Pernio-like eruption associated with COVID-19 in skin of color.

Introduction

Recently, the skin manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have emerged, with reports and series documenting petechial eruptions, transient livedo reticularis, erythematous rashes, urticaria, primary varicella-like like presentations, and pernio-like eruption.1, 2, 3, 4, 5 The pernio-like eruption, colloquially termed COVID toes, appears associated with an otherwise asymptomatic or mildly symptomatic disease course.,,

Several case series and case reports have been published with photos documenting the pernio-like eruption associated with coronavirus 2019 (COVID-19); however, most published photos have been of individuals with Fitzpatrick skin types (FST) I or II.3, 4, 5 It is not uncommon for skin disease to be misdiagnosed in patients with skin of color, which can lead to delayed care and treatment. Given the disparities in dermatologic educational resources, we present a series of 7 patients with diverse skin types from FST III to V with pernio-like eruptions during the COVID-19 pandemic.

Case series

Similar to prior reports, most of these patients reported no prior COVID-19–associated symptoms or mild, nonspecific symptoms that self-resolved without seeing a physician (Table I; Fig 1, Fig 2, Fig 3, Fig 4, Fig 5, Fig 6, Fig 7). The age range for these patients was from 25 to 44 and included 4 males and 3 females. At time of presentation to a dermatologist, patients reported having a pernio-like eruption from a range of 2 weeks to 8 weeks. Four patients could definitively pinpoint potential exposures, either through contact with a known COVID-19 positive individual or interactions with high-risk environments without personal protective equipment, such as health care settings or international travel. None of the patients had a history of pernio or prior rheumatologic disease (Table I). Additionally, these patients could not pinpoint cold or damp exposures that may have precipitated their skin findings, as most were sheltering in place indoors. Patients were seen in the clinic in Redwood City, California, where average nighttime low and daytime high temperatures were 43-62°F in February, 45-65°F in March, and 46-69°F in April. Patients were generally healthy at the time of presentation. Clinically, patients presented with a range of physical examination findings from erythema and swelling to purpuric and petechial macules, mostly on the toes, but also on the fingers in one case. No other cutaneous findings were reported. Compared with FST I and II findings previously reported in the literature, we note findings on FST III to V may be more subtle. Erythema can appear different in darker skin tones in which pink and red hues are often not seen, and these more subtle findings could lead to a delay in diagnosis.

Table I

Series of 7 patients with pernio-like eruption associated with COVID-19 with corresponding clinical information

Case, age, gender, FST	Symptoms described by patient	Onset of symptoms	Viral symptoms within 1 mo of presentation	COVID risk factors	Comorbidities	COVID respiratory PCR	COVID IgG and IgM serologies	Treatment(s)	Photos
Case A33 MFST III	5/5 right toes and left 4th and 5th toes with erythema and swelling, accompanied by a “raw sensation” and pruritus	March 2020	Yes (patient with baseline cough, mild nausea at presentation)	Multiple interactions with the health care system in early March 2020 as well as air travel from Los Angeles to San Francisco in March 2020	History of high-grade undifferentiated pleomorphic sarcoma of pulmonary artery, s/p resection and chemotherapy with no evidence of molecular or residual disease on imaging	Not tested	Positive for IgGNegative for IgM,4/15/20	Clobetasol 0.05% ointment twice daily with near resolution in early 5/2020	See Fig 1.
Case B39 FFST IV	8/10 fingers, 8/10 toes with swelling, pain, heat sensation, tingling, difficulty with ambulation	February 2020	Yes (occasional fatigue, occasional congestion and runny nose)	Unknown	Eczema, polyarthritis	Not tested	Negative for IgG and IgM, 4/18/20	Oral prednisone 30-mg taper for 10 days and improved for the first 4 days, no improvement thereafter; clobetasol ointment with improvement in early 5/2020	See Fig 2, A-C
Case C31 FFST IV	Swollen, tender, itchy red right third toe for a few weeks; not painful, itchy after showering	April 2020	No	Toddler was sick with a fever at the end of February/early March 2020	None	Negative PCR, 4/21/20	Not tested	None	See Fig 3, A and B
Case D44 MFST IV	Red and purple spots and blisters on toes and under right ring finger, itchy and tingling	March 2020	No	Works as a physician, exposed to PCR SARS-CoV-2–positive colleague	Autoimmune thyroiditis, dyslipidemia, sleep apnea	Negative PCR, 3/15/20	Negative for IgG and IgM, 5/8/20	None	See Fig 4, A and B
Case E31 MFST V	Toe swelling and blisters. First noticed a purplish rash on the feet along with burning and itch, particularly at night. Notes “night attacks” with burning/heat sensation in the toes.	March 2020	Yes (mild sore throat and rhinitis 4/2020)	Grocery store trip in mid March	None	Negative PCR 4/21/20	Negative for IgG and IgM, 4/21/2020	Triamcinolone 0.1% cream with some improvement. Cold Epsom baths were beneficial. Started aspirin 325 mg and clobetasol ointment in mid April with ongoing improvement, but recurrent symptoms thereafter	See Fig 5, A and B
Case F25 FFST IV	Bilateral foot swelling, redness, and bruising on multiple toes with swollen and bruised areas tender to palpation	End of March, early April 2020	No	Worked in New York city in public health and coworker that sat next to her was PCR positive for SARS-CoV-2.	None	PCR negative, 4/16/20	Negative for IgG and IgM, 4/22/20	Completed a course of Augmentin and treated feet with clotrimazole cream for 2 weeks with no relief. Was prescribed clobetasol 0.05% ointment with improvement.	See Fig 6, A-C
Case G28 MFPT IV	Purplish discoloration of toes, itching on one toe prior to skin changes	April 2020	Yes, (3 days after noticing skin changes, had a sore throat; 5 days after noting skin changes, noted a subjective fevers, severe headache, and dyspnea)	Travel to India in January	None	Outside PCR testing negative per patient, 4/29/20	Negative for IgG and IgM, 5/8/20	Treated with warm soaks x 3 days prior to presentation with unknown efficacy.	See Fig 7, A and B

Fig 1

The cutaneous findings noted in patient A, at the time of clinical presentation.

Fig 2

The cutaneous findings noted in patient B, at the time of clinical presentation.

Fig 3

The cutaneous findings noted in patient C, at the time of clinical presentation.

Fig 4

The cutaneous findings noted in patient D, at the time of clinical presentation.

Fig 5

The cutaneous findings noted in patient E, at the time of clinical presentation.

Fig 6

The cutaneous findings noted in patient F, at the time of clinical presentation.

Fig 7

The cutaneous findings noted in patient G, at the time of clinical presentation.

In patients who received a workup, no coagulation or rheumatologic abnormalities were found (Table I). Five patients had polymerase chain reaction (PCR) testing at some point, either because of the cutaneous symptoms or known exposure; all were negative. Six patients underwent serologic testing for IgG and IgM 2 to 8 weeks after initial symptoms (Table I); 5 were negative, and 1 patient tested positive for SARS-CoV-2 IgG antibodies. Patients generally noted improvement with supportive care and topical steroids.

Discussion

Understanding the link between SARS-CoV-2 and the pernio-like eruption is an ongoing area of study. Multiple case series have likewise noted negative PCR and serology findings despite a history of COVID exposure and symptoms., Recently, a pediatric case series of 7 patients found immunohistochemical and ultrastructural evidence of SARS-CoV-2 in skin biopsy samples despite negative respiratory PCRs.

We postulate that serologic negativity could be due to several reasons: (1) these findings are an epiphenomenon not associated with COVID-19; (2) serologic conversion happens later with milder or asymptomatic disease; (3) antibody titers caused by mild or asymptomatic disease do not meet the titer cutoff for positivity, as many serologic tests have been developed using symptomatic or hospitalized COVID-19 patients as the gold standard; (4) mild or asymptomatic disease does not elicit a robust immune response; or (5) antibodies to a different epitope are being elicited and not measured in current testing. Additional data establishing the causal link between COVID-19 and pernio-like eruption is needed; in order to facilitate understanding of the appearance of these lesions, we present clinical images across diverse skin types.