#dermpathJC June 2020:
Thursday, June 25th, 9 pm EST
#1: Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of 5 cases
- Authors: Cynthia Magro, J. Justin Mulvey, David Berlin, Gerard Nuovo, Steven Salvatore, Joanna Harp, Amelia Baxter-Stoltzfus, Jeffrey Laurence
#2: Skin manifestations of COVID-19
- Authors: Sarah Young, MD, Anthony P. Fernandez, MD, PhD
#3: Thrombotic occlusive vasculopathy in a skin biopsy from a livedoid lesion of a patient with COVID-19
- Authors: M. Llamas-Velasco, P. Muñoz-Hernández, J. Lázaro-González, A. Reolid-Pérez, B. Abad-Santamaría, J. Fraga, E. Daudén-Tello
#4-1: Digitate Papulosquamous Eruption Associated With Severe Acute Respiratory Syndrome Coronavirus 2 Infection/#4-2: Petechial Skin Rash Associated With Severe Acute Respiratory Syndrome Coronavirus 2 Infection
- #4-1 Authors: Adrien Sanchez, Pierre Sohier, Sarah Benghanem, Anne-Sophie L’Honneur, Flore Rozenberg, Nicolas Dupin, Bethsabée Garel
- #4-2 Authors: Borja Diaz-Guimaraens, MD, Miguel Dominguez-Santas, MD, Ana Suarez-Valle, MD, Cristina Pindado-Ortega, MD, Gerald Selda-Enriquez, MD, Sonia Bea-Ardebol, MD, Diego Fernandez-Nieto
#5: Chilblains in children in the setting of COVID-19 pandemic
- Authors: David Andina MD, Lucero Noguera-Morel MD, Marta Bascuas-Arribas MD, Jara Gaitero-Tristán MD, Jose Antonio Alonso-Cadenas MD, Silvia Escalada-Pellitero MD, Ángela Hernández-Martín MD, Mercedes de la Torre-Espi MD, Isabel Colmenero MD, Antonio Torrelo MD
#6: Histopathological Study of a Broad Spectrum of Skin Dermatoses in Patients Affected or Highly Suspected of Infection by COVID-19 in the Northern Part of Italy: Analysis of the Many Faces of the Viral-Induced Skin Diseases in Previous and New Reported Cases
- This article was not discussed during journal club but is recently published and included in the below summary
- Authors: Raffaele Gianotti, MD, Sebastiano Recalcati, MD, Fabrizio Fantini, MD, Cristina Riva, MD, Mario Milani MD, Emanuele Dainese, MD, and Francesca Boggio, MD
All articles are open access with freely accessible histologic images.
Summary prepared by: Suzy Bloomquist, MD (@BloomquistSuzy)
The June 2020 DermpathJC covered a variety of articles on a new topic relevant to the ongoing pandemic – COVID-19-related skin conditions, including the clinical presentations and varied histologic appearance of the eruptions. Articles on this topic are limited to case presentations and case series; however many dermatopathologists are beginning to see these lesions in their clinical practice, highlighting the importance of sharing our knowledge on these topics. The various articles present a spectrum of the possible histologic patterns present in skin lesions of COVID-19 positive (or suspected positive) cases. Participating dermatopathologists added to the discussion with their experience regarding similar cases.
- Skin manifestations are well known in the setting of viral illnesses. Some authors have reported skin involvement more than 20% of COVID-19 positive patients.
- We are at a relatively early stage in the description of skin lesions relating to COVID-19. Even at this early stage however it appears that COVID-19 may have unique skin manifestations when compared with other viral illnesses. Further study is needed to determine the true specificity of these skin lesions.
- The picture of cutaneous manifestations of COVID-19 is complicated by the fact that many patients are severely ill and being treated with medications at the time of biopsy; some of the cutaneous lesions may overlap with drug adverse effects.
- There are still relatively few articles detailing histologic descriptions of COVID-19-related skin lesions in patients seen in the outpatient setting and in hospitalized patients.
Summary of clinical presentations of COVID-19-related skin disease:
- Highly variable among patients and a single patient may present with multiple simultaneous cutaneous lesions of varying morphologies.
- Many presentations including:
- Lesions that are more non-specific:
- Exanthematous/morbilliform rash
- Petechial rash
- Pityriasis-like digitate papulosquamous eruption
- Erythema-multiforme like lesions
- SDRIFE-like eruption
- Others (a single patient exhibiting multiple different
- Lesions that may be more specific/unique to COVID-19:
- Acral perniosis/Chilblains (“COVID toes”) – despite the descriptor may be seen on fingers and toes, consists of acral erythemato-violaceous or purpuric macules with some cases showing dark ischemic areas with superficial blisters or swelling.
- Livedoid/retiform purpuric/vasculopathic lesions – these seem to be seen more frequently in cases of severe illness/acute respiratory failure in our chosen articles.
- Varicella-like vesicular eruptions
- Lesions that are more non-specific:
Summary of histologic descriptions of biopsied lesions:
- Retiform purpuric/livedoid lesions: thrombogenic vasculopathy at all levels of biopsy (including deep dermis) seen in either (or both) arteries or veins, accompanied in some cases by extensive necrosis of epidermis and adnexal structures, interstitial and perivascular neutrophil or lymphocytic infiltrate, prominent leukocytoclasia (one study noted deposition of C5b-9 in vessels in these cases with biopsy of normal skin in these patients also showing this deposition)
- Perniosis/chilblains lesions on acral skin (largest study is in children/adolescents): vacuolar degeneration of basal layer and lymphocytic exocytosis, perivascular (in-some cases dense/sleeve-like) and perieccrine lymphocytic infiltrate (prevalence of cytotoxic CD8+ lymphocytes), lymphocytic vasculopathy, acrosyringium, eosinophils in eccrine glands, microthrombi in small dermal vessels, scattered necrotic keratinocytes in one case, acute edema and severe vascular damage in cases of large bulla
- Vesicular eruptions: interface dermatitis with apoptotic keratinocytes (similar to findings in other viral exanthems).
- Exanthematous and maculopapular (non-specific) lesions:
- Summarization of findings: Dermal edema, dilated capillaries, prominent erythrocyte extravasation, lymphohistiocytic infiltrate which may be perivascular, dilated vessels
- Few cases also showed: spongiosis, minimal vacuolar dermal-epidermal junction changes, erythrocyte extravasation, eosinophils, nests of intraepidermal Langerhans cells.
- Other: acantholytic dermatitis resembling Grover disease (2 cases)
Short review of chilblains/pernio:
- A cutaneous localized inflammatory reaction resulting from maladaptive vascular response to non-freezing cold. Classified as primary or secondary to underlying disease. None of the cases of chilblains in suspected COVID-19 patients had other potential etiologies for chilblains. Chilblains in these cases should not be confused with the more thrombotic/livedoid complications observed in severely ill patients with COVID-19 (described more thoroughly in articles 1,3).
What can we learn from the skin of COVID-19 patients to infer its effect on other organs?
- It seems clear that SARS-CoV-2 travels rapidly through the vascular system via an unknown mechanism. Some theories behind this are activation of eosinophils leading to a prothrombotic state or activation of a mannose-binding lectin pathway via glycoprotein binding and direct interaction with endothelium.
- Deposition of C5b-9 was seen within dermal capillaries of even normal appearing skin of suspected COVID-19 positive patients in one study.
- Article #2 highlighted that medications being used to treat COVID-19 also have cutaneous adverse reactions.
- Little is known regarding the clinical value of recognition of cutaneous manifestations – for example, are there early cutaneous signs that may suggest a COVID-19 infection?
- RT-PCR was performed on fresh skin in study #4 and was negative for SARS-CoV-2
- The patient in article #4 had resolution of their rash within one week although the patient subsequently died of COVID-19-related illness.
- In article #5, all adolescent/pediatric patients with chilblains had an excellent outcome without complications or severe disease manifestations with symptoms beginning to fade after 7-10 days.
A very important caveat:
- Not all of the lesions described in these articles were in patients confirmed to have COVID-19, many were suspected cases. In study #5, while in the majority of cases (59%) a history of close contact with a COVID-19 symptomatic adult was noted, only 1 of 19 tested patients was PCR positive (however the study notes that PCR is positive in only 11.2% of children requiring hospital admission for suspected COVID-19).
In sum, there’s much to be learned about COVID19 #dermpath. We are grateful for open communications between dermatologists and pathologists, as clinicopathologic correlation is of paramount importance during these times.
Until our next journal club, be well and stay safe,