Urticaria is characterized by transient skin or mucosal swelling due to plasma leakage. Superficial dermal swellings are wheals, and deep swellings of the skin or mucosa are termed angioedema. Wheals are characteristically pruritic and pink or pale in the center, whereas angioedema is often painful, less well defined and shows no color change.

There are several recognizable clinical pattern of urticaria y different causes. The latter include allergy, autoimmunity, drugs, dietary pseudo allergens, and infections. Many cases remain unexplained even after an extensive evaluation.

Diagnosis is based primarily on the history and clinical examination. Determination of the etiology or triggers, as well as exclusion of other diagnoses, may require further investigation, including blood test, physical and dietary challenges, skin test and skin biopsy.

Urticaria has been used as a descriptive term for the swelling of the skin and Angioedema seen as a separate entity. However there is an increase in the degree of acceptance in the term “Urticaria” is more appropriate to define a disease where its clinical presentation is determined by the depth of the swelling.

Clinical classification of Urticaria and Angioedema

Because the underlying cause of hives, in most of the first consultations is unknown and the episode duration (on average disappears in less than 24 hrs), it has been necessary to classify it according to the clinic symptoms  instead of the causes.

  1. “Ordinary” (spontaneous) urticaria (all urticarias not classified below)
    Physical (inducible) urticarias (see Table 18.3).
  2. Urticarial vasculitis (defined by vasculitis on skin biopsy).
  3. Contact urticaria (induced by percutaneous or mucosal penetration).
  4. Angioedema without wheals.
  5. Distinctive urticarial syndromes

Note: All clinical patterns of urticaria can be acute, episodic or chronic.

Acute Urticaria versus Chronic Urticaria

All urticarias are acute initially. Some will become chronic after a period of time that is usually defined as 6 weeks or more. The term “chronic urticaria” should only be applied to continuous urticaria occurring at least twice a week off treatment. Urticaria occurring less frequently than this over a long period is better called episodic (or recurrent) because this presentation is more likely to have an identifiable environmental trigger. The causes of acute urticaria presenting to emergency dermatology clinics in one survey are shown in Figure 18.7.

Most of these patients probably fall into the ordinary category, because physical urticarias and urticarial vasculitis tend to persist beyond 6 weeks and contact urticarias would not normally present to the hospital. The high frequency of associated viral infections is notable, as is the lack of food allergy as a cause. The different clinical patterns of chronic urticaria and their causes (where known) are shown in Figure 18.8. These data reflect the experience of specialist urticaria clinics in dermatology departments and may not represent the experience of other medical practitioners, such as those in general practice, internal medicine, pediatrics and allergy.

“Ordinary” (Spontaneous) Urticaria.

The condition can present at any age. Acute urticaria is common in  young children with atopic dermatitis, but chronic urticaria peaks in the fourth decade. Multiple pruritic wheals of different sizes erupt anywhere on the body and then fade within 2-24 hours without bruising, angioedema lasts longer. Urticaria may occur at any time, but often appears in the evening or is present on waking. Irritation tends to be most intense at night and may disturb or prevent sleep. This, in turn, compounds the distress of the condition. Substantial impairment in quality of life measures, including self-image, sexual relationships and social interaction, has been demonstrated. Women may describe pre menstrual exacerbation. Systemic symptoms of fatigue, lassitude, sweats and chills, indigestion or arthralgias are common with severe attacks, but the occurrence of pyrexia or arthritis should alert the clinician to another explanation, such as urticarial vasculitis, Schnitzler’s

Urticaria Association with others diseases

Chronic urticaria has been associated with autoimmune thyroid disease and other autoimmune conditions, including vitiligo, insulin dependent diabetes, rheumatoid arthritis and pernicious anemia Patients with demonstrable histamine-releasing auto antibodies have a very strong association with HLA-DR4 and its associated allele HLA-Q8A.

A possible association between Helicobacter pylori gastritis and chronic urticaria was suggested by a systematic review of therapeutic studies, which showed a higher frequency of urticaria remission when the infection was eradicated than when it was not. Parasitic infection as intestinal strongyloidiasis, are an uncommon cause of urticaria in developed countries, but may be a significant problem where they are endemic. Acute urticaria due to gastric Anisakiasis simplex has been reported from Spain. Possible associations between dental infection or gastrointestinal candidiasis and chronic urticaria have not been substantiated by large epidemiological studies. Although there have been anecdotal reports linking urticaria to malignancy, no statistically significant association was found in a large Swedish survey

Physical (Inducible) Urticarias.

The physical urticarias represent a distinct subgroup of the urticarias that are induced by an exogenous physical stimulus rather than occurring spontaneously. Because cholinergic urticaria is triggered by factors that lead to sweating (e.g. a rise in core body temperature, stress or spicy foods), rather than an external physical stimulus, it is often classified separately from other inducible urticarias; for the sake of convenience, it will be included here. The physical urticarias are classified by the predominant stimulus that triggers whealing, angioedema or anaphylaxis (Table 18.3). Of all the urticarias, they may affect the quality of life most severely, particularly delayed pressure urticaria and chohergic urticaria. While the lesions of most physical urticarias occur within minutes of provocation and generally resolve within 2 hours, a
few physical urticarias (e.g. delayed pressure urticaria, dclayed dermographism) develop after a delay of several hours and persist for 24 hours or longer

The wheals are usually localized to the stimulated area of skin. However, sometimes the physical stimuli nced to produce a systemic effect, e.g. a rise or drop in core body temperature, to induce urticaria of a reflex type. Thus, gencralized heating of the body can induce cholinergic urticaria (which is common), and generalized cooling, cold reflex urticaria (which is rare). Here, multiple small wheals occur on
widespread areas of the body.

Angioedema may be seen with all the physical urticarias except with symptomatic dermographism. Vibratory angioedema manifests with subcutaneous swelling but not wheals. Also several forms of physical urticaria can coexist in the same patient. Common combination include symptomatic dermographism and cholinergic urticaria; cold and cholinergic urticaria; and delayed pressure urticaria and delayed dermographism. Delayed pressure urticaria may coexist with chronic urticaria.

Symptomatic dermographism
Fig. 1.1 Symptomatic dermographism within minutes os scratching

Urticaria due to mechanical stimuli.

Dermographism (literally “skin writing”) (syn. factitious urticaria) Immediate dermographism
This is divided into simple or symptomatic. Simple immediate dermophism occurs in ~5% of normal people in response to moderate stroking of the skin and may be regarded as an exaggerated physiologic response Symptomatic dermographism is the most common of the physical urticarias (Fig. 1.1). It manifests as linear wheals at sites of scratching or sites of friction, such as collars and cuffs of clothes. Wheeling occurs after gentle stroking of the skin in response to a shearing force. Patients most frequently young adults, often complain of pruritus before the wheals appear and may not associate them with scratching. It is worst in the evening within an hour. Mucosal involvement does not occur, but vulvar swelling during sexual intercourse has been reported. The general course is unpredictable, but usually there is a gradual tendency towards improvement over several years. Symptomatic dermographism occasionally follows scabies infestation and penicillin allergy. There is no association with systemic disease, allergy, food allergy or autoimmunity.

Delayed pressure urticaria
Fig. 1.2 Delayed pressure urticaria

Delayed pressure urticaria

Delayed pressure urticaria (DPU) is important because it can interfere severely with quality of life, it may be underdiagnosed and its treatment difficult”, DPU is characterized by the development of deep erythematous swellings at sites of sustained pressure to the skin, after a delay of 30 minutes to 12 hours (Fig. 1.2), sometimes it resembles angioedema. The swellings are usually pruritic, painful, or both, and may persist for several days, unlike the spontaneous wheals of ordinary
urticaria. Sites frequently involved are the waistline after wearing tight clothing, below the elastic of socks, the feet in tight shoes, the palms after manual work, the soles after walking or climbing ladders, and the genitalia after intercourse systemic features such as malaise, “flu-like” symptoms and arthralgias may occur. If the swellings occur over joints, the resulting restriction of motion may be mistaken for arthritis. The prognosis is variable but the mean duration in different series was 6-9 years. Up to 37% of patients with chronic ordinary urticaria attending a hospital specialist had associated DPU”. Conversely, nearly all patients with DPU use of this association and clinic have associated spontaneous wheals. Becaclayed onset, patients may not be aware of any relationship toe d pressure unless specifically questioned.

Vibratory angioedema

This is a very rare form of urticaria, where a vibratory stimulus induces localized swelling and erythema within minutes, lasting 30 minute Stimuli include jogging, vigorous rubbing with a towel, and the use of vibrating machinery such as lawnmowers and motorcycles. Avoidance of vibratory stimuli enables patients to live a normal life. Vibrator angioedema may be acquired or familial. The acquired form is often ilder, and it may be associated with other physical urticarias such as DPU and immediate symptomatic dermographism. The familial form is dominantly inherited, and intense vibratory stimuli may induce generalized erythema and headache.

Urticaria due to temperature changes

Heat exposure

Heat contact urticaria is one of the rarest forms of urticaria, where, within minutes of contact with heat from any source, itching and whealing occur at the site of contact, lasting up to 1 hour. This must be distinguished from cholinergic urticaria. Patients can present after contact with hot water e.g. washing dishes), but also after contact with radiant heat or warm sunlight. Systemic symptoms of faintness, headache, nausea and abdominal pain have occurred when the urticaria is extensive. There is an even rarer delayed form.

Cold exposure

Cold urticaria represents a heterogeneous group of conditions in which whealing occurs within minutes of rewarming after cold exposure

Cold urticaria
Fig. 1.3 Cold urticaria. Wheals developed on the forearm after placement of an ice cube for 10 minutes.

Primary cold contact urticaria.

The most commonly encountered form is primary cold urticaria; it accounts for at least 95% of cases Fig. 1.3) Although cold urticaria may follow respiratory infections, arthropod bites or stings, and perhaps HIV infection, the cause of most cases remains unknown. It may occur at any age, but is most frequently in young adults. Itching, burning and whealing occur in cold exposed areas minutes after rewarming the skin. Commonly, primary cold contact urticaria occurs in rainy, windy weather and after contact with cold objects, including ice cubes. Patients often relate symptoms to changes in temperature as much as to the absolute external temperature. Systemic symptoms of flushing, headache, syncope and abdominal pain can develop if large areas are affected. Cold baths and swimming should usually be avoided as there is a potential risk of anaphiylazis
The mean duration was 6-9 years in one series, though primary cold contact urticaria may be more transient if it follows a viral infection.

Secondary cold contact urticaria

Cases due to serum abnormalities such as cryoglobulinemia or cryofibrinogenemia are rare, and are associated with other manifestations such as Raynaud’s phenomenon or purpura. The wheals ase usually similar to those of primary cold contact urticaria, but may last longer. The presence of circulating cryoglobulins or cryofibrinogen should be determined, and serum protein and immunofixation electrophoreses performed. Underlying causes, such as hepatitis B or C viral infections,  lymphoproliferative disease or infectious mononucleosis, should be excluded

Reflex cold urticaria

In this form, generalized cooling of the body induces widespread whealing. Patients with this disorder can experience life-threatening reaction from exposures such as diving into a cold lake. The ice cube test is negative, but placing the patient in a cold room at 4 Celsius degree can reproduce the lesions. This is no longer performed, as fatal anafilaxis can occur.

Familial cold urticaria

Familial cold urticaria, also referred to as familial cold auto inflammatory syndrome, belongs to the group of disorders known as cryopyrin associated periodic syndromes (see Table 45.2) The patients have mutations in NLRP3, which encodes the protein cryopyrin, and they develop cold-induced urticarial papules

Urticaria due to sweating or stress

Cholinergic urticaria
Fig. 18.12 Cholinergic urticaria after exercising sweating

Cholinergic urticaria

Cholinergic urticaria is characterized by multiple, transient, papular wheals that are 2-3 mm in diameter and surrounded by an obvious flare. They occur within 15 minutes of sweat-inducing stimuli, such any form of physical exertion, hot baths or sudden emotionall stress (Fig. 18.12). Other eliciting stimuli include moving from a cold to a
hot room, drinking alcohol and eating spicy food. It occurs more frequently in young adults with an atopic diathesis and is unusuall in the elderly
After the appropriate stimulus, pruritus is followed by the developmet of small, monomorphic wheals that are symetricallly distributed. They are most prominent on the upper half ot the body, but can also affect the lower legs and forearms and even become genenalized.
Angioedema and systemic manifestations consisting of faintness, headache, palpitations, abdominal pain and wheezing may occur. Reduced forced expiratory volumes (in the absence of respiratory symptoms) have been recorded by spirometry. In more severely affeced individuals, cholinergic urticaria can cause severe personal and ocupational disability.
Cold urticaria, symptomatic dermographism or aquagenicurticaria may be associated with cholinergic urticaria. There is usally a gradual tendency towards improvement, but the condition may last for years.
Rarer forms include cholinergic pruritus, cholinergic erythema (in which pruritic, symmetric, small erythematous macules appear to be persistent, but individual lesions actually last for up to 1 hour), and cholinergic dermographism Severe exercise-induced urticaria may sometimes progress to anafilaxis

 Exercise-induced anaphylaxis (EIA)

This can occur without the typical wheals of cholinergic urticaria and appears to be a syndrome in its own right. Food- and exercise-induced anaphylaxis (FEIA) is an increasingly recognized syndrome. In FEIA, angioedema and/or anaphylaxis occur within minutes of exercise if it follows either prior ingestion of a specific food (e.g. α-gliadin in wheat), or sometimes within 4 hours of a heavy meal. FEIA may be due to priming of the mast cell by prior exposure to an allergen, or to an unknown mechanism.

Urticaria due to others exposures

Solar urticaria can cause itching and whealing occur within minutes of exposure to UV or visible wavelengths of solar radiation specific to the patient.

Aquagenic urticaria

In aquagenic urticaria, contact with water of any temperature induces an urticarial eruption resembling a sparse form of cholinergic urticaria. Lesions occur most frequently on the upper part of the body and last for less than an hour. Other physical urticaria must be excluded and the condition must be differentiated from acuagenic pruritus.

Urticarial Vasculitis
Urticarial Vasculitis

Urticarial Vasculitis

Urticarial vasculitis is a clinicopathologic entity in which cutaneous lesions last longer than 24 hours and histologically show evidence of leukocytoclastic vasculits.

Contact Urticaria

Contact Urticaria is defined by the development of urticaria at the sites of contact with skin or mucosa, but contact erythema and even burning  and stinging without erythema are sometimes embraced in the definition. Percutaneous or mucosal penetration of the urticant may have distant effects, including acute urticaria or even anaphylaxis. Contact urticaria may be more common than reported, as patients do not present to the hospital or tertiary care clinics, because the diagnosis can be self-evident.
Immunologic and non-immunologic forms are recognized, depending on whether the contact urticaria is due to allergen interaction with specific IgE or IgE-independent. Allergic contact urticaria can be seen in children with atopic dermatitis who become sensitized to environmental allergens, such as grass, animals and foods, or in glove-wearers who are allergic to latex. In those individuals repeatedly exposed to latex via mucosal surfaces (e.g. urinary catheterization in spina bifida patients), allergic contact urticaria can be complicated by anaphylasis. Non-immunologic (i.e. non-allergic) contact urticaria is due to direct effects of urticants on blood vessels, such as from exposure to sorbic acid an benzoic acid  in eye solutions and foods or cinnamic aldehyde
in cosmetics; it may be mediated by PGD, and can be inhibited by NSAIDs. Percutaneous microinjection of vasomediators (e.g. histamine, acetylcholine, serotonin) via nettle stings or contact with histamine liberators that degranulate mast cells (e.g. dimethylsulfoxide, cobalt chloride) can lead to contact urticaria within minutes.

 Treatment of Ordinary and physical Urticarias

ClassExamplesPlasma half-life (hours)Daily adult dose *
Classic (sedating) H, antihistaminesChlorpheniramine (1)12-154 mg three times daily (up to 12 mg at night)
Hydroxyzine (1)2010-25 mg three times dally o 75 mg at night)
Diphenhydramine (2)410-25 mg at night
Doxepin r  (1)1710-50 mg at night
Second generation H, antihistaminesAcrivastine ¹ (1)2-48 mg three times daily
Cetirizine y (1)7-1110 mg once daily
Loratadine (1)8-1110 mg once daily
Mizolastine W (1)1310 mg once daily
Newer second-generation H1 antihistaminesDesloratadine (1)19-355 mg once daily
Fexofenadine (1)17180 mg once daily
Levocetirizine (1)7-105 mg once daily
Rupatadine (1)610 mg once daily
H2 antagonists ãCimetidine (1)2400 mg twice daily
Ranitidine (1)2-3150 mg twice daily
* Current prescribing manuals should be consulted for details on doses in children.
r Possesses potent H, and H, antihistamine properties.
¹  Only available in the US as a combination product with pseudoephedrine for seasonal allergic rhinitis
y The active metabolite of hydroxyzine
W Not available in the US
ã Used in combination with Hi antagonists.
Generic nameDrugs classRouteDoseSpecial indication / associated diseases
Prednisone (2)CorticosteroidOral05 mg/kg dailySevere exacerbation (days only)
Epinephrine (2)SympathomimeticSub cutaneous, IM (self-administrated)300-500 mcgIdiopathic or allergic angioedema of throat/anaphylaxis
Montelukast (3)Leukotriene receptor antagonistOral10 mg dailyAspirin-sensitive urticaria, ? delayed pressure urticaria
Thyroxine (2)Thyroid hormoneOral50-150 mcg dailyAutoimmune thyroid disease
Colchicine (3)Neutrophil inhibitorOral0,5/0.6 – 1,5/1,8 mg* dailyNeutrophilic infiltrates in lesional biopsy specimens orlesional biopsy specimens or urticarial vasculitis
Sulfasalazine (3)AminosalicylatesOral2-4 g dallyDelayed pressure urticaria


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