Interleukin-31: The Inflammatory Cytokine Connecting Pruritus and Cancer.

Interleukin 31 (IL-31) is a proinflammatory cytokine, mainly secreted by Type II helper T cells. It signals through a heterodimeric receptor complex composed of IL-31 receptor α and oncostatin-M receptor ß chain. The hallmark feature of IL-31, in its pathological role, is its ability to induce pruritus in mammals. Pruritus is a common symptom and major reason of morbidity in cancer patients, compromising their quality of life. Although, IL-31 is differentially expressed in different tumor types and could promote or inhibit cancer progression, high expression of IL-31 is a contributing factor to advanced stage tumor and severity of pruritus. The simultaneous existence of pruritus and cancer could either result from the aberrations in common proteins that co-exist in both cancer and pruritus or the therapeutic treatment of cancer could indirectly induce pruritus. Although the biology of IL-31 has predominantly been described in skin diseases such as atopic dermatitis and other inflammatory diseases, the precise role of IL-31 in the tumor biology of different cancer types remains elusive. Herein, we summarize the current understanding on the role of this cytokine in the pathogenesis of different cancers.

Clinical observation of topical antipruritic spray acting on epidermal growth factor receptor tyrosine kinase inhibitor in the treatment of dermatitis.

To observe the efficacy of topical antipruritic spray (TAS) in the treatment of epidermal growth factor receptor (EGFR) tyrosine kinase-related rashes, and to evaluate its efficacy and safety. 120 malignant tumor patients with confirmed pathological diagnosis and rash after EGFR application were selected and randomly divided into an experimental group of 60 cases and a control group of 60 cases. The 2 groups were intervened with self-made antipruritic spray and erythromycin ointment for 14 consecutive days. To observe the changes in rash, itching degree, and quality of life index of skin diseases in both groups of patients before and after treatment. The decrease in the number of itching cases in the experimental group reached 53.84%, and after 7 weeks of intervention, the total effective rate of rash treatment in this group of patients (91.67%) was significantly better than that in the control group (36.67%); The symptoms of the dermatology life quality index (DLQI) scale in the experimental group patient table after intervention showed significant changes compared to before intervention. After statistical testing, there was a significant difference between the groups and outside the group (R < 0.05). And the comprehensive effect of the experimental patients with external spray after 14 weeks of intervention reached 93.16%. The self-made antipruritic spray has significant effect on improving EGFR rash and itching, and there is no obvious adverse reaction.

Adjunctive Management of Itch in Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin condition that can be difficult to treat due to a complex etiology and diverse clinical presentations. Itch is the most common symptom associated with AD with profound negative impact on quality of life. Thus, the adjunctive management of itch in patients with AD is needed to control and reduce disease burden. Supplemental treatment options are continuously emerging and undergoing testing in clinical trials. This article summarizes the latest data on topical and systemic adjunctive therapies for AD safety and efficacy in reducing itch.

Notalgia Paresthetica Dermatologist Report of Symptom Burden and Treatment: Results from a Physician Survey.

Notalgia paresthetica (NP) is a sensory neuropathy characterized by chronic pruritus, skin pain, and other pathologic sensations affecting the mid-to-upper back. NP may be under-recognized and under-diagnosed, with limited data available on its symptom presentation and treatment patterns. NP-DERM was an internet-based survey of dermatologists (n = 650) from 8 different countries on their perspectives on NP symptoms and current treatment practices. Dermatologists typically treated a median of 12 patients with NP per month. Dermatologists reported that itch (pruritus) was the most common symptom for their patients with NP, followed by hyperpigmentation and sensitive skin. The most burdensome NP symptom was pruritus, followed by burning or hot sensation, and painful or raw skin. The most prescribed treatments included non-medicated skin care, topical corticosteroids, oral antihistamines, medicated topicals, and gabapentin or pregabalin. Physicians reported low satisfaction with available treatments. The most common reason for physicians to discontinue patients' therapy was lack of response.

[A man with pruritic papules]. / Een man met jeukende bultjes.

A 24-year-old male patient was seen with generalized itch and papules located at the hands. Staining of a papule with a purple medical skin marker, followed by wiping of the ink with an alcohol-gauze revealed an ink-filled burrow. These findings are consistent with a positive burrow ink test, and a clinical diagnosis of scabies was made.

Interleukin 31 in vitiligo patients with and without pruritus.

INTRODUCTION: Vitiligo is a prevalent skin disorder characterized by the destruction of melanocytes, leading to depigmented patches across various areas of the body. Interleukin (IL)-31 has been implicated in the development of pruritus and skin inflammation, potentially contributing to cutaneous symptoms. This study measures IL-31 levels in vitiligo patients with and without pruritus, comparing them to healthy controls, and explores the relationship between IL-31 levels, disease activity, and other clinical factors to assess its potential role in the early diagnosis of vitiligo. METHODS: Ninety individuals were enrolled in the study and equally divided into three groups: vitiligo, vitiligo with pruritus, and healthy controls. The serum level of IL-31 was measured using the enzyme-linked immunosorbent assay (ELISA). RESULTS: Significant differences in IL-31 levels were observed across all groups. IL-31 levels were highest in vitiligo patients with pruritus, followed by those without pruritus, and lowest in healthy controls, with mean values and standard deviations of 196 ± 67.28, 152.10 ± 74.39, and 80.03 ± 32.30 pg/ml, respectively. In addition, IL-31 levels in serum showed significant differences in relation to disease activity in both vitiligo groups. Positive correlations were found between IL-31 levels and the Vitiligo Area Scoring Index (VASI) and Vitiligo Disease Activity (VIDA) in both patient groups, as well as between IL-31 levels and lesion extent in vitiligo patients without pruritus. In patients with pruritus, IL-31 levels also positively correlated with age and the 5-dimension itch scale score. CONCLUSION: IL-31 may serve as a crucial marker and play a significant role in the early diagnosis of vitiligo in patients both with and without pruritus.

The Effect of Placebo on Pruritus in Patients with Chronic Urticaria: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.

BACKGROUND: The anti-pruritic effect of placebo in patients with chronic urticaria has gained increasing attention in clinical research. However, the extent of placebo effect and its influencing factors in the treatment of chronic urticaria are not well understood. OBJECTIVE: The objective of this systematic review and meta-analysis was to investigate the effect of placebo on pruritus in patients with chronic urticaria and to explore relevant influencing factors. METHODS: PubMed, Embase, Web of Science, Cochrane Library, and PsycINFO were searched from inception to 10 July, 2024. Primary outcome included pruritus scores. The secondary outcomes focused on global symptoms and quality of life. Subgroup analyses and meta-regression analyses were conducted based on drug types, sample size, participants' age, and other variables. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system and a trial sequential analysis were employed to establish the reliability of evidence. RESULTS: A total of 65 eligible publications (including 67 randomized controlled trials) involving 10,704 patients with chronic urticaria were included. The pruritus scores decreased following placebo treatment (moderate evidence). In addition, favorable results were observed in global symptoms (moderate evidence) and quality of life (low evidence) after placebo treatment. Subgroup analyses indicated that the type of active medication in intervention groups was an influencing factor of placebo effect of pruritus. Meta-regression analyses demonstrated that the anti-pruritic effect of placebo was inversely correlated with sample size and positively correlated with participants' age. A trial sequential analysis provided further support for the anti-pruritic effect of placebo. CONCLUSIONS: A substantial improvement of pruritus after placebo treatment was observed in patients with chronic urticaria. The anti-pruritic effect of placebo varied with sample size, participants' age, and type of active medication used. Future research should further investigate the effect size of placebo and clarify the potential mechanism. PROSPERO REGISTRATION: The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) as CRD42023482608.

Comparison Between Pregabalin and Sertraline for Treatment of Uraemic Pruritus in Patients on Maintenance Haemodialysis: A Single-Centric Study.

OBJECTIVE: To compare oral pregabalin with oral sertraline for treatment of uraemic pruritus. STUDY DESIGN: Randomised controlled trial. Place and Duration of the Study: Department of Nephrology, Pak Emirates Military Hospital Rawalpindi, Pakistan, from October 2023 to January 2024. METHODOLOGY: Patients with end-stage renal disease having pruritus for at least 6 weeks were included. Exclusion criteria comprised other dermatological or systemic diseases associated with pruritus, mental health issues, thrice-a-week haemodialysis schedule, and use of other treatments for uraemic pruritus. They were randomised to receive either pregabalin 75mg daily or sertraline 50mg daily for six weeks using computer-generated sequences. The Urdu version of the 5-D Itch scale was used to document the severity of pruritus at the baseline and at the end of therapy. Side effects to the treatment were also monitored. RESULTS: There were 8 (16.67%) females and 40 (83.33%) males, with a mean age of 52.19 ± 12.19 years. The baseline 5-D Itch scale scores were equal in both groups. Mean improvement in 5-D Itch scale scores was 3.75 ± 1.26 and 2.08 ± 1.18 with pregabalin and sertraline, respectively (p <0.001). Side effects were reported by 2 (8.33%) patients on pregabalin and none using sertraline (p = 0.489). CONCLUSION: Pregabalin was found to be more effective than sertraline in treating uraemic pruritus, though with a statistically insignificant trend towards a higher frequency of side effects. KEY WORDS: Chronic renal failure, Pruritus, Renal dialysis, Selective serotonin reuptake inhibitors, Uraemia.

Correlation between disease severity indices and quality of life measurement tools in atopic dermatitis patients / Correlación entre los índices de gravedad de la enfermedad y las herramientas de medición de la calidad de vida en pacientes con dermatitis atópica

INTRODUCTION: Reports regarding the correlation and effect size of change of the full spectrum of quality of life and disease severity measures applied in-person to patients with atopic dermatitis are scarce. OBJECTIVES: To assess quality-of-life with 3 different instruments and to evaluate disease severity indices and to determine their correlation and effect size of change between two measurements. MATERIALS AND METHODS: Patient-level data were obtained through two in-person visits. Sociodemographic information and data related to disease distribution, severity (through the BSA, EASI, SCORAD, POEM, and itching scales), and the impact of atopic dermatitis on quality of life using the DLQI and Skindex-29, and EQ-5D, were assessed. The correlation between change in quality-of-life scores and disease severity scores in addition to the standardized effect size were also evaluated. RESULTS: Only 139 out of 212 patients completed the follow-up visit. BSA highly correlated with SCORAD and EASI, and the lowest correlation was found with POEM. The best correlation of pruritus VAS was found with sleep disturbance. The SCORAD score highly correlated with EASI, and the lowest correlation was found with POEM. The magnitude of the effect at initiation of the study vs follow-up was in average moderate to important. CONCLUSIONS: Patients with atopic dermatitis experience a substantial burden on quality of life. Disease activity correlates better with quality-of-life measurements when the disease is less severe after starting therapy. POEM and Skindex-29 seem to be optimal to determine disease severity and quality of life in adults with atopic dermatitis.

Introducción: La información publicada sobre la correlación entre la magnitud del efecto de todo el espectro de la calidad de vida y la gravedad de la enfermedad en pacientes con dermatitis atópica es escasa. Objetivos: Evaluar la calidad de vida con tres instrumentos diferentes y los índices de gravedad de la enfermedad en pacientes con dermatitis atópica para determinar su correlación y el tamaño del efecto del cambio. Materiales y métodos: Los datos de los pacientes se obtuvieron a partir de dos visitas. Se evaluó la información sociodemográfica y los datos relacionados con la distribución y la gravedad de la enfermedad (mediante de las escalas BSA, EASI, SCORAD, POEM, prurito) y el impacto de la dermatitis atópica en la calidad de vida utilizando el Dermatology Life Quality Index, Skindex-29 y EQ-5D. También se evaluó la correlación entre el cambio en las puntuaciones de calidad de vida y las de gravedad de la enfermedad, además del tamaño del efecto estandarizado. Resultados: Solo 139 de los 212 pacientes completaron la visita de seguimiento. El área de superficie corporal se correlacionó fuertemente con el SCORAD y el EASI, y la correlación más débil fue con el POEM. La mejor correlación del prurito medido con la escala visual análoga se halló con la alteración del sueño. El puntaje SCORAD se correlacionó altamente con el EASI mientras que la correlación más baja se encontró con el POEM. La magnitud del efecto al inicio del estudio respecto al seguimiento fue en promedio de moderada a importante. Conclusiones: Los pacientes con dermatitis atópica experimentan una carga sustancial en la calidad de vida. La actividad de la enfermedad se correlaciona mejor con las mediciones de calidad de vida cuando esta es menos grave, después de comenzar la terapia. Los índices POEM y Skindex-29 parecen ser óptimos para determinar la gravedad de la enfermedad y la calidad de vida en adultos con dermatitis atópica.

Association Between Pruritus and Fibromyalgia: Results of a Population-Based, Cross-Sectional Study.

Fibromyalgia is a common musculoskeletal condition that affects up to 3% of the worldwide population. Its pathogenesis is not entirely clear but is thought to involve neurogenic inflammation as well as aberrations in peripheral nerves and central pain mechanisms. It is believed that the same mechanism that causes hypersensitivity and pain in patients with fibromyalgia also predisposes them to pruritus. This population-based, retrospective, cross-sectional study was performed using a computerized database encompassing more than 4.5 million patients to examine the association between fibromyalgia and pruritus as well as pruritus-related skin conditions.

Atypical Presentation of Severe Bullous Pemphigoid: A Case Report.

Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disorder. Typically, patients will present with tense bullae and intense generalized pruritus with a skin biopsy demonstrating subepidermal split with eosinophils and a direct immunofluorescence highlighting autoantibodies against the basement membrane zone. Prognosis varies, and treatment involves an assessment of the severity of disease to determine whether to initiate topical or systemic immunosuppressive agents. We present an atypical presentation of BP that presented as a 3-to-4-week duration of pruritic small vesicular lesions in the upper chest, scabbed circular lesions along the upper extremity and pinnas of bilateral ear. Initially thought to be herpes zoster infection initially treated with valacyclovir for a week following a prior concern of a concomitant superficial skin infection with cephalexin and prednisone. With no clinical improvement, tissue biopsy was performed that confirmed bullous pemphigoid and treatment with steroid taper, doxycycline, and triamcinolone acetonide 0.1% cream was started. The aim of this case report is to present an atypical presentation of BP and to highlight maintaining a high index of suspicion of BP in patients presenting with disseminated significantly pruritic lesions.

Progressive familial intrahepatic cholestasis type 4: a case report.

BACKGROUND: Progressive familial intrahepatic cholestasis is an autosomal recessive genetic disorder that manifests primarily with jaundice and pruritus and can progresses from persistent cholestasis to cirrhosis and late childhood liver failure. Classically, progressive familial intrahepatic cholestasis is classified into three subtypes: 1, 2, and 3 and results from a defect in a biliary protein responsible for bile formation and circulation in the liver. In the last decade and with the increased use of genetic testing, more types have been known. CASE PRESENTATION: A 6-month-old Afrocentric boy presented with progressive jaundice and pruritus that started since the age of 2 months. He was thoroughly investigated to be finally diagnosed as progressive familial intrahepatic cholestasis type 4. A low-fat diet, ursodeoxycholic acid, fat-soluble vitamins, and cholestyramine were started. He showed initial improvement then had refractory pruritus and impaired quality of life. He underwent surgical biliary diversion at the age of 1 year with marked improvement of manifestations. CONCLUSION: Owing to the increased technology of genetic testing, more clinical subtypes of progressive familial intrahepatic cholestasis were diagnosed other than the classical three types. Surgical management using biliary diversion could be beneficial and delays or may even obviate the need for liver transplantation.

Disease burden and patient characteristics associated with systemic therapy utilization among adults with atopic dermatitis: data from CorEvitas Atopic Dermatitis Registry.

BACKGROUND: The decision to initiate advanced systemics in patients with atopic dermatitis (AD) is complex. OBJECTIVES: To explore disease burden and clinical characteristics of patients with moderate-to-severe AD and identify characteristics associated with initiating new systemics. METHODS: Data from prospective, longitudinal, non-interventional CorEvitas AD Registry were evaluated. Differences in demographic and clinical characteristics, comorbidities, disease severity (vIGA-AD™; body surface area (BSA); Eczema Area and Severity Index (EASI); SCORing AD [SCORAD]), and patient-reported outcomes (PROs) were assessed between systemic and non-systemic therapy groups. RESULTS: Of 883 patients, 673 were newly prescribed systemics and 210 were not. Non-systemic therapy group had higher than expected rates of severe disease at enrollment based on vIGA-AD = 4 (39%), mean BSA involvement (31%), and mean EASI (19). PROs for non-systemic therapy group indicated elevated burden from AD on quality of life and poor disease control. SCORAD, peak pruritus in the past 24 h, history of biologics, and facial pallor, were significantly associated with initiation of systemics at enrollment. CONCLUSION: While disease burden likely influences the initiation of systemic therapy, many patients with significant burden are not treated with systemics for unclear reasons. Further research is needed to identify other factors, beyond disease severity, that influence this decision.

Patient perspective on symptoms of Notalgia paresthetica: subpopulation results from the Neuropathic Itch Patient Survey (NIRVE).

Background: Notalgia paresthetica (NP) is a form of neuropathic itch characterized by recurrent itch in the mid back. Much about NP remains unclear, especially the patient experience.Objectives: The Neuropathic Itch Patient Survey (NIRVE) was a global, online survey conducted to better characterize the symptom burden of neuropathic itch from the patient perspective.Patients and methods: This report focuses on the symptom burden of the subpopulation of NIRVE participants with a self-reported diagnosis of NP (N = 91). Respondents reported visiting a median of 2 healthcare providers (HCPs) for their symptoms before receiving an accurate diagnosis of NP.Results: The most common cutaneous symptoms ever experienced were itch/pruritus, sensitive skin, painful or raw skin, numbness, and tingling. The symptoms reported by the most respondents as currently being experienced included itch/pruritus, numbness, painful or raw skin, tingling, and burning or hot sensation. Of patients currently experiencing symptoms, numbness and itch/pruritus were ranked as the most intense, followed by tingling, burning or hot sensation, and then painful or raw skin. Most patients consult multiple healthcare providers (HCPs) before receiving a diagnosis for their condition.Conclusion: Itch is overwhelmingly the most prevalent symptom of the condition, although half of patients also report experiencing sensitive skin, painful or raw skin, numbness, or tingling.

Exploring odevixibat's efficacy in alagille syndrome: insights from recent clinical trials and IBAT inhibitor experiences.

INTRODUCTION: Alagille syndrome (ALGS) is a rare, genetic, multisystem disorder commonly associated with cholestatic liver disease; patients with ALGS may experience elevated serum bile acids and severe pruritus with associated impaired sleep. The ileal bile acid transporter (IBAT) is located on the luminal surface of enterocytes in the terminal ileum; this transport protein mediates resorption of conjugated bile acids for recirculation back to the liver. Inhibition of IBAT disrupts the enterohepatic circulation and leads to fecal elimination of bile acids. AREAS COVERED: Here, the role of odevixibat as a novel, nonsurgical approach to interrupting the enterohepatic circulation from the intestine by inhibition of IBAT is reviewed, specifically in reference to currently available data on pharmacologic IBAT inhibition. IBAT inhibition has been shown to reduce serum bile acids and pruritus in trials of cholestatic liver diseases in children including ALGS. EXPERT OPINION: Odevixibat or IBAT inhibitor should be considered as a first-line treatment for ALGS to improve pruritis, quality of life and liver-related outcomes including absence of liver transplant, surgical biliary diversion, hepatic decompensation, and death.

Efficacy of Botulinum Type A Injection for the Treatment of Postherpetic Neuralgia and Pruritus Persisting for More Than Four Years-A Case Report.

Background: Postherpetic neuralgia (PHN) and postherpetic pruritus (PHP) are common complications of shingles that affect patients' quality of life. PHN and PHP can be managed using various medications and interventional procedures; however, complications persisting for at least six months may hamper recovery. Subcutaneous injections of botulinum toxin type A (BTX-A) can control persistent PHN and PHP. Case presentation: A 71-year-old man presented at our hospital with itching and pain. He had been diagnosed with shingles in the ophthalmic branch of the trigeminal nerve one year previously. As the pain and itching persisted despite medication, a supraorbital nerve block, Gasserian ganglion block, epidural nerve block, and radiofrequency thermocoagulation were performed. A subcutaneous injection of BTX-A was administered into the ophthalmic area of the trigeminal nerve three years after the initial presentation. A decrease of >80% in pain and itching was reported after the injection; however, the left eyelid drooped and the eyeball shifted downward and outward immediately after the injection. No deterioration in vision or pupil dilation was observed, and almost complete resolution of these symptoms occurred spontaneously three months after the injection. Pain and itching continued to improve without further side-effects until six months after the injection. Conclusions: The subcutaneous injection of BTX-A may be an alternative treatment option for chronic and refractory neurological diseases such as PHN and PHP, which persist for four years and are resistant to conventional treatments. Nevertheless, care must be taken to minimize the risk of ptosis.

Evaluating the safety and efficacy of seladelpar for adults with primary biliary cholangitis.

INTRODUCTION: Seladelpar (MBX-8025) is a once-daily administered highly specific PPAR-δ agonist in Phase 3 and extension trials for use in patients with primary biliary cholangitis (PBC). AREAS COVERED: This review provides background on current treatment options for PBC, and summarizes clinical trial data regarding the safety and effectiveness of seladelpar within the context of these treatments. EXPERT OPINION: Clinical trials results demonstrate the safety and tolerability of seladelpar use for PBC, including in patients with cirrhosis. The primary composite endpoint (ALP <1.67 times ULN, decrease ≥ 15% from baseline, and TB ≤ULN) was met in 61.7% of the patients treated with seladelpar and in 20% receiving placebo (p < 0.001). Moreover, pruritus - a cardinal and often intractable symptom of PBC - was improved with seladelpar treatment, as were overall quality of life measurements. Improvements in markers of inflammation were likewise observed. These biochemical and clinical findings therefore represent landmark developments in PBC treatment and offer a therapeutic option for PBC.