1 INTRODUCTION AND BACKGROUND

Cellulitis is a skin infection involving the dermis and sub cutaneous tissue and is usually caused by a break or wound in the skin, commonly allowing either staphylococcus or streptococcus bacteria to enter. Cellulitis is commonly interchanged with the term erysipelas and can affect any part of the body, however, 70%–80% are encountered in the lower limbs.^1-3 All age groups can be affected by cellulitis but it is more common in those over 60 years of age.⁴ The signs and symptoms of a cellulitis include redness, erythema, pain, oedema, bullae, blisters, bruising, petechiae as well as nausea, vomiting, lethargy and rigours. Not all signs and symptoms may be present and mild cases that are detected promptly can be effectively managed in primary care with oral antibiotics. However, more severe cases with systemic toxicity, uncontrolled morbidities or tissue necrosis may require intravenous antibiotics and admittance to hospital. Antibiotics are administered to prevent the infection from spreading and reduce the risk of sepsis, which is potentially fatal. The link between cellulitis occurrence and lymphoedema is well documented with nearly 50% of people with lower limb lymphoedema reporting an episode of cellulitis and half of those experiencing another cellulitis within a year. Recurrent cellulitis is associated with reduced patient quality of life as it caused physical, psychological, and functional impacts. Other risk factors evidenced include wounds, obesity, fungal infections, and venous insufficiency.^5-9

Antimicrobial resistance is a challenge globally; thus people with cellulitis should be accurately diagnosed and treated promptly and the risk factors adequately supported. Further, if these risk factors were reduced and the incidence of cellulitis was less then this would lead to reduced admissions, antibiotic costs, and financial savings.

There remains a dearth of knowledge concerning the economic costs associated with cellulitis from a whole National Health Service (NHS) system. In 2019–2020 over 37 000 Wales hospital bed days were recorded for cases of cellulitis admissions, but there is little understanding of the burden of cellulitis within primary care services.⁴ This is surprising, given that proactive models of care support prompt and appropriate care, with the potential to mitigate the 1.4% of emergency admissions owing to cellulitis in the United Kingdom (UK) in 2018–2019.¹⁰ Understanding the underlying contributory factors and comorbidities that increase the risk of cellulitis, including sex, age or social deprivation is also limited from a national perspective. By gaining a better understanding of these factors including the economic angle, it may be possible to prioritise care and reduce financial encumbrance on the NHS as a whole.

2 AIMS AND OBJECTIVES

This study aimed to estimate the costs associated with managing patients with cellulitis from the perspective of the Welsh/UK NHS using routine electronic health record data sources available within the Secure Anonymised Information Linkage (SAIL) Databank.

3 METHODS

The analysis was undertaken through the SAIL Databank,^11-13 sources within a privacy-protecting Trusted Research Environment. These data include primary care events from 80% of general practices around Wales (population coverage ~3.2 million people), General Practitioner (GP) records and secondary care in-patient hospital episodes. All data are anonymised within SAIL, but the individual-level linkage is possible through an encrypted anonymised linking field which allows associations between data sources and longitudinal patient pathway analyses. The patient cohort was identified through relevant clinical codes and the resource implications of their management were collected and estimated using published sources.^14-18

This approach provided an in-depth inventory of the contacts, consultations, and resources utilised in the current management of patients with cellulitis in NHS Wales.

4 RESULTS

5 DISCUSSION

Economic perspectives on clinical conditions can be important at local, national and global levels. This is the first attempt to estimate the economic burden of cellulitis using the SAIL Databank for both primary and secondary care costs in the Welsh NHS. The direct costs are considerable (£28 554 338) and would represent 0.35% of the annual budget in Wales. In-Patient events and length of stay costs are the main cost drivers with annual estimates of £19 664 126. This is followed by primary care costs of £8 890 212. At a UK level, the cellulitis burden would amount to around £571 086 752 per annum with an average of £1499 per patient. One American paper²² estimated cellulitis discharges in 2013 cost $3.74 billion (95% CI, $3.65 billion–$3.83 billion) with a median cost per visit of $5159. These costs are not directly comparable since only hospital data were used. Hospital admissions costs for Wales would be £7006 per patient (plus inflation).

Our study also reviewed the overall cellulitis expenditure by WIMD quintiles which demonstrated that resource usage expenditure was highest in WIMD Quintile area 1 (Most Deprived) with £97 939 134 (or a mean per-person cost of £1614), compared to £66 056 449 (or a mean per-person cost of £1259) for WIMD Quintile area 5 (Least Deprived). WIMD measures relative deprivation by geographical areas and takes into account factors such as income, employment, education, housing, and crime. More understanding is needed, but as cellulitis is associated with deprivation due to poor diet and nutrition, challenges with personal skin care, oedema management,^23-26 clothing, and environment, along with recreational substance misuse, the data presented here provides the impetus for risk reduction strategies.

One American study²⁷ reviewed cellulitis incidence using regional data from health insurance claims and found the rate to be 24.6 per 1000 people. They suggested that of male sex and increasing age were potential risk factors. We did not stratify the data per year to age and sex, but over the 20 years, we found that older age was a factor incurring most cellulitis costs in the 76–90 age group, with £132 217 754 followed closely by the age group 91+ with £124 928 422. In contrast, we did not establish that male sex was a risk factor with cellulitis incidence as our data suggested female sex was more dominant with 146 238 cases compared to males with 128 464 episodes. This is also contrary to a longitudinal Australian cohort study that also found male sex to be a risk factor for cellulitis.²⁷ However, our study was over 20-years, whereas others were over 10 and 3 years. Capturing incidence data via databanks uses codes rather than case reviews, so there is a possibility of data or coding errors. In this initial trial through the data, we did not distinguish between where on the body the cellulitis was located. Further data analysis may support or refute previous studies reporting a higher prevalence of lower limb cellulitis, but this could be a further paper.

Ellis Simonsen et al²⁸ also suggested that 78% of care for cellulitis was provided in an outpatient setting, whereas our data suggested that over the two decades, primary care provided 95% of the treatments. This is important and demonstrates that only those requiring emergency treatment were seen through acute hospital settings reducing the pressures on unscheduled care. However, with increasing pressures on general practice, this trend may alter as the incidence of hospital admissions has risen from 3116 to 3902 over the last 10-years.

Concern over antimicrobial resistance is important. Reducing inappropriate antibiotic use while expanding essential access is a difficult challenge at the international level and especially for low and middle-income countries. For UK-based health care, it remains a concern in secondary and primary care, therefore approaches that reduce the need for antibiotics are important. For example, the increasing evidence base that compression rather than prophylactic antibiotics is most useful in preventing recurrence of cellulitis, especially in the previously difficult to treat/higher-risk patients is relevant. Cellulitis is integrally linked to lymphoedema/chronic oedema, not only as a precursor but one can significantly exacerbate the other in a vicious circle.⁸ In a recent international study¹ involving 40 sites and 9 countries of 7477 chronic oedema patients, 16% had encountered cellulitis in the last 12 months with a prevalence of 37%. Other risk factors in Burian et al's study¹ included wounds, morbid obesity, obesity, midline oedema, male sex, and diabetes. Given the demonstrated financial encumbrance of cellulitis, a proactive model of cellulitis care, which includes lymphoedema/chronic oedema management to reduce the risk of cellulitis recurrence would seem logical.

Indeed, if prevention of cellulitis schemes could decrease the incidence by a modest 5%, the savings could be nearly 1.5 million per annum for the Welsh NHS alone (5% of £571 086 752, when extrapolated to the UK population = £28 554 337.6 for the UK). This information may nudge a change of practice, providing significant financial impact for health care providers and improved care for the patients at the fore. Possibly the best way of attacking these challenges is ensuring that there are local, regional, national, and international guidelines, protocols, algorithms and cellulitis care pathways with implementation monitoring.

Two decades ago Byford et al²⁹ criticised cost-of-illness (COI) studies for over-simplification, overestimation of savings and a lack of consideration of outcomes achieved. In this study, the assumptions have been made clear and acknowledging that not all costs can be saved, and that we propose a modest 5% saving. Methods of estimating the burden of costs of specific episodes of illness or particular conditions have expanded since then as access to larger data banks and more sophisticated software have developed. It is therefore important to acknowledge the strengths and limitations of the data used. SAIL data was previously used by members of the research team in 2016²⁹ and 2020.³⁰ Lessons learned in those previous studies (including issues with the use of READ codes, diagnosis, GP event definition, etc.) allowed for greater awareness of limitations in this study.

The purpose of this study was not to divert funding from one condition to another as Byford et al feared but to focus on one particular aspect which was considered ‘changeable’ by clinicians as a first step in understanding where efficiencies and improved patient experience could occur within a national service.

6 CONCLUSION

Cellulitis is a common and expensive problem for the NHS. This large data analysis showed that estimated annual direct costs for NHS Wales are substantial (over £28 million). Extrapolated for the UK, this amounts to over £571 million. In-Patient events and length of stay costs are the main cost drivers, with annual Welsh NHS estimates of £19 664 126 with primary care events costing £8 890 212. Initiatives to identify early signs/risks of cellulitis, improving the accuracy of initial diagnosis, and improved evidence-based treatment pathways to reduce incidence and severity by even small percentages would result in major financial savings and reduce the burden on patients.

FUNDING INFORMATION

This project has been commissioned by the Lymphoedema Network Wales as part of NHS Wales, with direct funding from the NHS to support its activities. This work was supported by Health Data Research UK, which receives its funding from HDR UK Ltd (HDR-9006) funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation (BHF) and the Wellcome Trust. This work was supported by the ADR Wales programme of work. The ADR Wales programme of work is aligned to the priority themes as identified in the Welsh Government's national strategy: Prosperity for All. ADR Wales brings together data science experts at Swansea University Medical School, staff from the Wales Institute of Social and Economic Research, Data and Methods (WISERD) at Cardiff University, and specialist teams within the Welsh Government to develop new evidence which support Prosperity for All by using the SAIL Databank at Swansea University, to link and analyse anonymised data. ADR Wales is part of the Economic and Social Research Council (part of UK Research and Innovation) funded ADR UK (grant ES/S007393/1).