Chronic pruritus, traditionally defined as itch persisting for >6 weeks, is a common affliction that can be associated with cutaneous or systemic disease, or may be idiopathic in nature. It affects patients of all ages and backgrounds and seems to have no predilection for sex or socioeconomic status1. The lifetime prevalence has been estimated between 22% and 26%1. It accounts for millions of outpatient clinic encounters every year2. Pruritus is associated with significant morbidity ranging from sleep disturbance to suicidal ideation in both pediatric and adult patients3.
The pathophysiology of pruritus is complex and multifactorial. An intricate and incompletely understood interplay between cytokines, sensory neurons, and a variety of cutaneous and central nervous system receptors and effector cells are responsible for the development of itch. Scores of therapies exist, with enormous variation in efficacy, for the amelioration of itch. Drugs aimed at virtually all of the aforementioned pathogenic factors in pruritus have been trialed or are being developed.
Nonpharmacologic therapies for chronic pruritus encompass a variety of methods for altering itch signaling or for changing the patient’s perception of pruritus. Although some of these interventions may be used as monotherapy, they are usually best utilized in combination with more conventional pharmacologic antipruritic therapies. This review evaluates the current understanding of the mechanisms and efficacy of these nonpharmacologic interventions and serves to expand the dermatologist’s armamentarium against chronic pruritus.
Light has been used for millennia in the treatment of skin disease. Ultraviolet light attenuates cutaneous inflammation and its use is commonplace in the treatment of skin disorders. However, there is some evidence to suggest that outside of the dermatology community, there is less experience with the utilization of phototherapy4. The mechanism by which phototherapy works remains obscure. UVB radiation, given its limited penetrance into the skin, appears to primarily modify inflammation via epidermal keratinocytes and Langerhans cells. Its antipruritic effects are due, in part, to alteration of mast cell membrane phospholipid metabolism which attenuates histamine release5. UVA light affects a wider host of inflammatory cells including T lymphocytes, mast cells, and dermal dendritic cells6. UVA is typically administered along with psoralen, a photosensitizing agent, and in this setting it carries a higher risk for carcinogenesis than narrowband UVB therapy. Long-term UVA phototherapy with psoralen is associated with development of melanoma and squamous cell carcinoma7. Although UVB radiation is generally considered carcinogenic8, long-term narrowband UVB therapy likely confers little risk for skin cancer9.
A European study in 2016 compared the efficacy of combination UVA (320–410 nm, peak 351 nm) and narrowband UVB (nbUVB) therapy with nbUVB monotherapy for chronic pruritus associated with eczematous dermatitis, psoriasis, prurigo, and pruritus sine materia. Enrolled patients were treated 3 times weekly for 16 weeks. Forty-five patients completed the study. All subjects reported statistically significant improvement in pruritus, quality of life measures improved for all enrolled, and there was no significant difference between the monotherapy and combination therapy groups10.
There are dozens of trials from the past century recommending the use of various phototherapies for inflammatory, pruritic skin disease. However, relatively few original studies have been published in the past decade. In general, the efficacy, tolerability, and safety profile of phototherapy is favorable. The commonest diseases associated with chronic pruritus that respond to phototherapy include psoriasis, atopic dermatitis (AD), mycosis fungoides, prurigo nodularis, uremic pruritus, lichen planus, and cutaneous mastocystosis11.
Although less expensive than some pharmacologic therapies, office-based phototherapy can be costly. A 2006 cost-effectiveness study for psoriasis estimated in-office phototherapy to cost between $4500 and $5700 per year (inflation-adjusted)12. Home nbUVB therapy is more cost-effective, associated with better adherence, and has comparable efficacy13. When these options are not practical, some patients may benefit from treatment at tanning salons or heliotherapy. This option necessitates a conversation with the patient about skin cancer risks. Despite the obstacles, phototherapy remains an important nonpharmacological option for many patients.
Nerve stimulation therapy
Transcutaneous electrical nerve stimulation (TENS) is a modality that utilizes electric current, applied with cutaneous patches, to treat a variety of disorders. It has been leveraged for the treatment of pain for decades14, but attention has turned to its use as an antipruritic therapy in recent years. The mechanism by which this intervention attenuates itch and pain is, in large part, due to inhibition of C fiber-mediated neurotransmission, a phenomenon known as “gating”15. Interestingly, TENS also attenuates expression of proinflammatory cytokines in wound healing16, suggesting its antipruritic effect may have a more involved mechanism than originally thought15.
Mohammad Ali and colleagues investigated the efficacy of TENS for chronic pruritus associated with AD, Lichen Simplex Chronicus (LSC), and hepatic pruritus. Patients were treated 3 times weekly for a maximum of 12 sessions. TENS electrodes were applied to patients’ pruritic lesions for 30 minutes per session. Patients reported statistically significant improvement in pruritus at 2 weeks and 4 weeks. AD and LSC patients experienced more marked improvement of pruritus compared with the hepatic pruritus group. The antipruritic effect was persistent 1 month after completion of the study for the AD and LSC group, but not for the hepatic group. Tolerability was excellent and side effects were minimal17.
TENS has been used to effectively treat pruritus associated with mixed-thickness flame burns in one patient18. Patients with eczematous dermatoses and 1 patient with scrotal neuropathic pruritus of years-long duration reported “good” itch improvement after using TENS19.
TENS devices are available for purchase without prescription and can cost less than a topical steroid in some cases. Nerve stimulation should not be done near the eyes or on the anterior neck, which can trigger a vasovagal response. Patients who are pregnant, have a seizure disorder, and those with pacemakers should not use TENS, but there are few contraindications to its use otherwise. Nerve stimulation represents an infrequently utilized, inexpensive intervention that may be useful particularly for patients with chronic pruritus limited to discrete skin lesions rather than those with diffuse itch.
Meditation can significantly decrease perception of pain in the presence of noxious stimuli. Activation of the primary somatosensory cortex, responsible for perception of both pain and pruritus, is reduced in the presence of noxious stimuli in meditating patients in magnetic resonance imaging studies20.
Chen and Jhaveri enrolled 10 adults with chronic pruritus in an 8 week meditation course to evaluate the effect of this modality on self-assessment of pruritus severity. Subjects who completed the course reported improvement in pruritus, quality of life, sleep quality, and ability to cope with stress21. These preliminary results indicate that meditation can be an effective adjunctive pruritus therapy, but interpretation of these positive results is limited by small study size.
Acupuncture has been used for millennia to treat a wide range of conditions and is a cornerstone of traditional Chinese medicine. The mechanisms by which acupuncture is thought to work within traditional Chinese medicine are perhaps more philosophical than evidence-based, but there are scientific interpretations for some of the findings22. Rigorous blinded clinical trials for acupuncture are inherently difficult to design. Many purported benefits of acupuncture therapy are indistinguishable from placebo effects, and studies touting therapeutic benefits of acupuncture are prone to bias in reporting23. Although the sea of literature supporting acupuncture for various diseases is mixed, there is some evidence that it may be beneficial for pruritus.
A 2005 investigation of acupuncture for uremic pruritus showed marked reductions in itch scores. Patients receiving thrice-weekly acupuncture for 1 month experienced an ~45% reduction in pruritus compared with placebo, which was maintained 3 months after treatment24. Lee et al25 similarly found acupressure to be efficacious in relieving AD-associated pruritus in a small pilot study of 15 patients. Both studies targeted the “Large Intestine 11” acupuncture point which is located adjacent to the lateral epicondyle of the humerus. There are other limited reports of acupuncture for the treatment of uremic pruritus26 and AD27,28, but interpretation of these results is limited by small study size, experiment design, and/or small clinical effect compared to placebo.
The mechanism behind the apparent antipruritic effect of acupuncture remains unclear. Pfab et al28 treated patients with AD with twice-weekly acupuncture treatments lasting twenty minutes each. They suggested that decreased basophil activation, which was observed in the treatment group, may help explain why acupuncture apparently quells itch. This effect was reported to be statistically significant, but P-values were not provided in the publication. Further, the control group did not receive any placebo or “sham acupuncture,” which may muddy the results of this study.
Murine studies suggest that acupuncture may affect transient receptor potential pathways29 or κ-opioid receptor activation30, but these studies likewise suffer from flaws in design. Alternatively, acupuncture may directly alter activation of C fibers which are responsible for transmission of pruritus31. While this ancient treatment approach continues to be utilized, much remains to be elucidated in terms of its modern use.
Psychotherapy represents a vast and varied field that can be leveraged to alter the perception of itch or behaviors associated with it. Further, these methods may decrease anxiety or sleep disturbances associated with chronic pruritus. As with many nonpharmacologic interventions for itch, the bulk of the psychotherapy literature focuses on AD-associated itch, but these methods can probably be effectively deployed for other chronic pruritic conditions.
Cognitive-behavior therapy (CBT), applied to chronic pruritus, guides patients to change “dysfunctional” thoughts or actions in order to improve their ability to cope with itch and to reduce frequency of scratching32. Ehlers et al33 conducted randomized trials to assess various methods of psychotherapy on the severity of symptoms, including itch, in AD. Patients were enrolled in 12 weekly group sessions and received either dermatologic educational sessions, CBT, relaxation therapy, or a combination thereof. All arms showed significant improvement in patient-reported measures of pruritus severity and frequency of scratching. The group receiving CBT along with dermatologic education showed a statistically significant reduction in topical steroid use compared with those receiving dermatologic education only.
Similarly positive results have been achieved with CBT in case reports of pediatric patients with severe AD34,35. CBT may be useful in breaking the “itch-scratch” cycle associated with prurigo nodularis36. However, its utility in psoriasis may be limited. In a randomized controlled trial of internet-based CBT for psoriasis, there was no significant improvement in pruritus37.
Habit reversal training is a variant of CBT originally developed to treat tic disorders but may also be useful in chronic pruritic skin disorders. Although quality studies are lacking, habit reversal training may be useful in treating itch associated with AD, prurigo nodularis, or other pruritic conditions38,39.
In children with AD, support groups improve quality of life measures and decrease patient-rated itch severity. Weber et al40 enrolled both patients and their parents in support groups that met every 2 weeks for 6 months. Children in the intervention group reported pruritus once or twice weekly, versus the control group which reported daily pruritus at the conclusion of the study.
Hypnosis is a form of psychotherapy that induces a “trance state” by use of deep breathing, meditation techniques, or guided imagery41. Hypnotizability is highly variable among patients which makes critical analysis of this modality somewhat challenging. Further, the quality of hypnotherapy studies is varied42. There is some evidence to support hypnosis for disorders of pain, sleep, and anxiety43,44. However, few rigorous studies of hypnosis for pruritus exist. Positive results have been reported with hypnotherapy combined with other well-established forms of psychotherapy such as biofeedback, relaxation therapy, or stress management for AD45 and chronic urticaria46.
Cryotherapy for the treatment of pruritus leverages cutaneous physiological changes that occur at cold temperatures to reduce the neurotransmission of itch. This probably occurs as conduction along cutaneous C fiber and Aδ nerves is altered at low temperatures47. Cryotherapy has not been studied extensively for pruritic skin disorders. As cryochambers are not widely accessible and liquid nitrogen cryotherapy is associated with skin atrophy and dyschromia, cryotherapy has not gained much traction as a treatment for chronic pruritus.
To date, there has been only 1 study to investigate the effects of whole-body cryochamber therapy for pruritus. A Finnish study47 enrolled patients with AD into a thrice-weekly whole-body cryotherapy regimen. Patients underwent 1 month of treatment which involved spending 1–3 minutes in a series of 3 increasingly cold chambers, the last of which reached −110°C. A modest decrease in VAS-rated pruritus from 46 to 31 was achieved, though there was no comparison placebo. Three patients reported mild acral frostbite during the study.
Cryotherapy for small plaque psoriasis may improve disease severity but is associated with hypopigmentation and atrophy48. Waldinger and colleagues used liquid nitrogen cryotherapy to treat a patient with severe prurigo nodularis. Treatment resulted in remarkable improvement of skin lesions and pruritus which was maintained for three months49. Positive results have also been reported in chronic pruritus ani. Liquid nitrogen, applied in 2–3 second bursts to the anus, ameliorated itch but was associated with intraprocedural pain and drainage at the treated area lasting several days50.
Clothing may play a role in relieving or exacerbating chronic pruritic skin disease51. In the past decade, several new textiles, treated or created with bioactive materials, have been developed to treat AD in particular. Clothing with anti-inflammatory or anti-pruritic properties could eventually become an important tool in treating itch, especially if there is enhanced adherence compared with application of topicals multiple times daily. Although these garments have been studied primarily in the context of AD, they may have a role in treating other nonatopic pruritic conditions.
Silk has been the subject of many studies for treatment of AD. In a 2016 randomized clinical trial of 282 pediatric patients, Thomas and colleagues sought to determine if silk clothing improves outcomes in AD. This study found no significant improvement in measures of AD severity, nor any improvement in pruritus as measured by POEM scores51.
However, silk garments impregnated with anti-inflammatory or anti-microbial agents appear to significantly ameliorate AD symptoms. A double-blinded 2013 Italian study comparing DermaSilk (clothing treated with a proprietary agent called AEGIS) with cotton clothing showed statistically significant reduction in both pruritus and volume of topical corticosteroid used in infants aged 4–18 months. Other DermaSilk studies have demonstrated improvement in AD-associated pruritus, achieving improvement similar to that seen with topical corticosteroid use52.
Combination seaweed-silver treated garments have emerged as a therapeutic textile for AD. The purported mechanism involves a combination of the anti-staphylococcal and anti-candidal activity of silver combined with barrier-restorative properties in seaweed53. A 2011 Korean pilot study reported significant improvement in pruritus as measured by SCORAD, but did not publish detailed measurements of pruritus54. A similar study by Araújo et al55 showed impressive reductions in pruritus severity and SCORAD, but results did not reach statistical significance as the placebo was unexpectedly efficacious.
New medical textiles are emerging at a rapid pace as these studies have been largely positive in AD. Clothing treated with zinc-oxide showed modest improvement in AD-related pruritus, but the pilot study did not include a placebo arm56. A novel textile containing tourmaline, which emits infrared radiation and is anion-producing, achieved statistically significant reduction in pruritus compared with cotton clothing in patients with AD57. Textiles coated with a chitosan biopolymer afforded improvement in overall severity of AD, but no significant improvement in pruritus specifically58. Textiles are perhaps an under-recognized treatment option for chronic pruritus. Further studies are warranted in this burgeoning field.
These nonpharmacologic therapies are a diverse group of treatments that are generally well-tolerated and deserve further investigation. They range from commonplace light therapy to radiation-emitting textiles that act synergistically with conventional medications to ameliorate chronic pruritus. These therapies may, in some cases, serve to decrease reliance on systemic agents and thus mitigate adverse effects associated with them. Although many of these modalities have been studied in the framework of chronic pruritus associated with AD, their antipruritic effects likely extend to other conditions of itch.
Conflict of interest disclosures
The authors declare that they have no financial conflict of interest with regard to the content of this report.
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