Hydroxychloroquine: A Safe, Effective and Inexpensive Maintenance Therapy for Chronic Spontaneous Urticaria

Background: Chronic spontaneous urticaria (CSU) is an autoimmune skin disorder that lasts for >6 weeks and may last for years. It is a disabling skin disease that impairs quality of life. Set-up treatment with antihistamines, immunosuppressives, immune modulators and lately Omalizumab are expensive or have significant side effects. In this retrospective study, we describe our experience with the use of hydroxychloroquine (HCQ) as a maintenance therapy for those with severe forms of CSU after Corticosteroids (C) induction phase. Patients and Methods: 16 adult patients (aged 44 ± 7) with severe CSU for 5 ± 1 months, were included in the study. Eight patients had attacks of angioneurotic oedema. Their previous treatments were antihistaminic and short-courses of C. Results: After 2 weeks of remission with C and HCQ 200 mg twice daily, the dose of C was tapered down and discontinued by the end of the first month. The seven days Urticaria Activity Score decreased from 30 ± 3 to 6 ± 1 by the first month and remained low at 3 ± 1 by the end of 2 years of follow-up. Moreover, IgE levels and CRP had similar trends. Remission persisted after 37 ± 9 months of follow-up. Conclusion: HCQ is a safe, efficacious and inexpensive drug for the treatment of CSU.

Systemic Amyloidosis Secondary to Psoriasis: A Rare, Autoimmune and Genetically-Determined Disorder That Is Amenable to Treatment with Cyclosporin A—Cyclosporin A for Psoriasis-Induced Amyloidosis

Background: Systemic secondary amyloidosis (SSA) is associated with chronic inflammatory disorders and/or chronic infections. Patients and Methods: Over the past 10 years;a total of 21 patients, with long-term (17 months) and extensive psoriasis (P) with psoriasis area severity index (PASI) >29, were evaluated. Results: Two patients had nephrotic syndrome (proteinuria 3.9 and 3.6 g/day) and decrease creatinine clearance (46 and 62 ml/minute). Their renal biopsy revealed Congo-red (+) nodular glomerulosclerosis that lacked immune-deposits and resisted wash with K-permanganate wash indicating SSA. Three months subsequent to Cyclosporin A (CyA) therapy with 100 mg twice daily;psoriasis improved in all patients with decrease in (PASI) from 29.5 to 3.5 1. In the 2 patients with SSA;proteinuria decreased to 2.1 and 1.8 g/day and creatinine clearance improved to 51 and 69 ml/minute. Such improvement persisted up to 2 years of follow up and up to 78 months in patients with SSA. Conclusion: psoriasis-induced SSA is an autoimmune disease, with genetic predisposition that is amenable to CyA therapy.

Rituximab Therapy for Persistent, Severe and Extensive Idiopathic Bullous Pemphigoid

Background: Idiopathic Bullous Pemphigoid (IBP) is a rare blistering autoimmune disease. Its morbidity and mortality have remained high owing to complications of extensive skin involvement as well as its conventional steroid therapy. We reviewed the medical literature and found indicators of an autoimmune etiology for its pathogenesis triggering genetically predisposed patients. Objective: to evaluate, prospectively, the role of Rituximab (R) therapy in its persistent, severe and extensive form. Patients and methods: A total of 12 patients, with disease duration of 6 ± 1 months, were treated with yearly R infusions (1 g followed by 1 g 2 weeks later). Results: Significant clinical improvement was achieved as documented by decrease in total score of Bullous Pemphigoid Disease Area Index from 60 ± 3 to 6 ± 2 that persisted for 26 ± 11 months of follow up. Moreover, IBP autoantibodies (anti-BP 180 and anti-320 IgG) levels fell from to 91 ± 3 and 81 ± 2 to 8 ± 2 and 9 ± 2, respectively. Conclusions: R is a safe and effective treatment for severe IBP and such response further confirms its autoimmune pathogenesis.

Relationship between acrosin activity of human spermatozoa and oxidative stress

Aim: To study the association between seminal oxidative stress and human sperm acrosin activity. Methods: It is a prospective study consisting of 30 infertile men and 12 fertile normozoospermic volunteers. A full history, clinical examination and scrotal ultrasound were done to exclude other related factors such as smoking and varicocele. Presence of white blood cells (WBCs) in semen samples was evaluated by peroxidase staining. Lipid peroxidation in spermatozoa was induced after incubating with ferrous sulphate (4 mmol/L) and sodium ascorbate (20 mmol/L). Induced peroxidation of spermatozoa was assessed by determining the production of thiobarbituric acid reactive substances (TBARS). Acrosin activity was measured using the gelatinolysis technique. The halo diameters around the sperm heads and the percentages of spermatozoa showing halo formation were evaluated. An acrosin activity index was calculated by multiplying the halo diameter by the halo formation rate. Results: A significant difference was observed in acrosin activity parameters and TBARS levels between samples with WBCs (>1×106/mL of ejaculate) and those without. This difference was also noted between the normozoospermic and the oligoasthenoteratozoospermic semen samples. The TBARS production by spermatozoa had a significant negative correlation with the acrosin activity index (r = -0.89, P <0.001). Conclusion: The presence of oxidative stress in an individual with leukocytospermia and/or abnormal semen parameters is associated with impaired sperm function as measured by its acrosin activity.

Comparison of post-urethroplasty complication rates in pediatric cases with hypospadias using Vicryl or polydioxanone sutures

Objective:Hypospadias is a common congenital problem among male newborns.Both rapid absorbable sutures(polyglactin,Vicryl)and delayed absorbable sutures(polydioxanone,PDO)are used in hypospadias repair based on the surgeon's preference.This study was conducted to compare post-urethroplasty complication rates in pediatric patients with hypospadias using Vicryl or PDO sutures.Methods:This is a retrospective study which was designed and performed on 583 children aged 1-7 years old who had undergone hypospadias repair from January 2012 to December 2018.Required data were obtained from the patients'medical records.Results:Overall,post-surgical complications were observed in 60(10.3%)patients comprising urethro-cutaneous fistula(n=39,6.7%),meatal stenosis(n=10,1.7%),urethral stricture(n=7,1.2%),and glans dehiscence(n=4,0.7%).The mean age of the children with complications was 3.0±1.3 years.According to Kaplan-Meier estimate,the interval between surgery and development of complications was significantly shorter in the Vicryl group(p=0.037).Overall,complications were more prevalent in Vicryl suture than PDO suture(15.1%vs.5.3%,p<0.001).Regression model revealed that in comparison to the distal type,proximal hypospadias(odds ratio[OR]:103.9,95%confidence interval[CI]:32.2-334.9,p<0.001)and mid-shaft hypospadias(OR:82.9,95%CI:25.9-264.6,p<0.001)while using Vicryl suture instead of PDO suture(OR:62.4,95%CI:21.2-183.8,p<0.001)increased the odds of developing post-urethroplasty complications.Conclusion:We suggest PDO suture in the repair of hypospadias due to its lower complication rate,especially in cases of proximal and mid-shaft hypospadias which can get more complicated than the distal type.

联用alefacept和依那西普治疗3例单用依那西普治疗无效的银屑病患者

This article reports on the combined use of alefacept and etanercept in 3 patients whose psoriasis failed to respond adequately to etanercept. All patients maintained improvement for at least 8 weeks after completing 12 weeks of alefacept. No adverse events or infections were reported, and CD4+ T-cell counts remained above normal limits.

A Novel Vehicle Formulation for Treatment of Inflammatory Skin Diseases

Objective: To test the efficacy of a new topical vehicle formulation containing cetirizine in emu oil in treating inflammatory skin conditions. Methods: A single blind half body comparative study of patients with psoriasis, atopic and stasis dermatitis were all treated with midpotency topical steroid (desoximethasone) in propylene glycol base, desoximethasone and cetirizine in propylene glycol base, desoximethasone in emu oil base and desoximethasone with cetirizine dissolved in emu oil. Results: Based on patients’ ranking of creams’ efficacy, and supported by photographic data and investigators’ clinical assessment, results clearly indicated that desoximethasone and cetirizine in emu base was statistically more efficacious than either desoximethasone alone or with cetirizine in neutral propylene glycol base or desoximethasone in emu oil base (without cetirizine). Conclusions: Cetirizine and emu oil, having inherent anti-inflammatory and other beneficial properties synergistically, and by different biochemical pathways, enhance and magnify each other’s pharmaceutical effects that are useful in treatment of skin inflammatory diseases.

Detection of Intracellular Cytokine Production in Peripheral Blood CD_^+ T Cells of Patients with Recurrent Genital Herpes

To study the role of Th1/Th2 cytokines in the pathogenesis of recurrent genital herpes (RGH), and to better understand the relationship between them. Methods: A two-color immunofluorescent staining of cell surface antigen and intracellular cytokines for flow cytometric analysis was used for CD3, IL-2, IL-10, IL-12, IFN-y and TNF-a in CD3^+ T-lymphocytes in activated peripheral blood mononuclear cells of patients with RGH. Results: Compared to controls, patients with RGH showed fewer CD3^+ T cells (P<0.05) and IL-2 producing and IFN-7 producing T cells (P<0.02 and P<0.001, respectively)after in vitro stimulation with PMA and ionomycin in the presence of a protein transport inhibitor. More IL-10 producing and IL-12 producing T cells were found in patients with RGH (P<0.01). There was no significant difference in the number of TNY-α producing cells between RGH patients and controls (P<0.05). Conclusion: RGH patients showed relatively more Th2 cytokines. The imbalance between Thl and Th2 cytokines results in inhibitory effects on a series of cell-immune responses, which may play an important role in the pathogenesis of RGH.

以色列士兵足癣的患病率和危险因素

Background: Tinea pedis is a common infection in soldiers. However, prevalence and risk factors for tinea pedis in soldiers were investigated in only a few studies. Objectives: To investigate the prevalence and risk factors for tinea pedis in Israeli soldiers. Methods: A cross-sectional study including interviews, clinical skin examination and mycological tests was performed in Israeli soldiers. The presence of tinea pedis was assessed using the Athlete s Foot Severity Index (AFSI), a scoring system that was developed in order to evaluate the presence and severity of tinea pedis. In soldiers with clinical evidence of tinea pedis (AFSI > 1), scrapings were taken for direct microscopic examination (20% KOH preparation) and fungal culture. Statistical analyses were performed using chi-square or Fisher s exact test for dichotomous variables (as needed), or t-tests for continuous variables. Logistic regression was used for multivariate analyses of dichotomous variables. Results: Two hundred and twenty-three soldiers were included in the study: 205 men (91.9% ) and 18 women (8.1% ). Mean age was 19.6 years (SD 1.0 year). Clinical point prevalence was 60.1% . Mycological point prevalence was 27.3% . Further analyses were performed using the clinical point prevalence. Univariate analyses demonstrated that the prevalence of tinea pedis varied with the setting of military training (basic training: 70.3% , advanced infantry training: 81.5% , armor commander training: 56.4% and armor officer training: 34.8% ) and was associated with male gender, frequency of sock changes and the length of military service. A multivariate analysis demonstrated that tinea pedis was associated with the setting of the military training (OR 1.6, 95% Cl 1.2- 2.1) and male gender (OR 4.3, 95% Cl 1.4- 13.8); however, there was no association with hygiene measures (e.g. frequency of changing socks or sleeping with socks) or the length of military service. Conclusion: Tinea pedis is highly prevalent in Israeli soldiers. Association of tinea pedis with the setting of military training suggests that contagious spread may be an important risk factor. We suggest that environmental interventions should be planned to in order to decrease the morbidity of tinea pedis among soldiers.

银屑病患者的心肌梗死风险

背景:银屑病是最常见的1型辅助性T细胞(TH1)免疫性疾病,有证据显示TH1疾病与心肌梗死(MI)相关。据悉,银屑病与心血管疾病相关,但这仅在未校正主要心血管危险因素的医院研究中被探讨过。

Detection of β-Glucuronidase Activity within Actinomadura madurae Grains of Human Actinomycetoma

Actinomycetoma syndrome by Actinomadura (A.) madurae is characterized by a subcutaneous chronic lesion that affects fascia, muscle and bone. A. madurae produces colonies that form grains of less than 1 mm in diameter. Grains are surrounded and infiltrated by neutrophils involved in the grain disruption by enzymes like β-glucuronidase released after the neutrophil degranulation. The aim of this work was to evaluate the polysaccharide degradation of grains treated with β-glucuronidase and to detect the presence and activity of β-glucuronidase within the A. madurae grains. Actinomadura madura grains from patients infected were processed to quantify the total content of polysaccharide with the phenol-sulfuric acid reaction. Grains were treated with β-glucuronidase at different conditions to evaluate the optimal polysaccharide degradation. Grains were analyzed to detect the enzyme by using anti-human β-glucuronidase antibody while enzymatic activity was assessed by evaluating the release of reduced sugars and by in situ enzymatic activity. Optimal degradation of polysaccharide in the grains treated with β-glucuronidase was found with 300 units/ml of enzyme and 24 hr of incubation at 37°C. Presence and activity of β-glucuronidase enzyme within the grains were detected. Results suggested that β-glucuronidase present within A. madurae grain resulted from degranulated neutrophils surrounding and/or infiltrated within the grain.

Liver-directed treatment is associated with improved survival and increased response to immune checkpoint blockade in metastatic uveal melanoma:results from a retrospective multicenter trial

Metastases of uveal melanoma(UM)spread predominantly to the liver.Due to low response rates to systemic therapies,liver-directed therapies(LDT)are commonly used for tumor control.The impact of LDT on the response to systemic treatment is unknown.A total of 182 patients with metastatic UM treated with immune checkpoint blockade(ICB)were included in this analysis.Patients were recruited from prospective skin cancer centers and the German national skin cancer registry(ADOReg)of the German Dermatologic Cooperative Oncology Group(DeCOG).Two cohorts were compared:patients with LDT(cohort A,n=78)versus those without LDT(cohort B,n=104).Data were analyzed for response to treatment,progression-free survival(PFS),and overall survival(OS).The median OS was significantly longer in cohort A than in cohort B(20.1 vs.13.8 months;P=0.0016)and a trend towards improved PFS was observed for cohort A(3.0 vs.2.5 months;P=0.054).The objective response rate to any ICB(16.7%vs.3.8%,P=0.0073)and combined ICB(14.1%vs.4.5%,P=0.017)was more favorable in cohort A.Our data suggest that the combination of LDT with ICB may be associated with a survival benefit and higher treatment response to ICB in patients with metastatic UM.

PIEZO1 channels in cutaneous free nerve endings:novel insights into itch-scratch-mechanisms

A recent study published in Nature by Hill et al.1 identified mechano-sensitive PIEZO1 ion channels in pruriceptive neurons.Remarkably,PIEZO1 is involved in acute itch transmission and in mechanical alloknesis in chronic pruritus(CP)states.Itch is defined as an unpleasant sensation leading to the desire to scratch.

Efficacy and safety of ixekizumab in Chinese patients with plaque psoriasis

To the Editor:Psoriasis is a common,chronic papulosquamous skin disease occurring worldwide,presenting at any age,and leading to a substantial burden for individuals and society.Interleukin(IL)-17A is considered the key effector cytokine inducing psoriatic inflammation and tissue damage.[1]Ixekizumab is a humanized monoclonal immunoglobulin G specifically binding to and inhibiting IL-17A.The efficacy and safety of ixekizumab in patients with psoriasis have been clearly demonstrated in several randomized clinical trials,namely UNCOVER-1,UNCOVER-2,UNCOVER-3,and UNCOVER-J.[2,3]However,the clinical research data on ixekizumab in Chinese psoriasis patients remain limited.

A case of familial incontinentia pigmenti in infancy without hyperpigmented stage

To the editor:Incontinentia pigmenti(IP)is a rare X-linked dominant neuroectodermal disorder primarily caused by mutations in the IKBKG(NEMO)gene.Cutaneous manifestations of IP typically progress through four stages:inflammatory(or vesicular)stage,verrucous stage,hyperpigmented stage,and hypopigmented(or atropic)stage.^(1)Throughout the disease course,most cases develop linear or whorled brownish reticular pigmentation following the lines of Blaschko.Additionally,some patients experience linear hypopigmentation and absence of hair,usually during adolescence.Here,we report a rare manifestation of this disease.

Reprogrammed CRISPR-Cas9 targeting the conserved regions of HPV6/11 E7 genes inhibits proliferation and induces apoptosis in E7-transformed keratinocytes

The persistence infection of low-risk type （type 6 or type 11） of human papillomavirus （HPV） is the main cause of genital warts. Given the high rate of recurrence after treatment, the use of a new molecular agent is certain to be of value. The aim of this study was to achieve targeted inactivation of viral E7 gene in keratinocytes using the reprogrammed clustered regularly interspaced short palindromic repeats （CRISPR）/CRISPR-associated （Cas） 9 system. To accomplish this, a universal CRISPR-Cas9 system for targeting both HPV6/11 E7 genes was constructed by using a dual guide RNA vector. After transfection of the vector into E7-transfromed keratinocytes, the expression level of E7 protein was measured using western-blot analysis and the sequence of the E7 gene was determined using Sanger sequencing. Cell proliferation was analyzed by CCK-8 assay, and cell apoptosis was evaluated by Hoechst 33258 staining, flow cytometry analysis and ELISA assay. The results indicated that both HPV6/11 E7 genes can be inactivated by the single CRISPR-Cas9 system. Furthermore, silencing of E7 led to inhibition of cell proliferation and induction of apoptosis in E7-transfromed keratinocytes but not in normal keratinocytes. Our data suggested that the reprogrammed CRISPR-Cas9 system has the potential for the development of an adjuvant therapy for genital warts.

Fungal infection in organ transplant patients

Purpose To review the characteristics and evolution of the fungal spectrum, and the risk factors causing fungal infection, and to make progress in diagnosing fungal infection after organ transplantation.Data sources An English-language literature search ( MEDLINE 1990 -2000) and bibliographic review of textbooks and review articles.Study selection Twenty-three articles were selected from the literature that specifically addressed the stated purpose.Results Fungal infections in organ transplant patients were generally divided into two types: (1) disseminated primary or reactivation infection with one of the geographically restricted systemic mycoses; ?opportunistic infection by fungal species that rarely cause invasive infection in normal hosts. The risk factors of fungal infection after a transplant can be evaluated and predicted according to the organ recipient's conditions before, during and after the transplant. Progress in early diagnostic methods during the past 10 years has mainly revolved around two aspects, culture and non-culture.Conclusions It is important to undertake a systemic evaluation on the condition of the organ recipient before, during and after a transplant; should any risk factor for fungal infection be suspected, diagnosis should be made as early as possible by employing mycological techniques including culture and non-culture methods.

Leech therapy in treatment of cutaneous leishmaniasis:a case report

1 IntroductionApplication of leeches has been a common treatment measure since ancient times and descriptions can be found in the works of Pliny,Galen,Avicenna and Themison.