Postherpetic neuralgia is defined as pain persisting more than 90 days following the occurrence of herpes zoster infection. It is the most common complication of HZV infection and occurs in 10–30 % of cases. The incidence and severity of herpes zoster infection increases with age, as does the likelihood of postherpetic neuralgia. Trigeminal neuralgia refers to postherpetic neuralgiaI occurring in the distribution of one of the branches of the trigeminal nerve (Pellissier et al. 2007).

Post-herpetic neuralgia and trigeminal neuralgia are conditions characterized by both neuropathic pain and neuropathic pruritus. As such, these conditions are particularly challenging to treat. Traditional treatment regimens include early high dose antiviral medications, oral analgesics such as nonsteroidal anti-inflammatory drugs, and high dose anti-epileptics, particularly gabapentin. Additionally, oral corticosteroids are often given to decrease inflammation-related pain. Topical analgesics, specifically lidocaine and capsaicin have also shown efficacy in pain and itch amelioration (Watson et al. 1993).

A 6-week randomized, double-blinded, vehicle-controlled study with 2-year open label follow-up demonstrated some amount of pain relief in 64 % of patients with postherpetic neuralgia treated with 0.075 % capsaicin cream compared to only 25 % of patients on placebo. A more recent Phase III trial of topical synthetic capsaicin (8 % transcapsaicin patch) documented a 30 % decrease in pain scores after 2–12 weeks when compared with placebo after 1 h exposure (Backonja et al. 2008). Although effect on pruritus was not mentioned, it may be speculated that itch was relieved to a similar extent.

The 8 % transdermal patch formulation is relatively new with limited data; however, this higher concentration preparation shows promise as a useful adjuvant therapy for the persistent pain of postherpetic neuralgia, particularly with repeat applications over the course of 2 years (Backonja et al. 2008).

Notalgia paresthetica is a common condition, presenting most frequently in middle-aged or older adults as focal pruritus typically located unilaterally on the mid or upper back. Usually, no primary lesion can be identified on examination, but often there is evidence of chronic rubbing or scratching seen as hyperpigmentation or mild lichenification in the area where the patient experiences the itch. Rare cases may have a bilateral and symmetric presentation. More extensive secondary changes may result from chronic scratching.

The pathogenesis of notalgia paresthetica is related to entrapment of the posterior rami of spinal nerves originating at T2–T6. Patients may have a history of back injury or complain of back and/or neck pain. Additionally, there is often evidence of spinal column degeneration or other vertebral pathology on imaging. Although pruritus may improve in many of these patients with surgical correction of their vertebral disease, a less invasive method for treating itch is preferred for patients who do not otherwise require surgery. Systemic therapy with gabapentin has shown some benefit, but topical therapy may be satisfactory in some cases without the side effects associated with gabapentin. Topical therapies include local anesthetics, corticosteroids, and capsaicin.

Both topical capsaicin cream (0.025 %) and the 8 % capsaicin patch have been shown to be efficacious in this condition. In a double-blind, vehicle-controlled crossover study with topical capsaicin, 20 patients with notalgia paresthetica were randomized to capsaicin 0.025 % cream or vehicle control group with crossover after 4 weeks of treatment and a 2 week washout period. Overall, 70 % of patients experienced improvement in their symptoms with capsaicin therapy while 30 % of patients had improvement with vehicle. While most patients experienced some relapse after 1 month of no treatment, repeat use of topical capsaicin cream 0.025 % again resulted in remission of their pruritus (Wallengren and Klinker 1995).

Additionally, a report of two cases of notalgia paresthetica treated with a 8 % capsaicin patch resulted in complete remission of itch in both patients immediately following removal of the patch. The patient who was able to tolerate the complete goal duration of therapy (60 min) remained symptom-free at 12 weeks. The other patient was able to tolerate the patch for only 20 min and experienced recurrence of pruritus after few days. While the authors admit that data for use of the capsaicin patch for neuropathic itch is currently limited, their experience does show efficacy of this formulation in the treatment of notalgia paresthetica with ease and convenience of application as a benefit over the cream (Metz et al. 2011).

Patients with brachioradial pruritus present with unilateral or bilateral pruritus of the distal, and less commonly, proximal arms. The pruritus is often felt to be worse during the summer months or after prolonged sun exposure and is most common in middle-aged or older patients with fair skin. As with notalgia paresthetica, there is no identifiable primary lesion, though secondary changes associated with chronic scratching and rubbing may be present.

The etiology of brachioradial pruritus is not completely understood. Because it apparently worsens with sun exposure in many patients, one theory suggests that brachioradial pruritus is a result of sun damage to peripheral nerve fibers in the sun-exposed skin of the arm. One study demonstrated a decrease of sensory nerve fibers in the distal arms of patients with brachioradial pruritus at the end of the summer season compared to number of nerve fibers during a symptom-free period (Wallengren and Sundler 2005). A second theory proposes that cervical spine disease causing entrapment of cervical nerve rami results in neuropathic itch in the distal arm distribution, analogous to the theoretical cause of notalgia paresthetica. Indeed, many patients complain of neck pain and have evidence of spinal column disease in the C5–C6 distribution on imaging. Current thinking is that cervical vertebral disease may predispose patients to brachioradial pruritus while ultraviolet light is an eliciting factor (Wallengren and Sundler 2005).

As with notalgia paresthetica, surgical treatment of cervical vertebral disease may result in amelioration of pruritus in some patients with brachioradial pruritus. Gabapentin has also been used with some success in treatment of this condition. Unfortunately, brachioradial pruritus is often resistant to topical or oral corticosteroids and antihistamines.

Topical capsaicin has been used successfully in some cases. Two studies done in tropical latitudes demonstrated 12 of 15 (80 %) patients experienced improvement of symptoms when treated with topical capsaicin (Knight and Hayashi 1994; Goodless and Eaglstein 1993). In another study carried out in a temperate climate, all patients experienced relief of itch during the treatment period but found that capsaicin 0.025 % cream was no better than vehicle. The authors postulate that one reason for this outcome is the difficulty in distinguishing laterality in pruritus. They also considered the possibility of spontaneous improvement as the weather changed to cooler temperatures (Wallengren and Sundler 2005). Regardless; capsaicin remains a safe alternative for treatment of brachioradial pruritus.

Lichen simplex chronicus (LSC) and prurigo nodularis are dermatologic conditions that present in patients who chronically scratch or rub their skin due to intractable pruritus from a variety of primary sources. The causative source may be a dermatologic condition such as atopic dermatitis, scabies, or pemphigoid, or it may be related to pruritus associated with systemic illness or malignancy. Lichen simplex chronicus and prurigo nodularis are not uncommon findings in patients with diabetes mellitus, obstructive biliary disease, chronic kidney disease, liver failure, endocrine dysfunction, or malignancies such as leukemia and lymphoma. Additionally, pruritus and secondary changes of lichen simplex chronicus and prurigo nodularis can be seen in patients with severe emotional stress or anxiety.

Lichen simplex chronicus presents as thickened, erythematous or hyperpigmented scaly plaques that may also show evidence of excoriation. Distribution is variable, and depends on the underlying source of pruritus. Regardless of the source, the lesions are usually located on easy-to-reach skin; that is, areas that the patient has access to rub or scratch repeatedly.

Prurigo nodularis is a similar condition in that it results from chronic mechanical irritation of the skin, however, it presents as discrete nodules of lichenification and excoriation rather than confluent plaques.

Treatment of both of these conditions is difficult. The pruritus is often intractable and the mechanical irritation caused by scratching or rubbing worsens the lichenification and inflammation, and subsequently, the pruritus. While treatment of the underlying condition can help significantly, often, that condition is not curable and therefore the pruritus persists. Therapeutic regimens aimed at easing the itch include topical medications such as emollients containing menthol and topical corticosteroids. These treatments are often insufficient on their own because as the stratum corneum thickens in these conditions, it inhibits penetration of the medication into the dermis. While intralesional steroids have been used with some success, the size of the plaque of LSC or the number of prurigo nodules may make this modality impractical. Systemic therapies that have been used with some success include antihistamines, ultraviolet light, corticosteroids, cyclosporine, thalidomide, and etretinate. Although these medications have been shown to be successful at ameliorating pruritus, each has side effects that limit the practicality of its use. Capsaicin is a reasonable alternative as it lacks systemic side effects and penetration through a thickened stratum corneum can be enhanced through occlusion.

To evaluate the efficacy of topical capsaicin in the treatment of prurigo nodularis, Stander et al. measured both the clinical and histologic features pre- and posttreatment in 33 patients. Each patient applied capsaicin to the lesional areas 4–6 times daily, starting with a concentration of 0.025 % and increasing as needed, to achieve complete cessation of pruritus. The highest concentration required was 0.3 % by a single patient. Treatment duration was also variable, lasting from 2 weeks to 33 months in one patient with poor compliance. However, all participants achieved complete remission within 12 days and 24 patients experienced flattening of lesions within 2 months. Although there was recurrence of pruritus once the capsaicin application was stopped in about half of the study patients, the majority experienced 2 weeks to 2 months of treatment-free remission. Patients also experienced relief when the medication was reinitiated following cessation and recurrence. The histologic changes accompanying the clinical changes showed thinning of the stratum corneum and epidermis, and decreased inflammation and scarring. Ultrastructurally, decreased reactivity to substance P was noted following treatment with capsaicin. The authors conclude that capsaicin is effective for symptomatic relief as well as clinical resolution of the nodules. They recommend regular application of topical capsaicin 4–6 times daily at a concentration that achieves complete cessation of pruritus with reapplication upon recurrence (Stander et al. 2001).

Pruritus of the anogenital skin and mucosa may be idiopathic or secondary to an underlying disorder. It presents as intractable itching in the perianal or genital area, often with secondary lichenification. In order to diagnose primary or idiopathic pruritus ani, vulvae, or scroti, possible secondary causes should be ruled out. Potential causes of secondary anogenital pruritus include irritant or allergic contact dermatitis, primary cutaneous conditions (psoriasis, atopic dermatitis, seborrheic dermatitis, lichen planus, lichen sclerosus), malignancy (anogenital carcinoma, paget’s disease), infection (pinworms, sexually transmitted diseases), hemorrhoids, rectal fistulas, or sinus tracts. In the absence of an underlying condition, idiopathic anogenital pruritus has been attributed to dietary causes such as excessive caffeine intake, personal hygiene, or psychogenic factors (Bolognia and Jorizzo 2012).