Itch

Itch, also known as pruritus, is an unpleasant sensation that results in an urge to scratch. We can feel itch at any location where itch occurs from the top of the head to the toes. However, there are topographical differences in itch intensity. Itch is mainly conducted by C nerve fibers from the skin where itch emanates to the central nervous system. However, the abundancy of C fibers does not necessarily lead to higher itch intensity.Interestingly reduction and/or structural changes of C fibers seem to play a role in itch sensation. In addition, C tactile fibers (CT afferents), which are activated by gentle "affective" touch and seem to be associated with scratching pleasurability and the reward system in the brain, can be involved in itch sensation and topographical differences of itch.

Barrier damage, dry skin and itch are intricately linked and form the basis of many common skin diseases. Damage from environmental insults, or genetic or inflammatory causes, can impair the skin barrier, resulting in an increase in transepidermal water loss and activation of itch-associated nerve fibres. The itch-scratch cycle can perpetuate skin barrier damage and itch. Topical therapeutic strategies are utilised to overcome dry skin and itch, primarily in the form of emollients. Recent advances in our understanding of the mechanisms underlying itch have enabled the development of new topical therapies, which may be incorporated into existing treatment regimes. Ultimately, treatment of dry skin and itch must be highly tailored to the individual according to their needs.

Chronic pruritus is a relevant symptom burden in various systemic diseases. It is most commonly observed in patients with chronic kidney disease, hepatobiliary and hematological disorders as well as adverse drug reaction. Recent basic research has unraveled novel treatment targets which are currently in pre-clinical phases, clinical trials or have already been licensed. While μ-opioid receptor antagonists have been used since decades mainly in cholestatic pruritus, the k-opioid receptor agonist nalfurafine has been licensed in Japan for chronic kidney disease associated pruritus (CKDaP) as well as cholestatic pruritus. Further κ-opioid receptor agonists are currently investigated in various clinical trials including CKDaP. In recent years, the calcium channel blockers gabapentin and pregabalin have also been recognized as effective anti-pruritus therapy in several internal diseases with the best evidence in chronic kidney disease associated pruritus. Neurokinin-1 receptor antagonists have been investigated with variable benefit in CKDaP, solid tumors and lymphoproliferative disorders such as cutaneous T-cell lymphoma, Sézary syndrome. Inhibitors of the ileal bile acid transporter (IBAT) represent a selective interruption of the enterohepatic circulation and are currently investigated in various hepatobiliary disorders associated with pruritus. The current development and testing of novel drugs in clinical trials offers hope to struggling physicians and suffering patients. This article is protected by copyright. All rights reserved.

Itch is a somatosensory sensation that informs the organism about the presence of potentially harmful substances or parasites, and initiates scratching to remove the threat. Itch-inducing (pruritogenic) substances activate primary afferent neurons in the skin through interactions with specific receptors that converts the stimulus into an electrical signal. These signals are conveyed to the dorsal horn of the spinal cord through the release of neurotransmitters such as natriuretic polypeptide b and somatostatin, leading to an integrated response within a complex spinal interneuronal network. A large sub-population of somatostatin-expressing spinal interneurons also carry the Neuropeptide Y (NPY) Y1 receptor, indicating that NPY and somatostatin partly regulate the same neuronal pathway. This review focuses on recent findings regarding the role of the NPY/Y1 and somatostatin/SST receptor in itch, and also presents data integrating the two neurotransmitter systems.

Chronic pruritus is defined by itching lasting 6 weeks or more and is known to be both a highly prevalent and burdensome symptom of many pruritogenic diseases. Its status as a symptom has many implications mainly that the symptom should evolve and subside with the disease. However, according to the clinical experience, chronic pruritus often does not parallel the disease course and requires an own management. It is speculated, that neuronal sensitization processes take place which lead to disconnection of the symptom from the underlying disease and establishment of an own course of pruritus. It is thus discussed that pruritus can be both – a symptom of diseases but also an entity by itself. Further studies are needed to learn more and improve our understanding of this condition. This article compares its role in pruritogenic diseases, encourages discussion on the topic and provides an overview of the proper questions to ask. This article is protected by copyright. All rights reserved.

Mast cells, eosinophils, and basophils are central effector immune cells in allergic skin inflammation including atopic dermatitis (AD). Recent studies revealed that the bidirectional interaction between these three immune cell types (mast cells, eosinophils, and basophils) and the nervous system is involved in the pathogenesis of neurogenic inflammation, pain, and pruritus. Emerging evidence shows that these cells are the main source of pruritogens such as histamine, neuropeptides, cytokines, which are potential new therapeutic targets for drug development in chronic pruritus. For instance, many Th2 cytokines including interleukin (IL)-4, 13, and 31 have been recognized as some of the most promising targets for the treatment of chronic pruritus in AD. In this review, we highlight the link between these three immune cell subsets and peripheral nerves, with emphasis on the development of chronic pruritus such as AD. We present cytokines and receptors of these three immune cells and peripheral nerves, and discuss the therapeutic potential of targeting these neuro-immunological processes. This article is protected by copyright. All rights reserved.

Chronic itch is common in the elderly patient and may be caused by a variety of known dermatologic and non-dermatologic conditions and can have a significant effect on quality of life. Age-related changes in barrier function, immunosenescence, and neuronal changes and neuropathies are common predisposing factors to chronic itch in this age group. Certain primary dermatologic conditions are more common in the elderly and can cause chronic itch. Also, co-morbid diseases particularly of the renal, hepatobiliary, or hematologic systems, psychologic conditions, or medications may contribute to chronic itch in this population. Thus, medical workup for an elderly patient with chronic itch requires special attention to the patient's medical history, current health status, and medications. Topical treatments and emollients may be recommended for elderly patients, with consideration of specific adverse effects and alternatives. Systemic medications pose a higher risk of adverse effects and many are contraindicated in the elderly for this reason. In addition, management in the elderly may be complicated by differential pharmacokinetics of medications, the presence of co-morbid health conditions, cognitive disorders, physical limitations, and polypharmacy. New and emerging treatment modalities hold promise for use in the elderly due to these special considerations.