Pruritus: Therapies for localized pruritus

INTRODUCTION — Pruritus is a common symptom that may be localized (affecting limited areas of skin) or generalized and occurs in a wide variety of clinical settings, such as dermatologic, systemic, neuropathic, or psychiatric disease. In addition to physical effects (eg, skin injury, secondary infections, scarring, and sleep deprivation), pruritus can contribute to emotional disturbances, such as agitation and depression [1]. In severe cases, pruritus can be incapacitating.

The inciting factor for localized pruritus and the severity of symptoms influence the approach to treatment. Examples of causes of localized pruritus include inflammatory, dermatologic disorders; burns; scars; and forms of neuropathic itch. (See "Pruritus: Etiology and patient evaluation", section on 'Potential causes'.)

While amelioration of pruritus is sometimes easily attained, treatment is challenging in some patients. A wide variety of therapies have been used for pruritus; however, efficacy data are limited for many treatment options (table 1A-B).

The treatment of localized pruritus will be discussed here. The management of generalized pruritus and the diagnostic evaluation of pruritus are reviewed separately.

●(See "Pruritus: Therapies for generalized pruritus".)

●(See "Pruritus: Etiology and patient evaluation".)

In-depth discussions of some presentations of localized pruritus are provided separately.

●(See "Treatment of atopic dermatitis (eczema)".)

●(See "Approach to the patient with anal pruritus".)

●(See "Management of burn wound pain and itching".)

GENERAL APPROACH — The inciting factor for pruritus and extent of pruritus influence the approach to treatment. (See "Pruritus: Etiology and patient evaluation", section on 'Potential causes' and 'Specific forms of localized pruritus' below.)

In general, management consists of:

●Treatment of the underlying cause (when feasible)

●Elimination of aggravating factors

●Pharmacologic, antipruritic therapies to reduce symptoms

Treatment of underlying cause — Successful treatment of the underlying cause of pruritus may result in resolution of symptoms [2]. Therefore, identification and treatment of the underlying cause is advised, whenever feasible. (See "Pruritus: Etiology and patient evaluation", section on 'Potential causes'.)

Elimination of aggravating factors — Elimination of aggravating factors, such as dry skin, heat exposure, skin irritants, and stress, may improve pruritus. Measures to reduce exposure to these factors are reviewed separately. (See "Pruritus: Therapies for generalized pruritus", section on 'Elimination of aggravating factors'.)

Selection of pharmacologic therapy — The cause of pruritus influences the approach to pharmacologic therapy. Topical therapies are the mainstays of treatment for localized forms of pruritus and are commonly used for initial therapy (table 1A). Options for topical therapy include cooling agents (eg, calamine, menthol, camphor), topical anesthetics (eg, pramoxine, lidocaine, compounded ketamine, amitriptyline, lidocaine), topical antihistamines (eg, diphenhydramine, doxepin), topical anti-inflammatory therapies (eg, corticosteroids, calcineurin inhibitors, crisaborole), and topical capsaicin.

Cooling agents and topical anesthetics (particularly pramoxine and lidocaine) are common first-line topical therapies, as they are widely available, generally well tolerated, and helpful for various forms of pruritus. (See 'Cooling lotions' below and 'Topical anesthetics' below.)

Approaches that may be helpful for specific presentations include:

●Inflammatory skin disorders – Topical anti-inflammatory therapies, with selection of the anti-inflammatory therapy based upon the underlying cause (see 'Topical anti-inflammatory agents' below)

●Neuropathic itch – Topical anesthetics, topical capsaicin (see 'Topical anesthetics' below and 'Topical capsaicin' below)

●Histamine-mediated itch (eg, insect bites) – Topical antihistamines (see 'Topical antihistamines' below)

Systemic therapies are generally incorporated when topical therapy is insufficient or impractical (table 1B). Oral sedating antihistamines are common initial therapies for pruritus that interferes with sleep. Gabapentin and pregabalin are common initial systemic therapies for neuropathic itch. Other systemic therapies used for generalized pruritus may also be beneficial for refractory, localized pruritus. The risks and benefits of such interventions should be weighed carefully. Systemic therapies for pruritus are reviewed in detail separately. (See "Pruritus: Therapies for generalized pruritus", section on 'Role of antihistamines' and 'Peripheral neuropathic itch' below and "Pruritus: Therapies for generalized pruritus".)

ANTIPRURITIC THERAPIES

Topical therapies — Topical antipruritic therapies include cooling lotions, topical anesthetics, topical antihistamines, topical capsaicin, and topical anti-inflammatory agents.

Cooling lotions — Topical agents that provide a cooling sensation on the skin, such as calamine lotion or lotions containing camphor and menthol, may provide temporary relief from pruritus:

●Indications – Cooling lotions may be helpful for various forms of localized pruritus and may be particularly helpful for patients who report cooling as an alleviating factor. However, there is also a subset of patients who report that cooling exacerbates itch [3].

●Rationale for use – Cooling sensation has an itch-relieving effect. Menthol activates the transient receptor potential TRPM8, also known as the cold receptor, contributing to antipruritic effects [4]. The mechanism of action of calamine lotion is unknown. Camphor is a mild analgesic.

●Administration:

•Calamine lotion – Calamine lotion is shaken well immediately prior to use and applied to the affected areas as often as needed. Application of products containing both calamine lotion and pramoxine, a topical anesthetic, should be limited to three to four times per day. (See "Calamine lotion: Drug information" and 'Topical anesthetics' below.)

•Camphor and menthol – Products containing camphor and menthol are available in a variety of forms. Lotion formulations are often used for pruritus. For individuals at least two years of age, camphor and menthol lotion can be applied three to four times daily, as needed.

Skin irritation is a potential adverse effect, and burning sensations may occur when applied to sites with skin excoriations or other superficial wounds. Camphor toxicity in children has been reported. (See "Camphor poisoning in children".)

Topical anesthetics — Examples of topical anesthetics used for pruritus include pramoxine; lidocaine; eutectic mixture of lidocaine and prilocaine (EMLA); polidocanol; and compounded ketamine, amitriptyline, and lidocaine (table 1A). Topical polidocanol is commercially available in Europe, Asia, and Australia but not in the United States:

●Indications – Topical anesthetics may be helpful for various forms of localized pruritus and are considered particularly helpful for managing neuropathic itch.

●Rationale for use – Topical anesthetics exhibit antipruritic effects. Pramoxine 1% cream, eutectic mixture of lidocaine 2.5% and prilocaine 2.5% cream (EMLA), and an ethyl chloride spray have demonstrated antipruritic effects in experimental settings [5-7].

Clinical studies have also supported the utility of topical anesthetics for pruritus. A four-week, randomized trial in 28 patients with uremic pruritus found that the percent reduction in itch intensity was greater after application of pramoxine 1% lotion twice daily to areas of pruritus than after application of a control lotion (61 versus 12 percent reduction) [8]. In addition, eutectic mixture of lidocaine 2.5% and prilocaine 2.5% (EMLA) was effective for postburn pruritus in a pilot study of five children [9], and topical lidocaine in an acid mantle cream reduced pruritus in an uncontrolled study of 50 patients [10].

Polidocanol is a nonionic surfactant primarily used for sclerotherapy that possesses both local, anaesthetic properties and moisturizing effects. An open-label study of 1611 patients with eczematous dermatitis or psoriasis found that a preparation with polidocanol and topical urea appeared to improve pruritus [11].

Patients with neuropathic itch have benefited from treatment with topical anesthetics [12,13]. In a retrospective study with 96 patients with various types of chronic itch (including 28 patients with neuropathic itch), use of compounded ketamine-amitriptyline-lidocaine was associated with improvement in symptoms [13]. (See 'Peripheral neuropathic itch' below.)

●Administration – Pramoxine 1%, a topical anesthetic commonly used for pruritus, is available in a variety of vehicles, including lotions, gels, foams, and creams. Pramoxine is applied up to three to four times daily.

Instructions for topical lidocaine vary based upon the specific product, with application generally limited to a maximum of two to four times daily. One reported regimen consists of use of compounded 5 or 10% ketamine, 5% amitriptyline, and 5% lidocaine on limited body areas (<30 percent total body surface area [TBSA]) up to three times daily [13].

Toxicity due to systemic absorption may occur with improper use of topical anesthetics. Methemoglobinemia is a potential consequence of EMLA use in young children. Systemic administration of ketamine has been associated with multiple side effects. (See "Clinical use of topical anesthetics in children", section on 'Lidocaine-prilocaine' and "Ketamine poisoning".)

Topical antihistamines — Examples of topical antihistamines used for pruritus include doxepin and diphenhydramine:

●Indications – Based upon mechanism of action, topical antihistamines are considered most appropriate for use in histamine-mediated pruritus, such as pruritus related to mosquito bites. However, topical antihistamines may also improve pruritus in other dermatologic disorders.

Use of topical doxepin is not recommended in children.

●Rationale for use – Several randomized trials support the use of topical doxepin for pruritus in the setting of skin disease, such as atopic dermatitis [14]. Data are insufficient to confirm efficacy of other topical antihistamines, including topical diphenhydramine [14].

●Administration – Doxepin 5% cream is applied four times per day for adults; applications should be separated by at least three to four hours. Potential adverse effects of topical doxepin include drowsiness, contact dermatitis, anticholinergic effects, and stinging or burning at the site of application. Application over more than 10 percent of the body surface area (BSA) may increase risk for systemic adverse effects. (See "Doxepin (topical): Drug information".)

Diphenhydramine 1% or 2% cream is applied to the affected area up to three to four times per day. Potential side effects include photosensitivity, rash, and urticaria. (See "Diphenhydramine (topical): Drug information".)

Topical anti-inflammatory agents — Topical anti-inflammatory therapies that may be helpful for pruritus include topical corticosteroids, topical calcineurin inhibitors, and topical crisaborole (a phosphodiesterase 4 [PDE4] inhibitor):

●Indications – Pruritus secondary to inflammatory, dermatologic disorders, such as atopic dermatitis, contact dermatitis, and psoriasis, can improve with topical anti-inflammatory therapies. Topical anti-inflammatory therapies are not indicated for pruritus that is not associated with cutaneous inflammation.

●Rationale for use – Suppression of cutaneous inflammation often results in relief of the associated pruritus.

In addition to the suppression of cutaneous inflammation, phosphorylation of transient release potential vanilloid 1 (TRPV1) has been proposed as a mechanism through which topical calcineurin inhibitors reduce pruritus [15].

PDE4 is present in a variety of inflammatory cells, including mast cells, eosinophils, neutrophils, and macrophages. Crisaborole has demonstrated anti-inflammatory and antipruritic effects for mild to moderate atopic dermatitis [16].

●Administration – Topical anti-inflammatory agents are applied directly to the skin, usually once or twice daily:

•Topical corticosteroids – Topical corticosteroids are generally applied once or twice daily. An alternative approach for thick plaques or nodular lesions is intralesional injection of corticosteroids. (See "Intralesional corticosteroid injection".)

Wet wraps applied with topical corticosteroids may be helpful for patients with significant pruritus due to a corticosteroid-responsive dermatosis, such as atopic dermatitis or other inflammatory dermatoses. Wet wraps involve the application of emollients or low- to medium-potency topical corticosteroids under moist dressings [17,18]. (See "Treatment of atopic dermatitis (eczema)".)

Potential adverse effects of topical corticosteroids include cutaneous atrophy and suppression of the hypothalamic-pituitary axis. The side effects of topical corticosteroids are reviewed in greater detail elsewhere. (See "Topical corticosteroids: Use and adverse effects", section on 'Adverse effects'.)

•Topical calcineurin inhibitors – Commercially available topical calcineurin inhibitors include tacrolimus 0.03% and 0.1% ointments and pimecrolimus 1% cream. These drugs are generally applied twice daily.

Adverse effects of topical calcineurin inhibitors include a burning sensation after application, which may be a result of initial release of substance P, as has been described with capsaicin [15]. Although concern has been raised over the possibility of an increased risk for malignancy with the use of these agents, a definitive causal relationship has not been established. (See "Treatment of atopic dermatitis (eczema)".)

•Crisaborole – Crisaborole 2% ointment is applied twice daily for the treatment of atopic dermatitis. Burning or stinging at the site of application is a potential adverse effect. (See "Treatment of atopic dermatitis (eczema)".)

Topical capsaicin — Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is a substance derived from chili peppers that has been used for the treatment of chronic pain and pruritus [19]:

●Indications – Neuropathic disorders, such as notalgia paresthetica, brachioradial pruritus, and postherpetic neuralgic itch, appear to be particularly responsive to this therapy. Prurigo nodularis, aquagenic pruritus, and pruritus associated with chronic renal disease are examples of other disorders that have been successfully treated with capsaicin [19-22]. (See 'Peripheral neuropathic itch' below.)

●Rationale for use – The mechanism of action for capsaicin involves its ability to activate TRPV1, an ion channel in cutaneous nerve fibers [23,24]. Activation of TRPV1 stimulates neurons to release and eventually deplete certain neuropeptides, including substance P. Capsaicin also induces lasting desensitization of neurons to a variety of stimuli. In sum, these effects lead to the inhibition of neuronal transmission of pain and pruritus.

Although a systematic review of randomized trials found insufficient evidence for definitive conclusions on the efficacy of capsaicin for pruritus [25], multiple studies have documented the efficacy of this agent [26-30].

●Administration – Capsaicin can be applied to the affected area three or four times daily. The main adverse effect of capsaicin is an initial burning sensation that can last for several days and lessens compliance. During the first two weeks of treatment, patients can apply a topical anaesthetic, such as EMLA or a lidocaine 5% patch, 30 to 60 minutes before application of capsaicin to reduce discomfort [19,31].

Systemic therapies — Systemic therapies for pruritus, including oral antihistamines, antidepressants, anticonvulsants, opioid receptor antagonists, opioid receptor agonists, and other agents, are reviewed separately. (See 'Selection of pharmacologic therapy' above and "Pruritus: Therapies for generalized pruritus", section on 'Antipruritic therapies'.)

SPECIFIC FORMS OF LOCALIZED PRURITUS — Approaches to the treatment of pruritus secondary to inflammatory skin disorders, lichen simplex chronicus, burns, and various forms of peripheral neuropathic itch are reviewed here. (See 'Inflammatory skin disorders' below and 'Lichen simplex chronicus' below and 'Burns' below and 'Peripheral neuropathic itch' below.)

Inflammatory skin disorders — Pruritus associated with inflammatory skin disorders often improves with successful treatment of the underlying disorder. Examples of common inflammatory skin disorders with localized involvement include:

●Atopic dermatitis (see "Treatment of atopic dermatitis (eczema)")

●Contact dermatitis (see "Management of allergic contact dermatitis in adults" and "Allergic contact dermatitis in children" and "Irritant contact dermatitis in adults")

●Asteatotic, dyshidrotic, and nummular eczema (see "Overview of dermatitis (eczematous dermatoses)")

●Eyelid dermatitis (see "Eyelid dermatitis (eczema)")

●Psoriasis (see "Treatment of psoriasis in adults" and "Psoriasis in children: Management of chronic plaque psoriasis")

Lichen simplex chronicus — Lichen simplex chronicus is a secondary skin disorder that results from excessive scratching. Lichenified plaques and excoriations are typically present.

The treatment of lichen simplex chronicus centers on the discontinuation of the itch-scratch cycle. Commonly used therapies include topical corticosteroids under occlusion and intralesional corticosteroids.

Burns — Pruritus is a common symptom of burns. The approach to treatment of burn-related pruritus is reviewed separately. (See "Management of burn wound pain and itching" and "Treatment of minor thermal burns".)

Peripheral neuropathic itch — A variety of treatments have been used for brachioradial pruritus, notalgia paresthetica, and postherpetic itch. Data on the treatment of these disorders are limited.

Brachioradial pruritus — Although there is some evidence that various topical and systemic antipruritic therapies can be useful for the treatment of brachioradial pruritus, further study is necessary to clarify efficacy.

Our typical approach consists of using oral anticonvulsants (gabapentin or pregabalin) combined with a topical anesthetic, typically compounded ketamine, lidocaine, and amitriptyline. In our experience, topical therapy alone is often insufficient for the intense pruritus of brachioradial pruritus. Topical capsaicin is another commonly used treatment. Topical 1% menthol may also offer some relief [32]. (See 'Topical anesthetics' above and "Pruritus: Therapies for generalized pruritus", section on 'Anticonvulsants'.)

Topical capsaicin 0.025% cream was associated with symptom improvement in 13 out of 15 patients in an open-label study [26] and in four out of seven patients in a small case series [27]. A small, open-label study of five patients suggested sustained benefit following a single application of a capsaicin 8% patch [33]. In contrast, a randomized trial of 13 patients with methodologic flaws showed no benefit of capsaicin 0.025% cream over a placebo cream [34].

Benefit of compounded amitriptyline and ketamine (with or without lidocaine) [13,35], gabapentin [36-40], pregabalin [41,42], antidepressants [43], ketoprofen [44], and lamotrigine [45] is documented in case reports or case series.

Surgical intervention is an option for patients with severe, intractable symptoms who fail to improve with other therapies. Patients who have undergone surgical intervention for treatment of cervical tumor or disc herniation have reported relief of pruritus [32,46].

Cervical spine manipulation appeared beneficial in 10 out of 14 patients in one retrospective study [47].

Notalgia paresthetica — The best approach to the treatment of notalgia paresthetica is unclear. Topical antipruritic agents, such as pramoxine, capsaicin, or compounded topical ketamine, lidocaine, and amitriptyline, are our mainstays of treatment [28,29,48]. We proceed to oral anticonvulsants (gabapentin or pregabalin) or injection of botulinum toxin type A when topical therapy is insufficient [49].

In a randomized, cross-over trial of 20 patients, more patients improved with topical capsaicin therapy than with vehicle (70 versus 30 percent) [28]. However, symptoms returned after the cessation of therapy. Case reports or case series describe benefit of the topical anesthetic eutectic mixture of lidocaine and prilocaine (EMLA) [12], oral gabapentin [50], and oxcarbazepine [51].

Botulinum toxin A and a paravertebral nerve block have also been reported as effective in case reports [52,53]. However, a placebo-controlled, randomized trial of 20 patients with notalgia paresthetica did not find a beneficial effect of botulinum toxin A treatment [54].

Other therapies may be useful. In an observational study, transcutaneous electrical nerve stimulation led to a significant decrease in the pruritus score among 15 patients [55]. Additionally, in a case series, four out of six patients with notalgia paresthetica and abnormalities on spinal radiograph (dorsal arthrosis or spinal static disequilibrium) improved with physiotherapy [56].

Postherpetic itch — Herpes zoster may result in severe, prolonged pruritus that persists after resolution of the acute disease. The best approach to the treatment of postherpetic itch has not been established. Symptoms may or may not respond to treatments for postherpetic neuralgia. (See "Postherpetic neuralgia".)

Topical anesthetics are often used for treatment [41]. The efficacy of other agents used for neuropathic pruritus, such as topical capsaicin, gabapentin, pregabalin, and tricyclic antidepressants, are unknown. Antihistamines and topical corticosteroids are generally considered ineffective. (See 'Topical anesthetics' above.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pruritus".)

SUMMARY AND RECOMMENDATIONS

●Overview – Pruritus is a common symptom that can be incapacitating in severe cases. A wide variety of therapies have been utilized for management (table 1A-B); however, data are limited on the efficacy of most treatments. (See 'General approach' above.)

●General approach – The inciting factor for pruritus and extent of pruritus influence the approach to treatment. (See 'General approach' above.)

Key components of therapy include:

•Treatment of the underlying cause

•Elimination of aggravating factors

•Antipruritic therapies

●Localized pruritus, initial treatment – For patients with localized forms of pruritus, topical therapy rather than systemic therapy is often used for first-line treatment. Treatment options include cooling lotions, topical anesthetics, topical antihistamines, topical anti-inflammatory agents (eg, corticosteroids, calcineurin inhibitors, crisaborole), and topical capsaicin. (See 'Selection of pharmacologic therapy' above and 'Topical therapies' above.)

Topical corticosteroids and topical calcineurin inhibitors improve pruritus through the suppression of cutaneous inflammation in dermatologic disorders, such as atopic dermatitis or psoriasis. We suggest against using these topical anti-inflammatory agents for the treatment of pruritus unassociated with cutaneous inflammation (Grade 2C). (See 'Topical anti-inflammatory agents' above.)

●Localized pruritus, refractory – Patients with localized pruritus that does not improve with treatment of the underlying disorder, elimination of aggravating factors, and topical therapy may benefit from systemic treatment. The risks and benefits of proceeding to systemic therapy should be weighed carefully. Oral sedating antihistamines are often used for initial treatment. (See 'Selection of pharmacologic therapy' above.)

●Brachioradial pruritus – The best approach to the treatment of brachioradial pruritus is unclear. For the initial treatment of most patients with brachioradial pruritus, we suggest an oral anticonvulsant (gabapentin or pregabalin) and topical anesthetic rather than topical therapy alone (Grade 2C). In our experience, topical therapy alone is often insufficient. Topical capsaicin is an additional treatment option. (See 'Brachioradial pruritus' above.)

●Notalgia paresthetica – The best approach to the treatment of notalgia paresthetica is unclear. For most patients, we suggest topical capsaicin or topical anesthetics rather than systemic antipruritic therapies for initial treatment (Grade 2C). Gabapentin, pregabalin, or botulinum toxin injections are options for patients who do not improve with topical therapy. (See 'Notalgia paresthetica' above.)