Itching

Synonym: pruritus

What is itching?

Itch has many similarities to pain. They are both unpleasant sensory experiences - pain elicits a reflex withdrawal and itch leads to a scratch reflex. However, both can lead to serious impairment of quality of life. Pruritus is defined as the desire to scratch. It can be peripheral, due to stimuli occurring in the skin, or central, when itching is perceived as occurring in the skin although it originates in the central nervous system.

Pathophysiology of itching¹

Itching may be associated with skin disease or have a systemic cause

Depending on the aetiology, a complex number of factors have been found that may be involved. Many different cells and mediators and modulators have been identified as having a role, both peripheral and central. Immune cells and glial cells may be involved to a greater extent than was previously thought. Agents which may be involved include histamines, leukotrienes, opioids, serotonin, cytokines (eg, interleukin-31), neuropeptides, itch-specific neurons and interneurons. Stress may also affect itch, along with the itch-reward cycle.

Itching symptoms

• This will depend on the underlying cause.

• Although itching is common and the vast majority of cases have an obvious and benign cause, it is essential to consider possible less common but serious causes. Examination should therefore include careful assessment of the abdomen and lymph nodes.

• Examination of the skin can help to elucidate the aetiology of the itch. A thorough examination may reveal lesions that the patient has not altered by scratching and therefore help in the diagnosis.

• The history should be tailored to suspected causes - certain symptoms may point the clinician in one direction or another:

  • Nocturnal itch suggests uraemia, cholestasis or psychogenic itch.

  • An itch which occurs as the skin cools after a hot bath or shower may be associated with polycythaemia vera.

  • An itch which brings to mind insects crawling over the skin may be due to delusional parasitosis - take a careful psychiatric history.

  • Burning can be due to lymphoma or to neuropathic pain.

  • Associated fever, night sweats, fatigue or weight loss should be taken seriously as red flags for a possible malignancy.

  • Itch in the family at the same time may suggest scabies.

Differential diagnosis²

Skin causes

• Contact dermatitis.

• Urticaria.

• Scabies.

• Lice.

• Dermatophytosis (tinea infections)

• Insect bites and stings.

• Atopic eczema.

• Pityriasis rosea.

• Psoriasis.

• Dermatitis herpetiformis.

• Lichen planus.

• Lichen simplex chronicus.

• Senile atrophy.

• Prickly heat.

Systemic causes

• Hepatic: cholestasis, especially primary biliary cirrhosis and drug-induced cholestasis.

• Pregnancy.

• Endocrine: diabetes mellitus, hyperthyroidism, hypothyroidism, hyperparathyroidism.

• Renal: chronic kidney disease.

• Haematological: polycythaemia vera, iron deficiency, myeloproliferative disorders.

• Neurological: multiple sclerosis, neuropathy, nerve root irritation or compression.

• Malignancy: Hodgkin's lymphoma, leukaemia, carcinoma (especially of the lung, prostate or stomach).

• Human immunodeficiency virus (HIV) infection.

• Drug allergies or side-effects (eg, opioid analgesics, allopurinol, amiodarone, statins).

• Psychological: obsessive states, schizophrenia, dermatitis artefacta.

Investigations

A detailed history and careful examination are necessary to determine the cause. Any suspicion of systemic cause, lack of obvious cause for itching, or any patient with pruritus that does not respond to conservative therapy should be evaluated for underlying systemic disease.

The National Institute for Health and Care Excellence (NICE) suggests the following tests where there is no sign of active skin disease to account for widespread itch:

• FBC, ESR, serum ferritin. (Iron-deficiency anaemia, polycythaemia, raised eosinophils in allergy. Raised white cell count in leukaemia and raised ESR in malignancy.)

• LFTs.

• Renal function and electrolytes.

A further set of tests may be appropriate, depending on the clinical presentation, suspected diagnosis and risk factors:

• Thyroid function

• HbA1c

• Bone profile

• HIV

• Hepatitis B and C

• Chest X-ray

Referral may be required where an underlying cause has not been identified.

Itching treatment and management³

The treatment of pruritus is aimed at identifying and treating the underlying cause as well as symptomatic treatment for the itch. Symptomatic treatment is primarily aimed at keeping the skin moist and cool.

General measures

• Advise the patient to avoid scratching the skin and to keep their fingernails short. Wearing gloves at night and tapping the skin or drumming the fingers on the skin rather than scratching may be helpful.

• Cooling: simple measures to create a cooler environment, such as wearing light clothing and keeping cool in bed, may help. Avoid use of vasodilators (caffeine, alcohol, spices, hot water) and excessive sweating.

• Advise avoidance of irritants such as soaps, bubble bath and detergents. Cotton clothes are usually preferable to woollen clothes.

Pharmacological

• Simple emollients may be effective when itching is associated with dry skin or in otherwise healthy elderly people. Advise liberal application as often as is required.

• Preparations containing crotamiton (eg, Eurax®) are sometimes used but are of uncertain value. Alternatively, aqueous cream containing menthol 0.5% or 1% may be helpful for some people.

• Topical antihistamines and local anaesthetics are not recommended, as they are not effective, or are only marginally effective and may occasionally cause sensitisation.

• Oral antihistamines may be effective but mainly in urticaria and insect bites where histamine is the main mediator. They are ineffective in most dermatoses and systemic causes. Sedating antihistamines may be useful for night-time use. (Note the 2015 warning about the risk of QT prolongation with hydroxyzine, and prescribing restrictions.)⁴

Other treatments which are used, mostly with specialised dermatologist advice, for specific causes of itch include:

• Topical corticosteroids (inflammatory skin conditions such as eczema).

• Oral colestyramine. This is the treatment of choice for pruritus due to biliary obstruction but its effect may be temporary and it is only effective if biliary obstruction is incomplete.⁵ Rifampicin, opioid antagonists and selective serotonin reuptake inhibitors (SSRIs) are also used.

• Thalidomide and naltrexone (uraemia). Nalfurafine has been found effective for itch related to uraemia but is not available in the UK.⁶

• Gabapentin (chronic kidney disease).

• Cimetidine and corticosteroids (Hodgkin's lymphoma).

• Paroxetine (paraneoplastic itch).⁷

• Aspirin and paroxetine (polycythaemia vera).

• Indometacin (HIV-positive patients).⁷

If these specific remedies fail, paroxetine and mirtazapine can be effective. Topical or systemic application of specific agonists such as cannabinoids or calcineurin inhibitors can influence neuroreceptors on sensory nerve fibres of the skin and suppress pruritus.⁸ Itch-selective neurons in the dorsal horn of the spinal cord can be targeted to inhibit the transmission of pruritus to the somatosensory cortex. Anticonvulsants, antidepressants and micro-opioid receptor antagonists interfere with the sensation of pruritus in the central nervous system.

Other^{1 9}

Ultraviolet light therapy may be more effective than medication for itch in certain conditions, such as chronic kidney disease, HIV and some dermatological causes.

In localised pruritus the use of transcutaneous electrical nerve stimulation (TENS) may help in the short term. Acupuncture has been used for localised pruritus. Evidence for these options is anecdotal.

Psychological strategies such as habit reversal training, relaxation therapy, and cognitive behavioural therapy (CBT) may have a role in breaking the itch-scratch cycle and the management of chronic itch.

A number of novel agents are being explored in trials.

Complications

Itch is a distressing, subjective symptom that may interfere significantly with the quality of a patient's life.