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

• At least 18 years of age
• >10% body surface affected
• History of atopic dermatitis for at least 3 years (as per patient history)

HEALTHY CONTROL COHORT

• At least 18 years of age

Exclusion criteria

ATOPIC DERMATITIS COHORT

• 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.
• Use of topical glucocorticosteroids or other immunosuppressive topical therapy within 1 week of treatment initiation. Emollients are allowed.
• Untreated skin malignancy
• Use of systemic anti-inflammatory medication in the last 4 weeks for more than 3 days
• Known photosensitivity: Hypersensitivity to sunlight or UVB light of any type or photosensitizing medication
• History of Lupus, Polymorphic light eruption (PMLE), or any disease known to be worsened by UV light exposure
• History of melanoma
• 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

• 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)