Systemic kappa opioid receptor agonists in the treatment of chronic pruritus: a literature review.

Chronic pruritus is frequently refractory to currently available treatments. Studies suggest that pruritus may arise from an imbalance of the mu- and kappa-opioid receptor system activity in either the skin or the central nervous system. Stimulation of kappa-opioid receptors by their agonists inhibits pruritus in both animals and humans. The antipruritic effect of kappa-opioid receptors agonists can currently be assumed to be related to their binding to kappa-opioid receptors on keratinocytes and cutaneous and/or central itch neurones. To date, several case reports and 2 controlled trials have demonstrated a beneficial effect of systemic kappa-opioid receptor agonists in the treatment of uraemic pruritus, prurigo nodularis, paraneoplastic and cholestatic pruritus. Nalfurafine hydrochloride (Remitch(®)), a selective kappa-opioid receptor agonist, is approved for the treatment of chronic pruritus in Japan. The aim of this review is to provide an overview of the promising role of kappa- opioid receptors and their agonist in the pathophysiology and treatment of pruritus.

Notalgia paraesthetica: a descriptive two-cohort study of 65 patients from Brazil and Germany.

Notalgia paraesthetica is a neuropathic pruritus on the back. The aim of this retrospective study was to examine patient characteristics in a consecutive cohort from Brazil and Germany. A total of 65 patients (49 women, 16 men; age range 25-80 years, mean 56.2 ± 12.7 years; median 57.0 years) were investigated in order to determine the spinal or peripheral origin of notalgia paraesthetica. Protein gene product 9.5-positive intraepidermal nerve fibers were significantly reduced in the pruritic compared with the non-lesional area (p < 0.05). In 32.3% of patients, radiological examinations showed a stenosis and in 47.7% a degeneration. A correlation between the radiological findings and the exact dermatomal localization of notalgia paraesthetica was found in 15.7% of the involved areas. The significant reduction in intraepidermal nerve fiber density suggests that damage to the peripheral nerves is a more important aetiological factor than spinal changes in notalgia paraesthetica.

Brachioradial pruritus as a result of cervical spine pathology: the results of a magnetic resonance tomography study.

BACKGROUND: Brachioradial pruritus (BRP) describes a rare form of itching occurring at the dorsolateral part of the forearms. Recent case reports suggest that BRP may be attributed to cervical lesions or spine neoplasms. OBJECTIVE: We sought to determine the incidence of cervical spine changes in BRP and to correlate the localization of spinal lesions with the dermatomal presence of pruritus. METHODS: Magnetic resonance tomography (MRT) of the cervical spinal cord, a chest x-ray, and a skin biopsy were performed in 41 patients (28 female, 13 male; 59.0 ± 10.6 years) with BRP. Patients completed an itch questionnaire (NeuroDerm Questionnaire) that included a dermatome chart and the Northwick Park Neck Pain Questionnaire. RESULTS: The patients marked the locations C5 (90.2%) and C6 (100%) on the dermatome chart. All patients had detectable MRT changes. In 80.5% of the patients, stenosis of the intervertebral foramen or protrusions of the cervical disk led to nerve compression. The location of the nerve compression lesions correlated significantly with the dermatomal localization of the pruritus (Spearman correlation coefficient 0.893; P < .01). No spinal neoplasm was observed, and 19.5% of the patients had degenerative changes without significant correlation to the dermatomal localization of pruritus. LIMITATION: No healthy control group without pruritus was investigated. CONCLUSION: BRP may result from cervical nerve compression, and rarely, it may also stem from degenerative changes. Our findings suggest that even slight cervical changes detected on MRT may alter itch afferents and lead to BRP. Spinal cord tumors are rare and should be ruled out by a cervical spine MRT.

Aquagenic pruritus: associated diseases and clinical pruritus characteristics.

BACKGROUND: Aquagenic pruritus (AP) can be induced by systemic diseases. The distribution of underlying diseases in a representative patient collective has not been investigated. This retrospective study aimed to determine the frequency and pruritus-specific parameter of systemic diseases in a series of patients. PATIENTS AND METHODS: Data of 39 patients with AP (24 f, 15 m; mean age: f: 51.3 ± 20.1, m: 57.2 ± 15.0 years) were obtained and statistically evaluated as follows: demographic data, pruritus characteristics, underlying diseases, family history. RESULTS: 30.8 % of patients exhibited polycythemia vera or myelofibrosis (Group 1: G1), in 69.2 % (G2) no underlying disease was found. 25.6 % had lactose intolerance as possible contributing factor. Women were significantly more common in G2 (p < 0.01), with a lower mean age (p < 0.01) and longer duration of AP (18.9 years, p < 0.01). CONCLUSIONS: AP occurs frequently with polycythemia vera. Other underlying diseases are rare; in over half of the patients no cause can be detected. In 25 % lactose intolerance is present which possibly acts as co-factor. Demographic parameters (age, gender) allow estimation of the possible underlying disease in AP. Pruritus characteristics are similar in all groups and not helpful in determining the origin of AP.

Antipruritic treatment with systemic µ-opioid receptor antagonists: a review.

During the past two decades, systemic µ-opioid receptor antagonists (MORA) have been used in the treatment of various forms of chronic pruritus. In a number of case reports, case series, and controlled trials, treatment with MORA has demonstrated considerable antipruritic effects. In double-blind controlled studies, significant antipruritic relief has been achieved by MORA in cholestatic pruritus, chronic urticaria, and atopic dermatitis. In case reports and case series, antipruritic efficacy of MORA has been reported in prurigo nodularis, mycosis fungoides, postburn pruritus, aquagenic pruritus, hydroxyethyl starch-induced pruritus, and pruritus of unknown origin. However, most of the evidence remains anecdotal, the design of these trials varies, and comparison of results is difficult. In this review we aim to present an overview of these reports and to assess the evidence for the antipruritic action of the drugs naloxone, nalmefene, and naltrexone, which are currently in use for the treatment of chronic pruritus of different origins. We will also evaluate recommendations for the use of MORA in daily medical practice.

Low density of sympathetic nerve fibers relative to substance P-positive nerve fibers in lesional skin of chronic pruritus and prurigo nodularis.

BACKGROUND: In prurigo nodularis (PN), an increase in the density of dermal substance P-positive (SP+) sensory nerve fibers has been demonstrated. In addition, the density of sympathetic nerve fibers is unchanged. OBJECTIVE: We aimed to investigate the density and balance of sensory and sympathetic dermal nerves in pruritus on normally appearing skin in comparison to PN. METHODS: In a parallel investigation in lesional and non-lesional skin routine histological and immunofluorescence staining against SP and tyrosine hydroxylase (TH) were performed. RESULTS: We found an increased density of dermal SP+ nerve fibers in PN and also in pruritus relative to sympathetic nerve fibers in affected areas compared to the unaffected site. The density of SP+ and TH+ nerves did not correlate with clinical parameters such as itch quality, duration or intensity. Sparse lymphocytic infiltration as found in affected pruritus skin may be a source of nerve growth factor and explain the hyperinnervation. CONCLUSION: Similar to the situation in PN, chronic pruritus lesions also demonstrate a preponderance of SP+ sensory nerve fibers relative to sympathetic nerve fibers, which probably acts as a causal pro-inflammatory signal in development of pruritus. These findings suggest new therapeutic approaches in patients with chronic pruritus.