Vascular cutaneous manifestations of COVID-19 and RNA viral pathogens: a systematic review.

BACKGROUND: COVID-19, the widely recognized and highly contagious respiratory tract infection, has had a substantial impact on the field of dermatology since its emergence in 2019. SARS-CoV-2, the causative virus of COVID-19, is classified as an RNA virus. Various skin-related symptoms have been reported in patients with COVID-19, most notably the distinctive purple-red acral rash resembling chilblain lesions, commonly referred to as 'COVID toe'; similarly, skin-related symptoms have been observed in connection with other RNA viruses. OBJECTIVES: To explore the relationship between RNA viruses and their associated vascular cutaneous manifestations vs. those observed in patients infected with SARS-CoV-2. METHODS: A systematic literature review was conducted using PubMed and medical subject heading terms related to RNA viruses and related skin manifestations. RESULTS: In total, 3994 patients diagnosed with COVID-19 presenting with skin rashes were included. Chilblain-like lesions were most frequently observed (30.2%), followed by erythematous maculopapular/morbilliform rashes (9.1%) and urticarial rashes (4.7%). Of 8362 patients diagnosed with RNA viruses, more than half of the skin findings reported were erythematous/maculopapular/morbilliform rashes (52.3%), followed by unspecified (11.3%) and purpuric rashes (10.6%). CONCLUSIONS: When comparing RNA viral infections with COVID-19 infection, we observed similarities in the reported skin manifestations and their presumed pathways, with many implicated in the proinflammatory response. Owing to the wide range of cutaneous symptoms associated with RNA viruses and our currently limited understanding of the underlying mechanisms, additional research is warranted to investigate the pathology behind viral-induced skin lesions.

Epidemiology, clinical profiles, and prognostic value of COVID-19-related cutaneous manifestations in African populations: a rapid narrative review.

BACKGROUND: Skin manifestations' true prognostic value, and clinical and epidemiological pictures in SARS-CoV-2 infection in African populations are poorly described and understudied. More familiarity with COVID-19 cutaneous manifestations may aid in early clinical diagnosis or guide prognosis. METHODS: In this literature review, we looked for potential studies published from December 2019 to March 2023 on COVID-19 cutaneous lesions in African populations. Our key questions were focused on the prognostic values of cutaneous manifestations related to COVID-19. RESULTS: Our findings show that cutaneous manifestations of COVID-19 vary by country and severity of COVID-19, primarily multisystem inflammatory syndrome (MIS). Significant differences were also found between various dermatological lesions, primarily MIS, erythema multiforme-like, livedoid, vesicular, or varicella-like rashes, urticarial, maculopapular or morbilliform rashes, and chilblain-like or pernio-like rashes. There were 47.5% (115/242) of MIS cases reported in nine published African studies. Our findings also revealed that MIS may be diagnosed in 2-7 days due to early onset rash. Advanced age, obesity, diabetes, cardiovascular disease, HIV, tuberculosis, asthma, atopic disease, underweight, malnutrition, and malignancy were found to be associated with COVID-19 cutaneous manifestations in African populations. CONCLUSIONS: COVID-19-related skin manifestations in African populations are important as a driving force in COVID-19 prognosis.

Chilblain-Like Eruption Unveiling Cutaneous Aleukemic Relapse of Acute Myeloid Leukemia.

ABSTRACT: Leukemia cutis corresponds to skin infiltration by malignant hematopoietic cells. It is most commonly reported in acute myeloid leukemia, particularly in subtypes with a monocytic component. Its clinical manifestations are extremely variable, and histopathologic diagnosis of cutaneous leukemic infiltrates may be challenging. We report the first case of cutaneous, that is, extramedullary, aleukemic relapse of acute myeloid leukemia within an unusual chilblain-like eruption that imposed a challenging clinical and histopathologic diagnosis. Primary chilblains are uncommon in the elderly, and a systemic underlying cause should be thoroughly investigated. In patients presenting with atypical chilblains (ie, persistent chilblains developing even without exposure to cold temperatures and/or refractory to therapy) and with a history of hematologic disorders such as leukemias, histopathologic examination is crucial to identify leukemic or aleukemic phases of relapse of underlying leukemia and initiate timely treatment.

Targetoid-like lesions and chilblain-like erythema manifested on hands and feet: A case of Rowell syndrome from China.

BACKGROUND: Rowell syndrome (RS) is an uncommon condition characterized by erythema multiforme (EM)-like lesions and lupus erythematosus. It is more common in females, and EM may be the first manifestation of the disease with positive autoantibodies, such as antinuclear antibody (ANA), SSA, SSB and rheumatoid factor. The pathogenesis of RS is unknown and is likely caused by drug induction, ultraviolet exposure and infection. METHOD: We describe a case of RS from China which presented as characteristic targetoid-like lesions and chilblain-like erythema on hands and feet. This is a case of RS in a female patient from the inpatient department of dermatology. RESULTS: A 41-year-old female with systemic lupus erythematosus exhibited chilblain-like erythema and characteristic EM lesions on her extremities. She tested positive for serum ANA (1:320) and anti-double-stranded DNA, as well as other autoantibodies. Systemic glucocorticoids and hydroxychloroquine worked effectively for her. CONCLUSION: The present case met diagnostic criteria of RS. Notably, there was a co-occurrence of facial butterfly erythema, chilblain-like erythema and EM lesions distributed on the limbs in this case.

Primary cutaneous marginal zone lymphoma presenting with secondary chilblains of the toes.

Cutaneous lymphoproliferative disorders include cutaneous manifestations of systemic B-cell or T-cell lymphoma and primary cutaneous lymphomas. Primary cutaneous B-cell lymphomas are subcategorised into four groups: primary cutaneous marginal zone lymphoma (PCMZL), primary cutaneous follicle centre lymphoma, primary cutaneous diffuse large B-cell lymphoma, leg-type and EBV-positive mucocutaneous tumour. Each of these cutaneous lymphoproliferative disorders has unique clinical and pathological features necessitating biopsy and staging to establish proper treatment. We present a case of PCMZL manifesting as secondary chilblains of the toes that was diagnosed with punch skin biopsy. The patient's chilblains resolved with rituximab. This case underscores the importance of considering PCMZL and other cutaneous lymphoproliferative disorders in patients with dermatological manifestations and wounds refractory to first-line treatment.

Antichilblain Components in Eggplant Based on Network Pharmacology and Biological Evaluation.

Eggplant, the fruit of Solanum melongena L. (Solanaceae), is applied externally to relieve the symptoms of chilblains in the folk in East Asia. However, the mechanisms and biological ingredients are not clear. A network pharmacology approach was used to shed light on the mechanisms of eggplant against chilblains, which illustrated that anti-inflammation and antioxidation are mainly involved in the curative effects. Bioassay-guided assays led to the isolation of 44 ingredients (1-44), including two new natural compounds (1-2) and 42 known compounds. Thirteen compounds (3-15) were first reported from the Solanum genus. The anti-inflammatory and antioxidative effects of all isolates were evaluated, and the results showed that 11 compounds have anti-inflammatory activity and 27 have antioxidant activity. Fatty acids, flavonoids, alkaloids, phenolic acids, saponins, and lignans from eggplant have certain anti-inflammatory and antioxidant effects. These results provide a scientific basis for eggplant to treat chilblains.

Intralesional Certolizumab for Refractory Lupus Pernio.

This case report describes a patient with refractory lupus pernio that responded to treatment with a series of intralesional certolizumab injections.

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.

Chilblain-Like Lesions (CLL) Coinciding With the SARS-CoV-2 Pandemic in Children: A Systematic Review.

Chilblain-like lesions (CLL) coinciding with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection have been described in the literature. Available reviews of the literature suggest that CLL are associated with younger age, an equal sex ratio, negative testing for SARS-CoV-2, and mild to no extracutaneous manifestations (ECM) associated with COVID-19 infection. This systematic review aims to provide a summary of reports of CLL associated with the early SARS-CoV-2 pandemic in children to clarify the prevalence, clinical characteristics, and resolution outcomes of these skin findings. Sixty-nine studies, published between May 2020 and January 2022, met inclusion criteria and were summarized in this review, representing 1,119 cases of CLL. Available data showed a slight male predominance (591/1002, 59%). Mean age was 13 years, ranging from 0 to 18 years. Most cases had no ECM (682/978, 70%). Overall, 70/507 (14%) of patients tested positive for COVID-19 using PCR and/or serology. In the majority the clinical course was benign with 355/415 (86%) of cases resolving, and 97/269 (36%) resolving without any treatment. This comprehensive summary of pediatric CLL suggests these lesions are rarely associated with COVID-19 symptoms or test positivity.

COVID 19-associated chilblain-like acral lesions among children and adolescents: an Italian retrospective, multicenter study.

BACKGROUND: Since the COVID-19 pandemic started, great interest has been given to this disease, especially to its possible clinical presentations. Besides classical respiratory symptoms, dermatological manifestations occur quite often among infected and non-infected patients, particularly in children. A prominent IFN-I response, that is generally higher in children compared to adults, may not only cause chilblain lesions, but it could also prevent infection and viral replication, thus justifying the negative swab results, as well as the absence of relevant systemic symptoms in positive cases. Indeed, reports have emerged describing chilblain-like acral lesions in children and adolescents with either proven or suspected infection. METHODS: Patients aged from 1 to 18 years old were enrolled in this study from 23 Italian dermatological units and were observed for an overall period of 6 months. Clinical pictures were collected along with data on the location and duration of skin lesions, their association with concomitant local and systemic symptoms, presence of nail and/or mucosal involvement, as well as histological, laboratory and imaging findings. RESULTS: One hundred thirty-seven patients were included, of whom 56.9% were females. Mean age was 11.97±3.66 years. The most commonly affected sites were the feet (77 patients, 56.2%). Lesions (48.5%) featured cyanosis, chilblains, blisters, ecchymosis, bullae, erythema, edema, and papules. Concomitant skin manifestations included maculo-papular rashes (30%), unspecified rashes (25%), vesicular rashes (20%), erythema multiforme (10%), urticaria (10%) and erythema with desquamation (5%). Forty-one patients (29.9%) reported pruritus as the main symptom associated with chilblains, and 56 out of 137 patients also reported systemic symptoms such as respiratory symptoms (33.9%), fever (28%), intestinal (27%), headache (5.5%), asthenia (3.5%), and joint pain (2%). Associated comorbid conditions were observed in 9 patients presenting with skin lesions. Nasopharyngeal swabs turned out positive in 11 patients (8%), whereas the remainder were either negative (101, 73%) or unspecified (25, 18%). CONCLUSIONS: COVID-19 has been credited as the etiology of the recent increase in acro-ischemic lesions. The present study provides a description of pediatric cutaneous manifestations deemed to be potentially associated with COVID-19, revealing a possible association between acral cyanosis and nasopharyngeal swab positivity in children and teenagers. The identification and characterization of newly recognized patterns of skin involvement may aid physicians in diagnosing cases of asymptomatic or pauci-symptomatic COVID patients.

Prevalence of phalangeal bone marrow edema on MRI before and during the COVID-19 pandemic and correlation with chilblain skin lesions.

OBJECTIVE: The purpose of this study is to establish the prevalence bone marrow edema of the phalanges of the feet and hands before and during the COVID-19 pandemic on MRI studies and correlate with clinically chilblain skin lesions and epidemiological data. METHODS: This observational retrospective study. In patients with confirmed bone marrow edema of the phalanges, epidemiological data and clinical findings were collected, including the history of current or remote COVID-19 infection and vaccination status. The two-proportion test was used to compare the frequency of bone marrow edema in the phalanges before and during the pandemic, and the comparison between the categories variables was performed using the one-proportion test. RESULTS: Of the total of 7215 patients, only 20 presented isolated bone marrow edema of the digits in MRI studies; 2 (0.05%) were found two years before the pandemic's beginning, and 18 (0.64%) after the pandemic's onset, demonstrating an increase of 13-fold in this period. 16 were women with a mean age of 40.3 years and 4 were men with a mean age of 53.5 years. The most frequently reported clinical symptoms by the patients were pain (85.0%), and erythema of the skin (45.0%). Of the 18 patients found after the pandemic's onset, only 27.8% had COVID-19 infections confirmed by RT-PCR before the imaging study, and all cases were mild. CONCLUSION: This study demonstrated a significant increase in the prevalence of bone marrow edema of the phalanges after the onset of the COVID-19 pandemic, particularly in middle-aged and younger women.

Cutaneous manifestations of COVID-19 and COVID-19 vaccination.

In December 2019, a new infectious pathogen named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in Wuhan, China. Transmitted through respiratory droplets, SARS-CoV-2 is the causative pathogen of coronavirus disease 2019 (COVID-19). Although this new COVID-19 infection is known to cause primarily interstitial pneumonia and respiratory failure, it is often associated with cutaneous manifestations as well. These manifestations with COVID-19 can be classified into seven categories: (i) chilblain-like skin eruption (e.g., COVID toes), (ii) urticaria-like skin eruption, (iii) maculopapular lesions, (iv) vesicular eruptions, (v) purpura, (vi) livedo reticularis and necrotic lesions, (vii) urticarial vasculitis, and others such as alopecia and herpes zoster. The pathogenesis of skin eruptions can be broadly divided into vasculitic and inflammatory skin eruptions. Various cutaneous adverse reactions have also been observed after COVID-19 mRNA vaccination. The major cutaneous adverse reactions are type I hypersensitivity (urticaria and anaphylaxis) and type IV hypersensitivity (COVID arm and erythema multiform). Autoimmune-mediated reactions including bullous pemphigus, vasculitis, vitiligo, and alopecia areata have also been reported. Several cases with chilblain-like lesions and herpes zoster after COVID-19 mRNA vaccination have been published. Various skin diseases associated with COVID-19 and COVID-19 vaccination have been reported, and the mechanism has been partly elucidated. In the process, for example, some papers have reported that it is not related to COVID-19 infection, although it was initially called COVID-toe and considered a COVID-19-associated cutaneous eruption. In fact, some COVID-19-associated skin reactions are indistinguishable from drug eruptions. In the future, the mechanisms of COVID-19- or COVID-19 vaccine-associated skin reactions need to be elucidated and verification of causal relationships is required.