Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Ogechukwu Hannah Nnabude, MD

An itch (Latin: pruritus) is a sensation felt on an area of skin that evokes the desire or reflex to scratch that area. Itching can be related to anything from dry skin to cancer. Itch has many similarities to pain and both are unpleasant sensory experiences but their behavioral response patterns are different. Pain creates a reflex withdrawal while itch leads to a scratch reflex. Unmyelinated nerve fibers for itch and pain both originate in the skin, however, information for them are conveyed centrally in two distinct systems that both use the same peripheral nerve bundle and spinothalamic tract.

Until recent times, sensations of itch were considered to be largely the same as those of pain. Currently, pruritus is considered to be an autonomous, pain-independent sensation. Itch, also known as medically pruritus, The first documented definition of itch was given by the German physician Samuel Hafenreffer as an “unpleasant sensation that elicits the desire or reflex to scratch” about 350 years ago. In recent years, pruritus has been determined to be an autonomous, pain-independent sensation. pruritus is a frequently misspelled word, often misspelled as “pruritis”. Historically, the sensations of itch and pain have not been considered to be independent of each other until recently where it was found that itch has several features in common with pain but exhibits notable differences. Pruritic stimuli mostly create the same reactions as noxious stimuli in experimental animals. As a result, it is difficult to study the physiologic mechanisms of itch in animal models as they lack the ability to discern the differences between both stimuli. Therefore human studies have provided most of the information regarding the processing of pruritic stimuli. It was initially thought histamine was the major chemical involved in mediating pruritus through binding to H1R and activating phospholipase Cβ3 (PLCβ3) and phospholipase A2 (PLA2). Bell et al. demonstrated that histamine promotes the influx of calcium at the axon terminals of the spinal cord neurons via a transient receptor vanilloid 1 (TRPV1) receptor activation and then, through the promotion of a series of intracellular signal activation, eventually lead to the generation of itching sensation. However, the current consensus is that there are other chemical mediators that are highly involved in the promotion of pruritus.

The pathogenesis of itch is characterized by dermal/pruritoceptive which originates in the skin, neuropathic which is due to damage along the afferent pathway of a nerve, neurogenic itch which originates centrally without the involvement of the peripheral nerves, a psychogenic itch which is associated with psychiatric disorders and phobias, and a mixed picture which is due to two or more causes of itching

There are many causes of itching. Examples include skin diseases, systemic diseases, allergies, medications, insect stings among many others

There is a very broad differential diagnosis for itching due to an extensive list of possible causes. Itching may be due to dermatologic disease, systemic disease, reactions to chemicals and medications, weather, or psychiatric disease. Symptoms, laboratory findings, and other diagnostic tests can help narrow down the list.

About 280 million people globally, roughly 4% of the world’s population, have difficulty with itchiness.

pruritusmay be associated with virtually any malignancy. Certain neoplasms, especially hematologic malignancies, have pruritus as a common symptom. For example, in patients with polycythemia vera, 48% to 70% have aquagenic pruritus, which is itching that is associated with water coming in contact with the skin. Also, about 30% of people with Hodgkin’s disease suffer from pruritus. The incidence of pruritus in other types of hematologic malignancies is currently not known, however, investigators have reported its presence in approximately 3% of patients with non‐Hodgkin’s lymphoma. Solid tumors may be associated with paraneoplasticpruritus. In fact, pruritus may one of the early symptoms, starting months or years before a patient is diagnosed. pruritus is also a frequent finding in cutaneous lymphomas. Additionally, it is frequently seen in cancers involving the biliary tract. Retrospective studies have revealed that 2% to 11% of chronic itch cases are attributable to malignancies.

pruritus has been reported to be an early symptom in some non-malignant diseases such as liver disease, renal insufficiency, thyroid disease, Sjögren’s syndrome, diabetes mellitus, iron deficiency, paraproteinemia, and other conditions. In internal diseases, itch has been best studied in cholestatic pruritus and uremic pruritus.

About a third of uremic patients treated without dialysis complain of uremic pruritus, and on maintenance hemodialysis, the incidence of uremic itching rises to 70%-80%.

Cholestatic pruritus]] affects nearly if not all patients with biliary cirrhosis and is the first symptom in nearly 50% of the patients with this disease. Furthermore, the prevalence of pruritus in patients with end‐stage HIV is over 20%.

Common risk factors in the development of itch are allergic reactions, cholestasis , diabetes mellitus, and drug side effect.

The scientific term for itching is pruritus. The word pruritusis derived from the Latin word Prurire which means to itch.

In 1660, the German physician Samuel Hafenreffer defined pruritus as “an unpleasant sensation associated with the desire to scratch”.

In modern medicine, pruritus is used in reference to a pathological condition in which the sensations of itch are intense and often generalized and stimulate repeated scratching in an attempt to alleviate the discomfort. pruritus is not a disease, but rather a common and still poorly understood symptom of both localized and systemic disorders that may accompany many conditions.

pruritus is important in many medical specialties, and notably to palliative care. Although pruritus is not the most commonly seen symptom seen in advanced terminal disease, it is among the most puzzling symptoms. It can cause considerable discomfort in patients receiving cancer therapy or in other types of terminal diseases. The itch‐scratch‐itch cycle adversely affects skin integrity, resistance to infections, and quality of life as much as pain can affect a patient. It can also lead to feelings of embarrassment which can impact a social patient’s life.

A proposed approach to the evaluation of itching can be summarized on Itch diagnosis page

A variety of over-the-counter and prescription anti-itch drugs are available. Some plant products have been found to be effective anti-pruritics, others not. Non-chemical remedies include cooling, warming, soft stimulation.

Sometimes scratching relieves isolated itches, hence the existence of devices such as the back scratcher. Often, however, scratching can intensify itching and even cause further damage to the skin, dubbed the “itch-scratch-itch cycle”.

The mainstay of therapy for dry skin is maintaining adequate skin moisture and topical emollients.

Effective measures for the primary prevention of [itch] include avoidance of causes, and emollients.

Effective measures for the secondary prevention of itch include anti-pruritics, scratching, cooling, warming, soft stimulation.

There has been no discussion on the cost-effectiveness of therapy foritch

There has been no discussion on future or investigational therapies for itch.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Ogechukwu Hannah Nnabude, MD

Until recent times, sensations of itch were considered to be largely the same as those for pain. Currently, pruritus is considered to be an autonomous, pain-independent sensation.

• Itch, also known medically as pruritus, The first documented definition of itch was given by the German physician Samuel Hafenreffer as an “unpleasant sensation that elicits the desire or reflex to scratch” about 350 years ago.^[1] In recent years, pruritus has been determined to be an autonomous, pain-independent sensation. ^[2]
• Pruritus is a frequently misspelled word, often misspelled as “pruritis” ^[3]
• Hyperknesis, a term introduced by LaMotte, is defined as “a pathological sensory state in which the itch threshold is lowered and/or a stimulus that does not normally evoke itch, but does now, and/or there is enhanced itch to normal itch‐provoking stimuli” ^[4]. It is derived from the Greek word knesis which means itching. Alloknesis is defined as “a type of hyperknesis in which certain stimuli that normally do not evoke itch, for example gently warming or stroking the skin, do so” ^[5]
• Atmoknesis (or aerogenic pruritus), a term that is defined as itching that is brought about, or seemingly brought about, by air touching the skin, as would be expected when a person undresses. It is feature often noted in psoriasis and atopic dermatitis patients ^[6].

• Historically, the sensations of itch and pain have not been considered to be independent of each other until recently where it was found that itch has several features in common with pain but exhibits notable differences.^[7] Pruritic stimuli mostly create the same reactions as noxious stimuli in experimental animals. As a result, it is difficult to study the physiologic mechanisms of itch in animal models as they lack the ability to discern the differences between both stimuli. Therefore human studies have provided most of the information regarding the processing of pruritic stimuli.Closing </ref> missing for <ref> tag ^{[8] [9] [10]}. Bell et al. demonstrated that histamine promotes the influx of calcium at the axon terminals of the spinal cord neurons via a transient receptor vanilloid 1 (TRPV1) receptor activation and then, through the promotion of a series of intracellular signal activation, eventually lead to the generation of itching sensation ^[8]. However, the current consensus is that there are other chemical mediators that are highly involved in the promotion of pruritus.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Ogechukwu Hannah Nnabude, MD

There are five main causes of itching:

• Dermal/pruritoceptive which originates in the skin,
• Neuropathic which is due to damage along the afferent pathway of a nerve,
• Neurogenic which originates centrally without the involvement of the peripheral nerves,
• Psychogenic which is associated with psychiatric disorders and phobias, and
• Mixed picture which is due to two or more causes of itching

The central chemical involved in itching is histamine, a molecule released by mast cells in the skin. Histamine is the chemical that causes itching and reddening. It binds to local nerve endings on specific receptors. Itch can originate in the peripheral nervous system (dermal or neuropathic) or in the central nervous system (neuropathic, neurogenic, or psychogenic).^[1]

Itch originating in the skin is considered pruritoceptive and can be induced by a variety of stimuli, including mechanical, chemical, thermal, and electrical stimulation. The primary afferent neurons responsible for histamine induced itch are unmyelinated C-fibers. In human C-fiber nociceptors, the two major classes that exist are mechano-responsive nociceptors and mechano-insensitive nociceptors. Mechano-responsive nociceptors have been shown in studies to respond to mostly pain and mechano-insensitive receptors respond mostly to itch induced by histamine. However, it does not explain mechanically induced itch or when itch is produced without a flare reaction which involves no histamine. Therefore it is possible that pruritoceptive nerve fibers have different classes of fibers, which is currently unclear in current research.^[2] Some classic examples that fall in this category include scabies, itching secondary to insect bites, and urticaria ^{[3] [4] [5]}. Studies have shown that itch receptors are found only on the two outermost layers of the skin, the epidermis, and the epidermal/dermal transition layers. Shelley and Arthur had verified the depth by injecting individual itch powder spicules (Mucuna pruriens) and found that maximal sensitivity was found at the basal cell layer or the innermost layer of the epidermis. Surgical removal of those skin layers removed the ability for a patient to perceive itch. Itch is never felt in muscle, joints, or inner organs, which shows that deep tissue does not contain itch signaling apparatuses.^[6] Sensitivity to pruritic stimuli is not even across the skin and has a random spot distribution with a similar density to that of pain. The same substances that elicit itch upon intracutaneous injection (injection within the skin) elicit only pain when injected subcutaneously (beneath the skin). Itch is readily abolished in skin areas treated with nociceptor excitotoxin capsaicin but remains unchanged in skin areas that were rendered touch-insensitive by pretreatment with saponins, an anti-inflammatory agent. Although experimentally induced itch can still be perceived under a complete A-fiber conduction block, it is significantly diminished. Overall, itch sensation is mediated by A-delta and C nociceptors located in the topmost layer of the skin.^[7]

Neuropathic itch can originate at any point along the afferent pathway as a result of damage to the nervous system. They could include diseases or disorders in the central nervous system or peripheral nervous system. It is often limited to a certain point^[6] Examples of itch of neuropathic origin are nostalgia paresthetica, postherpetic neuralgia, brachioradial pruritus, brain tumors, multiple sclerosis, peripheral neuropathy, and nerve irritation.^{[8] [9] [10] [11]}

Neurogenic itch, which is itch induced centrally by receptors and mediators but with no neural damage, is often associated with increased accumulation of endogenous opioids as seen in itching due to bile statsis, and possibly synthetic opioids.^{[6] [12] [13]}

Itch is also associated with some psychiatric disorders, psychological factors and phobias. Examples in this category are parasitic phobia or itching related obsessive-compulsive disorders, for example neurotic scratching.^{[6] [14] [15]}

This is itching brought about by two or more factors as is seen in atopic dermatitis which is a combination of neurogenic and dermal/pruritoceptive causes. ^[16]

The following table shows some of the mediators, receptors and drugs related to itching ^[17]:

The sensation of itch can be reduced by many painful sensations. Many studies done in the last decade have shown that itch can be inhibited by many other forms of painful stimuli, such as noxious heat, physical rubbing/scratching, noxious chemicals, and electric shock. Any stimuli that causes pain will inhibit itching.

The inhibition of itch by painful stimuli, including heat, physical stimulus, and chemical stimulus, has been shown experimentally. In an article written by Louise Ward and others, they studied the effects of noxious and non-noxious counterstimuli, such as heat, physical vibration, or chemical stimulation on skin, in healthy adults after they had experimentally induced itch (transdermal iontophoresis of histamine) and pain (with topical mustard oil) in their skin. They found that when they induced non-noxious counterstimuli, the reduction of pain and itch was reduced only for up to 20 seconds. However when they induced noxious counterstimuli, there was a significant inhibition of itch for an extended period of time but no inhibition of pain. In addition, it was found that brief noxious stimuli created an anti-itch state for more than 30 minutes. These findings show that itch is not a subliminal form of pain and that noxious counterstimulus is likely to act through a central instead of a peripheral mechanism.^[18]

Painful electrical stimulation reduced histamine-induced itch for several hours at a distance up to 10 cm from the stimulated site, which suggests a central mode of action. A new method had been recently found, by Hans-Jorgen Nilsson and others, that is able to relieve itch without damaging the skin called cutaneous field stimulation (CFS). CFS consists of a flexible rubber plate with 16 needle-like electrodes placed regularly at 2-centimeter intervals in a 4 by 4 matrix used to electrically stimulate nerve fibers in the surface of the skin. The electrodes were stimulated continuously at 4 Hertz per electrode, pulse duration of 1 millisecond, intensity 0.4-0.8 milliamperes, and for 25 minutes. CFS resulted in a pricking and burning sensation that usually faded away very quickly. The burning sensation was still present during a selective block of impulse conduction of A-fibers in myelinated fibers indicating that nociceptive C-fibers are activated by CFS. In addition, a flare reaction had been noted to develop around the CFS electrodes which indicate activation of axon reflexes in nociceptive C-fibers. Itch, which was induced by transdermal iontophoresis of histamine, was inhibited within the skin area treated with CFS, and it was reduced 10 cm distally to a significant amount. CFS proves to offer a new method of combating itch by using painful electrical stimulation as it creates a long lasting inhibitory effect, does not create any significant skin injuries, and is simple to manage. It is able to activate powerful itch inhibitory mechanisms possibly routed through central mechanisms, which could normally be activated by scratching of the skin.^[19]

A study done by Gil Yosipovitch, Katharine Fast, and Jeffrey Bernhard showed that noxious heat and scratching was able to inhibit or decrease itch induced by transdermal iontophoresis of histamine and most interestingly, decrease skin blood flow. Twenty-one healthy volunteers participated in their study. Baseline measurements of skin blood flow were obtained on the flexor part of the forearm and then compared with skin blood flow after various stimuli. Then transdermal iontophoresis of histamine was performed and tested with various stimuli. It is well known that skin blood flow is significantly increased during mechanical scratching, warming, and noxious heat. However it is quite interesting that this study is the first to examine the changes of blood flow by stimuli during iontophoresis of histamine and how itch is perceived in those conditions. Its examination provided an unexpected result that noxious heat and scratching has an inhibitory effect.^[20]

A negative correlation was found between pain sensitivity and itch sensitivity. In a study done by Amanda Green and others, they aimed to determine itch-related genetic factors, and establish a more useful animal model for itch. They looked at 11 different inbred mouse strains and compared their scratching behavior in response to two itch inducing agents, histamine and chloroquine. Every strain revealed an inverted-U shape dose response relationship from chloroquine, indicating that moderate dosages produced more scratching than at higher dosages. An explanation is that higher dosage produces more pain and the presence of pain inhibits pain thereby lowering the amount of overall scratching. Another notable result was that histamine-induced scratching occurred in female mice on average 23% more than males. Finally, it was found that mice having strains sensitive to pain were resistant to itch and vice versa.^[21]

Inflammatory mediators such as bradykinin, serotonin (5-HT) and prostaglandins, released during a painful or pruritic inflammatory condition not only activates pruriceptors but also causes acute sensitization of the nociceptors. In addition, expression of neuro growth factors (NGF) can cause structural changes in of nociceptors such as sprouting. NGF is high in injured or inflamed tissue. Increased NGF is also found in atopic dermatitis, a hereditary and non-contagious skin disease with chronic inflammation.^[22] NGF is known to up-regulate neuropeptides, especially substance P. Substance P has been found to have an important role in inducing pain however there is no confirmation that substance P directly causes acute sensitization. Instead substance P may contribute to itch by increasing neuronal sensitization and may the affect release of mast cells, which contain many granules rich in histamine, during long-term interaction.^[2]

Noxious input to the [[spinal cord] is known to produce central sensitization, which consists of allodynia, exaggeration of pain, and punctuate hyperalgesia, extreme sensitivity to pain. Two types of mechanical hyperalgesia can occur: 1) touch that is normally painless in the uninjured surroundings of a cut or tear can trigger painful sensations (touch-evoked hyperalgesia), and 2) a slightly painful pin prick stimulation is perceived as more painful around a focused area of inflammation (punctuate hyperalgesia). Touch-evoked hyperalgesia requires continuous firing of primary afferent nociceptors, and punctuate hyperalgesia does not require continuous firing which means it can persist for hours after a trauma and can be stronger than normally experienced. In addition, it was found that patients with neuropathic pain, histamine ionophoresis resulted in a sensation of burning pain rather than itch, which would be induced in normal healthy patients. This shows that there is spinal hypersensitivity to C-fiber input in chronic pain.^[2]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Ogechukwu Hannah Nnabude, MD

Common causes of itch include skin diseases, systemic diseases, allergies, medications, insect stings among many others

The feeling of itchiness can be caused by a movement of hair or the release of a chemical (histamine) from cells under the skin. Itchiness is regarded as protective, as it helps creatures remove parasites that land on their skin.

Causes of itching listed in alphabetical order:

• Allergic reactions due to contact with specific chemicals, such as Urushiol from Poison Ivy or Poison Oak.
• Cholestasis ^[1]
• Skin conditions (such as psoriasis, eczema, sunburn, athlete’s foot, Dandruff and many others). Most are of an inflammatory nature.
• Diabetes Mellitus^{[2] [3]}
• Drug Side Effect: acamprosate calcium, acetaminophen, acetylcysteine, acitretin, aldesleukin, alitretinoin, aprepitant, azficel-T, betamethasone valerate]], bicalutamide, butorphanol, capsaicin, caspofungin acetate, cetrorelix, Ceftazidime, clocortolone pivalate, conjugated estrogens, D-Aminolevulinic acid, denileukin diftitox, docetaxel, doxorubicin Hydrochloride, diphenoxylate hydrochloride and atropine sulfate, ecallantide, epinastine hydrochloride, epirubicin , ergotamine tartrate, ethambutol, felbamate, fosphenytoin sodium, gallium Citrate Ga 67, halcinonide, Histrelin, hydrochlorothiazide, hydrocodone bitartrate, hydrocortisone butyrate, Hydroxyprogesterone caproate, Idursulfase, imiglucerase, ipilimumab, ivermectin, ketorolac tromethamine, lidocaine (cream), meropenem, mometasone furoate, morphine,naproxen sodium, nivolumab, ofloxacin, omega-3-acid ethyl esters, panitumumab, Penciclovir, piroxicam, permethrin, ribavirin, rifampin, sargramostim, sertaconazole, siltuximab, sinecatechins, sodium aurothiomalate, spironolactone, sulconazole, tacrolimus,taliglucerase alfa tazarotene, thallous Chloride Tl 201, tolbutamide, travoprost, tretinoin, triazolam, Trimethoprim, Von Willebrand factor
• Hodgkin’s disease ^{[4] [5]}
• Iron deficiency anemia ^[6]
• Insect bites, such as those from mosquitos, ants, and ticks.
• Jaundice as (bilirubin is a skin irritant at high concentrations)
• Parasitic infections
• Photodermatitis – sunlight reacts with chemicals in the skin, leading to the formation of irritant metabolites
• Polycythemia, which can cause generalized itching due to increased histamine as a result of higher numbers of mast cells
• Psychiatric
• Related to pregnancy:
  • Gestational pemphigoid
  • Pruritic Urticarial Papules and Plaques of Pregnancy (PUPPP)
• Scabies or infection with lice or worms
• Thyroid disease ^[7]
• Uremia ^[8]
• Xerosis which is dryness of the skin, is the most common cause of itching and is frequently seen in winters. Associated with older age, frequent bathing in hot showers or baths, and high temperature and low humidity environments.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Ogechukwu Hannah Nnabude, MD

There is a very broad differential diagnosis for itching due to an extensive list of possible causes. Itching may be due to dermatologic disease, systemic disease, reactions to chemicals and medications, weather, or psychiatric disease. Symptoms, laboratory findings and other diagnostic tests can help narrow down the list.

Pain and itch have very different behavioral response patterns. Pain evokes a withdrawal reflex which leads to retraction and therefore a reaction trying to protect an endangered part of the body. Itch creates a scratching reflex that draws one to the affected skin site. For example, responding to a local itch sensation is an effective way to remove insects on the skin. Scratching has traditionally been regarded as a way to relieve oneself by reducing the annoying itch sensation. However, there are hedonic aspects of scratching as one would find noxious scratching highly pleasurable.^[1] This can be problematic with chronic itch patients, such as ones with atopic dermatitis, who may scratch affected spots until it no longer produces a pleasant or painful sensation instead of when the itch sensation disappears.^[2] It has been hypothesized 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.^[1]

Events of “contagious itch” are very common occurrences. Even a discussion on the topic of itch can give one the desire to scratch. Itch is likely more than a localized phenomenon in the place we scratch. Results from a recent study showed that itching and scratching were induced purely by visual stimuli in a public lecture on itching. There is currently little detailed data on central activation for contagious itching but it is hypothesized that a human mirror neuron system exists in which we imitate certain motor actions when we view others performing the same action. A similar phenomenon in which mirror neurons are used to explain the cause is contagious yawning.^[1]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ogechukwu Hannah Nnabude, MD

Pruritus is seen in about 4% of the population. It is seen in malignancies, especially hematological malignancies such as polycythemia vera. Uremia and biliary cirrhosis are other diseases in which a significant percentage of patients may have pruritus.

About 280 million people globally, roughly 4% of the world’s population, have difficulty with itchiness. ^[1]

Pruritus may be associated with virtually any malignancy. ^[2] Certain neoplasms, especially hematologic malignancies, have]] pruritus as a common symptom. For example, patients with polycythemia vera, 48% to 70% have aquagenic pruritus, which is itching that is associated with water coming in contact with the skin. Also, about 30% of people with Hodgkin’s disease suffer from pruritus. ^[3] The incidence of pruritus in other types of hematologic malignancies is currently not known, however, investigators have reported its presence in approximately 3% of patients with non‐Hodgkin’s lymphoma ^[4]. Solid tumors may be associated with paraneoplastic pruritus. In fact, pruritis may one of the early symptoms, starting months or years before a patient is diagnosed. Pruritus is also frequent finding in cutaneous lymphomas. ^[5] Additionally, it is frequently seen in cancers involving the biliary tract. Retrospective studies have revealed that 2% to 11% of chronic itch cases are attributable malignancies. ^[6]

Pruritus has been reported to be an early symptom in some non-malignant diseases such as liver disease, renal insufficiency, thyroid disease, Sjögren’s syndrome, diabetes mellitus, iron deficiency, paraproteinemia, and other conditions. In internal diseases, itch has been best studied in cholestatic pruritus and uremic pruritus. ^{[7] [8] [6]}

About a third of uremic patients treated without dialysis complain of uremic pruritus, and on maintenance hemodialysis, the incidence of uremic itching rises to 70%-80%. ^{[9] [10]}

Cholestatic pruritis affects nearly, if not all patients with biliary cirrhosis and is the first symptom in nearly 50% of the patients with this disease ^[11] Furthermore, the prevalence of pruritus in patients with end‐stage HIV is over 20% ^{[12] [13]}

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Common risk factors in the development of itch are allergic reactions, cholestasis , diabetes mellitus, and drug side effect.

• Exposure to chemicals and plants increases the risk for allergic reactions due to contact such as Urushiol from Poison Ivy or Poison Oak.
• Hepatobiliary disease increases the risk of Cholestasis ^[1]
• Family history of atopy and dermatologic diseases is associated with increased risk of Skin conditions (such as psoriasis, eczema.
• Excessive sun exposure without proper use of sunscreen puts one at risk of sunburn, especially among people of fairer skin.
• Walking barefoot on moist surfaces, sharing socks and poor foot hygiene increases the risk of athlete’s foot ^[2], while poor scalp care increases the risk of Dandruff.
• Immunosuppression such as in chemotherapy, AIDS, immunosuppresant medications, and poorly controlled Diabetes Mellitus ^{[2] [3] [4]}
• Drug Side Effect: acetaminophen, acetylcysteine, acitretin, doxorubicin Hydrochloride, ergotamine tartrate, ethambutol, felbamate, fosphenytoin sodium, hydrochlorothiazide, hydrocodone bitartrate, hydrocortisone butyrate, Hydroxyprogesterone caproate, ketorolac tromethamine, lidocaine (cream), meropenem, mometasone furoate, morphine,naproxen sodium, permethrin, ribavirin, rifampin, tretinoin, triazolam, Trimethoprim, Von Willebrand factor. Also, Photodermatitis can occur when sunlight reacts with chemicals in the skin, leading to the formation of irritant metabolites
• Malignancies such as polycythemia vera and Hodgkin’s disease ^{[5] [6]}
• Iron deficiency anemia ^[7]
• Homeless populations, residents of homeless shelters, and people who are exposed to wooded areas have a higher risk of exposure to insect bites, such as those from mosquitoes, ants, and ticks, and unhygienic condition such as Scabies or infection with lice or worms.
• Jaundice as (bilirubin is a skin irritant at high concentrations)
• Pregnancy: as seen in Gestational pemphigoid and Pruritic Urticarial Papules and Plaques of Pregnancy (PUPPP)
• Thyroid disease ^[8]
• End stage renal disease patients are at risk of Uremia ^[9]
• Xerosis which is dryness of the skin, is the most common cause of itching and is frequently seen in winters. Associated with older age, frequent bathing in hot showers or baths, and high temperature and low humidity environments.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ogechukwu Hannah Nnabude, MD

The history, progression, and complications of pruritus are diverse and based on the cause.

In patients with malignancies, pruritus could be the first sign. In allergic reactions, pruritus may be one of the hallmark features. Pruritus after hot baths is a finding associated with hematologic malignancies.

Secondary bacterial infections can occur when bacteria are introduced through breaks in the skin brought about by scratching. Lichenification, the thickening of skin as a result of chronic scratching, can also be seen ^[1].

Pruritus by itself never has a poor prognosis besides its effects on comfort and mental health. However, the underlying causes of pruritus have diverse prognoses, with malignancies being the poorest. Skin irritations such as with poison ivy often produce no lasting effects once treated.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ogechukwu Hannah Nnabude, MD

A proposed approach to the evaluation of itching can be summarized below: ^[1]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ogechukwu Hannah Nnabude, MD

An array of prescription and over-the-counter anti-itch therapies are can be used for relief of itchiness. Non-chemical remedies include cooling, warming, and soft stimulation.

A variety of creams and sprays are available for use as topical antipruritics and are often over-the-counter. Oral anti-itch medications are also available but are often only obtainable by prescription. The active ingredients usually belong to the following classes:

• Topical emollients with maintaining skin moisture when xerosis is the underlying cause for pruritis
• Antihistamines, such as diphenhydramine (Benadryl)
• Corticosteroids, such as hydrocortisone topical cream
• Local anesthetics, such as benzocaine topical cream
• Topical capsacin ^[1]
• 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.
• Counterirritants, such as mint oil, menthol, or camphor ^[2]
• Phototherapy is helpful for severe itching, especially if caused by kidney failure. The common type of light used is UVB.

Sometimes, scratching can relieve isolated itches, hence the existence of devices such as the back scratcher. Often, however, scratching can intensify itching and even cause further damage to the skin, dubbed the “itch-scratch-itch cycle.

There is no studies conducted to investigate the effectiveness of emollient creams, cooling lotions, topical corticosteroids, topical antidepressants, systemic antihistamines, systemic antidepressants, systemic anticonvulsants, and phototherapy on chronic itchiness of unknown origin.^[3]