Impact of Narrowband UVB Phototherapy on Systemic Inflammation in Patients With Atopic Dermatitis

Globally, the leading cause of death is cardiovascular disease, which is often linked to
chronic inflammation.

Recently, it has been shown that atopic dermatitis (AD), the most common chronic inflammatory
skin disease, shows increases in inflammatory and cardiovascular risk markers in patient
blood (proteins, microparticles, circulating inflammatory cells). Consistently, it has been
demonstrated that atopic dermatitis is associated with increased cardiovascular disease.
Whether these increases in inflammatory and/or cardiovascular risk markers in the peripheral
blood are due to skin inflammation, or due to other body sources (e.g. lung, lymphatic
system) is unknown.

To investigate whether some (or all) risk proteins present in patient blood are produced in
inflamed skin, the investigators want to treat patients suffering from moderate-to-severe AD
with ultra-violet light B (UVB) therapy, as this therapy is thought to be an exclusive skin
treatment, without direct systemic effects. This notion is corroborated by the fact that only
skin regions directly treated with UVB light, and not covered skin regions, respond to
phototherapy.

Ultra-violet light B (UVB) therapy has been used by dermatologists to treat AD for decades,
and in the 1990ies, narrow band-UVB (NB-UVB) wavelengths (311-312nm) were found to have the
best treatment effects. This is a safe and effective therapy for the majority of patients,
with the main drawback being that it is inconvenient, as patients need to attend the clinic
three times a week for at least 8 weeks. The mechanism of action appears to include killing
of skin immune cells, and it also appears to down regulate inflammatory molecules such as
IFNg, IL-12 and IL-23. However, a systematic study of the impact of NBUVB on blood biomarkers
has never been performed. In this study, participants will be treated with an appropriate
dose of NB-UVB three times a week for up to 12 weeks or a total of 36 treatments, and blood
will be drawn to assess inflammatory and cardiovascular risk markers (proteins,
microparticles, circulating blood cells). Results will be compared to levels in blood from
healthy control participants. This study could lead to a new understanding on the role of the
skin as a source of systemic inflammation, which would help to guide future treatment
approaches for this debilitating, chronic skin disease.

Inclusion Criteria:

ATOPIC DERMATITIS COHORT

1. At least 18 years of age

2. >10% body surface affected

3. History of atopic dermatitis for at least 3 years (as per patient history)

HEALTHY CONTROL COHORT

1. At least 18 years of age

Exclusion Criteria:

ATOPIC DERMATITIS COHORT

1. Unstable or persistent asthma (mild, moderate, or severe), i.e. all forms of allergic
asthma that are other than intermittent asthma. Intermittent asthma is allowed:
Difficulty breathing, wheezing, chest tightness, and coughing occur on fewer than 2
days a week, do not interfere with normal activities, and nighttime symptoms occur on
fewer than 2 days a month.

2. Use of topical glucocorticosteroids or other immunosuppressive topical therapy within
1 week of treatment initiation. Emollients are allowed.

3. Untreated skin malignancy

4. Use of systemic anti-inflammatory medication in the last 4 weeks for more than 3 days

5. Known photosensitivity: Hypersensitivity to sunlight or UVB light of any type or
photosensitizing medication

6. History of Lupus, Polymorphic light eruption (PMLE), or any disease known to be
worsened by UV light exposure

7. History of melanoma

8. History, physical, social or lab findings suggestive of any medical or psychological
condition that would, in the opinion of the PI make the candidate ineligible for the
study

HEALTHY CONTROL COHORT

1. self-reported chronic inflammatory diseases (IBD, rheumatoid arthritis, collagenoses,
chronic inflammatory skin disease, Atopic Dermatitis, autoimmune or autoinflammatory
disease, active tuberculosis, chronic infectious disease such as HIV and hepatitis)