Evaluation of thiol/disulfide homeostasis in patients with pityriasis rosea.

Purpose: Pityriasis rosea (PR) is a common, self-limiting, inflammatory skin disease with an acute onset. The etiology of PR is not yet clearly known but the defect in the oxidation system involved in many papulosquamous skin diseases may play a role. Thiol/disulfide homeostasis is a new marker of oxidative stress and has been studied in many diseases in recent years. The aim of this study to investigate thiol/disulfide homeostasis in PR patients. Material and methods: Thirty-four patients (18 females, 16 males; median age 26 years) that presented to the Dermatology Clinic of Istanbul Medipol Mega University Hospital between November 2017 and December 2018 and were clinically and/or histopathologically diagnosed with PR, and 30 healthy individuals (16 females, 14 males; median age 27 years) were included in the study. The serum native thiol and total thiol were measured by a novel colorimetric, automated method. The disulfide levels and disulfide/native thiol ratios were also calculated from these measured parameters. Results: There was no statistically significant difference in the serum native thiol and total thiol concentration between the PR and control groups (p = 0.711 and 0.788, respectively). Disulfide, disulfide/native thiol, and disulfide/total thiol levels were significantly higher in patients with PR (p = 0.002, 0.006 and 0.006, respectively). Conclusions: The thiol-disulfide balance shifted toward disulfide in patients with PR. This demonstrates the importance of oxidative stress in the etiopathogenesis of PR using a new marker.

Pityriasis Rosea during Pregnancy: Major and Minor Alarming Signs.

BACKGROUND: Pityriasis rosea (PR) is a self-limiting exanthematous disease associated with human herpesvirus (HHV)-6 and/or HHV-7 reactivation. In pregnant women, PR may be associated with pregnancy complications. OBJECTIVE: To determine relevant risk factors in the development of negative pregnancy outcome in PR. METHODS: Between 2005 and 2017 at the Department of Dermatology, University of Genoa, we recruited 76 women who developed PR during pregnancy. In 60 patients without known risk factors for intrauterine fetal death (30 with pregnancy complications and 30 without) we analyzed the pregnancy week of PR onset, presence of enanthem and of constitutional symptoms, PR body surface area involvement, age, and in 50 patients (20 with pregnancy complications and 30 without), the viral load of HHV-6 and HHV-7 (copies/mL). RESULTS: In logistic regression analysis, early onset of PR (p = 0.0017) and enanthem (p = 0.0392) proved to be significantly associated with pregnancy complications. HHV-6 viral load (copies/mL) (p < 0.0001), constitutional symptoms (p < 0.001), and PR body surface area involvement (p < 0.004) were also significantly associated with pregnancy complications. CONCLUSION: The onset of PR before week 15 and enanthem may be considered major risk factors that should alarm the dermatologist. Constitutional symptoms and involvement of > 50% of the body area may be considered minor risk factors.

The role of interleukin-22 in pityriasis rosea.

BACKGROUND: Pityriasis rosea (PR) is an exanthematous disease related to reactivation of human herpes virus (HHV) types 6 and 7. The pathogenesis and cytokine profile of PR are still poorly understood.There is a large amount of evidence indicating a viral aetiology for PR. AIM: To measure the serum level of interleukin (IL)-22, a cytokine expressed by T helper (Th)17 cells in patients with PR to explore the possible association of IL-22 with the pathogenesis of the disease. METHODS: This case-control study enrolled 25 patients with PR (mean ± SD age 20 ± 12 years) and a control group of 25 apparently healthy individuals (mean age 18 ± 12.1 years). Blood samples were collected from both patients and controls to measure serum IL-22. Scoring of PR was performed using the Pityriasis Rosea Severity Score (PRSS). RESULTS: There was a statistically significant difference in IL-22 serum level between the patient and control groups. The IL-22 serum level increased with increase in disease severity (PRSS), extent and duration. CONCLUSION: Through its proinflammatory cytokines, IL-22 plays a role in the inflammatory process of PR.

The Role of Cytokines, Chemokines, and Growth Factors in the Pathogenesis of Pityriasis Rosea.

INTRODUCTION: Pityriasis rosea (PR) is an exanthematous disease related to human herpesvirus- (HHV-) 6/7 reactivation. The network of mediators involved in recruiting the infiltrating inflammatory cells has never been studied. Object. To investigate the levels of serum cytokines, growth factors, and chemokines in PR and healthy controls in order to elucidate the PR pathogenesis. MATERIALS AND METHODS: Interleukin- (IL-) 1, IL-6, IL-17, interferon- (IFN-) γ, tumor necrosis factor- (TNF-) α, vascular endothelial growth factor (VEGF), granulocyte colony stimulating factor (G-CSF), and chemokines, CXCL8 (IL-8) and CXCL10 (IP-10), were measured simultaneously by a multiplex assay in early acute PR patients' sera and healthy controls. Subsequently, sera from PR patients were analysed at 3 different times (0, 15, and 30 days). RESULTS AND DISCUSSION: Serum levels of IL-17, IFN-γ, VEGF, and IP-10 resulted to be upregulated in PR patients compared to controls. IL-17 has a key role in host defense against pathogens stimulating the release of proinflammatory cytokines/chemokines. IFN-γ has a direct antiviral activity promoting NK cells and virus specific T cells cytotoxicity. VEGF stimulates vasculogenesis and angiogenesis. IP-10 can induce chemotaxis, apoptosis, cell growth, and angiogenesis. CONCLUSIONS: Our findings suggest that these inflammatory mediators may modulate PR pathogenesis in synergistic manner.

The detection of human herpesvirus-8 DNA in plasma and peripheral blood mononuclear cells in adult patients with pityriasis rosea by polymerase chain reaction.

BACKGROUND: Herpesvirus-like particles have been reported to be detectable by electron microscopy in lesional biopsy of patients with pityriasis rosea (PR). We report a study investigating the association of PR with human herpesvirus-8 (HHV-8) infection. METHODS: Our setting is a teaching clinic affiliated to a university. We recruited eight patients aged 28-47 years (mean: 34.5 years) diagnosed with PR during a one-year period. We collected acute blood specimens at presentation and convalescent blood specimens three to four weeks later. We also collected skin scrapings from the herald patch where present and from truncal secondary lesions. RESULTS: We detected HHV-8 DNA by a nested PCR (polymerase chain reaction) targeting, respectively, a 233-bp and a 160-bp fragment of ORF 26. PCR for HHV-8 DNA was negative in the peripheral blood mononuclear cells and plasma of acute and convalescent specimens of all patients, and negative in all skin scrapings. We detected anti-HHV-8 IgG and IgM antibodies by the indirect immunofluorescence. Four patients had IgG antibodies against HHV-8, but with no significant rise of titre. None were positive for anti-HHV-8 IgM antibody. CONCLUSION: We conclude that PR is not associated with HHV-8 infection.

Investigation of herpes simplex virus DNA in pityriasis rosea by polymerase chain reaction.

BACKGROUND: Pityriasis rosea (PR) is an acute, inflammatory disease of unknown cause. Clinical and experimental findings indicate an infectious etiology of PR. Our purpose is to examine the skin lesions and blood samples of PR patients by polymerase chain reaction (PCR) for the presence of HSV type 1 and 2 DNA. METHODS: The lesional skin biopsies from 10 patients and blood samples from two randomized patients with clinically and histologically confirmed pityriasis rosea were examined by PCR. RESULTS: No HSV 1 and HSV 2 DNA was detected in the lesional biopsy and blood samples. CONCLUSIONS: We could not identify a relationship between HSV 1, HSV 2 and PR.

Human herpesvirus 7 in patients with pityriasis rosea. Electron microscopy investigations and polymerase chain reaction in mononuclear cells, plasma and skin.

BACKGROUND: Clinical evidence suggests a viral etiology for pityriasis rosea (PR). OBJECTIVE: To evaluate human herpesvirus (HHV)-6 and HHV-7 as candidates for the etiology of PR. METHODS: Blood and skin tissue from 12 patients with acute PR, and 12 patients with other dermatoses were studied, as well as blood samples from 25 healthy persons. Serum interferon (IFN)-alpha and IFN-gamma were analyzed by ELISA. Analysis of morphological changes in cocultured peripheral blood mononuclear cells (PBMC) and electron microscopy (EM) to identify viral particles were performed. Polymerase chain reaction (PCR) with specific primers for HHV-6 and HHV-7 DNA sequences was performed on the plasma and PBMC of patients and healthy controls and on the skin of patients with PR and other skin diseases. RESULTS: PR plasma contained detectable IFN-alpha and IFN-gamma, whereas plasma from controls did not. PBMC from PR patients showed ballooning cells and syncytia after 7 days in culture whereas PBMC from controls and recovered PR patients did not. This cytopathic effect was also documented in a PR patient who relapsed and in Sup-T1 cell cultures inoculated with the cell-free supernatant from centrifuged cultured PBMC; in this supernatant, herpesvirus, virions were detected by EM, PCR identified HHV-7 DNA in PBMC, plasma and skin from all patients with active PR and in the PBMC only of 5 patients tested 10-14 months later. Weaker signals of HHV-7 DNA were detected in PBMC of 11 controls, but not in their plasma. Skin was negative for HHV-7 in all control specimens. CONCLUSIONS: Although the detection of HHV-7 DNA in PBMC and tissues does not prove directly a causal role, HHV-7 DNA in cell-free plasma corresponds to active replication which supports a causal relationship. We propose that PR is a clinical presentation of HHV-7 reactivation.

Immunological studies of pityriasis rosea (Gibert).

In order to elucidate the immunological mechanism in the pathogenesis of pityriasis rosea, immunofluorescent studies were performed on sera obtained from forty patients with this disease. Antibodies against the cytoplasm of normal human epidermal cells were demonstrated in the sera of all patients. The antibody titer showed a tendency to increase within 3 weeks after onset of secondary eruptions and then to decrease gradually until the period of recovery. The immunoglobulin class was determined to be IgM. Furthermore, by the direct immunofluorescent technique, deposits of IgM in the epidermal cells of skin lesions were demonstrated in 3 of 6 herald lesions and in 1 of 4 secondary eruptions. It is suggested that anti-cytoplasmic antibodies produced by some unknown cause may induce the development of secondary eruptions of this disease.