Pruritus: Management Algorithms and Experimental Therapies

Department of Surgery, University of California San Francisco, San Francisco, CA 94143, USA.
Seminars in cutaneous medicine and surgery (Impact Factor: 1.34). 06/2011; 30(2):127-37. DOI: 10.1016/j.sder.2011.05.001
Source: PubMed


Pruritus (itch) is a major symptom in many dermatologic as well as systemic diseases and has a dramatic impact on the quality of life in these patients. The symptom of itch has to be treated on the basis of its pathophysiology and its underlying disease. In daily practice, a "quick" diagnosis of the underlying disease is often difficult, although a rapid relief of the itch is desired. We often treat patients on the basis of the symptomatology. A rational therapeutic ladder for a symptomatic therapy is useful until the final diagnosis has been confirmed. There are probably many subtypes of pruritus, just as there are many diseases that cause itch. The pathophysiology in many subtypes of pruritus is still poorly understood, hindering a rapid and targeted treatment strategy. An extensive diagnostic workup is often required to determine the final cause(s) of the itch. Thus, in daily life, physicians often start with a more or less rational therapeutic strategy to combat the debilitating itch. We present possible therapeutic ladders that form the basis for effective therapeutic itch strategies in various diseases. On the basis of our current knowledge about the different pathophysiologies of itch, on clinical trials or case reports, and our own clinical experience, we aim to present therapeutic ladders for the rapid as well as long-term management of itch. Finally, we summarize current exciting developments of experimental strategies in itch research and in clinical development for itch therapy.

13 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: The literature survey 2011 is based on 1730 papers found in the databases MEDLINE and EMBASE with the keywords “thermography” or “thermometry” or “thermotherapy” or ‘skin temperature’ or ‘core temperature’ and restricted to “included in the databases between 01.01 and 31.12. 2011”. 36,5 percent of papers of this review are originated from Europe and 96 percent of all papers are written in English. 588 controlled studies using some kind of temperature measurement were included in this survey. Physiology, cardiovascular diseases, neurology, dermatology and clinical & experimental pharmacology were the predominant fields of applications of temperature measurement in medicine. As in previous years, therapeutic hypothermia and hyperthermia treatment was the topic of many papers. Fever attracted also a high number of publications. Some articles were related to sleep or pain. Only few papers were found for intravascular temperature measurement, Raynaud´s phenomenon or breast thermography.
    No preview · Article · Jan 2012 · Thermology International
  • [Show abstract] [Hide abstract]
    ABSTRACT: Itch/pruritus can be very distressing in palliative care population and often is difficult to treat. Conventional antihistamines lack efficacy. Cutaneous and central pathogenesis of itch is extremely complex and unclear, making its treatment challenging. Neuronal mechanisms have been identified in the pathophysiology of itch hence providing a myriad of therapeutic options. It has been established that pruritus and pain neuronal pathway interact with each other, hence neuropathic analgesics like gabapentin has shown to be efficacious antipruritic therapeutic option. Gabapentin impedes transmitting nociceptive sensations to brain, thus also suppressing pruritus. Gabapentin is safe and found to be effective in uremic pruritus, cancer/hematologic causes, opiod-induced itch, brachioradial pruritis, burns pruritus, and pruritus of unknown origin. Further research is required in this area to establish whether gabapentin is consistently effective.
    No preview · Article · May 2012 · The American journal of hospice & palliative care
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Itch, also known as pruritus, is a common, intractable symptom of several skin diseases, such as atopic dermatitis and xerosis. TLRs mediate innate immunity and regulate neuropathic pain, but their roles in pruritus are elusive. Here, we report that scratching behaviors induced by histamine-dependent and -independent pruritogens are markedly reduced in mice lacking the Tlr3 gene. TLR3 is expressed mainly by small-sized primary sensory neurons in dorsal root ganglions (DRGs) that coexpress the itch signaling pathway components transient receptor potential subtype V1 and gastrin-releasing peptide. Notably, we found that treatment with a TLR3 agonist induces inward currents and action potentials in DRG neurons and elicited scratching in WT mice but not Tlr3(-/-) mice. Furthermore, excitatory synaptic transmission in spinal cord slices and long-term potentiation in the intact spinal cord were impaired in Tlr3(-/-) mice but not Tlr7(-/-) mice. Consequently, central sensitization-driven pain hypersensitivity, but not acute pain, was impaired in Tlr3(-/-) mice. In addition, TLR3 knockdown in DRGs also attenuated pruritus in WT mice. Finally, chronic itch in a dry skin condition was substantially reduced in Tlr3(-/-) mice. Our findings demonstrate a critical role of TLR3 in regulating sensory neuronal excitability, spinal cord synaptic transmission, and central sensitization. TLR3 may serve as a new target for developing anti-itch treatment.
    Full-text · Article · May 2012 · The Journal of clinical investigation
Show more