The Impact of Targeted Therapy on Microorganism in Patients With Psoriasis

Background: Psoriasis is a chronic, immunologically-mediated, inflammatory skin disease and targeted therapies e.g. tumor necrosis factor (TNF)-α and TH-17 antagonists have become increasing important agents in the management of psoriasis. TNF, interleukin-17 (IL-17) and TH-17 play major roles in defense against infection. Large-scaled clinical trials and post-marking surveillance had shown these agents may increase susceptibility to infections. Most studies evaluate the reactivation of tuberculosis but the influence of targeted therapies on the viral infection has not been extensively investigated. TNF-α has been shown to contribute to the killing of cytomegalovirus (CMV)- and human papillomaviruses (HPV)-infected cells. Additionally, recent studies have shown a high prevalence of HPV DNA in psoriatic skin and increased HPV5 antibodies in patients with psoriasis. The prevalence of HPV in the skin was also affected by therapeutic modalities, such as psoralen-ultraviolet A (PUVA). Several case reports in which CMV, Epstein-Barr virus (EBV) and HPV infection complicated therapy with TNF-α antagonists have been reported. However, the study investigated the effect of TNF-α antagonists and other biologics on reactivation of latent viruses is limited. Only two studies investigated the short-term effect of infliximab on reaction of herpesviruses in patients of rheumatoid arthritis and Crohn's disease. The high prevalence of combination use of immunosuppressants, such as methotrexate alongside with TNF-α antagonists in these patients is different from patients with psoriasis. Additionally, various bacterium and fungi, such as Staphylococcus aureus, Malassezia are associated with provocation and/or exacerbation of psoriasis and recent studies had shown IL-17 is essential for the immune response to common fungus Candida albicans. Aim: The aim of this study is to prospectively investigate the effect of target therapies (TNF-α, TH-17 antagonist, IL-17 antagonists, tofacitinib and apremilast) on the activation of viruses, including CMV, EBV and HPV and the impact of biologics on the prevalence of surface colonization of microorganism, including HPV, bacteria and fungi, in patients with psoriasis. Methods and procedures: Our project consists of two related study. The first (Study 1), a prospective observational study, included patients with psoriasis who are going to undergo biologics therapy, the viral loads of CMV and EBV, HPV DNA detection in eyebrow hairs and skin scales, and bacterial, fungal cultures from skin scales were performed before the initiation, 12 and 24 weeks after initiation of the target therapies, 12 weeks after discontinuation of target therapies. This part of our project is to investigate the dynamic effect of biologics on the microorganisms in patients with psoriasis. The second part (Study 2), a case control study, recruits psoriasis patients who have started target therapies, they receive the sampling of blood, eyebrow hairs and skin scales for CMV, EBV and HPV investigations when they are enrolled. Control group compromised of age-and disease severity-matched psoriasis patients who are not treating with target therapies or other systemic antipsoriatic agents. Comparison of the prevalence of latent virus, virus reactivation, bacteria and fungi skin colonization between psoriasis patients who are treating with and without target therapies is performed. The aim of study 2 was to assess any difference of the status of latent virus or microorganism colonization in skins between psoriasis patients treated with and without target therapies.

Sex

All

Minimum age

20 Years

Maximum age

90 Years

Study 1

Inclusion Criteria:

* Clinical diagnosis of psoriasis/psoriatic arthritis and are going o receive target therapies in the near future
* Age more than 20 years old
* Will receive target therapies for psoriasis/psoriatic arthritis
* Willing to receive blood, hair and skin scale sampling

Exclusion Criteria:

* Pregnancy
* Not candidates for topical therapies, such as :

Active tuberculosis or HIV, human papillomaviruses, cytomegalovirus infection, Epstein-Barr virus infection Evidence of latent tuberculosis but refuse to receive isoniazid prophylaxis Have malignancy required for chemotherapy or radiotherapy Active uncontrolled hepatitis -Have received phototherapy, systemic immunosuppressants or target therapies within 14, 30, 84 days prior to enrollment, respectively Study 2 (case group)

Inclusion Criteria:

* Clinical diagnosis of psoriasis/psoriatic arthritis
* Age more than years old
* Have received target therapies for more than 3 months
* willing to receive blood, hair and skin scale sampling

Exclusion Criteria:

* Pregnancy
* Not candidates for topical therapies, such as :

Active tuberculosis or HIV, human papillomaviruses, cytomegalovirus infection, Epstein-Barr virus infection Evidence of latent tuberculosis but refuse to receive isoniazid prophylaxis Have malignancy required for chemotherapy or radiotherapy Active uncontrolled hepatitis

-Have received phototherapy, or systemic immunosuppressants within 14 and 30 days prior to enrollment,respectively Study 2 (control group)

Inclusion Criteria:

* Clinical diagnosis of psoriasis/psoriatic arthritis and are going o receive target therapies in the near future
* Age more than 20 years old
* Willing to receive blood, hair and skin scale sampling
* Without phototherapy, systemic immunosuppressants or target therapies within 84 days prior to enrollment, respectively

Exclusion Criteria:

* Pregnancy
* Have received phototherapy within 30 days prior to enrollment