Pyoderma gangrenosum (PG) is a rare disease where a person's own immune system causes painful... more Pyoderma gangrenosum (PG) is a rare disease where a person's own immune system causes painful skin ulcers, due to a complex and poorly understood mechanism. PG is extremely rare, affecting 3–10 people per million people per year globally; however, when it does occur it bears significant impact on quality of life and increases the risk of death. Current treatment includes a combination of systemic steroids (systemic meaning taken inside the body rather than applied to the skin), immune suppressing drugs, and topical (applied to the skin) treatments, but after decades of research we still do not know the best (or “gold‐standard”) treatment regimen. In this study, authors from Canada aimed to systematically review all of the available research evidence on systemic treatments for PG in order to determine the best treatment regimen. After critically reviewing 3326 research studies, 41 studies were deemed relevant to this research question. What they found was that systemic corticosteroids, cyclosporine, and biologic agents were most commonly studied and were most effective at treating PG. Often, these were combined with topically applied drugs such as steroid cream. Nonetheless, amongst included studies, there was a low cure rate of 15–50% after months of treatment; while cure was sometimes achieved after two to four months, there was a high rate of recurrence of ulcers. Furthermore, the authors found that most studies on PG therapies are of poor quality and thus call for higher quality research in this field.
ImportanceHidradenitis suppurativa/acne inversa (HS) is a chronic inflammatory skin disease chara... more ImportanceHidradenitis suppurativa/acne inversa (HS) is a chronic inflammatory skin disease characterized by occlusion of hair follicles as a primary pathogenic factor. There are scarce data regarding the prevalence of HS.ObjectiveTo estimate overall HS prevalence.Data SourcesThis review and meta-regression analysis was conducted using the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline. The academic search included PubMed, Cochrane registry, ClinicalTrials.gov, and evidence by NHS UK and Trip databases from inception through May 2020. To analyze HS prevalence, only cross-sectional studies or baseline assessments of longitudinal cohorts using census-based surveys or probabilistic and nonprobabilistic epidemiologic methods were considered. The search terms were (prevalence OR incidence OR epidemiology) AND (hidradenitis suppurativa OR acne inversa OR Verneuil’s disease). No language restriction was applied.Study SelectionOriginal investigations that reported HS prevalence were included. After exclusion criteria were applied, 17 studies qualified for qualitative analysis, but only 16 studies were quantitatively assessed.Data Extraction and MeasuresTwo reviewers extracted data by age, diagnostic criteria, presence of any comorbidity, sample sizes, continent/location, sex, and other characteristics. Assessment of bias risk used the Joanna Briggs Institute Critical Appraisal Instrument for Studies Reporting Prevalence Data using random-effects models to synthesize available evidence.Main Outcomes and MeasuresHidradenitis suppurativa prevalence (with 95% CI) among the overall population and among subgroups. Between-study heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic).ResultsIn 16 quantitatively assessed studies included, prevalence estimates were reported only from Western European and Scandinavian countries, the US, and Australia. Meta-analysis with random effects, after adjusting for publication bias in the prevalence estimates, revealed a 0.40% prevalence (95% CI, 0.26%-0.63%) for HS. Studies based on clinical samples revealed a higher pooled prevalence of HS (1.7%) than population-based studies (0.3%).Conclusions and RelevanceThe findings of this systematic review and meta-regression analysis may help facilitate policy formulation, channeling funding and guiding principles for better disease diagnosis using universal valid tools and management.
Premalignant cervical lesions occur at the squamo-columnar junction and in endocervical epitheliu... more Premalignant cervical lesions occur at the squamo-columnar junction and in endocervical epithelium and squamous ectocervical epithelium, in descending order of frequency. However, previously only ectocervical cells have been clearly shown to be immortalized in vitro by the oncogenic human papillomaviruses (HPVs). This report describes the immortalization of normal human ecto- and endocervical epithelial cells by the intact HPV 16 genome. Ectocervical epithelial cells (HEC) became immortalized (HEC-16) without crisis while endocervical cells (HEN) were immortalized (HEN-16) after undergoing crisis. HEN-16 and HEC-16 contained integrated HPV 16 DNA, expressed E6 and E7 mRNA, and were aneuploid and nontumorigenic. They also expressed cytokeratins in a pattern similar to their distinct normal parental cells. These results suggest that both squamous and simple epithelial cells of uterine cervix are targets for immortalization by HPV 16.
Hidradenitis suppurativa (HS) is a chronic, inflammatory, debilitating skin disease. The aim of t... more Hidradenitis suppurativa (HS) is a chronic, inflammatory, debilitating skin disease. The aim of the study was to systematically review the literature and critically answer the question: In patients with HS, do cardiovascular risk factors appear at a significantly higher rate compared with controls? The main search was conducted in Medline, Embase and the Cochrane Central Register. Studies eligible for inclusion were of case–control, cross‐sectional and cohort design, and included comparison of any cardiovascular risk factor(s) in patients with HS with those of control groups. An I2 value > 50% was considered to show substantial heterogeneity. In this case, DerSimonian and Laird random‐effect models were considered to compute pooled odds ratios (OR). Otherwise, a fixed‐effects model was suitable. Nine studies, with 6174 patients with HS and 24 993 controls, were included. Significant association of HS with obesity [OR 3·45, 95% confidence interval (CI) 2·20–5·38, P < 0·001], central obesity (OR 2·97, 95% CI 1·41–6·25, P = 0·004), active smoking (OR 4·34, 95% CI 2·48–7·60, P < 0·001), history of smoking (OR 6·34, 95% CI 2·41–16·68, P < 0·001), hypertriglyceridemia (OR 1·67, 95% CI 1·14–2·47, P = 0·009), low high‐density lipoprotein (HDL) (OR 2·48, 95% CI 1·49–4·16, P < 0·001), diabetes (OR 2·85, 95% CI 1·34–6·08, P = 0·007) and metabolic syndrome (OR 2·22, 95% CI 1·62–3·06, P < 0·001) was detected. Associations were significant both in population and hospital patients with HS, with hospital HS groups having uniformly higher ORs than the population HS groups. Causality could not be assessed. Heterogeneity was substantial in all analyses. This systematic review indicated that cardiovascular risk factors appear at a significantly higher rate in patients with HS compared with controls. The need for screening of patients with HS for modifiable cardiovascular risks is emphasized.
Journal of The European Academy of Dermatology and Venereology, Aug 25, 2021
BackgroundLong‐term, real‐word data are needed to help manage patients with hidradenitis suppurat... more BackgroundLong‐term, real‐word data are needed to help manage patients with hidradenitis suppurativa (HS) through this recurrent, painful and debilitating disease.ObjectivesTo primarily measure real‐world effectiveness of adalimumab in HS and to secondarily observe clinical course of HS in the light of patients’ response.MethodsIn SOLACE, adults with moderate‐to‐severe HS in need for change in ongoing therapy were treated with adalimumab for up to 52 weeks as per physician’s medical practice. Treatment effectiveness was measured by Hidradenitis Suppurativa Clinical Response (HiSCR). Inflammatory nodules, abscesses and draining fistulas were counted, Hurley stage was assessed, and disease severity was rated using the International HS Severity Scoring System (IHS4). A post hoc analysis further explored the HiSCR response by abscess and inflammatory nodule (AN) count at baseline (low, medium and high) and gender. Spontaneously reported safety events were collected.ResultsFrom 23 Canadian centres, 69% of the 138 patients achieved HiSCR at week 24, which increased to 82% and 75% at week 52 in patients with medium and high AN counts, respectively. Gender (4 times the odds for female) and age at HS onset (5% decrease with each additional year) had an effect on achieving HiSCR. Treatment with adalimumab led to an important decrease in number of lesions in responders, with most gains observed in inflammatory nodules, more frequently in the lower body area of patients in the high AN count group. The IHS4 scores of responders were substantially lowered, with a larger decrease in patients of the high AN count group. No new safety signal was detected.ConclusionsThe effectiveness of adalimumab was maintained during this 1‐year period, and an optimal gain was documented for patients with medium and high AN counts. These real‐world data support a prompt treatment of HS patients and the use of IHS4 to monitor treatment.
Psoriasis is associated with significant physical, psychological, social and economic burden, the... more Psoriasis is associated with significant physical, psychological, social and economic burden, the cumulative effect of which may result in failure to achieve &#39;full life potential&#39; in some patients, termed &#39;cumulative life course impairment&#39; (CLCI). In this concept, the burden of stigmatization, and physical and psychological comorbidities (risk factors for cumulative impairment) and coping strategies and external factors (having potential moderating effects), interact to cause lifetime impairment. Components of CLCI are supported by cross-sectional data; however, the cumulative nature of impairment in patients with psoriasis is not yet established. Nonetheless, CLCI makes intuitive sense to many dermatologists who recognize the cumulative impact of psoriasis on the lives of some patients. This supplement explores the causes and mechanisms of CLCI qualitatively by presenting cases which are representative of typical patients with moderate-to-severe psoriasis. These cases demonstrate the effect of psoriasis in influencing major life-changing decisions and altering the course of patients&#39; lives, preventing patients from attaining their life goals, pursuing their chosen career, gaining a desired educational level, developing social relationships, gaining full pleasure from family life or having children. All these patients believe that their lives would have taken a different course had they not had psoriasis. Additional research to determine how CLCI occurs and to identify the risk factors for cumulative impairment is required. Understanding the key risk factors for CLCI may help physicians identify patients who are more vulnerable to the cumulative impact of psoriasis, resulting in more appropriate treatment decisions earlier in the disease course.
Journal of The American Academy of Dermatology, Dec 1, 2002
In previous phase II studies, alefacept significantly improved psoriasis and was well tolerated. ... more In previous phase II studies, alefacept significantly improved psoriasis and was well tolerated. The clinical response to alefacept was durable. Our purpose was to further evaluate efficacy and tolerability of alefacept in a phase III study of patients (n = 553) with chronic plaque psoriasis. Two 12-week courses of once-weekly intravenous alefacept 7.5 mg or placebo were given in a randomized double-blind study; patients were followed up for 12 weeks after each course. During treatment and follow-up of course 1, a 75% or greater reduction in the Psoriasis Area Severity Index (PASI) was achieved by 28% of alefacept-treated and 8% of placebo-treated patients (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.001). Patients who received a single course of alefacept and achieved a 75% or greater reduction from baseline PASI during or after treatment, without the use of phototherapy or systemic therapies, maintained a 50% or greater reduction in PASI for a median duration of more than 7 months. Among patients who received 2 courses of alefacept, 40% and 71% of patients achieved a 75% or greater and 50% or greater reduction in PASI, respectively, during the study period. Alefacept was well tolerated over both courses. In course 1, the incidence of transient chills was higher in the alefacept group compared with the placebo group; more than 90% of cases occurred within 24 hours after the first few doses. Alefacept significantly improved psoriasis and produced durable clinical improvements among patients who responded. A second course of alefacept increased efficacy and was equally well tolerated.
Pyoderma gangrenosum (PG) is a rare disease where a person's own immune system causes painful... more Pyoderma gangrenosum (PG) is a rare disease where a person's own immune system causes painful skin ulcers, due to a complex and poorly understood mechanism. PG is extremely rare, affecting 3–10 people per million people per year globally; however, when it does occur it bears significant impact on quality of life and increases the risk of death. Current treatment includes a combination of systemic steroids (systemic meaning taken inside the body rather than applied to the skin), immune suppressing drugs, and topical (applied to the skin) treatments, but after decades of research we still do not know the best (or “gold‐standard”) treatment regimen. In this study, authors from Canada aimed to systematically review all of the available research evidence on systemic treatments for PG in order to determine the best treatment regimen. After critically reviewing 3326 research studies, 41 studies were deemed relevant to this research question. What they found was that systemic corticosteroids, cyclosporine, and biologic agents were most commonly studied and were most effective at treating PG. Often, these were combined with topically applied drugs such as steroid cream. Nonetheless, amongst included studies, there was a low cure rate of 15–50% after months of treatment; while cure was sometimes achieved after two to four months, there was a high rate of recurrence of ulcers. Furthermore, the authors found that most studies on PG therapies are of poor quality and thus call for higher quality research in this field.
ImportanceHidradenitis suppurativa/acne inversa (HS) is a chronic inflammatory skin disease chara... more ImportanceHidradenitis suppurativa/acne inversa (HS) is a chronic inflammatory skin disease characterized by occlusion of hair follicles as a primary pathogenic factor. There are scarce data regarding the prevalence of HS.ObjectiveTo estimate overall HS prevalence.Data SourcesThis review and meta-regression analysis was conducted using the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline. The academic search included PubMed, Cochrane registry, ClinicalTrials.gov, and evidence by NHS UK and Trip databases from inception through May 2020. To analyze HS prevalence, only cross-sectional studies or baseline assessments of longitudinal cohorts using census-based surveys or probabilistic and nonprobabilistic epidemiologic methods were considered. The search terms were (prevalence OR incidence OR epidemiology) AND (hidradenitis suppurativa OR acne inversa OR Verneuil’s disease). No language restriction was applied.Study SelectionOriginal investigations that reported HS prevalence were included. After exclusion criteria were applied, 17 studies qualified for qualitative analysis, but only 16 studies were quantitatively assessed.Data Extraction and MeasuresTwo reviewers extracted data by age, diagnostic criteria, presence of any comorbidity, sample sizes, continent/location, sex, and other characteristics. Assessment of bias risk used the Joanna Briggs Institute Critical Appraisal Instrument for Studies Reporting Prevalence Data using random-effects models to synthesize available evidence.Main Outcomes and MeasuresHidradenitis suppurativa prevalence (with 95% CI) among the overall population and among subgroups. Between-study heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic).ResultsIn 16 quantitatively assessed studies included, prevalence estimates were reported only from Western European and Scandinavian countries, the US, and Australia. Meta-analysis with random effects, after adjusting for publication bias in the prevalence estimates, revealed a 0.40% prevalence (95% CI, 0.26%-0.63%) for HS. Studies based on clinical samples revealed a higher pooled prevalence of HS (1.7%) than population-based studies (0.3%).Conclusions and RelevanceThe findings of this systematic review and meta-regression analysis may help facilitate policy formulation, channeling funding and guiding principles for better disease diagnosis using universal valid tools and management.
Premalignant cervical lesions occur at the squamo-columnar junction and in endocervical epitheliu... more Premalignant cervical lesions occur at the squamo-columnar junction and in endocervical epithelium and squamous ectocervical epithelium, in descending order of frequency. However, previously only ectocervical cells have been clearly shown to be immortalized in vitro by the oncogenic human papillomaviruses (HPVs). This report describes the immortalization of normal human ecto- and endocervical epithelial cells by the intact HPV 16 genome. Ectocervical epithelial cells (HEC) became immortalized (HEC-16) without crisis while endocervical cells (HEN) were immortalized (HEN-16) after undergoing crisis. HEN-16 and HEC-16 contained integrated HPV 16 DNA, expressed E6 and E7 mRNA, and were aneuploid and nontumorigenic. They also expressed cytokeratins in a pattern similar to their distinct normal parental cells. These results suggest that both squamous and simple epithelial cells of uterine cervix are targets for immortalization by HPV 16.
Hidradenitis suppurativa (HS) is a chronic, inflammatory, debilitating skin disease. The aim of t... more Hidradenitis suppurativa (HS) is a chronic, inflammatory, debilitating skin disease. The aim of the study was to systematically review the literature and critically answer the question: In patients with HS, do cardiovascular risk factors appear at a significantly higher rate compared with controls? The main search was conducted in Medline, Embase and the Cochrane Central Register. Studies eligible for inclusion were of case–control, cross‐sectional and cohort design, and included comparison of any cardiovascular risk factor(s) in patients with HS with those of control groups. An I2 value > 50% was considered to show substantial heterogeneity. In this case, DerSimonian and Laird random‐effect models were considered to compute pooled odds ratios (OR). Otherwise, a fixed‐effects model was suitable. Nine studies, with 6174 patients with HS and 24 993 controls, were included. Significant association of HS with obesity [OR 3·45, 95% confidence interval (CI) 2·20–5·38, P < 0·001], central obesity (OR 2·97, 95% CI 1·41–6·25, P = 0·004), active smoking (OR 4·34, 95% CI 2·48–7·60, P < 0·001), history of smoking (OR 6·34, 95% CI 2·41–16·68, P < 0·001), hypertriglyceridemia (OR 1·67, 95% CI 1·14–2·47, P = 0·009), low high‐density lipoprotein (HDL) (OR 2·48, 95% CI 1·49–4·16, P < 0·001), diabetes (OR 2·85, 95% CI 1·34–6·08, P = 0·007) and metabolic syndrome (OR 2·22, 95% CI 1·62–3·06, P < 0·001) was detected. Associations were significant both in population and hospital patients with HS, with hospital HS groups having uniformly higher ORs than the population HS groups. Causality could not be assessed. Heterogeneity was substantial in all analyses. This systematic review indicated that cardiovascular risk factors appear at a significantly higher rate in patients with HS compared with controls. The need for screening of patients with HS for modifiable cardiovascular risks is emphasized.
Journal of The European Academy of Dermatology and Venereology, Aug 25, 2021
BackgroundLong‐term, real‐word data are needed to help manage patients with hidradenitis suppurat... more BackgroundLong‐term, real‐word data are needed to help manage patients with hidradenitis suppurativa (HS) through this recurrent, painful and debilitating disease.ObjectivesTo primarily measure real‐world effectiveness of adalimumab in HS and to secondarily observe clinical course of HS in the light of patients’ response.MethodsIn SOLACE, adults with moderate‐to‐severe HS in need for change in ongoing therapy were treated with adalimumab for up to 52 weeks as per physician’s medical practice. Treatment effectiveness was measured by Hidradenitis Suppurativa Clinical Response (HiSCR). Inflammatory nodules, abscesses and draining fistulas were counted, Hurley stage was assessed, and disease severity was rated using the International HS Severity Scoring System (IHS4). A post hoc analysis further explored the HiSCR response by abscess and inflammatory nodule (AN) count at baseline (low, medium and high) and gender. Spontaneously reported safety events were collected.ResultsFrom 23 Canadian centres, 69% of the 138 patients achieved HiSCR at week 24, which increased to 82% and 75% at week 52 in patients with medium and high AN counts, respectively. Gender (4 times the odds for female) and age at HS onset (5% decrease with each additional year) had an effect on achieving HiSCR. Treatment with adalimumab led to an important decrease in number of lesions in responders, with most gains observed in inflammatory nodules, more frequently in the lower body area of patients in the high AN count group. The IHS4 scores of responders were substantially lowered, with a larger decrease in patients of the high AN count group. No new safety signal was detected.ConclusionsThe effectiveness of adalimumab was maintained during this 1‐year period, and an optimal gain was documented for patients with medium and high AN counts. These real‐world data support a prompt treatment of HS patients and the use of IHS4 to monitor treatment.
Psoriasis is associated with significant physical, psychological, social and economic burden, the... more Psoriasis is associated with significant physical, psychological, social and economic burden, the cumulative effect of which may result in failure to achieve &#39;full life potential&#39; in some patients, termed &#39;cumulative life course impairment&#39; (CLCI). In this concept, the burden of stigmatization, and physical and psychological comorbidities (risk factors for cumulative impairment) and coping strategies and external factors (having potential moderating effects), interact to cause lifetime impairment. Components of CLCI are supported by cross-sectional data; however, the cumulative nature of impairment in patients with psoriasis is not yet established. Nonetheless, CLCI makes intuitive sense to many dermatologists who recognize the cumulative impact of psoriasis on the lives of some patients. This supplement explores the causes and mechanisms of CLCI qualitatively by presenting cases which are representative of typical patients with moderate-to-severe psoriasis. These cases demonstrate the effect of psoriasis in influencing major life-changing decisions and altering the course of patients&#39; lives, preventing patients from attaining their life goals, pursuing their chosen career, gaining a desired educational level, developing social relationships, gaining full pleasure from family life or having children. All these patients believe that their lives would have taken a different course had they not had psoriasis. Additional research to determine how CLCI occurs and to identify the risk factors for cumulative impairment is required. Understanding the key risk factors for CLCI may help physicians identify patients who are more vulnerable to the cumulative impact of psoriasis, resulting in more appropriate treatment decisions earlier in the disease course.
Journal of The American Academy of Dermatology, Dec 1, 2002
In previous phase II studies, alefacept significantly improved psoriasis and was well tolerated. ... more In previous phase II studies, alefacept significantly improved psoriasis and was well tolerated. The clinical response to alefacept was durable. Our purpose was to further evaluate efficacy and tolerability of alefacept in a phase III study of patients (n = 553) with chronic plaque psoriasis. Two 12-week courses of once-weekly intravenous alefacept 7.5 mg or placebo were given in a randomized double-blind study; patients were followed up for 12 weeks after each course. During treatment and follow-up of course 1, a 75% or greater reduction in the Psoriasis Area Severity Index (PASI) was achieved by 28% of alefacept-treated and 8% of placebo-treated patients (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.001). Patients who received a single course of alefacept and achieved a 75% or greater reduction from baseline PASI during or after treatment, without the use of phototherapy or systemic therapies, maintained a 50% or greater reduction in PASI for a median duration of more than 7 months. Among patients who received 2 courses of alefacept, 40% and 71% of patients achieved a 75% or greater and 50% or greater reduction in PASI, respectively, during the study period. Alefacept was well tolerated over both courses. In course 1, the incidence of transient chills was higher in the alefacept group compared with the placebo group; more than 90% of cases occurred within 24 hours after the first few doses. Alefacept significantly improved psoriasis and produced durable clinical improvements among patients who responded. A second course of alefacept increased efficacy and was equally well tolerated.
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