Approach to Chronic Urticaria from Primary Care and Emergency Services: Case Reports in Spain

*Luis Geniz Rubio, Macarena Ávila Pérez, José Ángel López Díaz and Sara Alcántara Luna*

## **Abstract**

Urticaria is a common process. The true incidence is not known; it is believed that between 15 and 25% of the population may suffer at some point in his life. Acute urticaria has a prevalence of 20% and the chronic form 0.5–1%. Urticaria is a disease that affects the skin and mucosa, characterized by the presence of hives. It occurs as a localized intracutaneous edema circled and an area of redness (erythema), which is typically itchy. There are histaminergic foods and drugs that worsen the prognosis of the disease*.* Foods which rely on aging to taste nice are always presumed to be high in histamine (chocolate, yogurt, seafood, strawberries, etc.) and drugs like nonsteroidal anti-inflammatory drugs. For diagnosis we have several tools (urticarial activity score, chronic urticaria quality-of-life questionnaire (CU-Q2oL), urticaria control test, etc., among which the most useful, simple, and cost-effective is the clinic history). The treatment of choice are antihistamines, from a daily tablet up to four tablets as maximum dose. Corticosteroids are excluded to exacerbations and must be prescribed in short guideline (maximum 10 days) without progressive decrease. Severe forms of urticaria resistant to treatment with antihistamines are treated with biological agents like omalizumab.

**Keywords:** urticaria, hives, itching, angioedema, antihistamines

## **1. Introduction**

The interest in making this chapter was to explain the pathology of chronic urticaria as prevalent and its high morbidity.

We often see this problem in our primary care consultations and emergency services, so we consider its important to make a chapter about urticaria.

The current version of the EAACI/GA2 LEN/EDF/WAO urticaria guideline from 2018 contains new aspects about diagnosis and treatment.

At the end of the chapter, we show a series of cases treated in our practice (observed in a Juan Ramon Jimenez's dermatology room in Huelva, Spain), exposing results obtained with the different forms of treatment (**Figure 1**).

## **2. Epidemiology**

Urticaria is a common process. Although the true incidence is not known, it is believed that between 15 and 25% of the population may suffer at some point in his life. Acute urticaria has a prevalence of 20% and the chronic form 0.5–1% [1]. Age, race, sex, occupation, geographical region, and the season of the year may be implicated in urticaria and angioedema. The majority of acute episodes are due to adverse reactions to medications or food or, in children, to viral diseases.

Spontaneous chronic urticaria represents about 70% of all chronic hives and may persist for several years. Patients with chronic urticaria often describe a decrease in the quality of life because of itching and may have alterations of sleep, fatigue, social isolation, or emotional disorders (**Figures 2**–**4**).

## **2.1 Physiopathology**

Urticaria is a disease that affects the skin and mucosa, characterized by the presence of hives. It is a localized intracutaneous edema that circled an area of redness (erythema), which is typically itchy. Individual hives can persist from 30 minutes to 36 hours and can measure from only 1 millimeter up to 15–20 cm in diameter, named giant hives [2]. Increased dilation and permeability of blood vessels that characterize the hives are present in the superficial dermis and undertake the venous plexus located there (**Figure 5**). It is rare and it may occur with concomitant angioedema.

Another similar entity is angioedema, with a similar mechanism as urticaria [3], but the pathology is located in the deep dermis and subcutaneous tissue, and swelling is the main manifestation. The skin may be normal or erythematous. There is less itching, but it can cause pain or burning sensation. The mouth, lips, eyes, throat, feet, and hands are most commonly affected (**Figures 6** and **7**). When angioedema affects the throat, it can be life-threatening, because there is interference in

**41**

**Figure 2.**

**Figure 3.**

**2.2 Food histamine liberator**

*Epidemiology of chronic urticaria in Australia.*

*Approach to Chronic Urticaria from Primary Care and Emergency Services: Case Reports…*

breathing. It is caused by an allergic reaction, sometimes by a hereditary condition

Foods that require a ripening process to achieve a better taste are presumed to have a high histamine content. In the same way as foods that are made during

(hereditary angioedema), but normally we do not know the cause [3].

fermentation. These include de following [4] (**Table 1**).

*DOI: http://dx.doi.org/10.5772/intechopen.88369*

*Epidemiology of chronic urticaria in United States.*

*Approach to Chronic Urticaria from Primary Care and Emergency Services: Case Reports… DOI: http://dx.doi.org/10.5772/intechopen.88369*

**Figure 2.** *Epidemiology of chronic urticaria in United States.*

**Figure 3.** *Epidemiology of chronic urticaria in Australia.*

breathing. It is caused by an allergic reaction, sometimes by a hereditary condition (hereditary angioedema), but normally we do not know the cause [3].

## **2.2 Food histamine liberator**

Foods that require a ripening process to achieve a better taste are presumed to have a high histamine content. In the same way as foods that are made during fermentation. These include de following [4] (**Table 1**).

*Topics in Primary Care Medicine*

**2. Epidemiology**

**Figure 1.** *Chronic urticaria.*

**2.1 Physiopathology**

angioedema.

Urticaria is a common process. Although the true incidence is not known, it is believed that between 15 and 25% of the population may suffer at some point in his life. Acute urticaria has a prevalence of 20% and the chronic form 0.5–1% [1]. Age, race, sex, occupation, geographical region, and the season of the year may be implicated in urticaria and angioedema. The majority of acute episodes are due to

Spontaneous chronic urticaria represents about 70% of all chronic hives and may persist for several years. Patients with chronic urticaria often describe a decrease in the quality of life because of itching and may have alterations of sleep,

Urticaria is a disease that affects the skin and mucosa, characterized by the presence of hives. It is a localized intracutaneous edema that circled an area of redness (erythema), which is typically itchy. Individual hives can persist from 30 minutes to 36 hours and can measure from only 1 millimeter up to 15–20 cm in diameter, named giant hives [2]. Increased dilation and permeability of blood vessels that characterize the hives are present in the superficial dermis and undertake the venous plexus located there (**Figure 5**). It is rare and it may occur with concomitant

Another similar entity is angioedema, with a similar mechanism as urticaria [3], but the pathology is located in the deep dermis and subcutaneous tissue, and swelling is the main manifestation. The skin may be normal or erythematous. There is less itching, but it can cause pain or burning sensation. The mouth, lips, eyes, throat, feet, and hands are most commonly affected (**Figures 6** and **7**). When angioedema affects the throat, it can be life-threatening, because there is interference in

adverse reactions to medications or food or, in children, to viral diseases.

fatigue, social isolation, or emotional disorders (**Figures 2**–**4**).

**40**

#### **Figure 4.**

*Prevalence of chronic urticaria.*

**Figure 5.** *Urticaria. Picture with histological findings.*

The Spanish society of diamine oxidase (DAO) states on their website that the following food histamine liberators:


The department for dermatology in Bonn's paper lists the following foods as being capable of releasing endogenous histamine (**Table 2**).

## **2.3 Pathogenesis**

The mast cell is the main effector cell in urticaria and angioedema. Cutaneous mast cells attach to fibronectin and laminin through the integrin beta1 of Very Late

**43**

and beta3 integrin [5].

*Histamine liberator food.*

**Figure 6.** *Angioedema.*

**Figure 7.** *Angioedema.*

**Table 1.**

increase in histamine.

from the bloodstream to the skin.

*Approach to Chronic Urticaria from Primary Care and Emergency Services: Case Reports…*

Antigen (VLA), VLA-3, VLA-4, and VLA-5 activation and vitronectin through alfa1

Yogurt Soured cream Buttermilk Quark Cottage cheese Alcohol Hard cheeses, cheddar Vinegar Aged cheeses, brie Sauerkraut

Once activated, the mast cell releases granules containing histamine and other mediators of inflammation such as platelet activating factor (PAF) from, TNF alpha, IL-3, IL-4, IL-5, IL-6, IL-8, IL-13, GM-CSF, PGD-2, and leukotrienes (LTC4, LTD4, LTEA). Histamine, TNF alpha, and IL-8 also stimulate endothelial adhesion molecules that favors the migration of eosinophils, monocytes, and neutrophils

Histamine is an amine vasoactive located in granules of mast cells [5], basophils, and platelets. Its effects on the skin are mediated through histamine H1 and H2 receptors. H1 receptors mediate urticaria vasodilation, increased vascular permeability, and sensory nerve stimulation. Sensory nerve stimulation determines the release of neuropeptides such as substance P, peptide vasoactive intestinal (VIP), and somatostatin, which in turn induce the mast cell activation and

*DOI: http://dx.doi.org/10.5772/intechopen.88369*

*Approach to Chronic Urticaria from Primary Care and Emergency Services: Case Reports… DOI: http://dx.doi.org/10.5772/intechopen.88369*

**Figure 6.** *Angioedema.*

*Topics in Primary Care Medicine*

**Figure 4.**

**Figure 5.**

*Prevalence of chronic urticaria.*

The Spanish society of diamine oxidase (DAO) states on their website that the

• Alcohol, citrus fruits, strawberries, pineapple, kiwi, tomato sauce, seafood,

• Some food additives such as glutamate, benzoate, several colorants (yellow E-102 and E-110, E-124, amaranth E-123), sulfites, and nitrites can release

The department for dermatology in Bonn's paper lists the following foods as

The mast cell is the main effector cell in urticaria and angioedema. Cutaneous mast cells attach to fibronectin and laminin through the integrin beta1 of Very Late

chocolate, fish, mushrooms, pig, cereals, and egg white.

being capable of releasing endogenous histamine (**Table 2**).

following food histamine liberators:

*Urticaria. Picture with histological findings.*

endogenous histamine.

**2.3 Pathogenesis**

**42**

#### **Figure 7.** *Angioedema.*


#### **Table 1.**

*Histamine liberator food.*

Antigen (VLA), VLA-3, VLA-4, and VLA-5 activation and vitronectin through alfa1 and beta3 integrin [5].

Once activated, the mast cell releases granules containing histamine and other mediators of inflammation such as platelet activating factor (PAF) from, TNF alpha, IL-3, IL-4, IL-5, IL-6, IL-8, IL-13, GM-CSF, PGD-2, and leukotrienes (LTC4, LTD4, LTEA). Histamine, TNF alpha, and IL-8 also stimulate endothelial adhesion molecules that favors the migration of eosinophils, monocytes, and neutrophils from the bloodstream to the skin.

Histamine is an amine vasoactive located in granules of mast cells [5], basophils, and platelets. Its effects on the skin are mediated through histamine H1 and H2 receptors. H1 receptors mediate urticaria vasodilation, increased vascular permeability, and sensory nerve stimulation. Sensory nerve stimulation determines the release of neuropeptides such as substance P, peptide vasoactive intestinal (VIP), and somatostatin, which in turn induce the mast cell activation and increase in histamine.


#### **Table 2.**

*Foods as being capable of releasing endogenous histamine.*

#### **Figure 8.**

*Physiopathology of urticaria. Note like that the mast cells are the principal cells implicated.*

The vascular endothelium expressed a significant number of H2 receptors, so the vascular response in the UC is an immunomodulatory effect, to increase the synthesis of pro-inflammatory cytokines such as IL-1 and IL-6 of monocytes and IL-6 and IL-8 cell endothelial. In addition to histamine, other soluble factors synthesized by mast cells contribute to the increase of vascular dilation and permeability; favor chemotaxis, cell activation of leukocyte, and endothelial cells; and induce stimulation sensory. These are the cytokines, chemokines, and neuropeptides and arachidonic acid metabolites.

The degranulation is attributed to immunological causes (autoimmune, IgEdependent, immune complexes, complement-dependent), not immune (pseudoallergies, agents release by mast cells) and idiopathic. The path of the synthesis of prostaglandins and leukotrienes, hours later the mast cell activation, occurs in the synthesis of leukotrienes and prostaglandins from arachidonic acid via two-way enzymatic metabolism: the cyclooxygenase path and the lipoxygenase pathways.

Studies have shown that LTB4 has a potent chemotactic activity, which is produced by mast cells in the early and selective recruitment of leukocytes. At chronic urticaria (CU), these mediators appear to be the most important in the chronicity of the disease. There are no immune reactions (pseudoallergics); the mechanisms are not clear but may compromise the metabolism of arachidonic acid, prostaglandins, and leukotrienes [2] (**Figure 8**).

**45**

*Approach to Chronic Urticaria from Primary Care and Emergency Services: Case Reports…*

Recurrent urticaria: outbreaks recur over time, but its duration is limited.

Spontaneous chronic urticaria: spontaneous emergence of hives, angioedema, or

Inducible urticaria: physical urticarial (This hives occur at the site of the stimu-

Urticaria typically presents well circumscribed wheals (polimorphyc, serpenginous or round), with intensely pruritic for less than 24 hours of evolution. Wheals can be generalized, including arms, legs, face. Urticaria +/− angioedema (primarily in the face), can be acute (with an evolution of less than 6 weeks), or chronic

For diagnosis we have several tools, among which the most useful, simple, and cost-effective is the clinical history, but we can ask for additional tests in the case of

A detailed clinical history and a good physical examination of the patient are

According to the time evolution, urticaria can be divided into:

• Chronic urticaria\*: lesions appear for more than 6 weeks [6].

both for longer than 6 weeks, due to a known or unknown cause.

lation)l, cholinergic, aquagenic and contact urticarias (**Figure 9**).

Episodes of hives last less than asymptomatic intervals.

*DOI: http://dx.doi.org/10.5772/intechopen.88369*

• Acute urticaria: less than 6 weeks.

\* Chronic urticaria is divided into two:

**3. Classification**

**4. Symptomatology**

*Acute and chronic urticaria.*

**Figure 9.**

**5. Diagnosis**

**5.1 Clinical history**

necessary to make the diagnosis.

(greater than 6 weeks [7] (**Figures 10**–**15**).

diagnostic doubt or suspicion of systemic disease [8].

*Approach to Chronic Urticaria from Primary Care and Emergency Services: Case Reports… DOI: http://dx.doi.org/10.5772/intechopen.88369*

## **3. Classification**

*Topics in Primary Care Medicine*

**Table 2.**

**Figure 8.**

Citrus fruit Chocolate Papaya Fish Strawberries Crustaceans Pineapple Pork Nuts Egg white Peanuts Additives Tomatoes Liquorice Spinach Spices

*Foods as being capable of releasing endogenous histamine.*

The vascular endothelium expressed a significant number of H2 receptors, so the vascular response in the UC is an immunomodulatory effect, to increase the synthesis of pro-inflammatory cytokines such as IL-1 and IL-6 of monocytes and IL-6 and IL-8 cell endothelial. In addition to histamine, other soluble factors synthesized by mast cells contribute to the increase of vascular dilation and permeability; favor chemotaxis, cell activation of leukocyte, and endothelial cells; and induce stimulation sensory. These are the cytokines, chemokines, and neuropeptides and

*Physiopathology of urticaria. Note like that the mast cells are the principal cells implicated.*

The degranulation is attributed to immunological causes (autoimmune, IgEdependent, immune complexes, complement-dependent), not immune (pseudoallergies, agents release by mast cells) and idiopathic. The path of the synthesis of prostaglandins and leukotrienes, hours later the mast cell activation, occurs in the synthesis of leukotrienes and prostaglandins from arachidonic acid via two-way enzymatic metabolism: the cyclooxygenase path and the lipoxygenase

Studies have shown that LTB4 has a potent chemotactic activity, which is produced by mast cells in the early and selective recruitment of leukocytes. At chronic urticaria (CU), these mediators appear to be the most important in the chronicity of the disease. There are no immune reactions (pseudoallergics); the mechanisms are not clear but may compromise the metabolism of arachidonic acid, prostaglandins,

**44**

pathways.

arachidonic acid metabolites.

and leukotrienes [2] (**Figure 8**).

According to the time evolution, urticaria can be divided into:


Recurrent urticaria: outbreaks recur over time, but its duration is limited. Episodes of hives last less than asymptomatic intervals.

\* Chronic urticaria is divided into two:

Spontaneous chronic urticaria: spontaneous emergence of hives, angioedema, or both for longer than 6 weeks, due to a known or unknown cause.

Inducible urticaria: physical urticarial (This hives occur at the site of the stimulation)l, cholinergic, aquagenic and contact urticarias (**Figure 9**).

**Figure 9.** *Acute and chronic urticaria.*

## **4. Symptomatology**

Urticaria typically presents well circumscribed wheals (polimorphyc, serpenginous or round), with intensely pruritic for less than 24 hours of evolution. Wheals can be generalized, including arms, legs, face. Urticaria +/− angioedema (primarily in the face), can be acute (with an evolution of less than 6 weeks), or chronic (greater than 6 weeks [7] (**Figures 10**–**15**).

## **5. Diagnosis**

For diagnosis we have several tools, among which the most useful, simple, and cost-effective is the clinical history, but we can ask for additional tests in the case of diagnostic doubt or suspicion of systemic disease [8].

## **5.1 Clinical history**

A detailed clinical history and a good physical examination of the patient are necessary to make the diagnosis.

**Figure 10.** *Generalities of urticaria.*

**Figure 11.** *Dermatological manifestations of urticaria. Note the typical hives.*

#### **Figure 12.**

*Dermatological manifestations of urticaria. Note the erythema.*

Thanks to its history, we can classify chronic urticaria as spontaneous or inducible. For this, we must focus on the following aspects:

**47**

**Figure 13.**

*Linear hives made by compression.*

*Approach to Chronic Urticaria from Primary Care and Emergency Services: Case Reports…*

• Induction of urticaria due to exercise or exposure to physical agents.

• Frequency and duration of the hives, size, shape, and distribution.

• If associated symptoms are subjective such as pain, burning, etc.

Complementary tests serve as support to the diagnosis, to detect associated

New guidelines recommend not to perform additional exploration in a systematic way in acute urticaria and just a complete blood count with ESR and a suspension of nonsteroidal anti-inflammatory drugs (NSAIDs) in the CU

Basic laboratory tests, as blood count and biochemical reaction (determination of C-reactive protein, glomerular sedimentation rate), can help us rule out there is a systemic disease. The baseline of tryptase, antithyroid antibodies, and thyroid profile and study of complement and specific IgE where allergy is suspected, could also be useful. If an infection cause is suspected, hepatitis B and C virus or Helicobacter

• A history of allergies, infections, or any other cause that has been able to trigger

*DOI: http://dx.doi.org/10.5772/intechopen.88369*

• Work performed and hobbies.

• How the body reacts to insect bites.

• If the quality of life is affected.

• Duration of the disease.

**5.2 Complementary tests**

Pylori could be detected.

(**Figure 16**).

• If the patient has been on holidays or trip recently.

• If the patient has nocturnal or diurnal variation.

• How the response was to the treatments used.

systemic diseases or for differential diagnosis.

• If it has relationship with the menstrual cycle or stress.

hives.


*Approach to Chronic Urticaria from Primary Care and Emergency Services: Case Reports… DOI: http://dx.doi.org/10.5772/intechopen.88369*


*Topics in Primary Care Medicine*

**Figure 10.**

**Figure 11.**

**Figure 12.**

*Generalities of urticaria.*

**46**

Thanks to its history, we can classify chronic urticaria as spontaneous or inducible.

For this, we must focus on the following aspects:

*Dermatological manifestations of urticaria. Note the erythema.*

*Dermatological manifestations of urticaria. Note the typical hives.*

• A family history of atopy or urticaria.

• Commonly used drugs and relation with the hives.


#### **5.2 Complementary tests**

Complementary tests serve as support to the diagnosis, to detect associated systemic diseases or for differential diagnosis.

Basic laboratory tests, as blood count and biochemical reaction (determination of C-reactive protein, glomerular sedimentation rate), can help us rule out there is a systemic disease. The baseline of tryptase, antithyroid antibodies, and thyroid profile and study of complement and specific IgE where allergy is suspected, could also be useful. If an infection cause is suspected, hepatitis B and C virus or Helicobacter Pylori could be detected.

New guidelines recommend not to perform additional exploration in a systematic way in acute urticaria and just a complete blood count with ESR and a suspension of nonsteroidal anti-inflammatory drugs (NSAIDs) in the CU (**Figure 16**).

**Figure 13.** *Linear hives made by compression.*

**Figure 14.** *Coalescing urticarial papules.*

**Figure 15.** *Urticaria and angioedema.*

**49**

zumab [13].

similar.

*6.2.1 Clinical guidelines*

*Approach to Chronic Urticaria from Primary Care and Emergency Services: Case Reports…*

Different ways are approached for the treatment of urticaria: eliminating histaminergic food such as seafoods, canned goods, tomatoes, strawberries, bananas, pineapple, or apples and avoiding nonsteroidal anti-inflammatory drugs (NSAIDs) [9], nonsedative H1-antihistamines, and in severe cases systemic corticosteroids [10].

• The treatment of choice are antihistamines, from a daily tablet up to four

guideline (maximum 10 days) without progressive decrease.

• Forms resistant to treatment: biological agents (omalizumab\*).

**6.2 Severe forms of urticaria or exacerbations and associated angioedema**

• Nonsedative H1-antihistamines to full dose (four tablets in a day) [11].

• Systemic corticoids, preferably in short treatment (10-day short guideline).

\*Omalizumab is a recombinant humanized monoclonal antibody, which blocks the high-affinity Fc receptor of IgE (**Figure 18**). It has been approved for treatment in cases of moderate-to-severe asthma, but it has promising results in the management also of chronic urticaria [12]. The dose is 150 or 300 mg by subcutaneous injection every 4 weeks. Dosing is not dependent on body weight or serum IgE level. The appropriate duration for CIU has not been evaluated yet. It's necessary to periodically reassess the need for continued therapy with omali-

The European Academy of Allergy and Clinical Immunology (EAACI)/Global

Allergy and Asthma European Network (GA2LEN)/European Dermatology Forum (EDF)/World Allergy Organization (WAO) and the American Academy of Allergy, Asthma, and Immunology (AAAAI) have some differences in their recommendations for urticaria treatment, but the core recommendations remain

As first-line treatment, second-generation nonsedating H1 antihistamines. Remain in the treatment algorithm first-generation H 1 antihistamines (differs

Second-line options to consider: adding other second-generation H 1 antihistamines, up-dosing second-generation H 1 antihistamines, leukotriene receptor

A brief summary of *AAAAI guidelines* are as follows [14]:

from EAACI/GA 2LEN/EDF/WAO guidelines).

• Corticosteroids are excluded for exacerbations and must be prescribed in short

*DOI: http://dx.doi.org/10.5772/intechopen.88369*

**6. Treatment**

**6.1 Mild forms of urticaria**

• Avoid taking NSAIDs.

tablets as maximum dose.

• Avoid taking NSAIDs (**Figure 17**).

**Figure 16.** *Diagnosis algorithm.*

*Approach to Chronic Urticaria from Primary Care and Emergency Services: Case Reports… DOI: http://dx.doi.org/10.5772/intechopen.88369*

## **6. Treatment**

*Topics in Primary Care Medicine*

**48**

**Figure 16.** *Diagnosis algorithm.*

**Figure 15.**

**Figure 14.**

*Coalescing urticarial papules.*

*Urticaria and angioedema.*

Different ways are approached for the treatment of urticaria: eliminating histaminergic food such as seafoods, canned goods, tomatoes, strawberries, bananas, pineapple, or apples and avoiding nonsteroidal anti-inflammatory drugs (NSAIDs) [9], nonsedative H1-antihistamines, and in severe cases systemic corticosteroids [10].

## **6.1 Mild forms of urticaria**


### **6.2 Severe forms of urticaria or exacerbations and associated angioedema**


\*Omalizumab is a recombinant humanized monoclonal antibody, which blocks the high-affinity Fc receptor of IgE (**Figure 18**). It has been approved for treatment in cases of moderate-to-severe asthma, but it has promising results in the management also of chronic urticaria [12]. The dose is 150 or 300 mg by subcutaneous injection every 4 weeks. Dosing is not dependent on body weight or serum IgE level. The appropriate duration for CIU has not been evaluated yet. It's necessary to periodically reassess the need for continued therapy with omalizumab [13].

#### *6.2.1 Clinical guidelines*

The European Academy of Allergy and Clinical Immunology (EAACI)/Global Allergy and Asthma European Network (GA2LEN)/European Dermatology Forum (EDF)/World Allergy Organization (WAO) and the American Academy of Allergy, Asthma, and Immunology (AAAAI) have some differences in their recommendations for urticaria treatment, but the core recommendations remain similar.

A brief summary of *AAAAI guidelines* are as follows [14]:

As first-line treatment, second-generation nonsedating H1 antihistamines. Remain in the treatment algorithm first-generation H 1 antihistamines (differs from EAACI/GA 2LEN/EDF/WAO guidelines).

Second-line options to consider: adding other second-generation H 1 antihistamines, up-dosing second-generation H 1 antihistamines, leukotriene receptor


#### **Figure 17.**

*Nonsedative antihistamines.*

#### **Figure 18.**

*Monoclonal antibody that binds to the Cε3 domain of circulating IgE, which prevents IgE from binding to and activating receptors in mast cells (***Figure 19***).*

antagonists, adding H 2 antagonists or first-generation H 1 antihistamines at bedtime.

Omalizumab as third-line treatment.

Corticosteroids considered only for short treatment.

Cyclosporine A\* is used in refractory chronic urticaria not responsive to other treatments.

A brief summary of *EAACI/GA2LEN/EDF/WAO guidelines* are as follows: First-line treatment, second-generation H 1 antihistamines.

Up-dosing second-generation H1 antihistamines are the second-line therapy.

Omalizumab is the third-line treatment, which is recommended because it is less toxic than cyclosporine A.

**51**

treatments.

**Figure 19.**

recommends:

dose).

urticaria.

tation to prevent rejection.

The current version of the *EAACI/GA<sup>2</sup>*

*Recommended treatment algorithm for chronic urticaria.*

burden and control should be measured.

with cyclosporine is recommended.

life questionnaire, and urticaria control test (UCT).

**7. Assessment scales**

*Approach to Chronic Urticaria from Primary Care and Emergency Services: Case Reports…*

Not included in algorithm H2 antihistamines (used only on an individual case).

\*Cyclosporin A is an immunosuppressive agent, widely used in organ transplan-

When chronic inducible urticaria is suspected, differential diagnoses should be ruled out. The diagnosis should be confirmed by provocation test disease. The activity should be measured by determining the trigger threshold disease

Second-generation H1 antihistamines remain the treatment of first choice. If continuous treatment for 2–4 weeks does not lead to adequate control of symptoms, the guidelines recommend up-dosing (up to four times the standard

If there is no improvement with high-dose antihistamines, it is recommended to add omalizumab to the regimen in patients with chronic spontaneous

If there is no success after 6 months of omalizumab therapy, off-label treatment

Assessment scales serve to evaluate the treatment, as well as this pathological entity affects the quality of life of the patient. We have the urticarial activity score (UAS) [15] or angioedema activity score (AAS) [16], chronic urticaria quality-of-

*LEN/EDF/WAO urticaria guideline*

Avoid first-generation H1 antihistamines based on benefit to risk ratio. Corticosteroids may be considered only for the short-term intervention. Cyclosporine A for refractory chronic urticaria not responsive to other

*DOI: http://dx.doi.org/10.5772/intechopen.88369*

*Approach to Chronic Urticaria from Primary Care and Emergency Services: Case Reports… DOI: http://dx.doi.org/10.5772/intechopen.88369*

#### **Figure 19.**

*Topics in Primary Care Medicine*

**50**

bedtime.

**Figure 18.**

**Figure 17.**

*Nonsedative antihistamines.*

treatments.

toxic than cyclosporine A.

antagonists, adding H 2 antagonists or first-generation H 1 antihistamines at

Cyclosporine A\* is used in refractory chronic urticaria not responsive to other

*Monoclonal antibody that binds to the Cε3 domain of circulating IgE, which prevents IgE from binding to and* 

A brief summary of *EAACI/GA2LEN/EDF/WAO guidelines* are as follows:

Up-dosing second-generation H1 antihistamines are the second-line therapy. Omalizumab is the third-line treatment, which is recommended because it is less

Omalizumab as third-line treatment.

*activating receptors in mast cells (***Figure 19***).*

Corticosteroids considered only for short treatment.

First-line treatment, second-generation H 1 antihistamines.

*Recommended treatment algorithm for chronic urticaria.*

Not included in algorithm H2 antihistamines (used only on an individual case). Avoid first-generation H1 antihistamines based on benefit to risk ratio.

Corticosteroids may be considered only for the short-term intervention. Cyclosporine A for refractory chronic urticaria not responsive to other

treatments.

\*Cyclosporin A is an immunosuppressive agent, widely used in organ transplantation to prevent rejection.

The current version of the *EAACI/GA<sup>2</sup> LEN/EDF/WAO urticaria guideline* recommends:

When chronic inducible urticaria is suspected, differential diagnoses should be ruled out. The diagnosis should be confirmed by provocation test disease. The activity should be measured by determining the trigger threshold disease burden and control should be measured.

Second-generation H1 antihistamines remain the treatment of first choice.

If continuous treatment for 2–4 weeks does not lead to adequate control of symptoms, the guidelines recommend up-dosing (up to four times the standard dose).

If there is no improvement with high-dose antihistamines, it is recommended to add omalizumab to the regimen in patients with chronic spontaneous urticaria.

If there is no success after 6 months of omalizumab therapy, off-label treatment with cyclosporine is recommended.

#### **7. Assessment scales**

Assessment scales serve to evaluate the treatment, as well as this pathological entity affects the quality of life of the patient. We have the urticarial activity score (UAS) [15] or angioedema activity score (AAS) [16], chronic urticaria quality-oflife questionnaire, and urticaria control test (UCT).


**Figure 20.** *UAS.*


**Figure 21.**

*Urticaria control test.*

The current guideline endorses the urticaria activity score and/or the angioedema activity score to assess the disease activity in CSU patients [17] (**Figure 20**).

The urticaria control test should be used in all CSU patients. The UCT is a retrospective tool used to rapidly and reliably assess disease control with four simple questions (**Figure 21**). Patients answer each of the four UCT questions, and the corresponding points (0–4 per answer) are added up to yield a total score of 0–16. The cutoff for controlled urticaria is 12 points. A score of 11 or less indicates insufficient disease control, whereas a score of 12 or more suggests adequate disease control [18].

**53**

**Author details**

Luis Geniz Rubio1

and Sara Alcántara Luna1

\*, Macarena Ávila Pérez<sup>2</sup>

1 Hospital Juan Ramón Jimenez, Huelva, Spain

\*Address all correspondence to: luis.geniz@gmail.com

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

2 Hospital Reina Sofía, Córdoba, Spain

provided the original work is properly cited.

, José Ángel López Díaz1

*Approach to Chronic Urticaria from Primary Care and Emergency Services: Case Reports…*

We want to thank IntechOpen for the opportunity to publish this chapter. We also want to thank our friends and family for their patience and unconditional

*DOI: http://dx.doi.org/10.5772/intechopen.88369*

**Thanks**

support.

## **Conflict of interest**

None.

*Approach to Chronic Urticaria from Primary Care and Emergency Services: Case Reports… DOI: http://dx.doi.org/10.5772/intechopen.88369*

## **Thanks**

*Topics in Primary Care Medicine*

**52**

(**Figure 20**).

**Figure 21.** *Urticaria control test.*

**Figure 20.** *UAS.*

control [18].

None.

**Conflict of interest**

The current guideline endorses the urticaria activity score and/or the angioedema activity score to assess the disease activity in CSU patients [17]

The urticaria control test should be used in all CSU patients. The UCT is a retrospective tool used to rapidly and reliably assess disease control with four simple questions (**Figure 21**). Patients answer each of the four UCT questions, and the corresponding points (0–4 per answer) are added up to yield a total score of 0–16. The cutoff for controlled urticaria is 12 points. A score of 11 or less indicates insufficient disease control, whereas a score of 12 or more suggests adequate disease

We want to thank IntechOpen for the opportunity to publish this chapter. We also want to thank our friends and family for their patience and unconditional support.

## **Author details**

Luis Geniz Rubio1 \*, Macarena Ávila Pérez<sup>2</sup> , José Ángel López Díaz1 and Sara Alcántara Luna1

1 Hospital Juan Ramón Jimenez, Huelva, Spain

2 Hospital Reina Sofía, Córdoba, Spain

\*Address all correspondence to: luis.geniz@gmail.com

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

## **References**

[1] Zuberbier T et al. The EAACI/ GA(2) LEN/EDF/WAO guideline for the definition, classification, diagnosis, and management of urticaria: The 2013 revision and update. Allergy. 2014;**69**(7):868-887

[2] Greaves MW. Pathology and classification of urticaria. Immunology and Allergy Clinics of North America. 2014;**34**(1):1-9

[3] Maurer M, Magerl M, Metz M, et al. Practical algorithm for diagnosing patients with recurrent wheals or angioedema. Allergy. 2013;**68**:816-819

[4] Zuberbier T. The role of allergens and pseudoallergens in urticaria. The Journal of Investigative Dermatology. Symposium Proceedings. 2001;**6**:132-134

[5] Church MK, Kolkhir P, Metz M, Maurer M. The role and relevance of mast cells in urticaria. Immunological Reviews. 2018;**282**:232-247

[6] Bernstein JA, Lang MD, Khan DA. The diagnosis and management of acute and chronic urticaria: 2014 update. The Journal of Allergy and Clinical Immunology. 2014;**133**:1270-1277

[7] Kulthanan K. Clinical practice guideline for diagnosis and management of urticaria. Asian Pacific Journal of Allergy and Immunology. 2016;**34**(3):190-200

[8] Zuberbier T, Aberer W, Asero R, et al. The EAACI/GA 2LEN/ EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria. The 2017 revision and update. Allergy. 2018;**73**:1393-1414

[9] Guillén-Aguinaga S, Jáuregui Presa I, Aguinaga-Ontoso E, et al. Updosing

nonsedating antihistamines in patients with chronic spontaneous urticaria: A systematic review and meta-analysis. The British Journal of Dermatology. 2016;**175**:1153-1165

[10] Sánchez-Borges M, Ansotegui I, Montero Jimenez J, et al. Comparative efficacy of non-sedating antihistamine updosing in patients with chronic urticaria. World Allergy Organization Journal. 2014;**7**(1):33

[11] Maurer M, Staubach P, Raap U, et al. H1-antihistamine-refractory chronic spontaneous urticaria: It's worse than we thought–first results of the multicenter real-life AWARE study. Clinical and Experimental Allergy. 2017;**47**:684-692

[12] Maurer M, Metz M, Brehler R, et al. Omalizumab treatment in patients with chronic inducible urticaria: A systematic review of published evidence. The Journal of Allergy and Clinical Immunology. 2018;**141**:638-649

[13] Kaplan A, Ledford D, Ashby M, et al. Omalizumab in patients with symptomatic chronic idiopathic/ spontaneous urticaria despite standard combination therapy. The Journal of Allergy and Clinical Immunology. 2013;**132**:101-109

[14] Diakow M, James W. Chronic Urticaria Guidelines. Available in emedicine. Medscape. Article 1050052; 2017

[15] Hawro T, Ohanyan T, Schoepke N, et al. The urticaria activity score— Validity, reliability, and responsiveness. The Journal of Allergy and Clinical Immunology. In Practice. 2018;**6**:1185-1190

[16] Weller K, Magerl M, Peveling-Oberhag A, et al. The angioedema quality of life questionnaire

**55**

*Approach to Chronic Urticaria from Primary Care and Emergency Services: Case Reports…*

*DOI: http://dx.doi.org/10.5772/intechopen.88369*

(AE-QoL)-assessment of sensitivity to change and minimal clinically important difference. Allergy.

[18] Weller K, Groffik A, Church MK, et al. Development and validation of the urticaria control test: A patientreported outcome instrument for assessing urticaria control. The Journal of Allergy and Clinical Immunology.

2016;**71**:1203-1209

2012;**108**:20-24

2014;**133**:1365-1372

[17] Mathias SD, Crosby RD, Zazzali JL, et al. Evaluating the minimally important difference of the urticaria activity score and other measures of disease activity in patients with chronic idiopathic urticari. Annals of Allergy, Asthma and Immunology.

*Approach to Chronic Urticaria from Primary Care and Emergency Services: Case Reports… DOI: http://dx.doi.org/10.5772/intechopen.88369*

(AE-QoL)-assessment of sensitivity to change and minimal clinically important difference. Allergy. 2016;**71**:1203-1209

[17] Mathias SD, Crosby RD, Zazzali JL, et al. Evaluating the minimally important difference of the urticaria activity score and other measures of disease activity in patients with chronic idiopathic urticari. Annals of Allergy, Asthma and Immunology. 2012;**108**:20-24

[18] Weller K, Groffik A, Church MK, et al. Development and validation of the urticaria control test: A patientreported outcome instrument for assessing urticaria control. The Journal of Allergy and Clinical Immunology. 2014;**133**:1365-1372

**54**

*Topics in Primary Care Medicine*

[1] Zuberbier T et al. The EAACI/ GA(2) LEN/EDF/WAO guideline for the definition, classification, diagnosis, and management of urticaria: The 2013 revision and update. Allergy.

nonsedating antihistamines in patients with chronic spontaneous urticaria: A systematic review and meta-analysis. The British Journal of Dermatology.

[10] Sánchez-Borges M, Ansotegui I, Montero Jimenez J, et al. Comparative efficacy of non-sedating antihistamine updosing in patients with chronic urticaria. World Allergy Organization

[11] Maurer M, Staubach P, Raap U, et al. H1-antihistamine-refractory chronic spontaneous urticaria: It's worse than we thought–first results of the multicenter real-life AWARE study. Clinical and Experimental Allergy. 2017;**47**:684-692

[12] Maurer M, Metz M, Brehler R, et al. Omalizumab treatment in patients with chronic inducible urticaria: A systematic review of published evidence. The Journal of Allergy and Clinical Immunology. 2018;**141**:638-649

[13] Kaplan A, Ledford D, Ashby M, et al. Omalizumab in patients with symptomatic chronic idiopathic/ spontaneous urticaria despite standard combination therapy. The Journal of Allergy and Clinical Immunology.

[14] Diakow M, James W. Chronic Urticaria Guidelines. Available in emedicine. Medscape. Article 1050052;

[15] Hawro T, Ohanyan T, Schoepke N, et al. The urticaria activity score— Validity, reliability, and responsiveness.

angioedema quality of life questionnaire

The Journal of Allergy and Clinical Immunology. In Practice.

[16] Weller K, Magerl M, Peveling-Oberhag A, et al. The

2018;**6**:1185-1190

2013;**132**:101-109

2017

2016;**175**:1153-1165

Journal. 2014;**7**(1):33

[2] Greaves MW. Pathology and

classification of urticaria. Immunology and Allergy Clinics of North America.

[3] Maurer M, Magerl M, Metz M, et al. Practical algorithm for diagnosing patients with recurrent wheals or angioedema. Allergy. 2013;**68**:816-819

[4] Zuberbier T. The role of allergens and pseudoallergens in urticaria. The Journal of Investigative

Dermatology. Symposium Proceedings.

[5] Church MK, Kolkhir P, Metz M, Maurer M. The role and relevance of mast cells in urticaria. Immunological

[6] Bernstein JA, Lang MD, Khan DA. The diagnosis and management of acute and chronic urticaria: 2014 update. The Journal of Allergy and Clinical Immunology. 2014;**133**:1270-1277

[7] Kulthanan K. Clinical practice guideline for diagnosis and management of urticaria. Asian Pacific Journal of Allergy and Immunology.

Asero R, et al. The EAACI/GA 2LEN/ EDF/WAO guideline for the definition,

[9] Guillén-Aguinaga S, Jáuregui Presa I, Aguinaga-Ontoso E, et al. Updosing

2016;**34**(3):190-200

2018;**73**:1393-1414

[8] Zuberbier T, Aberer W,

classification, diagnosis and management of urticaria. The 2017 revision and update. Allergy.

Reviews. 2018;**282**:232-247

2014;**69**(7):868-887

**References**

2014;**34**(1):1-9

2001;**6**:132-134

**Chapter 4**

Nigeria

**Abstract**

**1. Introduction**

**57**

Cultural Adaptation of a

*Aina Olufemi Odusola and Ayoade Adedokun*

Cardiovascular Health Education

Primary Care Patients from Rural

Culturally adapted behavioral treatments can optimize care. Following standard guidelines we adapted and tested a hypertension education program among primary care patients with hypertension from rural Nigeria. We reviewed literature and collected qualitative information from hypertensive patients to implement the first three of five cultural adaptation stages: *Information gathering, Adaptation design, and Preliminary adaptation testing*. Information obtained was used to adapt a *Cardiovascular Health Education Program* (CHEP) from a similar program *Culturally Appro-*

*priate Hypertension Education* (CAHE). CHEP was evaluated among 149

**Keywords:** standardized cultural adaptation, behavioral health education, goal setting assessment, hypertension self-management, rural Nigeria

Hypertension is a major risk factor of cardiovascular diseases (CVD), and is highly prevalent in sub-Saharan Africa (SSA) [1, 2]. CVD including ischemic heart disease and stroke are the world's biggest killers, having killed 15.2 million people in 2016 alone [3], and being responsible for 17.9 million (31%) of global deaths annually [4]. To limit CVD, World health organization (WHO) advocated preventive

hypertensive patients using pre, post design, and performance of behavioral goals. Data were analyzed using descriptive statistics and thematic contents. CHEP retained essential features of CAHE and added new culturally relevant information. Local context factors like substitutability of dietary *salt* and exercisability with cultural activities motivated healthy behavior and enhanced cultural fitness. Culturally permissive unhealthy practices were discouraged; intentional weight gain (*big is beautiful*), and non-smoking tobacco use (*sniffing, licking*). Performance of behavioral goals was outstanding; over 60% practiced self-set goals effectively. Standard cultural adaptation of behavioral education program demonstrated potential to limit cardiovascular diseases among hypertensive patients. Guidelinebased culturally adapted intervention increased hypertension self-management capabilities among hypertensive primary care patients from rural Nigeria.

Program among Hypertensive

## **Chapter 4**
