Acute Adverse Events in the Phototherapy Service

A service evaluation looking at the rate of acute adverse events for narrow-band UVB and Psoralen-UVA phototherapy in the University Hospital of Wales over a 12-month period from March 2018 to February 2019.

ABSTRACT

Objective: The aim of this study is to review and analyse all of the acute adverse events experienced by patients receiving NB-UVB and PUVA phototherapy services at the University Hospital of Wales and calculate the rate of acute adverse events.

Method: Standardised adverse events forms of acute adverse events occurring between March 2018 and February 2019 were analysed retrospectively. Patients affected by these acute adverse events are further investigated to look into the nature of these adverse events.

Results: There is a total of 7057 phototherapy treatments (6163 NB-UVB, 954 PUVA). 24 acute adverse events were reported making the rate of acute adverse events in 1 year from March 2018 to February 2019 0.34%. The rates of acute adverse events for NB-UVB and PUVA were 0.26% and 0.84% respectively. 1 was considered to be severe (0.014% of all treatments). Furthermore, only 1 adverse event were identified as being due to operator error.

Conclusion: The rate of acute adverse events encountered over a 12-month period in a working phototherapy unit in this analysis was low. A higher number of reported adverse events were from NB-UVB treatments, however, PUVA treatments have a higher reported rate of acute adverse event compared to NB-UVB.

Introduction

Phototherapy is a common form of treatment for several skin conditions using ultraviolet (UV) radiation. Choice of the type of phototherapy to use is dependent on several factors such as the patient’s skin disease, skin type, and previous response to treatment.

The two most common types of phototherapy are (1):

–          Narrow-band UVB (NB-UVB): a specific range of the UVB spectrum lamps is used in a full body cabinet (2).

–          PUVA (Psoralen + UVA): UVA radiation is used in combination with a sensitiser (psoralens) to increase the effect of UVA on the skin. Psoralens come in several chemical forms, the most common, cost-effective and efficient form used is 8-MOP (3). 5-MOP is used as 2^nd line for patients who are intolerant to 8-MOP (4). Psoralen can either be taken orally or applied in the form of a solution mixed with water where affected areas are soaked (whole body bath or hand and/or foot soak) prior to exposure to UVA radiation.

Examples of common skin conditions treated with NB-UVB and PUVA are psoriasis, atopic eczema and vitiligo. PUVA is also indicated in localised plaque psoriasis or chronic plaque psoriasis when UVB has not been effective. See figure 1 for a more extensive list of key skin conditions treated with NB-UVB or PUVA. The minimal erythema dose (MED) is determined as a ‘gold standard’ for phototherapy protocols prior to the first treatment with a handheld MED device (5).

(catchment area?)

Patients living in the Cardiff and Vale area are referred to the phototherapy unit as secondary care from outpatient dermatology clinics. The treatment is run by trained phototherapy nurses where patients attend 2-5 times a week for 18-24 treatment per course (maximum of 30). The lifetime limit for phototherapy is 500 treatments. Patients are educated on precautions they need to take prior to treatment and after to avoid adverse events such as informing the staff of any new prescriptions or additional sun exposure, not using perfumed skin products prior to treatment and informing staffs of any skin changes (1). Sunscreen and sun protective clothing are recommended after treatment for 24 hours after treatment, sunglasses are also recommended if systematic psoralen is taken. Adverse events can be chronic or acute. Chronic adverse events include premature skin ageing and photo-carcinogenesis. Acute adverse events include erythema, xerosis, pruritus, blistering, hyperpigmentation, PLE, and nausea as a side effect of the psoralen tablets (1)(7). Increments will be given at each visit based on the percentage of the previous dose and the grade of the erythema (E0-4) (Figure 2)(8).

Figure 2: Increment regime and action to be taken (8, 9 (p23)).

Face visors and protective cloting are used during the treatment for uninvoled skin. Eye protection is provided to reduce the risk of photoconjuctivitis, photokeratitis and cataracts (7). We will be focussing on the acute adverse events only as the data can be gathered in a short scope of time.

Aims and objectives

The aim of this study is to review and analyse all of the acute adverse events experienced by patients receiving NB-UVB and PUVA phototherapy services at the University Hospital of Wales for 1 year with a view of improving the service further by understanding the adverse events, types of adverse events, rate of adverse events and explore any trends or contributing factors.

Methodology

Standardised adverse events forms of acute adverse events occurring between March 2018 and February 2019 were analysed retrospectively. Patients affected by these acute adverse events are further investigated by looking at their clinical letters and phototherapy profile (?) to look for possible variables that can affect the adverse events. Data collected by the phototherapy nurses on the number of different phototherapy treatments per day from March 2018 to February 2019 is collated and analysed for the rate of adverse events over 1 year. As the number of treatments varied between patients and conditions, results were formulated as a percentage of treatments, rather than a percentage of patients.

Results

323 patients had undergone phototherapy treatment in one year from March 2018 to February 2019. There is a total of 7057 phototherapy treatments with an average of 79.5 PUVA treatments and 508.6 NB-UVB treatments per month (see figure 3). 24 acute adverse events were reported making the rate of acute adverse events in 1 year from March 2018 to February 2019 0.34%. Due to the low number of acute adverse events per each subcategory of PUVA (bath PUVA, Hand and foot soak PUVA, and 8-MOPs PUVA), we will categorise it all under PUVA. The rate of acute adverse events for PUVA is higher than the rate of acute adverse events for NB-UVB at 0.84% and 0.26% respectively (see figure 4).

Figure 4: Adverse events per treatment modality

What’s considered severe? Is e3 severe

Of the 24 acute adverse events, 3 of the reported events are adverse events, 1 are asymptomatic side effect of the treatment, 19 are symptomatic side effect of the treatment, and 1 are non-treatment related (figure 5).

Half of the patient has risk factors such as prior phototherapy treatment, prior sunbed usage, family history of skin cancer, and skin type 1. 46% of the patients had adverse events reported in the past. The majority of the adverse events are described as E2 reactions (42%) and E3 reactions (25%). 1 patient (4%) reported having an E4 reaction with blistering which is categorised as a severe adverse event (see figure 6). No ocular phototoxicity has been reported. Only 6 patients stopped their phototherapy treatment after the adverse event, 73.9% continued with the treatment with no adverse events to date.

Most of the adverse events are treatment-related (erythema, pruritus, PLE) or due to patient’s noncompliance with standard operating procedures such as misalignment of clothing, uneven exposure of skin during treatment, and not being consistent with protective items worn. However, 1 adverse event reported is caused by an operator error where the treatment was increased by 10% rather than being reduced to the dose before the previous dose as per guidelines (figure 7) for patients that have missed 3 treatments (8 days between treatments). This error occurred after a period where the phototherapy unit was closed for a few days.

Figure 7: Missed treatment protocol (9 (p29))

Discussion

A similar study model was conducted in 2007 by the same phototherapy nurses looking at the rate of acute adverse events for NB-UVB and PUVA from October 2003 to September 2004. This is the first of its kind highlighting the acute adverse events of phototherapy and looking at the rate of acute adverse event in South East Wales. The rates of acute adverse events for each treatment modality in 2007 were “0.6% for narrow-band UVB, 1.3% for systemic PUVA, 1.3% for bath PUVA and 0.8% for hand/foot PUVA” (10). Despite a much smaller focus group in our analysis as only 1 phototherapy unit in South East Wales has been analysed (3 units were analysed in 2007), it is safe to say that there is an improvement in the rate of acute adverse events over the past 12 years. The overall rate of adverse events has been reduced from 0.83% in 2007 to 0.34% in 2019 (a total reduction of 0.49%). NB-UVB and PUVA adverse events rate have been reduced from 0.6% to 0.26% and 1.13% to 0.84% respectively.

One of the limitations to this study is that the data incorporated is obtained by the process of a retrospective clinical review of information already present rather than research, therefore, may be restricted by the possible error that may occur due to the pressures in a busy clinical service. Another limitation to this study is the subjectivity from both the staff and the patient in detailing the adverse events. Prior to treatment, patients are informed of any potential adverse events to expect and the importance of reporting any possible side effects. However, some may not think the reaction is serious enough to report or assumed it was unrelated to therapy, therefore, the true rate of acute adverse events may be underestimated.

Conclusion

In Conclusion, the rate of acute adverse events encountered over a 12-month period in a working phototherapy unit was low (24 out of 7057 treatments, 0.34%) and only 1 were considered to be severe (0.014% of all treatments). Furthermore, only 1 adverse event were identified as being due to operator error. It is unclear whether previous adverse events or risk factors predisposes the patient to a higher risk of acute adverse events as several factors are contributing to the adverse events such as patient non-compliance.

We never anticipate the acute adverse events to be 0%, however, further implementations can be made to reduce the adverse events even further. Our proposal is to try and reduce human error such as patient’s noncompliance with standard operating procedures by educating patient more on the importance of informing phototherapy staffs of any changes in their routine. This information can be added into the patient information leaflet along with information on preventative measures pre and post-treatment to reduce the risk of adverse events. Staffs at the phototherapy unit can also double check with the patient of any changes in their routine, possibly, via a checklist system. Operator error can be reduced by double checking the increment regime and missed treatment protocol prior to giving each treatment. Intensive staff training and regular review of adverse events will help maintain a regulated and high quality of care so all phototherapy staffs can manage and record adverse events in a standardised manner.

Reference List

1. British Association of dermatologists. How does phototherapy work?; [Accessed 11 June 2019]. Available from: http://www.bad.org.uk/shared/get-file.ashx?id=1991&itemtype=document
2. Oakley A. UVB phototherapy: DermNet NZ. Dermnetnz.org. 2007. [accessed 11 Jun 2019] Available from: https://www.dermnetnz.org/cme/phototherapy/uvb-phototherapy/
3. Oakley A. UVA photo(chemo)therapy: DermNet NZ. Dermnetnz.org. 2007. [accessed 11 Jun 2019] Available from: https://www.dermnetnz.org/cme/phototherapy/uva-photochemotherapy/
4.  Ruenger T. Photodermatology, edited by James Ferguson and Jeffrey S. Dover. Photodermatol Photoimmunol Photomed. 2006;121. doi: 10.1111/j.1600-0781.2006.00243.x
5. Lynch M, Carroll F, Kavanagh A, Honari B, Collins P. Comparison of a semiautomated hand-held device to test minimal erythema dose before narrowband ultraviolet B phototherapy with the conventional method using matched doses. J Eur Acad Dermatology Venereol. 2014; doi: 10.1111/jdv.12371
6. Ibbotson SH. A Perspective on the Use of NB-UVB Phototherapy vs. PUVA Photochemotherapy. Front Med. 2018; doi: 10.3389/fmed.2018.00184
7. Valejo Coelho MM, Apetato M. The dark side of the light: Phototherapy adverse effects. Clin Dermatol. 2016; doi: 10.1016/j.clindermatol.2016.05.005
8. British Photodermatology Group/ British Association of Dermatologists. Service Guidance and Standards for Phototherapy Units. NICE accredited. London: British Photodermatology Group/ British Association of Dermatologists; 2016. [Accessed 11 June 2019]. Available from: http://www.bad.org.uk/shared/get-file.ashx?itemtype=document&id=4151
9. Gwent healthcare NHS trust. Phototherapy and Photodynamic therapy service Standards and Protocols. Newport: Gwent healthcare NHS trust; 2009 [Accessed 11 June 2019]. Available from: http://www.bad.org.uk/shared/get-file.ashx?itemtype=document&id=1644
10. Martin JA, Laube S, Edwards C, Gambles B, Anstey A V. Rate of acute adverse events for narrow-band UVB and Psoralen-UVA phototherapy. Photodermatol Photoimmunol Photomed. 2007; doi: 10.1111/j.1600-0781.2007.00278.x