Manchester Research Activities

Diagnostic Criteria and Severity Form
The first task of the SUNALL collaboration was to define the disease that we would be working on for the next 3 years. This was a collaborative effort which involved input from all centres by email and during extensive debates at the two SUNALL meetings. The resulting form has now been translated into 5 languages for use in the collaborating centres.

Preliminary Quality of Life Survey
An initial pan-European assessment of the impact of PLE on quality of life was undertaken in early summer 2002. The questionnaires were given to patients that had previously been diagnosed by a hospital photodermatologist, with the majority being sent by mail. The questionnaire was asking questions about the effect of PLE on life relating to the previous week. Due to poor weather in early June the questionnaire was sent out in late June or July. The questionnaire consisted of a dermatology life quality index (maximum score 30) and a visual analogue score (VAS) (0-10 with 0 = not affected at all and 10 = severely affected) for effect on quality of life.

The overall response rate was 63% with a mean age of 42.2 years (range 18-73). The ratio of men to women was 1:4 which is similar to previous findings. The average DLQI was 7.3 which is comparable to the scores for eczema (8.6), psoriasis (8.9) (Finlay et al., 1994) and hospital based contact dermatitis (6.6) (Hutchings et al., 2001). The mean score for the VAS was 4.2. There was some correlation between the DLQI and VAS scores as illustrated here. These results suggest that PLE does have a significant effect on the lives of these patients.

Full Multi-Centre Quality of Life Survey
The study described above served as a basis to conduct a full study in which questionnaires have/will be distributed by the Manchester, Leiden, Turku, Athens and Besançon partners in the 1st week in April 03, July 03, October 03, January 04 with a follow-up telephone call if reply not received after two weeks.
This ‘four season’ approach will show how patients are affected when their condition is most symptomatic and when exposure to the sun is likely. It will allow comparisons to be made across seasons and from all the centres involved.

The following represents preliminary data (April, July 2003) from this collaborative study by the Manchester, Leiden, Turku, Athens and Besançon partners:

Correlation between DLQI and VAS in April:

(R2= 0.78)

Response of Normal and PLE Langerhan’s cells (LC) to UVB challenge
The number of LC in suction blister rooves 16h after challenges of 0, 0.66, 2 and 6 MED of broad-band (TL-12) UVB radiation were examined using a CD1a marker in buttock skin (data shown below).

There was no significant difference in mean numbers of LC in PLE vs Normals detected using this technique.

Cytokine Profiles in Suction Blister Fluids Following UVB Challenge
In collaboration with our sub-contractor, Syngenta we have used a Bio-PlexTM cytokine/chemokine array kit and a Luminex 100TM analyser to examine levels of IL-1ƒÒ, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, TNF-ƒÑ, MIP-1ƒÒ, GM-CSF, IFN-£^ in the fluid of the suction blisters raised for the LC study (see above).

Prevalence Survey
1000 completed prevalence questionnaires (98.4% response rate) have been contributed to the SUNALL prevalence study.

Technologies to Standardise Subject Phototesting
In collaboration with partner 2, we have adapted a grid template (see diagram below) for easy and reproducible testing of subject¡¦s minimal erythemal dose (MED) to UVB radiation. This is an essential part of the collaborative studies being conducted in different centres.

Technologies for Suction Blister Technique
The company originally making suction blister cups no longer operates so we have had to approach different manufacturers to source these essential pieces of experimental equipment. A Medical Physic department in the UK was therefore commissioned to make these suction cups for all participating partners.

Technologies for LC immunostaining and cytokine measurements
In discussions and meetings with our subcontractors Dr Ian Kimber and Marie Cumberbatch at Central Toxicology Laboratory, Syngenta plc, UK we have developed immunohistochemical staining methods for epidermal Langerhans cells in suction blister roves and cryostat sections. To quantify immunoregulatory cytokines in blister fluids we are using a Multiplex Cytokine Assay system which allows simultaneous measurement of up to 20 cytokines in a small (20ul) sample using a Luminex analyser.