A 16-Year-Old Girl With a Rash and Shortness of Breath - An Interesting Case Study

Clinical History: 
A 16-year-old girl presents to the emergency department with generalized pruritus, eye swelling, a full-body rash, and shortness of breath after playing basketball at school. She reports that she was playing basketball with her friends when she first noticed itchy palms. She stopped playing and washed her hands. The itch worsened and was followed by a rash and shortness of breath. She also felt that her throat was tightening, and she had difficulty swallowing. She was taken to the school nurse, paramedics were called, and she was brought to the local emergency department.

The patient has had several similar episodes within the past year and feels that the episodes are getting worse. The first episode occurred about 1 year ago while playing volleyball in a hot gym. She developed itchy palms and stopped to go drink some water; the itchiness went away without any medical attention. Recently, the episodes have been occurring more frequently and are more severe. Some episodes are associated with even mild physical exertion, especially when the temperature outside is hot. When she stops the physical activity, the symptoms typically go away. She cannot recall eating any specific foods that are related to her episodes. She is not taking any medications, vitamins, or herbal supplements.

The patient is otherwise healthy, with no significant medical history. She denies any malaise, fatigue, weight loss, nausea, vomiting, fever, or joint pain. She is in the 11th grade and does well in school, getting mostly A's and only a few B's. She wants to go to college. She has many friends at school. She enjoys biking, dancing, and texting. Occasionally, dancing causes her to feel itchy, but she just "takes a break," and the itch goes away.

Physical Examination and Workup

Upon physical examination, the patient is a well-nourished, well-developed teen in mild respiratory distress. Her temperature is 98.6o F, respiratory rate is 30 breaths/min, heart rate is 110 beats/min, and blood pressure is 100/60 mm Hg. Periorbital angioedema and facial erythema are noted. Extraocular eye movements are within normal limits. Her nasal cavity shows normal nasal mucosa, septum, and turbinates bilaterally.

Upon throat examination, no erythema or exudates are present, and the tonsils are normal, without enlargement or inflammation. No neck stridor or jugular venous distension is observed. Auscultation of the lungs reveals bilateral diffuse wheezes. Cardiovascular examination reveals sinus tachycardia, regular rhythm, and an absence of murmurs.

The patient's extremities are warm and well-perfused. No lower-extremity edema, cyanosis, or clubbing is noted. A skin examination reveals diffuse urticaria and generalized warmth,

Management: 

She was given epinephrine (0.3 mg intramuscularly), diphenhydramine (50 mg intravenously), and methylprednisolone (125 mg intravenously). She was given nebulized albuterol for wheezing. Her symptoms resolved within 30 minutes.

Question: 

Which of the following is the most likely diagnosis?
A. Hereditary angioedema
B. Cholinergic urticaria
C. Exercise-induced anaphylaxis
D. Systemic mastocytosis
E. Idiopathic anaphylaxis

Answer: C. Exercise-induced anaphylaxis

Discussion
Exercise-induced anaphylaxis (EIA) is a rare disorder in which anaphylaxis occurs after physical activity. The symptoms may include pruritus; hives; flushing; wheezing; and gastrointestinal involvement, including nausea, abdominal cramping, and diarrhea. If physical activity continues, patients may progress to more severe symptoms, including angioedema; laryngeal edema; hypotension; and, ultimately, cardiovascular collapse. Cessation of physical activity usually results in immediate improvement of symptoms. The typical age of onset of EIA is from adolescence to the third decade of life.

Patients with EIA often have prodromal symptoms that alert them to impending severe symptoms if physical activity continues.[2] Prodromal symptoms may include a feeling of fatigue, generalized warmth and pruritus, and cutaneous erythema. These early symptoms are followed by typical urticarial lesions and angioedema that can progress to gastrointestinal symptoms, laryngeal edema, and/or vascular collapse.

Symptoms may begin at any stage of exercise. Although cessation of the physical activity usually results in immediate improvement or resolution of symptoms, some patients may experience vascular collapse even after exercise cessation. The frequency of symptoms during exercise varies among patients with EIA. Most patients can exercise regularly and only occasionally experience attacks.

Vigorous forms of physical activity, such as jogging, tennis, dancing, and bicycling, are more commonly associated with EIA, although lower levels of exertion (eg, walking, yard work) are also capable of triggering attacks. In a long-term follow-up study, the physical activity most often associated with exercise-induced anaphylaxis was jogging.Other reports have implicated running, soccer, raking leaves, shoveling snow, and horseback riding.

EIA attacks may not be consistently elicited by the same type and intensity of physical activity in the same patient. Such cofactors as foods, alcohol, temperature, drugs (eg, aspirin, other nonsteroidal anti-inflammatory drugs), humidity, seasonal changes, and hormonal changes are important in the precipitation of attacks.

A distinct subset of EIA is food-dependent EIA (FDEIA), in which anaphylaxis develops only if physical activity occurs within a few hours after eating a specific food. Neither food intake nor physical activity by itself produces anaphylaxis. The foods most commonly implicated in FDEIA include wheat, shellfish, tomatoes, peanuts, and corn. However, the disorder has been reported with a wide variety of foods, including fruits, seeds, milk, soybean, lettuce, peas, beans, rice, and various meats. One case report described a patient who developed symptoms of anaphylaxis only after simultaneous ingestion of two foods (wheat and umeboshi) before exercise. In the nonspecific form of FDEIA, eating any food before exercise induces anaphylaxis.

Inhalant allergens have also been implicated in EIA. In a case report, a 14-year-old boy presented with severe EIA after ingestion of Penicillium mold-contaminated food and running at school. 

In another case report, a 16-year-old girl presented with EIA after ingestion of wheat flour contaminated with storage mites.

Differential Diagnosis: 

The differential diagnosis for EIA includes 

• cholinergic urticaria, 
• idiopathic cold urticaria, 
• mastocytosis, 
• cardiovascular disorders, 
• food allergy exacerbated by exercise, and 
• angioedema.

Cholinergic urticaria is a form of physical urticaria that can be precipitated by exercise. The skin lesions are distinctive and appear as 2- to 4-mm pruritic wheals surrounded by extensive areas of macular erythema. Rare reports describe patients with cholinergic urticaria who develop recurrent episodes of hypotension, which may mimic EIA. Key distinguishing features include the size of the skin lesions and the underlying pathophysiologic features. Cholinergic urticaria usually produces pinpoint hives, which may coalesce to larger lesions; in contrast, EIA produces giant hives.

Passive heat challenges are valuable in differentiating between cholinergic urticaria and EIA. In cholinergic urticaria, passive heating (eg, hot baths, saunas) with an increase in core body temperature of more than 33°F causes histamine release, urticaria, and anaphylactic symptoms. In contrast, patients with EIA do not react with passive heating.

Idiopathic cold urticaria is a form of physical urticaria characterized by the development of urticaria and/or angioedema after cold exposure. Other organ systems may become involved, which may progress to frank anaphylaxis. Anaphylaxis has resulted in deaths either directly from the anaphylactic reaction or by drowning when swimming in cold water. Patients with idiopathic cold urticaria who experience symptoms from exercising in cold weather may be misdiagnosed with EIA. Ascertaining whether passive cold exposure in the absence of exercise can elicit symptoms is important.

An ice-cube challenge test is useful in differentiating between cold-induced urticaria and EIA. This test entails the application of an ice cube for a certain period (usually 10 minutes), followed by a period of rewarming. Patients with idiopathic cold urticaria develop a wheal at the ice-cube site after the skin is rewarmed.

Mastocytosis is a disorder characterized by mast cell proliferation and accumulation within various organs, most commonly the skin. Patients with mastocytosis are susceptible to anaphylaxis from various triggers, including exercise.

A useful distinguishing feature between EIA and mastocytosis is the serum tryptase level. Patients with mastocytosis have persistent elevation in serum tryptase levels, whereas patients with anaphylaxis from other causes (EIA and FDEIA) demonstrate elevation of tryptase only during acute attacks. In addition, patients with mastocytosis may have characteristic cutaneous findings of urticaria pigmentosa, characterized by oval or round red-brown macules, papules, or plaques. Gently stroking normal skin may produce raised wheals and a burning or itching sensation (Darier sign).

Cardiac events, such as myocardial infarction and arrhythmias, can cause sudden fatigue, dyspnea, and vascular collapse during exercise. However, cardiovascular disorders do not cause pruritus, urticaria, angioedema, and laryngeal edema.

Patients with food allergy may have more severe and frequent reactions with concomitant exercise. Exercise increases gastrointestinal permeability, which may allow increased entry of intact or incompletely digested allergens into the circulation. In the case of FDEIA, demonstrating that patients can tolerate the offending food in the absence of physical activity is essential. A formal food challenge may be helpful in this regard.

Hereditary angioedema is an inherited disease resulting from a deficiency or dysfunction of the C1 inhibitor enzyme. 

Acquired angioedema is caused by autoimmune interference with C1 inhibitor enzyme function.

Both the hereditary and acquired forms are characterized by recurrent episodes of angioedema, without urticaria or pruritus, which most often affect the skin or the mucosal tissues of the upper respiratory and gastrointestinal tracts. Angioedema attacks may be precipitated by exercise, stress, and cold exposure. A key distinction between hereditary or acquired angioedema and EIA is the absence of urticaria and pruritus in hereditary and acquired angioedema.

Management: 

Intramuscular epinephrine is the drug of choice for acute attacks of EIA or FDEIA. Early administration of intramuscular epinephrine is associated with decreased mortality in patients with anaphylaxis.

Other medications play an ancillary role in the treatment of anaphylaxis. H1-antihistamines relieve itch and hives, but they do not relieve airway obstruction or shock. Beta-2–adrenergic agonists relieve bronchospasm, but they do not relieve upper-airway obstruction or shock. Glucocorticoids might prevent protracted or biphasic symptoms, but they do not provide rapid relief of upper or lower-airway obstruction, shock, or other symptoms of anaphylaxis.

Long-term management of EIA and FDEIA must be individualized to each patient because the severity, frequency, and intensity of exercise needed to trigger anaphylaxis and the possible association with other cotriggers all vary. Other medications, such as oral steroids, leukotriene-modifying agents, and omalizumab, are either unstudied or reported only in isolated cases.

Patients must understand the emergent nature of EIA and the proper use of emergency injectable epinephrine. Instruct patients with EIA to recognize the early warning signs and symptoms and stop physical activity to prevent progression of the syndrome. This includes limiting exercise and being cautious in temperature extremes.

Patients with FDEIA or medicine-dependent EIA need to be aware of the offending food or medication (if specific ones can be identified) and know how long to refrain from exercise after eating. Educate patients with EIA about the need to exercise with a partner who is aware of EIA and the emergent nature of an episode.

The prognosis of patients with EIA is generally favorable. Most patients experience fewer and less severe attacks over time. Although rare, several fatalities have been attributed to EIA or FDEIA. No cure for these disorders is known. With appropriate lifestyle changes, however, patients may be able to reduce or eliminate episodes of anaphylaxis, and prompt intervention can abort episodes that do occur.

The patient in this case was counseled and given appropriate instructions on necessary preparations and interventions, as described above.

Question:

Which of the following is the drug of choice for the treatment of EIA?
A. Albuterol
B. Antihistamines
C. Glucocorticosteroids
D. Epinephrine

Answer: D. Epinephrine

Discussion: Intramuscular epinephrine is the drug of choice for acute attacks of EIA or FDEIA. Early administration of intramuscular epinephrine is associated with decreased mortality in patients with anaphylaxis.
Other medications play an ancillary role in the treatment of anaphylaxis. H1-antihistamines relieve itch and hives, but they do not relieve airway obstruction or shock. Beta-2–adrenergic agonists relieve bronchospasm, but they do not relieve upper-airway obstruction or shock. Glucocorticoids might prevent protracted or biphasic symptoms, but they do not provide rapid relief of upper or lower-airway obstruction, shock, or other symptoms of anaphylaxis.

Question:
Which of the following foods is more commonly associated with FDEIA?
A. Egg
B. Milk
C. Soy
D. Wheat

Answer: D. Wheat

Discussion: The foods most commonly implicated in FDEIA include wheat, shellfish, tomatoes, peanuts, and corn.

[ The original article is taken from Medscape. Go to the link below for the original article:

http://reference.medscape.com/viewarticle/881373?src=wnl_casechlg_170619_mscpref&uac=279219PX&impID=1371339&faf=1]