Which Health-Related Quality of Life Items Most Affect Acne Patients?

BACKGROUND: Health-related quality of life (HRQoL) assessment in patients with acne is recommended by several national guidelines. There are several acne-specific HRQoL instruments. OBJECTIVES: Participants of the European Academy of Dermatology and Venereology (EADV) Task Forces (TFs) on QoL and Patient Oriented Outcomes (PO) and Acne, Rosacea, and Hidradenitis Suppurativa (ARHS) agreed to scrutinize aspects of existing acne-specific HRQoL instruments for their relevance in international study. METHODS: Consensus agreement on items related to QoL was reached after an independent assessment by seven experts from the EADV TFs on QoL and PO, and a list of 97 items was prepared and proposed to a group of acne patients. In order to have data from patients to check if any important topics were overseen, another group of acne patients from participating countries was asked to list how acne influenced different aspects of their lives. RESULTS: Based on results obtained from 601 acne patients from nine countries, most of the items and topics showed low relevance for acne patients especially during the previous month or shorter time periods. Based on percentage of relevance and factor analysis, short (6 items) and long (45 items) lists of the most relevant topics were formed. CONCLUSION: Most of the items and topics from the initial list showed low relevance for acne patients. None of the identified acne-specific HRQoL instruments contain all the items that were deemed most relevant to acne patients. For this reason, participating members of the EADV TFs on QoL and PO, and ARHs are in the process of developing a new acne-specific HRQoL instrument.

Value of reflectance confocal microscopy for the monitoring of rosacea during treatment with topical ivermectin.

BACKGROUND: Reflectance confocal microscopy (RCM) enables noninvasive Demodex mite detection in rosacea. Objective scoring of rosacea severity is currently lacking. OBJECTIVES: To determine the value of RCM for monitoring Demodex, inflammation and vascular parameters in rosacea during treatment. METHODS: In 20 rosacea patients, clinical and RCM examination were performed before, during, and 12 weeks after a 16-week treatment course with topical ivermectin. Using RCM, number of mites and inflammatory cells, epidermal thickness, and vascular density and diameter were measured. RCM features were correlated with clinical assessment. RESULTS: Treatment resulted in clinical reduction of inflammatory lesions. Mites were detected in 80% of patients at baseline, 30% at week 16, and 63% at week 28. The number of mites reduced significantly during treatment, but no changes in inflammatory cells, epidermal thickness or vascular parameters were observed. Correlation between number of inflammatory lesions and mites was low. None of the RCM variables were significant predictors for clinical success. CONCLUSIONS: RCM enables anti-inflammatory effect monitoring of topical ivermectin by determining mite presence. Quantifying exact mite number, and inflammatory and vascular characteristics is challenging due to device limitations. In its current form, RCM seems of limited value for noninvasive follow-up of rosacea in clinical practice.

[Terbinafine resistance explains treatment failure in a patient with tinea corporis]. / Terbinafineresistentie als verklaring voor therapiefalen bij tinea corporis.

BACKGROUND: Tinea corporis is a superficial fungal infection of the limbs, chest or back caused by dermatophytes. Local antifungal treatment is often sufficient to treat tinea corporis. Systemic treatment may be needed in more severe cases, in immunocompromised patients or when treatment failure is documented. Treatment failure is relative common and frequent causes are low compliance, low systemic antifungal drug concentrations, reduced penetration of topical agents or an immunocompromised status. Recently, antifungal resistance has been documented in dermatophytes. CASE DESCRIPTION: We describe a patient with terbinafine treatment failure caused by antifungal drug resistance. CONCLUSION: The frequency of terbinafine resistance in the Netherlands is unknown as no surveillance is performed. Recent reports from both India and European countries indicate that antifungal resistance should be considered in patients with terbinafine treatment failure.

Value of GPSkin for the measurement of skin barrier impairment and for monitoring of rosacea treatment in daily practice.

BACKGROUND: Stratum corneum hydration (SCH) and transepidermal water loss (TEWL) provide useful information about skin barrier function. This study aimed to determine the value of GPSkin Pro, a new handheld device determining both SCH and TEWL, to measure skin barrier impairment and to monitor barrier function in rosacea in daily practice. MATERIALS AND METHODS: Two pilots were performed. Pilot 1: in 27 healthy participants, GPSkin SCH and TEWL were compared to Aquaflux® and Epsilon® values at the forearm before and after skin barrier perturbation via tapestripping. Moreover, GPSkin values were measured at both cheeks without intervention. Pilot 2: in 16 rosacea patients, GPSkin measurements were performed at the forearm, and at both cheeks before and during anti-inflammatory treatment. They were compared to clinical symptoms and to GPSkin values from pilot 1. RESULTS: Pilot 1: after merging data from before and after tapestripping, a strong correlation was observed between GPSkin TEWL and Aquaflux® (Rs  = 0.9256), and GPSkin SCH and Epsilon® (Rs  = 0.8798). Pilot 2: SCH was significantly lower at the cheeks of rosacea patients compared to controls, with a normalizing trend during successful treatment. TEWL was comparable among patients and controls and did not change during treatment at all locations. CONCLUSION: The GPSkin determines TEWL and SCH accurately in healthy and impaired skin barrier state and can monitor skin barrier function in rosacea during treatment. The GPSkin device is much more practical compared to previous skin barrier tools when used in clinical practice. Its further validation in other inflammatory skin diseases is recommended.

Evaluation of a simple image-based tool to quantify facial erythema in rosacea during treatment.

BACKGROUND: Facial erythema is a common symptom in rosacea. To overcome subjectivity in scoring erythema severity, objective redness quantification is desirable. This study evaluated an image-based erythema quantification tool to monitor facial erythema in rosacea patients during treatment and compared these values to clinical scores. MATERIALS AND METHODS: Twenty-one rosacea patients were treated with topical ivermectin for 16 weeks. Clinical erythema scores and clinical photographs were taken at week 0, 6, 16 and 28. Using ImageJ, RGB images were split into red, green and blue channels to measure the green/red ratio of lesional skin compared with a green sticker. With CIELAB colour space, a* (indicating colour from green to red) of a lesional and non-lesional facial site was measured, calculating ∆a*. Interobserver concordance and correlation between quantitative and clinical erythema values were determined. RESULTS: Treatment resulted in reduction of clinical erythema scores. No significant changes in red/green ratios were measured. Lesional a* and ∆a* significantly decreased from baseline to week 16 and 28 (P < .05). A weak correlation existed between clinical scores and lesional a* (Rs  = 0.37), and between clinical scores and ∆a* (Rs  = 0.30), with a clear trend towards higher a* and ∆a* for higher clinical scores. Interobserver correlation was high (R2  = 0.82). CONCLUSION: ImageJ is a simple, rapid, objective and reproducible tool to monitor erythema in rosacea patients during treatment. The photographs allow retrospective analysis, evaluation of large and small lesions, and discrimination of subtle redness differences. We recommend using lesional a* to monitor erythema of inflammatory dermatoses in clinical practice.

Use of beta-blockers for rosacea-associated facial erythema and flushing: A systematic review and update on proposed mode of action.

BACKGROUND: Flushing and erythema are frequent skin symptoms in rosacea. Because their adequate treatment remains a clinical challenge, new treatment options are explored, such as oral ß-blockers. OBJECTIVES: To evaluate the efficacy of oral ß-blockers for rosacea-associated facial flushing and erythema. METHODS: PubMed, Embase, Web of Science, and Cochrane Library were systematically searched, including studies providing original data on the efficacy of oral ß-blockers in rosacea patients with facial flushing and/or persistent erythema. Risk of bias was assessed using the Cochrane Risk of Bias tool, Newcastle-Ottawa scale, and Quality in Prognosis Studies tool. RESULTS: Nine studies evaluating the use of carvedilol, propranolol, nadolol, and ß-blockers in general were included. Articles studying carvedilol and propranolol showed a large reduction of erythema and flushing during treatment with a rapid onset of symptom control. Bradycardia and hypotension were the most commonly described adverse events. LIMITATIONS: Most studies had a retrospective design with a small sample size, and outcome measurement was often subjective. CONCLUSIONS: Oral ß-blockers could be an effective treatment option for patients with rosacea with facial erythema and flushing that does not respond to conventional therapy. Larger prospective trials with objective outcome assessment are needed to validate the promising results of these studies.

Rosacea and Use of Continuous Positive Airway Pressure Mask for Obstructive Sleep Apnea Syndrome: Report of Five Cases.

Rosacea is a chronic inflammatory skin disease of unknown etiology. We noticed a series of patients who were diagnosed with rosacea as well as obstructive sleep apnea syndrome (OSAS), for which they used a continuous positive airway pressure (CPAP) mask. This case series aims to give insight in the possible relationship between rosacea and the use of a CPAP mask for OSAS. We present five patients with OSAS who developed or worsened rosacea symptoms after use of a CPAP mask covering nose and mouth. Two patients showed centrofacial symptoms consistent with the shape of the CPAP mask; three patients had nasal cutaneous symptoms. It is postulated that the occlusive effect of the CPAP mask, increasing skin humidity and temperature, can induce primary symptoms in patients with an underlying sensibility for rosacea. This could have implications for choice of CPAP mask type and topical therapeutic options for rosacea.

The value of (video)dermoscopy in the diagnosis and monitoring of common inflammatory skin diseases: a systematic review.

Clinical diagnosis of inflammatory skin disorders (ISD), including hair and nail disorders, is not always straightforward. Not uncommonly, a punch biopsy may be required. Dermoscopy and videodermoscopy (VD) are non-invasive techniques that are used for in vivo examination of the skin, hair, and nails. Both techniques can contribute to determining the accurate diagnosis of common ISD and can be useful for assessing treatment effects. However, the value of VD over conventional dermoscopy for ISD is undetermined. We systematically searched and reviewed the current published literature on ISD evaluated by VD and dermoscopy in the electronic databases, PubMed, Embase, the Cochrane Library, and Web of Science. All studies were assessed for quality using the Strengthening the Reporting of Observational studies in Epidemiology and Cochrane checklist. Finally, 82 studies were eligible for inclusion. An overview is presented of the (video)dermoscopic features for common ISD diagnoses, with details regarding the level of accuracy and features that should be monitored during treatment. Although both techniques are promising, studies of high methodological quality are necessary to determine the value of VD over conventional dermoscopy for common ISD.

Results of three analytical approaches on long-term efficacy of etanercept for psoriasis in daily practice.

BACKGROUND: A problem encountered when analyzing long-term efficacy is that the number of patients in follow-up decreases with time for different reasons. The method used to account for missing observations for the therapy under analysis has a great influence on the inference of efficacy. OBJECTIVE: To describe the long-term efficacy of etanercept for psoriasis in daily practice using 3 analytical approaches. METHODS: Prospective data from a cohort of patients with psoriasis treated with etanercept for at least 24 weeks were analyzed using 3 analytical approaches: as treated analysis, intention-to-treat analysis (ITT) with last observation carried forward (LOCF) and intention-to-treat analysis with modified nonresponder imputation (modified NRI). RESULTS: One hundred thirty-one patients were treated with etanercept during 134 treatment episodes with a mean treatment duration of 2.7 years. The maximum follow-up was 6.0 years. The methodological approach chosen had a great influence. Psoriasis Area and Severity Index (PASI) 75 response rates varied from 60% in the as-treated approach to 34% in LOCF and to 29% in modified NRI at week 264. LIMITATIONS: All analytical methods applied have limitations. Other outcome measures could be used to overcome the bias introduced by each method of analysis, such as drug survival. CONCLUSIONS: The methodological approach chosen to analyze long-term efficacy data has a great influence on the inferences that may be drawn regarding the degree of efficacy. Therefore we support the use of different methods to present long-term efficacy data.

Appropriate infliximab infusion dosage and monitoring: results of a panel meeting of rheumatologists, dermatologists and gastroenterologists.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Infliximab is an effective treatment for rheumatoid arthritis, ankylosing spondylitis, Crohn's disease (both adult and paediatric), ulcerative colitis, psoriatic arthritis and plaque psoriasis and national and international guidelines have been developed for each indication. WHAT THIS STUDY ADDS: This study is the first study which compared current international, national and local guidelines from the medical specialties involved in the treatment with infliximab on the following topics: indication, dosage, synergy and monitoring of vital signs. AIMS: Infliximab, an anti-TNF biologic agent, is currently indicated and reimbursed for rheumatoid arthritis, ankylosing spondylitis, Crohn's disease (both adult and paediatric), ulcerative colitis, psoriatic arthritis and plaque psoriasis. Development of national and international guidelines for rheumatology, gastroenterology and dermatology, was mostly based on clinical studies and expert opinion. The aim of this study was to compare available guidelines and local protocols for rheumatology, dermatology and gastroenterology, regarding dosage of infliximab, synergy of infliximab with concomitant medication and monitoring of vital signs during infliximab administration, for achieving optimal care. METHODS: Current international, national and local guidelines on the use of infliximab were reviewed and compared, differences and shortcomings were identified, and optimal treatment schedules discussed during a meeting (July 2008) of clinical experts and researchers from three departments of a Dutch university hospital. RESULTS: Recommended dosages of infliximab are not equal for different indications. Loss of response to infliximab is a common problem encountered within the three medical specialties, but indications for adjustments in treatment schedules are lacking in all of the guidelines. Monitoring of vital signs (blood pressure, pulse, temperature) during infusion with infliximab is common practice and recommended by some guidelines. Routine measurement of vital signs is not of any value in predicting or recognizing acute infusion reactions, in our experience, and this is confirmed by literature on inflammatory bowel disease. CONCLUSION: Different indications encompass different dosing schedules. National and internal guidelines do not provide advice regarding loss of response. Routine measurement of vital signs during infusion is not valuable in detecting acute infusion reactions and should only be performed in case of an acute infusion reaction. These topics need to be studied in future studies and covered in future guidelines.

Extent and clinical consequences of antibody formation against adalimumab in patients with plaque psoriasis.

OBJECTIVES: To investigate the extent antibodies to adalimumab are formed in patients with plaque psoriasis and whether these antibodies have clinical consequences. Also, to examine the relationship between antibodies to adalimumab and adalimumab trough titers. DESIGN: Prospective observational cohort study. SETTING: Two Dutch dermatology departments in university hospitals. PATIENTS: All consecutive patients starting a regimen of adalimumab for chronic plaque psoriasis. Patients were screened and fulfilled the Dutch reimbursement criteria for adalimumab to treat psoriasis. INTERVENTION: Adalimumab treatment (per label). MAIN OUTCOME MEASURES: The titer of antibodies to adalimumab, the adalimumab trough concentration, and the Psoriasis Area and Severity Index at weeks 12 and 24. RESULTS: Antibodies to adalimumab were detected in 13 of 29 patients (45%) during 24 weeks of treatment. Differences in response rates among patients with low, high, and no titers of antibodies to adalimumab were significant at weeks 12 and 24 (P = .04 and P < .001, respectively). The median adalimumab trough concentrations varied significantly among patients with low, high, and no titers of antibodies to adalimumab (1.30 [range, 0.01-5.50], 0.0 [range, 0.0-0.0], and 9.6 [range, 0.0-22.6] mg/L, respectively; P < .001). At week 24, the median adalimumab trough concentrations also differed significantly among good responders, moderate responders, and nonresponders (9.7 [range, 0.0-22.6], 8.9 [range, 3.2-12.6], and 0.0 [range, 0.0-13.3] mg/L, respectively; P = .01). CONCLUSION: Antibodies to adalimumab are associated with lower serum adalimumab trough concentrations and with nonresponse or loss of response to adalimumab in patients with plaque psoriasis.

Analysis of 4-year Dutch reimbursement application data of biological therapies for psoriatic arthritis.

OBJECTIVES: To get the approval for reimbursement of biological therapies for PsA, patients need to fulfil specific criteria in many countries. The aim of this study was to evaluate the 4-year Dutch reimbursement application data, including the diagnostic, disease activity and response criteria that were applied for treatment of PsA with biologics. METHODS: All initial and follow-up applications for approval of treatment with biologics were included for investigation. Data were analysed descriptively with regard to application characteristics, patient characteristics and response to therapy. RESULTS: In the period studied, 3723 application forms of 1991 patients were received. This concerned 2118 initial treatment applications and 1605 follow-up applications. Of all initial treatment applications, 2003 (94.6%) were approved. The major part of all applications concerned requests for etanercept (59.1%), followed by adalimumab (38.2%). Patients were suffering from polyarthritis in most cases (63.1%). MTX was used by nearly all patients, but only 55.8% had used the required dosage of 25 mg/week. Approximately 79.4% of all patients met the response criteria after 3 months of treatment. The mean number of affected joints declined from 7.7 at first application to 1.4 at follow-up. The initial visual analogue scale (VAS) score indicated by patients decreased from 71.2 to 24.1 at follow-up. The VAS score indicated by physicians decreased from 66.0 to 18.4. CONCLUSIONS: Biologics are expensive, but highly effective in the treatment of PsA. Careful compilation of treatment and reimbursement criteria is important for patients as well as for physicians and health insurance companies.

Cardiovascular risk factors in high-need psoriasis patients and its implications for biological therapies.

BACKGROUND: The associations between psoriasis and cardiovascular risk factors are reported to be stronger as psoriasis severity increases. This makes studying cardiovascular risk factors in high-need psoriasis patients, eligible for biological therapy, interesting. OBJECTIVE: To survey the prevalence of cardiovascular risk factors in high-need psoriasis patients and to compare these data to patients with other dermatological diseases. Furthermore, the implications of these findings for treatment with biologics were outlined. METHODS: The prevalence of cardiovascular risk factors was investigated in a high-need psoriatic patient cohort and compared to patients with other skin diseases who filled out a questionnaire about the presence of cardiovascular risk factors. RESULTS: A significantly higher prevalence of obesity, smoking, and hypertension was found for the high-need psoriatic patients' cohort compared with non-psoriatic controls. Striking differences were found with respect to body mass index and obesity, as 35.5% of all high-need psoriatic patients were obese. CONCLUSIONS: High-need psoriatic patients show a high prevalence of cardiovascular risk factors, and may consequently be predisposed to cardiovascular diseases. As this is relevant for therapy management in daily clinical practice, especially biologics, cardiovascular risk should be evaluated for each high-need psoriasis patient before and during systemic treatment.

Etanercept and efalizumab treatment for high-need psoriasis. Effects and side effects in a prospective cohort study in outpatient clinical practice.

BACKGROUND: Since the beginning of 2005, etanercept and efalizumab are officially registered and reimbursed for the treatment of recalcitrant psoriasis in The Netherlands. OBJECTIVE: The evaluation of the efficacy, safety and adverse events of etanercept and efalizumab treatment in daily practice. METHODS: A prospective cohort study was carried out for patients treated with etanercept or efalizumab between February 2005 and March 2006. RESULTS: Over the past 13 months 45 individuals were treated with etanercept and 17 subjects were treated with efalizumab. The cohort represented a high-need population. At week 12, 82% of the subjects treated with 2 x 50 mg etanercept/week and 71% of the subjects treated with 2 x 25 mg etanercept/week reached a PASI-50. Efficacy of etanercept treatment was comparable to the results of clinical trials. For efalizumab, efficacy in responding patients was also comparable to clinical trial data, but the percentage of dropouts was substantial. During biologic treatment, safety was preserved and mainly mild adverse events were reported. CONCLUSION: Etanercept and efalizumab are effective and safe treatments of psoriasis, even in a high-need population. Etanercept was able to sustain the clinical improvement throughout 24 weeks, whereas efalizumab was not in 47% of subjects.