Dermatology Update 2016

SESSIONS & ABSTRACTS

Montréal, Le Centre Sheraton - NOVEMBER 3-6, 2016

The Stuart Maddin Lecture Series

Understanding and treating Pruritis: where are we?

Note: Scroll down to watch an after-session interview with Prof. Martin Steinhoff

Although chronic pruritus (itch) is the most frequent symptom in dermatology, its diagnosis and treatment is still challenging and frustrating. Chronic itch is associated with several comorbidities like depression, anxiety, infection and sepsis, scarring, drug adverse events, and even suicide. Only a few drugs have been approved for the treatment of pruritus, but are ineffective in many cases, demanding improved therapeutic strategies.

Itch is regulated at different levels within our body systems: a) the cutaneous nerve endings equipped with a variety of mediators, receptors and cell signalling pathways; b) dorsal root ganglia (DRG) regulating expression levels and transport of mediators and receptors to the peripheral and central nerve endings; c) the central primary afferent synapse releasing different neuromediators and activating various receptors in the dorsal horn of spinal cord; d) the complex interaction of projection and interneurons in the spinal cord, e) ascending and descending neuronal pathways in the spinothalamic tract; and finally f) different centres in the brain regulating itch perception and response. Recent research indicates that various histamine-dependent as well as -independent itch pathways exist that are dependent on specific mediator-receptor interactions, endocytosis and exocytosis mechanisms that regulate mediator release and receptor sensitization or desensitization. Because all these mechanisms can be dysregulated during chronic pruritic diseases at different levels, new improved targeted therapies must consider the variety of mechanisms.

Recent findings indicate that a variety of biochemical mediator families are involved in mediating acute and chronic itch such as amines, cytokines, proteases, prostanoids, neurotrophins, neuropeptides, for example. The critical question for the improvement of itch therapy in the future is to identify the critical mediators, receptors and signalling pathways involved in chronic itch. Consequently, understanding the molecular mechanisms of itch have let to the development of several new drugs that are now in development at different levels like antagonists to IL4, IL-13, IL-31, PAR2, mu-opioids, NGF, ETAR, SP, BNP, GRP, TRP or sodium ion channels or kappa opioid or GABA agonists, for example. Thus, insights into the cell signalling cascades and manipulating the membrane cell maschinery involved in itch may be additional innovative advances leading to therapeutic improvements for patients with itch in the future. Intractable itch remains one of the major challenges for a dermatologist and the knowledge about the current drug repertoire and algorithms may lead to improved treatment options for this debilitating condition that has a significant impact on the patient and their families.

Speakers

Prof. Martin Steinhoff

Prof. Martin Steinhoff

Dermatologist, Doha, QT and Dublin, IE

References

  1. Steinhoff M., Bienenstock J., Schmelz M., Maurer M., Wei E., and Biro T. Neurophysiological, neuroimmunological, and neuroendocrine basis of pruritus. J Invest Dermatol 126: 1705-18 (2006).
  2. Cevikbas F, Wang X, Akiyama T, Kempkes C, Savinko T, Antal A, Kukova G, Buhl T, Ikoma A, Buddenkotte J, Soumelis V, Feld M, Alenius H, Dillon SR, Carstens E, Homey B, Basbaum A, Steinhoff M. A Sensory Neuron-expressed Interleukin-31 Receptor Mediates T helper Cell-dependent Itch: Involvement of TRPV1 and TRPA1. J Allergy Clin Immunol 2014 Feb;133(2):448-60.
  3. Kido-Nakahara M, Buddenkotte J, Kempkes C, Ikoma A, Cevikbas F, Akiyama T, Nunes F, Seeliger S,Hasdemir B, Mess C, Buhl T, Sulk M, Müller FU, Metze D, Bunnett NW, Bhargava A, Carstens E, Furue M, Steinhoff M. Neural peptidase endothelin-converting enzyme 1 regulates endothelin 1-induced pruritus. J Clin Invest. 2014Jun 2;124(6):2683-2695.
  4. Berger T.G. and Steinhoff M. Pruritus in elderly patients–eruptions of senescence. Sem Cutan Med Surgery 30: 113-7 (2011).
  5. Hong J., Buddenkotte J., Berger T.G., and Steinhoff M. Management of itch in atopic dermatitis. Sem Cutan Med Surgery 30: 71-86 (2011).
  6. Steinhoff M., Cevikbas F., Ikoma A., and Berger T.G. Pruritus: management algorithms and experimental therapies. Sem Cutan Med Surgery 30: 127-37 (2011).
  7. Suarez A, Feramisco J, Koo J, Steinhoff M. Psychoneuroimmunology of psychological stress and atopic dermatitis: pathophysiologic and therapeutic updates. Acta dermato-venereologica 92: 7-15 (2012).
  8. Steinhoff M, Geppetti P, Mentzer B, Pothoulakis H, Bunnett N. Tachykinins and Their Receptors: Contributions to Physiological Control, Disease and Therapy. Physiol Rev (2014) 94:265-301.