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ANTIHISTAMINES AND PRURITUS: Scratch the surface

Pruritus (itch) can arise from numerous causes, including atopic eczema as well as seasonal and perennial (year-round) allergic rhinitis.1, 2, 3 This CPD module focuses on the role of antihistamines in the management of pruritus in infants and children.

LEARNING OBJECTIVES

After studying this module you should:

  • Be aware of the causes of and triggers for pruritus
  • Be familiar with management strategies for pruritus
  • Understand the recommended use of antihistamines in the management of pruritus associated with allergic rhinitis and atopic eczema
  • Be better able to offer practical advice to parents and carers about the use of antihistamines  for the relief of pruritus

NEXT STEPS

  • Read the clinical review: if you don't have a printed version, click here to download a pdf
  • Complete the online assessment
  • Receive CPD certificate

AUTHORS

Written by: Health Professional Academy
Reviewed by: Allergy UK

 

Zinc code: CHGBI/CHPIRI/0049/18e

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Pre-learning reflection

Please take a moment to answer these pre-learning questions.  Once completed, click 'next step' below to start this module.  These answers will be logged on your CPD certificate which will be emailed to you on completion as evidence of your learning.


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Introducing pruritus

Pruritus (itch) is an unpleasant, irritating sensation that provokes a reflex or desire to scratch4, 5

Chronic pruritus - which lasts for at least 6 weeks6 – is often difficult to treat and can be distressing4, 5, 6

Broadly, the causes of chronic pruritus can be divided into: dermatological, systemic, neuropathic and psychogenic (see table)4

Pruritus is the hallmark of atopic eczema;2, 3 NICE notes that rashes that do not itch are unlikely to be atopic eczema3

Nasal and ocular itching is a characteristic symptom of seasonal and perennial allergic rhinitis1, 7


introducing

Examples of conditions associated with chronic prurius4,5,6

Already studied the clinical review? Go straight to the test here
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Nerve pathways in pruritus

Pruritus arises when a substance that triggers itch stimulates skin receptors and activates the peripheral nerve pathway of itch5

At least two groups of C-fibres (small, unmyelinated nerves) transmit the itch signal to the spinal cord5

Applying histamine to skin induces pruritus.4 Histamine stimulates C-fibres that have receptors in the epidermis and are insensitive to mechanical stimulation5

Polymodal C-fibres have receptors in the dermis and respond to mechanical stimulation, but not to histamine.5 Stimulation of these mechanosensitive nerves may help explain why people with atopic eczema find that certain materials (eg wool) irritate their skin8


nerve

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At least two groups of C-fibres transmit the itch signal to the spinal cord5

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Nerve pathways in pruritus

In the brain, the nerve pathways end in the thalamus, which is a “relay station for information” from the eyes, ears and body.9 Nerves from the thalamus convey information about itch to, for example, the cortex5

The cortex, among many other actions, is responsible for assembling conscious perceptions from the information that the brain  receives from the senses and then deciding on, and committing to, a behaviour9

Numerous parts of the brain seem to contribute to the sensation of pruritus, including those involved in perception, evaluation, motivation, attention, emotion and movement. The regions involved in pruritus are similar to, but not identical with, those linked to pain5

Central sensitisation may contribute to the sensation of pruritus5


nerve2

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The location of the thalamus in the brain. Nerves from the thalamus convey information about itch to, for example, the cortex5

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Histamine and pruritus

Triggering the allergic cascade causes atopic eczema in the skin, and rhinitis in the nasal mucosa7, 10

Histamine, which is released mainly from mast cells, is an important inflammatory mediator in allergic conditions4, 10

Histamine binds to specific receptors expressed by numerous types of cell in the surrounding blood vessels and tissues10

Currently, researchers have identified four subtypes of histamine receptors in humans. H1 receptors seem to mediate histamine-induced pruritus4

histamine

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Histamine binds to specific receptors expressed by numerous types of cell10

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The itch-scratch cycle

The pruritus and xerosis (dry skin) associated with atopic eczema can create an itch-scratch cycle, which damages the skin and can predispose to infection and food allergies11, 12

Many people with atopic eczema are colonised with Staphylococcus aureus on their skin and in their nasal passages, which increases the risk of cutaneous infection, especially when the skin barrier is compromised13

Certain viral infections – such as the herpes simplex virus (eczema herpeticum), Coxsackievirus (eczema coxsackium) and molluscum contagiosum virus – seem to increase the risk of an exacerbation of atopic eczema13

Exposure to food proteins through a broken skin barrier could increase the risk of allergic sensitisation12


itch-scratch

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Coxsackievirus (eczema coxsackium) seems to increase the risk of an exacerbation of atopic eczema13

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Pruritus can reduce quality of life

Pruritus makes an important contribution to the reduced quality of life (QoL) often experienced by children and infants with atopic eczema14, 15, 16

One study asked the parents of 102 infants aged 4 years or younger to complete the Infants’ Dermatitis QoL (IDQOL) index.  Itching and scratching, mood change and sleep disturbance were the three highest scoring questions,14 suggesting that these make the biggest contribution to the impaired QoL

A study that enrolled 151 children (aged 2-17 years) who had experienced atopic eczema for at least a year found that the frequency and intensity of pruritus increased with the severity of atopic eczema (see graph):16

  • 79.0% of children experienced difficulty falling asleep because of the itch, while 63.0% woke due to pruritus
  • 79.9% experienced mood swings due to pruritus
  • 7.6% of the children were depressed because of their pruritus16

pruritus

Impact and severity of pruritus in children with atopic eczema16

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Introducing antihistamines

Broadly, antihistamines are classified as first-generation or second-generation depending on their pharmacokinetics, pharmacodynamics and side-effects17

First-generation antihistamines readily cross the blood brain barrier and can cause CNS effects - especially sedation and cognitive impairment - and antagonise muscarinic cholinergic receptors, resulting in side effects such as dry mouth, urinary retention, constipation and tachycardia17,18

Second-generation antihistamines are long acting, do not cross the blood brain barrier to the same extent as the first-generation drugs and are more selective for the H1 receptor.17, 18 As a result, second-generation antihistamines are, in most people, non-sedating and without clinically significant anti-cholinergic activity at therapeutic doses18

Patients taking second-generation antihistamines vary, however, in their susceptibility to CNS and anti-cholinergic effects, some  second-generation antihistamines seem to cause cardiac arrhythmias18

introducingantiistamines

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Some antihistamines cross the blood brain barrier causing CNS effects17,18

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Antihistamines and rhinitis

According to guidelines published by the British Society of Allergy and Clinical Immunology, second-generation oral H1-antagonists are the first-line treatment for mild-to-moderate intermittent and mild persistent rhinitis18

In addition to alleviating nasal itch, oral H1-antagonists relieve pruritus in the conjunctiva, palate and skin18

Intranasal corticosteroids are the first-line treatment for moderate to severe rhinitis. Oral H1-antagonists can be added to intranasal steroids for patients with moderate or severe persistent rhinitis that is uncontrolled by intranasal corticosteroids alone18

Combination treatment may be particularly appropriate when the patient experiences eye symptoms18


antihistamines

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Second generation antihistamines are the first-line treatment for mild-to-moderate intermittent and mild persistent rhinitis18

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Antihistamines and eczema

NICE does not advocate the routine use of oral antihistamines to manage atopic eczema in children. However, oral antihistamines are appropriate in two circumstances:

  • NICE suggest offering a one-month trial of a non-sedatingantihistamine to children with severe atopic eczema or with mild or  moderate atopic eczema who experience severe itching or urticaria. If successful, NICE suggest continuing treatment while  symptoms persist. Treatment should be reviewed every 3 months2

  • HCPs should offer a trial lasting between 7 and 14 days of an age-appropriate sedating antihistamine to children aged 6  months or older if sleep disturbance during an acute flare significantly affects the child, parents or carers. If successful, NICE suggest repeating treatment with a sedating antihistamine during further flares2

antistamines2


Stepped care plan for the treatment options for atopic eczema in children younger than 12 years of age2, 20

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When to refer

If these approaches fail to alleviate pruritus adequately, parents and carers should consult a GP

HCPs should advise people to see a GP if the itch affects daily life, lasts more than two weeks or keeps returning19

Children should see a GP if the itch is associated with a new rash, lump or swelling or involves the entire body19

 


whentorefer

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HCPs should advise people to see a GP if the itch affects daily life19

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Assessment Q1

Now that you have reviewed the learning, please complete the following multiple choice questions to test what you've learnt and receive your CPD certificate. 
 
Which nerve fibres are involved in pruritus?
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Assessment – Q2

Which of the following can increase the risk of an exacerbation of atopic eczema? Please indicate all that might apply
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Assessment – Q3

Is the following statement true or false? Second-generation antihistamines are, in most people, non-sedating but show clinically significant anticholinergic activity at therapeutic doses
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Assessment – Q4

According to guidelines published by the British Society of Allergy and Clinical Immunology, which of the following are true? Please indicate all that might apply
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Assessment – Q5

According to NICE, HCPs can offer a trial of an age-appropriate sedating antihistamine to children aged 6 months or older if sleep disturbance during an acute flare significantly affects the child, parents or carers. How long should the trial last?
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Post-learning reflection

Please take a moment to answer these post-learning questions.  These answers will be logged alongside your pre-learning responses on your CPD certificate which will be emailed to you on completion as evidence of your learning.



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References and further reading

1. Seidman MD, Gurgel RK, Lin SY et al Clinical practice guideline: allergic rhinitis executive summary Otolaryngology - Head and Neck Surgery 2015;152:197-206
2. NICE Atopic Eczema in Under 12s: Diagnosis and Management Clinical guideline: CG57 Published: December 2007 Available at: www.nice.org.uk/guidance/cg57 Accessed: August 2018
3. NICE Clinical Knowledge Summaries Eczema - Atopic Last Revised: January 2018 Available at: cks.nice.org.uk/eczema-atopic  Accessed: February 2019
4. Han L and Dong X Itch mechanisms and circuits Annual Review of Biophysics 2014;43:331-355
5. Dhand A and Aminoff MJ The neurology of itch Brain 2014;137:313-322
6. Stander S, Weisshaar E, Mettang T et al Clinical classification of itch: a position paper of the International Forum for the Study of Itch Acta Derm Venereol 2007;87:291-4
7. May JR and Dolen WK Management of allergic rhinitis: A review for the community pharmacist Clinical Therapeutics 2017;39:2410-2419
8. Mei J (2011) The mechanisms and perception of itch Yale Scientific Available at: www.yalescientific.org/2011/05/the-mechanisms-and-perception-of-itch Accessed: February 2019
9. O’Shea M, The Brain: A Very Short Introduction 2005, Oxford: Oxford University Press pp 56-59
10. Fitzsimons R, van der Poel L-A, Thornhill W et al Antihistamine use in children Archives of Disease in Childhood - Education & Practice Edition 2015;100:122-131
11. Ng JPX, Liew HM, and Ang SB Use of emollients in atopic dermatitis Journal of the European Academy of Dermatology and Venereology 2015;29:854-857
12. Izadi N, Luu M, Ong PY et al The role of skin barrier in the pathogenesis of food allergy Children 2015;2:382-402
13. Simpson EL, Bruin-Weller M, Flohr C et al When does atopic dermatitis warrant systemic therapy? Recommendations from an expert panel of the International Eczema Council Journal of the American Academy of Dermatology 2017;77:623-633
14. Lewis-Jones MS, Finlay AY, and Dykes PJ The Infants’ Dermatitis Quality of Life Index British Journal of Dermatology 2001;144:104-110
15. Alanne S, Nermes M, Söderlund R et al Quality of life in infants with atopic dermatitis and healthy infants: a follow-up from birth to 24 months Acta Paediatrica 2011;100:e65-e70
16. Sanchez-Perez J, Dauden-Tello E, Mora AM et al Impact of atopic dermatitis on health-related quality of life in Spanish children and adults: the PSEDA study Actas Dermo-Sifiliográficas 2013;104:44-52
17. Hoyte FCL and Katial RK Antihistamine therapy in allergic rhinitis Immunology and Allergy Clinics of North America 2011;31:509-543
18. Scadding GK, Kariyawasam HH, Scadding G et al BSACI guideline for the diagnosis and management of allergic and non-allergic rhinitis (Revised Edition 2017; First edition 2007) Clinical & Experimental Allergy 2017;47:856-889
19. NHS Choices Itchy Skin Available at: www.nhs.uk/conditions/itchy-skin  Accessed: February 2019
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