Understanding allergic pruritus

Allergic pruritus, characterized by intense itching, arises from an allergic reaction where the immune system responds to allergens like pollen, food, or insect stings. This condition requires careful management and treatment because of its severe effects on quality of life and its tendency to cause scratching that can result in skin damage and secondary infections [17]. Furthermore, allergic pruritus is quite common as a 2018 study showed that around 45-55% of the Malaysian population have food allergies or incompatibilities [1,2]. This article will explore the diagnosis and treatment options for allergic pruritus and dive into its underlying mechanisms. 

Common triggers for allergic pruritus

Environmental triggers 

• Pollen
• Dust mites
• Animal dander

Food Allergens 

• Common foods: Peanuts, tree nuts, shellfish, fish, eggs, milk, soy, and wheat.
• Food additives: Preservatives, colorings, and flavorings.

Contact Allergens

• Metals: Nickel and cobalt, commonly found in jewelry and clothing fasteners.
• Cosmetics and personal care products: Perfumes, hair dyes, makeup, and skincare products.

Environmental Factors

• Extreme temperatures: Hot or cold weather can exacerbate itching.
• Humidity: High or low humidity can dry out or irritate the skin.

Mechanisms of allergic pruritus

When an allergen enters the human body, the immune system identifies it as a threat and overreacts. Initially, antigen-presenting cells (APCs), such as dendritic cells, encounter the allergen and activate T-helper cells to release cytokines. These cytokines then activate B-helper cells to produce Immunoglobulin E (IgE) antibodies against the allergens. This phase is known as initial sensitization [3].

Upon re-exposure to the allergen, it binds to the antibodies attached to mast cells, causing them to release histamine. Histamine is crucial in triggering itchiness by binding to H1 receptors on the skin. This binding activates specific itch sensory neurons called C-fibres in the dorsal root ganglia (DRG). Once activated, these C-fibre neurons send itch signals to the spinal cord and brain [8].

In the brain, itch signals travel from the spinal cord via the spinothalamic tract to the thalamus. After reaching the thalamus, the signals are projected to various areas for itch processing. The primary and secondary somatosensory cortex are the most frequently activated brain regions during itch processing, contributing to the localization, intensity, and recognition of itch. Other activated brain areas include the supplementary motor areas, striatum, and cerebellum, which control or initiate scratching behavior [4,5,6].

Symptoms of different types of allergic pruritus

The main symptom of allergic pruritus is itchiness due to allergic reactions. This itchiness can be localized, affecting a small area like an arm or leg or covering the entire body. Some patients may also experience redness, and skin lesions such as bumps, blisters, and itchiness [7].

Symptoms of different types of allergic pruritus 

Diagnostic methods

Diagnosing allergic pruritus starts with a physical examination and investigation of the patient's medical history. It is important to note that, pruritus in other words “itchiness” is a common presenting symptom of different medical conditions. Hence it is important to rule out other possible causes of itchiness. If the allergic reaction is suspected as the main cause of itchiness, the patient can undergo specific tests to confirm the diagnosis. 

Skin prick tests can be used to detect allergens that are causing overreaction in the body's defense system. Skin prick testing offers the advantages of being quick, informative for patients, and reasonably inexpensive. During the test, several allergens are pricked into the skin (multiple allergens can be pricked simultaneously). The skin is then closely observed for signs of allergic reaction such as redness or swelling [10]. 

Another method of detecting allergens is the serum-specific IgE test. It is a blood test that detects the presence of different IgE antibodies in a person's blood. IgE antibodies are normally present in small amounts in the blood. However, higher levels may indicate that the body overreacts to allergens, resulting in an allergic reaction such as allergic pruritus. There are two main types of serum-specific IgE tests, total IgE test and specific IgE test: 

• A total IgE test measures the overall amount of IgE antibodies in the blood.
• A specific IgE test measures the amount of IgE the body produces in response to a particular allergen, with a separate test conducted for each suspected allergen [11].

Importance of differential diagnosis to rule out other conditions

As mentioned before, pruritus is a prevalent symptom of several disease conditions. It is quite essential for healthcare professionals to accurately diagnose the patient and start a treatment plan as soon as possible. Some of the conditions are skin-related, including the formation of blisters and bumps on the skin and itchiness. However, not all pruritus dermatological conditions are caused by allergic reactions. For example, psoriasis is a skin condition caused by a complex immune-mediated process that triggers excessive skin cell production and itchiness is one of the symptoms as well. However, it is not caused by an allergic reaction like allergic contact dermatitis. Interestingly, systemic conditions such as diabetes can cause itchiness without concurrent skin disease. Therefore, it is of utmost importance to consider all the possible differential diagnoses of allergic pruritus to ensure that the patient receives the appropriate management [12,8].

Management and treatment 

Identifying the causes and triggers of allergic reactions is crucial for patients and they should avoid these triggers whenever possible. A skin prick test can be utilized to identify specific allergens, aiding patients in avoiding them effectively.

Avoidance strategies for allergens 

1. Ensure to keep the window closed and wear a mask during pollen season to avoid contact with pollen.
2. Use special dust-proof covers for the pillow and mattress. 
3. Regularly wash the bedding using hot water. 
4. Ensure the house is clean with a damp mop, rather than just dry-dusting [13].

Pharmacological treatment 

Topical medicated creams are an effective treatment option for skin disorders. Topical corticosteroids are the first-line treatment for acute pruritus for skin conditions such as allergic contact dermatitis psoriasis and atopic dermatitis. Though the exact mechanism is unclear, topical corticosteroids are believed to inhibit cytokine activation and reduce inflammation to manage itching. It is important to note that, topical corticosteroids are only effective in relieving inflammatory itch and would have no effect on patients with non-inflammatory itch. Most importantly, topical corticosteroids must be used for short periods as long-term use will lead to unwanted side effects such as acne and hyperpigmentation [15].

Topical calcineurin inhibitors

Topical calcineurin inhibitors (TCIs) are immunomodulators that have been effective in reducing itchiness in patients with atopic dermatitis. TCIs work by inhibiting T-cell activating and release of inflammatory cytokines. Thus, reduce inflammation and itchiness. Multiple studies have shown that topical calcineurin inhibitors successfully reduce pruritus in atopic dermatitis patients, including children [15].

Oral and topical antihistamines 

As implied by the name “anti-histamine”, this medication effectively blocks the impact of histamine within the body during an allergic reaction. Although anti-histamine is the first choice of drug for allergic conditions such as allergic rhinitis, it does have a lot of benefits in treating pruritic conditions. However, urticaria is the only skin condition where oral antihistamines showed treatment benefits. Furthermore, first-generation antihistamines are sedatives, which are valuable for patients with nocturnal pruritus (itchy skin at night that causes sleep disturbance) [14].

Similar to oral antihistamines, topical antihistamines showed limited benefit in treating pruritic conditions. However, topical antihistamines have been shown to reduce itchiness in patients with atopic dermatitis significantly. Unfortunately, topical antihistamines cause unwanted side effects such as allergic contact dermatitis and drowsiness. Therefore, even though it may have some advantages, its side effect profile limits its use, and it is advised to be used cautiously in older adults and best to avoid in children [15].

Emerging treatments and research in the field 

Most of the novel drug discoveries for pruritus focus on the immune and neural pathophysiology of itch. Many research studies show that the pain and itch process is quite similar. Therefore, painkillers such as naltrexone have the potential as anti-pruritus therapy. In a pilot study involving 18 patients with various chronic pruritic conditions, were administered topical 1% naltrexone cream. More than 70% of those patients experienced a significant reduction in itching. Subsequently, a randomized, placebo-controlled, crossover trial with the same formulation was conducted on 40 patients with atopic dermatitis (AD), showing that naltrexone was 29.4% more effective than the placebo, capable of reducing itch by 50% within 46 minutes [15,16].

IL-31 receptors have gained popularity as potential anti-pruritus drug targets as IL-31 receptors are overexpressed in humans with severe pruritus. Interestingly, IL-31 receptors are present in primary sensory afferent neurons and keratinocytes in the skin. Therefore, IL-31 receptors may be a sensible drug target for future novel anti-pruritic therapies [15].

Conclusion

In conclusion, allergic pruritus is an allergic reaction to allergens that leads to itchiness. Many types of allergic pruritus include atopic dermatitis, allergic contact dermatitis, and urticaria. It is important to diagnose a patient with the correct disease as itchiness is a common symptom of various dermatological disorders and systemic disorders Hence, it is crucial to consider all potential differential diagnoses of allergic pruritus to ensure the patient receives proper treatment.

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Written By

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wen yan

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shawn lim