Cholinergic UrticariaCholinergic urticaria is a common condition of young adults, affecting up to 15 per cent of adolescents and up to 7 per cent of subjects with chronic urticaria. It manifests as a pruritic, blotchy red rash (with or without superimposed 1-3 mm papules). It is triggered by sweating, emotional stress, elevation of core body temperature (e.g. saunas) or by hot or alcoholic beverages. These all activate sweat glands via the cholinergic, sympathetic nervous system.
Symptoms usually develop during or just after the cessation of exercise and normally resolve within an hour. Occasional patients develop bronchospasm / asymptomatic reduction in FEV1. Elevation of circulating histamine has been documented during episodes, consistent with mast cell degranulation being involved in pathogenesis. Whilst degranulation was initially thought to be due to acetylcholine released by nerve endings adjacent to mast cells, neuropeptides may in fact play a more important role.
Once patients fail to respond to prophylactic antihistamines, management is generally difficult. Elimination diets are only occasionally helpful. Attempts to "desensitize" the patient to increasing amounts of exertion rarely meet with success. Attenuated androgens have been used in case reports, although the side-effect profile is unacceptable to all but the most severely affected subjects.
Exercise-Induced
Urticaria and AnaphylaxisFirst described by Sheffer and Austen in 1980, exercise-induced anaphylaxis typically affects young adults. Manifestations include itch (92 %), urticaria (83 %), angioedema (78 %), bronchospasm (59 %), sweating (43 %), syncope (32 %), gut upset (30 %) or nasal congestion (rare).
Some patients have milder or unusual symptoms such as isolated exercise-related urticaria, abdominal pain or cardiovascular collapse. Unlike cholinergic urticaria, however, the weals are usually quite large and are not induced by heat or sweating alone. The mechanism appears to be related to the release of neuropeptides by nerve endings adjacent to mast cells, leading to degranulation.
Some experience symptoms with exercise alone; others will only do so if allergenic foods are ingested around the same time. Foods implicated in this syndrome include wheat and other cereals, celery, seafood, nuts, fruit and some vegetables. The severity of symptoms is generally influenced by the amount of food ingested, the vigor of exercise and the time between the two. Thus severe symptoms are usually due to food eaten only a few hours earlier.
Symptoms usually occur during exercise. Less commonly, symptoms are triggered when the allergenic food is ingested following exercise. Co-factors that enhance the likelihood or severity of an allergic reaction include exercise, alcohol, spicy food, NSAIDS or a high ambient temperature.
Patients at risk of anaphylaxis should wear an identifying MedicAlert bracelet, which will increase the likelihood that adrenalin will be administered in an emergency. They should avoid medication that may enhance the severity of anaphylaxis or complicate its treatment. Beta blockers (and perhaps ACE inhibitors) fall into the first group as they inhibit counter-regulatory mechanisms that may protect from uncontrolled hypotension.
Patients in whom episodes are unpredictable,
who are allergic to foods that are extremely difficult to avoid
or when the cause cannot be identified should carry injectable
adrenalin and be trained in its use. Patients in whom exercise
is a co-factor are best advised to premedicate with H1 and H2
antagonists, to exercise in the morning before eating, to carry
injectable adrenalin, to not exercise alone and to consider carrying
a mobile telephone.
The nasal cavity is richly innervated. Sympathetic nerves control vascular tone by innervating blood vessels and venous sinusoids. The fluctuation of sympathetic tone throughout the day results in variations in the patency of alternate nostrils every few hours (the "nasal cycle"). Various reflexes ensure that the upper nostril is relatively clear when recumbent.
Parasympathetic nerves, on the other hand, induce vasodilatation within the nose and glandular secretion. In most subjects (atopic or otherwise), exercise results in a transient increase in nasal patency due to sympathetic nerve stimulation.
Exercise rhinitis is associated with rhinorrhoea and nasal congestion related to autonomic imbalance, mediator release, or both. It affects a significant proportion of athletes and can influence performance. Whilst the mechanism is uncertain, hyperosmolarity of the nasal mucosa (as might occur with increased nasal ventilation rates) has been shown experimentally to result in prostaglandin D2, histamine, bradykinin, mast cell tryptase and leucotriene C4 release and may be one potential explanation.
This provides a rationale for trying to limit heat and moisture loss from the nasal epithelium by the wearing of masks or balaclavas, particularly when exercising in cool dry air, as has been used with some success to limit the severity of exercise-induced asthma. Unfortunately, antihistamines generally have a disappointing effect on symptoms even when taken prophylactically.
Cold-induced rhinorrhoea / congestion ("skiers nose") is an associated condition which has been associated with hyperosmolarity of the nasal mucosa and release of inflammatory mediators such as Prostaglandin D2 , histamines, kinins and TAME-esterase. "Late responses" are occasionally seen in experimental inhalation of cool dry air, analogous to that seen in patients exposed to allergen. Symptoms are usually refractory to treatment with antihistamines but partially responsive to intranasal ipratropium bromide. This suggests that the condition may be primarily a cholinergic reflex, although is likely to involve a complex mixture of neurogenic reflexes and the effects of local mediator release on parasympathetic nerve endings.
Patients with preexistent rhinitis may have their symptoms influenced by exercise. Non-allergic (vasomotor) rhinitis without eosinophilia is thought to represent an imbalance between sympathetic and parasympathetic nerve activity resulting in nasal congestion, rhinorrhoea or both. An increase (rather than decrease) in nasal congestion is typically observed with exercise, thought to be due to relative sympathetic hyporesponsiveness to the stimulating effects of exercise.
Those with allergic rhinitis, however, usually decongest with exercise in the usual way, but may then suffer a transient increase in congestion once the exercise stops, perhaps related to an exaggerated "nasal cycle" in some patients. Both forms of rhinitis may respond to regular administration of intranasal corticosteroids.
Exercise-induced asthma (EIA) has a prevalence in various surveys of 10 to 15 per cent of random adolescents, 40 to 50 per cent of subjects with allergic rhinitis and 40 to 90 per cent of patients with asthma. It is generally defined as a decrease in FEV1 of 15 per cent or more with exercise.
Whilst the mechanism is uncertain, the best evidence is for exercise-related hyperventilation and evaporative water loss from the airways, resulting in hyperosmolarity and mast cell degranulation. Not only is there evidence for release of preformed mediators such as histamine, but also for the production of synthesized mediators such as leucotrienes, isolated from bronchioalveolar washes in some studies.
Reproduction of symptoms occurs with "free runs", the inhalation of cool dry air or hyperosmolar saline, all of which are likely to induce airway hyperosmolarity. Climatic factors such as temperature and humidity, and the presence of recent aero allergen exposure, will increase bronchial hyperreactivity and the likelihood of EIA.
Methods of inhibiting EIA include a submaximal exercise warm-up period or the wearing of a mask (or scarf or balaclava) to minimize heat and moisture loss. Pharmacological agents display varying effectiveness. Short acting bronchodilators such as salbutamol or terbutaline protect for 2 to 3 hours. Salmeterol and eformoterol are active for up to 12 hours. Nedocromil and cromoglycate prevent early and late exercise induced bronchospasm. Leucotriene antagonists and long-term inhaled steroids are also effective.
