxygen, intravenous fluids, and transfer to an emergency facility if an airway cannot be maintained. The subacute treatment of EIA includes antihistamines and epinephrine (Adams, 2002; Sheffer, 1980).
No solid evidence indicates β-agonist inhalers or corticosteroids are helpful.
Table 11-1. Differentiating Exercise-Induced Angioedema/Anaphylaxis from Cholinergic Urticaria
Findings on Physical
Disease Complaint Examination
Cholinergic Shortness of breath 1. Expiratory lung wheezes urticaria Skin rash 2. Small discrete red papules
3. Appropriate blood pressure
4. Appropriate heart rate Exercise-induced Shortness of breath 1. Inspiratory stridor at
angioedema/ Skin rash larynx
anaphylaxis Lightheaded 2. Large areas of Heart racing angioedema
3. Hypotension 4. Tachycardia
Interestingly, more than 25% of athletes with EIA do not use medicine to manage their disease (Shadick et al., 1999).
Prevention
Prevention of EIA is crucial given its potential serious consequences. Obvi- ously avoiding exercise will prevent EIA; however, special techniques make con- tinued participation possible. Several factors increase the risk that an athlete with a predisposition for EIA will develop signs and symptoms (Adams, 2002;
Nichols, 1992; Shadick et al., 1999). Approximately 50% of athletes can prevent EIA attacks by not exercising in extreme hot or cold temperatures. Thirty percent of athletes can exercise without difficulty by not eating before their activity.
Several foods are particularly implicated, such as barley, beans, broccoli, cheese, chicken, egg, garlic, grapes, lettuce, peaches, peanuts, rye, shellfish, tomatoes, and wheat (Adams, 2004). Ingestion of various medicines is associated with EIA flares. These medicines include aspirin, β-lactam antibiotics, and nonsteroidal antiinflammatory drugs. It is important for athletes to avoid these products before competing (Table 11-2).
Regular use of antihistamines seems prudent during exercise and is recom- mended by many authors, although no evidence-based data support this practice (Adams, 2002; Briner and Sheffer, 1992; Kato et al., 1997; Fisher et al., 1999).
Ketotifen has been used to prevent the angioedema of EIA (Nichols, 1992), and cromolyn has been used to help prevent respiratory symptoms of EIA (Adams, 2002; Briner, 1993; Katz et al., 1989).
Athletes with EIA do not experience its signs and symptoms each time they exercise and may have a false sense of security. Afflicted athletes should not practice alone and should be cautioned to carry an epinephrine injectable.
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Table 11-2. Critical History Questions to Ask the Athlete with Suspected Exercise-Induced Angioedema/Anaphylaxis
Do you experience exercise-induced angioedema/anaphylaxis flares more frequently when you . . .
1. Exercise in very cold or very hot conditions?
2. Eat certain foods before exercising?
3. Take aspirin, ibuprofen (or other nonsteroidal antiinflammatory drugs), or antibiotics before exercising?
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