Pruritus L29.8

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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Synonym(s)

itchiness of the skin; Itching; Skin itching

Definition
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Frequently occurring (polyetiological) symptom with a very differentiated treatment for numerous skin diseases or also for diseases of internal organs or systems.

It can also occur without a visible cause (old name: pruritus sine materia) or as a somatoform disorder.

A distinction must be made between:

  • the localized (sometimes also punctiform) or the diffuse, possibly generalized itching
  • the acute or chronic
  • the pruritus resulting from external or internal influences.

Pruritus is often perceived as a different sensation of the skin and/or semi-mucosal membranes (tingling, stinging, burning, biting). Depending on its quality, it is answered reflexively with squeezing, scratching, rubbing or chafing.

Itching can also be accompanied by small fibre neuropathy.

Classification
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There are several methods for subjective evaluation of pruritus intensity, such as the English-language "Itch Severity Scale" or the Virtual Analogue Scale (VAS), which distinguishes between 5 qualities (analogue scale from 0-10), which is used here for the sake of simplicity:

  • 0 = no pruritus
  • 0.1-2.9 = low/mild pruritus
  • 3.0-6.9 = moderate / moderate pruritus
  • 7.0-8.9 = severe pruritus
  • 9.0-10.0 = very severe pruritus

Basically, a distinction should be made between whether pruritus develops in normal or inflamed skin.

Occurrence/Epidemiology
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Pruritus is the most frequently reported symptom in dermatology and yet there are still few reliable scientific studies on pathophysiology, incidence and prevalence of pruritus. The incidence of chronic pruritus in general medical conditions is estimated at about 8%.

It is now known that the nerve fibres that conduct the itching are free non-myelinated nerve endings with particularly dense branching in the epidermis of the skin, the mucous membranes and the cornea. The information recorded there is initially transmitted with the signals for pain and thermal sensations in the ipsilateral tract, and after synaptic connection in the contralateral tractus spinothalamicus lateralis. There is currently divergent information about the processing in the brain. Activity was found in both the motor and sensory areas of the cortex. Thus, pain and itching seem to use the same pathways, but in contrast to pain, subcortical activation has not been found for itching.

Etiopathogenesis
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  • So far, numerous potential chemical mediators of pruritus have been identified:
    • Histamine from mast cells and keratinocytes binds to H1 and H2 receptors on peripheral nerve endings. This results in depolarization of the nerve and release of the neuropeptide substance P. Histamine can inhibit SP release via H3 receptors.
    • Acetylcholine: Neurotransmitter of the autonomic nervous system. Release is also possible from keratinocytes. Binding to muscarinergic (M1-M5) and nicotinergic receptors. Functionally, it primarily mediates pain (nociception). Stimulation of M3-receptors and nicotinergic receptors mediates itching, e.g. in atopic eczema.
    • In the skin bradykinin mainly causes pain via the B2 receptor but also causes a degranulation of mast cells and enhances e.g. the histamine effect at the nerve fibre, the release of substance P and prostaglandin E.
    • Serotonin acts via serotonin 3 receptors to promote itching. However, serotonin 3-receptor antagonists do not show any effect on nephrogenic itching.
    • Endothelin is produced by endothelial cells and causes a neurogenic inflammatory response associated with burning itching by stimulating nerve fibres and releasing NO.
    • Vanilloid receptors on sensitive skin nerves are cation channels that bind vanilloids and are also activated by capsaicin and heat. They mediate burning pain and itching. Repeated capsaicin application leads to desensitization of the nerve fiber and suppression of itching.
    • Proteinases such as trypsin, chymotrypsin and papain also appear to trigger itching, which can be blocked by antihistamine administration. Trypsin from mast cells activates PAR-2 (proteinase activated receptor 2), which is expressed on peripheral nerve fibres. Elevated concentrations of trypsin and PAR-2 have been found in patients with atopic dermatitis.
  • Sensitivity modulation:
    • Prostaglandins potentiate histamine-induced itching and are also capable of inducing mild itching themselves.
    • Interleukins: IL-2 causes itching by activating C-nerve fibers. IL4 can cause atopic eczema-like skin changes in mice. IL-6 and the IL-6 receptor are expressed in nerve cells and are found in increased amounts e.g. in prurigo papules.
    • Neurotrophins and Nerve Growth Factor (NGF) cause nerve growth. NGF and neurotrophin-4 from keratinocytes are overexpressed in Prurigo nodularis and in atopic dermatitis.
    • Opioids (e.g. β-endorphin, enkephalins and endomorphins) seem to reduce the sensitivity of peripheral nerve endings via various opioid receptors by inhibiting e.g. substance P release. However, systemically administered opioids can induce itching.
    • Cannabinoids reduce histamine-induced itching via CB1 and CB2 receptors. For the treatment of chronic pruritus, cannabinoid agonists were used topically in one study. In 86.4% of the test persons a significant reduction of itching occurred after several weeks of therapy.
    • The activation of the cold receptors CMR1 and ANKTM1 (ion channels) by cooling of the skin surface leads to a reduction of itching.
  • Eosinophil granulocytes:
    • In the skin, eosinophil granulocytes are often found near peripheral nerve fibres in inflammatory allergic diseases. For example, eosinophilic granulocytes in Prurigo nodularis are in direct contact with peripheral nerves. EDN and ECP have neurotoxic effects. EDN can be detected in lesions of patients with Prurigo nodularis. Eosinophil granulocytes can release neurotrophins such as NGF (nerve growth factor) and BDNF (brain-derived neurotrophic factor). BDNF prevents the apoptosis of eosinophilic granulocytes. Neurotrophins are known for their neurotrophic and neuroprotective activity. Furthermore, neurotrophins induce chemotaxis of eosinophilic granulocytes. They are therefore important mediators for the influence of cutaneous inflammation. They play an important role in the process of sensitization and in the development of pruritus. Besides neurotrophins, eosinophil granulocytes can also release neuropeptides such as substance P, VIP (vasoactive intestinal peptide). Both mediators are involved in the mediation of pruritus.
  • mast cells:
    • Vasoactive intestinal peptide, neurotensin, somatostatin, secretin as well as substance P and corticotropin-releasing hormones (CRH) induce itching, wheals and erythema by degranulation of mast cells.
    • Substance P acts via neurokinin receptors on mast cells and the release of NO. Stress leads to increased substance P and CRH concentrations in the skin and thus to mast cell degranulation.
    • Together with substance P, the neuropeptide calcitonine-gene-related peptide (CGRP) is frequently found, which possibly has an inhibitory effect on substance P.
  • leukotrienes:
    • The role of leukotrienes (see below eicosanoids) in the development of itching is unclear. Leukotriene B4 causes itching in mice; nocturnal leukotriene B4 excretion in urine correlates with the intensity of itching in atopic dermatitis. Substance P, a potent pruritic mediator, initiates the arachidonic acid cascade for the production of prostaglandins and leukotrienes; leukotriene antagonists therefore have an antipruritic effect.
  • Haes:

Laboratory
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  • Laboratory tests that can lead to the clarification of the Prurigo symptom:
    • BSG, differential blood count, uric acid, urea, creatinine, transaminases, alkaline phosphatase, bilirubin, glucose, HbA1c thyroid function test (TSH, T3, T4), parathyroid function (calcium, phosphate), serum iron, ferritin, serum protein electrophoresis, serum immune electrophoresis, antinuclear antibodies (ANA), extranuclear antibodies (ENA), HIV diagnostics (ELISA, PCR)
    • chest x-ray
    • stool test for eggs, parasites, occult blood
    • Allergy diagnostics: Total IgE, histamine, serotonin, prick test (main allergens), epicutaneous test, urine diagnostics (sediment, 5-hydroxyindoleacetin acid, mast cell metabolites).

Diagnosis
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Pruritus is a subjectively felt symptom that cannot be measured by physical or biophysical methods. Therefore, various scales (categorical scales, interval scales, continuous scales) and questionnaires (Worchester Itch Index, Eppendorf Itch Questionnaire) have been developed for the direct or indirect (via scratching behaviour) evaluation of pruritus. In the indirect evaluation of itching via the scratching behaviour it should be noted that very itchy diseases such as urticaria and mastocytosis rarely lead to scratching but rather to rubbing and pressing.

Anamnestically important factors that can lead to clarification of the symptom:

  • onset (e.g. abrupt, gradual, already preceding itching episodes)
  • Time course (e.g. continuous, intermittent, cyclical, night-time)
  • Duration (e.g. days, weeks, months, years)
  • Character of the itching (e.g. tingling, burning, stinging)
  • Severe (e.g. affects everyday life or night's rest)
  • Localization (e.g. generalized, localized, unilateral, bilateral)
  • Relationship to certain activities (e.g. profession, hobbies)
  • Provoking factors (e.g. water, skin cooling, air, physical exertion)
  • Does scratching, rubbing or pressure already cause itching?
  • Patient's theory of the cause of pruritus (dosage, duration and frequency of application or taking topical or systemic medication
  • Targeted questioning after HAES infusions (see below pruritus after HAES infusions) or dialysis
  • Known local or systemic allergies
  • Atopic diathesis (eczema, allergic rhinitis, allergic asthma)
  • pre-existing conditions (thyroid, liver, kidney or other systemic diseases)
  • Family history of atopy, skin diseases and itching
  • Professional activity
  • Hobbies
  • Social environment (home environment, personal contacts, nutrition, stress factors)
  • Drugs (nicotine, alcohol, i.v. drugs)
  • skin care habits, use of cosmetics
  • Pets (type I sensitizations)
  • Sexual history (for genital pruritus)
  • Travel history (exclusion of epizootic or zoonotic diseases)
  • Suspected diagnoses already made.

Therapy
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To date, there is no antipruritic drug whose efficacy can be equated with the success of aspirin in pain therapy. Therefore, the therapy must be individually composed depending on the patient and the disease.

  • General:
    • Wear comfortable clothing (no wool or synthetic fibres, cotton clothing instead)
    • Avoid excessive extreme temperature baths. Warm water or a short shower without drying detergents is better.
    • Regular moisturizing of the skin with basic care products (basodexan, optiderm) according to the individual tolerance (rich emmolients for the night, creams for the day).
    • Follow advice to interrupt the itch-scratch cycle (e.g. put on cold washcloth, apply light pressure).
    • Moderate physical activity.
    • Avoid stress and anxiety.
    • Avoid contact with dust and dust mites.
    • Avoid hot food, drinks or other hot liquids.
    • Participation in relaxation therapy.
  • Topical therapy:
  • systemic therapy:
    • Antihistamines (also as high-dose therapy in mono- or multiple therapy)
    • Doxepin
    • Systemic glucocorticoids
    • Ciclosporin A
    • Ondansetron
    • Paroxetine
    • Thalidomide
    • Opioid antagonists (e.g. naloxone, naltrexone, nalmefene)
    • neurokinin receptor 1(NKR1) antagonists, e.g. aprepitant. The primary indication of aprepitant is chemotherapeutic vomiting (e.g. Emend 80 mg p.o./day). Alternatively, for patients with chronic itching, the NKR1 antagonist serlopitant (1.0-5.0mg/day) can be used.
  • physical therapy:
    • Cutaneous field stimulation
    • Acupuncture.
  • UV-irradiation:
  • psychotherapy:
    • Group therapy
    • Behavioural Therapy
    • Biofeedback
    • Support groups.

Naturopathy
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Order Therapy

The first commandment is the search for the cause (dermatological, internal or neurological basic illness, medication, infections, etc.), as well as the avoidance or therapy of the triggers. Depending on the cause, avoiding histamine liberators is also part of this.

Phytotherapy

Capsaicin is the active ingredient of Spanish pepper, a nightshade plant. Secured effect according to commission E/ESCOP as an analgesic for muscle pain, nerve pain, neuralgia and skeletal pain in external application.

Capsaicin works by draining, washing out neuropeptides from the free nerve endings, which leads to analgesia. Caution with simultaneous application of heat! Washing off the capsaicin-containing cream/ointment with an oily base - no water! Finished preparations: e.g. Dolenon ointment, Kneipp rheumatism ointment Capsaicin N, Thermo Bürger, Capsamol ointment or as magistral formulation with different concentration: New formulation Form NRF: Hydrophilic Capsaicin cream 0,025 / 0,05 or 0,1 %, NRF 11.125

Lavender oil, positive monograph by Commission E, has a simultaneous sedative and local anaesthetic effect and can be used as an additive in pruritus. Either as an essential oil (vaporized in the room, or a few drops on a cloth) or systemically in capsule form (e.g. Lasea), lavender oil has a direct, emotionally balancing effect on the limbic system, making it easier to fall asleep.

Systemic therapeutic agents with a sedative effect can be used as a support: Valerian and hops in combination have a sedative effect (positive monograph of Commission E), preparations e.g. Selon, Kytta-Sedativum f, Ardeysedon, Sensinerv f, Dormoverlan, Vivinox. It should be noted that valerian only develops its full effect after 14 days.

Tables
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Pruritus in diseases

Diagnosis

Occurrence of pruritus

Atopic eczema

100%

Urticaria

100%

Skabies

90-100%

Irritative and contact allergic eczema

80-90%

Insect bites

80-90%

Desiccation eczema

80%

Tinea (corporis)

80%

lichen planus

80%

lichen sclerosus et atrophicans

80%

Primary biliary cirrhosis

80-100%

Bullous autoimmune diseases

70-80%

Cutaneous T-cell lymphoma

70-80%

Drug exanthema

50-70%

Psoriasis

50-60%

Herpes zoster / post-zosterical neuralgia

58% / 30%

polycythemia vera

48%

HAES-induced pruritus

40%

Renal pruritus, dialysis

22-66%

Somatotropic disorders

40-50%

M. Hodgkin

25-35%

Pregnancy

18%

Hyperthyroidism

4-7,5%

diabetes mellitus

3%

Solid malignancies

Rare

Iron Deficiency

no known prevalence


Drugs that can induce pruritus

Substance class

Generic drugs (examples)

ACE inhibitors

Captopril, Enalapril, Lisinopril

Antiarrythmics

Amiodarone

Antidiabetics

Glimipiride, metformin, tolbutamide

Antihypertensives

clonidine, doxazosin, hydralazine, prazosin, reserpine

angiotensin-2 antagonists

irbesatan, telmisartan, valsartan

Beta blocker

acebutolol, atenolol, bisoprolol, metoprolol, propanolol

Potassium antagonists

Amlodipine, Diltiazem, Felodipine, Nifedipine, Verapamil

Diuretics

furosemide, hydrochlorothiazide, spironolactone

Lipid reducers

clofibrate, fenofibrate, fluvastatin,ovostatin, pravastatin, simvastatin

Tranquillizer

Oxazepam

Uricostatics

Allopurinol, Probenecid

Note(s)
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  • Severe pruritus usually leads to sleep disorders, which is rarely observed in psychogenic pruritus.
  • Psychiatric comorbidity with chronic pruritus was considered significantly high in a study of 109 subjects. Therefore, psychotherapeutic care (see below somatoform disorders) is additionally recommended.
  • Nocturnal, generalized pruritus in combination with B-symptoms (fever, night sweats, weight loss) can indicate the presence of a malignant disease!
  • The term"Pruritus sine materia" should be avoided.

Literature
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  1. Andoh T et al (2014) Antipruritic mechanisms of topical E6005, aphosphodiesterase
    4 inhibitor: Inhibition of responses to proteinase-activatedreceptor
    2 stimulation mediated by increase in intracellular cyclic AMP. JDermatol
    Sci doi: 10.1016/j.jdermsci.2014.10.005
  2. Kim TW et al (2014) Clinical Characteristics of Pruritus in Patients with Scalp Psoriasis and Their Relation with Intraepidermal Nerve Fiber Density. Ann Dermatol 26:727-732

  3. Lee HJ et al (2014) Clinical characteristics of postherpetic pruritus: assessment using a questionnaire, von-Frey filaments and neurometer. Br J Dermatol doi: 10.1111/bjd.13569

  4. Legroux-Crespel E et al (2004) A Comparative Study on the Effects of Naltrexone and Loratadine on Uremic Pruritus. Dermatology 208: 326-330
  5. Samson Yashar S (2003) Narrow-band ultraviolet B treatment for vitiligo, pruritus, and inflammatory dermatoses. Photodermatol Photoimmunol Photomed 19: 164-168
  6. Singh F (2003) HIV-associated pruritus: etiology and management. At J Clin Dermatol 4: 177-188
  7. Schneider G et al (2006) Psychosomatic cofactors and psychiatric comorbidity in patients with chronic itch. Clin Exp Dermatol 31: 762-767
  8. Stand S et al (2006) Topical cannabinoid agonists. An effective new possibility for treating chronic pruritus. dermatologist 57: 801-807
  9. Ständer S et al (2010) Targeting the neurokinin receptor 1 with aprepitant: a novel antipruritic strategy. PLoS One 5:e10968
  10. White hair E (2003) Pruritus: a review. Acta Derm Venereol Suppl (Stockh) 213: 5-32
  11. Yosipovitch G (2003) Itch associated with skin disease: advances in pathophysiology and emerging therapies. At J Clin Dermatol 4: 617-622

Disclaimer

Please ask your physician for a reliable diagnosis. This website is only meant as a reference.

Authors

Last updated on: 29.10.2020