Pernio-like eruptions in COVID-19

Pernio-like eruptions in COVID-19

Dermatologists are rapidly becoming reacquainted with pernio (chilblains), given the increasing reports of pernio-like acral eruptions and other dermatologic manifestations occurring in association with COVID-19. This raises an important clinical question: under normal (non-COVID-19) circumstances, what should be the proper workup for patients who present to the dermatology office with skin findings suggestive of pernio?

Read the view of David A. Wetter, MD, from the US,

that was published in Dermatology World Insights and Inquiries on 6th of May:  

To try and answer this question, I reflected upon a patient I encountered during my dermatology residency. She was an otherwise healthy woman in her forties who presented acutely with painful, red-to-purple patches on her fingers. Since I was unable to provide a definitive diagnosis based upon her physical examination findings, I performed a skin biopsy. When I received the dermatopathology report “consistent with pernio,” I immediately wondered, “Why did I overlook this diagnosis?” After reviewing the literature for potential causes of pernio, I ordered a panoply of tests including: complete blood count, peripheral blood smear, monoclonal gammopathy screen, cryoglobulins, antinuclear antibodies, extractable nuclear antigen antibodies, rheumatoid factor, antiphospholipid antibodies, cold agglutinins, and hepatitis B and C serology. Fortunately (and not surprisingly in retrospect), the results of my extensive (and expensive) test panel were normal. Was any portion of my laboratory workup necessary for this patient?

In an insightful editorial, Simon Barton opined: “Chilblains are a common self-limiting disorder, managed by most GPs every winter in a 10-minute consultation. In secondary care the same condition warrants blood tests, a skin biopsy, presumably multiple consultations, and a fancy name. Are GPs under-investigating? Or are secondary care doctors over-investigating?”


pernio COVID-19
Image from Kolivras A, et al. "Coronavirus (COVID-19) infection-induced chilblains: A case report with histopathologic findings." JAAD Case Reports. 2020 (in press).


Now years post-residency, the “proper” workup of pernio continued to baffle me, prompting Jon Cappel, MD, (then a dermatology resident) and I to retrospectively review our Mayo Clinic experience of pernio (4) to attempt to unravel this conundrum.

The study analyzed 104 patients

This study analyzed 104 patients (mean age at diagnosis, 38.3 years; 79% women) with a clinical diagnosis of pernio. (Patients with chilblains lupus [a subtype of chronic cutaneous lupus] were excluded from the analysis.) Although 38 patients (37%) had at least 1 abnormal laboratory test result, oftentimes the results were nonspecific and unassociated with the presence of a concerning or associated systemic disease. Specifically, only 7 patients (6.7%) had a (possibly) associated hematologic or rheumatologic (non-lupus) disease: rheumatoid arthritis (2 patients), Sjögren syndrome (1), undifferentiated connective tissue disease (1), myelodysplastic syndrome (1), multiple myeloma (1), and aplastic anemia (1). Cold agglutinins were found in 11 of 20 tested patients, but were of unclear clinical significance. Only 2 (of 34 tested) patients had weakly positive antiphospholipid antibodies (without clinical features of thrombosis or rheumatologic disease) and all patients (of 53 tested) had negative cryoglobulins. A limitation of the study was that laboratory testing was not standardized among the patient cohort.

In order to provide clinical guidance we used our study data to create proposed diagnostic criteria for pernio. (4) These consist of one major criterion (localized erythema and swelling involving acral sites and persistent for >24 hours) and three minor criteria ([a] onset and/or worsening in cooler months [between November and March]; [b] histopathologic findings of skin biopsy consistent with pernio and without findings of lupus erythematosus; and [c] response to conservative treatments [i.e. warming and drying of affected areas]). A diagnosis of pernio requires the major criterion and at least one of the minor criteria.
Given a potential practice gap between this study’s data and tests ordered during routine clinical practice, we devised recommendations for evaluating patients with pernio (Table 8 of cited reference): (4)

• Review of systems for associated systemic conditions (such as autoimmune connective tissue disease and malignant disease)
• Skin examination of unaffected areas to assess for cutaneous findings of lupus
• In patients who do not meet proposed diagnostic criteria of pernio, consider skin biopsy to exclude other causes of acral erythema (e.g. lupus, cryoglobulinemia, vasculitis, and cutaneous thrombosis)
• In patients with review of systems or other physical examination findings concerning for an associated systemic condition, consider the following laboratory studies: complete blood cell count, peripheral blood smear, monoclonal gammopathy screen, cold agglutinins, and antinuclear antibody. Extractable nuclear antigen antibodies, rheumatoid factor, antiphospholipid antibodies, and cryoglobulins can also be considered in selected circumstances
• Skin biopsy and/or laboratory studies are not needed in patients who meet proposed diagnostic criteria of pernio and who do not have symptoms or signs concerning for an associated systemic condition.


Pernio-like eruptions tend to affect younger patients

The pernio-like eruptions associated with COVID-19 are forcing us to examine which clinical scenarios (during the pandemic) should trigger our suspicion of current (or recent) infection with SARS-CoV-2. In this context, pernio-like eruptions tend to affect younger patients; (1, 2, 5) although it is unclear if it is a dermatologic marker of active (including asymptomatic) COVID-19 or if it represents a delayed immune-mediated host response to the virus characterized by the production of type I interferons. (1, 5) Further studies are needed to determine whether pernio-like eruptions associated with COVID-19 portend a better or worse prognosis for systemic complications including respiratory, coagulopathic, and neurologic (e.g. stroke) sequelae (currently published studies suggest a better prognosis). As testing for SARS-CoV-2 becomes more widespread, dermatologists may consider testing patients with pernio-like eruptions using both nasopharyngeal swab for PCR (to detect active infection) and serology testing for the presence of IgG antibodies (to detect immune response to recent infection), although specific national guidelines do not yet exist for this scenario. Hopefully in the upcoming months, studies will more closely examine SARS-CoV-2 test results (PCR and serology) in patients with pernio-like eruptions to better understand the significance of this dermatologic manifestation of COVID-19.

An opportunity for a targeted testing approach

Additionally, our “re-examination” of pernio outside of the context of COVID-19 provides dermatologists with the opportunity to develop a targeted testing approach that can be employed now (and in future years) to help bridge the practice gap of pernio testing in non-COVID-19 patients. Indeed, I think Simon Barton was prescient when he wondered whether specialists tend to “over-investigate” pernio; (3) as the subsequent Mayo Clinic study seems to suggest this, too. (4) Although my patient from dermatology residency will not directly benefit from my belated knowledge, I hope that our dermatologic community will learn from my cautionary tale and gently “test the waters” before making a big “(laboratory test) splash” with their pernio patients!

Point to remember: Pernio is usually not associated with underlying rheumatologic or hematologic diseases (only 6.7% of patients in the Mayo Clinic study). Use of the aforementioned proposed diagnostic criteria and suggested evaluation may help to guard against “over-evaluation” of pernio by dermatologists and other specialists.

Read the editor’s comment to this approach HERE

All content found on Dermatology World Insights and Inquiries, including: text, images, video, audio, or other formats, were created for informational purposes only. The content represents the opinions of the authors and should not be interpreted as the official AAD position on any topic addressed. It is not intended to be a substitute for professional medical advice, diagnosis, or treatment.


  1. Piccolo V, Neri I, Filippeschi C et al. Chilblain-like lesions during COVID-19 epidemic: A preliminary study on 63 patients. J Eur Acad Dermatol Venereol. 2020 Apr 24. [Epub ahead of print]
  2. Heymann WR. The profound dermatological manifestations of COVID-19 – Cutaneous features. Dermatology World Insights and Inquiries. Vol. 2, No. 16. April 22, 2020.
  3. Barton SR. What’s in a name? BMJ. 2011;342:d3694.
  4. Cappel JA, Wetter DA. Clinical characteristics, etiologic associations, laboratory findings, treatment, and proposal of diagnostic criteria of pernio (chilblains) in a series of 104 patients at Mayo Clinic, 2000 to 2011. Mayo Clin Proc. 2014;89(2):207-215.
  5. Kolivras A, Dehavay F, Delplace D et al. Coronavirus (COVID-19) infection-induced chilblains: A case report with histopathologic findings. JAAD Case Rep. 2020 (in press)
  6. Alramthan A, Aldaraji W. A case of COVID-19 presenting in clinical picture resembling chilblains disease: First report from the Middle East. Clin Exp Dermatol 2020 Apr 17. doi: 10.1111/ced.14243. [Epub ahead of print]
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  8. Zagurly-Orly B. Schwartzstein RM. Covid-19 – A reminder to reason. New Engl J Med 2020 Apr 28 [Epub ahead of print].