Urticaria and urticaria-like conditions

Urticaria describes a group of conditions in which there are wheals (or weals) in the skin, i.e., itchy white or red lumps. Urticaria can occasionally be a sign of systemic disease.

Ordinary urticaria

Spontaneous or 'ordinary' urticaria is divided into acute urticaria (lasting a few hours or days or up to six weeks) and chronic urticaria (persisting more than six weeks, and sometimes life-long).

• Acute urticaria is self-limiting and often related to infection, food or medicine
• Chronic urticaria has no specific external cause and is considered autoimmune in most cases
• Ordinary urticaria may be accompanied by angioedema

The wheals are well defined raised lesions with a smooth surface. They may be red or white in colour, surrounded by a red or white flare. Wheals range in size from a few millimetres to many centimetres in diameter. Shape also varies: round, polycyclic (overlapping circles), annular (ring-shaped), geographic (like a map). They are randomly distributed on the body and may affect any site. They last no more than 24 hours and do not leave any marks behind.

Ordinary urticaria: asymmetrical weals that clear within 24 hours

More about ordinary urticaria ...

Physical urticaria

Physical urticarias are a response to an external factor. They are classified according to the provoking factor: stroking the skin in dermographism (skin writing), acetyl choline released during sweating in cholinergic urticaria, cold air or water in cold urticaria, a contact factor in contact urticaria, sun exposure in solar urticaria and firm pressure in delayed pressure urticaria. Physical urticarias have the following characteristics.

• Wheals occur at the site of the provoking factor
• Wheals lasting about 15 minutes, nearly always less than one hour (with the exception of delayed pressure urticaria, which lasts hours to days)

Physical urticaria: short-lasting weals at the site of provoking factor

Dermographism

Solar urticaria provoked experimentally

Cold urticaria provoked by ice cube

Urticarial skin lesions

Insect bites

Insect bites often result in itchy bumps (papules) or wheals. Their characteristics include:

• Initial sting is often felt
• On exposed sites
• Central blister (vesicle)
• Groups of lesions, often distributed asymmetrically
• More commonly arise in summer and autumn months
• Individual lesions persist for days to weeks
• Brownish discolouration that persists for months is often seen in skin that tans easily.

Childen and, less frequently, adults may develop papular urticaria, which is interpreted as a hypersensitivity reaction to insect bites. No initial sting is felt and old lesions may reappear.

Biopsy reveals an inflammatory infiltrate that includes eosinophils, and spongiosis of the epidermis.

Insect bites: grouped urticarial lesions with central punctum or blister

Urticarial dermatitis

Urticarial dermatitis presents with both urticaria-like and eczema-like lesions. It may be a drug eruption.

• Urticarial dermatitis usually affects elderly patients
• Persistent red itchy plaques may have a smooth surface (urticaria-like) or dry scratched surface (eczema like)
• They are distributed symmetrically on trunk, upper arms and thighs

Biopsy may be reported as dermal dermatitis with mixed inflammatory cells in the dermis and minimal spongiosis in the epidermis.

Urticarial dermatitis: persistent red plaques with smooth or dry surface

Contact dermatitis

Contact dermatitis sometimes appears urticarial rather than eczematous, with most of the inflammation in the dermis rather than the more superficial epidermis.

• It appears at the site of contact with the responsible agent
• It may arise in irritant contact dermatitis or allergic contact dermatitis
• Lesions clear up over days to weeks
• Patch tests may reveal an allergen in allergic cases

Contact dermatitis should be distinguished from contact urticaria, which is a short-lasting type of physical urticaria (see above).

Contact dermatitis: sometimes predominantly dermal

Erythema multiforme

Classic erythema multiforme presents with an acute eruption of target-shaped lesions on the hands, feet, knees and elbows. However target-shaped lesions may also be seen in ordinary urticaria.

• Target lesions are urticaria-like plaques characterised by concentric rings
• In erythema multiforme, blisters often arise in the centre of the plaques
• Individual lesions persist for 10 days to 3 weeks
• Mucosal lesions occur in more severe cases
• Erythema multiforme may be recurrent, usually due to herpes simplex virus infection

Biopsy is usually characteristic.

Erythema multiforme: crops of target lesions on hands and knees

Urticarial drug eruptions

Drug eruptions include urticaria and urticaria-like eruptions. Individual lesions resolve within hours in urticaria, and persist for days in urticaria-like eruptions. They are often described as morbilliform or maculopapular eruptions. Characteristics of drug eruptions include:

• The rash starts within 14 days of a new medication (except in drug hypersensitivity syndrome, when they arise within 8 weeks of starting a new medication)
• They arise sooner on re-challenge
• The medication may have already been stopped when the rash appears
• Red macules (small flat spots) and papules (small raised spots) may merge together to form large patches (large flat areas) and plaques (large raised areas)
• The rash is symmetrical and tends to be most severe on the trunk
• The rash may or may not be itchy
• There may or may not be a low-grade fever
• As the lesions fade, the surface peels
• Dark marks may persist for days to weeks

Biopsy reveals a subtle inflammatory infiltrate that includes eosinophils, and lymphocytes and apoptotic keratinocytes in the epidermis.

Drug eruptions: symmetrical urticated papules and plaques

Urticaria pigmentosa

Urticaria pigmentosa is a form of cutaneous mastocytosis in which there are brown macules and papules.

• Urticaria pigmentosa is mostly seen in infants and improves with age
• It may also arise in adults, when it tends to persist
• Lesions may affect trunk and limbs, and less often scalp and face
• The lesions urticate when they are rubbed or spontaneously, i.e. the papules swell into wheals, and these persist for up to an hour
• Lesions may blister in young children
• There may be few to hundreds of lesions
• Systemic involvement may result in flushing and faintness

Biopsy may reveal increased numbers of mast cells, but these can be difficult to identify and the tissue may look the same as normal skin.

Urticaria pigmentosa: brown spots that urticate

Autoimmune blistering diseases

The subepidermal autoimmune blistering diseases may initially present with urticarial lesions several days or weeks before blisters appear. These urticarial lesions may be seen in:

• Bullous pemphigoid
• Pemphigoid gestationis (pemphigoid associated with pregnancy)
• Linear IgA bullous dermatosis
• Epidermolysis bullosa acquisita

The characteristics of autoimmune blistering diseases include:

• Symmetrical distribution
• Tendency to involve trunk and skin folds (flexures)
• Often affects the elderly (pemphigoid) or pregnant patient (pemphigoid gestationis).

Skin biopsy for routine histopathology and direct immunofluorescence studies are necessary to confirm the diagnosis.

Urticarial plaques in autoimmune blistering diseases

Bullous pemphigoid

Bullous pemphigoid

Pemphigoid gestationis

Pruritic urticarial papules and plaques of pregnancy

PUPPP or Pruritic Urticarial Papules and Plaques of Pregnancy is an eruption occurring during the last few weeks of pregnancy, usually in a first pregnancy.

• Small pink papules may join to form plaques
• Urticarial lesions are most common, but eczematous and blistered plaques may also arise
• Lesions mostly affect the trunk, upper arms and thighs
• The spots usually start in the stretch marks (striae gravidarum)
• PUPPP clears up within a few weeks of delivery

PUPPP: symmetrical urticated plaques favouring stretch marks

Annular erythema

Annular erythema usually begins as small raised pink-red spot that slowly enlarges and forms a ring shape while the central area flattens and clears. They may resemble an urticarial wheal but often have a trailing scale. They are asymptomatic. The rings enlarge at a rate of about 2-5 mm/day until they reach a diameter of about 6-8 cm. Sometimes the lesions do not form complete rings but grow into irregular shapes.

Annular erythema: slowly enlarging rings

Autoimmune progesterone dermatitis

Autoimmune progesterone dermatitis is a rare, recurrent and itchy rash affecting women during their childbearing years.

• Skin lesions appear during the second half of the menstrual cycle and resolve during the menstrual period
• Urticaria, urticaria-like wheals, eczema-like lesions, blisters and target lesions may occur
• It is prevented when ovulation is prevented, e.g. by oral contraceptive agent

Interstitial granulomatous dermatitis

Interstitial granulomatous dermatitis is a distinctive pathological entity of an unusual persistent skin eruption often of an urticarial type. Other lesions described with the same pathology include papules, nodules and plaques that are skin coloured, red or brown. These may be oval, annular or cord-like.

Interstitial granulomatous dermatitis is associated with autoimmune diseases, particularly seronegative polyarthritis, and is occasionally seen in association with lymphoma, lung cancer, drugs and infections

Interstitial granulomatous dermatitis

Wells syndrome

Wells syndrome, also called eosinophilic dermatitis, also presents with urticarial lesions. Eosinophils are seen in the blood in 50% of patients.

• The lesions may be confined to one site or more generalised
• Individual lesions are itchy red to purple, swollen papules or plaques that resolve over days to weeks
• They may ressemble insect bites or cellulitis
• Lesions may be followed by brown marks that last for weeks to months
• Blisters may arise within the lesions
• Lesions may recur in the same site

Skin biopsy is characterised by eosinophils and flame figures.

Wells syndrome

Neutrophilic eccrine hidradenitis

Neutrophilic eccrine hidradenitis is a rare condition occurring in patients with acute myelogenous leukaemia, either while on or after receiving chemotherapy.

• Solitary or grouped urticaria-like papules and plaques are associated with fever

Skin biopsy reveals neutrophils around the eccrine sweat glands and some destruction of eccrine cells.

Neutrophilic eccrine hidradenitis: irregular urticated plaques with fever in chemotherapy patient

Urticaria – as a feature of systemic disease

Patients with ordinary urticaria do not usually have systemic symptoms, so if these are present, other diagnoses should be considered.

Scombroid fish poisoning

Sudden onset of a red itchy rash within 30 minutes of consuming decomposing scombroid fish may be due to scombroid fish poisoning in which large amounts of histamine are ingested. Unlike urticaria, there are no wheals. Other symptoms include headache, palpitations, nausea, diarrhoea and collapse.

Scombroid fish poisoning (tuna)

Urticarial vasculitis

Urticarial vasculitis is defined by histology showing small vessel vasculitis on skin biopsy.

• Urticarial skin lesions persist for longer than 24 hours
• They sting and burn rather than itch
• They leave brown marks or bruises behind as they fade
• They may be accompanied by purpura and other features of cutaneous vasculitis
• It can be a local process or associated with systemic disease
• It may be accompanied by migratory arthritis, heart disease, lung disease, kidney disease, gastrointestinal symptoms and/or neurological complications.
• Associations include systemic lupus erythematosus, systemic sclerosis, infections, inflammatory bowel disease, lymphoma and solid organ cancer.

Hypersensitivity vasculitis, cutaneous polyarteritis nodosa and Churg-Strauss syndrome may also present with urticaria-like lesions.

Urticarial vasculitis: urticarial lesions resolve with bruising

Sweet syndrome

Tender urticaria-like plaques may be seen in Sweet syndrome (acute neutrophilic dermatosis). The lesions often blister, and may affect mucosal surfaces as well as skin surfaces. They are often seen on the neck but may occur on any site. The plaques enlarge and persist for days to weeks. Sweet disease results in fever, malaise, arthralgia and other systemic symptoms.

Sweet syndrome: urticarial plaques are often blistered

Neutrophilic urticarial dermatosis

Neutrophilic urticarial dermatosis presents with urticarial lesions that are defined by a histological reaction pattern revealing neutrophils lined up between collagen fibres.

• Fever and arthritis may accompany the skin lesions
• Blood tests reveal raised ESR / CRP and neutrophil leucocytosis (raised white cell count)
• Underlying inflammatory conditions such as rheumatoid arthritis are often present
• Unlike Sweet syndrome (acute neutrophilic dermatosis), there is no blistering or mucosal involvement

Neutrophilic urticarial dermatosis in patients with rheumatoid arthritis

Autoinflammatory syndromes

The autoinflammatory syndromes are a group of mainly genetic diseases that affect the skin and other organs.

• Urticarial wheals, macules and papules may occur
• Skin lesions are accompanied by fever and joint disease
• Onset is frequently during childhood
• The inflammation involves activation of the cytokine, interleukin IL-1beta