Source: Podiatry Today; April 22, 2020
By Tracey Vlahovic DPM
While determining the evolution of this viral disease, health-care providers are sharing their observations in peer-reviewed journals and on social media in order to diagnose COVID-19 faster. Specifically, a colleague sent me a video via Facebook that was originally a lecture from Dr. Maria Del Mar Ruiz Herrera in Spain.1 One of Dr. Herrera’s PowerPoint slides lists the pedal skin manifestations of COVID-19 as a chilblains-like lesion or as a vasculitis-like presentation on fingers and toes that can occur in children, teenagers and adults who have been diagnosed as positive for COVID-19 or are asymptomatic.
These individuals can experience urticaria or no symptoms of these lesions. Following that slide is a series of photograph that correlate with the lesion descriptions. However, there is failure to state if these are pictures of the feet of COVID-19-positive patients and if providers noticed these lesions before or after the diagnosis. From viewing the recent statement given by the Spanish General Council of Official Podiatrist Colleges and the similar pictures shown in their statement, I believe these pictures are examples of what these skin lesions look like rather than photos taken from actual COVID-19-positive patients.
Many podiatrists and dermatologists are not taking photographs due to the risk of having the phone/camera in the treatment room. Unfortunately, the Spanish General Council of Official Podiatrist Colleges did not give any concrete numbers of patients who experienced these skin manifestations nor did the Council discuss the evolution of these lesions during the illness. These manifestations are clinical observations with no reported histopathologic correlation.
The New York Post and other media outlets reported that same statement by the Spanish General Council of Official Podiatrist Colleges that stated lesions like those observed in chickenpox, measles or chilblains presented on the toes of young patients in France, Italy, and Spain.
They did note that there is currently not enough scientific evidence to support these findings. They also did not report concrete numbers of patients affected, if the patients were on medication at the time of observation of these skin manifestations or when clinicians noted these lesions (before or after patients were diagnosed as being COVID-19 positive). However, the aforementioned Council has opened a registry for podiatrists to report COVID-19-positive patients who have pedal skin manifestations.
Sifting Through The International Literature On Pedal Manifestations of COVID-19
Supporting these findings from Spain is a case report from the International Federation of Podiatrists of a 13-year-old boy in Italy who had pedal purpura that progressed to blistering and necrotic lesions that ultimately resolved.4 Due to the other symptoms of fever, muscle pain, headache and intense itching of the lesions, a physician diagnosed the patient as having a spider bite. Of note, the patient’s mother and sister had respiratory symptoms a week before the patient’s skin lesions appeared. Physicians formed a working diagnosis of COVID-19 but this diagnosis was not confirmed prior to this blog being published.
In Italy, health-care practitioners confirmed dozens of reports of acrocyanotic lesions in asymptomatic COVID-19-positive children and adolescents who were generally in good health prior to the skin rash onset.4 These patients tend to have lesions on their feet although the hands may be affected as well. For the foot lesions in these patients, they affect the toes and plantar aspect more commonly, but may not affect all the toes. According to these reports from Italy, the lesions may appear red to blue, may become bullous or develop “blackish crusts,” be painful and evolve over two weeks, but ultimately resolve on their own.
As I read these cases, they remind me of the cutaneous polyarteritis nodosa lesions I see on the feet of my own patients. One should note that various skin lesions that present as red to purple to blue lesions on the toes, such as pernio, Henoch-Schonlein purpura and acrocyanosis, will have different disease evolutions, histories, and extra-pedal/systemic manifestations that one should still look for and consider even with these case reports.
Zhang and colleagues, in a study published in the Chinese Journal of Hematology, presented a retrospective analysis of seven critically-ill COVID-19 patients admitted to the hospital.5 All seven lived in Wuhan, China, had fever/respiratory symptoms and had various stages of limb ischemia. Three of the seven had underlying diseases such as diabetes, hypertension and coronary heart disease. Their limb ischemia presented as plantar to digital discoloration to dry gangrene. The average time from onset to limb ischemia was 19 days. These lesions correlated with progression/aggravation of the disease and occurred either a few days before or a few days after mechanical ventilation.
All seven patients had an increased D-dimer level more than 20 times the upper limit of normal.5 This study also showed a statistically significant increase in D-dimer level between ICU and non-ICU patients. Fibrin and fibrinogen degradation product (FDP), a test to diagnose disseminated intravascular coagulation (DIC), were also greatly increased in ICU patients. Six of the patients deemed to be in a hypercoagulable state received low-molecular weight heparin therapy, which decreased those FDP values. Unfortunately, the benefit of the anti-coagulation therapy was not overwhelming as five of the seven patients died prior to the study being published. One of the remaining patients had worsening of digital ischemia while the other patient had improvement with the anticoagulation therapy. Ultimately, the conclusion of this article is to monitor the COVID-19 patients with limb ischemia for coagulation dysfunction and commence anticoagulation therapy when appropriate.
From the dermatology world, there are preliminary reports in the literature that speak of skin manifestations in COVID-19 patients in general. Based in Italy, Recalcati noted that slightly over 20 percent of 88 patients with the COVID-19 virus developed cutaneous manifestations.6 Eight patients had skin rashes at the onset of symptoms while the rest developed lesions after being hospitalized. Recalcati observed erythematous rash (78 percent), urticaria (3 patients) and chickenpox-like vesicles (1 patient) in his study, and that the trunk was the main area of cutaneous involvement. However, he noted that there did not seem to be a correlation between the rash and viral disease severity, and that the rashes were like skin manifestations he had observed with common viral infections.
In a case report from Thailand, Joob and Wiwanitkit discussed a patient who was originally diagnosed with dengue fever due to the presence of petechiae and a low platelet count, but ultimately was COVID-19 positive.7 The final diagnosis occurred upon hospital admission for respiratory problems. In this case, a skin rash that looked like something more common in that region was masquerading as the viral infection.
Coronavirus in general may present as a petechial rash and livedoid eruptions. In two cases reported by Manalo and colleagues, livedo reticularis (which may be a sign of disseminated intravascular coagulation (DIC)) was a finding in patients with the COVID-19 virus.8 They hypothesized that the microthrombi present in critically ill patients with the COVID-19 virus was the most likely cause for the livedo reticularis presentation. Biopsies did not occur in either case due to the transient nature of the livedo presentation so the researchers could not confirm a histopathologic correlation.
What Podiatrists Should Know About Including The Coronavirus In A Differential Diagnosis
What does this mean to a practicing podiatrist, whether you are treating these patients in the hospital, via telemedicine or in the office? First, keep in mind that not every patient with the COVID-19 virus will develop skin lesions, especially in the lower extremity. Skin lesions may be primarily on the trunk so ask the patient if he or she has recently developed a skin rash somewhere else on the body.
Second, many viral diseases cause exanthems (rashes) on the skin. Those diseases you are familiar with include chickenpox (Varicella-Zoster), measles and Fifth disease. It is entirely possible the rash you are seeing may be caused by a different viral entity itself or could be related to the coronavirus. The reported petechiae and purpura can occur with a lot of different skin conditions and is not specific to COVID-19.
If you see petechiae or purpura (lesions that do not blanch when you press on them or when the patient does this via telemedicine) on the plantar surface or digits that may or may not have symptoms of burning, tingling or itching, you want to keep the various main differential diagnoses in mind. These can include vasculitis due to sepsis/infection, drug reaction or an underlying connective tissue disorder. As the literature is variable in regard to skin lesions being the harbinger of the viral diagnosis or as the result of complications of coronavirus, obtain vitals, a thorough history and review of systems. If you need to perform a biopsy to ascertain more information, use your clinical judgement to do so.
If these lesions present on a child, as researchers have reported in Italy and Spain, ask about symptoms of other members of the household as the child may be asymptomatic for the COVID-19 virus.3,4 In adults, be cautious of clinical signs of limb ischemia (unilateral or bilateral) and order lab tests such as D-dimer, fibrinogen degradation product and prothrombin time (PT) to determine if the patient has disseminated intravascular coagulation. Also remember that critically ill patients may have underlying conditions that may contribute to ischemia so obtain as thorough of a patient history as possible.
The American Academy of Dermatology started a registry for skin lesions and patients with the COVID-19 virus.9 This is accessible for any health care professional to upload patient data and I encourage you to utilize it. As more evidence begins to disseminate from around the world regarding these pedal lesions and their correlation to the virus, we will be able to determine the causality, frequency and meaning, if any, of the skin manifestation to the viral presence. However, until the medical community can assess the fruits of these efforts, one should reserve any definitive statements regarding a correlation between the coronavirus and dermatologic manifestations in the lower extremities until researchers can analyze more evidence.
References
del Mar Ruiz M. Available at: https://clinicamariadelmarruiz.es/ . Accessed April 16, 2020.
Salo J. Foot sores could be an early sign of coronavirus, experts say. New York Post. Available at: https://nypost.com/2020/04/14/foot-sores-could-be-an-early-sign-of-coronavirus-experts-say/ . Published April 14, 2020. Accessed April 16, 2020.
Consejo General de Colegios Oficiales de Podólogos de España. Registro de casos compatibles COVID-19. Available at: https://cgcop.es/2020/04/09/registro-de-casos-compatibles-covid-19/?fbclid=IwAR2wv4ocR2eLQGPVSChBuPeDjub6Ay7tAZwqiuWISwYe0EqCPPklhRb3Rdg . Published April 9, 2020. Accessed April 16, 2020.
Mazzotta F, Troccoli T. Acute acroischemia in the child at the time of COVID-19. International Federation of Podiatrists. Available at: https://www.fip-ifp.org/wp-content/uploads/2020/04/acroischemia-ENG.pdf . Accessed April 16, 2020.
Zhang Y, Cao W, Xiao M, et al. Clinical and coagulation characteristics of 7 patients with critical COVID-2019 pneumonia and acro-ischemia. Zhonghua Xue Ye Xue Za Zhi. 2020;41(0):E006. doi: 10.3760/cma.j.issn.0253-2727.2020.0006. [Epub ahead of print]
Recalcati S. Cutaneous manifestations in COVID-19: a first perspective. J Eur Acad Dermatol Venereol. 2020. Available at: https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdv.16387 . Accessed April 16, 2020.
Joob B, Wiwanitkit V. COVID-19 can present with a rash and be mistaken for dengue. J Am Acad Dermatol. 2020;82(5):e177.
Manalo IF, Smith MK, Cheeley J, Jacobs R. A dermatologic manifestation of COVID-19: transient livedo reticularis. J Am Academy Dermatol. 2020. Available at: https://doi.org/10.1016/j.jaad.2020.04.018 . Accessed April 16, 2020.
American Academy of Dermatology. COVID-19 Dermatology Registry. Available at: https://www.aad.org/member/practice/coronavirus/registry. Accessed April 20, 2020.
Additional References
10. Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061-1069.
11. Chesser H, Chambliss JM, Zwemer E. Acute hemorrhagic edema of infancy after coronavirus infection with recurrent rash. Case Rep Pediatr. 2017;2017:5637503. Doi: 10.1155/2017/5637503 . Epub 2017 Jan 24.