Intractable Itching Research Articles

Homozygous variants in WDR83OS lead to a neurodevelopmental disorder with hypercholanemia

WD repeat domain 83 opposite strand (WDR83OS) encodes the 106-aa (amino acid) protein Asterix, which heterodimerizes with CCDC47 to form the PAT (protein associated with ER translocon) complex. This complex functions as a chaperone for large proteins containing transmembrane domains to ensure proper folding. Until recently, little was known about the role of WDR83OS or CCDC47 in human disease traits. However, biallelic variants in CCDC47 were identified in four unrelated families with trichohepatoneurodevelopmental syndrome, characterized by a neurodevelopmental disorder (NDD) with liver dysfunction. Three affected siblings in an additional family share a homozygous truncating WDR83OS variant and a phenotype of NDD, dysmorphic features, and liver dysfunction. Using family-based rare variant analyses of exome sequencing (ES) data and case matching through GeneMatcher, we describe the clinical phenotypes of 11 additional individuals in eight unrelated families (nine unrelated families, 14 individuals in total) with biallelic putative truncating variants in WDR83OS. Consistent clinical features include NDD (14/14), facial dysmorphism (13/14), intractable itching (9/14), and elevated bile acids (5/6). Whereas bile acids were significantly elevated in 5/6 of individuals tested, bilirubin was normal and liver enzymes were normal to mildly elevated in all 14 individuals. In three of six individuals for whom longitudinal data were available, we observed a progressive reduction in relative head circumference. A zebrafish model lacking Wdr83os function further supports its role in the nervous system, craniofacial development, and lipid absorption. Taken together, our data support a disease-gene association between biallelic loss-of-function of WDR83OS and a neurological disease trait with hypercholanemia.

MATERNAL AND FETAL OUTCOMES IN WOMEN RECEIVING URSODEOXYCHOLEIC ACID (UDCA) AS TREATMENT FOR INTRAHEPATIC CHOLESTASIS OF PREGNANCY (IHCP), A SINGLE CENTER EXPERIENCE: ARE WE DOING ENOUGH?

Intrahepatic cholestasis of pregnancy (IHCP) is a common type of hormonally driven cholestasis in the late second or early third trimester of pregnancy. It's a reversible condition and has a genetic predisposition. This study aimed to analyze the maternal and fetal outcomes of women being treated with Ursodeoxycholic acid (UDCA) for IHCP. Seventy-five pregnant women with IHCP were included in this observational cross-sectional study, with a study duration of one year. SPSS software version 24.0 was used to analyze the data collected by the investigating officer. Laboratory and clinical parameters were assessed at presentation and after treatment. Results showed that 92% of pregnant women with IHCP had significantly raised serum bile acid levels. However, UDCA treatment caused complete resolution of itching in 57.7% of patients, reduced to mild in 40.4%, and moderate itching in 1.9% of patients. Mean Alkaline Phosphatase and ALT levels significantly decreased after UDCA treatment, with p-values of 0.001 and 0.004, respectively. The dose of UDCA required ranged from 10-25 mg/kg/day. A positive family history of IHCP was found in 36.5% of patients, while 33% had a history of IHCP in previous pregnancies, and 16% had twin pregnancies. The incidence of early delivery was high at 98%, with a mean gestational age of 36.4 weeks. Among these early deliveries, 8% had vaginal delivery, and 92% had C-sections. The indications of delivery were intractable itching and no improvement in LFTS in 15%, PROM and fetal distress in 21%, failed induction in 31%, previous cesarean in 23%, and other reasons in 10%. The study found that 99% of babies had good APGAR scores and no morbidity. However, 1% mortality was reported due to severe IHCP in the mother. In conclusion, UDCA treatment significantly improved physical and laboratory parameters and effectively treated IHCP. Early delivery had better maternal and fetal outcomes.

Analysis of the mechanism of Sophorae Flavescentis Radix in the treatment of intractable itching based on network pharmacology and molecular docking.

Sophorae Flavescentis Radix (Kuh-seng, SFR), a Traditional Chinese Medicine (TCM), is widely used alone or within a TCM formula to treat pruritus, especially histamine-independent intractable itching. In the previous study, potential antipruritic active components of the SFR were screened based on cell membrane immobilized chromatography (CMIC), revealing oxymatrine (OMT) as an antipruritic agent. However, the low oral bioavailability (OB) of OMT cannot explain the antipruritic effect of SFR when administered orally in clinic. In this study, we investigated the antipruritic effects and underlying mechanisms of orally administered SFR. A network pharmacology and molecular docking were employed to screen the active components of SFR and predict their binding to disease-related target proteins, while the potential mechanisms were explored with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The binding energy between components and target proteins was calculated by molecular docking. The SFR-components-targets-intractable itching Protein-Protein Interactions (PPI) network was established, and 22 active components and 42 targets were screened. The GO enrichment analysis showed that the key target genes of SFR were related to nuclear receptors, transcription factors, and steroid hormone receptors. The results of the KEGG enrichment pathway analysis include Hepatitis B, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance, advanced glycation end product (AGE)-receptor for AGE (RAGE) signaling pathway in diabetic complications, etc. Molecular docking showed that three key target proteins in the network, the vascular endothelial growth factor A (VEGFA), epidermal growth factor receptor (EGFR) and caspase-3 (CASP3), have higher binding activities with inermine, phaseolin and kushenol O, respectively; the binding energy of each pair is stronger than that of the target protein-corresponding inhibitors. The complexity of the SFR-components-targets-intractable itching network demonstrated the holistic treatment effect of SFR on intractable itching. The partial coherence between results screened by CMIC in the previous study and network pharmacology demonstrated the potential of network pharmacology in active component screening. Inermine screened from both CMIC and network pharmacology is a VEGFA inhibitor, which possibly accounts for the antipruritic effect of orally administered SFR.

A Review of Moisturizing Additives for Atopic Dermatitis

Atopic dermatitis, the most common form of eczema, is a chronic, relapsing inflammatory skin condition that occurs with dry skin, persistent itching, and scaly lesions. This debilitating condition significantly compromises the patient’s quality of life due to the intractable itching and other associated factors such as disfigurement, sleeping disturbances, and social stigmatization from the visible lesions. The treatment mainstay of atopic dermatitis involves applying topical glucocorticosteroids and calcineurin inhibitors, combined with regular use of moisturizers. However, conventional treatments possess a certain degree of adverse effects, which raised concerns among the patients resulting in non-adherence to treatment. Hence, the modern use of moisturizers to improve barrier repair and function is of great value. One of the approaches includes incorporating bioactive ingredients with clinically proven therapeutic benefits into dermocosmetics emollient. The current evidence suggests that these dermocosmetics emollients aid in the improvement of the skin barrier and alleviate inflammation, pruritus and xerosis. We carried out a critical and comprehensive narrative review of the literature. Studies and trials focusing on moisturizers that include phytochemicals, natural moisturizing factors, essential fatty acids, endocannabinoids, and antioxidants were identified by searching electronic databases (PubMed and MEDLINE). We introduce the current knowledge on the roles of moisturizers in alleviating symptoms of atopic dermatitis. We then further summarize the science and rationale of the active ingredients in dermocosmetics and medical device emollients for treating atopic dermatitis. Finally, we highlight the limitations of the current evidence and future perspectives of cosmeceutical research on atopic dermatitis.

Etiopathgenesis of Dadru in Ayurveda: A Review

In recent years, Twak Vikar (Dermatological manifestations) are common and more so frequent in the elder age. There is a definite increase in its incidence especially, in the tropical region and developing countries like India due to various reasons like unhygienic environmental conditions, poverty, poor sanitation, illiteracy, malnutrition, improper skin care etc. The patients of skin disease are additionally prone to experience physical, emotional & socio-economic embarrassment in the society due to disfigured appearance. Dadru is one of the commonly occurring skin diseases which can be defined as an entity manifested by intractable itching, scaling, erythema with the lesions discoid in shape. Dadru, is a Kapha (Energy that forms the body’s structure) Pitta (Body’s metabolic system) Pradhan (prominent) Vyadhi (Disease). Acharya Charak has placed Dadru under Kshudra Kushth (Minor skin disease) but Acharya Sushrut and Acharya Vagbhata kept it under Mahakushth (Major skin disease). Acharyas did not explained separate Nidan (causative and diagnostic factor) for Dadru Kushth. The knowledge of Nidan is helpful for proper Diagnosis, prevention and treatment of disease.

Efficacy of topical adapalene monotherapy for symptomatic relief in a long‐standing vulvar syringoma: A case report and literature review with treatment update

We present a middle-aged Japanese female case of vulvar and facial syringomas, a very rare clinical phenotype of the disease, with severe intractable itching. The skin manifestation and symptom were unresponsive to topical corticosteroids and persisted for more than a decade, but her vulvar itching dramatically improved with topical adapalene monotherapy. We discuss the treatment dilemma of vulvar syringomas and the pharmaceutical mechanism of action of adapalene for satisfactory symptomatic relief in our case. Dear Editor, Vulvar syringoma is a benign adnexal skin tumor of eccrine duct origin, localizing to the female genital area.1 It is the second-most clinical variant following periorbital disease and often accompanies intractable pruritus,2 representing a disease morbidity and treatment dilemma. We report such a case of vulvar and facial syringomas, whose persisted vulvar pruritis unresponsive to topical corticosteroids improved with topical adapalene monotherapy. An otherwise healthy 53-year-old Japanese woman presented with a 10-year history of papules on her vulva with severe pruritis. Repeated topical corticosteroids were ineffective. Examination revealed miliary-sized, yellowish-white, multiple papules localized to the bilateral labia majora (Figure 1A,B). Similar eruptions were distributed on her periorbital region and cheeks (Figure 1C). She had neither family history nor experience of exacerbation during menstruation. Histopathology of biopsied vulvar skin revealed numerous small ducts in the fibrous dermal stroma (Figure 1D). The duct walls consisted of row epithelial (cuboidal) cells, which were lined by cuticle cells in the luminal inside (Figure 1E). Some of the ducts possessed comma-shaped tails of surrounding epithelial cells, so-called “tadpole” appearance (Figure 1F). This clinicopathology suggests facial and vulvar syringomas. Considering the inefficacy of preceded topical corticosteroids, we challenged a topical adapalene gel of 0.1% (Differin® Gel 0.1%). Within 4-weeks of adapalene use, intractable vulvar pruritus dramatically faded with decreased swelling. By 3-months, the vulval papules became relatively smaller in size, some of which disappeared (Figure 1G,H). There were no adverse events. During 6-months of follow-up, the vulvar lesions remained a favorable symptomatic control, albeit without much difference in appearance. Vulvar syringoma typically appears in puberty of females and tends to become worse during pregnancy or with the use of oral contraceptives, implicating a hormonal imbalance. Conservative treatments may be applicable because topical corticosteroid remains a value of choice as initial treatment and spontaneous regression may occur. The English literature search found 118 cases with syringoma at least appeared in the vulvar area.3-5 Of these, 46 cases (38.9%) had pruritus, requiring some sort of anti-pruritic treatment. A half (59/118, 50%) received any of the treatments, most frequently with topical corticosteroids (30/59, 50.8%), which were mostly unhelpful (20/30, 66.7%). Adapalene is a low-molecular-weight naphthoic acid derivative (MW 412.5) with retinoid-like activity and is widely approved for acne treatment. The literature search found only four cases, including ours, with syringomas at least affecting the vulva and whose skin lesions responded to either adapalene or all-trans retinoid tretinoin.6, 7 All cases had a previous history of topical corticosteroid that was unhelpful but achieved flattening and/or size reduction of individual papules. Our case obtained a significant improvement of intractable pruritis within a few weeks of adapalene initiation. Adapalene harbors variable pharmacological actions, including anti-inflammatory effects via inhibition of proinflammatory cytokines released from the corresponding keratinocytes and inflammatory infiltrates, and increase of extracellular matrix synthesis with a decrease of matrix metalloproteinase activity in dermal fibroblasts expressing adapalene-bound retinoic acid receptor-β.8, 9 One may consider that adapalene stimulates the turnover and remodeling of dermal matrix/appendages, together with anti-inflammatory and anti-comedogenic actions,10 contributing to the favorable clinical efficacy in our case. Approval of the research protocol: No human participant was involved in this study. Informed Consent: Written informed consent was obtained from the patients. Registry and the Registration No. of the study/trial: N/A. Animal Studies: N/A. The authors declare no conflict of interest.

Chemogenetic activation of central gastrin-releasing peptide-expressing neurons elicits itch-related scratching behavior in male and female mice.

Several lines of evidence have clarified that the key transmission pathways of itching sensation travel from the periphery to the central nervous system (CNS). Despite the functional significance of gastrin‐releasing peptide (GRP) and its cognate receptor in the itch processing mechanism in the spinal dorsal horn (SDH), the roles of GRP‐expressing (GRP+) neurons in different regions remain unclear. This study aimed to determine whether GRP+ neurons in the CNS directly modulated itch processing. To specifically activate spinal and supraspinal GRP neurons by the designer receptors exclusively activated by designer drugs (DREADDs) system, CAG‐LSL‐Gq‐DREADD mice were crossed with GRP‐Cre mice, resulting in the development of GRP‐hM3Dq mice. Immunohistochemistry showed that hM3Dq was highly expressed in the SDH and brainstem closely related to sensory processing. The intraperitoneal, intrathecal, or intracerebroventricular administration of clozapine‐N‐oxide, an agonist of hM3Dq, strongly elicited dermatome‐dependent itch‐related scratching behavior, but did not change pain sensitivity. Importantly, GRP‐Gq‐DREADD‐mediated scratching behavior in GRP‐hM3Dq mice was not affected by the ablation of transient receptor potential vanilloid 1+ sensory C‐fibers, and it was also observed to a similar degree under chronic itch conditions. Furthermore, there were no significant sex differences in the scratching behavior elicited by GRP‐Gq‐DREADD, suggesting that itch‐dominant roles of central GRP+ neurons might be common in both sexes, at least under normal physiological conditions. These novel findings not only contribute to understanding the functional roles of central GRP+ neurons further, but also propose the development of future effective therapeutics for intractable itching.

Anti-pruritic effect of nemolizumab in hemodialysis patients with uremic pruritus: a phase II, randomized, double-blind, placebo-controlled clinical study

BackgroundThe pathophysiology of uremic pruritus (UP), which is characterized by systemic and intractable itching, remains unclear. As interleukin (IL)-31 may be involved, we conducted a phase II, randomized, controlled study to evaluate nemolizumab (anti-IL-31 receptor A antibody) in Japanese hemodialysis patients with UP.MethodsPatients were randomly assigned (1:1:1:1:1) to one of four double-blind groups (receiving a single subcutaneous injection of nemolizumab 0.125, 0.5, or 2.0 mg/kg, or placebo on Day 1) or an open-label reference group (receiving oral nalfurafine hydrochloride 2.5–5 μg once daily for 12 weeks). The primary endpoint was the difference in the absolute change in pruritus visual analog scale (VAS) at Week 4 between placebo and each nemolizumab group.ResultsThe primary efficacy endpoint was not met. The mean change from baseline with all three nemolizumab doses at Week 1, and with 0.5 mg/kg at Week 4, was greater than with placebo. Least square mean differences (95% confidence intervals) in the absolute changes between the placebo arm and each nemolizumab arm were − 2.4 (− 19.7, 14.9) for 0.125 mg/kg, − 8.7 (− 26.6, 9.2) for 0.5 mg/kg, and 0.4 (− 17.0, 17.8) for 2.0 mg/kg. Secondary efficacy parameters including the Shiratori severity score and 5-D itch score failed to show between-group differences. Patients with higher serum IL-31 levels at screening tended to have greater pruritus VAS reductions following nemolizumab treatment.ConclusionsIn this phase II study in patients with UP, the primary efficacy parameter was not met. Nemolizumab was generally well tolerated with no clinically significant safety concerns.Clinical trial registrationJAPIC: JapicCTI-152961, https://www.clinicaltrials.jp/cti-user/trial/ShowDirect.jsp?japicId=JapicCTI-152961.

Clinicoepidemiological profile of steroid modified dermatophytosis following abuse of irrational combination of topical corticosteroid containing preparations (ICSP)

Topical corticosteroids are the most commonly used drug and mainstay of dermatotherapeutics for many dermatoses. Topical corticosteroids are irrationally combined with other medications and widely available as the over the counter preparations (OTC) and are widely misused for various conditions. Dermatophytosis is a superficial fungal infection which is becoming resistant and difficult to treat because of inappropriate usage of irrational combination of topical corticosteroid containing preparations (ICSP).To study the prevalence and factors which promotes the abuse of Irrational combination of topical corticosteroid containing preparations(ICSP) in dermatophyte infection.A Prospective observational study conducted at department of Dermatology, Venereology & Leprosy in a tertiary care centre, South India. The sample size of this study is n=55.Out of 55 patients most common age group is 15 -30 years (n=16,29.09%).Females (n=30,54.54%) predominated over males with male:female ratio of 0.83:1.The most common complaint was intractable itching (n=46,83.64%) .The majority of study group had disease duration was 0-1 months (n=27,49.1 %) with mean duration of 4 months. The main source of referral was Over the counter (OTC) (n=32,58.18%). The most common irrational combination was FDC 3 combination(30.9%). Most commonly abused brand was betnovate GM(n=17,30.9%).Most of the patients used Clobetasol propionate 0.05% (n=25,45.5%).Patients were using ICSP mostly for less than 1 month (n=27,49.1%),with intermittent(n=19,34.5%) frequency of application. Most common side effect was tinea incognita (n=33,60%).Potassium hydroxide mount was positive in 25 patients(45.45%).Fungal culture was done in all patients and 12 patients(21.81%) showed growth. The commonest organism isolated among culture positive specimen was Trichophyton rubrum(12.72%).Inappropriate usage of irrational combination of topical corticosteroid containing preparations (ICSP) in dermatophyte infection induces short term clearance whereas the long term side effects results in variable presentation. Awarness of this problem leads to prevention of steroid modified dermatophytosis which is the rising menace.

Saponin from Periploca forrestii Schltr Mitigates Oxazolone-Induced Atopic Dermatitis via Modulating Macrophage Activation.

Atopic dermatitis (AD) is a relapsing, acute, and chronic skin disease featured by intractable itching, eczematous skin. Conventional therapies based on immunosuppression such as corticosteroids are associated with multiple adverse reactions. Periploca forrestii Schltr saponin (PFS) was shown to potently inhibit murine arthritis by protecting bone and cartilage injury and suppressing NF-κB activation. However, its therapeutic effect on oxazolone-induced atopic dermatitis (AD) and the underlying mechanisms on macrophage are still unclear. The AD-like dermatitis was induced by repeated oxazolone challenge to the skin of BALB/c mice in vivo. Blood and ears were biochemically or histologically processed. RT-PCR, western blotting, and ELISA were conducted to evaluate the expression of macrophage factors. Mouse bone marrow-derived macrophages (BMDMs) stimulated with lipopolysaccharide (LPS) were used as a model in vitro. PFS treatment inhibited AD-like dermatitis development. PFS downregulated epidermis thickness and cell infiltration, with histological analysis of the skin lesion. PFS alleviated plasma immunoglobulin (Ig) E, IgG2a, and IgG1 levels. PFS downregulated the expression of M1 macrophage factors, tumor necrosis factor- (TNF-) α, interleukin- (IL-) 6, monocyte chemotactic protein-1 (MCP-1), and nitric oxide synthase2 (NOS2), and M2 macrophage factors, IL-4, arginase1 (Arg1) and CD163 in AD-like skin, which were confirmed by western blot and ELISA analysis. In addition, PFS inhibited LPS-induced macrophage polarization via the inhibition of the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and nuclear translocation of NF-κB p65. These results suggest that PFS exerted an antidermatitis effect against oxazolone by modulating macrophage activation. PFS administration might be useful in the treatment of AD and inflammatory skin diseases.

Post-Burn Pruritus.

Post-burn pruritus is the pruritus that occurs after burn during the rehabilitation and healing process of burn wounds. The post-burn pruritus is a common and serious complication of burn injury, which severely lowers the quality of life of the patient. Many potential treatments are available for pruritus but there is no consensus of the best single treatment yet. The precise mechanism of post-burn pruritus has not been elucidated, but it appears to have pruritogenic and neuropathic aspects. Clinically, post-burn pruritus tends to be intractable to conventional treatment but rather responds to neuroleptic agents, such as gabapentin and pregabalin. During wound healing, various neuropeptides secreted from the nerves of the skin control epidermal and vascular proliferation and connective tissue cells. When keratinocytes are activated by an itch-inducing substance, they secrete a variety of inflammatory substances that increase the susceptibility of the itch receptor. There are two mechanisms underlying post-burn neuropathic pruritus. The first one is peripheral sensitization. The second one is the intact nociceptor hypothesis. An effective treatment for post-burn pruritus will also be effective in other neuropathic and intractable itching. In this review, we summarized the interaction and mechanism of keratinocytes, immune cells, and nerve fibers related to post-burn pruritus.

Identification of novel loci for pediatric cholestatic liver disease defined by KIF12, PPM1F, USP53, LSR, and WDR83OS pathogenic variants

PurposeGenetic testing in pediatric cholestasis can be very informative but genetic causes have not been fully characterized. MethodsExome sequencing and positional mapping in seven families with cholestatic liver disease and negative clinical testing for known disease genes. ResultsKIF12, which encodes a microtubule motor protein with a tentative role in cell polarity, was found to harbor three homozygous likely deleterious variants in three families with sclerosing cholangitis. KIF12 expression is dependent on HNF-1β, deficiency which is known to cause bile duct dysmorphogenesis associated with loss of KIF12 expression. In another extended family, we mapped an apparently novel syndrome of sclerosing cholangitis, short stature, hypothyroidism, and abnormal tongue pigmentation in two cousins to a homozygous variant in PPM1F (POPX2), a regulator of kinesin-mediated ciliary transport. In the fifth family, a syndrome of normal gamma glutamyltransferase (GGT) cholestasis and hearing loss was found to segregate with a homozygous truncating variant in USP53, which encodes an interactor with TJP2. In the sixth family, we mapped a novel syndrome of transient neonatal cholestasis, intellectual disability, and short stature to a homozygous variant in LSR, an important regulator of liver development. In the last family of three affected siblings, a novel syndrome of intractable itching, hypercholanemia, short stature, and intellectual disability was mapped to a single locus that contains a homozygous truncating variant in WDR83OS (C19orf56), known to interact with ATP13A2 and BSEP. ConclusionOur results expand the genetic heterogeneity of pediatric cholestatic liver disease and highlight the vulnerability of bile homeostasis to a wide range of molecular perturbations.

Cataract, Glaucoma, and Dry Eye Disease in Adults with Atopic Dermatitis: A Nationwide Cross-Sectional Study from the Republic of Korea.

BackgroundAtopic dermatitis (AD) is an inflammatory skin disorder characterized by relapsing eczema with intractable itching. Ocular diseases in patients with AD, including cataract, retinal detachment, blepharitis, glaucoma, keratoconjunctivitis, and keratoconus, have frequently been reported worldwide. However, only a few studies using a large-sample, population-based study design have been reported so far.ObjectiveWe investigated the association between cataract, glaucoma, and dry eye disease and AD in an adult population in the Republic of Korea.MethodsA total of 14,900 adults who participated in the Korean National Health and Nutrition Examination Survey, a nationwide, population-based, cross-sectional survey, between 2010 and 2012 were included in the study. Multiple logistic regression analyses identified the possible association between cataract, glaucoma, and dry eye disease and AD relative to matched controls.ResultsAfter we adjusted for confounding factors in patients with AD, cataract and glaucoma were significantly associated with AD. Moreover, patients with AD had a higher prevalence of ophthalmic surgery compared to those without AD.ConclusionDermatologists should therefore be aware of possible ocular disorders in patients with AD and should recommend regular ophthalmic screening for early detection.

Anti-CCR4 Monoclonal Antibody, Mogamulizumab, Demonstrates Significant Improvement in PFS Compared to Vorinostat in Patients with Previously Treated Cutaneous T-Cell Lymphoma (CTCL): Results from the Phase III MAVORIC Study

Anti-CCR4 Monoclonal Antibody, Mogamulizumab, Demonstrates Significant Improvement in PFS Compared to Vorinostat in Patients with Previously Treated Cutaneous T-Cell Lymphoma (CTCL): Results from the Phase III MAVORIC Study

EOSINOPHIL CATIONIC PROTEIN IN UREMIC DIALYZED PATIENTS WITH INTRACTABLE PRURITUS

We have analyzed 6 patients(pts) with chronic uremic pruritus(UPG) treated with intermittent hemodialysis more than 5 years,and 7 uremic pts treated under the same conditions but without pruritus(UG).In all pts and in appropriate control group(CG)of healthy subjects(N 0 = 5)we have measured the serum concentration of s.c.eosinophil cationic protein(ECP) known as a protein of allergic states(bronchial asthma as a classic example).We have found elevated serum concentrations of ECP in uremic pts(XECP cg = 2.03±0.02 µg/L vs X ECP ug = 2.63 ±0.29 µg/L),but especially at the uremics with intractable itching(X ECP upg = 8.37±1.67 µg/L). The aim pf the paper:The dialyzed pts with transitory uremic pruritus(u.p)or itching related to the other additioned conditions (like hepatocellular or obstructive jaundice)not differ significantly from the uremics without itching bearing in consi- deration the serum concentration of ECP. Material and methods:1.patients and control group: we have analyzed 6 patients(pts)with chronic imperative u.p(duration more than 6 months!)treated with intermittent hemodialysis more than 5 years(Department of nephrology,Clinical Centre,Skopje,R.of Macedonia) and 7 uremics treated under the same conditions but without up.In all pts(age and sex matched,N 0 = 13)and in the appropriate control group of healthy subjects(c.g,N 0 = 5),we have measured the serum concentrations of s.c.eosinophil cationic protein(ECP)known as a protein of allergic states(allergic rhinitis and conjunctivitis,atopic dermatitis and bronchial asthma as a classic example).The blood was picked up at 8 a clock for investigated persons and before hemodialysis for uremic pts to.Results: From the precedent tables is evident almost the same frequency in men and women(males = 10,females=8),with the mean age(all groups included) of about 44 years.The serum concentration of ECP is lowest(≈ 2 µg/l) in the CG with coefficient of variation(CV) under 2%!The UG is not so compact regarding sECP with CV ≈ 30%,and finally the uremic pts suffering from intractable itching(UPG) are heterogenous group with more elevated level of sECP(at p 1.96 SEM) but especially evident comparing the CG and UPG(Z= 3.8 SEM),respectively UG and UPG(Z >3.3 SEM).We have concluded that in the cases of very promounted u.p,the allergic component is higly included.The further investigations are needed to detect indoubtely the presence of ECP,EPX or eosinophils in the selected planes of the skin tissue and to develop more efficacious antipruritus drugs. Index trems: uremic intractable pruritus eosinophil cationic protein(ECP),Hemodialysis

Sclerotic atrophic plaques associated with a tattoo

Lichen sclerosus is a chronic inflammatory disease, usually of the anogenital area, that causes intractable itching and soreness. Less commonly, it may have extragenital involvement in 15 to 20% of cases. Lichen sclerosus has been reported at sites of injury as a Koebner phenomenon. We report a case of lichen sclerosus at the site of a tattoo with simultaneous genital involvement.

Ondansetron to Treat Pruritus Due to Cholestatic Jaundice

Intractable itching is a symptom of cholestatic liver disease of various causes that is bothersome and difficult to manage. Although treatment of the primary cause of cholestasis is paramount in resolving the issue, given the debilitating consequences of pruritus, symptomatic treatment is frequently necessary. Although many medications including cholestyramine, rifampin, opioid antagonists (i.e., naloxone, naltrexone), phenobarbital, and antihistamines have been used to treat cholestatic-induced pruritus, none has resulted in uniform success. We report anecdotal success with the use of ondansetron to treat pruritus associated with cholestasis following prolonged intensive care unit course of a 16-year-old. The theories accounting for pruritus with cholestasis are presented, treatment options are reviewed, and the role of ondansetron in the treatment of pruritus is discussed.

Intractable Post-Herpetic Itching with Sacral Dermatomal Involvement: A Case Report

BackgroundPost-herpetic itching [PHI] was found in four percent of all herpes zoster patients. They may even describe this itching complaint without any pain. It may not respond to regular anti-pruritus drugs or anti-histaminics. Sympathetic nerve block has been used with different degrees of success as a component of therapy for post-herpetic neuralgia [PHN] in cranial, cervical, thoracic, and lumbar distributions. Sacral dermatomal involvement of PHN occurs in only three percent of patients.FindingsA 40-year-old female patient had a complaint of intractable sacral itching. She had a total colectomy operation one year ago. At the early postoperative period, vesicular lesions appeared at the sacral region. These vesicular lesions were completely healed after anti-viral medications. However, the complaint of itching started thereafter. The patient was treated with various anti-itching medical therapies at different hospitals. We started gabapentin by increasing the dose from 1.8 to 2.4 mg/day. With a parti...

Clinical evaluation of the efficacy of Khadiradi yoga avachoornana in Kachchu with special reference to genitoinguinal intertrigo

Kachchu is a simple localized dermatological infection of the genitoinguinal region, which occurs because of unhygienic observance, and manifests in the form of inflammation followed by secondary bacterial or fungal infections that can be best correlated to genitoinguinal intertrigo. Even though it rarely causes systemic manifestations, its mere presence itself is disturbing because of intractable itching and pain. It may delay the proper healing of the episiotomy wound and may cause difficulty in walking because of severe pain. Candida powder is the highest selling medicine for the intertrigo, as the incidence of intertrigo is as high as 40% in some particular seasons. In the Ayurveda fraternity, there is no established preparation that can be preserved safely in all the epochs of life in females and which is easy to apply. After understanding the disease in the perspective of the ayurvedic and modern medicinal systems, Khadiradi yoga choorna — a new ayurvedic formulation — was prepared on the basis of stringent ayurvedic principles. Hence, an attempt has been made to study the efficacy of the khadiradi yoga avachurnana1 in Kachchu, with special reference to genitoinguinal intertrigo in females.

Serial Stellate Ganglion Blocks for Intractable Postherpetic Itching in a Pediatric Patient: A Case Report

While intractable itching may be rarely associated with postherpetic neuralgia, it can have catastrophic complications if present. We highlight a severe case of postherpetic itching in a 10-year-old male with Fanconi's and aplastic anemia, refractory to conventional treatments and requiring intravenous sedation. Our use of 3 sequential stellate ganglion blocks with 5.5 mL of 0.25% bupivacaine provided significant improvement of the symptoms for 4 months after the last procedure. Although further evaluation is needed, we feel that novel use of sympathetic blockade may provide treatment for intractable itching. Highlighted is the possible influence of the sympathetic system in the pathophysiology of postherpetic itch. The use of serial stellate ganglion blocks may be a treatment option for patients with intractable itching and postherpertic neuralgia of the neck and arm region. This technique may lead to more permanent solutions such as pulse radiofrequency lesion or chemical neurolysis of sympathetic ganglions for postherpetic itch.