Skin manifestations overlap in COVID-19 patients: A continuous spectrum?

Abstract

Dear Editor Several studies have reported diverse skin manifestations in COVID-19 patients, such as acral lesions (pseudo-chilblain), vesicular eruptions, urticarial lesions, maculopapular rashes, and vascular lesions.1, 2 These are considered isolated entities, with different suspected etiologic factors and prognosis.1 However, a possible overlap in cutaneous findings may also exist. An otherwise healthy 29-year-old male presented to the Emergency department with a 1-week history of cough, shortness of breath and fever, testing positive for SARS-CoV-2. He had not received any medication during the previous months. Physical examination revealed erythematous papules and vesicles, with an asymmetrical distribution on elbows, buttocks, and lower abdomen (Figure 1). No other lesions were present. Therapy with hydroxychloroquine and azithromycin was started, with a significant improvement of systemic symptoms. Four days after the medication was discontinued, the patient progressively developed millimetric vesicular papules with a purpuric component on his feet, without acral ischemic lesions (Figure 2). Within 5 days, trunk lesions started to disappear, while feet lesions persisted and resolved within the next month. No further treatment was prescribed. COVID-19 has been associated with a wide variety of skin manifestations, producing multiple reactive patterns. This is an uncommon finding in other viral infections. Pathophysiology of these lesions remains unknown, although several hypotheses have been made. COVID-19 maculopapular exanthema has been associated with a postviral immunological reaction.2 Viral particles have been detected inside the endothelium of affected skin, suggesting the involvement of cytokine-related activation of cytotoxic and NK lymphocytes.3 However, thrombosis of the dermal vessels has also been described in exanthematic skin rashes.4 Furthermore, some of the drugs used in COVID-19 treatment, including hydroxychloroquine and azithromycin, may cause cutaneous adverse drug reaction (CARD), such as maculopapular exanthema.5 In the present case, however, the trunk rash started before any drug intake making drug involvement very unlikely. Acral skin manifestations have also been described, including both chilblain-like lesions (CLL) in mildly symptomatic patients,1 and ischemic lesions of dry gangrene in severely-ill patients with coagulation disorders.6 An immunologic response mediated by type I interferon (IFN-I) may be responsible for microangiopathic changes in CLL.7 Moreover, coagulation disorders related to COVID-19 can also lead to thrombosis, resulting in acral cyanosis or gangrene.6 CLL have been described and classified as the genuine chilblain-like (or erythematous-oedematous type) and the erythema multiforme-like (or blistering type).8, 9 Even if there is no consensus on the nomenclature of these lesions, the present case corresponds to the second group of CLL. A vesicular and only acral-located CARD would be very unlikely, however we cannot rule out that these lesions have been occurred in the context of CARD. Vesicular and CLL appear to be more specific COVID-19 skin manifestations than urticarial or maculopapular lesions.1, 10 There is a tendency to merge all acral lesions into “chilblain-like” and to separate this group from other COVID-19 skin manifestations in terms of etiological factors. In this particular case, both acral and corporal lesions had a similar clinical appearance. However, the late-onset development and prolonged duration of feet papules are consistent with CLL. We thus believe that clinical differences found in acral lesions ranging from true ischemic, chilblain-like and vesicular, should all be regarded as a continuum, in which both an immunological activation and abnormal coagulation parameters may coexist. In conclusion, different COVID-19 skin patterns may coexist in the same patient.11 We should consider them as a continuous spectrum, probably occurring as a result of several etiological factors, including both inflammatory and coagulation cascades. CARDs should be consider in these patients given the high prevalence of medication intake. Depending on the main predominant clinical features and other concomitant COVID-19 symptoms, we could adjust complementary tests and even the therapeutic approach. The patient in this manuscript have given written informed consent to publication of his case details. The authors declare no conflict of interest. Gerald Selda-Enriquez had full access to all data in the study and takes responsibility for the integrity of the data and the accuracy of data analysis. Study concept and design: Selda-Enriquez, Fernandez-Nieto, Fernandez-Guarino. Acquisition, analysis and interpretation of data: Selda-Enriquez, Fernandez-Nieto, Burgos-Blasco, Melian-Olivera. Drafting of the manuscript: Selda-Enriquez, Fernandez-Nieto, Burgos-Blasco, Melian-Olivera. Critical revision of the manuscript for important intellectual content: Fernandez-Nieto, Fernandez-Guarino. The data that support the findings of this study are available from the corresponding author upon reasonable request.