Facteurs prédictifs d'une poussée de psoriasis après une infection par le SARS-CoV-2 chez l'enfant

Introduction: La pandémie à SARS-CoV-2 a été source de nombreuses questions quant à l'impact de l'infection sur les dermatoses inflammatoires chroniques, et de l'impact des traitements de ces dermatoses sur la sévérité de l'infection. Le registre international Chi-PsoCov (enfants psoriasique souffrant de psoriasis et ayant développé une infection à SARS-CoV-2) a permis de montrer que les biothérapies n'augmentaient pas le risque de formes sévères de COVID-19 chez les enfants atteints de psoriasis. Par ailleurs, il était montré que le COVID-19 était responsable du développement de psoriasis de novo ou de l'aggravation d'un psoriasis connu chez certains enfants.Dans cette partie du travail nous nous sommes concentrés sur les enfants ayant développé une poussée de psoriasis après l'infection : aspects phénotypiques des poussées, et recherche de facteurs de risque liés à la maladie, au psoriasis, ou aux traitements, associés à l'aggravation du psoriasis après l'infection. Matériel et méthodes: Les données ont été collectées de février 2021 à mai 2022 en provenance de 14 pays. Les enfants étaient inclus s'ils avaient moins de 18 ans, un antécédent de psoriasis ou psoriasis apparu dans le moins suivant l'infection COVID-19, et avaient été infectés par le SARS-CoV-2 avec ou sans symptômes. Les enfants ayant développé un psoriasis de novo étaient exclus de cette étude. Résultats: Sur les 152 inclusions du registre Chi-PsoCov, dix enfants ont développé un psoriasis dans le mois suivant l'infection et n'ont pas été retenus dans ce travail. L'analyse a porté sur 135 enfants ayant développé 142 COVID-19. Le psoriasis était stable dans 120 cas (84,5 %) et s'aggravait dans le mois suivant l'infection dans 22 cas (15,5 %).Dans 20 cas, lors de la poussée, le phénotype était inchangé, et dans 2 cas, il y avait un changement de phénotype : psoriasis en plaques en psoriasis en gouttes (n = 1) ou inversé (n = 1).Ni les caractéristiques démographiques, ni les aspects du psoriasis (notamment psoriasis actif vs en rémission), ni la sévérité de l'infection à SARS-CoV-2 n'étaient associés à des poussées de psoriasis. Seule l'utilisation de traitements systémiques du psoriasis, conventionnels ou biothérapies, lors de l'infection semblait protectrice de la survenue de poussées (50,0 % dans le groupe stable vs 27,3 % dans le groupe poussées, p = 0,049). Discussion: L'infection à SARS-CoV-2 est responsable dans environ 15 % des cas de poussées de psoriasis. Dans la grande majorité des cas, le phénotype précédent l'infection est conservé. Ces poussées ne sont pas associées à la sévérité du psoriasis, de l'infection ou autres paramètre cliniques. Seuls les traitements systémiques semblent réduire ce risque, probablement en « contrôlant » la poussée. Il est possible qu'une susceptibilité d'ordre génétique, non explorée ici, explique aussi cette susceptibilité à l'infection.

COVID-19 et psoriasis de l'enfant : facteurs associés à une évolution défavorable de la COVID-19 et impact de l'infection sur le psoriasis. Registre Chi-PsoCov

Introduction: La pandémie à SARS-CoV-2 a soulevé de nombreuses questions sur la prise en charge des maladies chroniques et leurs traitements. Les données concernant l'utilisation des biothérapies chez les adultes atteints de psoriasis sont rassurantes, mais manquent chez l'enfant. Par ailleurs, l'infection à SARS-CoV-2 pourrait influencer l'évolution du psoriasis chez l'enfant. L'objectif de cette étude était d'évaluer l'impact de l'infection à SARS-CoV-2 sur le psoriasis, et la sévérité de l'infection selon le traitement systémique reçu. Matériel et méthodes: Les données ont été collectées de février 2021 à février 2022 en provenance de 14 pays. Les enfants étaient inclus s'ils avaient moins de 18 ans, un antécédent de psoriasis ou apparu dans le moins suivant l'infection COVID-19, et avaient été infectés par le SARS-CoV-2 avec ou sans symptômes. Résultats: Au total, 117 enfants ont été inclus (filles : 49,6 %, âge moyen : 12,4 ans) avec 120 infections) SARS-CoV-2. La principale forme de psoriasis était le psoriasis en plaques (69,4 %) ;le psoriasis était actif avant l'infection dans 70,1 % des cas. La majorité des enfants ne prenaient pas de traitement systémique au moment de l'infection (54,2 %), 33 enfants (28,3 %) étaient sous biothérapie (principalement anti-TNF alpha et ustékinumab), et 24 (20,0 %) sous traitement systémique conventionnel (principalement méthotrexate). L'infection était confirmée chez 106 enfants (88,3 %) et 3 ont eu la maladie 2 fois (1 enfant asymptomatique sous ustékinumab et 2 enfants symptomatiques sans traitement systémique). L'infection était symptomatique chez 75 enfants (62,5 %) avec une durée moyenne des symptômes de 6,5 jours, significativement plus longue chez les enfants sous traitement systémique conventionnel (p = 0,002) ou sans traitement systémique (p = 0,006) par rapport aux enfants traités par biothérapies. Six enfants ont nécessité une hospitalisation, dont un enfant en réanimation ;ils étaient plus fréquemment sous traitements systémiques conventionnels par rapport aux autres enfants (p = 0,01), et principalement sous méthotrexate (p = 0,03). Aucun enfant sous biothérapie n'a été hospitalisé, et aucun décès n'a été rapporté.Après l'infection, le psoriasis s'est aggravé dans 17 cas (15,2 %), sans modification du phénotype sauf pour un enfant avec un psoriasis initialement en plaques qui a eu suite à l'infection une poussée de psoriasis en gouttes. Neuf enfants (8,0 %) ont développé un psoriasis de novo dans le mois qui a suivi l'infection, plus souvent un psoriasis en gouttes (p = 0,01) par rapport aux enfants ayant un antécédent connu de psoriasis. Ces enfants avaient un antécédent familial de psoriasis dans 75,0 % des cas. Discussion: L'utilisation des biothérapies semble rassurante sans augmentation du risque de forme sévère de COVID-19 chez les enfants atteints de psoriasis. L'infection à SARS-CoV-2 était responsable du développement de psoriasis de novo ou de l'aggravation d'un psoriasis connu chez certains enfants.

CHARACTERISTICS ASSOCIATED with POOR COVID-19 OUTCOMES in PEOPLE with PSORIASIS and SPONDYLOARTHRITIS: DATA from the COVID-19 PSOPROTECT and GLOBAL RHEUMATOLOGY ALLIANCE PHYSICIAN-REPORTED REGISTRIES

Background: Some factors associated with severe COVID-19 outcomes have been identifed in patients with psoriasis (PsO) and infammatory/autoimmune rheumatic diseases, namely older age, male sex, comorbidity burden, higher disease activity, and certain medications such as rituximab. However, information about specifcities of patients with PsO, psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), including disease modifying anti-rheumatic drugs (DMARDs) specifcally licensed for these conditions, such as IL-17 inhibitors (IL-17i), IL-23/IL-12 + 23 inhibitors (IL-23/IL-12 + 23i), and apremilast, is lacking. Objectives: To determine characteristics associated with severe COVID-19 outcomes in people with PsO, PsA and axSpA. Methods: This study was a pooled analysis of data from two physician-reported registries: the Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection (PsoProtect), comprising patients with PsO/PsA, and the COVID-19 Global Rheumatology Alliance (GRA) registry, comprising patients with PsA/axSpA. Data from the beginning of the pandemic up to 25 October, 2021 were included. An ordinal severity outcome was defned as: 1) not hospitalised, 2) hospitalised without death, and 3) death. A multivariable ordinal logistic regression model was constructed to assess the relationship between COVID-19 severity and demographic characteristics (age, sex, time period of infection), comorbidities (hypertension, other cardiovascular disease [CVD], chronic obstructive lung disease [COPD], asthma, other chronic lung disease, chronic kidney disease, cancer, smoking, obesity, diabetes mellitus [DM]), rheumatic/skin disease (PsO, PsA, axSpA), physician-reported disease activity, and medication exposure (methotrexate, lefunomide, sulfasalazine, TNFi, IL17i, IL-23/IL-12 + 23i, Janus kinase inhibitors (JAKi), apremilast, glucocorticoids [GC] and NSAIDs). Age-adjustment was performed employing four-knot restricted cubic splines. Country-adjustment was performed using random effects. Results: A total of 5008 individuals with PsO (n=921), PsA (n=2263) and axSpA (n=1824) were included. Mean age was 50 years (SD 13.5) and 51.8% were male. Hospitalisation (without death) was observed in 14.6% of cases and 1.8% died. In the multivariable model, the following variables were associated with severe COVID-19 outcomes: older age (Figure 1), male sex (OR 1.53, 95%CI 1.29-1.82), CVD (hypertension alone: 1.26, 1.02-1.56;other CVD alone: 1.89, 1.22-2.94;vs no hypertension and no other CVD), COPD or asthma (1.75, 1.32-2.32), other lung disease (2.56, 1.66-3.97), chronic kidney disease (2.32, 1.50-3.59), obesity and DM (obesity alone: 1.36, 1.07-1.71;DM alone: 1.85, 1.39-2.47;obesity and DM: 1.89, 1.34-2.67;vs no obesity and no DM), higher disease activity and GC intake (remission/low disease activity and GC intake: 1.96, 1.36-2.82;moderate/severe disease activity and no GC intake: 1.35, 1.05-1.72;moderate/severe disease activity and GC intake 2.30, 1.41-3.74;vs remission/low disease activity and no GC intake). Conversely, the following variables were associated with less severe COVID-19 outcomes: time period after 15 June 2020 (16 June 2020-31 December 2020: 0.42, 0.34-0.51;1 January 2021 onwards: 0.52, 0.41-0.67;vs time period until 15 June 2020), a diagnosis of PsO (without arthritis) (0.49, 0.37-0.65;vs PsA), and exposure to TNFi (0.58, 0.45-0.75;vs no DMARDs), IL17i (0.63, 0.45-0.88;vs no DMARDs), IL-23/IL-12 + 23i (0.68, 0.46-0.997;vs no DMARDs) and NSAIDs (0.77, 0.60-0.98;vs no NSAIDs). Conclusion: More severe COVID-19 outcomes in PsO, PsA and axSpA are largely driven by demographic factors (age, sex), comorbidities, and active disease. None of the DMARDs typically used in PsO, PsA and axSpA, were associated with severe COVID-19 outcomes, including IL-17i, IL-23/IL-12 + 23i, JAKi and apremilast.

Children with psoriasis and COVID-19: factors associated with an unfavourable COVID-19 course, and the impact of infection on disease progression (Chi-PsoCov registry).

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.

The impact of methotrexate and targeted immunosuppression on cellular and humoral immune responses to COVID-19 vaccine BNT162b2: a cohort study

Individuals on immunosuppression were excluded from COVID-19 vaccine trials. We evaluated immune responses to COVID-19 vaccine BNT162b2 (Pfizer-BioNTech) in people taking methotrexate and biologics. Given the roll out of extended interval vaccination programmes to maximise population coverage, we present findings following the first dose. We recruited individuals with psoriasis (n=84) established on methotrexate or biologic monotherapy (TNF, IL-17 or IL-23 inhibitors) and healthy controls (n=17). Immunogenicity was evaluated pre and post (day 28) vaccine. Seroconversion rates were lower in patients taking immunosuppression (78%, 95%CI 67-87%) compared to controls (100%, 95%CI 79-100%), with the lowest rate in those on methotrexate (50%, 95%CI 26-74%). Neutralising activity to wild-type SARS-CoV-2 was lower in patients receiving methotrexate (median ID50 152, IQR 47-257) compared to controls (median ID50 316, IQR 212-481, p<0.01), but preserved in those receiving biologics (median ID50 280, IQR 137-428). Neutralising titres against B.1.1.7 were comparably low in all participants. Spike-specific T cell responses (including IFNγ, IL-2, IL-21) were induced in all groups, and were equivalent among individuals receiving methotrexate, biologics and controls. Functional humoral immunity to a single dose of BNT162b2 is impaired by methotrexate but not by biologics, while cellular responses are unaffected. Seroconversion alone may not adequately reflect vaccine immunogenicity in individuals with immune-mediated disease receiving immunosuppression. Real-world pharmacovigilance studies will determine whether these findings translate to clinical effectiveness.

Factors associated with hospitalization due to COVID-19 in patients with psoriasis: Insights from a global registry

Psoriasis is a common immune-mediated inflammatory skin disease with frequent multimorbidity, and immunosuppressants are the mainstay of treatment in moderate-to-severe disease. An understanding of the impact of COVID-19 on individuals with psoriasis and the effect of psoriasis therapies on the course of COVID-19 is urgently required to inform clinical decision-making. This study sought to characterize the clinical course of COVID-19 in patients with psoriasis and to identify factors associated with hospitalization. Clinicianreported cases of confirmed or suspected COVID-19 in psoriasis were collected via an international online registry. Multivariable-adjusted logistic regression identified factors associated with hospitalization. Patient risk-mitigating behaviours were characterized using an independent global selfreport registry. In total, 334 clinician-reported cases (median age 50 years, 62% male, median body mass index 28 kg m-2, 85% white) from 22 countries [most frequently, the U.K. (35%), Italy (22%) and Spain (16%)] were available between 27 March and 20 June 2020. Altogether, 245 (73.3%) patients were receiving a biologic, 54 (16.2%) a nonbiologic and 31 (9.3%) no systemic treatment. Overall, 311 (93.1%) achieved a full recovery, 71 (21.2%) were hospitalized and nine (2.7%) died. Risk factors associated with hospitalization were older age [adjusted odds ratio (aOR) 1.71, 95% confidence interval (CI) 1.26-2.32], male sex (aOR 2.37, 95% CI 1.11-5.04) and nonwhite ethnicity (aOR 3.40, 95% CI 1.27-9.11), in addition to chronic lung disease (aOR 4.37, 95% CI 1.62-11.74) and hypertension (aOR 2.23, 95% CI 1.05-4.74). Reduced risk of hospitalization was associated with use of a biologic (aOR 0.42, 95% CI 0.18-0.98) vs. nonbiological systemic therapy. There was no difference in risk of hospitalization between classes of biologics. An independent selfreport psoriasis registry (1167 patients from 39 countries) suggested increased social isolation (76% vs. 66%;P < 0.05) but similar nonadherence to medication (18% vs 22%) in patients receiving biologics vs. nonbiological systemic treatments. In this international moderate-to-severe psoriasis case series, most patients fully recovered from COVID-19;older age, being male and being of nonwhite ethnicity increased risk of hospitalization. Use of biologics, when compared with nonbiological systemic therapies, was associated with reduced risk of hospitalization;however, this requires further study owing to potential selection bias and unmeasured confounding such as a difference in risk-mitigating behaviours.

EuroGuiDerm Guideline on the systemic treatment of Psoriasis vulgaris - Part 2: specific clinical and comorbid situations.

This evidence- and consensus-based guideline on the treatment of psoriasis vulgaris was developed following the EuroGuiDerm Guideline and Consensus Statement Development Manual. The second part of the guideline provides guidance for specific clinical and comorbid situations such as treating psoriasis vulgaris patient with concomitant psoriatic arthritis, concomitant inflammatory bowel disease, a history of malignancies or a history of depression or suicidal ideation. It further holds recommendations for concomitant diabetes, viral hepatitis, disease affecting the heart or the kidneys as well as concomitant neurological disease. Advice on how to screen for tuberculosis and recommendations on how to manage patients with a positive tuberculosis test result are given. It further covers treatment for pregnant women or patients with a wish for a child in the near future. Information on vaccination, immunogenicity and systemic treatment during the COVID-19 pandemic is also provided.

Risk-mitigating behaviours in people with inflammatory skin and joint disease during the COVID-19 pandemic differ by treatment type: a cross-sectional patient survey.

BACKGROUND: Registry data suggest that people with immune-mediated inflammatory diseases (IMIDs) receiving targeted systemic therapies have fewer adverse coronavirus disease 2019 (COVID-19) outcomes compared with patients receiving no systemic treatments. OBJECTIVES: We used international patient survey data to explore the hypothesis that greater risk-mitigating behaviour in those receiving targeted therapies may account, at least in part, for this observation. METHODS: Online surveys were completed by individuals with psoriasis (globally) or rheumatic and musculoskeletal diseases (RMDs) (UK only) between 4 May and 7 September 2020. We used multiple logistic regression to assess the association between treatment type and risk-mitigating behaviour, adjusting for clinical and demographic characteristics. We characterized international variation in a mixed-effects model. RESULTS: Of 3720 participants (2869 psoriasis, 851 RMDs) from 74 countries, 2262 (60·8%) reported the most stringent risk-mitigating behaviour (classified here under the umbrella term 'shielding'). A greater proportion of those receiving targeted therapies (biologics and Janus Kinase inhibitors) reported shielding compared with those receiving no systemic therapy [adjusted odds ratio (OR) 1·63, 95% confidence interval (CI) 1·35-1·97]. The association between targeted therapy and shielding was preserved when standard systemic therapy was used as the reference group (OR 1·39, 95% CI 1·23-1·56). Shielding was associated with established risk factors for severe COVID-19 [male sex (OR 1·14, 95% CI 1·05-1·24), obesity (OR 1·37, 95% CI 1·23-1·54), comorbidity burden (OR 1·43, 95% CI 1·15-1·78)], a primary indication of RMDs (OR 1·37, 95% CI 1·27-1·48) and a positive anxiety or depression screen (OR 1·57, 95% CI 1·36-1·80). Modest differences in the proportion shielding were observed across nations. CONCLUSIONS: Greater risk-mitigating behaviour among people with IMIDs receiving targeted therapies may contribute to the reported lower risk of adverse COVID-19 outcomes. The behaviour variation across treatment groups, IMIDs and nations reinforces the need for clear evidence-based patient communication on risk-mitigation strategies and may help inform updated public health guidelines as the pandemic continues.