Aetiology, pathogenesis and management of neuropathic itch: A narrative review with recent updates.

Neuropathic itch is a relatively common yet under-reported cause of systemic pruritus. It is a debilitating condition often associated with pain, which impairs the patient's quality of life. Although much literature exists about renal and hepatic pruritus, there is a dearth of information and awareness about neuropathic itch. The pathogenesis of neuropathic itch is complex and can result from an insult at any point along the itch pathway, ranging from the peripheral receptors and nerves until the brain. There are several causes of neuropathic itch, many of which do not produce any skin lesions and are thus, often missed. A detailed history and clinical examination are necessary for the diagnosis, while laboratory and radiologic investigations may be needed in select cases. Several therapeutic strategies currently exist involving both non-pharmacological and pharmacological measures, the latter including topical, systemic, and invasive options. Further research is ongoing to clarify its pathogenesis and to design newer targeted therapies with minimal adverse effects. This narrative review highlights the current understanding of this condition, focusing on its causes, pathogenesis, diagnosis, and management, along with newer investigational drugs.

Pseudoxanthomatous or xanthelasmoid mastocytosis: Reporting a rare entity.

Mastocytosis is a disease characterized by abnormal and pathologic increase in mast cells in the cutaneous tissue and extracutaneous organs such as the bone marrow, liver, spleen, lymph node and gastrointestinal tract. Cutaneous mastocytosis comprises of four major clinical variants: solitary and multiple mastocytomas, urticaria pigmentosa, diffuse cutaneous mastocytosis and telangiectasia macularis eruptiva perstans. Cutaneous mastocytosis of the xanthelasmoid type is a rare variant of diffuse mastocytosis. It is clinically characterized by the typical yellowish hue and is accompanied histologically by mast cells infiltrating far into the lower dermis. Here we report one such rare case.

A retrospective study of the utility of targeted phototherapy in vitiligo.

BACKGROUND: Targeted phototherapy is a recent advance in the treatment of vitiligo, involving selective treatment of vitiligo patches with no effect on surrounding areas. Although it has been in use for a few years, little data is available regarding its safety and efficacy. AIMS: A retrospective study to determine efficacy and safety of targeted phototherapy in vitiligo. METHODS: One hundred and thirty four patients (male: 53, female: 81) who received targeted phototherapy and completed 11 or more sittings were included. Treatment was given once a week using the Lumera phototherapy system, a broadband ultraviolet B source, starting at 150 mJ/spot and after excluding a sunburn reaction, with increments of 50 mJ every week up to a maximum of 1000 mJ/patch. Chi-square test for linear trends was used for statistical analysis. RESULTS: The most common sites involved were the legs and a majority (70.9%) had non-segmental vitiligo. Response was mild in 78 (58.2%) patients, moderate in 50 (37.3%) and excellent in 6 (4.5%) patients. Response was directly proportional to the number of sittings with more patients showing moderate and excellent responses with an increase in the number of sittings. The most common site for an excellent response was the trunk while the lower limbs were involved in most cases with a moderate or mild response. Side effects were seen in 27 (20.2%) patients, the commonest being erythema. LIMITATIONS: This is a retrospective uncontrolled study. Further, the effects of adjuvant treatment were not assessed. CONCLUSIONS: Targeted phototherapy is a useful treatment for vitiligo with mild adverse effects, though response is mild or moderate and appears to be directly proportional to the number of treatments received.

Understanding itch: an update on mediators and mechanisms of pruritus.

Pruritus is the most common symptom secondary to skin diseases. Advances in the fields of neurobiology, immunology and physiology have made it possible for us to understand and unravel the deeper pathophysiological basis of pruritus. This review aims to update our current understanding of the mechanisms and mediators of pruritus. Special attention is paid to endogenous itch mediators particularly newly identified ones like endovanilloids, opioids, neurotrophins, cannabinoids, proteases and cytokines. Various theories explaining the peripheral encoding of itch are reviewed. Multiple neural pathways including the central itch pathways as well as supraspinal processing of itch and brain areas involved in pruritus are highlighted. Apart from peripheral itch mediators, spinal neural receptors are also involved in control of itch and should form part of the development of a novel antipruritic strategy. Further studies are required to fill the lacunae in our current understanding of the pathophysiology of pruritus.

The efficacy of azithromycin in pityriasis rosea: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Macrolides are prescribed in the treatment of pityriasis rosea despite conflicting results of the limited number of studies evaluating their role in its treatment. AIM: A randomized double-blind placebo-controlled trial was conducted to evaluate the effect of azithromycin on the clinical course of pityriasis rosea. METHODS: Seventy patients of pityriasis rosea were given either azithromycin (n=35) or placebo (n=35) and were followed-up at 2, 4 and 6 weeks. Pruritus was assessed in both groups using the visual analogue scale (VAS) . Change in the pityriasis rosea severity score (PRSS) and in the VAS were recorded as outcome measures and were compared statistically. RESULTS: The decrease in PRSS from baseline through 2, 4 and 6 weeks within both treatment (P<0.001) and placebo (P<0.001) arms was found to be statistically significant; however, this change was not significantly different in the two groups (P=0.179). Similarly, the decrease in VAS was found to be statistically significant within both groups (P<0.001); however, the change was comparable between the two groups (P<0.937). Analysis by Fisher's exact test did not find a significant difference between the two groups for PRSS and VAS. CONCLUSION: Azithromycin is not effective in pityriasis rosea and the use of macrolides for this disease should not be encouraged in clinical practice.

Pruritic porokeratotic peno-scrotal plaques: porokeratosis or porokeratotic epidermal reaction pattern? A report of 10 cases.

BACKGROUND: Porokeratosis restricted to the genital region is rare with few cases described in the literature. Cases of porokeratosis restricted to the genital region are similar to plaque type of porokeratosis of Mibelli seen elsewhere on the body. We encountered 10 young males with pruritic plaques restricted to the peno-scrotal region, which clinically were not diagnosed as porokeratosis, but on biopsy revealed multiple cornoid lamellae, some of which were seen to arise from eccrine and follicular structures. AIMS: The aim of this study is to study lesions restricted to the peno-scrotal region in males, which on biopsy showed cornoid lamellae suggestive of porokeratosis. METHODS: Retrospective analysis of available data of patients who were rendered a histological diagnosis of genital porokeratosis. The database consisted of biopsies received in private consultation by the first author in the period January 2000 to March 2013. RESULTS: Ten young men, 8 in their third decade, presented with pruritic plaques restricted to the peno-scrotal region of variable duration. The lesions were well-demarcated on the penis, but ill-defined with a rough granular surface on the scrotum. None of patients were diagnosed clinically as porokeratosis. The lesions were poorly responsive to topical steroid/antifungal treatment, but two patients showed partial improvement with oral isotretinoin. Biopsy in nine patients revealed multiple cornoid lamellae involving epidermis (6) and adnexal structures (3). One patient had a single cornoid lamella. CONCLUSION: The clinical and histological presentation of these patients is different from typical genital porokeratosis described in the literature and we postulate that these patients have an unusual porokeratotic reaction pattern of the epidermis with multiple cornoid lamellae.

Gaining a comprehensive understanding of pruritus.

Pruritus is a common symptom associated with many dermatoses, systemic abnormalities, and psychiatric / psychosomatic diseases. Additionally, pruritus is one of the most intractable symptoms due to its complex pathogenesis involving an increasing number of mediators and receptors, undefined neurophysiologic pathways, unclear cerebral processing, and psychophysiology interaction. Clinically, the first challenge of dermatologists is how to get general and interdisciplinary vision of pruritus and to preliminarily figure it out whether there might be underlying systemic or psychosocial disorders. The second challenge is to select efficient individual tailored anti-pruritic treatment, which includes targeted drugs and cognitive-behavioral therapy.

Lichen simplex chronicus of anogenital region: a clinico-etiological study.

BACKGROUND: Lichen simplex chronicus (LSC) of the anogenital region, is a benign, extremely uncomfortable disease. AIMS: As very little is known about the cause of anogenital LSC (AGLSC), we undertook this study to determine various clinico-etiological factors involved in it and to assess the frequency of AGLSC. METHODS: This was a descriptive study, including 105 patients with AGLSC, who attended the Dermatology clinic in our institute from September 2007 to June 2009. Detailed history, physical examination, and relevant investigations were done. The collected data were tabulated and analyzed. RESULTS: The frequency of AGLSC among patients presenting with anogenital pruritus was 2.54%. Primary AGLSC was more common than secondary AGLSC (69.5% vs. 30.5%). AGLSC manifested more commonly in males than in females (56.2% vs. 43.8%). The mean duration of the disease was 30.6 months. The common triggering factors for itching were sweating (41.9%), rubbing of thighs while walking for long distances (9.5%), and mental stress (5.7%). Pruritus of AGLSC was related to the intake of various food items in 37.1% of patients. In males, scrotum was the predominant site involved (89.8%), whereas in females, labia majora was the predominant site involved (78.2%). Nearly one-third of cases (30.5%) of AGLSC had some other dermatoses in the anogenital region. CONCLUSIONS: Though psychological factors are thought to play an important role in disease causation and perpetuation among AGLSC patients, their significance could not be ascertained by us.

Effect of oral granisetron in uremic pruritus.

BACKGROUND: Renal itch is a relatively common and distressing problem for patients with chronic renal failure. Granisetron, is a potent and selective inhibitor of 5-HT3 receptors. There have been some studies about the effect of ondansetron in uremic pruritus and one case report has recently described relief of renal itch with granisetron. AIMS: To evaluate the effect of Granisetron on uremic pruritus in Continuous Ambulatory Peritoneal Dialysis (CAPD) and Hemodialysis (HD) patients. METHODS: To study the prevalence of uremic pruritus, patients on CAPD and HD were asked to complete a pruritus questionnaire. Their replies were scored based on numerical scales. Pruritus was graded, according to the total points for each patient, as mild, moderate or severe. Fourteen patients with moderate to severe pruritus were enrolled in the trial. During treatment, patients received granisetron (1 mg tablet twice a day P.O), for a period of 1 month. They were asked to score the severity of pruritus twice a day. RESULTS: Seventy seven percent of the patients responded to the treatment and at 1 st, 2 nd and 4 th week the mean values of the pruritus scores were 23, 16 and 8 points respectively. Before starting treatment the score was 31 points (P =0.03). Weekly clinical and laboratory examination showed no important side effects. CONCLUSION: Granisetron might be an effective, safe and well tolerated drug for the treatment of uremic pruritus.

The efficacy and safety of bile Acid binding agents, opioid antagonists, or rifampin in the treatment of cholestasis-associated pruritus.

OBJECTIVES: The objective of this review was to evaluate the efficacy and safety of rifampin, opioid antagonists, or bile acid binding agents in the treatment of cholestasis-related pruritus (CAP) from available randomized controlled trial evidence. METHODS: In addition to a comprehensive gray literature search, the Cochrane Library, MEDLINE, EMBASE, PubMed, and Web of Science were searched. Only full-text RCTs in participants (>75% adult) with CAP on at least one of the three medications were included. The primary outcome was change in pruritus score, recorded as a continuous or dichotomous outcome. Two independent reviewers performed trial selection and quality assessment. RESULTS: From 487 citations, 12 RCTs were included. Rifampin (standardized mean difference [SMD]-1.62, 95% CI -3.05 to -0.18) and opioid antagonists (SMD -0.68, 95% CI -1.19 to -0.17) significantly reduced CAP. The two cholestyramine studies were too heterogeneous to pool. Although cholestyramine (P= 0.35) and rifampin (P= 0.96) were not associated with greater side effects compared with placebo, opioid antagonists were (number needed to harm = 2.6, 95% CI 1.4-25). CONCLUSIONS: The available RCTs are small, few in number, and use varying scales for measuring pruritus. Although both opioid antagonists and rifampin demonstrated a reduction in pruritus, there were insufficient data to judge the efficacy of cholestyramine. Opioid antagonists were associated with transient side effects in a significant proportion of patients. A longer well-designed randomized controlled trial is needed to confirm the efficacy of bile acid binding agents and accurately assess adverse events.