1st July 2023

Allergy and Sensitivity

Allergic Skin Disorders

Background

Allergic skin disorders are very common in dermatology, and are important to understand as they have a huge global burden of disease. These conditions have a large impact on a patient’s quality of life and can affect the economy as they are a major cause of occupational disease.

The most common allergic skin disorders are allergic contact dermatitis and acute urticaria. Other differentials for allergic skin disorders include; angioedema, atopic dermatitis, drug hypersensitivity reactions and skin manifestation of food allergies. Urticaria and angioedema will be covered in the next section. Please refer to the dermatology topic ‘Inflammatory disorders’ where dermatitis (contact and atopic) will be covered in more detail.

Aetiology

Allergic skin disorders are triggered by exposure to an allergen which generates an immune response. They are normally caused by Type 1 (acute) or Type 4 (delayed) hypersensitivity reactions.

Clinical Features

Contact dermatitis due to poison ivy

Image Source: Wikimedia Commons (2013). Poison ivy contact dermatitis, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Poison_ivy_contact_dermatitis.jpg (Accessed on: 1 May 2022).

Urticaria

Image Source: Wikimedia Commons (2014). Have Urticaria 3, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Have_Urticaria_3.jpg (Accessed on: 1 May 2022).

Clinical presentations of cutaneous allergic skin diseases vary, so a differential diagnosis will be determined by a thorough history and examination. Asking specifically about the symptoms, duration, and pattern of the eruption will assist with this.

Investigations

Patch testing is appropriate if you are considering contact dermatitis. Various allergens are placed on the patient’s back, usually for 48 hours. The dermatologist might assess the skin after a further 48 hours as some contact dermatitis reactions can take longer to develop.

Serum IgE or skin prick testing may be appropriate for urticaria.

Management

Identifying and removing the allergen is important to treat these conditions. Topical treatments, including steroids and calcineurin inhibitors, are helpful to relieve symptoms and inflammation.

Urticaria and Angioedema

Urticaria

Background

Mast cells release histamine which causes superficial skin swellings (wheals). Wheals are itchy, may sometimes have a burning sensation, and last for less than 24 hours.

Clinical features

Urticaria can present as discrete linear, round or ring-shaped wheals or swellings. They may be skin coloured, red or white, with or without an erythematous flare.

Erythematous wheals on the arm.

Image Source: Wikimedia Commons (2010). EMminor2010, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:EMminor2010.JPG (Accessed on: 1 February 2022).

Wheals on the chest wall.

Image Source: Wikimedia Commons (2010). Hives2010, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Hives2010.JPG (Accessed on: 1 February 2022).

Classification/Causes

Urticaria is classified as acute (< 6 weeks duration) or chronic (>6 weeks duration).

Acute urticaria can be triggered by infection, allergy to drugs and/or food (IgE mediated type 1 hypersensitivity reaction), stings and vaccinations. However, it can often be idiopathic.

Chronic urticaria can be spontaneous or inducible. Spontaneous is often idiopathic however associations with systemic conditions include thyroid disease, vitiligo, H. pylori infection and coeliac disease. Autoantibodies are also sometimes seen – anti-IgE or anti-FceRI antibodies.

Inducible causes:

• Symptomatic dermographism – scratching the skin
• Cold urticaria – exposure to cold, cold water on the skin
• Cholinergic urticaria – sweating after exercise
• Contact urticaria – substances that trigger an IgE mediated allergic response, e.g. cosmetics, latex, fabrics 
• Delayed pressure urticaria – pressure on the skin, e.g. carrying a heavy object
• Solar urticaria – sun exposure
• Heat urticaria – exposure to heat
• Vibratory urticaria – handling a vibrating object
• Aquagenic urticaria – exposure to water

Assessment

Activity of urticaria is assessed using an Urticaria Activity Score (UAS7). The number of wheals (<20, 20-50, >50) and severity of itch (mild, moderate, intense) are scored every 24 hours for 7 days, giving a maximum score of 42.

The Dermatology Life Quality Index (DLQI) can also be used to measure the impact of the rash on quality of life.

Investigations

• Normally a clinical diagnosis
• Skin biopsy – histology may reveal oedema in the dermis, dilated blood vessels, and mixed inflammatory infiltrate
• If indicated, blood tests to rule out a systemic cause: e.g. full blood count and autoimmune screen
• Skin prick testing if suspected food allergy

Treatment

• Avoid triggers if known/identified
• Antihistamines (2nd generation)
• Short course of oral steroids
• Chronic spontaneous urticaria: Ciclosporin, Omalizumab
• Epipen if there is cardiovascular compromise or breathing difficulties

Angioedema

Background

Angioedema is characterised by a sudden, localised, deep swelling of the subcutaneous tissue of the skin and mucous membranes, caused by increased endothelial permeability and plasma extravasation in the dermis and submucosa. It varies in severity and can be life threatening.

Classification and Pathophysiology

• Histaminergic – histamine and other vasoactive molecules are released. This type of angioedema can present with associated urticaria, anaphylaxis and bronchospasm.
• Non-histaminergic – bradykinin and complement derived mediators are released.

Aetiology

• Acute allergic
• Hereditary – C1 inhibitor deficiency (type I) or low activity (type II) causes an increase in bradykinin levels
• Acquired C1 inhibitor deficiency– secondary to autoimmune disease, malignancy or infection
• Iatrogenic – NSAIDs, ACE inhibitors (non-allergic)

Clinical Features

• Skin coloured or pale red swellings of the skin or submucosal tissue
• Lesions vary in size and are asymmetrical
• Generally affects the face or genital skin, however limbs, airways and abdomen can also be affected
• Associated urticaria in 1/3 of cases

Angioedema causing periorbital swelling. 

Image Source: Wikimedia Commons (2008). Angioedema2010, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Angioedema2010.JPG (Accessed on: 1 February 2022).

Investigations

• Routine blood tests: full blood count, liver function tests, renal function, c-reactive protein
• Other blood tests: thyroid stimulating hormone, tryptase, IgE, thyroid antibodies, C1 inhibitor concentration and function, complement, ANA, ANCA
• Skin biopsy

Treatment

• Stop triggering factor
• Keep the airways patent
• Treat any underlying infection
• Antihistamines
• Corticosteroids
• C1INH concentrate (for non-histaminergic angioedema)
• Prophylaxis: Danazol

Prognosis

Self-limiting after a few hours or days.

Cutaneous Reactions to Drugs

Background

There are various types of cutaneous reactions to drugs which can range from mild to life threatening. One of the most common types is morbilliform or maculopapular drug eruption. The rash usually appears 1 to 2 weeks after starting the drug, such as antibiotics. It usually initially appears on the trunk then spreads to the neck and limbs symmetrically. Serum sickness occurs when the body produces antibodies to foreign proteins, often from non-human antitoxins or antivenoms. Fixed drug eruption occurs as a recurrent lesion at the same site after re-exposure to the causative drug.

On the more severe end of the spectrum, Severe Cutaneous Adverse Reactions (SCAR) include a number of conditions which are important to be aware of. These include Stevens-Johnson syndrome /Toxic Epidermal Necrolysis (SJS/TEN), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) and acute generalised exanthematous pustulosis (AGEP).

SJS/TEN is a rare but serious condition that can be caused by several drugs such as antibiotics, e.g. cotrimoxazole, penicillin, anticonvulsants (such as carbamazepine and phenytoin), and allopurinol. In SJS/TEN, patients usually develop prodromal flu-like illness for several days before the rapid development of a painful blistering rash. It is known as SJS when <10% of skin is involved, SJS/TEN overlap when 10-30% of skin is involved, and TEN when >30% of skin is affected.

DRESS is also called drug induced hypersensitivity syndrome (DIHS). Symptoms may start 2-6 weeks after drug exposure. It usually affects several organs and is associated with swollen lymph nodes, eosinophilia, thrombocytopenia and abnormal liver function tests.

In AGEP, the rash appears around 2 days after starting the medication. It usually develops on the face and becomes widespread with pustules. It is associated with neutrophilia and raised inflammatory markers.

Causes

There are several causes of drug reactions including

1. Allergic reactions
   • Immediate reaction is mediated by IgE antibodies
   • Delayed reactions mediated by IgG antibodies, immune complexes and cytotoxic T cells
2. Pseudoallergic reactions
3. Dose-related reactions

A careful history and skin examination is required to diagnose the eruption. Blood tests, including full blood count (noting neutrophils and eosinophils), renal function and liver function, may also be useful.

Morbilliform drug eruption on back. 

Image Source: Wikimedia Commons (2013). Drug reaction, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Drugreaction.jpg (Accessed on: 1 April 2022).

Management

For more severe reactions, hospital admission may be required. The mainstay of treatment would be to stop the causative drug. A short course of topical steroids may be necessary, and regular emollients will keep the skin moisturised. Further treatment may be needed as indicated if systemic symptoms are involved.

Photosensitivity

Background

Photosensitivity describes a group of symptoms, diseases and conditions that are exacerbated by sunlight. Photodermatosis is a rash caused by photosensitivity, whereas it is called photodermatitis if the rash is eczematous. There are many different classifications of photosensitive rashes:

• Primary – exposure to sun causes a specific disease, e.g. polymorphic light eruption, solar urticaria, juvenile spring eruption
• Exogenous – photodermatoses rash is caused by an external photosensitiser such as food, drug or chemical that increases sensitivity to light, e.g. thiazide, tetracycline, NSAID, quinine
• Metabolic – the photodermatitis is caused by a metabolic defect, e.g. porphyria cutanea tarda
• Genetic – associated with a genetic disorder, e.g. xeroderma pigmentosum

Light Spectrum

Image Source: Flickr (2020). Light spectrum, Licensed under a creative commons licence. Available for free at: https://www.flickr.com/photos/rosenfeldmedia/49781640696 (Accessed on: 1 April 2022).

Clinical Features

In photodermatosis, the affected areas are those that are exposed to the sun. There is often a sharp line of demarcation between exposed and non-sun exposed areas of the skin. Skin folds and furrows are usually spared. Sometimes, it can only affect certain areas, e.g., photodermatosis on top of the ears in juvenile spring eruption.

Polymorphic Light Eruption on the Chest

Image Source: Wikimedia Commons (2013). Polymorphic Light Eruption on the chest, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Polymorphic_Light_Eruption_on_the_chest.jpg (Accessed on: 1 April 2022).

Investigations

Photosensitivity is usually a clinical diagnosis, but investigations can be done to try and identify the underlying cause. This includes blood tests (full blood count, renal profile, liver function tests, iron studies, autoimmune screen and porphyrias) and stool and urine samples. Autoimmune screens are to look for connective tissue conditions and stool/urine samples are used to check for porphyrins if suspecting porphyria. Rarely, contact photosensitivity tests can be carried out where a photosensitising patch is applied to the skin and checked 2 days after the light is shone to the area.

Management

This mainly involves ensuring adequate sun protection, e.g. sun cream, long sleeved clothing, wide brimmed hat.