Yeast Colonization and Infection in Patients With Inflammatory Skin Diseases
Yeast Colonization and Infection in Patients With Inflammatory Skin Diseases
The pathogeneses of many inflammatory diseases are not completely understood, yet,
 dysregulation of the human microbiota is increasingly being investigated as a possible
 contributing factor. The human microbiota includes bacteria, archaea, viruses and fungi. In
 general, little is known about the fungal colonization in inflammatory skin diseases.

 This study aims to examine the prevalence of yeast colonization and yeast infection in skin
 and oral mucosa of a variety of patients and healthy volunteers visiting the Dermatological
 outpatient clinic.

 The study is designed as a case-control study comparing the incidence of yeast colonization
 or infection in skin and oral mucosa of patients with different skin diseases and healthy
 volunteers.

 Patients with selected skin diseases, staff at Zealand University Hospital in Roskilde,
 relatives to staff and students with relation to the Dermatologic Department will be asked to
 fill out a short questionnaire and have swaps taken from oral mucosa, as well as skin
 scrapings and tape strips from lesional skin (only patients) and non-lesional skin (all).
Background and aim The pathogeneses of many inflammatory diseases are not completely
 understood, yet, dysregulation of the human microbiota is increasingly being investigated as
 a possible contributing factor. The human microbiota includes bacteria, archaea, viruses and
 fungi. In general, little is known about the fungal colonization in inflammatory skin
 diseases although Candida species in oral mucosa, skin and feces seem to be increased in
 patients with psoriasis and atopic dermatitis. Inflammation is also an important part of the
 pathogenesis in other skin diseases such as hidradenitis suppurativa, acne, vasculitis and
 inflammatory ulcers. Possibly, increased fungal colonization may be present in many
 inflammatory skin diseases, yet, this has not previously been investigated. Studies of
 inflammatory diseases involving other body areas such as systemic lupus erythematosus,
 Sjögren's disease, multiple sclerosis, and spondyloarthritis have also demonstrated increased
 colonization with Candida species. However, it is unclear, whether colonization with Candida
 is a cause or a result of inflammatory disease. Treatment of inflammatory diseases with
 systemic immune-modulating drugs or recurrent antibiotic therapy may also affect yeast
 colonization. Emergence of biological therapies that directly or indirectly modulates the
 Interleukin (IL) 17-pathway emphasizes the need for further knowledge, since the IL-17
 pathway is involved in the defense against yeast infections in healthy individuals. Until
 now, investigations of yeast colonization have primarily focused on Candida and Malassezia.
 Whether other species of yeasts may be of interest is still uncertain.

 This study aims to examine the prevalence of yeast colonization and yeast infection in skin
 and oral mucosa of a variety of patients and healthy volunteers visiting the Dermatological
 outpatient clinic.

 Methods Study execution The project is carried out as a collaboration between Dermatological
 Department, Roskilde University Hospital and the Department of Microbiology, Slagelse
 University Hospital under the leadership of primary investigator, Senior Doctor in
 Dermatology, PhD, Ditte Marie Lindhardt Saunte. The project is supported by Medical Doctor in
 Dermatology, PhD Elisabeth Hjardem Taudorf, Dermatological study nurse Helle Anette Jensen,
 and the established research group at the Dermatological Department.

 The samples will be analyzed at the Department of Microbiology, Slagelse University Hospital
 under the surveillance of specialist registrar doctor Dennis Back Holmgaard and Professor
 Jens Jørgen Elmer Christensen. Dept. of Mycology, Statens Serum Institute, which is a
 national reference laboratory for fungal infections, may be involved in cases where special
 tests are needed. Prof. Maiken Cavling Arendrup is the main contact person.

 Study design A case-control study comparing the incidence of yeast colonization or infection
 in skin and oral mucosa of patients with different skin diseases and healthy volunteers.
 Patients with selected skin diseases, staff at Zealand University Hospital in Roskilde,
 relatives to staff and students with relation to the Dermatologic Department will be asked to
 fill out a short questionnaire and have swaps taken from oral mucosa, as well as skin
 scrapings and tape strips from lesional skin (only patients) and non-lesional skin (all).

 Swaps will be examined at the Department of Microbiology, Slagelse University Hospital.
 Samples will be cultured and cultures positive for yeast will be identified using MALDI-TOF
 ms (Matrix-assisted laser desorption-ionization Time of flight mass spectrometry). Skin
 scrapings and tape strips will be investigated for the presence of yeasts, i.e. Candida and
 Malassezia, and when possible investigated for subtypes. The subgroup of patients initiating
 systemic therapy for their skin disease at the first examination will be asked to repeat the
 questionnaire, swaps, skin scrapings and tape strips after approximately three months.

 Clinical photos of lesional skin or mucosa will be taken and stored at a secure IT site
 (Sharepoint and in SP clinical report) after written consent.

 Statistics Prevalence and Odds Ratios (OR) will be determined. With a two-sided significance
 level of 95%, a power of 80 %, an expected ratio of healthy controls vs. patients with skin
 disease of 0.5 and an expected OR of 2.73 a minimum sample size of 127 patients per skin
 disease and 64 healthy controls are needed. We aim to include approximately of 130 patients
 per skin disease. In total, a maximum of 700 individuals will be included, of which 70 will
 be healthy controls. Inclusion of patients with rare skin diseases may necessitate fewer
 patients in some groups.

 Risks, side effects and drawbacks All samples consist of non-invasive mucosal swaps, skin
 scrapings or superficial tape strips which holds no risk of known adverse effects. It may be
 associated with minimal discomfort during sample collection and participants may use an
 additional 15 minutes of their time in order to receive information regarding the project.
 Apart from that, this project causes no known risks, side effects or drawbacks.

 Biologic material Swaps from mucosal membranes, skin scrapings and superficial tape strips
 from the skin surface will be collected and analyzed for the presence of yeasts whereupon
 samples will be destroyed. There is no biobank involved in this project.

 Economy The Dermatologic Department, Roskilde University Hospital provides sample materials
 and Department of Microbiology, Slagelse University Hospital analyzes the samples. Both
 departments cover their own expenses. The project is completely independent and does not
 receive financial support from third parties. None of the involved research workers receive
 payment for participation or has conflicts of interest related to the project.

 Remuneration for trial participants Participants will not receive any remuneration or
 compensation related to study participation.

 Recruitment of trial participants and informed consent Patients, relatives and staff
 associated to the Dermatologic Department in Roskilde will be asked to participate. Patients
 and relatives will be recruited during a routine visit to the clinic, while staff will be
 offered participation during a regular staff meeting. A private consultation will take place,
 where each participant will receive individual oral and written information about the project
 in a quiet atmosphere. The participant can bring a bystander and will be offered time for
 consideration. If requested, an extra interview with repeated possibility to bring a
 bystander will be provided. If a person wants to participate in the project and meet criteria
 for inclusion, informed consent will be signed, a short questionnaire filled out and samples
 will be collected during their regular outpatient visit or by individual appointment.

 Publication of results Positive as well as negative results will be published in relevant
 international Scientific Journals and presented at Scientific meetings and congresses.

 Research ethics Many patients, staffs and relatives will be asked to participate in this
 case-control study, spend a short amount of extra time during an appointment at the clinic
 and may experience minimal discomfort during collection of samples. In contrast, information
 about yeast colonization in different skin diseases may provide a completely new insight and
 form the basis for further studies to detect the possible causality between yeast
 colonization and inflammatory skin diseases. Thus, the potential small disadvantages for
 project participants can by far be justified by the large amount of new knowledge obtained.
Inclusion Criteria:

 -  Legally competent women and men

 -  Age 18 years or older

 Exclusion Criteria

 -  Actual systemic or topical antifungal therapy

 -  Pregnant or lactating women