Vincristine-Induced Acrocyanosis and Erythema Pernio.

INTRODUCTION: Acrocyanosis and erythema pernio are 2 dermatologic manifestations of vasospastic changes. Primary care providers should consider that these conditions can occur as primary or idiopathic conditions and as secondary conditions related to another disease or medication. Herein we describe a case of acrocyanosis and erythema pernio attributed to vincristine therapy. CASE DESCRIPTION: A 22-year-old man was evaluated for discomfort and red lesions involving the toes of both feet for several weeks. He had completed chemotherapy 1 month earlier for Ewing sarcoma in the right femur. Local control for the primary tumor included wide local excision and reconstruction with a vascularized fibular allograft from the right fibula. On examination, his right foot was dark blue and cool. Toes on both feet had nonpainful erythematous papules. After the case was discussed with the patient's oncology team, the diagnosis was medication-induced acrocyanosis of the right foot and bilateral erythema pernio. Treatment consisted of supportive care to keep the feet warm and promote circulation to the feet. At 2-week follow-up, the patient's symptoms and the appearance of his feet had markedly improved. DISCUSSION: Primary care clinicians should be able to recognize dermatologic manifestations of vasospastic changes, including acrocyanosis and erythema pernio, and rule out possible secondary causes, such as pharmacologic agents. This patient's history of therapy for Ewing sarcoma prompted consideration of medication-induced vasospastic changes most likely related to the adverse vasospastic effects of vincristine. Symptoms should improve with cessation of the offending medication.

Cilostazol as a Treatment for COVID Toes: A Case Report.

During the Coronavirus Disease 2019 (COVID-19) pandemic, skin lesions resembling those seen in pernio (chilblains) have been observed in patients with COVID-19 infection. The term "COVID toes" has been used when there is toe involvement. We describe the case of a fully vaccinated, 56-year-old woman with no prior diagnosis of COVID-19 who developed pernio-like lesions many months after being vaccinated. Her skin lesions resolved after treatment with cilostazol, suggesting that this medication may be a viable treatment for pernio in the setting of COVID-19 infection.

Early Cutaneous Manifestations of COVID-19: A Systematic Review and Public Health Implications.

INTRODUCTION: Cutaneous manifestations before other symptoms have great potential for early COVID-19 diagnosis to prevent surge. METHODS: We conducted a search of PubMed and Embase databases through April 11, 2021 to include 39 studies reporting skin manifestations occurring prior to any other COVID-19 symptoms in laboratory-confirmed cases. RESULTS: Ninety-seven patients were included. Urticarial (24.7%) and maculopapular (22.7%) lesions were most common, followed by pernio (17.5%), vesicular (14.4%), papulosquamous (8.2%), and purpuric (5.1%) lesions. Cutaneous to systemic symptom latency ranged from 2 to 20 days in cases that reported it (26%), while skin lesions were the only presentation in 23 cases (23.7%). Skin lesions were the only COVID-19 manifestation in 58.8% of pernio, 40% of vesicular, 16.6% of urticarial, 18.2% of maculopapular, and 12.5% of papulosquamous presymptomatic cases. Although sample size is limited, all purpuric cases developed other symptom(s) later. CONCLUSIONS: Pernio and purpuric lesions have been well-associated with COVID-19, but papulosquamous, vesicular, mild maculopapular, and urticarial lesions can easily be dismissed as unrelated to COVID-19. Pernio lesions are thought to be related to strong immune response and low contagiousness, while purpuric and vesicular cases are speculated to be related to higher SARS-CoV2 viral load, severity, and contagiousness. All rashes, even without other symptoms, should necessitate high level of suspicion for isolation or contact tracing.

Histopathology of persistent long COVID toe: A case report.

During the 2020 coronavirus (SARS-CoV-2) pandemic, several cutaneous lesions were identified, including pseudo-chilblain, vesicular, urticarial, maculopapular, and livedo/necrosis. A 59-year-old obese man with probable COVID-19 developed painful cyanosis with histopathologic capillary thrombosis of toes, and the cyanosis persisted for nearly 22 months. Shortly after initial exposure to family members with documented SARS-CoV-2, he developed upper respiratory symptoms, yet his anti-SARS-CoV-2 antibody and nasal swab RT-PCR tests were repeatedly negative. Two family members were hospitalized and one of them succumbed with documented SARS-CoV-2 pneumonia within 10 days of exposure. Biopsy specimen of the distal toe 16 weeks after initial exposure showed papillary dermal capillary thrombosis with endothelial swelling, telangiectasia, and peri-eccrine lymphocytic infiltrates resembling pernio. Overall, this is the first case of biopsy specimen of "long COVID toe" following presumed SARS-CoV-2 exposure, with a demonstration of thrombotic vasculopathy, toe cyanosis, and pernio-like pathology.

Pandemic chilblains: Are they SARS-CoV-2-related or not?

The exact etiopathology of chilblains observed during the Coronavirus Disease 2019 (COVID-19) pandemic is still unclear. Initially, SARS-CoV-2 appeared as the obvious causing agent, but two years of various investigations have failed to convincingly support its direct implication. Most affected individuals have no detectable virus, no anti-SARS-CoV-2 antibodies and no symptoms of COVID-19. Analyses of skin biopsies similarly failed to unambiguously demonstrate presence of the virus or its genome. In a recent hypothesis, SARS-CoV-2 would cause the lesions before being promptly eliminated by unusually strong type I interferon responses. With others, we feel that environmental factors have not been sufficiently considered, in particular cold exposure related to unprecedented containment measures. The cause of pandemic chilblains remains a stimulating puzzle which warrants further investigation.

A clinicopathological description of COVID-19-induced chilblains (COVID-toes) correlated with a published literature review.

BACKGROUND: The abundance of publications of COVID-19-induced chilblains has resulted in a confusing situation. METHODS: This is a prospective single-institution study from 15 March to 13 May 2020. Thirty-two patients received PCR nasopharyngeal swabs. Of these, 28 patients had a thoracic CT-scan, 31 patients had blood and urine examinations, 24 patients had skin biopsies including immunohistochemical and direct immunofluorescence studies, and four patients had electron microscopy. RESULTS: COVID-19-induced chilblains are clinically and histopathologically identical to chilblains from other causes. Although intravascular thrombi are sometimes observed, no patient had a systemic coagulopathy or severe clinical course. The exhaustive clinical, radiological, and laboratory work-up in this study ruled-out other primary and secondary causes. Electron microscopy revealed rare, probable viral particles whose core and spikes measured from 120 to 133 nm within endothelium and eccrine glands in two cases. CONCLUSION: This study provides further clinicopathologic evidence of COVID-19-related chilblains. Negative PCR and antibody tests do not rule-out infection. Chilblains represent a good prognosis, occurring later in the disease course. No systemic coagulopathy was identified in any patient. Patients presenting with acral lesions should be isolated, and chilblains should be distinguished from thrombotic lesions (livedo racemosa, retiform purpura, or ischemic acral necrosis).

Post-vaccination COVID Toes (Chilblains) Exacerbated by Rituximab Infusion Suggests Interferon Activation as Mechanism.

Coronavirus disease (COVID) toes are pernio-like skin lesions associated with severe acute respiratory syndrome coronavirus 2. We observed pernio-like skin findings presenting after a Pfizer BioNTech vaccine, which significantly worsened after an infusion of rituximab. This suggests that the mechanism for COVID toes is interferon activation. Military providers may avoid unnecessary referrals for this self-limiting condition by anticipating this adverse effect.

An unusual case of T-cell prolymphocytic leukemia mimicking a cutaneous vasculitis.

T-cell prolymphocytic leukemia (T-PLL) is an aggressive post-thymic T-cell malignancy, which accounts for 2% of mature lymphocytic leukemias in adults. Though typically presenting with a brief history of B symptoms, hepatosplenomegaly, and marked lymphocytosis, erythematous or nodular skin rashes involving the trunk or limbs may be seen in 25% to 30% of patients, as well as a purpuric rash in a periorbital distribution. Cutaneous involvement typically presents in the context of patients with an established history of T-PLL, but it can less frequently present as an initial symptom heralding the diagnosis. An unusual case of T-PLL is described, presenting initially as palmoplantar ulcerated nodules with an initial biopsy suggestive of perniosis, followed by rapid progression of dark violaceous and bright red papules throughout the body after initiation of obinutuzumab. The diagnosis of T-PLL was subsequently fully supported by the clinical, laboratory, cytologic, and immunophenotypic findings. This case highlights the importance of a multidisciplinary team approach to address such rare and atypical presentations.

Bilateral Chilblain-like Lesions of the Toes Characterized by Microvascular Remodeling in Adolescents During the COVID-19 Pandemic.

Importance: Chilblain-like lesions have been one of the most frequently described cutaneous manifestations during the COVID-19 pandemic. Their etiopathogenesis, including the role of SARS-CoV-2, remains elusive. Objective: To examine the association of chilblain-like lesions with SARS-CoV-2 infection. Design, Setting, and Participants: This prospective case series enrolled 17 adolescents who presented with chilblain-like lesions from April 1 to June 30, 2020, at a tertiary referral academic hospital in Italy. Main Outcomes and Measures: Macroscopic (clinical and dermoscopic) and microscopic (histopathologic) analysis contributed to a thorough understanding of the lesions. Nasopharyngeal swab, serologic testing, and in situ hybridization of the skin biopsy specimens were performed to test for SARS-CoV-2 infection. Laboratory tests explored signs of systemic inflammation or thrombophilia. Structural changes in peripheral microcirculation were investigated by capillaroscopy. Results: Of the 17 adolescents (9 [52.9%] male; median [interquartile range] age, 13.2 [12.5-14.3] years) enrolled during the first wave of the COVID-19 pandemic, 16 (94.1%) had bilaterally localized distal erythematous or cyanotic lesions. A triad of red dots (16 [100%]), white rosettes (11 [68.8%]), and white streaks (10 [62.5%]) characterized the dermoscopic picture. Histologic analysis revealed a remodeling of the dermal blood vessels with a lobular arrangement, wall thickening, and a mild perivascular lymphocytic infiltrate. SARS-CoV-2 infection was excluded by molecular and serologic testing. In situ hybridization did not highlight the viral genome in the lesions. Conclusions and Relevance: This study delineated the clinical, histologic, and laboratory features of chilblain-like lesions that emerged during the COVID-19 pandemic, and its findings do not support their association with SARS-CoV-2 infection. The lesions occurred in otherwise healthy adolescents, had a long but benign course to self-resolution, and were characterized by a microvascular remodeling with perivascular lymphocytic infiltrate but no other signs of vasculitis. These results suggest that chilblain-like lesions do not imply a concomitant SARS-CoV-2 infection. Ongoing studies will help clarify the etiopathogenic mechanisms.

A Review of COVID-19 Chilblains-like Lesions and Their Differential Diagnoses.

GENERAL PURPOSE: To familiarize wound care practitioners with the differential diagnoses of chilblains-like lesions that could be associated with the complications of COVID-19. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will:1. Identify the population most often affected by COVID toes.2. Select the assessments that help differentiate the various conditions that cause chilblains-like lesions.3. Choose appropriate treatment options for the various conditions that cause chilblains-like lesions.

This review article focuses on the pathogenesis, clinical features, and diagnostic testing of the common pathologies that can manifest as chilblains-like lesions. These differentials include "COVID toes," Raynaud phenomenon, acrocyanosis, critical limb ischemia, thromboangiitis obliterans, chilblains associated with lupus erythematosus, and idiopathic chilblains. The authors present a helpful mnemonic, ARCTIC, to assist clinicians in recognition and diagnosis.

Management of a Child vs an Adult Presenting With Acral Lesions During the COVID-19 Pandemic: A Practical Review.

During the coronavirus disease 2019 (COVID-19) pandemic, there has been a rise in the diagnosis of acral lesions, including chilblains-like lesions, ischemia, and retiform purpura. Understanding the differences in presentation and severity of illness between children and adult patients is important for physicians to understand risk stratification and management of these lesions. We reviewed the literature on the acral lesions seen in children and adults with COVID-19 infection to offer guidelines for diagnosis and treatment.

COVID-19: The experience from Italy.

A wide range of cutaneous signs are attributed to COVID-19 infection. This retrospective study assesses the presence and impact of dermatologic manifestations related to the spread of COVID-19 in Lombardy, the geographic district with the first outbreak in Italy. A cohort of 345 patients with laboratory confirmed COVID-19 was collected from February 1, 2020 to May 31, 2020. Cutaneous signs and dermatologic diagnoses were recorded on admission, and during the course of the disease. Of the 345 patients included in the study, 52 (15%) had new-onset dermatologic conditions related to COVID-19. We observed seven major cutaneous clinical patterns, merged under 3 main groups: Exanthems, vascular lesions, and other cutaneous manifestations. Each subset was detailed with prevalence, age, duration, prognosis, and histology. Cutaneous findings can lead to suspect COVID-19 infection and identify potentially contagious cases with indolent course.

Clinicopathologic correlations of COVID-19-related cutaneous manifestations with special emphasis on histopathologic patterns.

Skin is one of target organs affected by the novel coronavirus SARS-CoV-2, and in response to the current COVID-19 pandemic, a fast body of literature has emerged on related cutaneous manifestations. Current perspective is that the skin is not only a bystander of the general cytokines storm with thrombophilic multiorgan injury, but it is directly affected by the epithelial tropism of the virus, as confirmed by the detection of SARS-CoV-2 in endothelial cells and epithelial cells of epidermis and eccrine glands. In contrast with the abundance of epidemiologic and clinical reports, histopathologic characterization of skin manifestations is limited. Without an adequate clinicopathologic correlation, nosology of clinically similar conditions is confusing, and effective association with COVID-19 remains presumptive. Several patients with different types of skin lesions, including the most specific acral chilblains-like lesions, showed negative results at SARS-CoV-2 nasopharyngeal and serologic sampling. The aim of this review is to provide an overview of what has currently been reported worldwide, with a particular emphasis on microscopic patterns of the skin manifestations in patients exposed to or affected by COVID-19. Substantial breakthroughs may occur in the near future from more skin biopsies, improvement of immunohistochemistry studies, RNA detection of SARS-CoV-2 strain by real-time polymerase chain reaction-based assay, and electron microscopic studies.

Acute acral eruptions in children during the COVID-19 pandemic: Characteristics of 103 children and their family clusters.

BACKGROUND: A marked increase in frequency of acute acral eruptions (AAE) was observed in children during the COVID-19 pandemic in the spring period. OBJECTIVES: In this observational multicenter study, based on children with AAE, we aimed to assess the proportion of household members possibly infected by SARS-CoV-2. METHODS: We collected data from all children observed with AAE, prospectively from April 7, 2020 to June 22, 2020, and retrospectively since February 28, 2020. The primary outcome was the household infection rate, defined as the proportion of family clusters having at least one member with COVID-19 infection other than the child with AAE ("index child"). The definition of a case was based on characteristic clinical signs and a positive PCR or serology. RESULTS: The study included 103 children in 10 French departments and in Quebec. The median age was 13 years and the interquartile range [8-15], with a female-to-male ratio of 1/1.15. In children with AAE, all PCR tests were negative (n=18), and serology was positive in 2/14 (14.3%) cases. We found no significant anomalies in the lab results. A total of 66 of the 103 families (64.1%) of included children had at least one other infected member apart from the index child. The total number of household members was 292, of whom 119 (40.8%) were considered possibly infected by SARS-CoV-2. No index children or households exhibited severe COVID-19. DISCUSSION: Among the 103 households included, 64.1% had at least one infected member. Neither children with AAE nor their households showed severe COVID-19.