ABSTRACT
BACKGROUND: New highly effective drugs for moderate-to-severe cutaneous psoriasis are regularly marketed, and the hierarchy of treatments thus requires frequent review. OBJECTIVES: A Delphi method was used to enable a structured expert consensus on the use of systemic treatments and phototherapy among adults with moderate-to-severe psoriasis. METHODS: The Delphi method consists in achieving a convergence of opinions among a panel of experts using several rounds of questionnaires with controlled feedback between rounds. A two-part Delphi questionnaire was administered online to French psoriasis experts. In the first part, 180 items related to the prescription of systemic treatments and phototherapy for adult patients with moderate-to-severe psoriasis were grouped into 21 sections covering different lines of treatment and different forms of cutaneous psoriasis. The experts voted on each proposal using an ordinal 7-point Likert scale. The second part comprised 11 open-ended questions about special indications for each therapeutic class. These were converted into 101 questions for subsequent rounds. Consensus was deemed to have been reached if more than 80% of the experts agreed with a given proposal. RESULTS: Three rounds of questionnaires were sequentially sent to 35 participants between November 2021 and March 2022. Thirty-three (94%) completed all three rounds. For plaque psoriasis, only methotrexate was recommended by the experts as first-line systemic treatment (89% of votes). Cyclosporin was advocated in pustular and erythrodermic psoriasis, and acitretin was suggested for hyperkeratotic and palmoplantar psoriasis. In the event of failure of or intolerance to non-biological systemic treatments, guselkumab, risankizumab, ixekizumab or secukinumab were recommended by more than 80% of the experts. Tumor Necrosis Factor (TNF) inhibitors remain useful for patients with cardiovascular risk factors. Special indications were provided for each therapeutic class (methotrexate/narrowband ultraviolet B phototherapy, psoralen/ultraviolet A phototherapy, cyclosporin, acitretin, apremilast, TNF inhibitors, interleukin (IL)-12/23 inhibitors, IL-17(R)A inhibitors, and IL-23 inhibitors). CONCLUSIONS: This expert consensus statement indicate that newly available IL-17 and IL-23 inhibitors may be favored over TNF and IL-12/23 inhibitors as first-line biologics. The Centre of Evidence of the French Society of Dermatology has drawn up a decision-making algorithm to guide clinicians in the therapeutic management of moderate-to-severe psoriasis.
ABSTRACT
BACKGROUND: Despite the availability of a wide range of therapies for the systemic treatment of moderate to severe psoriasis, many psoriasis patients do not receive adequate treatment, suggesting that guidelines may not be correctly applied by physicians. OBJECTIVES: The aim of this study was to analyze data on physicians' implementation of, and reasons for noncompliance with, guidelines for the systemic treatment of moderate to severe psoriasis. METHODS: We conducted a systematic literature review according to the Preferred Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched the PubMed and Embase databases for studies on guideline adherence in the systemic treatment of moderate to severe psoriasis. All eligible articles were retrieved in full text and the relevant references of retrieved articles were included. RESULTS: A total of 20 studies were selected. Four studies investigated knowledge of the guidelines, six studies examined their application, and five studies focused on the various barriers to implementation. Finally, five studies discussed ways to improve implementation. Several studies on the quality of psoriasis care have revealed discrepancies between the reality and the optimal care described in national and international guidelines. CONCLUSION: Various barriers to implementation of recommendations exist, such as economic barriers, lack of dermatologic orientation towards, lack of knowledge of recommendations by other specialists, lack of applicability, and country- and practice-specific features (e.g., different benefit/risk ratios, different reimbursement rates and conditions). This review can help the everyday practitioner to better understand these barriers, which will have a direct impact on improving the quality of life of psoriasis patients.
Subject(s)
Guideline Adherence , Practice Guidelines as Topic , Psoriasis , Psoriasis/therapy , Psoriasis/drug therapy , Humans , Severity of Illness IndexABSTRACT
BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease. Due to the burden of the disease, some patients try complementary and alternative medicine (CAM). OBJECTIVE: To identify characteristics associated with CAM use in children and adults with AD. METHODS: We conducted a literature review in accordance with the PRISMA international guidelines for literature reviews and meta-analyses. A systematic search was performed in the PubMed database. Qualitative and quantitative analyses using a χ2 test were performed to compare characteristics between CAM users and non-users. A p-value of <0.05 was considered statistically significant. RESULTS: Out of 514 articles retrieved, 12 studies were included, giving a total of 2240 patients. Our statistical analysis identified an association between CAM use and rhino-conjunctivitis (pâ¯=â¯0.015 in children, pâ¯=â¯0.041 in adults), topical corticosteroid use (pâ¯=â¯0.042 in children, pâ¯=â¯0.008 in adults), and daily application of moisturizing cream (pâ¯=â¯0.002 in children, pâ¯<â¯0.001 in adults). Gender did not affect the decision to use CAM (pâ¯>â¯0.05). In studies, a higher number of affected eczema sites (pâ¯<â¯0.001), prior use of more than two conventional treatments (pâ¯=â¯0.047), and food avoidance diets (pâ¯=â¯0.016) were predictive of CAM use in children. In adults, a younger age (pâ¯<â¯0.05), higher education level (pâ¯=â¯0.043), and lower age at AD onset (pâ¯=â¯0.004) were related to CAM use. DISCUSSION: To our knowledge, this is the first literature review focusing on socio-demographic and disease determinants related to CAM use among AD patients. The lack of homogeneity in measuring tools makes it difficult to compare and synthesize the studies.
Subject(s)
Complementary Therapies , Dermatitis, Atopic , Dermatitis, Atopic/therapy , Humans , Child , Adult , Adrenal Cortex Hormones/therapeutic use , Adrenal Cortex Hormones/administration & dosage , Female , MaleSubject(s)
COVID-19 , Psoriasis , Child , Humans , COVID-19/complications , SARS-CoV-2 , Tomography, X-Ray Computed , Psoriasis/complications , Psoriasis/epidemiologyABSTRACT
BACKGROUND: Dupilumab is the first biotherapy available for the treatment of moderate-to-severe childhood atopic dermatitis (AD). OBJECTIVE: The aim of this study was to evaluate the effectiveness and safety of dupilumab in daily practice. METHODS: Patients aged 6-11, who had received a first dose of dupilumab, were included in this multicentre retrospective cohort study. The primary endpoint was change in SCORAD after 3 months of treatment. Secondary endpoints were change in IGA score at 3 months, proportion of patients with SCORAD50 and SCORAD75, description of adverse events and proportion of children in our cohort who would be excluded from pivotal phase 3 clinical trial. RESULTS: Eighty patients were included. After 3 months of treatment, there was a significant decrease in SCORAD (mean: 21.8 ± 13.8 vs 53.9 ± 18.5; P < 0.0001) and IGA (1.3 ± 0.8 vs 3.5 ± 0.7; P < 0.0001). Conjunctivitis was observed in 11.3% (n = 9/80); three patients experienced dupilumab facial redness (DFR); 17.5% (n = 14/80) reported injection site reactions; 6.3% (n = 5/80) discontinued treatment. 61.2% (n = 49/80) children were ineligible in the phase 3 trial. LIMITATIONS: There is no control group. Because it was a real life study based on information from patient medical records in a French multicentre cohort, we cannot rule out the presence of reporting bias generated by the use of patient reported characteristics and missing information. CONCLUSION: These real-life data confirm the efficacy and safety of dupilumab in children with moderate to severe AD extended to dyshidrosis and atopic prurigo, but it also revealed a lower frequency of DFR and conjunctivitis. However, administration in injectable form may be a barrier in this age group.
Subject(s)
Conjunctivitis , Dermatitis, Atopic , Child , Humans , Dermatitis, Atopic/drug therapy , Retrospective Studies , Severity of Illness Index , Treatment Outcome , Conjunctivitis/chemically induced , Cohort Studies , Immunoglobulin AABSTRACT
BACKGROUND: The COVID-19 pandemic has raised questions regarding the management of chronic skin diseases, especially in patients on systemic treatments. Data concerning the use of biologics in adults with psoriasis are reassuring, but data specific to children are missing. Moreover, COVID-19 could impact the course of psoriasis in children. OBJECTIVES: The aim of this study was therefore to assess the impact of COVID-19 on the psoriasis of children, and the severity of the infection in relation to systemic treatments. METHODS: We set up an international registry of paediatric psoriasis patients. Children were included if they were under 18 years of age, had a history of psoriasis, or developed it within 1 month of COVID-19 and had COVID-19 with or without symptoms. RESULTS: One hundred and twenty episodes of COVID-19 in 117 children (mean age: 12.4 years) were reported. The main clinical form of psoriasis was plaque type (69.4%). Most children were without systemic treatment (54.2%); 33 (28.3%) were on biologic therapies, and 24 (20%) on non-biologic systemic drugs. COVID-19 was confirmed in 106 children (88.3%) and 3 children had two COVID-19 infections each. COVID-19 was symptomatic for 75 children (62.5%) with a mean duration of 6.5 days, significantly longer for children on non-biologic systemic treatments (P = 0.02) and without systemic treatment (P = 0.006) when compared with children on biologics. The six children who required hospitalization were more frequently under non-biologic systemic treatment when compared with the other children (P = 0.01), and particularly under methotrexate (P = 0.03). After COVID-19, the psoriasis worsened in 17 cases (15.2%). Nine children (8%) developed a psoriasis in the month following COVID-19, mainly a guttate form (P = 0.01). DISCUSSION: Biologics appear to be safe with no increased risk of severe form of COVID-19 in children with psoriasis. COVID-19 was responsible for the development of psoriasis or the worsening of a known psoriasis for some children.
Subject(s)
Biological Products , COVID-19 , Psoriasis , Adolescent , Adult , Biological Factors/therapeutic use , Biological Products/therapeutic use , COVID-19/complications , Child , Disease Progression , Humans , Methotrexate/therapeutic use , Pandemics , Psoriasis/complications , Psoriasis/drug therapy , Psoriasis/epidemiology , RegistriesABSTRACT
Dupilumab has demonstrated a great reduction in chronic pruritus that is the hallmark of atopic dermatitis (AD). Underscoring relevant pathogenesis similarities emerging from AD, chronic idiopathic pruritus (CIP) and chronic prurigo (CP), several authors suggested the beneficial role of dupilumab in these conditions. The evidence on this subject is limited with no precise data available. In this study, we carried out a systematic literature review in order to evaluate the efficacy of dupilumab on both pruritus and skin manifestations in the two largest retrospective cohorts of patients with CP and CIP and tried to identify potential response predictors. Electronic searches were conducted on 4 databases. Our primary outcome was the improvement in pruritus measured by a reduction in the patient's reported numerical rating scale of itch (NRSI) by >4. Secondary outcomes included the proportion of patients with a complete response at the end of treatment, reduction in the number of lesions by the Investigator Global Assessment (IGA), improvement in numerical rating scale of sleep (NRSS), improvement in quality of life measured by the Dermatology Life Quality Index (DLQI), time until patient perceived any improvement (Time-First) and time until the patient-reported absence of pruritus (Time-Final). Descriptive statistics were calculated for each demographic and clinical variable. Univariate logistic regression analyses were conducted to explore the association between response to dupilumab and potential predictive factors. We included 25 articles in the analysis, counting a total of 153 patients. Based on CP patients' cohort (n = 132), the mean NRSI at baseline was 8.79 ± 0.86 and the NRSI final was 2.32 ± 1.27. The mean time to first improvement was 5.18 ± 3.13 weeks, while the time to complete improvement of pruritus (Time-final) was 13.6 ± 12.0 weeks. Ninety patients out of 109 (83%) noticed an improvement in pruritus before 4 weeks of dupilumab therapy. At the end of treatment, 18 patients out of 126 (14%) had a complete remission of pruritus and 110 patients out of 123 (89%) had a reduction of NRSI >4. The reduction in NRSI was significantly greater in patients improving before 4 weeks of treatment (6.57 ± 1.71) compared with patients improving in more than 4 weeks (5.49 ± 1.39, P < 0.001). Patients with history of AD and those who have been previously treated with cyclosporine or methotrexate had a significantly lower reduction in NRSI (e.g. 6.05 ± 1.34 vs. 7.08 ± 1.90, P < 0.01 for nonassociated AD patients). Based on CIP patient's cohort (n = 21), the mean NRSI at baseline was 8.33 ± 0.80 and the NRSI final was 0.95 ± 0.59. The mean time to first improvement was 2 ± 0 weeks, while the time to complete improvement (Time-final) was 14.6 ± 10 weeks. At the end of treatment, 3 patients out of 21 (14%) had a complete remission of pruritus and 100% of patients had a reduction of NRSI >4. No serious treatment-emergent adverse events were reported. The most common adverse event was mild conjunctivitis (13 cases). We highlight the importance of one early sign of improvement as a predictor of the future response to dupilumab: the improvement before 4 weeks of treatment that leads significantly to a greater final reduction in NRSI. Furthermore, patients with the presence or history of atopy appear to be less responsive to dupilumab than nonatopic patients and develop more side effects, in particular conjunctivitis.
Subject(s)
Conjunctivitis , Dermatitis, Atopic , Prurigo , Antibodies, Monoclonal, Humanized , Dermatitis, Atopic/complications , Dermatitis, Atopic/diagnosis , Dermatitis, Atopic/drug therapy , Humans , Prurigo/complications , Prurigo/drug therapy , Pruritus/drug therapy , Pruritus/etiology , Quality of Life , Retrospective Studies , Severity of Illness Index , Treatment OutcomeSubject(s)
Dermatitis, Atopic , Child , Dermatitis, Atopic/diagnosis , Humans , Infant , Parents , Severity of Illness Index , Surveys and QuestionnairesABSTRACT
Many patients are treated for glaucoma. Like other drugs, anti-glaucoma eye drops may induce dermatological adverse effects. We aim to review the dermatological adverse effects secondary to the active agents in anti-glaucoma eye drops through a literature review. In January 2020, we queried PubMed using the following MeSH terms: glaucoma/drug therapy or glaucoma, open angle/drug therapy cross-referenced with parasympathomimetics/adverse effects or adrenergic agonists/adverse effects or carbonic anhydrase inhibitors/adverse effects or prostaglandins F, synthetic/adverse effects or adrenergic beta antagonists/adverse effects or ophthalmic solutions/adverse effects. The initial search identified 1128 studies, of which 49 were excluded for being in a foreign language, 15 for not involving eye drops, 968 for not focusing on adverse dermatological effects, and 11 for insufficient documentation or redundancy. After adding 38 linked studies, we finally analyzed 123 studies. The ocular and periocular dermatological adverse effects of eye drops are contact dermatitis, hyperpigmentation, prostaglandin analog periorbitopathy, mucous membrane pemphigoid, eyelash depigmentation, skin hypertrichosis, and rare cases of melanoma and skin depigmentation. The reported distant dermatological adverse effects are psoriasis, excessive sweating, lichen planus, alopecia, toxic epidermal necrolysis, erythema multiforme, erythroderma, subacute cutaneous lupus erythematosus, nail pigmentation, and bullous pemphigoid. Most of the cutaneous adverse effects of anti-glaucoma eye drops are ocular and periocular and induced by prostaglandin analogs. Distant adverse effects are rare and sometimes questionable but should be kept in mind, especially mucous membrane pemphigoid, which could lead to blindness. The role of preservatives, such as benzalkonium chloride, should also be considered.
Subject(s)
Glaucoma , Pemphigoid, Bullous , Antihypertensive Agents , Glaucoma/chemically induced , Glaucoma/drug therapy , Humans , Ophthalmic Solutions , Pemphigoid, Bullous/drug therapy , Preservatives, Pharmaceutical/adverse effects , Prostaglandins, Synthetic/adverse effectsABSTRACT
BACKGROUND: Atopic dermatitis (AD) is a chronic, relapsing, inflammatory skin disease. Therapeutic patient education (TPE) has been demonstrated to be effective in AD in reducing disease severity and improving coping and quality of life. OBJECTIVES: To describe the sociodemographic and clinical characteristics of children and adolescents with AD who had attended TPE sessions, as well as the characteristics of their parents, and compare them with those who did not attend TPE. METHODS: Parents of children with AD aged 6-17 years old were recruited from a representative sample of the French population contacted by e-mail. Sociodemographic data and clinical information were collected in patients and parents. Clinical severity was assessed by parents using a proxy version of the Patient-Oriented Eczema Measure (POEM). Attendance to TPE sessions was assessed by the following question 'did your child or one or both parents attended TPE for AD?'. Also, the number of sessions was recorded. Determinants of TPE attendance were evaluated by univariable and multivariable analyses. RESULTS: Data were collected on 1063 parents and children with AD. A total of 131 (12.3%) children and/or parents attended TPE sessions. Most of them attended 2-5 TPE sessions. In that group, there were 85 boys (64.9%), and severity evaluated by POEM was mild in 29.8%, moderate in 52.7% and severe in 17.6% of patients. In the multivariable model, attending TPE sessions was significantly associated with sex of the child (boy vs. girl), consultation with a dermatologist or a paediatrician, high clinical severity and presence of AD in parents. CONCLUSIONS: Despite recommendations, the use of TPE in children with AD is still low in France. There is a need for implementing such programmes in the management of the disease, in particular when the disease is severe.
Subject(s)
Dermatitis, Atopic , Eczema , Adolescent , Child , Dermatitis, Atopic/therapy , Female , Humans , Male , Parents , Patient Education as Topic , Quality of Life , Severity of Illness IndexABSTRACT
BACKGROUND: Dermatomyositis (DM) in an auto-immune inflammatory myopathy with skin lesions, and, occasionally, organ involvement. Herein, we report a case of DM during anti-MDA5 antibody therapy associated with interstitial lung disease (ILD) and pneumocystosis. PATIENTS AND METHODS: A 64-year-old woman was hospitalized for impairment of her general health and skin lesions. Dermatological examination revealed classic signs of DM associated with hyperkeratotic papules on the palm creases. This led us to suspect DM with anti-MDA5 antibodies, which was subsequently confirmed by immunologic tests. We also noted dysphonia, exertional dyspnea and proximal muscles weakness. Despite early corticosteroid therapy, combined later with azathioprine, the patient's dyspnoea worsened; one month later, sudden pulmonary decompensation resulted in her admission to intensive care. A chest scan showed evidence of ILD and infectious signs, and the bronchoalveolar lavage was positive for Pneumocystisjiroveci. Despite treatment of this opportunist infection with cotrimoxazole and intensified immunosuppression, the patient died in intensive care. DISCUSSION: Anti-MDA5 antibodies are associated with a specific clinical phenotype and a high degree of risk that should alert the dermatologist to the high likelihood of ILD having a poor prognosis. Associated clinical signs are erythematous, hyperkeratotic or ulcerated papules on the palm creases, as well as fingertip or periungual ulcerations or digital necrosis. This situation is associated with a high risk of pneumocystosis. However, no recommendations concerning prophylaxis are currently available.
Subject(s)
Dermatomyositis , Lung Diseases, Interstitial , Pneumocystis , Pneumonia, Pneumocystis , Autoantibodies , Dermatomyositis/complications , Female , Humans , Interferon-Induced Helicase, IFIH1 , Lung Diseases, Interstitial/etiology , Middle Aged , Pneumonia, Pneumocystis/complications , Pneumonia, Pneumocystis/diagnosisABSTRACT
INTRODUCTION: Psoriasis affects 0.5% of children in Europe, with moderate to severe clinical forms in 15-35% of cases warranting the use of systemic treatments. Few treatments are licensed for childhood psoriasis. In this study, we analyzed the frequency of such prescriptions. MATERIALS AND METHODS: Our study was based on 3 retrospective cohort trials conducted in France between 2012 and 2018: χ-Psocar (313 children with psoriasis seen in hospitals), PsoLib (207 children seen in a private practice), and BiPe (134 children on biotherapies). Our evaluation was centered on off-label use. To avoid duplicates between cohorts, analysis focused on each cohort independently. RESULTS: In the χ-Psocar study, in 34.8% of cases, use of at least one off-label treatment, mainly topical vitamin D (36.0%), and systemic treatments (methotrexate and cyclosporine) was noted, on account of either the clinical type of psoriasis (13.7%) or patient age (24.6%). In the PsoLib study, in 41.5% of cases, at least one off-label treatment was noted, mainly combined calcipotriol-betamethasone (24.2%), ciclopirox shampoo (7.2%) and systemic treatments (n=20). The main reason was patient age (41.5%). In the BiPe study, in 97.0% of cases, at least one off-label treatment was noted. These prescriptions mainly concerned a combination of calcipotriol-betamethasone (68.7%) and tacrolimus (11.2%) along with systemic treatment comprising methotrexate, cyclosporin, methoxsalen or apremilast (n=125), but also biotherapies (n=85). The biotherapies were used off-label since at that time they had not yet been granted marketing authorisation. DISCUSSION: This study focused on 3 cohorts of children with psoriasis seen either in private practice or in a hospital setting, and it involved all types of treatment. Off-label prescriptions ranged from one-third to almost 100% of the children, depending on the individual cohorts. The prescribed drugs were topical treatments, conventional systemic drugs and biotherapies. Off-label prescription is not strictly prohibited in France provided it is within a well-defined regulatory framework. Where there is a rich bibliography, confident recommendations may be made. Unfortunately, in childhood psoriasis, the literature and recommendations are very limited, leaving prescribers with considerable individual responsibilities. Review of the license concerning children with psoriasis, a push to conduct therapeutic studies and the drafting of recommendations all appear necessary.
Subject(s)
Off-Label Use/statistics & numerical data , Psoriasis/drug therapy , Adolescent , Child , Child, Preschool , Cohort Studies , Female , Humans , Male , Retrospective StudiesABSTRACT
BACKGROUND: Epidermolysis bullosa acquisita (EBA) is a rare auto-immune blistering disease. We report a case of Brunsting-Perry pemphigoid diagnosed by immunoelectron microscopy (IEM). PATIENTS AND METHODS: A 46-year-old man presented very pruriginous vesicles on the face and neck present for 6 years and which were difficult to diagnose and treat. The appearance of atrophic scars and milium cycts evoked EBA, which was confirmed at IEM. Due to limited involvement of the face and the neck, we conclude on EBA of the Brunsting-Perry pemphigoid variant. Treatment with dapsone produced a favorable outcome. DISCUSSION: Diagnosis of EBA is often difficult. In a case review, Asfour et al. collated 60 cases of Brunsting-Perry pemphigoid. These patients had either anti-collagen VII or anti-BP180 and anti-BP230 antibodies. IEM showed cleavage either under the lamina densa or within the lamina lucida, suggesting that Brunsting-Perry pemphigoid is a subtype of EBA or bullous pemphigoid (BP), depending on the paraclinical elements, and localized to the head and neck. The majority of EBA-like cases required systemic therapy, whereas in the presence of BP antibodies, topical corticosteroids were effective. CONCLUSION: We report a case of EBA of the Brunsting-Perry pemphigoid type, diagnosed by IEM after 6 years of progression. We highlight the diagnostic and nosological difficulties of Brunsting-Perry pemphigoid. Classification of this dermatosis as a subtype of EBA or BP may enable effective adaptation of therapeutic management, which has not as yet been coded.