What is Itching: Signs, Etiology, Underlying Mechanisms and Causes


Pruritus or itching is an unpleasant sensation of the skin that causes the urge to scratch. It is a characteristic feature of many skin diseases and an unusual sign of some systemic diseases.

Pruritus may be localized or generalized and may occur as an acute or chronic condition. Pruritus that lasts more than six weeks is called chronic itching.

Pruritus can be intractable and incapacitating and a diagnostic and therapeutic challenge. It is the medical term for itching. Itching is an unpleasant sensation on the skin that causes the desire to rub or scratch the area for relief.

Itching can cause discomfort and frustration; In severe cases, it can lead to sleep disorders, anxiety, and depression.

Constant scraping for relief can damage the skin (abrasion, lichenification) and reduce its effectiveness as the primary protective barrier.

It is often a symptom of an underlying disease process such as a skin problem, a systemic disease, or abnormal nerve impulses.


What are the signs of itching?

There are no specific cutaneous signs associated with pruritus, apart from scratch marks (excoriations) and underlying condition symptoms.

Persistent scratching over some time can lead to:

Lichenification (thickened skin, simple lichen).

Prurigo papules and nodules.

Who is prone to suffer from this itching?

The epidemiology of pruritus depends on its underlying cause or causes. However, in general, chronic pruritus increases with age and is more common in women and people of Asian origin.


Itching is associated with dermatological and systemic causes, and it is essential to determine if there is an associated skin rash. A characteristic rash usually establishes the diagnosis of a primary dermatological disorder.

Pruritus is an essential component of some disorders (atopic eczema, dermatitis herpetiformis, chronic lichen simplex, and prurigo nodular), and these diseases are rarely diagnosed in their absence.

In conditions such as mild urticaria or watery pruritus, histamine levels are sufficient for a sensory response but not vascular, and there may be no skin findings.

Bullous pemphigoid may manifest with a pruritic phase for several months before the characteristic blisters appear.

An invisible form of mycosis fungoides can present as pruritus without skin rash and is diagnosed by biopsy.

Underlying mechanisms

Itching, like pain, can originate anywhere along the neural pathway of the itch, from the central nervous system (brain and spinal cord) to the peripheral nervous system and skin.

The mechanisms underlying pruritus are complex.

The itching signal is transmitted mainly through tiny selective CC fibers in the skin, in addition to the histamine-activated and non-histaminergic neurons.

These connect with secondary neurons that cross the opposite side of the spinothalamic tract and ascend to parts of the brain involved in sensation, emotion, reward, and memory. These areas overlap with those activated by pain.

Patients with chronic pruritus usually have peripheral and central hypersensitization (increased reaction).

This means they tend to overreact to noxious stimuli that usually inhibit itching (such as heat and scratching) and misinterpret non-harmful motivations as itching.)

How it stops the itching has been explained by an interaction with the pain pathways inside the dorsal horn of the spinal cord.


The causes of pruritus can be classified into five main.

Localized itching.

Localized pruritus is itching limited to a specific part of the body. It can occur in association with a primary rash (for example, dermatitis) or due to hypersensitive nerves in the skin (neuropathic pruritus).

Neuropathic pruritus is due to compression or degeneration of the nerves in the skin, in the path to the spine, or in the spine itself. Neuropathic itching is sometimes associated with reduced or absent sweating in the affected area of ​​the skin.

Typical causes of locomotor skin rashes

  • Scalp: seborrheic dermatitis, head lice.
  • Grover’s disease.
  • Hands: pompholyx, irritant, and allergic contact dermatitis.
  • Genitals: vulvovaginal infection of Candida albicans, lichen sclerosus.
  • Legs: venous eczema
  • Pies: tinea pedis.

Neuropathic causes of localized pruritus without primary eruption

  • Face: trigeminal trophic syndrome.
  • Arm: brachioradial pruritus
  • Back: notalgia paraesthetica.
  • Genital: vulvar pruritus, pruritus ani.
  • Dermatomal: herpes zoster (shingles) during the recovery phase.

Scratching a localized itch can lead to simple lichen, prurigo, or nodularis.

Systemic causes

Systemic diseases can cause generalized pruritus. This is sometimes called metabolic itching. There is nothing wrong with the skin itself until you see scales or skin lesions.

Metabolic disorders include chronic renal failure (dialysis) and liver disease (with or without cholestasis).

Uremic pruritus arises in patients undergoing dialysis due to xerosis (dry skin), secondary hyperparathyroidism, peripheral neuropathy (nerve disorders), and inflammation.

The secondary hyperparathyroidism in dialysis patients leads to microprecipitation (deposition) of calcium and magnesium salts in the skin, triggering the degeneration of mast cells and releasing serotonin and histamine.

Once the chronic pruritus has occurred, there may be secondary changes in the skin and central nervous system nerves that increase the itching sensation.

Hepatogenic pruritus is more common in intrahepatic than extrahepatic cholestasis. Examples of intrahepatic cholestasis are chronic viral hepatitis, primary biliary cirrhosis, and cholestasis related to pregnancy.

Extrahepatic cholestasis is associated with pressure on the bile ducts, such as pancreatic tumors or pseudocysts. It is believed that cholestasis releases toxic substances from the liver, which stimulates the neural fibers of itchy skin.

Characteristically, cholestatic pruritus is more severe at night; it affects the hands, feet, and areas where clothing rubs on the skin. Hematological disorders include iron deficiency anemia and polycythemia vera.

In iron deficiency anemia, generalized pruritus, glossitis (inflammation of the tongue), and angular cheilitis (rash of the corners of the mouth).

In polycythemia vera, the itching is usually precipitated by contact with water (watery pruritus), for example, after a shower. This is believed to be mediated by the effect of platelets, serotonin, and prostaglandins.

Endocrine disorders include thyroid disease and diabetes mellitus.

In Graves’ disease (thyrotoxicosis), increased blood flow, skin temperature, and decreased itch threshold mediated by increased thyroid hormones lead to itching.

The pruritus associated with myxoedema and hypothyroidism is rare, and, if present, the result of xerosis (dry skin) is more likely.

In diabetes mellitus, localized itching occurs in the perianal/genital region, usually due to Candida albicans or dermatophytic infections.

It is unclear whether metabolic abnormalities such as renal failure, autonomic failure, or diabetic neuropathy contribute to this.

Paraneoplastic itching is associated with lymphoma (Hodgkin’s disease), leukemia, and solid organ tumor (e.g., lung, colon, brain).

Paraneoplastic pruritus refers to the itching associated with malignancy, commonly Hodgkin’s lymphoma. In Hodgkin’s lymphoma, pruritus is thought to be caused by the release of histamine, which may be related to eosinophilia.

Infections that cause itching include infection with the human immunodeficiency virus (HIV) and hepatitis C virus.

Patients with HIV commonly complain of itching. This may be associated with skin infections/infestations, dry skin, drug reactions, hypereosinophilia (increased levels of eosinophils), and cutaneous T-cell lymphoma.

There is a possible correlation between intractable pruritus and the increased viral load of HIV. In chronic hepatitis C infection, the mechanisms responsible for itching are unclear.

In the absence of cholestasis, pruritus may be related to antiviral therapy; It has been observed in patients treated with combination therapy (interferon alfa and ribavirin).