Reactivation of human polyomavirus JC in patients affected by psoriasis vulgaris and psoriatic arthritis and treated with biological drugs: Preliminary results

Abstract

Psoriasis vulgaris (PsV) and psoriatic arthritis (PSA) are inter‐related heritable inflammatory skin diseases. Psoriatic lesions develop as a result of abnormal immune responses, hyperproliferation and altered differentiation of keratinocytes, and a notable subset of psoriatic patients develops PsA, characterized by joints inflammation. Recently, biological drugs were introduced to treat these diseases. However, this therapy has already been associated with the development of serious life‐threatening infections, such as the reactivation of human polyomavirus JC (JCV), responsible for the progressive multifocal leukoencephalopathy (PML), a lethal demyelinating disease caused by oligodendrocytes lytic infection. Therefore, the aims of our study were the investigation of the possible JCV reactivation in PsV and PsA patients treated with adalimumab, etanercept, and methotrexate, performing quantitative real‐time PCR in sera and skin biopsies at the time of recruitment (T0) and after 3 (T3) and 6 (T6) months of treatment, and the sequencing analysis of the JCV non‐coding control region (NCCR). We found JCV DNA in 5/15 PsV patients and in 2/15 PsA patients and JCV NCCR sequence analysis always showed a structure similar to non‐pathogenic CY archetype, with random occurrence of a few irrelevant point mutations. Nevertheless the poor number of patients analyzed, our preliminary data can pave the way for taking into account that the follow‐up of JCV DNA detection and the JCV NCCR sequence analysis in psoriatic patients may be important to evaluate the risk of PML onset, considering that patients affected by autoimmune diseases and treated with biologics continue to rise. J. Cell. Physiol. 227: 3796–3802, 2012. © 2012 Wiley Periodicals, Inc.

Prevalence of human polyomavirus DNA in eyebrow hairs plucked from patients with psoriasis treated with TNF inhibitors

“…In this scenario, PyV could leave its latent state, 2,4 allowing the virus reactivation. 5 Our study demonstrates for the first time the high prevalence of PyV DNA in eyebrow hair follicles from psoriasis patients with no significant difference between patients treated with TNFi or methotrexate. MCPyV DNA was previously detected in cutaneous swabs (40-62%) of healthy controls as well as PyV6 and PyV7 genomes (14% and 11%, respectively).…”

“…4 Chlorphenesin is reported to have bactericidal activity against Gram (+) and Gram (À) bacteria and fungicidal activity against Aspergillus niger and Candida albicans. 5 According to the Voluntary Cosmetic Registration Program, chlorphenesin is used in more than 1300 cosmetic products and should be considered safe. 5 Although chlorphenesin up to now seems to be an unusual sensitizer, it is important to consider it as a possible allergen, as it is now an ingredient in moisturizers that are used in the basic treatment and skin care of eczema patients as illustrated by our case.…”

“…Furthermore, JCV viremia was also detected in psoriasis patients treated with biological drugs. 5 TNF-a blocking in psoriatic patients leads to a decrease in pro-inflammatory cytokine levels and to inhibition of lymphocytes recruitment, involving the anti-viral state control. In this scenario, PyV could leave its latent state, 2,4 allowing the virus reactivation.…”

Reactivation of latent viruses after treatment with biological therapies

“…63 Other studies have demonstrated the presence of JC virus DNA in the blood whilst on biologic therapy but not fulminant reactivation causing multifocal leukoencephalopathy. 64,65 Like herpes zoster, JC virus remains in a latent phase and has been found in oligodendrocytes and astrocytes of the human brain; reactivation of the transcriptional process of JC virus may be the initial trigger in the lead-up to multifocal leukoencephalopathy. 66…”

Increased Prevalence of Human Polyomavirus JC Viruria in Chronic Inflammatory Rheumatic Diseases Patients in Treatment with Anti-TNF α: A 18 Month Follow-Up Study

“…Poor data are present in literature regarding the possible link between administration of etanercept and JCV infection or reactivation in treated patients. However, in 2012, Nardis et al, found JCV DNA in 2/15 PsA patients and in the same year, in a 23-year-old Native American woman with a history of systemic lupus erythematosus and erosive polyarthritis treated with prednisone and etanercept, PML was diagnosed (Graff-Radford et al, 2012 ; Nardis et al, 2012 ).…”