Atopic dermatitis (AD) is a chronic, inflammatory, skin disorder associated with significant disease burden. The burden of AD mainly derives from signs and symptoms of AD which cause severe sleep loss in the first instance, then subsequently has a strong impact on quality of life (QoL), leading to the development of pathologies/conditions such as mental health disturbance, anxiety and depression as well as work/study impairment [ 1 , 2 ] .

Consensus based European guidelines recommend that adults with severe AD whose symptoms are not adequately controlled with topical agents should be considered for systemic treatments as well as immunosuppressants, phototherapy, or short-term oral corticosteroids for the management of acute flares [ 3 ] . Systemic therapy can be useful to reduce the total amount of topical corticosteroids in patients who need large amounts of potent topical corticosteroids for large body areas over prolonged periods to control their AD.

Indeed, the area of systemic therapy for the treatment of AD has flourished in the past few years, as many new substances (including inhibitors of IL-4 and IL-13 signaling pathways as well as Janus kinase; JAK inhibitors) have been marketed, licensed, or are in the last stages of clinical development [ 3 – 5 ] . Development programs for these novel biologics are providing much better levels of evidence compared to older traditional drugs.

Substantial gaps in our understanding remain with regards to the overall burden of AD on patient health and wellbeing, particularly in patients with moderate-to-severe disease [ 6 – 9 ] .

Recent studies in moderate-to-severe AD report the presence of a multidimensional disease burden [ 10 – 13 ] that includes other atopic comorbidities associated with pruritus such as sleep disturbance and functional impairment, and secondary consequences including neuropsychiatric issues (anxiety, depression) and reduced health related QoL (HRQoL) [ 1 , 14 – 16 ] .

Nevertheless, few studies worldwide have specifically examined the burden of moderate-to-severe AD across a wide spectrum of QoL measures, particularly from the patients perspective [ 11 , 13 , 17 – 22 ] .

To address these gaps, this sub-analysis of the global cross-sectional MEASURE-AD study was performed on the adult population in Italy to collect information on disease burden experienced by patients in terms of itching, skin pain, sleep and mental disturbance as well as work productivity and out-of-pocket expenses.

In AD, it is recognized that increased disease severity is frequently correlated with a worsening in QoL of the patient [ 13 , 34 ] . Indeed, we observed that the proportion of patients with moderate (~30%) or severe (~20%) disease by the EASI or BSA closely reflect the proportion of patient with worse reported outcomes such as the proportion of patients affected by sleep problems (58.8%), severe pruritus (50.0%) and reporting a flare in the past week (42.4%). According to the DLQI, the impact of AD was reported to be moderate or severe in 21.2% or 37.3%, respectively. Similarly, about one-third of patients were judged as having clear or mild disease (by EASI) corresponding to a similar proportion of patients reporting no impact of their AD on sleep, pruritus or QoL measures.

Previous real-life studies in Italy have recently evaluated the association of factors affecting QoL in AD patients [ 17 , 20 , 21 , 35 , 36 ] . Ferrucci and colleagues evaluated factors associated with poor QoL in 300 AD patients with severe disease (mean EASI was 29.45±7.1 and DLQI was 16.8±6.8) [ 35 ] . Poor quality of sleep was found to be a predictor of anxiety symptoms, which is not surprising as anxiety disorders are frequently associated with insomnia [ 37 ] . Approximately half of patients had clinical anxiety or depressive symptoms (considering a HADS of ≥8) compared to approximately 30% in our study, likely reflecting the difference in the severity of AD in patients in their cohort. Similarly, in their study, poor sleep, itch and depression were correlated with each other, which again is to be expected and in turn to negatively impact upon daily activities and consequently QoL [ 38 ] .

These results corroborate with observations by Miniotti et al where POEM, NRS for pruritus and sleep disturbance were significantly associated with DLQI and also in a small study by Milanesi et al where itch severity positively correlated with sleep quality [ 17 , 21 ] .

In a post-hoc analysis of two randomized placebo-controlled phase-3 trials, Offidani et al., evaluated the improvement in signs and symptoms and QoL in patients with an EASI score of ≥20 to <24 or ≥24 treated with dupilumab for 16 weeks [ 36 ] . A weak correlation at baseline was observed between physician-assessed outcomes (reflected by EASI), patient-reported symptoms and QoL (reflected by pruritus NRS and DLQI) suggesting that patients with baseline EASI score of 20–24 can have substantial burden of disease and poor QoL. Indeed, patients with a substantially lower EASI (such as 11.2±11.5 in our study) can still be significantly burdened by their AD.

The impact of AD on work productivity observed in our study confirm evidence from previous studies of AD [ 39 – 41 ] . Indeed, we observed a significant impact of AD on both presenteeism and absenteeism with almost 2 hours missed from work in the past week.

In addition to the well-recognized work productivity and healthcare associated costs [ 42 ] , the total monthly cost due to AD was estimated to be 148.6±134.7 Euro, similar to direct AD-related costs reported elsewhere [ 43 ] .

Information with regards to the current treatment patients’ satisfaction and their experience of this disease in terms of its multi-faceted impact on an array of socio-physical issues are still limited.

In our cross-sectional study we did observe that 37.3% of patients had ≥3 flares in the past 6 months and over half of patients were affected by disturbed sleep experienced severe itching and markedly worse QoL. Over half of patients were assessed (by a dermatologist) as having moderate- severe disease corresponding to a similar proportion of patients receiving systemic treatment. However, in our cohort, we also observed long delays in diagnosis (~2 years), diagnosis to first treatment (~10 years) and to first systemic treatment (~19 years), pointing towards an important unmet need in the awareness of this skin disorder and the appropriate therapeutic management of these difficult-to-treat patients.

A recent nationwide campaign by The Italian Society of Dermatology and Venereology, provided direct access to 27 dermatologic centers dedicated to the management of AD and it was revealed that as many as 35% of patients received an incorrect diagnosis, almost 32% of patients were untreated (either with topical or systemic agents) whereas 44.3% used routine topical compounds, similar to the proportion in our study [ 22 ] . However, although mean EASI was similar in this cohort compared to our study (11.2), only 21.5% of patients had moderate-to-severe AD compared to ~55% in our study, where we specifically selected these patients. It is widely accepted that there is an unmet need in the management of AD and recent expert consensus has endeavored to provide guidance in this regard [ 6 ] in addition to recently published guidelines [ 3 ] .

As well as studies undertaken in Italy, data are also available from other large real-life studies evaluating the burden and treatment patterns in AD patients from different countries [ 11 , 13 , 44 ] . Collectively, these studies and ours, reveal that patients with moderate-to-severe AD report significant disease burden, highlighting unmet treatment needs, with particularly attention focused on the lack of/underuse of systemic treatments.

Although not available at the time the present study was undertaken, it is worth noting that in recent years, other novel systemic therapies are available that have been shown to be effective in the management of pruritus [ 45 – 47 ] . Further studies are needed to understand how and to what extent novel targeted systemic therapy can improve patient reported outcomes in moderate-severe AD.

This was a cross-sectional observational study, and the long-term effects or trends were therefore not assessed. However, the sample size of 118 patients allowed us to provide a detailed snapshot of the current real-life management and patient-centered perspective of their disease burden in Italy.

This study assumed that most patients with moderate-to-severe AD would attend dermatology clinics or underwent office visits over a period of 6 months. Patients attending a routine visit were enrolled consecutively over a 6-month period, thereby reducing the potential for selection bias.

Patients were required to describe their sleep and QoL over the previous week, thereby introducing the potential for recall bias. In general, a major limitation of population-based studies of the burden of AD is that they solely rely on patient responses.

Strengths of our study lie in the multicenter design of current real-life management and treatment of adult patients with moderate-to-severe AD. Our findings grant a unique and in-depth perspective of the disease burden experienced by these patients.

This real-life study highlights the impact of moderate-to-severe AD experienced by patients, a burden that is extensive and varied. Besides physical symptoms such as pain and itching, patients also experience a negative impact of AD on their QoL as reflected by disturbed sleep, reduced workability, out-of-pocket costs, increased anxiety/depression, and reduced ability to carry out normal daily activities. Delays in diagnosis to first treatment and to first systemic therapy and a high proportion of patients still receiving topical treatment (44.9%) may explain in part why approximately one-quarter of patients were not satisfied with their current treatment. An awareness of the wide ranging and extensive burden from this chronic inflammatory illness are paramount in order to make important steps towards improving patient QoL.