Cutaneous Pathology of COVID-19 as a Window into Immunologic Mechanisms of Disease.

Many skin manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection reflect activation of cutaneous and systemic immune responses involving effector pathways of both the innate and adaptive arms of the immune system. This article reviews evidence from the recent clinical and scientific literature that informs the current understanding of the consequences of coronavirus disease 2019 (COVID-19)-induced immune cell activation, as relevant to dermatology. Topics include the clinical consequences of autoantibody production in patients with COVID-19, immunologic evidence for chilblains as a manifestation of SARS-CoV-2 infection, and the relationship between type I interferons and COVID-19 disease severity.

Cutaneous Manifestations of COVID-19.

Patients with coronavirus disease 2019 (COVID-19) present with multisystem signs and symptoms, including dermatologic manifestations. The recent literature has revealed that dermatologic manifestations of COVID-19 often are early onset and provide helpful cues to a timely diagnosis. We compiled the relevant emerging literature regarding the dermatologic manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) so that physicians can be aware of the various clinical cutaneous presentations in this time of high incidence of COVID-19.

Cutaneous manifestations of COVID-19.

The severe acute respiratory syndrome coronavirus two (SARS-CoV-2), which causes the 2019 coronavirus disease (COVID-19), has infected patients worldwide. Physicians have increasingly identified cutaneous findings as a significant clinical manifestation of COVID-19. In this review, we describe the clinical presentation, onset, duration, associated symptoms, treatment, and outcome of cutaneous manifestations thus far reported to be related to COVID-19. We have included data from 63 studies and subdivided reported cutaneous manifestations into the categories of viral exanthem, urticarial, vesicular, chilblains/chilblains-like, non-chilblains vasculopathy-related, pityriasis rosea-like, erythema multiforme-like, Kawasaki/Kawasaki-like disease, and others. Physicians should be aware of the known common cutaneous manifestations of COVID-19 and future research is required to better understand the pathophysiology and prognosis of each COVID-19-related skin manifestation.

Pityriasis rosea: elucidation of environmental factors in modulated autoagressive etiology and dengue virus infection.

INTRODUCTION: A retrospective epidemiological study was conducted to study seasonal variation in the incidence of pityriasis rosea (PR) and its temporal association with various meteorological variables, and dengue virus infection. METHODS: The study was conducted at a tertiary referral center in Guwahati, Assam, India. We searched for and retrieved all medical records of patients diagnosed with PR by dermatologists from December 1st, 2014 to July 31st, 2017. The diagnosis was made only if the patient fulfilled at least three out of the following four clinical features: 1) herald patch, 2) peripheral collaret scales, 3) predominant truncal and proximal limb distribution of the lesions, and 4) orientation of lesions along the lines of cleavage. For each visit by every patient, we retrieved data for the monthly mean air temperature, mean total rainfall, and mean relative humidity. PR patients that had dengue fever with NS1 antigen and/or IgM/IgG antibody positivity were studied along with healthy controls. RESULTS: Overall, PR occurred more frequently in the colder months and months with less rainfall. However, these associations were insignificant (p = 0.23, R = -0.38, and R = -0.55, respectively). Upon further examination of the data, we found that the monthly incidence of PR was significantly lower in March and April than the other months during the study period (F = 8.31, p = 0.002). A statistically significant higher incidence was detected in September, November, and December (p < 0.01 for 2014 and 2017, but not in the 2016 seasonal cohort) and also in January and February (p < 0.05 for 2016 and 2017). Interestingly, a retrospective history of dengue fever emerged as a significant correlate. CONCLUSIONS: In our setting, there was significant temporal clustering and seasonal variation among patients with PR. The incidence of dengue fever is significantly correlated with PR.

Gestational Pityriasis Rosea: Suggestions for Approaching Affected Pregnant Women.

Dear Editor, Pityriasis rosea is a common, acute, and self-limiting dermatosis, which is associated with the endogenous systemic reactivation of human herpesvirus (HHV)-6 and/or HHV-7 (1). It predominantly affects individuals of both sexes in their second or third decade of life and is clinically characterized by the occurrence of an initial erythematosquamous plaque followed by the appearance of disseminated similar but smaller lesions one or two weeks later. Several patients develop systemic symptoms such as nausea, anorexia, malaise, headache, fever, arthralgia, and lymphadenopathy that may precede or accompany the eruption; the latter follows the cleavage lines of the trunk creating the configuration of a Christmas tree and spontaneously resolves within 4 to 8 weeks. Mainly based on the nature of the underlying viral reactivation, pityriasis rosea is classified into five different forms (2): 1) Classic and 2) Relapsing (characterized by sporadic and relapsing HHV-6/7 systemic reactivation, respectively), 3) Persistent (persistence of HHV-6/7 viremia), 4) Pediatric (longer activity of HHV-6/7 infection; recent primary infection) and 5) Gestational (HHV-6/7 reactivation and possible intrauterine transmission). Clearly, the inevitable impairment of immune response in pregnancy favors viral reactivation and possibly also the intrauterine transmission of HHV-6/7. Indeed, it is well known and documented that pityriasis rosea more frequently occurs in pregnant women (18%) as compared to the general population (6%) (3). However, the literature concerning the possible effect of pityriasis rosea on the outcome of pregnancy is surprisingly sparse. Only an Italian group, Drago et al (4,5), has systematically investigated the impact of this disorder on pregnant women. They found that 22 out of 61 women (36%) who developed pityriasis rosea during pregnancy had unfavorable outcomes, whereas 8 others miscarried (13%). None of the latter had any risk factors, other than pityriasis rosea, for intrauterine fetal death. All miscarrying women reportedly revealed an aggressive course of widespread eruption and severe constitutional symptoms; all of them had HHV-6 DNA in the plasma, placenta, skin lesions, and fetal tissues, whereas HHV-7 DNA was detected in the plasma and skin lesions in 3 out of 8 (37.5%) miscarrying women. HHV-6 DNA was found only in the plasma of 2 out of 31 women (6.45%) with normal pregnancy, whereas HHV-7 DNA was detected in the plasma of 3 (9.45%) and in the skin lesions of 2 women (6.45%) with normal pregnancy. The total abortion rate in women who developed pityriasis rosea during their pregnancy (13%) does not differ from that observed in the general population. Nevertheless, it is markedly higher in cases affected during the first 15 gestational weeks (57%) (4,5). Surprisingly, this devastating impact of pityriasis rosea on the outcome of pregnancy is almost completely unknown not only to the public but also to many members of the medical community. It is also largely unknown that, particularly during the first 15 gestational weeks, all pregnant women should avoid any contact with patients known to have pityriasis rosea. Since we have received a considerable number of requests for consultation with pregnant women with pityriasis rosea over the last few years, our group has compiled suggestions approaching the affected patients: 1. If an eruption suggestive for pityriasis rosea occurs in a pregnant woman, the following factors should be excluded: a. Exposure to drugs prior to the development of the rash (biologic agents, captopril, clonidine, hydrochlorothiazide, atenolol, lamotrigine, nortriptyline, barbiturates, metronidazole, terbinafine, omeprazole, non-steroidal anti-inflammatory drugs, and isotretinoin), which are capable of inducing a pityriasis rosea-like eruption (6) and b. Disorders included in the differential diagnosis (syphilis and infections due to parvovirus, herpes virus, cytomegalovirus, and Epstein-Barr virus). 2. The clinical diagnosis of pityriasis rosea should be made according to the morphological criteria (peripheral collarette scaling with central clearance on at least two lesions) put forth by Chuh (7). 3. Since specific anti-HHV-6 and -7 IgM antibodies are detected only in a low percentage of infected pregnant women (8), HHV-6 and -7 DNA should be assessed in plasma by nested PCR. Especially during the first 15 gestational weeks, pregnant women with positive PCR results deserve, apart from close monitoring, appropriate information about the existing risks in order to be able to make informed decisions. 4. Reliable and definite data from adequate and controlled human studies on the safety of acyclovir or valacyclovir in pregnant women and their efficacy in pityriasis rosea are lacking. Thus, the decision on whether these antiviral compounds will be administered should be tailored to each individual pregnant woman, subsequent to a meticulous assessment of the potential risks and their balancing against the potential benefits.

Pitiriasis rosada de Gibert en paciente de raza negra / Pityriasis rosea Gibert in a black patient

Los cambios poblacionales, los movimientos migratorios y el aumento de adopciones han condicionado la aparición de nuevas patologías en nuestras consultas, así como presentaciones diferentes de las patologías más habituales. Presentamos las imágenes y la revisión bibliográfica de un caso de pitiriasis rosada de Gibert en una paciente de cuatro años de raza negra (AU)

Population changes, migration and increasing number of adoptions have conditioned the emergence of new diseases in our consultations, as well as different forms of the most common diseases. We present the images and the medical literature review of a case of pityriasis rosea Gibert in a black four years old patient (AU)

What is the news? A difference between men and women.

It is a common observation that women and men react differently to stress and illness. We questioned 63 consecutive patients with pityriasis rosea and found that the women were overwhelmingly more likely than men to ask to hear unpleasant information before positive information.

Pitiríase rósea: estudo clínico-terapêutico e apresentação de aspectos clínicos atípicos / Pityriasis rosea: clinical-therapeutic study and atypical clinical aspects presentation

A pitiríase rósea (PR) é uma dermatose inflamatória aguda, autolimitada, caracterizada por lesões eritematodescamativas. É uma doença relativamente comum, apesar da sua etiologia ainda não ter sido identificada. Tem distribuição mundial, acometendo todas as raças e qualquer faixa etária, particularmente adultos jovens. O diagnóstico dos casos típicos é simples e essencialmente baseado nos aspectos clínicos. No entanto, formas atípicas de PR podem representar um desafio ao diagnóstico

Pityriasis rosea-like eruption during treatment with imatinib mesylate: description of 3 cases.

Imatinib mesylate (IM) represents the first-line treatment for chronic myeloid leukemia (CML). We hereby relate 3 cases of an IM-induced pityriasis rosea (PR)-like cutaneous eruption. Patients developed an erythematous, slightly pruritic, macular skin eruption, with many lesions having a peripheral collarette of desquamation, confined to the trunk, limbs, and arms with a vaguely dermatomal diffusion. The histologic findings suggested a reactive process to the drug. Full dermatological recovery was obtained after IM discontinuation, but lesions reappeared upon restoring therapy, suggesting the drug-related nature of the rash. To our knowledge this is the first reported PR-like cutaneous eruption to IM.

Additional evidence that pityriasis rosea is associated with reactivation of human herpesvirus-6 and -7.

To elucidate the role of human herpesvirus (HHV)-6 and -7 (HHV-7) in pityriasis rosea (PR), we measured their DNA load in plasma, peripheral blood mononuclear cells (PBMC), and tissues using a calibrated quantitative real-time PCR assay. We also studied HHV-6- and HHV-7-specific antigens in skin by immunohistochemistry and anti-HHV-7 neutralizing activity using a syncytia-inhibition test. Plasma and PBMC were obtained from 31 PR patients (14 children, 17 adults), 12 patients with other dermatites, and 36 blood donors. Skin biopsies were obtained from 15 adults with PR and 12 with other dermatites. HHV-6 and HHV-7 DNA were detected in 17% and in 39% of PR plasmas, respectively, but in no controls. HHV-7 viremia was associated with a higher PBMC load and, in adults, with systemic symptoms. HHV-7, but not HHV-6, levels in PBMC were higher in PR patients than in controls. HHV-6 and HHV-7 antigens were found only in PR skin (17% and 67% of patients analyzed, respectively), indicating a productive infection. Syncytia-neutralizing antibodies were found in PR patients and controls, but their titers were lower in patients with HHV-7 viremia. These data confirm the causal association between PR and active HHV-7 or, to a lesser extent, HHV-6 infection.