PHYSIOLOGY

Urticaria is characterized by an erythematous wheal accompanied by a subjective sensation of itching [4]. The urticarial response has been described as a defense mechanism against an unwanted intrusion, a contact with an allergen with which continued exposure leads to the release of IgE antibodies [5].

All forms of urticaria seem to involve the irritability and degranulation of cutaneous mast cells. Mast cells are located in the loose connective tissue and are more concentrated in the perivascular areas such as the lips, eyelids, and scalp [3]. Multiple stimuli, both immunologic and non-immunologic, are considered unwanted intruders and lead to the release of preformed mediators and the generation of newly formed mediators [5,6]. Many inflammatory mediators have been identified in urticaria; the most common of these is histamine, which is vasoactive and generally causes symptoms such as pruritus, erythema, inflammation, angioedema, and potentially fatal hypotension. While histamine is the primary mediator found in all physical urticarias, the variable success rate with histamine blockers strongly suggests the presence of other mediators [5,7]. The measurement of these mediators in the blood, however, is difficult due to rapid metabolism.

There are numerous types of urticarias, and countless etiologies. Physical urticarias constitute approximately 17% to 20% of all urticarias [5,8]. There are a number of ways of classifying the urticarias; for example, they can be classified on the basis of immunologic or non-immunologic etiologies, or by whether they are chronic or acute. Table 1 depicts an overview of the urticarias based on etiology and presenting cause.

The physical urticarias are different from other urticarias in that the characteristic wheals can be reproduced by a physical stimulus such as cold, heat, pressure, vibration, sunlight, water, exercise, and increases in core body temperature [9]. In addition to being a distinct group of reactions, the physical urticarias can also be classified as acute, persisting for less than 4 to 6 weeks, or chronic, persisting for more than 6 weeks [3].

The physical urticarias include cholinergic urticaria, cold urticaria, dermographism, delayed pressure urticaria, solar urticaria, aquagenic urticaria, vibratory urticaria, external localized heat urticaria, and exercise-induced anaphylaxis. These reactions may coexist, and the symptoms may not be present to the same extent in different individuals. It may be helpful to think of the physical urticarias as being on a continuum, with some individuals having mild occasional symptoms, and others experiencing life-threatening crises. Because an individual may have mixed symptoms suggestive of several different types of urticarias, it can be confusing to ascertain specifically which urticaria exists.

The physical urticarias are distinguished by the following characteristics [2]:

1. All can usually be reproduced with the appropriate stimulus.

2. Wheal formation is intermittent and occurs soon after the application of the stimulus (except in the case of delayed pressure urticaria).

3. The eruption usually lasts less than two hours.

4. The condition occurs most frequently in young adults.

5. The wheals have a distinctive appearance and location.

6. There may be systemic features such as flushing, headaches, dizziness, or hypotension.

Cholinergic Urticaria

Thirty-four percent of all the physical urticarias are cholinergic urticarias [2]. They occur with exercise, anxiety, sweating, and passive warming (such as with a hot bath or shower). The precipitating factor in this reaction is elevated core body temperature. The rash of cholinergic urticaria is smaller than classic urticaria (2 to 4 millimeter wheals), surrounded by large areas of macular erythema. Intense pruritus almost always occurs, and may occur without the presence of obvious wheals. The reaction usually occurs within 2 to 30 minutes of the onset of exercise or passive warming. Usually the rash begins on the upper thorax and neck, and may spread to the entire body; however, the rash may be isolated to specific areas of the body such as the legs. Itching, erythema, and wheals usually subside within 30 minutes of the termination of the stimulating activity. The affected individual may also experience other symptoms of cholinergic stimulation such as lacrimation, salivation, bronchospasm, and diarrhea. Cholinergic urticaria is not usually associated with angioedema, vascular collapse, or hypotension.

Rare variants of cholinergic urticaria include persistent erythema, exercise-induced anaphylaxis (see discussion on exercise-induced anaphylaxis), cold-induced cholinergic urticaria[10], and food-dependent, exercise-induced urticaria.

Cold-Induced Urticaria

Cold urticaria, first described by Blanchez in 1872, is a physical allergy with varying dermal responses to cold stimuli [6,11]. It is said to account for 1% to 3% of all physical urticarias [12], although this is probably an underestimation due to unreported and untested cases. Cold urticaria can occur alone or along with other physical urticarias.

Cold urticaria usually presents as an acquired condition, which is divided into two major categories. The most common type of acquired cold urticaria is primary cold urticaria, an idiopathic disorder. Secondary acquired cold urticaria is associated with mononucleosis, connective tissue diseases, chronic lymphocytic leukemia, and some diseases with pathological cold-dependent immunoglobulins [4,6,13]. Atypical acquired cold urticaria syndromes include localized cold-reflex urticaria, systemic atypical acquired cold urticaria, cold-dependent dermographism, delayed cold urticaria, and cold-induced cholinergic urticaria [11,14]. Wanderer [15] noted an increasing frequency of systemic atypical acquired cold urticaria. The majority of urticarias have no identifiable, underlying cause [5].

All forms of cold urticaria are induced by cold stimuli of varying duration, particularly damp and windy weather; they most frequently present as urticaria, pruritus, and/or angioedema on exposed areas [7,16]. Involving the superficial layers of the skin, urticaria are usually multiple, short-lived, pruritic erythematous wheals between 1 and 3 centimeters, generally lasting less than 24 hours. Angioedema may or may not include itching, and involves the deeper dermis and subcutaneous tissues. Wheals associated with angioedema may reach several centimeters in diameter but are generally short-lived, completely disappearing within 12 to 24 hours [5]. Symptoms such as dizziness, hypotension, tachycardia, and nausea have also been noted in primary cold urticaria, although with less frequency. Such symptoms are believed to be associated with the severity of the disorder [7] or the intensity of the cold stimulus [5,17].

Dermographism

In dermographism, which accounts for an estimated 8.5% of all cases of physical urticaria [18], wheals and flares occur in response to simple rubbing of the skin. Urticaria accompanies the wheal and flare, and seems disproportionate to the degree of stimulation and the appearance of the wheal and flare. Wheals appear within 5 to 10 minutes following stimulus application, and usually resolve completely in 15 to 20 minutes [2]. Symptoms may occur with the rubbing of the skin that occurs with clapping the hands, the pressure of shower jets, or stimulation of a belt or watchband; symptoms can be aggravated by hot baths, stress, or exercise. Since a wheal and flare without urticaria can occur normally [5], the presence of pruritus is needed to suggest a pathological response.

Delayed Pressure Urticaria

This rare condition makes up about 1% of all the urticarias. In delayed pressure urticaria, edema, itching, and pain occur as a delayed response to pressure against the skin. The pressure may be from a belt, a bra strap, pressure against the soles of the feet from walking, or from leaning a part of the body against a table or other object. Symptoms do not usually appear for at least 30 minutes, and appear most often in four to six hours; they may persist for up to 48 hours [5]. Although the reported number of cases of delayed pressure urticaria is low, Barlow, et al [1] found the incidence to be 37% in a tested population of clients with urticaria ofown etiology. They attributed this increased incidence to be due to undertesting for the physical urticarias, and hypothesize that the actual incidence is higher.

Solar Urticaria

This condition is also rare, occurring in less than 1% of all clients with urticaria. Urticaria in response to sunlight can occur as an itching or burning sensation with wheals and erythema, most often only on the skin exposed to the sun. However, related bronchospasm and syncope have also been reported [19]. Most often the skin that reacts the most severely is that which is not usually exposed to sunlight, and may occur in response to any of the light wavelengths. It is an immediate response, occurring within 5 to 10 minutes after exposure and persisting for 1 to 2 hours afterward. This immediate response distinguishes solar urticaria from the more commonly occurring polymorphic light eruption that occurs hours after exposure [5].

Variations of solar urticaria that are reported include urticaria that occurs on sun-exposed skin following bruising [20] and fixed solar urticaria, in which wheals appear in the same areas during each exposure to sun. Although solar urticaria is usually idiopathic, systemic causes such as porphyria cutanea tarda are occasionally implicated [2]. Although solar urticaria is considered rare, it may be underreported, as usually the condition is not incapacitating and may not induce the sufferer to seek treatment [19].

Aquagenic Urticaria

Aquagenic urticaria, originally described in 1964, is a rare form of physical urticaria [21,22], with fewer than 25 cases reported in the literature [9]. This condition is manifested via small urticarial wheals after contact with water. Drinking water, however, does not produce a reaction. The disorder is distinguishable from cold urticaria, as the allergic response is independent of water temperature [23]. The use of topical atropine as a pretreatment can be used to differentiate this condition from cholinergic urticaria in that the atropine will not prevent wheal formation in aquagenic urticaria [22].

Vibratory Urticaria

Vibratory urticaria, or vibratory angioedema [5], is a rare familial condition [24] consisting of erythema and edema following the stretching of skin which occurs, for example, when one is rubbing a towel across one's skin. In some cases, symptoms may last for days, and may be associated with headaches [25].

Localized Heat Urticaria

This condition is also rare, with fewer than 30 known reported cases [26]. Heat, when applied locally, results in edema and erythema at the site of heat contact. The reaction may last up to 2 hours after contact with the heat source.

Although this anaphylactic reaction can be associated with exercise alone, the reaction has also occurred with the ingestion of specific foods followed by exercise. Foods known to trigger the reaction include celery, wheat, nuts, shrimp, and shellfish. Aspirin-related compounds may also be a factor [27]. Occurrence of menses seems to be a factor for women [28,29]; episodes of EIA may occur in childbirth [30]. However, there are no definitive studies that associate these factors with episodes of exercise-induced anaphylaxis. A history of one anaphylactic episode does not mean that other episodes will occur in the future [27]. Conversely, fatal episodes of exercise-induced anaphylaxis can occur in the absence of a history of suggestive symptoms.

As noted in the discussion of cholinergic urticaria, exercise-induced anaphylaxis can overlap with cholinergic urticaria in symptoms and etiology. Some classifications describe exercise-induced anaphylaxis as a variant of cholinergic urticaria. However, most authorities differentiate between the two conditions. Because a case of cholinergic urticaria that presents with systemic symptoms occasionally can be mistaken for exercise-induced anaphylaxis [31], it is important to understand the differences.

Exercise-induced anaphylaxis is probably the most dangerous of the physical urticarias, as it is often unpredictable, dramatic, and life-threatening. Symptoms progress quickly, moving from the presence of 5 to 10 mm wheals accompanied by itching and flushing, to laryngospasm, bronchospasm, and vascular collapse. Other systemic symptoms that can occur include wheezing, gastrointestinal symptoms, and headache [32].

More than 1,000 cases of exercise-induced anaphylaxis are documented, with one reported death in the literature [29]. Although most reports of exercise-induced anaphylaxis involve individuals who developed symptoms without prior histories, some researchers [32] have documented the possibility of a hereditary variety of the phenomenon.

ASSESSMENT AND DIAGNOSIS

When an individual presents with acute urticaria, a cursory initial assessment of symptoms, manifestations, and precipitating factors should be performed, as immediate treatment may be a necessary priority. For patients whose primary manifestation is dermatological, removing the offending stimulus (if known) and the administration of antihistamines can provide immediate symptomatic relief. Those with systemic reactions can be treated with 0.3 ml of epinephrine (1:1000 solution) subcutaneously [3]. Once the safety and comfort of the individual has been secured, a more thorough history and physical exam is necessary.

Physical urticarias and their causes frequently go unrecognized and untreated by affected individuals and their health care providers. A thorough history is the key to discerning the presence of a physical urticaria, and should include both the individual's past medical history as well as recent events. As many individuals are unaware that physical stimuli, such as heat and cold, may evoke an urticarial response, it is critical to ask specifically about these as possible precipitating factors. Figure 1 provides a guide for evaluating the physical urticarias. The following sections offer more specific diagnostic information.

Cholinergic Urticaria

The development of fine wheals, pruritus, and erythema that occur in response to increased body temperature are evidence of cholinergic urticaria. Cholinergic urticaria, like the other urticarias, can be difficult to accurately diagnose. In addition to the fact that currently used diagnostic tests are often unreliable [34], people who have urticaria often have mixed reactions [35]. For example, individuals with cholinergic urticaria often find that their symptoms are exacerbated by cold weather; they may also show evidence of dermographism and vibratory urticaria that appear with exercise. Some individuals may also experience symptoms of both cholinergic urticaria and exercise-induced anaphylaxis. Because the degree of severity ranges from mild to severe, cholinergic urticaria can be thought of as being on a continuum of severity [12,36]. For some clients, symptoms may not develop at all when the individual experiences heat that is not accompanied by exercise.

Because the rash of cholinergic urticaria is typically associated with sweating, diagnostic tests involve stimulation of sweating by local or central means [37]. Immersion of the hand or body part in hot water is sometimes used to induce sweating, as is exercise such as running in place in warm clothes until sweating is induced [37]. Intradermal injection of substances known to induce sweating, such as acetylcholine and nicotinic acid, has also been used as diagnostic tests [37]; however, intradermal tests are much less reliable than exercise and heat immersion.

Cold-Induced Urticaria

The most commonly used diagnostic tests are the ice cube challenge and water immersion tests. Using the former, an ice cube is placed on the ventral aspect of the client's forearm for 4 to 5 minutes. In the water immersion test, the client's forearm and hand are submerged in cold or ice water for a similar time-frame. The appearance of a pruritic wheal on the cold-exposed area either during, or within minutes of, exposure is diagnostic [6].

While commonly used, both of these tests warrant caution in diagnosis due to the polymorphism of cold urticarial syndromes. For example, the response to the cold challenge tests may vary depending on the duration of the challenge. Very sensitive clients with cold urticaria may exhibit positive signs after a short challenge (usually 3 minutes) [15]. Prolonged water immersion could evoke systemic reactions in a very cold-sensitive person [31]. Conversely, there are those for whom induction of symptoms requires a longer duration of cold stimulation (10 minutes or more). Differing response times have the potential to lead to missed diagnosis or misdiagnosis.

Moreover, although rare, there are some persons with cold urticaria who exhibit cold sensitivity only on certain regions of their body, or only after total body cooling. If tested only at an unresponsive site, the client would be misdiagnosed. Repeated negative cold-challenge tests may rule out primary acquired cold urticaria for most persons, but without further testing (e.g., systemic exposure to cold), secondary acquired cold urticaria may be missed in evaluation [11,15,16].

Standard tests such as the cold challenge tests are the most convenient and economical to use in the diagnosis of cold urticaria. However, careful and specific interviewing of symptomatic clients, along with the cautious use of standardized tests, will yield the safest and most accurate diagnosis of those with cold urticaria syndromes.

Dermographism

Diagnosis is made by recording the skin responses to graded pressure from a dermographometer; in a clinical setting, a presumptive diagnosis of dermographism can be made by observing the wheal, flare, and itching that occur in response to gentle scratching of the client's skin.

Delayed Pressure Urticaria

Diagnosis is made by applying pressure with a dermographometer, or by applying sustained pressure against the skin, and evaluating the site 6 hours later [1,5].

Solar Urticaria

Diagnosis can be made by exposing the client's skin to natural or artificial light, using appropriate filters to evaluate different light wavelengths [2].

Aquagenic Urticaria

Diagnosis is confirmed by applying tepid water to the client's skin (for example, by having the client take a tepid bath or shower.)

Vibratory Urticaria

Kaplan and Beaven [24] were able to induce vibratory urticaria in a laboratory setting by vibrating a vortex against a subject's skin.

Localized Heat Urticaria

Local contact with a heat source at 45° centigrade for 30 seconds should produce localized urticaria within a few minutes [33].

Exercise-Induced Anaphylaxis

Diagnosis of exercise-induced anaphylaxis is obviously difficult if there is a severe episode with no prior history of symptoms. Sometimes, however, clients may describe episodes of mild symptoms that are suggestive of exercise-induced anaphylaxis. Cholinergic urticaria and exercise-induced anaphylaxis both occur with exercise, and may appear similar, so that a thorough assessment is needed to differentiate the conditions. Because exercise-induced anaphylaxis is potentially fatal, while cholinergic urticaria is not, it is essential to differentiate the two. A client who is diagnosed as having exercise-induced urticaria, but who in reality has cholinergic urticaria, faces a much more restrictive lifestyle, as well as a vastly increased anxiety level.

An accurate diagnosis can be made with warm water immersion, as histamine levels will increase with cholinergic urticaria but not with exercise-induced anaphylaxis [28­30]. In addition, clients with cholinergic urticaria will sometimes demonstrate wheezing, whereas those with exercise-induced anaphylaxis will not wheeze but will instead experience choking and stridor [29]. Additionally, the wheals of cholinergic urticaria are typically small, 1 to 3 mm, while those of exercise-induced anaphylaxis are usually larger, 10 to 15 mm [29].

As is true when evaluating for cold urticaria, care should be taken when performing these challenges, especially with individuals who have experienced angioedema or anaphylaxis in the past. In susceptible clients, the challenge may precipitate a more severe reaction than the client has experienced previously. When exposing a client with a possible physical urticaria to a challenge test, the clinician should be sure that emergency supports are readily available. In situations where the diagnosis is uncertain, or the risk of potential anaphylaxis is unclear, the primary care provider should consider referral to an allergy specialist for further evaluation and diagnosis.

TREATMENT

Non-Pharmacological Treatments

Many different interventions have been suggested for the treatment of the various urticarias. A number of these have undergone evaluation through research, with varying degrees of success. Because response to treatment varies widely from individual to individual, treatment must be tailored to the particular patient and must often be a matter of trial and error.

In addition to medications, other treatments for urticaria include avoidance of the stimulus, desensitization, and stress reduction. Many sufferers of chronic urticaria have already learned to avoid the offending stimuli [see Case Study I]. For some physical urticarias, such as vibratory urticaria, there is no definitive treatment other than avoidance of the vibrating stimulus that has been found to be helpful [25]. Individuals with solar urticaria may find that using sunscreen may help to avoid direct contact with pruritus-inducing sunlight.

In the case of exercise-induced anaphylaxis, it is prudent to consider avoiding the precipitating activity altogether and defer eating for 4 to 6 hours prior to exercise. The client should be instructed that if mild symptoms occur, such as pruritus, they should cease exercise immediately. If exercise-induced anaphylaxis is considered a possibility for an individual client who is unable or unwilling to discontinue the offending exercise, the client should be instructed to consider keeping injectable epinephrine on hand. Clients who are at risk for exercise-induced anaphylaxis should also be instructed to exercise with a partner (never alone), preferably a partner who is familiar with the risk and understands the administration of epinephrine.

Desensitization may be helpful for some clients in reducing the severity of their symptoms. For example, individuals with cholinergic urticaria may find that regular exercise decreases symptoms to an extent that permits exercise (see Case Study II). Higgins and Friedman [33] described an empirical treatment of desensitization for a specific client with localized heat urticaria. This consisted of gradually increasing immersion of larger parts of the body into 45° centigrade water over a period of time until the client was able to tolerate total submersion of her body without experiencing urticaria, along with administration of terfenadine. With the combination of 5 minutes daily immersion and daily terfenadine, this client remained symptom-free.

The presence of anxiety as a precipitating factor is difficult to evaluate, as the condition itself is often responsible for anxiety. Other treatments, such as the use of relaxation techniques, have also been used. The results of these techniques are variable, and their uses are described in other literature.

Medications

A number of medications have been utilized to treat urticaria. Medications used to treat physical urticarias are often used to treat urticarias of other etiologies as well. It should be remembered that for any individual client, finding the right medication for a given urticaria is often a matter of trial and error.

First generation H₁ receptor antagonists (see Table 2) have a long history of use in treatment of urticaria [38,39] and are the medications most often prescribed. H₁ antagonists relieve urticaria by decreasing wheal size and decreasing histamine-stimulated vasodilation [38]. It is helpful to give an H₁ antagonist before an anticipated allergic reaction, as this may decrease the intensity of the reaction and increase the medication's efficacy [38]. For some clients, concurrent use of an H₁ antagonist with an H₂ antagonist such as cimetidine may enhance relief of the symptoms of chronic urticaria [38]. The major drawback of using first generation H₁ antagonists is their sedative effect.

While second generation H₁ receptor antagonists such as terfenadine and astemizole are commonly used for treatment of allergic rhinitis, they are also effective in treating urticaria (see Table 2). Second-generation H₁ antagonists are probably as effective as first generation H₁ antagonists, although some researchers have questioned this [38]. The second generation antagonists have the advantage of being less sedating than the older medications, and so may be more easily tolerated. However, the potential cardiovascular risks (e.g., torsades de pointes) of combining terfenidine or astemizole with other drugs such as erythromycin should be weighed when prescribing [40].

H₂ receptor antagonists may also be effective in treatment of urticaria. In addition to blocking gastric acid secretion, the H₂ receptor antagonists such as cimetidine and ranitidine are potent histamine blockers and may be effective in treating urticarias of various etiologies [40]. H₂ blockers should be used in combination with other medications, as H₂ blockers may counteract the normal feedback inhibition of histamine on mast cell degranulation and thus act counterproductively [25].

Often a combination of different medications will be more effective than a single drug alone. For example, hydroxyzine and cyproheptadine may be used together for an individual with combined cold and cholinergic urticaria, and hydroxyzine and cimetidine may be used for dermographism [12,39].

Tricyclic antidepressants (TCAs) have also been used by some clinicians with varying degrees of success. TCAs have been used for other chronic conditions such as chronic pain and burning sensations associated with diabetic neuropathy. These sensations share neural pathways with pruritus, which may explain their clinical effectiveness in treating chronic urticaria [41]. As can be seen from Table 2, much smaller doses are usually needed to treat urticaria than to treat depression. In addition, results are often obtained in 2 to 4 weeks when treating urticaria, as opposed to the several months often needed when treating depression [41]. Cardiovascular risks and sedative side effects should be considered when prescribing TCAs. The two most commonly used TCAs that have been found to be effective for urticaria are listed in Table 2.

In addition to medications that can be used to treat urticaria on a preventive or long-term basis, individuals at risk for anaphylaxis should keep injectable epinephrine on hand at all times.

IMPACT ON LIFE

One of the outcomes of a chronic condition such as urticaria is the interference with lifestyle. For many, the condition is an irritant. As seen in the case studies, the individual learns what triggers the symptoms, and modifies her/his behavior accordingly. Activities such as hiking or running may be impossible if they precipitate uncontrollable itching and hives for someone with cholinergic urticaria. Canoeing, rafting, or swimming may be impossible for the individual with severe cold urticaria. For those whose symptoms are severe or life-threatening, the potential for accidentally finding themselves in situations that produce the urticaria can be a major source of fear and anxiety.

Another issue affecting the life of a person with urticaria is the discovery that others do not understand (or have not heard of) the condition. Many health care providers are not familiar with, and do not screen for, the physical urticarias. In the larger picture of overall health care, these problems are often dismissed as minor annoyances, without due consideration for diagnosis and treatment. However, worse than health care providers' lack of interest and knowledge may be the response of the individual's family, friends or acquaintances, who are likely to be much less aware of the condition than health care providers. The fact that the majority of urticaria sufferers are female [3] produces interesting speculation regarding the possibility that urticarial symptoms may be dismissed more readily than if the symptoms were experienced by men.

As is true of other conditions about which little is known [42], it can be difficult for health care providers to help a person whose symptoms do not fit into a recognizable framework. If there is not a familiar explanation or ready diagnosis, it is often too easy for a health care provider, as well as a lay person, to dismiss the symptoms and the impact they may have on someone's life.

DISCUSSION AND CONCLUSIONS

There is a lack of awareness of the physical urticarias, both by health care professionals and by the general public. This may be due to the fact that symptoms often tend to be mild, are sometimes self-limiting, and are often vague. In addition, many individuals tend to have mixed conditions, with symptoms that cross over the different physical urticarias.

However, like other conditions for which diagnosis and treatment are difficult, the physical urticarias tend to be invisible because they are frustrating to treat [42]. Therefore, the diagnosis of physical urticaria tends not to be made, as both the sufferer and the health care provider may not believe that a legitimate problem is present.

Both quantitative and qualitative research is needed around this problem. Quantitatively, an accurate evaluation of the numbers of individuals in the population who encounter symptoms suggestive of the physical urticarias would help to delimit the extent of the problem. In addition, evaluations of interventions which are used to treat the conditions are needed.

Qualitatively, studies are needed of the lived experiences of individuals with physical urticarias. Individuals with these urticarias often find that the boundaries of their lives contract significantly because of the limits of their symptoms. In addition, a qualitative evaluation of individuals' stories could yield important data both about the range of experience (for example, the ways in which the various urticarias overlap in the same person) and ways in which individuals learn to cope with this limitation.

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40. Krause H: Therapeutic advances in the management of allergic rhinitis and urticaria. Otolaryngol Head Neck Surg 1994;111(3):364-72.

41. Gupta M, Gupta A, Ellis C: Antidepressant drugs in dermatology: an update. Arch Dermatol 1987;123:647-52.

42. Saunders JM: Nursing management of persons with disease about which little is known: Prototype--AIDS. In: Baird S, McCorkle R, Grant M, eds. Cancer Nursing: A Comprehensive Textbook. Philadelphia: W.B. Saunders, 1991:708-16.

SELECTED WORLD WIDE WEB RESOURCES RELATED
TO THIS ARTICLE

A description of Urticaria http://indy.radiology.uiowa.edu/Providers/ClinRef/FPHandbook/13.html and its treatments can be found at the Virtual Hospital (VH), a digital health sciences library that is a project of the Electric Differential Multimedia Laboratory in the Department of Radiology at the University of Iowa College of Medicine.

Urticaria-Hives http://tray.dermatology.uiowa.edu/PIPs/Urticaria.html can be found on AAD Derminfo Net, information from the American Academy of Dermatology.

PROVIDER INFORMATION

The Nursing Institute is an affiliate of Springhouse Corporation, publisher of The Nurse Practitioner. The Institute is accredited as a provider of continuing education (CE) in nursing by the American Nurses Credentialing Center's Commission on Accreditation. The Nursing Institute is also an approved provider of CE in states where it is mandatory for license renewal.* Your Nursing Institute­issued CE contact hours are valid wherever you reside.

*Provider numbers: Alabama, ABNP0210; California, 5264; Florida, 27I0600; and Iowa, 136 (Category 1), Texas (Type 1).

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