2012/01/01 by Hjalte Holm Andersen, Lars Arendt‐Nielsen, Jesper Elberling +1 · 1 citation
Medicine · Neuroscience · Social Sciences · #Allergic Rhinitis and Sensitization #Dermatology and Skin Diseases #Ion Channels and Receptors #Urbanism, Landscape, and Tourism Studies
paper · doi:10.1111/ced.13114
openalex publication_date 2012/01/01 · openalex created_date 2016/06/24 · openalex updated_date 2026/06/23
Chronic itch has an estimated point prevalence of 8–15% in the general population. It is associated with decreased quality of life, and is a well‐known symptom of an array of skin diseases such as urticaria, atopic dermatitis and psoriasis. Aetiologically, these relatively common itch conditions all arise from diseases of the skin and are hence classified as being of dermatological origin. The management of itch in these conditions is challenging, but can, and should be, directed towards the identified underlying aetiology and neural mechanisms.1 A less common and more sparsely investigated group of chronic itch syndromes are those of neuropathic origin,2 which may share common mechanisms with chronic neuropathic pain. Such itch conditions include brachioradial pruritus, notalgia paresthetica, small‐fibre neuropathies and postherpetic itch (PHI).2 These conditions are characterized by poorly elucidated pathogeneses, under‐recognition and frequent intractability, and the evidence regarding their treatment is mostly based on case report.2 It is known that antihistamines are ineffective in the treatment of neuropathic itch (as is also the case for many other ‘nonhistaminergic’ itch conditions of dermatological origin, such as atopic dermatitis)1 and corticosteroids also lack efficacy in neuropathic itch conditions, leaving few therapeutic options.2 These remaining options include topical local anaesthetics, doxepin, intracutaneous botulinum toxin and systemic gabapentin, all of which have shown moderate promise in case studies/series, as well as topical capsaicin 8%, which has recently been approved for the treatment of peripheral nondiabetic neuropathic pain. Capsaicin 8% treatment has arguably been shown to be the most effective approach by several independent case‐series/studies.3 4 Here, we summarize the pharmacodynamics, practical application and expected outcomes from treatment with capsaicin 8% patches (Qutenza®; Grünenthal GmbH, Achen, Germany) in patients with neuropathic itch. Itch signalling is conveyed by at least two separate primary afferent nociceptive pathways; one relying on mechano‐insensitive C‐fibres and one relying on C‐mechano–heat fibres.5 Notably, both of these primary afferent fibre types are predominantly transient receptor potential vanilloid 1‐positive (TRPV1+). Pharmacodynamically, capsaicin works by causing intense depolarization of epidermal TRPV1‐expressing nociceptive/pruriceptive C‐fibres,6 again highlighting similar mechanisms between itch and pain. This results in acute burning/stinging pain and occasionally itching at the application area, as well as a prolonged dose‐dependent, reversible degeneration of terminal arborizations and defunctionalization of cutaneous TRPV1+ fibres (Fig. 1a). (a) The mechanisms involved in the prolonged antipruritic effect of topical capsaicin in high concentrations. Desensitization of transient receptor potential vanilloid (TRPV)‐expressing units is thought to mediate the short‐lasting effect. The prolonged effect is considered a consequence of vigorous influx and release of Ca2+ from the endoplasmic reticulum, which has a deleterious effect on the cytoskeletal structure of the involved terminal branches. Moreover, capsaicin in high concentrations inhibits normal mitochondrial function. ER, endoplasmic reticulum; TRPV1, transient receptor potential cation channel V1. (b) Using von Frey stimuli and visualized stimulation paths, an area of touch‐evoked itch can be readily quantified prior to capsaicin treatment. The acute pain associated with the treatment differs substantially between patients.3 4 In those patients unable to tolerate capsaicin‐induced pain, it can be successfully alleviated by pretreatment with local anaesthetic cream (e.g. EMLA®; AstraZeneca, Luton, Bedfordshire, UK) cream for 60 min under occlusion or tramadol 50 mg administered 30–45 min before capsaicin application and/or use of cooling ice packs during the treatment.3 6 Use of EMLA cream has been shown not to reduce the effectiveness of capsaicin treatment in patients with neuropathic pain.6 To apply the patch correctly, it is necessary to accurately identify the treatment area. Capsaicin‐evoked pain exhibits spatial summation, and hence treating a larger area than necessary should be avoided. As itch sensation is characterized by low spatial resolution, locating and quantifying the itching area is not always a trivial task.3 It can be particularly difficult in cases of notalgia paraesthica without hyperpigmentation, or in PHI when located on the back (Fig. 2). The area of touch‐evoked itch (alloknesis) can be quantified using a medium‐force (e.g. 1–10 g) von Frey filament or by lightly stroking the skin with a finger, following radial stimulation paths from well outside the reported area and towards the centre (see Fig. 1b) and having instructed the patient to report when the tactile stimuli elicit or increases itch sensation. After the area has been quantified, an appropriately sized capsaicin patch is cut, using between one and four pieces of 280 cm2 patch rectangles. The application itself should be performed with the operator wearing nitrile gloves, and the patch can advantageously be secured with additional medical grade tape (e.g. Tegaderm®; 3M Medical, St Louis, MO, USA). Achieving ample contact between the entire patch and the skin is recommended. The patch is applied for 60 min unless it is used on the feet, in which case it is applied for 30 min (to avoid systemic capsaicin exposure). Upon removal, an axon‐reflex erythema will be clearly visible (Fig. 2d). The supplied rinsing gel is used immediately after removal of the patch, and the entire treatment can, if necessary, be repeated after 3 months. (a–d) Treatment with capsaicin 8% patch of a patient with chronic post‐herpetic itch. (a) The area of itch is mapped; (b) the capsaicin patch is applied; (c,d) after 60 min of application the patch is removed, and a significant axon‐reflex flare extending 20–50 mm beyond the application area is visible. It is common for patients to experience slight soreness and heat hyperalgesia in the area for several hours after the treatment. With regards to antipruritic efficacy, case reports indicate that the effect starts within a few hours or days after patch removal. Often complete abolition of itch is seen for days, weeks or even months after a single treatment, followed by a slow recurrence of the itch. This recurrence usually transpires in the span of weeks or months, but several cases have been described in which the itch had not recurred 1 year after a single treatment.3 4 Recent experimental studies indicate that prolonged application (> 60 min) can vastly improve the effect of topical capsaicin 8%. In fact, a very recent experimental study showed that human skin can be rendered almost completely devoid of pruriceptive responsiveness to the two most commonly studied pruritogens (histamine and cowhage) following prolonged capsaicin 8% treatment.7 This indicates that high‐concentration capsaicin may be useful not only for the treatment of neuropathic itch, but also for more common itch conditions of dermatological origin. However, these findings remain to be confirmed in a clinical setting. In conclusion, case‐based evidence suggests that topical capsaicin 8% is a useful and feasible option for chronic neuropathic itch, and is particularly relevant for patients not responding to conventional therapy. However, future RCTs are needed to confirm the antipruritic efficacy of the treatment. HHA was supported by the EliteForsk 2016 Travel Grant of the Danish Ministry of Higher Education and Science. Conflict of interest: the authors declare that they have no conflicts of interest.