Chronic itching: from underestimation to personalised medicine with new blood tests

A vicious circle amplifies the psychological distress and further worsens the quality of life and makes clinical management even more complex'.

The origins behind itching are numerous and heterogeneous. Itching is the main symptom of most chronic inflammatory skin diseases, such as psoriasis and atopic dermatitis, and is also present in parasitic diseases such as scabies.

However, it is also frequently associated with systemic diseases: haematological diseases such as lymphomas and polycythaemia vera, liver and kidney failure.

It can sometimes represent a real medical emergency, as in the case ofcholestatic pruritus of pregnancy, which can jeopardise the course of the pregnancy and the survival of the foetus.

However, the cause is not always organic. Pruritus may reflect a psychological discomfort (psychogenic pruritus) or, despite thorough investigations, remain without an identifiable cause, configuring the so-called 'chronic pruritus of unknown origin'.

'Precisely because of the multiplicity of causes, the clinical, diagnostic and subsequently therapeutic approach to the patient with chronic pruritus can be complex,' emphasises Paolo Amerio, 'imposing on the dermatologist, the main referral specialist, a solid knowledge of internal medicine.

Research has made significant progress in understanding the pathophysiological mechanisms. In addition to histamine, which until recently was considered the main cause of itching, other inflammatory mediators produced by the body - so-called 'pruritogens' - have been identified in numerous chronic inflammatory diseases such as atopic dermatitis, psoriasis and other systemic diseases.

'These inflammatory mediators interact with immune cells, skin cells and neuronal networks, involving both the peripheral and central nervous system, producing the characteristic scratch response,' explains Prof Amerio.

Recent discoveries have paved the way forinnovative and targeted therapies, capable of acting on specific molecules such as interleukins 4 and 31, with rapid benefits on both skin inflammation and itching, sometimes within a few hours'.

Important progress is also being made in forms not related to skin diseases. "Paradigmatic is paresthetic notalgia, an itchy condition localised at the level of the back associated with postural disorders of the spine, or chronic renal insufficiency (uremic pruritus). In these conditions itching seems to be mediated by particular molecules called opioid receptors, which can now be blocked by targeted drugs,' adds Maglie.

The most recent research has shown how distinctly different signalling pathways can be activated within the same pathology. "One example is prurigo nodularis,' Amerio further clarifies, 'a pathology characterised by the appearance of excoriated nodules on the back, trunk, and limbs and accompanied by intense and disabling itching.

One study showed that although the disease always presents with the same clinical appearance, some patients have a similar molecular profile and a specific association with atopic dermatitis, while others seem to have a less active inflammatory profile and a specific association with spinal diseases.

Recognising these differences means being able to choose more targeted, effective therapies, avoiding unnecessary treatments and also reducing costs for the healthcare system and the patients themselves'.

The future perspective is to identify, even through a simple blood test, the specific mechanism underlying itching in each patient so as to directly select the most appropriate treatment, increasing effectiveness and reducing side effects.

"In the future, we will be able to profile each patient and immediately choose the most suitable therapy," conclude Paolo Amerio and Maglie, "because this is the direction of modern dermatology: to make a frequently underestimated symptom a clinical priority, to be managed with increasingly advanced and tailored instruments.