Materiały źródłowe

• #1 Pityriasis Rosea – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK448091/

  The exact cause of PR is unknown; however, features like seasonal variation and community clustering suggest that it has an infection-based origin. Infections from viruses, bacteria, and spirochetes, as well as noninfective causes like atopy and autoimmunity, are known causes of PR. […] Recently, reactivation of latent human herpesvirus (HHV)-6 and HHV-7 infections have been identified as possible etiologic agents. […] The pathophysiology of PR is not entirely understood. However, a lack of natural killer (NK) cell and B-cell activity in PR lesions has been noted, suggesting a predominantly T-cell mediated immunity. Increased CD4 T-cells and Langerhans cells are present in the dermis, possibly reflecting viral antigen processing and presentation.

• #2 Pityriasis Rosea: An Update on Etiopathogenesis and Management of Difficult Aspects

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4966395/

  Pityriasis rosea (PR) is a benign papulosquamous disorder seen commonly in clinical practice. […] The etiopathogenesis of PR has always been a dilemma, and extensive research is going on to elicit the exact cause. […] Numerous hypotheses have been postulated about the exact cause of PR, incriminating both infective agents such as viruses, bacteria, spirochetes, and noninfective etiologies such as atopy and autoimmunity. […] There are various factors which have pointed toward an infectious etiology for this condition such as seasonal variations, presence of a prodrome, familial clustering in some cases and presence of herald patch (which may be correlated with the inoculation point of organism) followed by the secondary eruption and infrequent recurrences. […] However, despite repeated efforts, there is no definite evidence for a single infectious agent for this disorder. […] Recently, there is an increasing evidence to suggest the role of human herpes virus (HHV) in PR. […] In light of the above studies, HHV 6 and 7 are the most likely etiologic agents for PR and further studies should be targeted toward establishing their definite role.

• #3 Herald Patch as the Only Evidence of Pityriasis Rosea: Clinical, Laboratory and Pathogenetic Features

  https://www.mdpi.com/1999-4915/17/1/119

  Pityriasis rosea (PR) is a self-limited exanthem associated with the endogenous systemic reactivation of human herpesvirus (HHV)-6 and HHV-7. […] A large body of evidence supports the causal role of the endogenous systemic active human herpesvirus (HHV)-6 and HHV-7 infections in PR pathogenesis. […] The cytopathic effects specific to HHVs, such as ballooning cells and syncytia formation, were observed in the culture of peripheral blood mononuclear cells (PBMCs) from PR patients, the detection of cell-free HHV-6 and HHV-7 DNA in the plasma of PR patients, and the presence of their viral antigens and messenger RNA expression in PR skin lesions are all markers of active viral replication. […] Furthermore, HHV virions in various stages of morphogenesis have been detected by electron microscopy in skin lesions and the supernatant of co-cultured PBMCs from PR patients.

• #4 Commentary on: ”Pityriasis Rosea Recurrence is Much Higher than Previously Known: A Prospective Study” | HTML | Acta Dermato-Venereologica

  https://www.medicaljournals.se/acta/content/html/10.2340/00015555-3265

  We agree with the author that the rate of recurrence of PR is probably greater than that reported in the literature. […] Indeed, a large body of evidence highlighted a close relationship between PR and human herpesvirus (HHV)-6 and/or -7 endogenous reactivation. […] Several studies have identified HHV-6 and HHV-7 DNA by PCR and calibrated quantitative real-time PCR in plasma, peripheral blood mononuclear cells (PBMCs) and lesional skin of patients with PR. […] Importantly, the detection of cell-free viral DNA in plasma, mRNA and antigens in skin lesions and cytopathic effects in culture are considered as markers of active viral replication. […] All these data emphasize the role of both viruses in the pathogenesis of PR; in only a few diseases is there is so much evidence proving a viral aetiology.

• #5 Pityriasis Rosea: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1107532-overview

  Pityriasis rosea (PR) has often been considered to be a viral exanthem, a view supported by the conditions seasonal occurrence, its clinical course, the possibility of epidemic occurrence, the presence of occasional prodromal symptoms, and the low rate of recurrence. […] However, a 4-year recurrence rate of 25.9% was documented in one survey of 212 patients. […] Oxidative stress may play a role too. […] One survey noted a significant temporal clustering and seasonal variation, and the incidence of dengue fever significantly correlated. […] Pityriasis rosea has been linked to upper tract respiratory infections. […] Some immunologic data also suggest a viral etiology. […] A lack of natural killer (NK) cell and B-cell activity in pityriasis rosea lesions has been noted, suggesting a predominantly T-cell mediated immunity in the development of the condition. […] Increased amounts of CD4 T cells and Langerhans cells are present in the dermis, possibly reflecting viral antigen processing and presentation. […] A classification based on pathogenetic mechanisms associated with the different presentations of pityriasis rosea has been proposed.

• #6 Pityriasis Rosea | AAFP

  https://www.aafp.org/pubs/afp/issues/2004/0101/p87.html

  Pityriasis rosea is a common, acute exanthem of uncertain etiology. Viral and bacterial causes have been sought, but convincing answers have not yet been found. […] Although the etiology of pityriasis rosea is unclear, several factors indicate an infectious cause. First, outbreaks of the condition occur in clusters, suggesting that an infectious agent is circulating within a community. Second, recurrence of pityriasis rosea outside the acute phase is rare, suggesting that there is long-lasting immunity after the infection. Third, up to 69 percent of patients with pityriasis rosea have a prodromal illness before the herald patch appears. […] Unfortunately, even though electron microscopy shows some viral changes and possible viral particles, antibody and polymerase chain reaction tests for known viruses have failed to identify an offending virus.

• #7 Herald Patch as the Only Evidence of Pityriasis Rosea: Clinical, Laboratory and Pathogenetic Features

  https://www.mdpi.com/1999-4915/17/1/119

  Pityriasis rosea (PR) is a self-limited exanthem associated with the endogenous systemic reactivation of human herpesvirus (HHV)-6 and HHV-7. […] A large body of evidence supports the causal role of the endogenous systemic active human herpesvirus (HHV)-6 and HHV-7 infections in PR pathogenesis. […] The cytopathic effects specific to HHVs, such as ballooning cells and syncytia formation, were observed in the culture of peripheral blood mononuclear cells (PBMCs) from PR patients, the detection of cell-free HHV-6 and HHV-7 DNA in the plasma of PR patients, and the presence of their viral antigens and messenger RNA expression in PR skin lesions are all markers of active viral replication. […] Furthermore, HHV virions in various stages of morphogenesis have been detected by electron microscopy in skin lesions and the supernatant of co-cultured PBMCs from PR patients.

• #8 Pityriasis rosea during COVID-19 and its pathogenesis | CoLab

  https://colab.ws/articles/10.1016%2Fj.jdin.2022.05.015

  The article by Nussbaum et al stated that PR has inconsistent association with human herpesvirus (HHV)-6 and HHV-7. […] A large body of evidence from studies by different authors highlighted a close relationship between PR and systemic active infection with both HHV-7 and HHV-6. […] Several studies have identified HHV-6 and HHV-7 DNA by polymerase chain reaction in plasma, a direct marker of viral replication, in peripheral blood mononuclear cells and in lesional skin of patients with PR; HHV-6 and HHV-7 messenger RNA expression and specific antigens have been demonstrated in PR skin lesions by in situ hybridization and immunohistochemistry, respectively. […] The credit given to the role of HHV-6/7 systemic reactivation in PR pathogenesis is easily detectable from the quotes reported by different authors in the articles about PR during COVID-19 and after COVID-19 vaccination.

• #9

  https://link.springer.com/article/10.1007/s40257-024-00915-7

  Pityriasis rosea (PR) is a prevalent dermatological condition characterized by a distinctive herald patch, followed by secondary eruptions, often forming a Christmas tree pattern on the trunk. […] Despite its recognizable clinical presentation, the etiology of PR remains uncertain, with hypotheses pointing to both infectious and noninfectious origins. Human herpesviruses (HHV) 6 and 7 have been implicated, with evidence suggesting viral reactivation as a potential trigger. […] This review evaluates the current understanding of PR’s pathogenesis, highlighting both infectious and noninfectious hypotheses, including viral reactivation and immune response mechanisms. […] Notably, human herpesviruses (HHV) 6 and 7 have been implicated in its pathogenesis, with evidence pointing to viral reactivation as a potential trigger for the condition.

• #10

  https://journals.lww.com/ijd/fulltext/2016/61040/pityriasis_rosea__an_update_on_etiopathogenesis.3.aspx

  Numerous hypotheses have been postulated about the exact cause of PR, incriminating both infective agents such as viruses, bacteria, spirochetes, and noninfective etiologies such as atopy and autoimmunity. […] There are various factors which have pointed toward an infectious etiology for this condition such as seasonal variations, presence of a prodrome, familial clustering in some cases and presence of herald patch (which may be correlated with the inoculation point of organism) followed by the secondary eruption and infrequent recurrences. However, despite repeated efforts, there is no definite evidence for a single infectious agent for this disorder. […] Recently, there is an increasing evidence to suggest the role of human herpes virus (HHV) in PR. In 1997, Drago et al. first suggested the role of HHV 7 in etiology of PR by detecting HHV 7 in peripheral blood mononuclear cells and plasma of patients with PR and not in controls, thus suggesting a probable causal relationship. […] In light of the above studies, HHV 6 and 7 are the most likely etiologic agents for PR and further studies should be targeted toward establishing their definite role.

• #11 Pityriasis rosea during COVID-19 and its pathogenesis | CoLab

  https://colab.ws/articles/10.1016%2Fj.jdin.2022.05.015

  Indeed, PR is not related to a primary infection but to an endogenous viral reactivation, as in the case of shingles and varicella-zoster virus. […] The psychologic stress linked to the pandemic and the immunosuppression associated with SARS-CoV-2 infection may act in enabling the reactivation of latent infections, such as HHV-6/7, causing, thereby indirectly, the onset of PR. […] We emphasize the relevance of looking for any viral reactivation in patients infected with SARS-CoV-2.

• #12 Herald Patch as the Only Evidence of Pityriasis Rosea: Clinical, Laboratory and Pathogenetic Features

  https://www.mdpi.com/1999-4915/17/1/119

  The levels of several interleukins (ILs) and chemokines, such as IL-17, IL-22, IL-36, IFN-γ, vascular endothelial growth factor (VEGF), CX3CL1/fractalkine, and CXCL10, were found to be upregulated in the sera of PR patients compared to controls. […] These cytokines and chemokines networks are further hints that PR is associated with activation of cellular immunity and induction of an inflammatory response against a virus. […] Several mechanisms may trigger HHV-6 and HHV-7 reactivation and, therefore, the occurrence of PR: exhaustion, post-surgery or post-traumatic stress, fever, states of immunosuppression, pregnancy, and inappropriate exposure to ultraviolet rays. […] Recently, it has been suggested that Toll-like receptors (TLRs) may play a role in the pathogenesis of PR. […] It must be emphasized that TLRs 3, 7, 8, and 9 are involved in the responses against several viral infections.

• #13 ATYPICAL PITYRIASIS ROSEA IN A YOUNG COLOMBIAN WOMAN. CASE REPORT

  http://www.scielo.org.co/scielo.php?script=sci_arttext&pid=S2462-85222021000200008

  Pityriasis rosea is an acute and self-limited exanthem first described by Gilbert in 1860. Its treatment is symptomatic, and although there is no conclusive evidence, it has been associated with the reactivation of the human herpesviruses 6 and 7 (HHV-6 and HHV-7). […] This condition has been associated with the reactivation of human herpesviruses 6 and 7 (HHV-6 and HHV-7), as well as with infection with Legionella micdadei, Mycoplasma pneumoniae, enterovirus, COVID-19, and others, although conclusive evidence is lacking. […] Other theories, notably the one given by Burch and Rowell, have proposed that it has an auto-immune origin and are backed by some published research. One of such studies reported that 28% of the patients included in their sample had anti-lymphocyte antibodies, suggesting an autoimmune role.

• #14 Comment on “Pityriasis rosea in a COVID-19 Pediatric Patient” | Actas Dermo-Sifiliográficas

  http://www.actasdermo.org/en-comment-on-pityriasis-rosea-in-articulo-S0001731022000175

  The authors correctly state that PR is associated with HHV-6 and/or HHV-7 systemic reactivation but include in the PR pathogenesis also autoimmunity, psychogenic factors, vaccines and drugs without making any distinctions between PR and PR-like eruptions. […] In fact, though is true that different factors, including autoimmunity, psychogenic factors, vaccines and drugs may cause HHV-6/7 systemic reactivation and thereby indirectly cause the onset of PR, actually, vaccines and drugs are mostly involved in causing PR-like eruptions. […] Unfortunately, the patient described by nc INS et al. did not perform serology and polymerase chain reaction (PCR) in serum for HHV-6/7 DNA nor for SARS-CoV-2 RNA. These investigations would have been useful to clarify the possible role of SARS-CoV-2 in the pathogenesis of PR associated with COVID-19. In fact, SARS-CoV-2 may play a role as a trans-activating agent, triggering HHV-6 and/or HHV-7 reactivation and causing, thereby indirectly, the onset of PR, as the authors hypothesized.

• #15 Pityriasis Rosea – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK448091/

  The exact cause of PR is unknown; however, features like seasonal variation and community clustering suggest that it has an infection-based origin. Infections from viruses, bacteria, and spirochetes, as well as noninfective causes like atopy and autoimmunity, are known causes of PR. […] Recently, reactivation of latent human herpesvirus (HHV)-6 and HHV-7 infections have been identified as possible etiologic agents. […] The pathophysiology of PR is not entirely understood. However, a lack of natural killer (NK) cell and B-cell activity in PR lesions has been noted, suggesting a predominantly T-cell mediated immunity. Increased CD4 T-cells and Langerhans cells are present in the dermis, possibly reflecting viral antigen processing and presentation.

• #16 Subsets of T lymphocytes in the lesional skin of pityriasis rosea* | Anais Brasileiros de Dermatologia

  https://www.anaisdedermatologia.org.br/en-subsets-t-lymphocytes-in-lesional-articulo-S0365059620302634

  Pityriasis rosea is a common papulosquamous disorder. However, its etiology and pathogenesis remain unclear. […] We investigate the types of inflammatory cells infiltrating the lesional skin of pityriasis rosea and demonstrate whether T-cell-mediated immunity is involved in the pathogenesis of this condition or not. […] Our findings support a predominantly T-cell mediated immunity in the development of pityriasis rosea. […] The pathogenesis of PR remains unknown. […] Therefore, we proposed that weakened Th1 response is most likely to contribute to the pathogenesis of PR. […] Our findings support that a predominantly T-cell-mediated immunity participated in the development of PR.

• #17 Pityriasis Rosea: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1107532-overview

  Pityriasis rosea (PR) has often been considered to be a viral exanthem, a view supported by the conditions seasonal occurrence, its clinical course, the possibility of epidemic occurrence, the presence of occasional prodromal symptoms, and the low rate of recurrence. […] However, a 4-year recurrence rate of 25.9% was documented in one survey of 212 patients. […] Oxidative stress may play a role too. […] One survey noted a significant temporal clustering and seasonal variation, and the incidence of dengue fever significantly correlated. […] Pityriasis rosea has been linked to upper tract respiratory infections. […] Some immunologic data also suggest a viral etiology. […] A lack of natural killer (NK) cell and B-cell activity in pityriasis rosea lesions has been noted, suggesting a predominantly T-cell mediated immunity in the development of the condition. […] Increased amounts of CD4 T cells and Langerhans cells are present in the dermis, possibly reflecting viral antigen processing and presentation. […] A classification based on pathogenetic mechanisms associated with the different presentations of pityriasis rosea has been proposed.

• #18

  https://link.springer.com/article/10.1007/s40257-024-00915-7

  Research suggests that cell-mediated immunity plays a role in PR’s development. […] Aiba and Tagami discovered immunohistological evidence of cellular immune responses in affected skin, noting an increase in mononuclear cells, active CD4+ T-helper cells, and Langerhans cells. […] Further studies by Neoh et al. and Baker et al. confirmed these findings, showing increased markers for T cells and Langerhans cells, but not for B cells or natural killer (NK) cells. […] These studies highlight immune responses typical of viral infections, providing indirect evidence for PR’s proposed viral origin. […] The presence of anti-immunoglobulin M (IgM) keratinocytes in PR patients also suggests that this immune response is responsible for the clinical signs of PR. […] Studies suggest a link between primary infection of HHV-6 or HHV-7 in early childhood and its manifesting as PR in future systemic reactivation.

• #19 Herald Patch as the Only Evidence of Pityriasis Rosea: Clinical, Laboratory and Pathogenetic Features

  https://www.mdpi.com/1999-4915/17/1/119

  The levels of several interleukins (ILs) and chemokines, such as IL-17, IL-22, IL-36, IFN-γ, vascular endothelial growth factor (VEGF), CX3CL1/fractalkine, and CXCL10, were found to be upregulated in the sera of PR patients compared to controls. […] These cytokines and chemokines networks are further hints that PR is associated with activation of cellular immunity and induction of an inflammatory response against a virus. […] Several mechanisms may trigger HHV-6 and HHV-7 reactivation and, therefore, the occurrence of PR: exhaustion, post-surgery or post-traumatic stress, fever, states of immunosuppression, pregnancy, and inappropriate exposure to ultraviolet rays. […] Recently, it has been suggested that Toll-like receptors (TLRs) may play a role in the pathogenesis of PR. […] It must be emphasized that TLRs 3, 7, 8, and 9 are involved in the responses against several viral infections.

• #20 Pityriasis Rosea | Calgary Guide

  https://calgaryguide.ucalgary.ca/pityriasis-rosea/pityriasis-rosea/

  Pityriasis Rosea: Pathogenesis and clinical findings […] Preceding viral infection, reactivation of latent Human Herpesvirus (HHV-6 or HHV-7) […] Exact mechanism unknown […] Activation of T-cell mediated host immune response […] Signal proteins in serum including interleukin 17 (IL-17), interferon gamma (IFN-), vascular endothelial growth factor (VEGF), and induced protein 10 (IP-10), leading to increased capillary permeability […] CD4 lymphocytes, monocytes, eosinophils and Langerhans cell infiltration into the dermis and epidermis […] Activation of B cells and production of anti-keratinocyte IgM antibodies […] Parakeratosis (incomplete keratinocyte maturation) and proliferation of epidermal cells (known as psoriasiform hyperplasia).

• #21 Serum Interleukin-36 in Pityriasis Rosea: A Potential Biomarker for Disease Severity | JCAD – The Journal of Clinical and Aesthetic Dermatology

  https://jcadonline.com/serum-interleukin-36-in-pityriasis-rosea-disease-severity/

  Interleukin 36 (IL-36) is a proinflammatory cytokine that is thought to coordinate innate and adaptive immune responses. […] Disturbed expression of IL-36 was suggested in inflammatory dermatoses, with psoriasis being the most abundantly studied condition. […] A crucial role of IL-36 was also reported in microbial diseases, in both in-vivo and in-vitro laboratory work various bacteria and fungi were able to induce IL-36 cytokines in lung tissue. […] Growing evidence suggests that IL-36 may be considered a double-edged sword that defends and clear pathogens while amplifying an immune reaction that causes marked tissue damage. […] We investigated levels of IL-36 in sera of patients with PR in order to elucidate the etiological and pathological pathway of the disease and contribute more information to the possible link with COVID-19 infection, if any.

• #22 Serum Interleukin-36 in Pityriasis Rosea: A Potential Biomarker for Disease Severity | JCAD – The Journal of Clinical and Aesthetic Dermatology

  https://jcadonline.com/serum-interleukin-36-in-pityriasis-rosea-disease-severity/

  The results of current work revealed a significantly increased serum IL-36 level in patients with PR compared to matched healthy control subjects. […] Moreover, the serum level correlates positively with the severity of the disease as assessed by PRSS. […] The maximum IL-36 activities are most frequently encountered at barrier sites, particularly skin, namely keratinocyte in epidermal layer, suggesting a role of IL-36 -as a pro-inflammatory cytokine- in defending the body from external attackers with a potential antimicrobial function. […] This may explain the increased serum level in our patients than comparable controls, particularly if infectious agent is suspected as a triggering factor. […] We detected a significantly higher level of IL-36 in patients of PR with history of COVID-19 infection -but not with vaccination- and more severe disease as assessed by PRSS despite the history of COVID-19 infection was only reported in 5 percent of patients.

• #23 Serum Interleukin-36 in Pityriasis Rosea: A Potential Biomarker for Disease Severity | JCAD – The Journal of Clinical and Aesthetic Dermatology

  https://jcadonline.com/serum-interleukin-36-in-pityriasis-rosea-disease-severity/

  The results of current work revealed a significantly increased serum IL-36 level in patients with PR compared to matched healthy control subjects. […] Moreover, the serum level correlates positively with the severity of the disease as assessed by PRSS. […] The maximum IL-36 activities are most frequently encountered at barrier sites, particularly skin, namely keratinocyte in epidermal layer, suggesting a role of IL-36 -as a pro-inflammatory cytokine- in defending the body from external attackers with a potential antimicrobial function. […] This may explain the increased serum level in our patients than comparable controls, particularly if infectious agent is suspected as a triggering factor. […] We detected a significantly higher level of IL-36 in patients of PR with history of COVID-19 infection -but not with vaccination- and more severe disease as assessed by PRSS despite the history of COVID-19 infection was only reported in 5 percent of patients.

• #24 Serum Interleukin-36 in Pityriasis Rosea: A Potential Biomarker for Disease Severity | JCAD – The Journal of Clinical and Aesthetic Dermatology

  https://jcadonline.com/serum-interleukin-36-in-pityriasis-rosea-disease-severity/

  Considering that IL-36 is a member of the IL-1 superfamily, it has been suggested as an important regulator of host defence response against micro-pathogens, not only in humans, but within different other species. […] Scant literature is found when it comes to the role of cytokines in PR pathogenesis. […] To the best of our knowledge, we are the first to investigate the level of IL-36 in sera of patients with PR. […] Serum level of IL-36 in patients with PR could be considered a potential biomarker for disease activity.

• #25 Higher Expression of Toll-like Receptors 3, 7, 8, and 9 in Pityriasis Rosea

  https://www.jpatholtm.org/journal/view.php?number=16667

  Pityriasis rosea (PR) is a common papulosquamous skin disease in which an infective agent may be implicated. […] Our aim was to determine the possible roles of TLRs 3, 7, 8, and 9 in the pathogenesis of PR. […] Significantly elevated expression of all studied TLRs were detected in PR patients relative to healthy controls (p .001). […] TLRs 3, 7, 8, and 9 might be involved in the pathogenesis of PR. […] The current study highlights the possible roles played by different TLR pathways in the pathogenesis of PR. […] A significantly elevated expression of the studied TLRs 3, 7, 8, and 9 was documented in PR cases relative to healthy controls. […] Our results revealed non-significant correlations among the studied TLRs in the patient group. […] This could suggest that each TLR can play an individual role in the pathogenesis of PR.

• #26 Herald Patch as the Only Evidence of Pityriasis Rosea: Clinical, Laboratory and Pathogenetic Features

  https://www.mdpi.com/1999-4915/17/1/119

  The levels of several interleukins (ILs) and chemokines, such as IL-17, IL-22, IL-36, IFN-γ, vascular endothelial growth factor (VEGF), CX3CL1/fractalkine, and CXCL10, were found to be upregulated in the sera of PR patients compared to controls. […] These cytokines and chemokines networks are further hints that PR is associated with activation of cellular immunity and induction of an inflammatory response against a virus. […] Several mechanisms may trigger HHV-6 and HHV-7 reactivation and, therefore, the occurrence of PR: exhaustion, post-surgery or post-traumatic stress, fever, states of immunosuppression, pregnancy, and inappropriate exposure to ultraviolet rays. […] Recently, it has been suggested that Toll-like receptors (TLRs) may play a role in the pathogenesis of PR. […] It must be emphasized that TLRs 3, 7, 8, and 9 are involved in the responses against several viral infections.

• #27 Higher Expression of Toll-like Receptors 3, 7, 8, and 9 in Pityriasis Rosea

  https://www.jpatholtm.org/journal/view.php?number=16667

  The possible role of TLRs in PR can be attributed to several mechanisms. […] TLR 3 triggering activates specific signaling pathways that mount an effective immune response through the induction of cytokines and other pro-inflammatory mediators. […] TLRs 3, 7, 8, and 9 have been shown to be involved in responses to viral infection, but no studies have referred to their involvement with HHV. […] In conclusion, the current study indicated that TLRs 3, 7, 8 and 9 have a positive role in PR.

• #28 Higher Expression of Toll-like Receptors 3, 7, 8, and 9 in Pityriasis Rosea

  https://www.jpatholtm.org/journal/view.php?number=16667

  The possible role of TLRs in PR can be attributed to several mechanisms. […] TLR 3 triggering activates specific signaling pathways that mount an effective immune response through the induction of cytokines and other pro-inflammatory mediators. […] TLRs 3, 7, 8, and 9 have been shown to be involved in responses to viral infection, but no studies have referred to their involvement with HHV. […] In conclusion, the current study indicated that TLRs 3, 7, 8 and 9 have a positive role in PR.

• #29 Pityriasis rosea: a distinct entity or viral exanthem?

  https://www.termedia.pl/Pityriasis-rosea-a-distinct-entity-or-viral-exanthem-,56,54777,1,1.html

  It seems that PR might be caused by human herpes virus 6 (HHV-6) and human herpes virus 7 (HHV-7). […] However, Kempf et al., Yasukawa et al., Yoshida, Kosuge et al., Offidani et al., Chuh et al., Wong et al., Karabulut et al. and Yildirim et al. are against this etiology. […] In addition to studies on the viral etiopathogenesis and genetic material of viruses in PBMC, plasma or other human specimens, there are also studies on the immunological mechanisms that accompany pityriasis rosea. […] Indirectly, the viral etiology of the disease is supported by the cytokines and chemokines increased during PR. […] Taking everything into consideration, more research is required to fully understand the etiopathogenesis of pityriasis rosea. […] Although pityriasis rosea seems to be a well-known and common skin disease with the clinical symptoms easy to manage, there are some controversial points which need more attention. […] Taking into consideration the circumstances of the disease onset mentioned in our manuscript, we would like to point out that PR may be considered as a reactive disease associated with decreased immunity caused by infections or pregnancy rather than sui generis disease.

• #30 Pityriasis rosea – An update – Indian Journal of Dermatology, Venereology and Leprology

  https://ijdvl.com/pityriasis-rosea-an-update/

  Recent controversies on the etiology, diagnosis and treatment have led to increased interest in pityriasis rosea (PR). […] Despite active labor for nearly one and a half century by generations of researchers, the etiology of pityriasis rosea (PR) fails to be demystified. Recent controversy is centered on the association of PR with HHV-7 infection. […] There is convincing evidence that PR is not associated with cytomegalovirus, Epstein-Barr virus, parvovirus B19, picornavirus, influenza virus, parainfluenza virus, Chlamydia pneumoniae, C. trachomatis, Legionella longbeachae, L. micdadei, L. pneumophila, and Mycoplasma pneumoniae infections. […] A study reported that 28% of patients with PR have T lymphocytotoxic antibodies. […] The role of autoimmunity in PR warrants further investigations.

• #31 Pityriasis Rosea | AAFP

  https://www.aafp.org/pubs/afp/issues/2004/0101/p87.html

  Several other viruses have been examined, but none has been found to be causative. […] Chlamydia pneumoniae, Legionella pneumophila, and Mycoplasma pneumoniae also have been suggested as potential infectious agents in pityriasis rosea. However, the results of a small prospective case-control study did not show a significant rise in antibodies to these bacteria when affected patients were compared with matched control patients.

• #32 ATYPICAL PITYRIASIS ROSEA IN A YOUNG COLOMBIAN WOMAN. CASE REPORT

  http://www.scielo.org.co/scielo.php?script=sci_arttext&pid=S2462-85222021000200008

  Pityriasis rosea is an acute and self-limited exanthem first described by Gilbert in 1860. Its treatment is symptomatic, and although there is no conclusive evidence, it has been associated with the reactivation of the human herpesviruses 6 and 7 (HHV-6 and HHV-7). […] This condition has been associated with the reactivation of human herpesviruses 6 and 7 (HHV-6 and HHV-7), as well as with infection with Legionella micdadei, Mycoplasma pneumoniae, enterovirus, COVID-19, and others, although conclusive evidence is lacking. […] Other theories, notably the one given by Burch and Rowell, have proposed that it has an auto-immune origin and are backed by some published research. One of such studies reported that 28% of the patients included in their sample had anti-lymphocyte antibodies, suggesting an autoimmune role.

• #33 Pityriasis rosea – DermNet

  https://dermnetnz.org/topics/pityriasis-rosea

  The exact cause is not known. Viral, bacterial, and non-infective causes have been hypothesised. […] Reports suggested pityriasis rosea may be caused by: […] Herpesviruses 6 and 7 (HHV-6/7) have the strongest known association, however studies have not been confirmatory. […] Other viral infections, such as H1N1 influenza A and COVID-19, may also be causative. […] Many drugs have been associated, such as angiotensin-converting enzyme inhibitors, nonsteroidal anti-inflammatory drugs, hydrochlorothiazide, gold, captopril, atypical antipsychotics barbiturates, D-penicillamine, imatinib, metronidazole, isotretinoin, clozapine, and clonidine. […] Pityriasis rosea may be triggered by the Bacillus Calmette-Guerin (BCG), H1N1, diphtheria, smallpox, hepatitis B, Pneumococcus, and COVID-19 vaccines.

• #34

  https://journals.lww.com/ijd/fulltext/2024/03000/a_cross_sectional_study_of_epidemiological_and.6.aspx

  Pityriasis Rosea (PR) is a common, yet enigmatic, dermatological condition characterized by a distinctive clinical presentation. Despite its prevalence, the aetiology and pathogenesis of PR remain elusive. […] The aetiology of PR remains unclear. Multiple hypotheses have been formulated suggesting both infectious (viral and bacterial) and noninfectious aetiology (autoimmunity, atopy, drugs, and vaccines). However, it is thought to be caused by viral agents based on clustering of cases, seasonal variation, presence of prodromal symptoms, course of rash similar to viral exanthem (herald patch followed by developing a secondary eruption), and fewer relapses. […] The histopathological features of PR are nonspecific but essential to rule out other differentials of PR, especially in atypical cases. In our study, we performed a biopsy of patients with atypical morphology and cases in which the clinical diagnosis was questionable. PR shows a predominantly spongiotic tissue reaction pattern. Other findings include parakeratosis, irregular acanthosis, RBC extravasation, perivascular dermal lymphocytic infiltrate, necrotic keratinocyte, dermal melanophages, mucin in the papillary dermis, presence of eosinophils, and dermal oedema. Salute sign was seen in five cases which correlated clinically with collarette scaling. […] The correlation of dermoscopic findings with histopathology revealed a diffuse red background correlated with vascular dilation, collarette scaling with salute sign, and patchy scaling with focal parakeratosis.

• #35 Pityriasis Rosea in a 17-Year-Old Girl

  https://www.contemporarypediatrics.com/view/pityriasis-rosea-17-year-old-girl

  A viral etiology has been proposed because of the seasonal variation, clustering in communities, and the symptoms of antecedent upper respiration tract infection (presumed to be viral) found in up to 20% of affected patients. Human herpesvirus 7 and, to a lesser degree, human herpesvirus 6 have been implicated, but the causative role is still controversial. Histologically, focal parakeratosis, spongiosis, and a superficial lymphohistiocytic perivascular infiltrate might be present.

• #36 Pityriasis Rosea | Calgary Guide

  https://calgaryguide.ucalgary.ca/pityriasis-rosea/pityriasis-rosea/

  Pityriasis Rosea: Pathogenesis and clinical findings […] Preceding viral infection, reactivation of latent Human Herpesvirus (HHV-6 or HHV-7) […] Exact mechanism unknown […] Activation of T-cell mediated host immune response […] Signal proteins in serum including interleukin 17 (IL-17), interferon gamma (IFN-), vascular endothelial growth factor (VEGF), and induced protein 10 (IP-10), leading to increased capillary permeability […] CD4 lymphocytes, monocytes, eosinophils and Langerhans cell infiltration into the dermis and epidermis […] Activation of B cells and production of anti-keratinocyte IgM antibodies […] Parakeratosis (incomplete keratinocyte maturation) and proliferation of epidermal cells (known as psoriasiform hyperplasia).

• #37 Herald Patch as the Only Evidence of Pityriasis Rosea: Clinical, Laboratory and Pathogenetic Features

  https://www.mdpi.com/1999-4915/17/1/119

  Therefore, it is plausible that following the HHV-6 and HHV-7 systemic reactivation and their arrival in the skin, an increased expression of TLRs can be induced (both systemically and in the skin lesions of patients with PR). […] The pathogenic mechanism underlying the manifestation of PR with HP as the only sign of the disease has never been investigated before. […] The findings of our study may suggest some pathogenic mechanisms that could explain the clinical differences between this form of atypical PR and classical PR. […] Therefore, an attempt to explain the pathogenesis of PR characterized only by the HP is the hypothesis that it could be considered an abortive form of the disease that happens when the HHV-6 and/or HHV-7 reactivation from latency is countered by an immunological response (mainly orchestrated by T CD4+ and T CD8+ lymphocytes) that is more effective than in classic PR.

• #38 A Case of Persistent Pityriasis Rosea Successfully Treated by a Short | CCID

  https://www.dovepress.com/a-case-of-persistent-pityriasis-rosea-successfully-treated-by-a-short–peer-reviewed-fulltext-article-CCID

  Pityriasis rosea (PR) is a common inflammatory, erythematous and scaly skin condition that usually affects individuals aged from 20 to 40 years old. […] The exact pathogenesis of pityriasis rosea remains unclear. Neoh et al identified a lack of natural killer cells and B cell activity in active lesions, indicating a predominantly T-cell-mediated immune response. […] Mokadem et al demonstrated the role of IL-22 through its proinflammatory cytokines in the inflammatory process of pityriasis rosea. […] Immunohistochemical studies further supported the significant role of T lymphocyte-mediated cellular immunity in the pathogenesis of pityriasis rosea. […] The JAK-STAT pathway is an intracellular signaling pathway closely associated with many cytokines, participating in various critical biological processes such as cell proliferation, differentiation, apoptosis and immune regulation. […] Therefore in this case, we believed that abrocitinib could be useful for patients with persistent pityriasis rosea at least in alleviating skin rashes and improving severe pruritus by blocking the various inflammatory cytokine pathways.

• #39 Herald Patch as the Only Evidence of Pityriasis Rosea: Clinical, Laboratory and Pathogenetic Features

  https://www.mdpi.com/1999-4915/17/1/119

  Therefore, it is plausible that following the HHV-6 and HHV-7 systemic reactivation and their arrival in the skin, an increased expression of TLRs can be induced (both systemically and in the skin lesions of patients with PR). […] The pathogenic mechanism underlying the manifestation of PR with HP as the only sign of the disease has never been investigated before. […] The findings of our study may suggest some pathogenic mechanisms that could explain the clinical differences between this form of atypical PR and classical PR. […] Therefore, an attempt to explain the pathogenesis of PR characterized only by the HP is the hypothesis that it could be considered an abortive form of the disease that happens when the HHV-6 and/or HHV-7 reactivation from latency is countered by an immunological response (mainly orchestrated by T CD4+ and T CD8+ lymphocytes) that is more effective than in classic PR.

• #40 Pityriasis Rosea: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1107532-overview

  Pityriasis rosea (PR) has often been considered to be a viral exanthem, a view supported by the conditions seasonal occurrence, its clinical course, the possibility of epidemic occurrence, the presence of occasional prodromal symptoms, and the low rate of recurrence. […] However, a 4-year recurrence rate of 25.9% was documented in one survey of 212 patients. […] Oxidative stress may play a role too. […] One survey noted a significant temporal clustering and seasonal variation, and the incidence of dengue fever significantly correlated. […] Pityriasis rosea has been linked to upper tract respiratory infections. […] Some immunologic data also suggest a viral etiology. […] A lack of natural killer (NK) cell and B-cell activity in pityriasis rosea lesions has been noted, suggesting a predominantly T-cell mediated immunity in the development of the condition. […] Increased amounts of CD4 T cells and Langerhans cells are present in the dermis, possibly reflecting viral antigen processing and presentation. […] A classification based on pathogenetic mechanisms associated with the different presentations of pityriasis rosea has been proposed.

• #41 Commentary on: ”Pityriasis Rosea Recurrence is Much Higher than Previously Known: A Prospective Study” | HTML | Acta Dermato-Venereologica

  https://www.medicaljournals.se/acta/content/html/10.2340/00015555-3265

  Furthermore, the aetiopathogenesis of PR as the consequence of HHV-6 and/or HHV-7 reactivation may explain the cases of recurrent PR. […] Recurrences of PR would happen in the patients in whom the immune response is not fully in control of viral reactivation, preferably within a limited period of time. […] The less severe course of the disease may be explained by the increasing response of the immune system against HHV-6 and HHV-7 reactivation, so that the immune response is at least partially effective and the virus load declines.

• #42 Pityriasis rosea: a distinct entity or viral exanthem?

  https://www.termedia.pl/Pityriasis-rosea-a-distinct-entity-or-viral-exanthem-,56,54777,1,1.html

  It seems that PR might be caused by human herpes virus 6 (HHV-6) and human herpes virus 7 (HHV-7). […] However, Kempf et al., Yasukawa et al., Yoshida, Kosuge et al., Offidani et al., Chuh et al., Wong et al., Karabulut et al. and Yildirim et al. are against this etiology. […] In addition to studies on the viral etiopathogenesis and genetic material of viruses in PBMC, plasma or other human specimens, there are also studies on the immunological mechanisms that accompany pityriasis rosea. […] Indirectly, the viral etiology of the disease is supported by the cytokines and chemokines increased during PR. […] Taking everything into consideration, more research is required to fully understand the etiopathogenesis of pityriasis rosea. […] Although pityriasis rosea seems to be a well-known and common skin disease with the clinical symptoms easy to manage, there are some controversial points which need more attention. […] Taking into consideration the circumstances of the disease onset mentioned in our manuscript, we would like to point out that PR may be considered as a reactive disease associated with decreased immunity caused by infections or pregnancy rather than sui generis disease.

• #43

  https://www.ijord.com/index.php/ijord/article/view/844

  Human herpes virus (HHV) 6 and 7 belongs to Betaherpesviridae a sub-family of Herpesviridae. […] The cause of PR and the disease caused by HHV is not well established. […] The association of HHV 6 and HHV 7 with pityriasis rosea (PR) is under controversy. […] The HHV DNA is also detected in normal controls which evidence the non-significance of HHV in the pathogenesis of PR. […] In contrary to the expected outcome that HHV-6 and HHV-7 positivity would correlate to the possible pathogenesis of the disease, the PCR results of all the 35 samples from clinically suspected PR cases were found to be negative. […] We conclude that HHV-6 and HHV-7 viruses may not always play a role in the pathogenesis of the disease. […] Thus PR speculated to have more than one etiology may have agents other than HHV6 and HHV7 involved in the pathogenesis of the disease.

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