Clinical Evaluation of the Efficacy of Itch-Relief Moisturizers Containing Maltotetraose for Dry, Itchy, and Sensitive Skin.

Itching is a prominent clinical manifestation of sensitive skin; it reduces cutaneous barrier function, mainly caused by dryness. Scratching to relieve itching destroys the skin barrier, thus forming the itch-scratch cycle that results in additional disruption of skin barrier and chronic itching. Treatment involves alleviation from itching for sensitive skin. Recently, substance P (11-amino acid neuropeptide of the tachykinin family) and neurokinin 1 receptor (NK1R) have been considered to provide a key pathway to treat chronic itching. A single-center, open-label study was conducted comprising subjects with dry, itchy, and sensitive skin to evaluate the efficacy of two types of itch-relief moisturizers, mist and lotion, containing maltotetraose (MTO). In all, 35 subjects used mist containing MTO, resulting in significant improvement in itch score from 1 minute to 2 hours following single application. On the other hand, 34 subjects applied lotion containing MTO for 1 week, resulting in significant improvement in itch score, skin hydration, and clinical scores of erythema/redness and dryness; however, in both cases, improve-ment was not observed in the measurement of transepidermal water loss (TEWL). It was concluded that two types of itch-relief moisturizers containing MTO were effective for dry, itchy, and sensitive skin.

The efficacy and safety of difelikefalin for pruritus in hemodialysis patients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Chronic kidney disease-associated pruritus (CKD-ap) is a common complication that negatively affects the quality of life. Difelikefalin has emerged as a novel FDA-approved drug to manage CKD-ap. This systematic review and meta-analysis will assess the efficacy and safety of Difelikefalin versus placebo to manage CKD-ap. METHODS: PubMed, Scopus, WOS, Central, and Embase were systematically searched until November 2023. RevMan was used to perform meta-analysis. Quality assessment was conducted using the Cochrane RoB 2.0 tool. Results were reported as risk ratio (RR) and mean difference (MD) with a 95% confidence interval (CI). PROSPERO ID: (CRD42023485979). RESULTS: Five RCTs with a total of 896 participants were included. Difelikefalin significantly decreased the weekly mean WI-NRS score (MD: -0.99 [-1.22, -0.75], p ˂ .00001), 5-D itch scale total score (MD: -1.51 [-2.26, -0.76], p > .0001), and Skindex-10 total score (MD: -7.39 [-12.51, -2.28], p = .005), but showed significantly higher adverse events (RR: 1.26 [1.03, 1.55], p = .03), versus placebo. However, there was no significant difference between both groups in serious adverse events (RR: 1.42 [0.78, 2.57], p = .25) or death (RR: 0.81 [0.19, 3.34], p = .77). CONCLUSION: Difelikefalin appears to be a promising agent for the management of CKD-induced pruritus in patients with end-stage renal disease. However, evidence is still underpowered due to the paucity of the current data; therefore, more robust RCTs are required to confirm the benefit of Difelikefalin.

Mucocutaneous Manifestations in Patients with Dengue Fever: From the EPIDENGUE Cohort on Reunion Island.

Nearly 4 billion people live in a dengue risk area worldwide. The prevalence of dengue-related mucocutaneous manifestations and their association with severe dengue differ across studies. The aim of the study was to describe the characteristics of patients with dengue-related mucocutaneous manifestations and to investigate those were associated with severe dengue. A retrospective study was conducted in 2019 among patients with a positive RT-PCR for dengue at the University Hospital of Reunion, which has been experiencing a re-emergence of dengue since 2018. Of 847 patients with confirmed dengue, 283 (33.4%) developed mucocutaneous manifestations. Only manifestations of dehydration such as glossitis, dysgeusia, or conjunctivitis were associated with severe dengue, unlike pruritus and rash, in bivariate analysis but not in multivariate analysis. The rash and pruritus of dengue appear to be accompanied by a pronounced flu-like syndrome in younger people without comorbidity or severity, although careful examination of mucous membranes would better identify signs of dehydration and thus cases likely to worsen.

The Severity, Quality of Life, and Correlated Factors of Chronic Kidney Disease-associated Pruritus between Hemodialysis and Kidney Transplant Patients: A Cross-sectional Study.

BACKGROUND: Chronic kidney disease-associated pruritus (CKD-aP) mainly occurs in hemodialysis (HD) patients and could persist in kidney transplant (KT) recipients. This study aims to compare the severity, correlation of various biochemical factors, and quality of life (QoL) concerning pruritus in CKD. METHODS: A cross-sectional study was conducted on HD and KT recipients with chronic pruritus, where the 5-Dimensional (5-D) Itch Scale and Dermatology Life Quality Index (DLQI) were used to evaluate pruritus severity and QoL. Results: Among the 60 subjects, 76.7% of HD patients had moderate-to-severe pruritus, whereas in the KT group, 83.3% experienced mild pruritus (p < 0.001). The median DLQI score was 5 (3-6) and 3 (2-4), respectively (p < 0.001). There was a correlation between hs-CRP and the 5-D itch score in the HD group (r = 0.443; p < 0.05), whereas e-GFR was correlated with the 5-D itch score in the KT group (r = -0.424; p < 0.05). CONCLUSION: Moderate-to-severe pruritus was more common in HD patients. While pruritus in KT recipients had a mild effect on QoL, pruritus in the HD group had a mild-moderate impact on QoL. There was a correlation between hs-CRP and e-GFR and the severity of pruritus in HD and KT recipients, respectively.

Treatment of patients with evidence of mast cell-mediated itch in the absence of hives with omalizumab.

PURPOSE: The presence of wheals or hives has been viewed as a hallmark symptom of urticaria, a highly debilitating disease. This study explores our experience with omalizumab in patients with apparent mast-cell mediated pruritus in the absence of hives. MATERIALS AND METHODS: This is a retrospective case series examining all patients with mast cell-mediated pruritus in the absence of hives from April 2022 to May 2024 at a tertiary referral clinic at Icahn School of Medicine at Mount Sinai in New York. Peak pruritus-numerical rating scale (PP-NRS) itch score changes over time were recorded and analyzed. RESULTS: Six patients (67% women; mean [SD] age, 47.67 [13.52] years) were included in the analysis. The median [IQR] pruritus PP-NRS itch score before omalizumab injection was 9 [6 - 10] and the final median [IQR] PP-NRS itch score was 2.5 [0 - 5]. The mean [SD] reduction in the PP-NRS itch score was 6 [3.16]. CONCLUSIONS: This study suggests that patients with evidence of mast cell-mediated pruritus can be identified based on clinical features and may benefit from omalizumab therapy.

Spinal histamine H4 receptor mediates chronic pruritus via p-ERK in acetone-ether-water (AEW)-induced dry skin mice.

Dry skin is common to many pruritic diseases and is difficult to improve with oral traditional antihistamines. Recently, increasing evidence indicated that histamine H4 receptor (H4R) plays an important role in the occurrence and development of pruritus. Extracellular signal-regulated kinase (ERK) phosphorylation activation in the spinal cord mediates histamine-induced acute and choric itch. However, whether the histamine H4 receptor regulates ERK activation in the dry skin itch remains unclear. In the study, we explore the role of the histamine H4 receptor and p-ERK in the spinal cord in a dry skin mouse model induced by acetone-ether-water (AEW). q-PCR, Western blot, pharmacology and immunofluorescence  were applied in the study. We established a dry skin itch model by repeated application of AEW on the nape of neck in mice. The AEW mice showed typically dry skin histological change and persistent spontaneous scratching behaviour. Histamine H4 receptor, instead of histamine H1 receptor, mediated spontaneous scratching behaviour in AEW mice. Moreover, c-Fos and p-ERK expression in the spinal cord neurons were increased and co-labelled with GRPR-positive neurons in AEW mice. Furthermore, H4R agonist 4-methyhistamine dihydrochloride (4-MH)induced itch. Both 4-MH-induced itch and the spontaneous itch in AEW mice were blocked by p-ERK inhibitor U0126. Finally, intrathecal H4R receptor antagonist JNJ7777120 inhibited spinal p-ERK expression in AEW mice. Our results indicated that spinal H4R mediates itch via ERK activation in the AEW-induced dry skin mice.

Neural pathways that compel us to scratch an itch.

Itch is a unique sensory experience that is responded to by scratching. How pruritogens, which are mechanical and chemical stimuli with the potential to cause itch, engage specific pathways in the peripheral and central nervous system has been a topic of intense investigation over the last few years. Studies employing recently developed molecular, physiological, and behavioral techniques have delineated the dedicated mechanisms that transmit itch information to the brain. This review outlines the genetically defined and evolutionary conserved circuits for itch ranging from the skin-innervating peripheral neurons to the cortical neurons that drive scratching. Moreover, scratch suppression of itch is attributed to the concurrent activation of pain and itch pathways. Hence, we discuss the similarities between circuits driving pain and itch.

The effect of photobiomodulation on histamine and Mucuna pruriens-induced pruritus, hyperknesis and alloknesis in healthy volunteers: A double-blind, randomized, sham-controlled study.

BACKGROUND: Photobiomodulation, also referred to as Low-Level Light Therapy (LLLT), has emerged as a promising intervention for pruritus, a prevalent and often distressing symptom. OBJECTIVES: This study investigated the efficacy of low-level light therapy (LLLT) in alleviating pruritus, hyperknesis, and alloknesis induced by histamine and Mucuna pruriens. METHODS: In a double-blind, randomized, sham-controlled trial with a split-body design, healthy volunteers underwent 6 minutes of LLLT and sham treatments in separate upper back quadrants. The histamine model was applied to the upper quadrants, and Mucuna pruriens to the lower quadrants. Pruritus intensity, alloknesis, hyperknesis, flare area, and skin temperature were measured pre and post treatment. RESULTS: Seventeen individuals (eight females, nine males) participated in the study. In the histamine model, LLLT notably reduced itch intensity (difference = 13.9 (95% CI: 10.5 - 17.4), p = 0.001), alloknesis (difference = 0.80 (95% CI: 0.58-1.02), p = 0.001), and hyperknesis (difference = 0.48 (95% CI: 0.09-0.86), p = 0.01). Skin temperature changes were not significantly different between the two groups (difference = -2.0 (95% CI: -6.7-2.6), p = 0.37). For the Mucuna pruriens model, no significant differences were observed in any measures, including itch intensity (difference = 0.8 (95% CI: -2.3 - 3.8), p = 0.61) hyperknesis (difference = 0.08 (95% CI: -0.06-0.33), p = 0.16) and alloknesis (difference = 0. 0.09 (95% CI: -0.08-0.256), p = 0.27). CONCLUSIONS: LLLT effectively reduced histamine-induced pruritus, alloknesis, and hyperknesis; however, LLLT was ineffective against Mucuna pruriens-induced pruritus. Further investigations are required to determine LLLT's effectiveness of LLLT in various pruritus models.

The involvement of keratinocytes in pruritus of chronic inflammatory dermatosis.

Frequent itching and incessant scratching are commonly observed in various chronic inflammatory skin conditions, including atopic dermatitis and psoriasis. The persistent and prolonged nature of pruritus can worsen one's quality of life. Keratinocytes (KCs), the predominant cells of the epidermis, have been confirmed to interact with sensory neurons and immune cells and be involved in chronic skin inflammatory diseases associated with pruritus. Initially, KCs and sensory neurons form a unique synapse-like connection within the epidermis, serving as the structural foundation for their interaction. Additionally, several receptors, including toll-like receptors and protease-activated receptor 2, expressed on KCs, become activated in an inflammatory milieu. On the one hand, activated KCs are sources of pro-inflammatory cytokines and neurotrophic factors, such as adenosine triphosphate, thymic stromal lymphopoietin, and nerve growth factor, which directly or indirectly participate in stimulating sensory neurons, thereby contributing to the itch sensations. On the other hand, KCs also function as primary transducers alongside intraepidermal nerve endings, directly initiating pruritic responses. This review summarizes the current literature and highlights the critical role of KCs in the development and persistence of chronic itch in inflammatory skin disorders.

LPS exacerbates TRPV4-mediated itch through the intracellular TLR4-PI3K signalling.

Pruritus is often accompanied with bacterial infections, but the underlying mechanism is not fully understood. Although previous studies revealed that lipopolysaccharides (LPS) could directly activate TRPV4 channel and TRPV4 is involved in the generation of both acute itch and chronic itch, whether and how LPS affects TRPV4-mediated itch sensation remains unclear. Here, we showed that LPS-mediated TRPV4 sensitization exacerbated GSK101-induced scratching behaviour in mice. Moreover, this effect was compromised in TLR4-knockout mice, suggesting LPS acted through a TLR4-dependent mechanism. Mechanistically, LPS enhanced GSK101-evoked calcium influx in mouse ear skin cells and HEK293T cells transfected with TRPV4. Further, LPS sensitized TRPV4 channel through the intracellular TLR4-PI3K-AKT signalling. In summary, our study found a modulatory role of LPS in TRPV4 function and highlighted the TLR4-TRPV4 interaction in itch signal amplification.

Sleep-loss related to itch in atopic dermatitis: assessing content validity and psychometric properties of a patient-reported sleep-loss rating scale.

BACKGROUND: Sleep loss is a key factor contributing to disease burden in people with atopic dermatitis (AD). Mitigating itch to improve sleep is an important outcome of AD treatment. This study explored the content validity and measurement properties of the Sleep-Loss Scale, a single-item rating scale for assessing itch interference with sleep in clinical trials of AD treatments. METHODS: Concept elicitation and cognitive debriefing interviews were conducted with 21 adults and adolescents (12-17 years of age) with moderate-to-severe AD to develop a conceptual model of patient experience in AD and explore the content validity of the scale. Data collected from adults with moderate-to-severe AD enrolled in a phase 2b study (NCT03443024) were used to assess Sleep-Loss Scale's psychometric performance, including reliability, construct validity, and ability to detect change. Meaningful within-patient change (MWPC) thresholds were also determined using anchor-based methods. RESULTS: Qualitative findings from concept elicitation highlighted the importance of sleep-loss related to itch in AD. Debriefing analysis of the Sleep-Loss Scale indicated that the scale was relevant, appropriate, and interpreted as intended. Trial data supported good reliability, construct validity and ability to detect improvement. MWPC was defined as a 1-point improvement using trial data, a finding supported by qualitative data. CONCLUSIONS: The Sleep-Loss Scale provides a valid and reliable patient-reported measure of the impact of itch on sleep in patients with AD, and can detect change, indicating it is fit-for-purpose to evaluate the efficacy of AD treatments in moderate-to-severe patients.

A case report on acquired reactive perforating collagenosis.

INTRODUCTION: Acquired reactive perforating collagenosis (ARPC) is a rare perforating skin disease with unclear pathogenesis, often leading to misdiagnosis. Utilizing noninvasive skin microscopy improves diagnostic accuracy while reducing misdiagnosis rates. PATIENT CONCERNS: Given its association with systemic diseases, comprehensive examinations are crucial for early detection of related diseases such as tumors. Clinically, it still lacks standardized guidelines for the treatment. Clinical treatment is mostly based on symptomatic treatment. Oral administration of pregabalin capsules can significantly relieve itching symptoms, and narrow-wave ultraviolet irradiation can accelerate the recovery of skin lesions. DIAGNOSIS: Dermoscopy and skin biopsy was used to confirm this case was ARPC. INTERVENTIONS: Treatment was based on oral administration of 20 mg prednisone, 1 tablet of loratadine, 1 tablet of pregabalin in the morning and evening, and external application of halomethasone ointment. OUTCOMES: Itching symptoms were significantly relieved. CONCLUSION: This case report demonstrates that clinical dermoscopy can improve the diagnosis rate of ARPC, and pregabalin capsules can significantly relieve itching symptoms.

Itch and Pain Behaviors in Irritant Contact Dermatitis Produced by Sodium Lauryl Sulfate in Mice.

Irritant contact dermatitis (ICD) is a nonspecific skin inflammation caused by irritants, leading to itch and pain. We tested whether differential responses to histamine-dependent and -independent pruritogens can be evoked in ICD induced by sodium lauryl sulfate (SLS). An ICD mouse model was established with 5% SLS in acetone versus a vehicle topically applied for 24 h to the cheek. Site-directed itch- and pain-like behaviors, occurring spontaneously and in response to mechanical, thermal, and chemical stimuli (histamine, ß-alanine, BAM8-22, and bradykinin) applied to the cheek, were recorded before (day 0) and after irritant removal (days 1, 2, 3, and 4). Skin inflammation was assessed through visual scoring, ultrasound, and measurements of skin thickness. SLS-treated mice exhibited hyperalgesia-like behavior in response to mechanical and heat stimuli on day 1 compared to the controls. SLS mice exhibited more spontaneous wipes (pain) but not scratching bouts (itch) on day 1. Pruritogen injections caused more scratching but not wiping in SLS-treated mice compared to the controls. Only bradykinin increased wiping behavior compared to saline. SLS-treated mice developed noticeable erythema, scaling, and increased skin thickness on days 1 and 2. SLS induced cutaneous inflammation and behavioral signs of spontaneous pain and itching, hyperalgesia to mechanical and heat stimuli and a chemical algogen, and enhanced itch response to pruritogens. These sensory reactions preceded the inflammation peak and lasted up to two days.

Eosinophils in hidradenitis suppurativa patients exhibit pro-inflammatory traits, implicating a potential pathogenic role in the disease.

Hidradenitis suppurativa (HS) is an inflammatory skin disease characterized by painful nodules, abscesses and purulent secretions in intertriginous regions. Intense pruritus frequently accompanies HS lesions, adding further discomfort for patients. While Th17 pathway activation is implicated in HS pathogenesis, disease mechanisms are still not fully understood, and therapeutics are lacking. Previous reports raise a potential role for eosinophils in HS, showing a strong association of eosinophil levels with disease severity. To investigate eosinophils in HS, we recruited patients and matched healthy controls and then performed flow-cytometry studies, eosinophil stimulation assays, and lesional skin staining for eosinophils. We found that HS patients reported similar levels of pain and itch. Compared to matched controls, HS blood exhibited decreased mature eosinophils and increased numbers of immature eosinophils, coupled with a significant increase in dermal eosinophilic infiltrates. Additionally, IL-17RA+ eosinophils were highly and significantly correlated with multiple HS-related clinical scores. In both stimulated and unstimulated conditions, HS eosinophils showed an inflammatory phenotype versus controls, including an increase in costimulatory T- and B-cell markers (e.g. CD5 and CD40) following all stimulations (TNFα/IL-17A/IL-17F). These findings highlight the significance of pruritus in HS and suggest a higher turnover of eosinophils in HS blood, potentially due to the consumption of eosinophils in skin lesions. Our data delineate the features and functions of eosinophils in HS and suggest that eosinophils participate in disease pathogenesis, advancing Th17-related inflammation. Further studies are needed to investigate eosinophils' response to current HS treatments and their potential as a therapeutic target in the disease.

Attentiveness and mental health in adolescents with moderate-to-severe atopic dermatitis without ADHD.

Patients with moderate-to-severe atopic dermatitis (AD) experience intense chronic itch and impaired sleep. Reports from parents and teachers suggest that AD patients may also have attention problems. However, attention has not yet been directly assessed in AD patients. We utilized an objective, computer-based continuous performance test (CPT) validated for use in attention-deficit/hyperactivity disorder (ADHD) diagnosis to formally evaluate attention in adolescent AD subjects. This was a single-visit, cross-sectional, non-interventional study of moderate-to-severe (Investigator's Global Assessment [IGA] ≥ 3) AD subjects aged 12-17 years without clinician-diagnosed ADHD. Attention was evaluated using two performance-based measures: Conners, CPT-3 and the Stroop Color and Word Test. The primary parameter was CPT-3 detectability (d') measure. Lesional severity measures included Eczema Area and Severity Index (EASI) and body surface area (BSA) involvement. Subjects completed self-report rating scales assessing sensory responsiveness patterns (Adult/Adolescent Sensory Profile [AASP]), itch (Peak Pruritus Numerical Rating Scale [PP-NRS]), skin pain, quality of life, sleep, anxiety, and depressive symptoms. A total of 44 subjects were included in the study (61.4% female; mean age 15.0 [SD 1.78] years; mean EASI 20.4 [SD 7.8]; mean PP-NRS 7.0 [SD 1.8]). Results indicated substantial disease impact on sleep, quality of life, and comorbid anxiety and depressive symptoms. The mean (SD) Conners, CPT-3 d' T-score was 48.7 (SD 10.7), similar to the expected mean from a randomly selected age/gender-matched sample of the general population (50 [SD 10], by definition). Overall, 13.6% of subjects exhibited a d' T-score ≥ 60 (clinically significant poor performance), which was not greater than the expected general population value (15.9%). Subject-level data review by two psychologists determined that only 2 subjects demonstrated an overall response pattern that clearly indicated attention deficit. Many subjects had atypical sensory responsiveness profiles: sensory hypersensitivity (38.6%), sensory avoidance (50%), and low registration (hypo-sensitivity, 36.4%). Adolescents with moderate-to-severe AD without existing ADHD diagnosis did not demonstrate greater attention problems on performance-based measures than would be expected in age/gender-matched peers.Trial registration NCT05203380.

Atopic dermatitis (often shortened to AD) is a long-term skin disease that causes intense itching. It affects patients' lives in many ways, including interrupting their sleep. Parents and teachers of young people with AD have sometimes suggested that AD may also cause attention problems. But this has never been tested properly.We measured the attention of 44 adolescents aged between 12 and 17 years who all had moderate-to-severe AD. We used computerized tests of attention that were developed for young people with ADHD (attention deficit hyperactivity disorder). Also, we made sure that none of the 44 patients had also been diagnosed with ADHD. The severity and extent of the patients' AD was measured by doctors. We also used some measures that allowed the patients to report how AD affected their lives, including things like itch, skin pain, quality of life, sleep, anxiety, and depression.The adolescent patients reported that AD had a negative effect on various areas of their lives, including sleep and quality of life, and that it resulted in anxiety and symptoms of depression. However, the results of the attention tests in adolescents with AD were similar to what would usually be expected in adolescents without AD. Only 2 of the 44 patients with AD were found to have clear evidence of attention problems.The study concluded that adolescents with moderate-to-severe AD did not have any greater attention problems than would usually be expected in adolescents without AD.

Plasma metabolomic profiling reveals a novel circulating biomarker signature in chronic pruritus of unknown origin.

Chronic pruritus of unknown origin (CPUO) is characterized by chronic itch for 6 weeks or greater without an identifiable primary cause. Studies are needed to investigate circulating blood biomarkers to elucidate disease pathogenesis. The objective of this study was to investigate changes in circulating blood metabolites in CPUO patients and to identify potential therapeutic targets. Our cross-sectional study collected plasma from 11 CPUO patients and 11 matched control patients for mass-spectrometry based metabolite data analysis. 15 metabolites differed significantly in the blood of CPUO patients compared to controls, including nine amino acids (isoleucine, L-tyrosine, threonine, DL-tryptophan, L-valine, methionine, glycine, lysine, and L-phenylalanine), four amino acid derivatives (creatinine, DL-carnitine, acetyl-L-carnitine, and indole-3-acrylic acid), and two aromatic and fatty acid derivatives (2-hydroxycinnamic acid and oleamide). These metabolites were also correlated with itch severity. Metabolic set enrichment analysis (MSEA) identified downregulation of several pathways in CPUO: phenylalanine, tyrosine, tryptophan biosynthesis; catecholamine biosynthesis; and glycine, serine, and threonine metabolism. Our study identified decreases in several circulating plasma metabolites in CPUO patients and downregulation of pathways related to catecholamine biosynthesis and tryptophan biosynthesis, providing insight into the pathogenesis of CPUO.

A Diterpenoid of the Medicinal Plant Andrographis paniculata Targets Cutaneous TRPV3 Channel and Relieves Itch.

Transient receptor potential vanilloid subtype 3 (TRPV3) is an ion channel implicated in skin physiology and itch. TRPV3 inhibitors can present a novel strategy for combating debilitating itch conditions, and medicinal plants are a natural pool of such compounds. Here, we report the isolation of a TRPV3-inhibiting compound from Andrographis paniculata, a medicinal plant with anti-inflammatory properties whose bioactive components are poorly characterized in terms of molecular targets. Using 1H and 13C NMR and high-resolution mass spectrometry, the compound was identified as a labdane-type diterpenoid, 14-deoxy-11,12-didehydroandrographolide (ddA). The activity of the compound was evaluated by fluorescent calcium assay and manual whole-cell patch-clamp technique. ddA inhibited human TRPV3 in stably expressing CHO and HaCaT keratinocytes, acting selectively among other TRP channels implicated in itch and inflammation and not showing toxicity to HaCaT cells. Antipruritic effects of the compound were evaluated in scratching behavior models on ICR mice. ddA suppressed itch induced by the TRPV3 activator carvacrol. Additionally, ddA potently suppressed histamine-induced itch with efficacy comparable to loratadine, a clinically used antihistamine drug. These results suggest the potential of ddA as a possible safe and efficacious alternative for antipruritic therapy.

Systematic review on antipruritic therapies for patients with Epidermolysis bullosa.

INTRODUCTION: Itch is one of the most burdensome symptoms in epidermolysis bullosa (EB), indicating a hitherto unmet therapeutic need. This review leverages existing data on efficacy of itch treatment in EB to support sound decision making. METHODS: A systematic literature search was performed on 29 March 2022. Studies written later than 1991 and reporting outcomes in patients with EB treated for itch were considered. RESULTS: Of the 3,099 articles screened, 21 studies met eligibility criteria, comprising 353 patients (65.9%) diagnosed for recessive dystrophic EB. Only two studies (9.5%) evaluated itch as primary endpoint, of which solely one revealed a significant relief of self-reported itch upon topical skin care. In those studies assessing itch as secondary endpoint (19/21, 90.5%), only 36.8% studies (n = 7/19) revealed a statistically significant itch reduction of up to 42%. Methodological limitations (heterogeneity of outcomes, inconsistent data assessment) in addition to limited superiority over control were implicated to account for low treatment efficacy observed in most studies. CONCLUSION: Current data quality impairs comparative efficacy analyses of itch treatments in EB. Large scale randomized clinical trials and more personalized approaches applying validated measurement instruments for core outcomes are needed to substantiate evidence-based treatment approaches for EB-associated itch.