Summary

Pruritus is defined as an unpleasant itching sensation that leads to intensive scratching. The terms pruritus and itching are used synonymously. Pruritus is the most common symptom in dermatology that may occur with or without visible skin lesions. It may be of localised or generalised character.

It is important to distinguish between acute and chronic pruritus. Pruritus lasting >6 weeks is defined as chronic pruritus. Based on aetiology, chronic pruritus may be classified as being of dermatological, systemic, neurological, psychogenic/psychosomatic, mixed, or unknown aetiology. Chronic pruritus can be very distressing and refractory to treatment. Its intensity frequently correlates with degree of quality of life impairment, level of stigmatisation, severity of depression, and emotional stress. [1]

According to the newest clinical classification, [2] patients with pruritus may be characterised as those with itching on primarily diseased, inflamed skin; pruritus on primarily normal, non-inflamed skin; and chronic secondary scratch lesions.

Epidemiology

Itching is a common ailment. A large epidemiological study performed in Germany on 11,730 individuals demonstrated the point prevalence of chronic pruritus (at least 6 weeks prior to data collection) of 16.8% and it increased with age from 12.3% (16-30 years) to 20.3% (61-70 years). [3] In a self-reported morbidity study, itch was the most frequently mentioned skin symptom (7%), and it was reported significantly more often by men from East Asia (18%) and the Middle East/North Africa (13%). [4] In another study, patients reporting this symptom were younger, predominantly female, and more distressed; they had lower income, poorer social support, and experienced more negative life events. [5]

Pruritus is a common symptom of many skin diseases. For example, it is a cardinal symptom of atopic eczema, and all patients with this disease are believed to have pruritus at some point during their illness. [6] Similarly, about 70% to 90% of patients with psoriasis have pruritus. [7] [8] [9] Pruritus may also complicate other systemic diseases, such as chronic renal failure, [10] blood malignancies, or liver disorders. For instance, the frequency of chronic pruritus in haemodialysis patients has been estimated to be between 22% and 70%. [11] [12] [13]

Pathophysiology

This depends on the underlying disease. Itch may be induced or modulated by many different mediators, including histamine, acetylcholine, catecholamines, haemokinins, chemokines, cytokines (interleukin 2, interleukin 31), neuropeptides, endothelin, endovanilloids, endocannabinoids, hormones of the hypothalamus-pituitary axis, kallikreins, proteases, prostaglandins, leukotriene B4, neurotrophic peptides, and opioids. [14]

A specific neuronal pathway for itch has been identified. Pruritic stimuli are transmitted mainly by mechano-insensitive unmyelinated afferent C-fibres that have a particularly low conduction velocity, large innervation territories, and high transcutaneous electrical threshold.

In the spinal cord, the pruritic stimuli are transferred by specific pruriceptive neurons of dorsal horns to the posterior part of the ventromedial thalamic nucleus, which projects to the dorsal insular cortex. Specific itch pathway neurons have been identified in the spinal cord showing expression of gastrin-releasing peptide receptors. [15] Induced itch stimuli co-activate the anterior cingulate cortex, supplementary motor area, and inferior parietal lobe predominantly in the left hemisphere.

Following itch induction, the multiple activated sites in the brain argue against the existence of a single itch centre and reflect the multidimensionality of pruritus. [16] Importantly, it has been demonstrated that the brain activity in patients suffering from chronic itch upon pruritic stimuli differs significantly from that observed in healthy subjects. [17]