Treatment of moderate-to-severe psoriasis in adults: An expert consensus statement using a Delphi method to produce a decision-making algorithm.

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.

Unmet clinical needs and burden of disease in hidradenitis suppurativa: real-world experience from EU5 and US.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, inflammatory, debilitating skin disease characterized by painful deep lesions and associated with substantial disease burden. OBJECTIVES: The objective of this study was to describe physician- and patient-reported clinical unmet needs from a real-world perspective. METHODS: This study used data from the Adelphi HS Disease Specific Programme, a point-in-time survey of dermatologists and their patients with HS in Europe and the United States. Dermatologists completed patient record forms (PRFs) for 5-7 consecutively consulting patients with HS; patients or carers of patients also optionally completed a patient/carer self-completion questionnaire (PSC/CSC). Data collection included demographics, symptomatology and impact on quality of life (QoL). RESULTS: Dermatologists (N = 312) completed PRFs for 1787 patients with HS; patient- and carer-reported questionnaires (PSC/CSC) were completed for 33.1% (591/1787) of patients. The mean age was 34.4 ± 12.2 years and 57.6% of patients were female (1029/1787). Physician-judged disease severity at sampling was categorized as mild in 66.0% (1179/1787), moderate in 29.3% (523/1787) and severe in 4.7% (85/1787) of patients. Deterioration or unstable condition over the previous 12 months was described by 17.1% [235/1372] and 12.6% [41/325] of physician- and patient/carer-reported cases, respectively. Despite receiving treatment, high proportions of patients still experienced symptoms at sampling (general pain/discomfort [49.5%, 885/1787]; inflammation/redness of lesions/abscesses [46.1%, 823/1787] and itching [29.9%, 535/1787]); these symptoms were more frequent in patients with moderate or severe disease. Patients reported a mean Dermatology Life Quality Index score of 5.9 ± 5.4 (555/591; mild, 4.1 ± 4.3; moderate, 9.4 ± 5.4; severe, 13.3 ± 5.5) and a mean Hidradenitis Suppurativa Quality of Life score of 11.0 ± 10.6 (518/591; mild, 7.6 ± 8.3; moderate, 17.7 ± 10.0; severe, 31.0 ± 15.4) indicating a substantial impact on QoL. CONCLUSIONS: Patients with HS experienced a high disease burden despite being actively treated by a dermatologist. This study demonstrates that the burden of HS disease is generally poorly managed with a considerable impact observed on patients' QoL.

Treatment of Eosinophilic Annular Erythema: Retrospective multicenter study and literature review.

BACKGROUND: Eosinophilic annular erythema (EAE) is a rare eosinophil-related skin disease which typically manifests with annular erythematous plaques and severe pruritus. Besides the diagnosis, the treatment of EAE is challenging since relevant published data are sparse. METHODS: The aim of this study was to assess the underlying diseases, treatments and outcomes of patients with EAE. To this end, we conducted a retrospective multicenter study and a systematic review of the MEDLINE database. RESULTS: We included 18 patients with EAE followed in 8 centers. The MEDLINE database search yielded 37 relevant publications reporting 55 cases of EAE with 106 treatment sequences. The most common and efficient treatments included topical or systemic corticosteroids, hydroxychloroquine and dapsone. In refractory patients, a combination of systemic corticosteroids with hydroxychloroquine was associated with 88% of complete clinical response. DISCUSSION: To improve the management of EAE patients, we discuss the following treatment strategy: in topical steroid-resistant patients, hydroxychloroquine can be given as first-line systemic treatment. Dapsone, hydroxychloroquine or systemic corticosteroids are second-line options to consider. Last, monoclonal antibodies or JAK inhibitors targeting type 2 inflammation could represent promising last-resort options in refractory patients.

Cutaneous ulcers revealing diphtheria: A re-emerging disease imported from Indian Ocean countries?

INTRODUCTION: Diphtheria due to Corynebacteriumdiphtheriae (C. diphtheriae) has become rare in developed countries. In France only 10 cases of toxigenic diphtheria have been reported since 1989, in all cases causing pharyngitis and all emanating from endemic countries with exception of one contact case. We report herein 13 cases with cutaneous diphtheria, in 5 of which diphtheria toxin was produced, and all imported into France between 2015 and 2018. OBSERVATIONS: Thirteen patients aged 4 to 77 years presented painful and rapidly progressive round ulcerations of the legs, that were superficial and in some cases purulent, with an erythematous-purple border covered with greyish membrane. Bacteriological sampling of ulcers revealed the presence of C. diphtheriae. Only 6 patients had been properly immunized over the preceding 5 years. DISCUSSION: These cases underline the resurgence of cutaneous diphtheria and the circulation of toxigenic strains in France following importation from Indian Ocean countries. This may constitute an important reservoir for ongoing transmission of the disease. Re-emergence of this pathogen stems from the current migratory flow and decreased adult booster coverage. CONCLUSION: Cutaneous diphtheria should be considered in cases of rapidly developing painful skin ulcers with greyish membrane, especially among patients returning from endemic areas, regardless of their vaccination status. The clinician should order specific screening for C. diphtheriae from the bacteriologist, since with routine swabbing Corynebacteriaceae may be reported simply as normal skin flora. Vaccination protects against toxigenic manifestations but not against actual bacterial infection. Early recognition and treatment of cutaneous diphtheria and up-to-date vaccination are mandatory to avoid further transmission and spread of both cutaneous and pharyngeal diphtheria.

[French guidelines on the use of systemic treatments for moderate-to-severe psoriasis in adults]. / Recommandations françaises sur l'utilisation des traitements systémiques chez les patients adultes atteints de psoriasis modéré à sévère.

AIM: These guidelines for the treatment of psoriasis have been developed by the Psoriasis Research Group of the French Society of Dermatology with the aim of providing updated decision-making algorithms for the systemic treatment of adult patients with moderate-to-severe psoriasis. METHODS: Our algorithms were generated after rigorous evaluation of existing guidelines on the treatment of psoriasis and of publications concerning new systemic treatments, not yet incorporated into existing guidelines. A total of nine existing guidelines and 53 publications related to new systemic treatments were found to meet our criteria for use in generating the algorithms. RESULTS: We propose two new algorithms to assess therapeutic response, both of which incorporate emerging criteria for evaluating treatment goals. Updated therapeutic strategy algorithms, incorporating both established and new systemic therapies, were also generated for the treatment of plaque psoriasis and psoriatic arthritis, together with recommendations for the treatment of particular forms of psoriasis and treatment of patients with comorbidities.

French guidelines on the use of systemic treatments for moderate-to-severe psoriasis in adults.

These guidelines were developed by the psoriasis research group of the French Society of Dermatology with the aim of providing updated decision-making algorithms for the systemic treatment of adult patients with moderate-to-severe psoriasis. Our algorithms were generated after rigorous evaluation of existing guidelines on the treatment of psoriasis and of publications concerning new systemic treatments, not yet incorporated into existing guidelines. A total of nine existing guidelines and 53 publications related to new systemic treatments were found to meet our criteria for use in the generation of the algorithms. We have proposed two new algorithms to assess therapeutic responses, both of which incorporate emerging criteria for evaluating treatment goals. Updated therapeutic strategy algorithms, incorporating both established and new systemic therapies, were also generated for the treatment of plaque psoriasis and psoriatic arthritis, together with recommendations for the treatment of particular forms of psoriasis and treatment of patients with comorbidities.

Evidence-based recommendations on the role of dermatologists in the diagnosis and management of psoriatic arthritis: systematic review and expert opinion.

BACKGROUND: Psoriatic arthritis (PsA) can develop at any time during the course of psoriasis. AIMS: The aims of these practical recommendations are to help dermatologists identify patients at risk of PsA, to diagnose PsA in collaboration with rheumatologists and to gain a better understanding of initial PsA management. MATERIALS AND METHODS: A scientific committee consisting of 10 dermatologists and a rheumatologist selected clinically relevant questions to be addressed by evidence-based recommendations using the DELPHI method. For each question, a systematic literature review was performed in Medline, Embase and the Cochrane Library databases. The levels of evidence of all selected and reviewed articles were appraised according to the Oxford levels of evidence. RESULTS: An expert board of 30 dermatologists reviewed and analysed the evidence and developed recommendations for the selected questions. Agreement among participants was assessed on a 10-point scale, and the potential impact of the recommendations on clinical practice was evaluated. Among the 6960 references identified, 190 relevant articles were included in the reviews. Three recommendations regarding risk factors for PsA and one regarding PsA prevalence were issued. The mean agreement score between participants varied from 7.8 to 9.6. Three recommendations on PsA screening tools that can be used by dermatologists were issued. The mean agreement score between participants varied from 7.7 to 9.4. Initial PsA treatment options according to published guidelines were critically appraised for axial and peripheral involvement and enthesitis/dactylitis. Three recommendations were issued. The mean agreement score between participants varied from 7.6 to 8.7. DISCUSSION: The systematic literature research and meta-analyses did not provide high-quality evidence to support recommendations regarding PsA screening. Conversely, PsA treatment options were supported by strong evidence. CONCLUSION: Cooperation between dermatologists and rheumatologists should be emphasized to better identify and manage PsA patients.

Treatment for palmoplantar pustular psoriasis: systematic literature review, evidence-based recommendations and expert opinion.

BACKGROUND: Palmoplantar pustular psoriasis (PPPP) is a variant of psoriasis whose the association with psoriatic arthritis (PsA) has been recently described. There is limited evidence regarding how to best reduce palmoplantar pustular psoriasis severity and to maintain remission once achieved. OBJECTIVE: The aim of this study was to elaborate evidence-based recommendations for PPPP treatment supported by a systematic literature review. METHODS: A systematic literature search was carried out in Embase, Medline and Cochrane Library databases from 1980 to February 2013 searching for any trial in patients with PPPP assessing therapeutic interventions not including a systemic biotherapy. The selection of articles was limited to human subjects and English or French languages. RESULTS: Among the 675 articles identified, 29 including one Cochrane review were analysed. The Cochrane review summarised 23 randomised controlled trials (RCTs) in chronic PPPP until February 2003, including 724 patients. The authors concluded that oral retinoid therapy (acitretin), photochemotherapy or combination of both, low dose of ciclosporin or topical corticosteroids under occlusion appeared to be helpful in relieving symptoms of PPPP. Since the publication of this review, 9 open studies on PPPP treatment have been published. Three new studies evaluated the benefits of PUVA on PPPP. They all showed a better efficacy of PUVA compared to UVB therapy. One open study concluded that a retinoid treatment with an arotinoid ethylesther showed a good efficacy. Five prospective studies (level of evidence of 3) assessed Laser Excimer UVB-NB (Excimer 308 nm) in PPPP. The combined analysis of these studies showed that 64% of patients experienced an improvement of 70% at the end of treatment. CONCLUSION: Phototherapy, ciclosporin and topical corticosteroids seem to be able to control PPPP. However, the standard of care for PPPP remains an issue and there is a strong need for reliable RCTs to better define treatment strategies for PPPP.

Is there a psoriasis skin phenotype associated with psoriatic arthritis? Systematic literature review.

Psoriatic arthritis (PsA) is associated with psoriasis with a prevalence varying from 5.94% to 23.9%. The aim of this study was to assess if some psoriatic skin features are associated with a higher risk of PsA. A systematic literature search was carried out from 1980 to January 2013, in the Embase and Pubmed databases, using a combination of keywords including (Psoriasis) AND (PsA). Of the 2746 articles retrieved, 25 references were selected. Meta-analysis was performed when possible. Mean age at psoriasis onset appeared to be similar among patients with skin disease alone and in those with PsA. There was no clinical type of psoriasis specifically associated with PsA, including pustular psoriasis of palms and soles. Nonetheless specific psoriasis localizations were significantly associated with an increased risk of developing PsA in one cohort study: scalp lesions [Hazard Ratio (HR) 3.89 (95% confidence interval (CI):2.18-6.94)] and intergluteal/perianal lesions [HR 2.35 (95%CI:1.32-4.19)]. A similar association was found in two cross-sectional studies. Nail involvement was significantly associated with PsA in the meta-analysis [Odds Ratio (OR) 2.92 (95% CI 2.34-3.64)], particularly onycholysis [OR 2.38 (95% CI 1.74-3.26)]. Moreover, nail psoriasis was also associated with distal interphalangeal joint arthritis. The extent of psoriasis appeared to be associated with PsA in one cohort study [≥3 sites: HR 2.24 (95% CI 1.23-4.08)], one case-control study [body surface area >75%: OR 2.52 (95% CI 1.33-4.75)] and three cross-sectional studies. The meta-analysis suggested a trend for an association between high PASI and PsA risk [mean difference 3.39 (95% CI 0.94-5.83)]. Therefore, psoriasis patients with such clinical features may require a particular attention for early and close detection of PsA during the course of the cutaneous disease.

Symptoms dermatologists should look for in daily practice to improve detection of psoriatic arthritis in psoriasis patients: an expert group consensus.

BACKGROUND: Up to 29% of patients with psoriasis seen by dermatologists have undiagnosed psoriatic arthritis (PsA). As early detection of PsA may be associated with improved joint and skin outcomes, it is essential for dermatologists to improve their ability to diagnose PsA. Skin and nail features of psoriasis associated with PsA are well known to dermatologists but they may feel less confortable assessing other symptoms and they rarely use PsA screening questionnaires. OBJECTIVE: To develop a limited list of clinical signs and symptoms that a dermatologist should be looking for in a psoriasis patient in addition to specific skin features and nail involvement, to improve PsA detection. METHODS: A systematic search was performed in Pubmed, Cochrane and Embase databases to identify clinical key symptoms associated with PsA. It yielded 27 studies in which we extracted a list of clinical signs and symptoms observed in PsA and submitted it to a panel of dermatology experts through a DELPHI selection process. The experts had to determine which minimal set of signs and symptoms dermatologists should look for in daily practice to improve detection of PsA in patients with psoriasis. RESULTS: The four items that received a score higher than 90% in the DELPHI process were finally selected. Those items were as follows: peripheral inflammatory pain (100%), axial inflammatory pain (95.3%), dactylitis (93%), buttock and sciatic pain (90.7%). The remaining items: distal interphalangeal joints (DIPs) involvement (83.7%), Talalgia (79.1%), swollen Achille's tendon (41.9%), costo-chondral involvement (32.6%), uveitis (7%), mouth ulcerations (2.3%), were not retained. CONCLUSION: We propose a set of four items to screen psoriasis patients for psoriatic arthritis for routine clinical use by dermatologists.

Treatment (biotherapy excluded) of psoriatic arthritis: an appraisal of methodological quality of international guidelines.

BACKGROUND: Some international guidelines have been published to provide the best care for patients with psoriatic arthritis (PsA) but little is known about their quality. OBJECTIVE: The primary aim of this study was to examine the quality of guidelines that concern treatment (biotherapy exluded) of PsA. The secondary aim was to review studies published since the publication of the most recent guideline. METHODS: A systematic literature search was carried out from 2007 to February 2013, in the Embase, Medline and Cochrane Library databases, in English and French using a combination of keywords including 'Arthritis, Psoriatic/therapy' NOT 'Biological Therapy' OR 'Antibodies, Monoclonal' OR 'Recombinant Fusion Proteins' OR 'tumour necrosis factor-alpha'. The AGREE instrument (Appraisal of Guidelines Research and Evaluation) was used by four reviewers to evaluate the quality of selected guidelines according to the proposed methodology. RESULTS: Of the 518 identified references, six guidelines and two studies were selected. There was considerable variation in the quality of clinical guidelines across the AGREE domains. The least well-addressed domains were 'applicability', 'stakeholder involvement', 'scope and purpose' and 'quality of development', whereas 'editorial independence' and 'clarity and presentation' were less problematic. CONCLUSION: Although guidelines development was of good quality, many of the studies that they included are of poorer quality. This work indicates that the current guidelines can be improved, particularly the stakeholder domain and the applicability domain. The prospective use of the AGREE instrument should improve the guideline quality. More controlled trials should be required but are unlikely to be conducted, given the lack of interest in studying old drugs.