Validation of psoriasis disability index (PDI) questionnaire Sinhala version.

INTRODUCTION/OBJECTIVES: Psoriasis is a chronic inflammatory dermatosis with significant physical and psychological impact leading to negative influence on the quality of life among patients with psoriasis. Other than the disease characteristics many external factors could operate in South Asian context. Lack of a reliable disease-specific instrument prevents objective estimation and monitoring of disability in patients with psoriasis and hence we aim to validate assess the psychometric properties of the Sinhala version of PDI. METHODS: A cross-sectional study conducted at dermatology clinic at a tertiary care National Hospital in Sri Lanka. Patients with psoriasis and on therapy at least 4 weeks prior to enrollment, aged more than 18 years, were included while those with already diagnosed psoriatic arthritis and/or nail psoriasis alone without any skin involvement and generalized pustular psoriasis de novo were excluded. All patients were examined by dermatologist to obtain disease characteristics. The reliability was assessed by internal consistency using Cronbach's α and item-total correlation. Convergent validity was measured with the known groups. RESULTS: Of 199 patients studied, the PDI Sinhala version showed Cronbach's α of 0.86 (all 15 items) and ranged from 0.57 to 0.77 for subscales. PDI score and Dermatology Life Quality Index (DLQI) showed good correlation of coefficient 0.76 (p < 0.01). Positive associations were noted with extent and severity of psoriasis when using sample medians (p < 0.05). The dimensionality of the PDI was determined using exploratory factor analysis and four factors were structured. CONCLUSION: The PDI Sinhala version is proved to be valid and reliable tool to assess the burden of psoriasis among Sinhala conversant patients in Sri Lanka.

Conjunctivitis in adult patients with moderate-to-severe atopic dermatitis: results from five tralokinumab clinical trials.

BACKGROUND: Tralokinumab, a fully human IgG4 monoclonal antibody that specifically binds with high affinity to interleukin-13, effectively reduces moderate-to-severe atopic dermatitis (AD) when given every 2 weeks. The incidence of conjunctivitis is elevated vs. placebo, but severity and aetiology have not been examined. OBJECTIVE: To analyse conjunctivitis data recorded in five randomized, placebo-controlled trials of tralokinumab in adult patients with moderate-to-severe AD. METHODS: Overall, 2285 adults with AD were studied up to 16 weeks. Cochran-Mantel-Haenszel weights were applied to calculate the adjusted incidence of adverse events. RESULTS: The incidence of conjunctivitis was higher (7·5%) with tralokinumab than with placebo (3·2%). Most events were mild or moderate in severity, and 78·6% and 73·9% of events resolved during the trial in the tralokinumab and placebo groups, respectively. Two (1·4%) events led to the permanent discontinuation of tralokinumab. An increased incidence of conjunctivitis, regardless of treatment group, was associated with more severe baseline AD, and history of allergic conjunctivitis/atopic keratoconjunctivitis, as well as the number of atopic comorbidities. LIMITATIONS: This analysis reports events up to week 16 only, with limited confirmation of conjunctivitis and its aetiology by an ophthalmologist, and insufficient reporting of ophthalmic treatments. CONCLUSIONS: Treatment with tralokinumab was associated with an increased incidence of conjunctivitis vs. placebo, but these cases were mostly mild and transient.

Validation of Sinhala version of Psoriasis Epidemiology Screening Tool.

INTRODUCTION/OBJECTIVES: Psoriatic arthritis (PsA) occurs in one-third of patients with psoriasis and mostly remains undetected leading to debilitating deforming arthritis, eventually. The Psoriasis Epidemiology Screening Tool (PEST) is a quick and valid tool, widely used to detect PsA in clinical practice, and it has been validated to many languages. In this study, we intended to validate a Sinhala version of the PEST and assess its psychometric properties. METHODS: The Sinhala version of the questionnaire was tested on 199 patients with psoriasis attending the dermatology clinic at a tertiary care National Hospital in Sri Lanka. Patients who were detected to have PsA previously (n = 5) and those with other rheumatologic conditions (n = 12) were excluded. All patients were examined by a dermatologist, and demographic and disease characteristics were obtained. All patients were assessed by two rheumatologists who were blinded to the answers provided in the questionnaire. The diagnosis of PsA was made based on the CASPAR criteria. RESULTS: We observed the total PEST score of 3 or more to be the best cutoff value to screen for PsA. This cutoff value showed the highest Youden index (sensitivity = 0.89, specificity = 0.95). In the ROC analysis, the area under the curve of the PEST_sv was 0.95 (SE 0.02, p < 0.001). PEST_sv total score showed a significant correlation with body surface area involved but not with Dermatology Life Quality Index or Psoriasis area and severity index score. CONCLUSION: The Sinhala version of PEST demonstrated satisfactory performance as a screening tool for PsA. Key Points • Psoriatic arthritis (PsA) is the most debilitating complication of psoriasis and lack of quick, valid screening tool is a limiting factor for early identification in Sri Lankan context. • Sinhala version of the Psoriasis Epidemiology Screening Tool (PEST_sv) was tested on 199 patients with psoriasis and examined for the diagnosis of PsA according to Classification of Psoriatic Arthritis (CASPAR) criteria. • PEST_sv score of 3 or more was observed to be the best cutoff value to screen for PsA with sensitivity and specificity of 0.89 and 0.95 respectively. • PEST_sv demonstrated satisfactory performance as a screening tool for PsA.

Efficacy and safety of dupilumab in Japanese adults with moderate-to-severe atopic dermatitis: a subanalysis of three clinical trials.

BACKGROUND: Dupilumab, a human monoclonal antibody, blocks the shared receptor unit for interleukin-4 and interleukin-13. International phase II and III studies have evaluated the efficacy and safety of dupilumab in adults with moderate-to-severe atopic dermatitis (AD), but the effects of dupilumab in Japanese patients have not been reported. OBJECTIVES: To evaluate the efficacy and safety of dupilumab in Japanese patients with moderate-to-severe AD. METHODS: We analysed the efficacy and safety of dupilumab in the Japanese cohorts of a 16-week, phase IIb dose-finding trial (AD-1021; NCT01859988); a 16-week, phase III, placebo-controlled monotherapy trial (LIBERTY AD SOLO 1; NCT02277743) and a 52-week, phase III, placebo-controlled study of dupilumab with topical corticosteroids (LIBERTY AD CHRONOS; NCT02260986). RESULTS: Twenty-seven, 106 and 117 Japanese patients were enrolled in AD-1021, SOLO 1 and CHRONOS, respectively. Baseline disease severity was numerically higher in the Japanese cohort than in the overall study population. Generally, dupilumab significantly improved signs and symptoms of AD, including pruritus and patient quality of life, compared with placebo in the Japanese cohort, consistent with the overall study population. The combined safety profile of dupilumab in the Japanese cohort was similar to that in the total study populations; dupilumab was associated with an increased incidence of injection-site reactions and conjunctivitis compared with placebo. Dupilumab was associated with rapid reduction in thymus and activation-regulated chemokine and gradual IgE reductions. CONCLUSIONS: Dupilumab alone or with topical corticosteroids improved signs and symptoms of AD, had an acceptable safety profile, and suppressed biomarkers of type 2 inflammation compared with placebo in Japanese adult patients with moderate-to-severe AD. What's already known about this topic? Differences in atopic dermatitis (AD) pathology have been reported between Asian and Western populations, in which distinct helper T-cell activation profiles have been observed. International clinical studies in adults with moderate-to-severe AD have evaluated the efficacy and safety of dupilumab, which blocks interleukin-4 and interleukin-13, key molecules in type 2 inflammation. The effects of dupilumab in Japanese patients specifically have not yet been reported. What does this study add? Dupilumab alone or with topical corticosteroids improved signs and symptoms of AD and had an acceptable safety profile compared with placebo in Japanese patients with moderate-to-severe AD. The effects were comparable with those observed in the overall study population. Reported immunological differences in AD pathology in Asian patients may be secondary to type 2 immune activation.

Benefit-risk profile of tofacitinib in patients with moderate-to-severe chronic plaque psoriasis: pooled analysis across six clinical trials.

BACKGROUND: Although existing psoriasis treatments are effective and well tolerated in many patients, there is still a need for new effective targeted treatment options. Tofacitinib is an oral Janus kinase inhibitor that has been investigated in patients with moderate-to-severe chronic plaque psoriasis. OBJECTIVES: To consider the benefits and risks of tofacitinib in patients with moderate-to-severe psoriasis. METHODS: Data were pooled from one phase II, four phase III and one long-term extension study comprising 5204 patient-years of tofacitinib treatment. Efficacy end points included patients achieving Physician's Global Assessments of 'clear' or 'almost clear', ≥ 75% and ≥ 90% reduction in Psoriasis Area and Severity Index (coprimary end points) and improvements in Dermatology Life Quality Index score, Hospital Anxiety and Depression Scale depression score and Itch Severity Item score, at weeks 16 and 52. Safety data were summarized for 3 years of tofacitinib exposure. RESULTS: Tofacitinib 5 and 10 mg twice daily (BID) showed superiority over placebo for all efficacy end points at week 16, with response maintained for 52 weeks of continued treatment. Tofacitinib improved patients' quality of life and was well tolerated. Rates of safety events of interest (except herpes zoster) were similar to those in the published literature and healthcare databases for other systemic psoriasis therapies. Tofacitinib 10 mg BID demonstrated greater efficacy than 5 mg BID. CONCLUSIONS: Tofacitinib has a benefit-risk profile in moderate-to-severe psoriasis consistent with that of other systemic treatments.

Sentinel node biopsy for high-risk cutaneous squamous cell carcinoma.

AIM: The use of sentinel node biopsy (SNB) has not been established for cutaneous squamous cell carcinoma (SCC), and its clinical significance has not been clarified. We investigated the usefulness of and indication criteria for SNB for cutaneous SCC. MATERIALS AND METHODS: Twenty-six patients with high-risk cutaneous SCC that had undergone SNB were retrospectively reviewed. SNB was performed with either the dye method or a combined dye and radioisotope method. RESULTS: Of the 26 patients, recurrence or metastasis was observed in 5 cases (19.2%). Six cases (23.1%) were sentinel node (SN) metastasis-positive. All cases that were SN metastasis-negative survived, and 4 of 6 SN metastasis-positive (66.7%) cases died of the original disease. The 3-year survival rates of all cases, SN metastasis-negative cases, and SN metastasis-positive cases were 82.2%, 100%, and 20.8%, respectively. Tumour thickness was a significant risk factor for SN metastasis (p = 0.049). Recurrence occurred in 4 of 7 cases involving external genitalia, 3 of which died. The 3-year survival rates of external genitalia and nongenital cases were 47.6% and 94.1%, respectively (p = 0.016). CONCLUSIONS: SNB aided the early discovery and treatment of latent lymph node metastasis and helped predict whether SN metastasis had occurred, and therefore helped predict patient prognosis. These results suggest that thickness of the primary lesion is an indication criterion for the use of SNB in cases of cutaneous SCC. SNB should be considered in cases where tumour thickness is ≥2 mm and actively performed in cases ≥5 mm.

One-year follow-up of zoster-associated pain in 764 immunocompetent patients with acute herpes zoster treated with famciclovir (FAMILIAR study).

BACKGROUND: Herpes zoster (HZ), a reactivation of varicella zoster virus manifested by skin blisters and neuralgia, can lead to postherpetic neuralgia in 10-20% of affected subjects. METHOD: In this study, a cohort of 764 patients with HZ was treated with 1500 mg/day of famciclovir for 7 days, and zoster-associated pain (ZAP) was monitored monthly thereafter for up to 12 months until pain resolution was achieved. Patients were questioned monthly by telephone, and pain was recorded using a numerical rating scale (NRS, 0-10). KEY RESULTS: A total of 751 of 764 (98.3%) patients completed follow-up. The percentage of patients with ZAP was 12.4% at day 90, 7.1% at 6 months and 4.0% at 1 year. After the third month, the NRS were 3 or less in most of the remaining patients with ZAP. Stratified analysis revealed significant persistence of ZAP in patients aged ≥50 years and in those aged ≥65 years, and in patients with either moderate-to-severe skin symptoms or severe pain at the initial consultation.Stratified analyses unexpectedly showed patients who commenced famciclovir at 0-2 days after onset of the eruption had a higher prevalence of ZAP at day 90 than those treated at 3-5 days or ≥6 days after rash onset (P = 0.0164, log-rank test). On further analysis, a higher proportion of patients (45.4%) treated at 0-2 days had moderate to severe symptoms compared with those treated at 3-5 days (40.5%) or ≥6 days (37.0%) (P = 0.0987, Cochran-Armitage test). CONCLUSION & INFERENCE: This study, with an exceptionally high follow-up rate, revealed several new findings, including the influence of disease severity on the delay between the onset of symptoms and seeking medical attention. Six adverse drug reactions were reported in five of 721 patients in the safety analysis, including two severe cases of vomiting and convulsions.

Rhabdomyolysis due to Multiple Wasp Stings.

Wasp sting is a relatively common arthropod assault, but is sometimes fatal because of anaphylaxis. Rhabdomyolysis is a serious condition, with destruction of striated muscles, and can be induced by various causes such as drugs, heart attacks, CRASH syndrome, and viper bites. Mass envenomation by multiple wasp stings can also cause rhabdomyolysis followed by acute renal failure, although it is extremely rare. We herein report a case who had an anaphylaxis-like reaction and rhabdomyolysis due to multiple wasp stings.

Topical vitamin D3 analogues induce thymic stromal lymphopoietin and cathelicidin in psoriatic skin lesions.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease of unknown aetiology, and an active form of vitamin D(3) (1α,25-dihydroxyvitamin D(3)) and its analogues (VD3As) are widely used topical reagents for psoriasis treatment. Besides their well-known calcium homeostasis functions, VD3As have been shown to have various immune-modulating effects including the induction of thymic stromal lymphopoietin (TSLP), a master cytokine for inducing Th2 inflammation, in mouse models, but not yet in human psoriasis. VD3As also have been shown to induce cathelicidin, an antimicrobial peptide and strong inducer of innate immunity. Cathelicidin is overexpressed in psoriatic skin lesions; however, its role in this disease seems as yet inconclusive. OBJECTIVES: To clarify whether topical VD3As induce TSLP and cathelicidin, and to examine the modulation of expression patterns of related cytokines in human psoriatic lesions. METHODS: Skin biopsy samples from psoriatic lesions with or without VD3A treatment were subjected to immunohistochemical staining and quantitative reverse transcription-polymerase chain reaction analyses to measure the expression levels of various cytokines. RESULTS: Significantly higher levels of TSLP, thymus and activation-related chemokine and CCR4 expression were observed in VD3A+ skin samples than in VD3A- samples. In contrast, significantly lower levels of interleukin (IL)-12/23 p40, IL-1α, IL-1ß and tumour necrosis factor (TNF)-α expression were observed in the VD3A+ samples than in the VD3A- samples. Expression of cathelicidin was elevated in VD3A+ samples. CONCLUSIONS: Topical VD3As induce TSLP and cathelicidin in psoriatic lesions, resulting in suppression of IL-12/23 p40, IL-1α, IL-1ß and TNF-α, thereby ameliorating psoriatic plaques.

Expression of insulin-like growth factor-1 receptor, p-AKT and p-ERK1/2 protein in extramammary Paget's disease.

BACKGROUND: The insulin-like growth factor-1 (IGF-1) receptor (R)-induced phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK)/ERK signal transduction cascade, which have critical roles in prevention of apoptosis and regulation of cell cycle progression, plays an important role in tumorigenesis. The expression of IGF-1R, AKT and ERK1/2 has been described in some human malignancies, but not in extramammary Paget's disease (EMPD). OBJECTIVES: To study the expression of IGF-1R, p-AKT and p-ERK1/2 in EMPD and to evaluate the relationships among them. METHODS: Thirty-six tissue samples of 34 patients with primary EMPD were subjected to immunohistochemical staining for IGF-1R, p-AKT and p-ERK1/2. RESULTS: Of thirty-six EMPD tissue samples, 34, 34 and 28 were positive for IGF-IR, p-AKT and p-ERK1/2 expression, respectively; 27, 23 and 17 of the 36 specimens stained positive for IGF-IR, p-AKT and p-ERK1/2 in more than half of Paget's cells, respectively. There were significant correlations between the IGF-1R and p-AKT expression as well as between IGF-1R and p-ERK1/2 expression. Taken together, these results indicate that IGF-1R is overexpressed, and AKT and ERK1/2 are frequently phosphorylated in EMPD. CONCLUSIONS: Our study shows that the expression of IGF-1R and the induction of p-AKT and the p-ERK1/2 pathway may play an important role in the pathogenesis of EMPD. The IGF-IR system might be a potential therapeutic target in EMPD.

Expression of phosphorylated Stat3, cyclin D1 and Bcl-xL in extramammary Paget disease.

BACKGROUND: Stat3 (Signal transducer and activator of transcription-3) is an oncogene that plays a critical role in regulating fundamental processes associated with malignant transformation and cell survival. It participates in oncogenesis through upregulation of genes encoding apoptosis inhibitors (Bcl-xL) and cell cycle regulators (cyclin D1). The expression of Stat3, Bcl-xL and cyclin D1 protein has not been investigated in extramammary Paget disease (EMPD). OBJECTIVES: To study the expression of phosphorylated Stat3 (p-Stat3), Bcl-xL and cyclin D1 protein in EMPD and to evaluate the relationships among them. METHODS: Thirty-six tissue samples from 34 patients with primary EMPD were subjected to immunohistochemical staining for p-Stat3, cyclin D1 and Bcl-xL. RESULTS: Thirty-five of 36 specimens were clearly positive for p-Stat3 in EMPD, while 30 of 36 and 32 of 36 were positive for cyclin D1 and Bcl-xL expression, respectively. In all of four invasive EMPD specimens, strong and frequent expression of these three molecules was evident; moreover, two invasive EMPD specimens with lymph nodal metastasis showed very strong nuclear and membranous p-Stat3 staining. Two metastatic lymph node specimens showed very strong nuclear and local membrane p-Stat3 staining. There were significant correlations between p-Stat3 and cyclin D1 expression and between p-Stat3 and Bcl-xL expression. CONCLUSIONS: Our study shows that the expression of p-Stat3, cyclin D1 and Bcl-xL may play a pivotal role in the pathogenesis of EMPD.

CD1a+, CD3+, CD4+, CD8+, CD68+ and cutaneous lymphocyte-associated antigen-positive cells in Bowen's disease.

BACKGROUND: Bowen's disease (BD) is a squamous cell carcinoma in situ that rarely invades into the underlying dermis. However, little is known about its immunohistology. Objectives To evaluate the relationship between the cytological properties of the tumour cells in BD and the host immune response. METHODS: We examined the expression of p53, proliferating cell nuclear antigen (PCNA) and Ki67 antigen, and the number of mitotic cells, together with the number of intratumoral and dermal infiltrating CD1a+, CD3+, CD4+, CD8+, CD68+ and cutaneous lymphocyte-associated antigen (CLA)+ cells in 18 cases of genital BD. RESULTS: When compared with normal genital skin (n = 10), there was a significantly higher number of mitotic cells as well as higher expression of p53+, PCNA+ and Ki67+ cells in BD. There was significant mutual correlation between CD3+, CD4+ and CD68+ cells in the tumoral epidermis. The number of CD1a+ Langerhans cells significantly decreased in BD epidermis; however, dermal CD1a+ cells were increased. Interestingly, numbers of dermal CD1a+ cells significantly correlated with those of intratumoral CD3+, CD4+ and CD68+ cells. In situ hybridization for human papillomavirus (HPV) demonstrated that HPV-infected BD had significantly less infiltration of intratumoral CD3+ cells and CLA+ cells. CONCLUSIONS: The present data suggest that dermal CD1a+ cells may participate in the immune surveillance and that HPV infection may interfere with the intratumoral infiltration of CLA+ cells in BD.