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Cutaneous Manifestation During COVID-19: Don’t Let the Rash Fool You

Children With Wounds: Asking the Right Questions

Cutaneous Manifestation During COVID-19: Don’t Let the Rash Fool You

Introduction

Many rashes may not be simple to diagnose, but the urgency and risk of complications are generally low. Most have a good prognosis, rare association with life-threatening morbidity, and can be observed over time. Today, while we live in a world conquered by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) illness, diagnosing a viral rash or unusual skin manifestation may potentially be a clue to a life-threatening disease that leaves its mark on many organs. Missing the connection between cutaneous manifestations and COVID-19 may unfold into bigger catastrophes—coronary artery aneurysm, myocarditis, cardiomyopathy, arrhythmia, kidney damage, and vessel occlusion—leading to devastating sequelae and sometimes death. 

The impact of SARS-CoV-2 started in late November 2019 in Wuhan, a province of Hubei, China, and quickly progressed around the planet, with the first cases in North America reported by mid-January 2020.1 As the virus enveloped different countries, thousands and then millions were infected, ill, and admitted to hospitals; thousands died. Many of the first patients were adults with comorbidities. Then reports of healthy adults and children began to appear.2 As demographic data were being gathered, the initial impression of pediatric SARS-CoV-2 infection was positive: children were not infected as often as adults, children who were infected were not suffering as much as adults, sequelae were not seen, and vertical perinatal transmission was not observed.3–5 By and large, these statements seemed correct until the middle of April 2020, when pediatric professionals in Europe and New York started reporting clusters of children with multisystem inflammatory syndrome who were showing features similar to Kawasaki disease (KD).

Kawasaki disease is a multisystem vasculitis and a mucocutaneous lymph node syndrome that occurs primarily in young children with a potential of life-long coronary artery and cardiac disease.6 Multisystem inflammatory syndrome in children (MIS-C) is a new syndrome that shares many similarities with KD, but age and prominent clinical manifestation show some differences. Myocardial involvement with acute heart failure, shock, and multi-organ failure are feared sequalae.

At my institution, we are careful to consider a diagnosis of SARS-CoV-2 disease when fever, cough, malaise, and respiratory symptoms are present, but an astute professional may recognize cutaneous manifestations of COVID-19 disease even without other symptoms, leading to an improved differential diagnosis and earlier disease recognition. The following section is from my colleague, Dr. Alisha Oropallo. In it, she highlights what has been seen in her outpatient wound center, the Northwell Comprehensive Wound Center in Hempstead, NY.

From Dr. Oropallo

One of the challenges of working in an outpatient wound center is identifying SARS-CoV-2 lesions without obvious symptomatology. There is a paucity of literature regarding how to identify SARS-CoV-2 cutaneous lesions. Lesions have been described as a truncal red rash, hives, or blisters resembling chickenpox on the trunk; there is also a “pseudo-frostbite” condition nicknamed “COVID toes” or pernio-like lesions (Figure 1). Nondescriptive findings, such as dark bruise-like bumps and swelling, may be confused with other differential diagnoses of rashes.1,2 However, patients will generally present with a new finding of a rash from an unknown origin. Patients may complain of discomfort localized to the area. However, because the pain can be mild, these findings can be missed without a thorough history and physical examination. Without clear COVID-19 concomitant symptomatology, work-up is similar to obtaining a diagnosis of exclusion. In my practice, I have seen these lesions have a prolonged course of healing. Keeping the wound clean of biofilm, optimizing nutrition, and offloading can help provide a proper wound healing environment. Correlation of these lesions to Covid-19 is due to a positive nasopharyngeal swab for SARS-CoV-2 within 72 hours. However, testing for SARS-CoV-2 can be challenging. The procedural requirements vary among hospitals. Because of the difficulty in establishing proper guidelines to transfer specimens, analysis of biopsy samples for SARS-CoV-2 has not been well established. In fact, to date, there have been no reports of SARS-CoV-2 in wound tissue or fluid. However, despite the ability to obtain testing, this has not deterred me from taking a biopsy if needed to rule out other causes.

Pediatric Skin Manifestations in Published Case Reports and the Author’s Practice

COVID-19 enters cells via angiotensin-converting enzyme-2 receptors, replicates in the respiratory tract, and causes multi-organ injury. We know that angiotensin-converting enzyme-2 receptors exist in the lungs, heart, kidney, gastrointestinal tract, and vascular endothelium. Pediatric skin manifestations have been described as livedoid rash, purpuric lesions (Figure 2), macular or morbilliform rash (Figure 3), desquamation on extremities and/or buttocks (Figure 4), and occasionally targetoid lesions on the trunk or extremities. COVID toes (Figure 5) or chilblain-like lesions (reddish, purple skin discoloration) have been described in children as well. Studies from the United Kingdom, Italy, and Spain were first to describe case reports of children with chilblain noted on the extremities.7,8 Children’s ages ranged from 5 to 17 years, and they often presented with cough and rhinorrhea that developed a few days prior. Acral lesions were described as red, purple, blistery, and sometimes painful or itchy. Symptoms often progressed to fever, hypotension, and organ dysfunction. Similar to adults, some children had elevated D-dimer levels leading to coagulopathy evaluation.8 Biopsy specimens revealed dense lymphocytic perivascular cuffing and peri-adnexal infiltration. The Italian group suggested that the etiology was a vaso-occlusive phenomenon, supporting coagulation work-up in all children with acrovasculitis-like findings.7,8 Few children had a negative initial COVID-19 Prevention, Retention, and Contingency (PRC) test result; some had a positive follow-up test result, whereas others could have had a false-negative result because sensitivity of the real-time polymerase chain reaction (RT-PCR) depends on the quality of the sample. All children in the above studies healed.

Nonexudative conjunctivitis, mucositis, and cracked erythematous lips have also been noted. Initial presentation of COVID-related illness in children is often described as fever, rash, nonspecific weakness, extremity pain, and gastrointestinal symptoms.9 Many would consider a broad differential diagnosis at this point: common viral exanthems, streptococcal scarlet fever, or contact dermatitis (if only rash is present). With prolonged fever, desquamation, and erythroderma, staphylococcal scalded skin syndrome and toxic epidermal necrolysis should be considered in the differential diagnosis; mucosal membrane involvement adds toxic shock syndrome, Stevens-Johnson syndrome, and KD. Let us not forget SARS-CoV-2 in our differential diagnosis, as running an RT-PCR test may allow a practitioner to anticipate potential developments or complications seen with acute SARS-CoV-2 or 2- to 3-week post sequalae such as KD-like disease or MIS-C.

We do not know the etiology of KD, but we know that there is a triggering event. Could SARS-CoV-2 be that triggering event leading to atypical KD? Or can the infection cause cytokine storm (hyperexcitability of the immune system, release of pro-inflammatory interleukins [eg, IL-6], hypercoagulation, and hypoxia), resulting in the injury of multiple organs via inflammation following the acute phase of COVID-19? We do not know for sure, but what we do know at this point is as follows.

It does not seem that there is vertical transmission to neonates from COVID-19–positive mothers, but cases of COVID-positive children as young as 2 days have been reported.3–5 The transmission is likely from person-to-person exposure as there are no studies showing RT-PCR–positive tests of amniotic fluid, placenta, or cord blood.5 Neonates may present with respiratory symptoms, occasionally fevers, and cutaneous findings such as desquamation, erythematous or lacy purpuric rash, and purpuric macules (Figures 2–4). There are discussions in the literature questioning if there are transplacental transmissions via infected maternal cells passing to the fetal side of the cytotrophoblast or by transcytosis of free virus.11 If those mechanisms are viable, will SARS-CoV-2 infection become additional viral TORCH infections (ie, toxoplasmosis, other [syphilis, varicella-zoster, parvovirus B19], rubella, cytomegalovirus, and herpes infections)?12 Not enough data are available now, but animal studies have shown that previous SARS viruses did have such in utero transmission.

Young children present with fever, cough, rhinorrhea, diarrhea, vomiting, and weakness. Some have pharyngitis and tachypnea later. Children younger than 10 presenting with cardiorespiratory failure may have KD, atypical KD, or COVID-induced myocardial disease.9–11 They have the above-described rash and, in addition, may have COVID toes and mucosal membrane involvement. The feared cardiovascular complications of coronary artery aneurysm, myocarditis, and cardiomyopathy can be prevented or treated if recognized in a timely manner. Fever and rash might be the early clues.

Adolescents who had a simple rash and viral symptoms may present with complex heart failure symptoms 2–3 weeks later or acutely as SARS-CoV-2 progresses. In our system, all children who presented with this condition were either COVID PRC- or serology-positive. Heart failure and shock, as opposed to respiratory failure, can result in intensive care unit (ICU) admission, intubation, and use of vasopressors and extracorporeal membrane oxygenation (ECMO) support. Many believe that SARS-CoV-2 triggers immune dysregulation and hyperinflammation. Timely and appropriate treatment can be lifesaving. Immunoglobulins and steroids seem to restore cardiac function in children with MIS-C.12 Aspirin and immunoglobulin are traditional treatments of KD.9

Timely recognition is paramount not only for life-saving treatments, but for skin injuries seen in these children as the result of SARS-CoV-2 disease. Those in the ICU suffer from extravasations and pressure injuries. I have seen children with “purple” lesions that resemble deep tissue injury and are often in pressure-transmitting locations, such as the sacral area or buttocks, but it is not clear whether a pressure injury or COVID-related vasculitis is the etiology (Figure 6). Most do not become open wounds. I treat them as a stage 1 deep tissue injury by using protection with foam, repositioning, and frequent observation.

Conclusion

There is so much that is currently unknown about SARS-CoV-2. The primary author is now treating a neonate who was born with compromised perfusion to an upper extremity, with hand and partial forearm necrosis that will lead to an amputation. COVID-19 infection and illness developed in her mother during the second to third trimester. At this point, the neonate’s coagulation work-up is negative. The injury is secondary to an arterial thrombus in the vessels of the wrist and hand that clearly formed in utero and worsened immediately after birth. We are considering hypercoagulability and ischemia as a consequence of maternal COVID-19 infection in our differential diagnosis work-up. 

As we write this article, the United States is reopening and feeling hopeful. Multiple vaccines are in the making, various treatments are being evaluated, and trials of sensitive antibody tests are being reported. Yet the reality of today is still grim; as such, we hope that practitioners pay attention to all symptoms, including cutaneous manifestations of this powerful virus.

Affiliations

Dr. Boyar is the director of Neonatal Wound Services, Cohen Children’s Medical Center of New York, New Hyde Park; and assistant professor of Pediatrics, Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY.

Dr. Oropallo is an attending surgeon, Department of Vascular Surgery, Northwell, and the director of Northwell Comprehensive Wound Center, Hempstead, NY; and associate professor, Zucker School of Medicine at Hofstra/Northwell, Hempstead NY.

All photos provided are with the consent of the patients’ parents.

This article was not subject to the Wound Management & Prevention peer-review process.