Objectives To determine the presenting features of ocular surface disease in patients with atopic dermatitis (AD) treated with dupilumab at a tertiary, university hospital. To establish the need for treatment of dupilumab-associated ocular surface disease and report any long-term effects on the ocular surface. Methods A retrospective analysis of consecutive patients treated with dupilumab for AD between January 2017 and August 2019 was undertaken. Data were collected on demographics, incidence and type of ocular disease features, natural history and treatment. Results A total of 50% (14/28) patients developed ocular symptoms with a mean time of onset of 6.75 (±6.1) weeks from starting dupilumab. Of these, 69% (9/13) were diagnosed with conjunctivitis associated with cicatrisation in two patients and periorbital skin changes in four. Of these nine, four had prior history of atopic keratoconjunctivitis. All were treated with topical steroids; two required additional ciclosporin drops. In all, 67% (6/9) patients went on to have on-going ocular inflammation requiring maintenance drops at a mean of 16 (±6.9) months of follow-up. All patients had improvement in their AD severity; only one patient discontinued dupilumab due to ocular side effects. Conclusion The rate of dupilumab-associated ocular surface disease was 32%. Periorbital skin changes and conjunctival cicatrisation were noted in association with conjunctivitis. Ocular surface disease improved on topical steroids and ciclosporin but 67% of patients needed on-going treatment. Close liaison with an ophthalmologist should be considered in those patients who develop conjunctivitis or have a past history of severe ocular surface disease.
IntroductionWhen the UK entered lockdown in March 2020 amidst the COVID-19 pandemic, routine dermatology work was suspended as per national guidance 1 to allow for redeployment of staff to the front line and also reducing risk of patient exposure and travel.New patient referrals from primary care into dermatology services usually enter via one of three routes:(i) 2 week wait for suspected serious skin malignancies, (ii) routine non-urgent cases and (iii) emergency referrals (via an on call service). All these patients are assessed via a face-to-face consultation, after various waiting times depending on their urgency.As a result of this suspension just over 800 new routinely referred patients had their appointments temporarily suspended, covering a six week period. Many of these patients had already waited up to 18 weeks for an initial assessment. Furthermore, with the dual challenge of a depleted dermatology workforce and the need for reduced face-to-face consultations during the lockdown, it became imperative to develop new solutions to ensure this cohort of patients would receive care within an appropriate timeframe.To evaluate our response to this challenge we prospectively collected data, with the aim to investigate whether the strategy deployed was an efficient way of assessing this large number of referred patients.We also initiate discussion as to whether this novel method of working could yield a framework for providing a future dermatology service in the event of prolonged social distancing. MethodThe national electronic booking system (ESR) identified the 816 routinely referred patients whose appointments were cancelled, between the dates of 23 rd March to 30 th April 2020. This patient worklist was divided between 15 clinicians (consultants, associate specialists and registrars) working in the department, including those shielding/working from home. 1 www.england.nhs.uk 17.03.2020 Letter to NHS bodies from Sir Simon Stevens Accepted ArticleThis article is protected by copyright. All rights reserved Referral letters were reviewed and patients were contacted via telephone or video calling (Attend Anywhere) 2 . For telephoned patients, each clinician decided if patient photographs would be useful. If so, the patient was directed to send good quality images to a secure NHS email account. Follow-up contact was made with the patient to relay the diagnosis and any further management required.A patient was deemed to be 'uncontactable' if they did not respond to three telephone calls, on separate occasions.Data collected included patient demographics; whether the referral was for a lesion or dermatosis; if a visual element was used in assessing the case (photo or video consultation); and the clinicians' opinion as to who could have made the first contact with the patient (doctor, nurse or administrator) to streamline any future processes.Outcomes recorded included: urgent review; direct booking for non-urgent surgery; routine clinic review (with/without management initiated); and those who could be discharged ...
Purpose To determine the incidence of ocular surface disease in patients with atopic dermatitis (AD) treated with dupilumab at a tertiary, university hospital. To describe the features of dupilumab-associated ocular surface disease, establish the need for treatment and report any long-term effects on the ocular surface. Methods A retrospective analysis of consecutive patients treated with dupilumab for AD between January 2017 and August 2019 was undertaken.. Data was collected on demographics, incidence and type of ocular disease features, natural history and treatment. Results 50% (14/28) patients developed ocular symptoms with a mean time of onset of 6.75 (+/- 6.1) weeks from starting dupilumab. 69% of these (9/13) were diagnosed with conjunctivitis - associated with cicatrisation in two patients and periorbital skin changes in four. Of these nine, four had prior history of atopic keratoconjunctivitis. All were treated with topical steroids; two required additional ciclosporin drops. 67% (6/9) patients developed chronic ocular inflammation requiring maintenance drops at a mean of 16 (+/- 6.9) months of follow up. All patients had improvement in their AD severity; only one patient discontinued dupilumab due to ocular side effects. Conclusion The rate of dupilumab-associated ocular surface disease was 32%. Periorbital skin changes and conjunctival cicatrisation were noted in association with conjunctivitis. Ocular surface disease improved on topical steroids and ciclosporin but 67% of patients needed ongoing treatment. Patients should be referred to an ophthalmologist prior to starting dupilumab as a large proportion develops chronic ocular inflammation.
Regulation of cutaneous immunity is severely compromised in inflammatory skin disease. To investigate the molecular crosstalk underpinning tolerance versus inflammation in atopic dermatitis, we utilise a human in vivo allergen challenge study, exposing atopic dermatitis patients to house dust mite. Here we analyse transcriptional programmes at the population and single cell levels in parallel with immunophenotyping of cutaneous immunocytes revealed a distinct dichotomy in atopic dermatitis patient responsiveness to house dust mite challenge. Our study shows that reactivity to house dust mite was associated with high basal levels of TNF-expressing cutaneous Th17 T cells, and documents the presence of hub structures where Langerhans cells and T cells co-localised. Mechanistically, we identify expression of metallothioneins and transcriptional programmes encoding antioxidant defences across all skin cell types, that appear to protect against allergen-induced inflammation. Furthermore, single nucleotide polymorphisms in the MTIX gene are associated with patients who did not react to house dust mite, opening up possibilities for therapeutic interventions modulating metallothionein expression in atopic dermatitis.
Accurate regulation of cutaneous immunity is fundamental for human health and quality of life but is severely compromised in inflammatory skin disease. To investigate the molecular crosstalk underpinning tolerance vs inflammation in human skin, we set up a human in vivo allergen challenge study, exposing patients with atopic dermatitis (AD) to house dust mite (HDM). Analyses of transcriptional programmes at the population and single cell levels in parallel with immunophenotyping of resident and infiltrating immune cells indicated that inflammatory responses to HDM were associated with immune activation in Langerhans cells (LCs) and cutaneous T cells. High basal level of TNFα production by cutaneous Th17 T cells predisposed to an inflammatory reaction and resulted in formation of hub structures where LCs and T cells interacted, leading to loss of functional programming in LCs. Additionally, single nucleotide polymorphisms in MT1X gene associated with enhanced expression of metallothioneins and transcriptional programmes encoding antioxidant defences across skin cell types in non-reactive patients, were protective against T cell mediated inflammation. Our results provide a unique insight into the dynamics of immune regulation in the human skin and define regulatory circuits that can be harnessed to improve skin health and treat disease.
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