[ZKKL] Academic Sharing | Pityriasis Rosea and Viral Infection

[Abstract] Pityriasis rosea (PR) is an acute inflammatory skin disorder characterized by erythematous, papular, and scaling lesions. The hallmark of this condition is the development of oval or round, pale red or yellow‑brown macules covered with bran‑like scales, commonly affecting the trunk and proximal extremities. A herald patch is typically present, followed within 1–2 weeks by the sequential appearance of numerous secondary eruptions that resemble the initial lesion; the long axis of these lesions often aligns with the direction of skin lines. Pruritus is usually reported. Pityriasis rosea is self‑limiting, with most cases resolving spontaneously in about 4–6 weeks, leaving behind transient hypopigmentation or hyperpigmentation. In rare instances, the course may extend beyond six months before complete resolution. In 1798, the Scottish dermatologist Willan first described annular pityriasis and regarded it as a distinct disease. In 1860, the French dermatologist Gilbert named the condition “pityriasis rosea” based on its clinical features, a term that has remained in use to this day. The etiology and pathogenesis of pityriasis rosea remain unclear; various hypotheses have been proposed, including viral infection, allergic reactions, autoimmunity, and hereditary predisposition, with the viral theory receiving the most extensive attention and considered the most plausible. The present review summarizes current evidence regarding the role of viral infection in the pathogenesis of pityriasis rosea.

[Keywords] Pityriasis rosea 、 virus 、 Disease

Pityriasis rosea typically follows a history of upper respiratory tract infection prior to the onset of the rash. Mubki et al. reported cases of pityriasis rosea occurring in patients with influenza A, suggesting that the influenza A virus may be an etiologic factor or could activate other viruses, thereby triggering pityriasis rosea. Chuh employed PCR and serological assays to detect cytomegalovirus (CMV), Epstein–Barr virus, parvovirus B19 DNA, and antiviral antibodies in 12 patients with pityriasis rosea and 12 healthy controls. No viral DNA was detected in the patient group, and antibody titers for the three viruses did not differ significantly from those in the control group. Two patients tested positive for anti‑CMV and anti‑EBV IgM; based on findings from other studies, these IgM responses were attributed to cross‑reactivity. Thus, infection with CMV, EBV, or parvovirus B19 does not appear to be clearly associated with the development of pityriasis rosea. Evidence further indicates that infections with picornaviruses, influenza and parainfluenza viruses, Legionella, and Chlamydia spp. are likewise unrelated to this condition. Drago et al., by comparing serum IFN‑γ levels between patients with pityriasis rosea and healthy controls, found that IFN‑γ concentrations were significantly elevated in the former group compared with the latter. This finding supports the involvement of viral infection in the pathogenesis of pityriasis rosea, as IFN‑γ exhibits direct antiviral activity and is likely produced by NK cells and T cells in response to invasion by viruses or other pathogens.

Recently, mounting evidence suggests that human herpesviruses play a significant role in the pathogenesis of pityriasis rosea. Research on the viral etiology of this condition has primarily focused on two types: human herpesvirus (HHV)-6 and HHV-7. In 1997, Drago et al. employed electron microscopy and PCR to detect HHV‑7 in mononuclear cells, plasma, and skin samples from patients with pityriasis rosea. They also used ELISA to measure levels of interferon‑α and interferon‑γ in serum, examined morphological changes in peripheral blood mononuclear cells cultured in vitro, and identified viral particles by electron microscopy. Furthermore, PCR was utilized to determine whether HHV‑6 and HHV‑7 DNA sequences were present in all specimens. The results demonstrated that interferon‑α and interferon‑γ could be detected in the plasma of pityriasis rosea patients but not in that of control subjects. Peripheral mononuclear cells isolated from pityriasis rosea patients exhibited ballooning degeneration and inclusion bodies under light microscopy after 3–7 days of in vitro culture, whereas such findings were absent in the control group and in patients during the recovery phase. Moreover, the supernatant obtained by centrifuging the culture medium supported the replication of Sup‑T1 cells infected with HHV‑7, and electron microscopic analysis revealed particles characteristic of herpesviruses in this supernatant. Finally, HHV‑7 DNA sequences were detected in peripheral blood mononuclear cells, plasma, and skin samples from patients in the acute phase of pityriasis rosea, strongly suggesting active viral involvement. Although no virus was isolated from these patients, the findings indicate that viruses play an important role in the disease’s development. Consequently, it has been proposed that pityriasis rosea may represent a clinical manifestation of HHV‑7 reactivation. Chuh et al. used nested PCR to test for HHV‑8 DNA in peripheral blood mononuclear cells, serum, and epidermal scales from mother patches in eight patients with pityriasis rosea; however, no HHV‑8 DNA fragments were detected. Indirect immunofluorescence likewise failed to identify anti‑HHV‑8 IgM antibodies, although four patients did exhibit anti‑HHV‑8 IgG antibodies, with titers showing no significant difference between the acute and later phases of the disease. Based on these findings, HHV‑8 was deemed unrelated to pityriasis rosea. In contrast, Prantsidis et al. employed PCR to analyze skin lesions from 34 patients with Kaposi’s sarcoma complicated by typical pityriasis rosea, revealing that 20.5% of the lesions contained HHV‑8 genomic material. This suggests that, under certain circumstances, HHV‑8 may indeed be associated with the onset of pityriasis rosea.

As research has progressed, it has become apparent that pityriasis rosea may not be caused by a single viral infection; rather, it could result from the synergistic action of two viruses or from interactions among multiple viral agents. Watanabe et al. examined skin lesions, non-lesional skin, peripheral blood mononuclear cells, serum, and saliva from patients with pityriasis rosea for DNA of HHV‑6, HHV‑7, and cytomegalovirus (CMV). They found that the detection rates of HHV‑7 DNA were 93% in lesional skin, 86% in non‑lesional skin, 100% in saliva, 83% in peripheral blood mononuclear cells, and 100% in serum samples. For HHV‑6, the corresponding rates were 86% in lesional skin, 79% in non‑lesional skin, 80% in saliva, 83% in peripheral blood mononuclear cells, and 88% in serum samples. In contrast, no HHV‑6 or HHV‑7 DNA was detected in these tissues from healthy volunteers or from the serum and skin samples of 10 patients with psoriasis, suggesting that pityriasis rosea is associated with systemic activation of HHV‑6 and HHV‑7, whereas CMV does not appear to play a role in this condition. The presence of virus in saliva led the authors to hypothesize that patients with pityriasis rosea may experience viral reactivation rather than primary infection, given that salivary glands serve as reservoirs for previously acquired infections. Furthermore, the low viral load observed in skin lesions indicates that these viruses may not directly infect the skin but instead represent a response to systemic viral replication. The authors also speculated that earlier negative findings might have resulted from the use of conventional PCR techniques and/or from DNA extraction only from formalin‑fixed, paraffin‑embedded tissue. Another study by Drago et al. employed electron microscopy to examine lesion specimens from 21 patients in the acute phase of pityriasis rosea. In 15 cases (71%), they identified HHV particles at various stages of morphogenesis, measuring approximately 160–200 nm in diameter, with a densely electron‑dense cylindrical core, a capsid, spike‑like projections on the envelope, and an inner layer between the capsid and envelope. These findings further support the involvement of HHV‑6 and HHV‑7 in pityriasis rosea. Using real‑time quantitative PCR, Broccolo et al. demonstrated that healthy volunteers and patients with other inflammatory skin diseases showed no detectable HHV‑6 or HHV‑7 DNA, whereas among patients with pityriasis rosea, HHV‑6 DNA was detected in 16% of samples and HHV‑7 DNA in 39%, providing additional evidence for the role of these viruses in the disease. As in previous studies, they concluded that pityriasis rosea arises primarily from viral reactivation rather than from a de novo infection. Their work also suggested that reactivation of HHV‑7 may precede reactivation of HHV‑6, but not vice versa. In another observation, Drago et al. noted that patients with pityriasis rosea lasting more than three months exhibited higher and more prolonged viral loads of HHV‑6 and/or HHV‑7 compared with typical cases. Moreover, they found that viremia and oropharyngeal symptoms in pediatric patients were linked to systemic reactivation of HHV‑6 and/or HHV‑7. Additionally, they reported one case of chronic hepatitis C in which, upon the onset of pityriasis rosea, liver enzyme levels rose, while HCV‑RNA, HHV‑6 DNA, and HHV‑7 DNA were actively detectable and markedly elevated. Following antiviral therapy, liver enzymes normalized, HCV‑RNA and HHV‑7 DNA became undetectable in serum, the rash resolved, and serological testing for HHV‑6 DNA showed a significant decline compared with baseline. These observations suggest that reactivation of HHV‑6 can trigger activation of HHV‑7 and HCV, thereby precipitating pityriasis rosea. Based on the foregoing investigations, human herpesviruses 6 and 7 are considered the most likely causative agents of pityriasis rosea, and future studies should aim to establish a clear causal relationship between them.