The spectrum of COVID-19-associated dermatologic manifestations: an international registry of 716 patients from 31 countries

BACKGROUND: Coronavirus disease 2019 (COVID-19) has associated cutaneous manifestations. OBJECTIVE: To characterize the diversity of cutaneous manifestations of COVID-19, and facilitate understanding of underlying pathophysiology. METHODS: Case series from an international registry from the American Academy of Dermatology and International League of Dermatological Societies. RESULTS: The registry collected 716 cases of new-onset dermatologic symptoms in patients with confirmed/suspected COVID-19. Of the 171 patients in the registry with laboratory-confirmed COVID-19, the most common morphologies were morbilliform (22%), pernio-like (18%), urticarial (16%), macular erythema (13%), vesicular (11%), papulosquamous (9.9%), and retiform purpura (6.4%). Pernio-like lesions were common in patients with mild disease, while retiform purpura presented exclusively in ill, hospitalized patients. LIMITATIONS: We cannot estimate incidence or prevalence. Confirmation bias is possible. CONCLUSION: This study highlights the array of cutaneous manifestations associated with COVID-19. Many morphologies were non-specific, while others may provide insight into potential immune or inflammatory pathways in COVID-19 pathophysiology

Cutaneous reactions reported after Moderna and Pfizer COVID-19 vaccination: A registry-based study of 414 cases

BACKGROUND: Cutaneous reactions after messenger RNA (mRNA)-based COVID-19 vaccines have been reported but are not well characterized. OBJECTIVE: To evaluate the morphology and timing of cutaneous reactions after mRNA COVID-19 vaccines. METHODS: A provider-facing registry-based study collected cases of cutaneous manifestations after COVID-19 vaccination. RESULTS: From December 2020 to February 2021, we recorded 414 cutaneous reactions to mRNA COVID-19 vaccines from Moderna (83%) and Pfizer (17%). Delayed large local reactions were most common, followed by local injection site reactions, urticarial eruptions, and morbilliform eruptions. Forty-three percent of patients with first-dose reactions experienced second-dose recurrence. Additional less common reactions included pernio/chilblains, cosmetic filler reactions, zoster, herpes simplex flares, and pityriasis rosea-like reactions. LIMITATIONS: Registry analysis does not measure incidence. Morphologic misclassification is possible. CONCLUSIONS: We report a spectrum of cutaneous reactions after mRNA COVID-19 vaccines. We observed some dermatologic reactions to Moderna and Pfizer vaccines that mimicked SARS-CoV-2 infection itself, such as pernio/chilblains. Most patients with first-dose reactions did not have a second-dose reaction and serious adverse events did not develop in any of the patients in the registry after the first or second dose. Our data support that cutaneous reactions to COVID-19 vaccination are generally minor and self-limited, and should not discourage vaccination

Upregulation of the Human Alkaline Ceramidase 1 and Acid Ceramidase Mediates Calcium-Induced Differentiation of Epidermal Keratinocytes

Extracellular calcium (Cao2+) potently induces the growth arrest and differentiation of human epidermal keratinocytes (HEKs). We report that Cao2+ markedly upregulates the human alkaline ceramidase 1 (haCER1) in HEKs; and its upregulation mediates the Cao2+-induced growth arrest and differentiation of HEKs. haCER1 is the human ortholog of mouse alkaline ceramidase 1 that we previously identified. haCER1 catalyzed the hydrolysis of very long-chain ceramides to generate sphingosine (SPH). This in vitro activity required Ca2+. Ectopic expression of haCER1 in HEKs decreased the levels of D-e-C24:1-ceramide and D-e-C24:0-ceramide but elevated the levels of both SPH and its phosphate (S1P), whereas RNA interference-mediated knockdown of haCER1 caused the opposite effects on the levels of these sphingolipids in HEKs. Similar to haCER1 overexpression, Cao2+ increased the levels of SPH and S1P, and this was attenuated by haCER1 knockdown. haCER1 knockdown also inhibited the Cao2+-induced growth arrest of HEKs and the Cao2+-induced expression of keratin 1 and involucrin in HEKs. In addition, the acid ceramidase (AC) was also upregulated by Cao2+; and its knockdown attenuated the Cao2+-induced expression of keratin 1 and involucrin in HEKs. These results strongly suggest that upregulation of haCER1 and AC mediates the Cao2+-induced growth arrest and differentiation of HEKs by generating SPH and S1P