Chronic itching: a common but often ignored symptom

Germany's first research group for pruritus – researchers from Universitätsklinikum Erlangen are also involved

Chronic itching, or pruritus as it is known by its medical term, affects up to 25 percent of the population during the course of their lives. ‘It’s an important issue that is greatly underestimated by the medical profession’, says Dr. Andreas Kremer from the Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology at Universitätsklinikum Erlangen. Researchers throughout Germany have now joined forces to form the first research unit in Germany to carry out research on the subject of chronic itching as part of a translational project called PRUSEARCH. The group is being funded by the German Research Foundation (DFG) and is led by Prof. Dr. Martin Schmelz from Ruprecht-Karls-Universität Heidelberg. In Erlangen, the Department of Medicine 1 and the Institute of Physiology and Pathophysiology at FAU Erlangen-Nürnberg are involved.

Chronic itching lasting six weeks or more severely affects patients’ quality of life. It occurs not only with dermatological conditions such as psoriasis or eczema, but also with conditions that affect the liver and the gall bladder, kidney failure, diabetes and cancer, after cancer treatment and in psychiatric and neurological conditions. Older people are more frequently affected by chronic itching. However, targeted treatments are still not available.

‘Symptoms are often negated as treatment is difficult, as was the case with chronic pain 30 years ago’, explains Dr. Kremer. The research unit’s main aim therefore is to identify mediators of chronic itching in patients, characterise structural and functional changes in nociceptors (free sensory nerve endings) in chronic pruritus and define possible mechanisms of neuronal sensitization.

Liver disease causes itching

In a sub-project of PRUSEARCH and in collaboration with Prof. Dr. Peter Reeh from the Institute of Physiology and Pathophysiology at FAU, the working group led by Dr. Andreas Kremer is investigating cholestatic pruritus, which is caused by diseases of the liver and gall bladder. ‘Whether it’s an inflamed biliary tract, hepatitis C, liver cirrhosis or a liver tumour – chronic pruritus can occur with all conditions that affect the liver or the biliary tract.

Chronic pruritus is often a symptom of cholestatic conditions, when the secretion of bile acids is disrupted’, explains Andreas Kremer. Cholestatic pruritus is particularly uncomfortable and scratching offers no relief. Patients report that it is most severe particularly in the evenings and during the early hours of the night. It occurs on patients’ extremities in particular, but can also occur on the entire body.

There have been some breakthroughs in research during the last few years and some clinical trials have started with the aim of stopping chronic itching. Dr. Kremer and his team now want to draw on this research. Dr. Andreas Kremer has already identified one trigger for itching – lysophosphatidic acid or LPA. This small lipid is an interim product of intercellular fat metabolism and it has been known for some time that LPA influences muscle cells and platelets, blood pressure and inflammation processes as well as the development and spread of tumours, amongst others.

Now it has been shown that it can also cause itching. In this context, Dr. Kremer discovered that the LPA-forming enzyme autotaxin (ATX) is an important factor contributing towards chronic pruritus. ‘We are currently investigating exactly how LPA works on the molecular level and how the lipid activates neuronal and non-neuronal cells in translational studies – that is, from in-vitro research to research in humans’, says Kremer.

In humans, the researchers in Erlangen are observing the influence of LPA using psychophysics. This involves injecting the substance directly in the skin of test subjects and asking them to evaluate what they feel, such as itching, but also pain. Furthermore, the researchers intend using microneurography to investigate which sub-classes of somatosensory nerve fibres are activated by LPA. ‘To do so, we puncture the peroneal nerve with a very thin metal microelectrode and insert a second electrode into the skin. Such electrodes enable us to tap the impulses of individual nerve fibres like a telephone wire and ‘listen in’ and stimulate single nerve fibres using electricity’, says PD Dr. Barbara Namer, who is also part of the research team.

To test the characteristics of these nerve fibres, various stimuli are applied to the back of the foot in addition to LPA such as pressure, heat, cold or histamine. ‘We hope to not only improve our understanding of LPA, but also to identify further mediators for itching in future. This is the basis for new medication to treat the cause of the itching’, says Dr. Kremer.

Members of PRUSEARCH

In addition to the universities in Heidelberg/Mannheim and Erlangen, Westfälische Wilhelms-Universität Münster, Johannes Gutenberg-Universität Mainz, Julius-Maximilians-Universität Würzburg, Heinrich-Heine-Universität Düsseldorf and Carl von Ossietzky Universität Oldenburg are involved in PRUSEARCH. Prof. Dr. Martin Schmelz, spokesperson of the new DFG research unit, is a former employee of the Institute of Physiology and Pathophysiology at FAU and is now working in Mannheim.

Further information:

Website of the link to the DFG research group: prusearch.net

Dr. Dr. Andreas Kremer
Phone: +49 9131 85 35000 or -45211
andreas.kremer@uk-erlangen.de