"COVID" Terminology in Dermatology.

Ever since the beginning of COVID-19 pandemic, mucocutaneous manifestations started being noticed and are still being documented. Many of these have been described with the prefix "COVID" and may occur due to the infection (e.g., COVID rash), use of personal protective equipment in healthcare workers (e.g., COVID hand dermatitis) or extensive use of novel vaccines (e.g., COVID arm). This article attempts to summarize such entities with clinical relevance to dermatologists and physicians in general and to create awareness about this fast-evolving COVID lexicon. Copyright:

Introduction

COVID-19, an acronym for Coronavirus Disease-2019, a multisystem disease caused by the novel coronavirus, SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus type 2). Ever since the first cases reported from Wuhan, China in December 2019, this disease has taken the world by storm, causing significant morbidity and mortality globally, leading to declaration of this pandemic by WHO in March 2020. Recurring waves of infection due to mutant forms of the virus continue to threaten a large population of the globe. The use of hand hygiene, personal protective equipment, social distancing and vaccination form the backbone of preventive strategies. Since the disease results in a multisystem involvement, mucocutaneous manifestations were soon noticed, and are still being documented. These could be a result of COVID-19 per se, treatment effects as well as due to vaccines. In addition, the chemical and mechanical effects of PPE on skin in health care workers can also manifest in different forms. Many of these clinical entities have been described with the prefix “COVID”. There has been a veritable explosion in COVID-19 related scientific literature over the past one and a half year and since these terminologies form a part of evolving COVID lexicon, we attempt to summarize them below for a clearer understanding of dermatologists and physicians in general.

COVID toes

COVID toe was a term coined to represent chilblain-like lesions, initially encountered in younger patients with mild to moderate COVID-19. In literature, these are described as chilblains, pseudo-chilblains, or chilblain-like lesions, presenting as asymmetrical acral erythema with itching, edema, and overlying vesicles or pustules [Figure 1]. The associations between chilblain-like lesions and SARS-CoV-2 were difficult to confirm in view of negative RT-PCR and antibody tests; however, it could be because of the rapid interferon (IFN) based response to the infection, inducing microangiopathic changes.[12] Nevertheless, histopathology showing interface changes with apoptotic keratinocytes and identification of SARS-CoV-2 viral particles by immunostaining goes in favor of viral causality.[3] IFN-I inhibition of viral replication may explain the mild symptoms and early cure in these patients, but the lack of other features of interferonopathies cannot be explained. [4] To conclude, even though the causal link between these lesions and SARS-CoV-2 infection remains enigmatic, it has been proposed that these lesions in paucisymptomatic young patients should alert the clinician for immediate testing and isolation of such patients. These lesions should also not be confused with acral ischemia caused by thrombosis in severely ill COVID patients, which portend a bad prognosis.[45]

Figure 1

COVID toes presenting as chilblains or pseudo-chilblains with asymmetric acral erythematous and edematous plaque

COVID fingers

Though, toe involvement is more common with chilblain like lesions of COVID, rarely fingers can also be involved, with or without COVID toes. In addition, ears and cheeks can also be involved as in classical perniosis but the terms COVID ears or COVID cheeks/face has not been proposed for the same.[6]

COVID arm

This refers to an atypical and delayed rash that develops on or near the vaccination site over the arm after 1 week of receiving the first dose of mRNA COVID-19 vaccines, predominantly in females.[7] It can present as an asymptomatic or pruritic and painful erythematous plaque or patch with or without secondary skin changes in the form of scaling and/or vesiculation.[8] Rarely, they may be associated with systemic symptoms of fever and chills. All the cases have been reported following administration of Moderna® vaccine except one following 2nd dose of Pfizer vaccine; hence it is also known as “Moderna arm”.[7] The pathogenesis is unknown, though a delayed-type hypersensitivity (DTH) response seems likely on skin biopsy. However, the lack of prior sensitization and delayed occurrence compared to conventional DTH, is yet to be explained.[9] The delayed occurrence of “COVID arm” could be explained on the basis of the mRNA vaccine being dependent on host translatory mechanisms to produce the viral spike protein, which elicits the immune response. As the process presumably takes more time than the conventional killed or live attenuated vaccines, the DHT is delayed. An absence or attenuation of DHT after the second dose could be due to the moderation of immune response induced by the first dose.[7]

COVID nails

Beau's lines on all the nails following COVID-19 infection have been popularly reported as COVID nails [Figure 2]. [10] Though Beau's lines can occur following any major surgery, severe systemic illness, autoimmune diseases or as a side effect of medications causing transient and partial damage to the nail matrix, this term has been circulating to signify the changes seen 2-3 months after severe COVID. The width and the depth of the nail depression correlate with the duration and severity of the illness respectively.[11] If the disease process involves the entire width of the matrix for more than 1-2 weeks there occurs proximal separation of the nail plate from the nail bed, known as onychomadesis, which has also been reported following COVID-19, though no new term has been assigned [Figure 3].[12]

Figure 2

COVID nails presenting with Beau's lines on all the nails following COVID-19 infection

Figure 3

Onychomadesis following COVID-19 infection

COVID “red half-moon nail” sign

COVID “red half-moon nail” sign has been described as a novel nail sign occurring 2 weeks after symptom onset in a 60-year-old woman as half-moon shaped transverse red band, with a distal convex edge, seen at the distal edge of the lunula. It was hypothesized to occur due to microvascular injury to the distal subungual arcade secondary to systemic inflammatory immune response and consequent procoagulant state.[1314]

COVID tongue

Lingual erythema migrans or benign migratory glossitis is colloquially known as Geographic tongue (GT) owing to the wandering circinate “map-like” erythematous patches on tongue.[15] Recently the term “COVID tongue” has been coined for GT occurring in COVID-19 patients but the diagnostic value of GT as a COVID-19 symptom is doubtful as it is a benign chronic relapsing recurring inflammatory condition of the oral cavity associated with psoriasis, diabetes, asthma, eczema, allergic rhinitis, and other diseases. Thus, such a finding may be coincidental, even though it continues to appear in literature.[1516]

COVID mask

COVID mask is a term coined to refer to an atypical livedoid manifestation of COVID-19, presenting as transient and blanchable livedoid macules over face involving forehead, dorsum of nose and bilateral periorbital skin in a mask-like distribution. It was first reported in 62-year-old women hospitalized for COVID pneumonia developing 21 days after symptom onset, concomitant with livedoid patches on the back and abdomen, resolving with anticoagulant therapy.[17] The mechanism is same as for livedo elsewhere, with cutaneous manifestations occurring due to vasospasm, thrombosis or emboli within cutaneous microvasculature leading to reduction in blood flow and consequent ischemia.[18]

Kawa-COVID-19

This term refers to a pediatric systemic inflammatory syndrome resembling atypical Kawasaki disease, with temporal association with SARS-CoV-2 infection and represents one of the phenotypes described under “Multisystem Inflammatory Syndrome in Children (MIS-C)” by the Center for Disease Control and Prevention (CDC) along with Kawasaki shock syndrome, toxic shock syndrome and macrophage activation syndrome/hemophagocytic lymphohistiocytosis. Like Kawasaki disease, it presents with fever, conjunctivitis, skin rash, myocarditis and hemodynamic shock but differs by older age at onset, lower platelet count, higher rate of myocarditis and resistance to first IVIg treatment[19] The development of Kawa-COVID-19 is possibly related to a heightened endothelial inflammation after infection, potentiated by pneumonia, rendering the endothelium more susceptible.[20] Being more severe than classic Kawasaki disease, it has poorer outcome (especially for patients >5 years and serum ferritin >1400 μg/L) with more frequent need for intensive care due to myocarditis.[19] However, this associations needs further validation.

COVID foot

This term has been used to refer to the spectrum of COVID-19 related signs and symptoms manifests in the foot and lower limbs. The changes range from visible changes like petechiae, erythema, ischemia, chilblain and gangrene or symptom-based complaints like burning feet or gait abnormalities.[21]

COVID hand dermatitis

Irritant contact dermatitis of the hands is the most common dermatosis among healthcare workers, particularly during COVID era. This is attributable to frequent hand washing, use of gloves, alcohol-based products, etc., and has been called “COVID hand dermatitis”. Manifestations include dry, scaly and fissured hands with symptoms of burning or pruritus [Figure 4].[22] Wearing gloves for prolonged periods and frequent hand washing disrupts the epidermal barriers making it more permeable and susceptible to penetration by irritants and allergens.[23]

Figure 4

COVID hand dermatitis presenting as dry hands with keratolysis exfoliative like scaling following prolonged use of gloves

COVID rash

Diverse cutaneous manifestations of COVID-19 have been reported and clubbed under the umbrella term “COVID rash”. However, based on accumulated data in literature and through COVID-19 dermatology registries, the cutaneous manifestations of COVID-19 have been classified into six patterns based on clinical morphology and association with disease state including:

(I) Chilblain-like acral pattern/pseudo-chilblain [Figure 1]

(II) Urticarial rash [Figure 5]

Figure 5

Urticarial rash presenting as blanchable papules and plaques over trunk and limbs

(III) Confluent erythematous/maculopapular/morbilliform rash

(IV) Papulovesicular exanthem [Figure 6]

Figure 6

Papulovesicular exanthem with erythematous papules and vesicles

(V) Livedo reticularis or livedo racemosa-like lesions [Figure 7]

Figure 7

Livedo reticularis-like lesions presenting as lace-like, dusky patches

(VI) Purpuric “vasculitic” pattern [Figure 8]

Figure 8

Purpuric “vasculitic” rash presenting with variable-sized purpura

Their salient clinical and histopathological features along with the proposed treatment is summarized in Table 1.[24]

Table 1

Morphological classification of “COVID rash”, histopathological features and proposed treatment

Severity of COVID symptoms	Asymptomatic patients	Intermediate (mild to moderate COVID)				High (severe disease)
Type	Chilblain-like acral pattern	Urticarial rash	Confluent erythematous/maculopapular/morbilliform rash	Papulovesicular exanthem	Livedo reticularis-like lesions	Livedo racemosa-like lesions	Purpuric “vasculitic” pattern
	Pseudo-chilblains
Morphology	Erythematous or violaceous patches/plaques	Blanchable papules and plaques	Erythematous macules, papules, and purpura	Papules, vesicles and pustules of different sizes	Symmetrical, lace-like, dusky patches forming annular lesions surrounding a pale center	Large, irregular and asymmetrical, violaceous, annular lesions	Purpura of variable sizes
	Associated with itchy vesicles/pustules
Distribution	Localized	Localized	Generalized	Both	Localized	Generalized	Both
Site(s) involved	Toes>Fingers	Trunk > limbs	Trunk centrifugal progression	Trunk	Lower limbs>trunk	Localized - extremities and intertriginuos lesions
Histopathological features
Epidermal changes	-	-	-	Acantholysis, dyskeratosis, intraepidermal vesiculation	-	-	-
Interface dermatitis	Present	Present with vacuolar changes	-	-	-	-	-
Perivascular infiltrate	Present	Present	Present	Present	Pauci-immune	Pauci-immune	Present
Lymphocytic	Present	Present	Present	Present	Very few	Very few	Present
Neutrophilic	-	Present	Present	Present	Very few	Very few	Present
Blood vessels	-	-	-	Microthrombotic vasculopathy	Microthrombotic vasculopathy	Leukocytoclastic vasculitis with fibrin and endothelial swelling
Treatment
Mild cases	Wait and watch	Non-sedating antihistamines	Topical corticosteroids	Wait and watch	Wait and watch	Wait and watch	Topical corticosteroids
Severe cases	Topical corticosteroid	Low-dose systemic corticosteroids	Systemic corticosteroids	Anticoagulants	Anticoagulants	Systemic corticosteroids

Other than this, various unique dermatological manifestations have been described in this one and a half year like “maskne”, a variant of acne mechanica, resulting from follicular occlusion due to textile-skin friction and microbiome dysbiosis, presenting within 6 weeks of regular mask use over the masked area (O-zone) of face [Figure 9].[25] Mask-induced Köebner phenomenon leading to the development of psoriatic lesions over ears has also been reported.[26] These are not being described in detail here as we are restricting the description to “COVID” terminology.

Figure 9

Maskne presenting as follicular papules and pustules over chin crease

Conclusion

Though many dermatological terms have been linked with the acronym COVID, some may not be true associations and may also represent many known diseases. Through this summary we wish to make the readers aware of what these terms actually mean in this fast-evolving glossary.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.