Introduction^[1]

The medical term for itchiness is Pruritus. The condition causes a sensation causing you to feel the need or reflex to scratch your skin to get relief.^[2] There are several possible causes for Pruritus, including an underlying medical condition, contact with an irritant or a reaction to a medication. Itch has resisted many attempts to be classified as any one type of sensory experience but has many similarities to pain – while both are unpleasant sensory experiences, their behavioural response patterns are different. Pain creates a withdrawal reflex, whereas itch leads to a scratch reflex.^[3]

Caption: “Woman Scratching Skin” by NIAID is licensed under CC BY 2.0

Myelin is the coating around nerve fibres. Myelin protects the nerve fibres in the central nervous system, which helps messages travel quickly and smoothly between the brain and the rest of the body. Unmyelinated nerve fibres (having no coating) for both itch and pain originate in the skin, but information for them is conveyed centrally in two distinct systems that use the same nerve bundle and
spinothalamic tract.^[4] There are two main and adjacent parts of the spinothalamic tract:

• The lateral spinothalamic tract transmits pain and temperature.
• The anterior spinothalamic tract (or ventral spinothalamic tract) contains crude touch and firm pressure information.

In the spinal cord, the spinothalamic tract has what is medically known as somatotopic organisation. This is the segmental organisation of its cervical, thoracic, lumbar, and sacral
components, which is arranged from most medial to most lateral, respectively. The pathway crosses over (decussates) at the level of the spinal cord rather than in the brainstem, like the dorsal column-medial lemniscus pathway and lateral corticospinal tract. It is one of the three tracts which make up the anterolateral system.

Pruritus is a general sensation arising from the irritation of skin cells or nerve cells associated with the skin. Although it is uncomfortable and a nuisance, it acts as an important sensory and self-protective mechanism, as do other skin sensations such as touch, pain, vibration, cold and heat. Since Pruritus is a symptom of some other disorder, a complete cure of Pruritus depends on control of the primary illness, such as^[5]:

• pruritus a’ni – intense chronic itching in the anal region.
• pruritus seni’lis – itching in the aged due to degeneration of the skin.
• uremic Pruritus – generalised itching associated with chronic renal failure and not attributable to other internal or skin disease.
• pruritus vul’vae – intense itching of the external genitalia in the female.

“Itchiness”

Pruritus is the medical term for itchiness. The condition causes you to feel the need to scratch your skin to get relief. Certain systemic diseases are known to cause Pruritus that range in intensity from a mild annoyance to an intractable, disabling condition.

Etymology
The etymology of Pruritus (“affection of the skin characterised by simple itching without visible eruption”) comes from the Latin pruritus, the past participle of prurire “to itch” (see prurient). The word was used earlier in English via Old French as prurite (early 15^th century).

Caption: A man trying to reach for a scratch an itch sensation on his upper back.
Attribution: Orrling and Tomer S, CC BY-SA 3.0 <https://creativecommons.org/licenses/by-sa/3.0&gt;, via Wikimedia Commons
Page URL: https://commons.wikimedia.org/wiki/File:Itch.jpg

This file is licensed under the Creative Commons Attribution-Share Alike 3.0 Unported license.

Signs and Symptoms
Pain and itch have very different behavioural response patterns. Pain elicits a withdrawal reflex, which leads to retraction and, thus, a reaction trying to protect an endangered part of the body. In contrast, itch creates a scratch reflex, which draws one to the affected skin site. Itch generates stimulus of a foreign object underneath or upon the skin and also the urge to remove it. For example, responding to a local itch sensation is an effective way to remove insects from one’s skin.

Scratching has traditionally been regarded as relieving oneself by reducing the annoying itch sensation. However, there are hedonic aspects to scratching, as one would find noxious scratching highly pleasurable.^[6] This can be problematic with chronic itch patients, such as ones with atopic dermatitis, who may scratch affected spots until they no longer produce a pleasant or painful sensation instead of when the itch sensation disappears.^[7] It has been hypothesised that motivational aspects of scratching include the frontal brain areas of reward and decision-making. These aspects might therefore contribute to the compulsive nature of itch and scratching.^[8]

Medical Classification
Itch has resisted many attempts to be classified as any one type of sensory experience. Itch has many similarities to pain, and while both are unpleasant sensory experiences, their behavioural response patterns are different. Pain creates a withdrawal reflex, whereas itch leads to a scratch reflex.^[9]

Unmyelinated^[10] nerve fibres for itch and pain both originate in the skin; however, information for them is conveyed centrally in two distinct systems that use the same nerve bundle and spinothalamic tract.^[11]

An itch is commonly felt in one place, but if it is felt all over the body, it is called generalised itch or generalised Pruritus.^[12] If the sensation of itching persists for six weeks or longer, then it is called chronic itch or chronic Pruritus.^[13]

Chronic idiopathic Pruritus or Chronic Pruritus of Unknown Origin is a form of itch that persists for longer than six weeks and for which no clear cause can be identified.^[14]

Causes
There are several common causes of itchy skin. Dry skin is a common cause of itchiness, particularly in an air-conditioned environment or during the winter months when the air is dry. These are the main causes:

• Skin conditions such as eczema, psoriasis, and hives.
• Allergic reactions to certain foods, medications, or environmental triggers such as pollen or pet dander.
• Insect bites and stings, as well as parasitic infections such as scabies.

There have been advances in identifying the different aspects of itchy skin, including the development of tools for measuring the severity of itch and understanding the mechanisms that cause itchiness. Researchers are also studying new treatments for itch, such as drugs that target specific nerve fibres and the use of probiotics to regulate the skin microbiome.

Treatment and Prevention^[15]
Treatment for itchy skin depends on the underlying cause. For example, if dry skin is the culprit, regular moisturising can help alleviate symptoms. Over-the-counter anti-itch creams containing ingredients such as hydrocortisone or calamine can help relieve itching caused by insect bites, rashes, or other skin conditions.

In cases where the itching is severe or persistent, a doctor may prescribe medications such as antihistamines, corticosteroids, or immunosuppressants. In some cases, light therapy may be used to treat skin conditions that cause itching.

Preventing itchy skin involves avoiding triggers such as harsh soaps, detergents, and other irritants. Maintaining good skin hygiene, avoiding scratching, and wearing loose-fitting clothing can also help prevent itchy skin. It is important to consult a healthcare professional if you experience persistent or severe itching, as it may be a symptom of an underlying medical condition.

A variety of over-the-counter and prescription anti-itch drugs are available. Some plant products have been found to be effective antipruritics, others not so. Non-chemical remedies include cooling, warming, and soft stimulation. Topical antipruritics in the form of creams and sprays are often available over-the-counter. Oral anti-itch drugs also exist and are usually prescription drugs. The active ingredients generally belong to the following classes:

• Antihistamines, such as diphenhydramine (Benadryl)^[16]
• Corticosteroids, such as hydrocortisone topical cream
• Counterirritants, such as mint oil, menthol, or camphor^[17]
• Crotamiton (trade name Eurax) is an antipruritic agent available as a cream or lotion, often used to treat scabies. Its mechanism of action remains unknown.
• Local anaesthetics, such as benzocaine topical cream (Lanacane)

Phototherapy is helpful for severe itching, especially if caused by kidney failure. The common type of light used is UVB.^[18]

Sometimes scratching relieves isolated itches, hence the existence of devices such as a back scratcher. Often, however, scratching only offers temporary relief and can intensify itching, even causing further damage to the skin, dubbed the “itch-scratch cycle”.^[19]

The mainstay of therapy for dry skin is maintaining adequate skin moisture and topical emollients. No studies have been conducted to investigate the effectiveness of emollient creams, cooling lotions, topical corticosteroids, topical antidepressants, systemic antihistamines, systemic antidepressants, systemic anticonvulsants, and phototherapy on chronic Pruritus of unknown origin.^[20] Clinical trials are underway with Dupilumab, which is thought to alleviate itch by acting on the IL-4 receptor^[21] on sensory neurons.  The effectiveness of therapeutic options for people who are terminally ill with malignant cancer is unknown.^[22]

Itch Oddities

• ‘Contagious itch’ refers to the phenomenon where watching someone scratch or hearing about someone’s itch can cause the viewer/listener also to start itching, even if they don’t have an itch themselves. This response is thought to be due to the power of suggestion and the brain’s mirror neuron system, which is involved in empathy and imitation.
• ‘Itch induced by stimuli’ refers to itching triggered by external factors, such as a mosquito bite, exposure to irritants like poison ivy, or an allergic reaction to food or medication.
• Three classes of human C-fibre nociceptors exist: mechano-insensitive, mechano-responsive, and polymodal.
• Studies have shown that itch receptors are primarily found in the top two layers of the skin, the epidermis and the dermis. These receptors, called pruriceptors, are specialised nerve endings that respond to specific itch-inducing substances, such as histamine^[23].
• Itch is generally not felt in muscles or joints, as these tissues do not have the specialised receptors that are responsible for transmitting the sensation of itch. However, some medical conditions can cause itching in these areas, such as neuropathic itch, which is caused by damage or dysfunction of the nerves that transmit itch signals.
• Itch is readily abolished in skin areas treated with the nociceptor excitotoxin capsaicin because capsaicin destroys the nerve endings responsible for transmitting the itch sensation. In contrast, anti-inflammatory saponins do not affect the itch receptors directly but instead reduce inflammation and pain, which can alleviate some types of itching. However, they may not be effective for all kinds of itch, and some studies have suggested that they may even worsen certain types of itching.

Types of Pruritus^[24]
There are several different types of Pruritus categorised by the cause of itchiness and the location of the itch on the body. Some of the most common types of Pruritus include:

• Generalised Pruritus: Itching occurs all over the body due to various causes like skin conditions, allergies, infections, drug reactions, and systemic disorders like kidney or liver disease.
• Localised Pruritus: Itching is limited to specific areas of the body and can be caused by various factors like insect bites, contact with irritants, allergic reactions, and skin diseases like eczema, psoriasis, or lichen planus.
• Aquagenic Pruritus: Itching occurs after contact with water, and it can be a symptom of various medical conditions like polycythemia vera or aquagenic urticaria.
• Brachioradial Pruritus: Itching of the upper arm caused by nerve damage, often due to conditions like cervical disc disease or nerve entrapment.
• Cholestatic Pruritus: Itching occurs due to liver disease or bile duct obstruction that affects the normal flow of bile.
• Hematologic Pruritus: Itching occurs due to various blood disorders, such as Leukaemia, Hodgkin’s Lymphoma, and Polycythemia Vera.
• Neurogenic Pruritus: Itching occurs due to damage or dysfunction of the nervous system, which can be caused by conditions like multiple sclerosis, stroke, or nerve injuries.
• Nocturnal Pruritus: Itching that occurs at night with several possible causes that include a reaction to your body’s natural functions, a reaction to a medication or contacting a skin irritant.
• Prurigo Nodularis: Itching caused by the development of multiple, hard, itchy nodules on the skin.
• Pruritus Ani: Itching of the skin surrounding your anus caused by haemorrhoids, an infection, or a skin irritant.
• Psychogenic Pruritus: Itching occurs due to psychological factors, such as anxiety, depression, or stress.
• Senile Pruritus: Itching caused by changes to your skin that affect people over the age of 65.
• Uremic Pruritus: Itching occurs as a symptom among people diagnosed with renal disease who receive dialysis.

Several conditions have itching as a symptom. Some of the most common conditions that cause itching include:

• Diabetes.
• Liver or kidney disease.
• Pregnancy.
• Eczema.
• Psoriasis.
• Cholestasis.
• Obsessive-compulsive disorder.
• Allergies.
• Dermatitis.
• Thyroid disease.

Why do we Itch?
When you read the following, it’s easy to recognise why we itch, and almost surprising that we don’t do it all the time. When we itch, it is the body’s way of responding to irritation or damage to the skin. It can be triggered by a variety of factors, including infections, allergies, skin disorders, and underlying medical conditions. When the skin is exposed to these triggers, it releases histamines, which cause the nerves in the skin to send signals to the brain, resulting in an itching sensation. In some cases, itching may also be related to psychological factors, such as stress and anxiety. Understanding the underlying cause of itching is important in determining the most effective treatment approach.

Infections ^[25]

• Body louse, found in substandard living conditions.
• Cutaneous larva migrans – a skin disease caused by hookworm infection.
• Head lice, if limited to the neck and scalp.
• Herpes, a viral disease.
• Insect bites, such as those from mosquitos or chiggers.
• Pubic lice, if limited to the genital area.
• Scabies, especially when several other persons in close contact also itch.
• Shaving, which may irritate the skin.
• Swimmer’s itch, a short-term immune reaction.
• Varicella – i.e. chickenpox, prevalent among young children and highly contagious.
• Tungiasis, ectoparasite of skin.

Environmental and Allergic ^[26]

• Allergic reaction to contact with specific chemicals, such as urushiol, derived from poison ivy or poison oak, or Balsam of Peru, found in many foods and fragrances.^[27] Certain allergens may be diagnosed in a patch test.^[28]
• Foreign objects on the skin are the most common cause of non-pathological itching.
• Photodermatitis – sunlight reacts with chemicals in the skin, leading to the formation of irritant metabolites.
• Urticaria (also called hives) usually causes itching.

Skin Disorders ^[29]

• Dandruff – an unusually large amount of flaking is associated with this sensation.
• Punctate palmoplantar keratoderma – a group of disorders characterised by abnormal thickening of the palms and soles.
• Skin conditions (such as psoriasis, eczema, seborrhoeic dermatitis, sunburn, athlete’s foot, and hidradenitis suppurativa). Most are of an inflammatory nature.
• Scab healing, scar growth, and the development or emergence of moles, pimples, and ingrown hairs from below the epidermis.
• Xerosis: dry skin, frequently seen in the winter and also associated with older age, frequent bathing in hot showers or baths, and high-temperature and low-humidity environments.

Other Medical Disorders ^[30]

• Diabetes mellitus, a group of metabolic diseases in which a person has high blood sugar.
• Hyperparathyroidism – overactivity of the parathyroid glands resulting in excess production of parathyroid hormone (PTH).^[31]
• Iron deficiency anaemia – a common anaemia (low red blood cell or haemoglobin levels).
• Cholestasis, where bile acids leaking into the serum activate peripheral opioid receptors, resulting in the characteristic generalised, severe itching.
• Malignancy or internal cancer, such as lymphoma or Hodgkin’s disease.^[32]
• Polycythemia, which can cause generalised itching due to increased histamines.
• Psychiatric disease (“psychogenic itch”, as may be seen in delusional parasitosis).
• Thyroid illness.
• Uraemia – the itching sensation this causes is known as uremic Pruritus.

Primary Skin Disorders

Pruritus, or itch, is most commonly associated with a primary skin disorder such as xerosis, atopic dermatitis, drug eruption, urticaria, psoriasis, arthropod assault, mastocytosis, dermatitis herpetiformis, or pemphigoid. However, when a primary skin condition cannot be identified as the cause of pruritus, then a systemic or neuropathic cause must be sought. 

What Does the NHS say about Itching?^[33]
Itchy skin is not usually a sign of anything serious. You can often treat it yourself, and the itch will usually go away after a few weeks. Sometimes, itching is caused by dry, cracked or irritated skin. There are simple things you can do to help ease the itching: the following things may also help stop itchy skin from returning and avoid skin being damaged from scratching.

Do

• pat or tap your skin instead of scratching it
• hold something cool on your skin, like a damp towel
• have cool or warm baths or showers
• use an unperfumed moisturiser or emollient regularly
• keep your nails clean, short and smooth
• wear loose cotton clothing
• use a laundry liquid or powder that is designed for sensitive skin

Don’t

• do not wear tight clothes or clothes made from wool or synthetic fabrics
• do not spend a long time in the bath or shower
• do not use perfumed/scented soaps, deodorants or moisturisers

Help from a Pharmacist
A pharmacist can recommend the best products to help with itchy skin. For example, creams, lotions or a medicine called an antihistamine. Tell the pharmacist where your skin is itchy and if you have any other symptoms. They might be able to tell you:

• what you can do to treat it yourself
• if you need to see a GP

You can find a pharmacy at this link: https://www.nhs.uk/service-search/find-a-pharmacy/

Seeing a GP
You should see a GP if itchy skin:

• is affecting your daily life
• does not get better with self-care, or it keeps coming back
• is caused by a new rash, lump or swelling that you’re worried about
• is all over your body; this could be a sign of something more serious

Treatment from a GP
To help find the cause of your itchy skin, the GP might prescribe creams, lotions or tablets, depending on what’s causing the itching. They will look at your skin and ask about your symptoms. The GP might arrange a blood test, or wipe a cotton bud over the area of itchy skin (a swab), or gently scrape off some skin cells so that they can be tested. The GP may also refer you to a doctor specialising in skin problems (dermatologist).

Causes of itchy skin
Itchy skin has many possible causes. If you have other symptoms (such as a rash or swelling), this might help to find the cause but do not try to diagnose yourself. See a GP if you’re worried. Itchy skin is also common during pregnancy or after menopause. Hormonal changes cause this, and it usually gets better over time. In rare cases, itchy skin can be a sign of a more serious condition, such as thyroid, liver or kidney problems.

Expertise
Leading experts in the field of Pruritus include Dr Gil Yosipovitch, Dr Ethan Lerner, and Dr Brian Kim, among others. These researchers have contributed significantly to the understanding of itch and its underlying mechanisms as well as developing new treatments for itch.

Dr Gil Yosipovitch
Dr Gil Yosipovitch is a renowned dermatologist and researcher who has made significant contributions to the field of Pruritus. He is currently a professor of dermatology and director of the Miami Itch Center at the University of Miami Miller School of Medicine. Dr Yosipovitch has published numerous articles and book chapters on Pruritus, including the first textbook on the subject, “Itch: Mechanisms and Treatment.” His research has focused on the neurobiology of itch and the development of novel therapies for chronic itch conditions such as atopic dermatitis and chronic kidney disease.

Dr Ethan Lerner
Dr Ethan Lerner is a professor of dermatology at Harvard Medical School and the director of the Center for the Study of Itch at Massachusetts General Hospital. Dr Lerner’s research focuses on the molecular mechanisms of itch and the development of targeted therapies for chronic itch conditions. He has discovered several important molecules involved in the itch sensation, including gastrin-releasing peptide (GRP) and its receptor. His work has led to the development of novel therapies for chronic itch, such as monoclonal antibodies that target GRP.

Dr Brian Kim
Dr Brian Kim is an associate professor of dermatology and immunology at the Washington University School of Medicine in St. Louis. He is a leading expert in the field of Pruritus and has published extensively on the neurobiology of itch, the immune system’s role in itch, and the development of novel therapies for chronic itch conditions. Dr Kim’s research has focused on the role of cytokines and immune cells in the development of chronic itch conditions such as atopic dermatitis and psoriasis. He has also led clinical trials of novel therapies for chronic itch, including the use of monoclonal antibodies and Janus kinase inhibitors.

Caption: “Scratch that itch.” by Neil. Moralee is licensed under CC BY-NC-ND 2.0.

Experts from the Past
There were many experts in the past who made significant contributions to the field of dermatology and the study of Pruritus. One notable figure is Sir Samuel Wilks, a British physician who lived in the 19^th century. Wilks was one of the first physicians to recognise that itching was a distinct symptom that could be caused by various underlying medical conditions. He also recognised that itching could be a symptom of systemic diseases, such as liver disease and kidney disease.

Another important figure in the study of Pruritus is Josef Jadassohn, an Austrian dermatologist who lived in the late 19^th and early 20^th centuries. Jadassohn conducted extensive research on the causes and treatments of itching, and he is credited with developing some of the first effective treatments for Pruritus, including topical creams and lotions.

In the mid-20^th century, researchers such as Claude Bernard and Julius H. Comroe Jr. began to study the neurophysiology of itching, exploring the mechanisms by which the sensation of itching is transmitted from the skin to the brain. This work laid the foundation for the modern study of Pruritus, which continues to advance with the contributions of the contemporary experts mentioned above.

Caption: “Day 344 – It Itches” by lintmachine is licensed under CC BY-NC-SA 2.0.

 Sources and Further Reading

• https://dermnetnz.org/topics/pruritus
• https://emedicine.medscape.com/article/1098029-overview
• https://en.wikipedia.org/wiki/Itch
• https://en.wikipedia.org/wiki/Pruritus_ani
• https://familydoctor.org/condition/pruritus/
• https://greatist.com/health/itchy-skin-at-night
• https://my.clevelandclinic.org/health/diseases/11879-pruritus
• https://my.clevelandclinic.org/health/diseases/21181-brachioradial-pruritus
• https://nationaleczema.org/blog/mind-body-techniques-to-stop-scratching/
• https://odylique.co.uk/blog/home-remedies-for-eczema-7-practical-tips/
• https://pubmed.ncbi.nlm.nih.gov/31549284/
• https://stage.e45.com/uk/e45-about-skin/e45-skin-symptoms/itchy-skin-3/
• https://www.aaaai.org/tools-for-the-public/conditions-library/allergies/what-makes-us-itch
• https://www.aad.org/public/diseases/a-z/dry-skin-self-care
• https://www.aad.org/public/diseases/psoriasis/skin-care/itch-relief
• https://www.aad.org/public/everyday-care/itchy-skin/itch-relief/relieve-uncontrollably-itchy-skin
• https://www.aad.org/public/everyday-care/itchy-skin/itch-relief/relieve-itchy-skin
• https://www.aafp.org/pubs/afp/issues/2003/0915/p1145.html
• https://www.dictionary.com/e/medical-term-for-itching/
• https://www.getharley.com/
• https://www.healthline.com/health/itching
• https://www.healthline.com/health/itchy-skin-cancer
• https://www.healthline.com/health/liver-disease-and-itching
• https://www.mayoclinic.org/diseases-conditions/itchy-skin/symptoms-causes/syc-20355006
• https://www.medicalnewstoday.com/articles/311473
• https://www.medicalnewstoday.com/articles/321465
• https://www.medicalnewstoday.com/articles/323491
• https://www.medicalnewstoday.com/articles/326848
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2885583/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2924137/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033328/
• https://www.nhs.uk/conditions/itchy-skin/
• https://www.nhsinform.scot/illnesses-and-conditions/skin-hair-and-nails/itching
• https://www.nivea.co.uk/advice/skin/what-causes-itchy-skin
• https://www.pennmedicine.org/for-patients-and-visitors/patient-information/conditions-treated-a-to-z/rash
• https://www.pranicura.com/anal-itching-treatment/
• https://www.prevention.com/health/a30519707/itchy-skin-treatments/
• https://www.scripps.org/news_items/4577-what-can-i-do-to-treat-my-dry-itchy-skin
• https://www.webmd.com/skin-problems-and-treatments/guide/skin-conditions-pruritus
• https://www.wederm.com/2021/05/11/what-causes-itchy-skin-at-night/

Books:

• The 2023-2028 World Outlook for Anti-Itching Skin Treatments, Paperback, by Prof Philip M. Parker, PhD (Author), published by ICON Group International, Inc. (2022), available from https://www.amazon.co.uk/2023-2028-World-Outlook-Anti-Itching-Treatments/dp/B09WCHFBD8/
• How To Relieve Skin Itching: Do It Yourself DIY Home Remedy, Paperback, by Robert S. Pardo (Author), independently published (20^th August 2022), available from https://www.amazon.co.uk/How-Relieve-Skin-Itching-Yourself/dp/B0BB5Z9CQ6/
• Pruritus, Hardcover, by Laurent Misery (Editor), Sonja Ständer (Editor), published by Springer (27^th July 2016), available at: https://www.amazon.co.uk/Pruritus-Laurent-Misery/dp/331933140X/
• Pruritus Ani: All You Need to Know About Pruritus Ani (Itchy Bottom, Anusitis) and How To Finally Get Relief From Anal Itching!, Paperback, by Joel Connor (Author), published by CreateSpace Independent Publishing Platform (1^st June 2016), available at: https://www.amazon.co.uk/Pruritus-Ani-Anusitis-Finally-Itching/dp/153355837X/

CAUTION: This paper is not medical advice. No advice is implied or given in this paper but is only for general information. You should always seek the advice of your GP or other qualified health provider with any questions you may have regarding a medical condition. This paper should never be used as a substitute for obtaining advice from a medical specialist or other qualified consultant or dietitian. Any medications mentioned may include names for US drugs which may have a different name to those available in the UK. This paper is compiled from the sources stated but has not been medically reviewed. Parts of this paper include information provided via artificial intelligence which, although checked by the author, is not always accurate or reliable. No warranty or guarantee is given or implied as to the accuracy, timeliness, performance, completeness or suitability of the information and materials covered in this paper for any particular purpose. Such information and materials may contain inaccuracies or errors and the publisher and author expressly exclude liability for any such inaccuracies or errors to the fullest extent permitted by law. Your use of any information or materials on this website is entirely at your own risk, for which we shall not be liable. It shall be your own responsibility to ensure that any products, services or information available through this paper meet your specific requirements and you should neither take action nor exercise inaction without taking appropriate professional advice. The hyperlinks were current at the date of publication. There is no implied endorsement or promotion of any organisation by the author or publisher.

End Notes and Explanations

1. Sources: Compiled from research using information at the sources stated throughout the text, together with information provided by machine-generated artificial intelligence at: bing.com [chat] and https://chat.openai.com ↑
2. Source: Andersen HH, Elberling J, Arendt-Nielsen L (September 2015). “Human surrogate models of histaminergic and non-histaminergic itch”. Acta Dermato-Venereologica. 95 (7): 771–777. doi:10.2340/00015555-2146. PMID 26015312 ↑
3. Source:  Ikoma A, Steinhoff M, Ständer S, et al. (July 2006). “The neurobiology of itch”. Nature Reviews. Neuroscience. 7 (7): 535–547. ↑
4. Source:  Greaves MW, Khalifa N (October 2004). “Itch: more than skin deep”. International Archives of Allergy and Immunology. 135 (2): 166–172. doi:10.1159/000080898. PMID 15375326. S2CID 13376216. ↑
5. Source: https://medical-dictionary.thefreedictionary.com/pruritus ↑
6. Source: Ikoma A, Steinhoff M, Ständer S, et al. (July 2006). “The neurobiology of itch”. Nature Reviews. Neuroscience. 7 (7): 535–547.doi:10.1038/nrn1950. PMID 16791143. S2CID 9373105. Cited at: https://en.wikipedia.org/wiki/Itch ↑
7. Source: Karsak M, Gaffal E, Date R, et al. (June 2007). “Attenuation of allergic contact dermatitis through the endocannabinoid system”. Science. 316 (5830): 1494–1497. Bibcode:2007Sci…316.1494K. Cited at: https://en.wikipedia.org/wiki/Itch ↑
8. Source: Ikoma A, Steinhoff M, Ständer S, et al. (July 2006). “The neurobiology of itch”. Nature Reviews. Neuroscience. 7 (7): 535–547.doi:10.1038/nrn1950. PMID 16791143. S2CID 9373105. Cited at: https://en.wikipedia.org/wiki/Itch ↑
9. Source: Ikoma A, Steinhoff M, Ständer S, et al. (July 2006). “The neurobiology of itch”. Nature Reviews. Neuroscience. 7 (7): 535–547.doi:10.1038/nrn1950. PMID 16791143. S2CID 9373105. Cited at: https://en.wikipedia.org/wiki/Itch ↑
10. Explanations: (a) Unmyelinated means pertaining to nerve fibers that are not covered with a myelin sheath (myelin is a soft, white, fatty material in the membrane of Schwann cells and certain neuroglial cells: the substance of the myelin sheath). Source: Dictionary.com, and (b) Neuroglial cells, also known as glial cells or simply glia, are a type of cell in the nervous system that provides support and protection to neurons (nerve cells). They outnumber neurons and come in several types, including astrocytes, oligodendrocytes, microglia, and ependymal cells. Neuroglial cells perform a variety of functions, including maintaining the chemical environment of the brain and spinal cord, providing physical and nutritional support to neurons, and repairing damage to neural tissue. They also play a role in neurological disorders and diseases. Source: Artificial Intelligence at: https://chat.openai.com ↑
11. Source: Greaves MW, Khalifa N (October 2004). “Itch: more than skin deep”. International Archives of Allergy and Immunology. 135 (2): 166–172. doi:10.1159/000080898. PMID 15375326. S2CID 13376216. Cited at: https://en.wikipedia.org/wiki/Itch ↑
12. Source: Molkara S, Sabourirad S, Molooghi K (July 2019). “Infectious differential diagnosis of chronic generalized pruritus without primary cutaneous lesions: a review of the literature”. International Journal of Dermatology. 59: 30–36. doi:10.1111/ijd.14587. PMID 31364165. S2CID 198998956. Cited at: https://en.wikipedia.org/wiki/Itch ↑
13. Sources: (a) Molkara S, Sabourirad S, Molooghi K (July 2019). “Infectious differential diagnosis of chronic generalized pruritus without primary cutaneous lesions: a review of the literature”. International Journal of Dermatology. 59:30 36.doi:10.1111/ijd.14587. PMID 31364165. S2CID 198998956, and (b) Harrison IP, Spada F (July 2019). “Breaking the Itch-Scratch Cycle: Topical Options for the Management of Chronic Cutaneous Itch in Atopic Dermatitis”. Medicines. 6 (3): 76. doi:10.3390/medicines6030076. PMC 6789602. PMID 31323753. Cited Ibid. ↑
14. Sources: (a) Erickson S, Nahmias Z, Rosman IS, Kim BS (July 2018). “Immunomodulating Agents as Antipruritics”. Dermatologic Clinics. 36 (3): 325–334. doi:10.1016/j.det.2018.02.014. PMID 29929604. S2CID 49336771, and (b) Hinkle JL, Cheever KH (2018-08-30). Brunner and Suddarth’s Textbook of Medical-Surgical Nursing. Wolters kluwer india Pvt Ltd. p. 1269. ISBN 978-93-87963-72-6. Cited at: https://en.wikipedia.org/wiki/Itch ↑
15. Source: https://en.wikipedia.org/wiki/Itch ↑
16. Source: Andrade A, Kuah CY, Martin-Lopez JE, et al. (Cochrane Skin Group) (January 2020). “Interventions for chronic pruritus of unknown origin”. The Cochrane Database of Systematic Reviews. 1 (1): CD013128. doi:10.1002/14651858.CD013128.pub2. PMC 6984650. PMID 31981369. Cited Ibid. ↑
17. Source: Hercogová J (2005). “Topical anti-itch therapy”. Dermatologic Therapy. 18 (4): 341–343. doi:10.1111/j.1529-8019.2005.00033.x. PMID 16297007. S2CID 31573591. Cited at: https://en.wikipedia.org/wiki/Itch ↑
18. Source: Botero F (June 1978). “Pruritus as a manifestation of systemic disorders”. Cutis. 21 (6): 873–880. PMID 657843. Cited Ibid. ↑
19. Source: Rinaldi G (April 2019). “The Itch-Scratch Cycle: A Review of the Mechanisms”. Dermatology Practical & Conceptual. 9 (2): 90–97. doi:10.5826/dpc.0902a03. PMC 6502296. PMID 31106010. Cited at: https://en.wikipedia.org/wiki/Itch ↑
20. Source: Andrade A, Kuah CY, Martin-Lopez JE, et al. (Cochrane Skin Group) (January 2020). “Interventions for chronic pruritus of unknown origin”. The Cochrane Database of Systematic Reviews. 1 (1): CD013128. doi:10.1002/14651858.CD013128.pub2. PMC 6984650. PMID 31981369. Cited Ibid. https://en.wikipedia.org/wiki/Itch ↑
21. Explanation: IL-4 receptor is a type of receptor protein found on the surface of certain immune system cells that specifically binds to interleukin 4 (IL-4) cytokine. IL-4 is a type of protein molecule that acts as a signaling molecule in the immune system, and it is involved in regulating various immune responses, including inflammation, antibody production, and cell differentiation. When IL-4 binds to its receptor on immune cells, it triggers a series of intracellular signaling events that ultimately lead to the activation of various genes and the production of proteins involved in immune responses. Dysregulation of IL-4 receptor signaling has been implicated in the development of certain autoimmune diseases, allergic reactions, and cancer. ↑
22. Source: Siemens W, Xander C, Meerpohl JJ, et al. (November 2016). “Pharmacological interventions for pruritus in adult palliative care patients”. The Cochrane Database of Systematic Reviews. 2016 (11): CD008320. doi:10.1002/14651858.CD008320.pub3. PMC 6734122. PMID 27849111. Cited at: https://en.wikipedia.org/wiki/Itch ↑
23. Explanation: Itching is often triggered by histamine, a chemical in the body associated with immune responses. It causes the itch and redness you see with insect bites, rashes and skin dryness or damage. Histamine is released by the body during allergic reactions, such as those to pollen, food, latex and medications. ↑
24. Adapted from: https://my.clevelandclinic.org/health/diseases/11879-pruritus ↑
25. Source: https://en.wikipedia.org/wiki/Itch ↑
26. Ibid ↑
27. Sources: (a) Pfützner W, Thomas P, Niedermeier A, et al. (2003-02-20). “Systemic contact dermatitis elicited by oral intake of Balsam of Peru”. Acta Dermato-Venereologica. 83 (4): 294–295. doi:10.1080/00015550310016599. PMID 12926805., and (b) Usatine RP, Riojas M (August 2010). “Diagnosis and management of contact dermatitis”. American Family Physician. Aafp.org. 82 (3): 249–255. PMID 20672788. Cited at: https://en.wikipedia.org/wiki/Itch ↑
28. Sources: (a) Byers, Jerry P. (2006). Metalworking Fluids (Second ed.). CRC Press. ISBN 142001773X, and (b) Feingold BF (1973). Byers JP, Introduction to clinical allergy. the University of Michigan. ISBN 0398027978. Cited at: https://en.wikipedia.org/wiki/Itch ↑
29. Source: https://en.wikipedia.org/wiki/Itch ↑
30. Source: https://en.wikipedia.org/wiki/Itch ↑
31. Source: LaBagnara, James. eMedicine –Hyperparathyroidism. emedicine.com Cited at: https://en.wikipedia.org/wiki/Itch ↑
32. Source: Botero F (1978). “Pruritus as a manifestation of systemic disorders”. Cutis. 21 (6): 873–880. PMID 657843 Cited at: https://en.wikipedia.org/wiki/Itch ↑
33. Source: https://www.nhs.uk/conditions/itchy-skin/ © Crown copyright acknowledged. ↑