"I know quite a few people around here just lose their legs, but I put that down to the way they’re living and the way they look after themselves. They’re not really cleaning their wounds or whatever".
The above quote is from a participant in the first study I came to the UK to work on – ‘Staying Safe’. I was interviewing people who had been injecting for the long term in North and South London to understand the factors informing hepatitis C risk and protection. Hepatitis C was of minimal priority for many.
Instead, I was struck by severity and debilitating impact of skin and soft tissue infections (SSTIs) – such as cellulitis, abscesses and leg ulcers – among this population. Despite my not having a medical background, participants regularly shed their clothes to show me injecting related wounds and groin fistulas – asking “Am I going in the right place ...?” Barriers to care were evident, exacerbated by the stigma and discrimination many experienced in the health care system – particularly around disclosing injecting related wounds and infections. My identification as a peer may have reduced this discomfort for some.
After presenting on the Staying Safe study a blood-borne virus nurse working in drug services and hostels got in touch with me to talk about SSTIs among the clients she was seeing and the relationship between SSTIs and a devastating kidney disease – AA amyloidosis. Five clients in her London borough were currently living with the disease, with nine having died in the past decade:
"The outcome for the clients we’ve worked over the last 10 years is usually death within 24 months from diagnosis or dialysis start. Our HCV/HIV/TB clients are often still with us with or without treatment".
Introducing AA amyloidosis: a serious SSTI sequelae
The nurse put me in touch with a nephrologist at the National Amyloidosis Centre (NAC), Royal Free Hospital, who outlined the connection between chronic SSTIs, AA amyloidosis and renal failure. Briefly – AA amyloidosis is caused by persistent inflammation, a feature of untreated SSTIs. The primary population impacted have been older people with Rheumatoid Arthritis and other inflammatory conditions. As anti-inflammatory medications have improved incidence of AA amyloidosis among those with arthritis has decreased, but it appears to be a growing issue for people who inject drugs (PWID). He described the difficulties faced by patients with an injecting history presenting to the NAC. PWID were invariably referred late, at a stage of advanced renal failure, and often experienced profound difficulty in adhering to dialysis treatment and keeping dialysis catheters clean. Dialysis-line related infection is the cause of death for the majority of PWID diagnosed by the NAC, with a median survival rate of 19 months for PWID with AA amyloidosis once dialysis has ensued. This compares to 52 months for all patients with AA amyloidosis on haemodialysis in the UK. The nephrologist expressed frustration that drug services did not conduct urine screening (a simple dipstick test) for proteinuria as this could indicate AA amyloidosis risk, allow early intervention, and potentially prevent the need for dialysis and reduce mortality.
I became – how can I say this – a little obsessed with exploring this issue further. Prevalence of AA amyloidosis among PWID is unknown and no UK drug treatment services provide routine AA amyloidosis risk screening or early intervention. None of my contacts in the harm reduction or drug service provision community had ever heard of AA amyloidosis.
Kidney disease, and even care for skin and soft tissue infections, did not appear to be a priority for many.
The study: Care & Prevent
After a substantive, failed, attempt to obtain funding – I was finally successful! Awarded as an NIHR Career Development Fellowship, the study (Promoting skin and soft tissue infection care & preventing AA amyloidosis renal failure among people who inject drugs in the United Kingdom) started in January this year. Although a fellowship, I have a team of supportive people around me. Our aim is to:
Improve SSTI prevention, care and treatment interventions for PWID, including through assessing the feasibility of AA-amyloidosis screening, diagnosis & treatment referral.
Two primary questions are asked:
1. What is the prevalence of AA amyloidosis among PWID and is a national screening study needed?
2. What are the barriers and facilitators to accessing or practicing timely SSTI care from PWID perspectives?
So, what exactly are we doing?
The study consists of 5 phases: 1) A systematic review and mapping of the evidence for AA amyloidosis among PWID; 2) Questionnaire (exploring SSTI history, risk factors, health care access and injecting practices) and urine screening for proteinuria among 400 PWID in London with supported referral to specialist care; 3) Qualitative longitudinal interviews following participants referred for care to the NAC; 4) Qualitative interviews with a sample of participants with, and without, SSTI to explore barriers and facilitators to SSTI prevention and care; and 5) the development of SSTI and AA amyloidosis care and prevention resources with service users and providers.
What have we found so far?
Phase 1: The systematic review is due to be submitted for publication – 37 papers from eight countries were included; comprising data on 805 PWID, of whom 177 had AA-amyloidosis. All PWID with AA-amyloidosis had SSTI. Notably, given the population in question, NO studies were published in addiction or Harm Reduction journals; perpetuating a lack of awareness among drug treatment service providers. Disease causality among PWID is overwhelmingly attributed to chronic inflammation caused by injecting-related SSTIs. The typical trajectory for PWID after being diagnosed with AA-amyloidosis was rapid deterioration of renal function requiring haemodialysis. Treatment difficulties, end-stage renal failure, and premature death from sepsis were common. Good outcomes, including reversibility of AA-amyloidosis, were noted and attributed to rapid treatment of the underlining inflammation and injecting cessation. Awareness of the opportunity for good outcomes among those diagnosed early and supported to receive care for their SSTIs, was a strong motivator for our screening study.
Phase 2: We have conducted the questionnaire and urine screen with 100 people to date – this takes about 20 minutes of their time, for which they are reimbursed a £10 voucher. Recruitment has been a little slow and time consuming, but we are aiming for 400 people by mid (or late) 2018. Given the difficulties with laboratory pathways at some services we are testing urine samples using a portable CLINITEX Status Analyzer machine with reagent strips which provides an albumin: creatinine ratio reading on the spot. All participants with macroalbuminuria (high abnormal, albumin:creatinine ratio >33mg/mmol) are to receive a referral to the NAC, and funding is allocated for Groundswell peer support services to accompany and support these participants through the process. To date, we have found two participants with macroalbuminuria – who may potentially be at risk of AA amyloidosis. Unanticipated, however, is the high percentage of participants with microalbuminuria (abnormal, albumin: creatinine ratio 3.4-33.9mg/mmol). Forty of the 100 participants (40%) have come back with an abnormal reading, indicating raised risk for cardiovascular or progressive kidney disease. For these participants, we have (with their consent) sent a letter to their GP alerting of this finding and asking for monitoring and implementation of cardiovascular risk reduction measures, if appropriate.
Why is this study important?
The London service experiencing AA amyloidosis among its clients had been planning to implement urine screening for AA amyloidosis risk. It is important however, that screening feasibility, acceptability and need is properly evidenced before any formal implementation. And, if warranted – that these findings are to inform practice more broadly than just at one service. We might find that there is no need for risk screening for AA amyloidosis per se – but indications are that cardiovascular and kidney disease risk warrant enhanced attention among this population. The 40% prevalence so far is potentially significant, given general population-based study findings of microalbuminuria prevalence ranging from 3.3% (women in the UK) to 7.2% (the Netherlands) and, in the USA, 6% (men) and 9.7% (women).
This study has dual, inter-related aims. We know that timely health care access for SSTIs is suboptimal among PWID in the UK and places a huge burden not only on the health care system (in the region of £77M p/a) but on individual PWID in terms of suffering, stigma and loss of mobility. Up to 60% (~120,000) of UK PWID report recent SSTIs with 10% reporting SSTI-related hospital admissions per year. The majority of these hospitalisations are avoidable; due to delays in primary care access. There is a pressing need to explore how PWID can be supported to access timely care and prevention for SSTI and related conditions. This may involve supporting self-care initiatives, such as wound care packs and caring/cleaning instructions for partners. Any diagnosed with AA amyloidosis will be advised to cease injecting (although other routes of administration are okay) – a challenge for many PWID. This study will work with PWID to explore facilitators to SSTI care and needed resources, including those for aiding transitions away from injecting (foil for smoking etc). My ethos is firmly one of harm reduction – so I will leave abstinence-based initiatives up to the services! If findings indicate a need for screening this will be taken up by Public Health England, with the potential to inform National Surveillance studies of PWID. Study findings will inform the co-collaboration of STI and AA-amyloidosis resources with the affected community and inform recommendations for future interventions.
We welcome any comments, suggestions and advice – particularly on kidney disease amongst PWID and the potential implications of high rates of microalbuminuria among this population.
My previous studies have been primarily hepatitis C related, so I am learning quickly about kidney disease! I’d like to acknowledge my research assistant Rachel Braithwaite who has been invaluable in every aspect of the study – and has coped incredibly with being thrown into this challenging and slightly gory project (we’ve looked at many pictures of wounds). Also Kate O’Brien whose enthusiasm and dedication have been invaluable, Dr Julian Gilmore of the NAC, Catherine McGowen, LSHTM, and mentors: Jenny Scott, Vivian Hope, Dan Ciccarone, Chris Bonell and Gail Gilchrist for your support. Finally, thank you to all the wonderful London drug treatment service providers and service users who are involved. And NIHR for believing in and funding the study [CDF-2016-09-014]
Feel free to contact me via email.
Magdalena Harris, November 2017.