Reconstructive Limb Salvage After COVID-19-Induced Gangrene and Amputation.

This case series describes the clinical course and reconstructive methods utilized for patients with diabetes and significant gangrene and necrosis following coronavirus disease 2019 (COVID-19) infection. COVID-19 produces mainly respiratory symptoms but has a variety of atypical presentations and sequelae. Serious complications are increased in patients with underlying medical conditions such as diabetes mellitus. By generating a prothrombotic milieu, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) increases the risk for arterial and venous thromboses. Inflammatory damage and micro-thromboses are thought to contribute to acro-ischemia, colloquially known as 'COVID toes,' which presents cutaneously as chilblain-like lesions. Necrosis can be severe and devastating, often resulting in major amputation. Two exemplary case reports are presented herein: first, a 57-year-old female presented for vascular evaluation with pedal gangrene to the midfoot one month after developing painful discoloration in her right toe. After angioplasty restored pedal blood flow, she received a transmetatarsal amputation (TMA) with a local tissue flap. Second, a 41-year-old female presented for vascular evaluation with extensive pedal gangrene three months after hospitalization for COVID-19. After arteriotomy improved pedal blood flow, she underwent a Lisfranc amputation followed by superficial circumflex iliac artery perforator (SCIP) flap reconstruction. Sufficient evidence suggests that COVID-19 impairs microcirculatory function and can be especially detrimental in diabetic patients. Reconstructive techniques in patients with severe gangrene with COVID toes help patients regain functionality.

Diagnosis and management of COVID toes in outpatients: a case report.

BACKGROUND: Since the beginning of the coronavirus disease 2019 pandemic, the most common skin lesions observed due to infection with the severe acute respiratory syndrome coronavirus 2 are pseudochilblains (or coronavirus disease toes). However, this pathology remains infrequent and difficult to diagnose, as no specific test exists. CASE PRESENTATION: Two Caucasian women, 30 and 22 years old, presented to our General Medicine Unit with perniosis lesions on the feet during the first two waves of the coronavirus disease 2019 pandemic. They did not have respiratory or general symptoms of severe acute respiratory syndrome coronavirus 2 infection, the reverse transcription polymerase chain reaction on nasopharyngeal swabs was negative, and the serology was positive only in the first case. The clinical presentation differed for the two cases, as the second patient suffered from swelling and burning after cold application. The diagnosis was based on clinical presentation, temporality, exclusion of other differential diagnoses, and blood test results (positive serology in the first case and high level of CXCL13 and VEGF in the second), supported by current literature. Lesions resolved spontaneously in the first patient. The second case was hospitalized for pain management and received corticosteroid therapy with resolution of the symptoms. CONCLUSION: These two cases with different clinical presentations illustrate the diagnostic approach to coronavirus disease 2019, a challenging disease with diverse manifestations, including, in some cases, coronavirus disease toes. We present a literature review that illustrates the progression of scientific research. Skin lesions associated with coronavirus disease 2019 infection could be the expression of an important interferon type 1 response and should be considered in the differential diagnosis in a primary care setting.

A curious case of 'COVID toes' in pregnancy.

The novel coronavirus of 2019 (COVID-19) can affect multiple organ systems with a wide spectrum of illness severity. Its effect on the respiratory tract is well-documented and has resulted in considerable excess mortality worldwide. However, observed cutaneous manifestations of COVID-19 are rising, ranging from short-lived viral exanthems to vesicular eruptions and urticaria. An unusual subgroup of these manifestations - pseudo-chilblains, also referred to as pernio-like lesions or 'COVID toes' - describes the acral areas of erythema and oedema that can affect young individuals following COVID-19. We present a case associated with pustule and vesicle formation occurring in the context of pregnancy.

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.

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.

Right Foot Trans Metatarsal Amputation Following COVID-19 Infection.

A 60-year-old male patient with a prior coronavirus disease 2019 (COVID-19) pneumonia diagnosis presented with a right foot ulcer. The ulcer progressed to osteomyelitis of his right fifth metatarsal with eventual amputation and resection of the affected digit. The infection recurred two months later and spread to the right fourth metatarsal and gangrene, leading to the amputation and partial metatarsal head resection of the fourth toe. A month later, the infection recurred for a second time and a decision to perform a right trans metatarsal amputation of the foot was evaluated to avoid further progression of the infection and the need for more invasive surgical intervention.

Chilblains observed during the COVID-19 pandemic cannot be distinguished from classic, cold-related chilblains

Background: Type 1 interferon (IFN-I) response induced by SARS-CoV-2 has been hypothesized to explain the association between chilblain lesions (CL) and SARS-CoV-2 infection. Objective: To explore direct cytopathogenicity of SARS-CoV-2 in CL and to focus on IFN-I expression in patients with chilblains. Materials & Methods: A monocentric cohort of 43 patients presenting with CL from April 2020 to May 2021 were included. During this period, all CL were, a priori, considered to be SARS-CoV-2-related. RT-qPCR on nasopharyngeal swabs and measurements of anti-SARS-CoV-2 antibodies were performed. Anti-SARS-CoV-2 immunostainings as well as SARS-CoV-2 RT-qPCR were performed on biopsy specimens of CL and controls. Expression of MX1 and IRF7 was analysed on patients' biopsy specimens and/or PBMC and compared with controls and/or chilblains observed before the pandemic. Serum IFN-α was also measured. Results: RT-qPCR was negative in all patients and serological tests were positive in 11 patients. Immunostaining targeting viral proteins confirmed the lack of specificity. SARS-CoV-2 RNA remained undetected in all CL specimens. MX1 immunostaining was positive in CL and in pre-pandemic chilblains compared to controls. MX1 and IRF7 expression was significantly increased in CL specimens but not in PBMC. Serum IFN-α was undetected in CL patients. Conclusion: CL observed during the pandemic do not appear to be directly related to SARS-CoV-2 infection, either based on viral cytopathogenicity or high IFN-I response induced by the virus.

A novel presentation of childhood systemic lupus erythematosus in a 6-year-old child.

Childhood systemic lupus erythematosus (cSLE) is an autoimmune disorder, characterized by the formation of autoantibodies, that most often presents in children around the age of 12. Antiphospholipid antibody syndrome (APS) is a condition in which antiphospholipid antibodies produced by the patient cause the formation of thromboses. While reports estimate that 30%-40% of cSLE patients have antiphospholipid antibodies, only 4% develop symptomatic APS, with venous thromboses being more common than arterial. Overall, thrombosis has an incidence of about 0.1/10,000 in the pediatric population and usually only occurs in the setting of underlying disease or in relation to medical procedures. Here, we report a case of a 6-year-old female who presented with abdominal pain, arthralgia, fever, and right popliteal artery thrombus. Further testing revealed an abundance of autoantibodies including antinuclear, lupus anticoagulant, and anticardiolipin which resulted in a diagnosis of cSLE with associated APS. This presentation is novel due to both the young age of the patient at disease onset and the presence of concurrent cSLE and APS at initial diagnosis. Childhood systemic lupus erythematosus can be difficult for providers to recognize as it can present with varied nonspecific symptoms but being aware of the potential for onset in children significantly younger than the average will allow for early detection and potentially better outcomes.

Chilblains-Like Lesions in Pediatric Patients: A Review of Their Epidemiology, Etiology, Outcomes, and Treatment.

Vascular pathologies associated with SARS-CoV-2 infection are poorly understood. Color and sensory changes to the extremities, often referred to as "COVID toes" or chilblains-like lesions, have been widely reported in children and adolescents since the onset of the pandemic, raising the concern that they could be a vasculitis secondary to the infection. However, it is unclear if the lesions are a result of the infection or an epiphenomenon. Most literature focuses on adults, and while there are reports on children and adolescents, many of them are small. This review will help medical care providers better understand the epidemiology, etiology, outcomes, and potential treatments for chilblains-like lesions seen in children and adolescents during the pandemic.

SURGICAL ISCHEMIC ASPECTS OF COVID-19: MANAGEMENT OF PATIENTS WITH COVID TOES AND FINGERS.

OBJECTIVE: The aim: Study of clinical manifestations and management of patients with COVID toes and fingers. PATIENTS AND METHODS: Materials and methods: 1,841 patients with laboratory-confirmed SARS-CoV-2 infection were hospitalized. All patients were divided into two groups: without surgical pathology - 1,693 (91.96%) and with surgical pathology (patients with COVID toes and fingers and abdominal syndrome) - 148 (8.04%). The diagnosis of COVID-19 was made on the basis of clinical data, laboratory test results (PCR test for SARS-CoV-2) and computed tomography of the chest. On admission, in addition to the general laboratory tests, mandatory special methods of examination included determination of D-dimer, procalcitonin (PCT), C-reactive protein, and interleukin-6 (IL-6). RESULTS: Results: Surgical ischemic manifestations were observed in 8.04% of all patients with COVID-19, of which 86.48% presented with ischemic abdominal syndrome and 13.52% with COVID toes and fingers. C-reactive protein and procalcitonin are the markers that may indicate the development of ischemic surgical problems. A direct statistically significant linear correlation was found between the severity of the underlying disease and the mean D-dimer (r = 0.815; p = 0.01). CONCLUSION: Conclusions: The confirmed phenomenon of COVID toes and fingers does not require active surgical tactics. It is necessary to conduct pathogenetic treatment of COVID-19 and dynamic monitoring of its clinical course.

COVID toes following vaccination.

Cutaneous manifestations of COVID-19 infections include "COVID toes." These are pernio-like, pale purple, painful, ill-defined cyanotic lesions that have inflammatory infiltrates on histologic studies. COVID toes can also develop following COVID vaccination. COVID toes was reported by 29 individuals to the Vaccine Adverse Event Reporting System maintained by the Centers for Disease Control and Prevention through May 25, 2021. The mean age of these individuals was 52 ± 18 years; 23 (79%) were women. They had received both mRNA vaccines and the adenovirus vector-based vaccine. This discoloration developed 4.5 ± 9.8 days following vaccination, usually after the first dose. Four individuals required hospitalization for systemic symptoms, and one died. This information indicates that some individuals develop important clinical syndromes following vaccination and suggests that some of the manifestations of COVID-19 infection represent immune responses and not necessarily active tissue infection.

"COVID toes": A true viral phenomenon or a diagnosis without a leg to stand on?

"COVID toes" is the colloquial name of chilblain-like lesions thought to be a sequela of COVID-19 infection. Over two years and approximately 300 publications later, this association remains controversial. Here, we summarize key clinical, serological, biological, histological, and immunological evidence that supports and rejects this relationship and discuss alternate theories underlying the pathogenesis of chilblain-like lesions.

Cutaneous manifestation of COVID-19: What have we learned an year into the pandemic?

Coronavirus disease-19 (COVID-19) is an emerging health situation caused by the "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2). The ongoing COVID-19 pandemic which emerged from the Chinese city of Wuhan in December 2019 has spread to over 188 countries and infected over 100 million people across the globe in over one year. Most common symptoms of COVID-19 include fever and respiratory illness. Among extrapulmonary signs associated with COVID-19, dermatological manifestations have been increasingly reported from different geographical regions. The exact incidence or prevalence of COVID-19 associated skin manifestation remains largely unknown and the pathophysiological mechanisms are still unclear. In this article, we have attempted to give a comprehensive overview of what has been learned an year into the pandemic on the epidemiology, clinical and histopathological features, pathophysiological mechanisms and clinical management of COVID-19 associated cutaneous manifestations.

Cutaneous manifestation of COVID-19: What have we learned an year into the pandemic? / Manifestaciones cutáneas de la COVID-19: ¿Qué hemos aprendido tras un año de pandemia?

Coronavirus disease-19 (COVID-19) is an emerging health situation caused by the “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2). The ongoing COVID-19 pandemic which emerged from the Chinese city of Wuhan in December 2019 has spread to over 188 countries and infected over 100 million people across the globe in over one year. Most common symptoms of COVID-19 include fever and respiratory illness. Among extrapulmonary signs associated with COVID-19, dermatological manifestations have been increasingly reported from different geographical regions. The exact incidence or prevalence of COVID-19 associated skin manifestation remains largely unknown and the pathophysiological mechanisms are still unclear. In this article, we have attempted to give a comprehensive overview of what has been learned an year into the pandemic on the epidemiology, clinical and histopathological features, pathophysiological mechanisms and clinical management of COVID-19 associated cutaneous manifestations (AU)

La enfermedad por coronavirus de 2019 (COVID-19) es una situación sanitaria emergente causada por el “síndrome respiratorio agudo severo por coronavirus 2” (SARS-CoV-2). La pandemia por COVID-19 en curso, que surgió de la ciudad china de Wuhan en Diciembre de 2019, se ha propagado en 188 países, y ha infectado a más de 100 millones de personas a nivel mundial a lo largo de un año. Los síntomas más comunes de la COVID-19 incluyen fiebre y enfermedad respiratoria. Entre los signos extrapulmonares asociados a COVID-19 se han reportado cada vez más manifestaciones dermatológicas en las diferentes regiones geográficas. La incidencia o prevalencia exactas de las manifestaciones cutáneas asociadas a la COVID-19 son bastante desconocidas, y los mecanismos patofisiológicos siguen sin dilucidarse. En este artículo hemos tratado de aportar una visión general amplia de lo que hemos aprendido en un año de inmersión en la pandemia en cuanto a epidemiología y características clínicas e histopatológicas, mecanismos patofisiológicos y manejo clínico de las manifestaciones cutáneas asociadas a la COVID-19 (AU)

[Artículo traducido] Manifestaciones cutáneas de la COVID-19: ¿Qué hemos aprendido tras un año de pandemia? / Cutaneous Manifestation of COVID-19: What Have we Learned an Year Into the Pandemic?

La enfermedad por coronavirus de 2019 (COVID-19) es una situación sanitaria emergente causada por el “síndrome respiratorio agudo severo por coronavirus 2” (SARS-CoV-2). La pandemia por COVID-19 en curso, que surgió de la ciudad china de Wuhan en Diciembre de 2019, se ha propagado en 188 países, y ha infectado a más de 100 millones de personas a nivel mundial a lo largo de un año. Los síntomas más comunes de la COVID-19 incluyen fiebre y enfermedad respiratoria. Entre los signos extrapulmonares asociados a COVID-19 se han reportado cada vez más manifestaciones dermatológicas en las diferentes regiones geográficas. La incidencia o prevalencia exactas de las manifestaciones cutáneas asociadas a la COVID-19 son bastante desconocidas, y los mecanismos patofisiológicos siguen sin dilucidarse. En este artículo hemos tratado de aportar una visión general amplia de lo que hemos aprendido en un año de inmersión en la pandemia en cuanto a epidemiología y características clínicas e histopatológicas, mecanismos patofisiológicos y manejo clínico de las manifestaciones cutáneas asociadas a la COVID-19 (AU)

Coronavirus disease-19 (COVID-19) is an emerging health situation caused by the “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2). The ongoing COVID-19 pandemic which emerged from the Chinese city of Wuhan in December 2019 has spread to over 188 countries and infected over 100 million people across the globe in over one year. Most common symptoms of COVID-19 include fever and respiratory illness. Among extrapulmonary signs associated with COVID-19, dermatological manifestations have been increasingly reported from different geographical regions. The exact incidence or prevalence of COVID-19 associated skin manifestation remains largely unknown and the pathophysiological mechanisms are still unclear. In this article, we have attempted to give a comprehensive overview of what has been learned an year into the pandemic on the epidemiology, clinical and histopathological features, pathophysiological mechanisms and clinical management of COVID-19 associated cutaneous manifestations (AU)

Paucity of cutaneous manifestations of COVID-19 among inpatients at a referral hospital in India.

Background: Varied cutaneous manifestations of COVID-19 have been described, but most studies are based on photographic or application-based observations, without a direct observed-based evaluation by dermatologists. Objective: To study the types of cutaneous manifestations of COVID-19 among confirmed inpatients admitted to COVID-19 wards and intensive care units (ICUs). Methods: This cross-sectional analysis was conducted at a referral hospital in Delhi, India. Four hundred forty consecutive reverse transcription-polymerase chain reaction (RT-PCR)-confirmed cases diagnosed with moderate or severe COVID-19 and admitted to COVID-19 wards or ICUs, respectively, were included. A cutaneous finding was considered to be associated with COVID-19 if it had been described earlier as a consequence of COVID-19 and was observed at the time of or within the first 48 hours of admission (after excluding drugs and comorbidities as causes). Results: Two hundred seventy patients with moderate COVID-19 were admitted to COVID-19 wards, whereas 170 with severe disease were admitted to ICUs. Only 7 of the 270 ward patients (2.59%) and 3 of the 170 ICU patients (1.76%) had cutaneous findings associated with COVID-19. Conclusion: Cutaneous findings attributable to COVID-19 are infrequent, and we believe that these might have been overestimated or overemphasized in earlier studies. Although coagulopathic findings may be associated with severe COVID-19, causation cannot be established in this cross-sectional study.

Chilblain or perniosis-like skin lesions in children during the COVID-19 pandemic: A systematic review of articles.

COVID toes or chilblain-like skin lesions represent a widespread and specific skin presentation mostly in the feet that may be attributed to COVID-19 infection. They may last for several months. We conducted this study to investigate chilblain-like lesions in children during the COVID-19 pandemic, any predisposition, location, clinical course, and prognosis. We searched Google Scholar, Scopus, and Medline (PubMed) databases using the following keywords: "Coronavirus" OR "COVID-19" AND "Chilblains" OR "Pernio" OR "Perniosis" OR "Children" OR "Cutaneous" OR "skin." The inclusion criteria were: (a) Studies that described the specific vascular skin lesion. (b) Studies that included patients aged >1 month till 18 years. (c) Case reports, case series, retrospective or prospective cohort studies, case-control studies. A total of 28 articles were included. The total number of children with chiblain-like lesions (CLL) was 433. The mean age of children presenting CLL during the COVID-19 pandemic was estimated as 12.58 ± 2.15. Of note, 53.6% of them were male. The nasopharyngeal SARS-CoV-2 RT-PCR test and anti-SARS-CoV-2 antibodies were mostly negative for the virus. In conclusion, it is crucial to be familiar with various presentations of COVID-19 infection and their clinical significance to approach the earliest diagnosis, immediate treatment, estimate the prognosis, and finally isolate the patients to prevent spreading. Chilblain-like lesions as a possible cutaneous presentation of COVID-19 in children may last several months with the indolent course.

COVID Toes: Concurrent Lower Limb Arterial and Venous Thromboembolism in a Patient with COVID-19 Pneumonitis Presenting with Foot Ischaemia.

We present a 74-year-old gentleman, who presented with foot ischaemia requiring bilateral amputation in the absence of radiological signs of occlusive peripheral arterial disease. He was found to have COVID-19 pneumonitis and concurrent arterial and venous thromboemboli despite no initial respiratory symptoms or signs, nor pre-existing risk factors for cardiovascular disease. Patients who present with foot ischaemia with or without respiratory symptoms or signs warrant a high index of suspicion for COVID-19 infection, particularly in those with no predisposing risk factors.

[Cutaneous Manifestation of COVID-19: What Have we Learned an Year Into the Pandemic?] / [Artículo traducido] Manifestaciones cutáneas de la COVID-19: ¿Qué hemos aprendido tras un año de pandemia?

Coronavirus disease-19 (COVID-19) is an emerging health situation caused by the "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2). The ongoing COVID-19 pandemic which emerged from the Chinese city of Wuhan in December 2019 has spread to over 188 countries and infected over 100 million people across the globe in over one year. Most common symptoms of COVID-19 include fever and respiratory illness. Among extrapulmonary signs associated with COVID-19, dermatological manifestations have been increasingly reported from different geographical regions. The exact incidence or prevalence of COVID-19 associated skin manifestation remains largely unknown and the pathophysiological mechanisms are still unclear. In this article, we have attempted to give a comprehensive overview of what has been learned a year into the pandemic on the epidemiology, clinical and histopathological features, pathophysiological mechanisms and clinical management of COVID-19 associated cutaneous manifestations.

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).