Clinical and histopathological findings of cutaneous manifestations of COVID-19 patients.

Coronavirus disease (COVID-19) became pandemic since this is a disease with a high infection rate. The study's object is to identify clinical and histopathological findings of cutaneous manifestations of COVID-19 patients. The evidence was analyzed in PubMed, CINAHL, Cochrane, Web of Science, and Scopus, with the search strategy (covid 19 OR covid-19 OR corona OR coronavirus OR sars-cov-2) AND (cutaneous or cutaneous manifestations OR), and 17 studies were included, involving 351 cases with COVID19 and skin manifestations. The lesions were classified mainly as maculopapular, erythematous, vesicular, and urticarial. Histopathological analyses suggest a predominance of spongiosis, perivascular infiltrate of lymphocytes, and thrombogenic vasculopathy.

INTRODUCTION

Coronavirus disease (COVID‐19) became pandemic since this is a disease with a high infection rate. Studies indicate cutaneous manifestations as symptoms from COVID‐19. , , However, they are still superficially reported and the consequences of identifying cutaneous lesions early on and its progression were not extensively studied. Therefore, the disease's cutaneous and histopathological manifestations must be an object of study among specialists to favor the resolution of the clinical picture.

To comprehend how COVID‐19 causes dermatological alterations, affected areas, the types of cutaneous manifestations, the period of appearance, cure, and histological findings can provide subsidies for the disease's early recognition, to support a more effective clinical management of cutaneous lesions and give assistance in the screening and risk stratification.

The study's object is to identify clinical and histopathological findings of cutaneous manifestations of COVID‐19 patients.

METHOD

The bibliographic research was made in June 2020, using the research strategy (covid 19 OR covid19 OR corona OR coronavírus OR sars‐cov‐2) AND (cutaneous OR cutaneous manifestations) in the following databases: PubMed, CINAHL, Cochrane, Web of Science, and Scopus. The publication period was limited to 2020. A total of 142 articles were identified in the search, two reviewers independently analyzed abstract and complete texts.

Clinical and histopathological findings

Seventeen studies that involved 351 cases with COVID‐19 and skin manifestations were included, most were adults, female, and their age varied between 12 to 89 years (Table 1).

TABLE 1

Characterization of the articles concerning cutaneous manifestations from the coronavirus 2019 disease (COVID‐19), Brazil 2020

Study type/sample/country	Age and gender	Cutaneous manifestation	Appearance period and clinical evolution	Place of cutaneous symptoms	Histopathological findings
Series of cases 3 /14/Italy	11 children (13‐18 years old) and 3 adults (23‐39 years old); 57, 14% were female	Eruption of maculopapules that are purple erythematous and mild pruritus	15 days after the symptoms began/evolution bullous lesions or digital edema	Hands, elbows, and feet	Infiltration of lymphocytes in the dermis and hypodermis, signals of endothelial activation, and mild superficial perivascular dermatitis.
Case report 2 /05/United States	62, 73, 32 years old, male; 66 and 40 years old, female	Surrounding inflammation, dark purple patches, slightly purple, reticulated rashes	Unavailable	Buttocks, hands, chest, and legs	Thrombogenic vasculopathy, necrosis in the epidermis and adnexal structure, vascular ectasia, arterial thrombus, and perivascular infiltrate of lymphocytes
Case report 6 /01/France	57 years old, female	Urticarial rash, stationary and diffuse erythematous bleaching and, maculopapules	2 days before the symptoms' beginning/Healing in 9 days	Torso, upper, and lower members	Spongiosis, basal vacuolization of the cells, and mild perivascular infiltration of lymphocytes
Case report 7 /01/Italy	67 years old, male	Pruritic erythematous rash and digital bleaching.	Unavailable	Neck, torso, back, and superior and inferior members	Superficial perivascular infiltration of lymphocytes, dilation of the blood vessels in the mid and papillary cavities from the dermis.
Case report 8 /04/Spain	66.7 years old (average), female	Erythematous papules and purple erythematous patches	Average period of 19.5 days (16‐24 days) after the symptoms/resolution within 2‐3 weeks	Face, back, and superior and inferior members	Mild to moderate spongiosis in the epidermis, dilation of blood vessels that are full of neutrophils, extravasation of red blood cells and interstitial infiltration
Retrospective descriptive study 9 /24/Spain	Average age of 40.5 years old; 3 were male and 15, female	Urticarial vesicle rash and atopic dermatitis	Median of 14 days after the diagnostic/The average duration of skin rashes were 10 days	Torso and feet	Intraepidermal vesicles with mild acantholysis and keratinocytes in a balloon shape
Case report 10 /01/Spain	61 years old, male	Livedoid cyanotic vesicles	Asymptomatic/unavailable	Hands and feet	A slightly necrotic epidermis, dilation of the vessels from the papillary dermis filled with hyaline thrombus, and some mild neutrophilic component
Case report 11 /02/United States	68 years old, male; 39 years old, female	Rashes, morbilliform exanthem, acral purpura, and necrosis with livedoid boarders	01 day after the symptoms' beginning/unavailable	Torso, thighs, abdomen, buttocks	Apoptosis of keratinocytes in the epidermis and thrombotic vasculopathy
Case report 12 /06/United States	12‐17 years old, 5 were male and 1, female	Red to purple maculopapular injuries and purpuric plaques	03 days after the symptoms' beginning/unavailable	Hands and feet	Lymphoid infiltration in the dermis, with purple and vacuolar alterations; and hemorrhagic parakeratosis in the stratum corneum
Case report 13 /01/Spain	71 years old, female	Purple maculopapular injuries	07 days after the symptoms' beginning/unavailable	Inferior members	Fibrinoid necrosis of the vessels' walls, transmural infiltration by neutrophils, leukocytoclasia, spilled erythrocytes, and granular deposition of the vessels' walls
Case report 14 /03/Spain	59 and 89 years old, female; 57 years old, male	Erythematous maculopapular injuries and exanthem	03 days after hospitalization/the exanthem spontaneously improved after 8 days	Superior and inferior members and abdomen	Perivascular dermatitis, lymphocytic exocytosis, thrombosis in the vessels and edema, neutrophils and eosinophils in the dermis and vesicular superficial perivascular dermatitis.
Case report 15 /08/Spain	72.2 years old (average), 50% were male	Erythematous patches and maculopapules	Unavailable	Torso	Spongiosis, non‐follicular subcorneal pustules, exocytosis and interstitial infiltration of neutrophils and scarce eosinophils
Retrospective descriptive study 16 /277/France	27 years old (average); 50% were male	Urticaria, vesicles, petechiae and reticular livedo	Unavailable	Hands and feet	Dermatitis with lichen, perivascular mononuclear infiltration and vascular microthrombus
Case report 17 /01/Spain	12 years old, male	Hemorrhagic purple rashes and vesicular blisters	Unavailable/healing of the injuries in 4 days	Feet	Thrombotic vasculopathy
Case report 18 /01/Italy	47 years old, male	Elevated, isolated or grouped erythematous papules, some with a central and purple hyperpigmentation	4 days after the healing of Covid‐19/healing in 7 days	Head, torso, and superior member	Spongiosis, vacuolar degeneration of basal keratinocytes and focal lymphocytic exocytosis, morphonuclear infiltration, mild inflammation of the dermis, perivascular neutrophils, damage to the vessels' walls.
Case report 19 /01/Spain	83 years old, female	Purple papules and blisters	30 days after the symptoms' beginning/improvement after 10 days	Feet	Vasculitis of dermal vessels, extravasation of red blood cells, necrosis in the basal epidermal layer, infiltration of perivascular neutrophils in the dermis, and fibrin deposition
Case report 20 /01/ France	39 years old, male	Skin rash with erythema and annular stationary plaques that are not pruritic edematous	Unavailable/healing of the eruption after 7 days	Superior members, chest, neck, abdomen, and hands	Perivascular infiltration of lymphocytes, papillary dermal edema, epidermal spongiosis, mild lymphocytic exocytosis, dermatitis with lichen, and vacuolar interface with com keratinocytes in the basal layer

The lesions were classified, mainly as maculopapular, erythematous, vesicular, and urticarial. , , , However, such lesions must be cautiously analyzed, because they are common and may have divergent origins. Cutaneous polymorphism can be related to different reasons such as differences in the virus and the host.

The predominant places were the torso and body's extremities and the latency period of the cutaneous symptoms varied from one to 30 days, in contrast, the lesions' progressive disappearance varied from 4 days to 3 weeks.

Histological analysis and biopsies of the skin suggest the prevalence of spongiosis, perivascular infiltration of lymphocytes, and thrombogenic vasculopathy. , , Spongiosis can been related to the immune response to the infection, which leads to the activation of Langerhans' cells and vasodilation. The thrombotic vasculopathy occurs due to the deposition of C5b‐9 and C4d, in addition to their colocation with glycoprotein arising from COVID‐19.

CONCLUSION

COVID‐19 can manifest several skin changes and mostly are maculopapular, erythematous, vesicular, and urticarial. These lesions differ from their intensity, appearance period, and duration. Histopathological findings suggest spongiosis, thrombogenic vasculopathy, and perivascular infiltration of lymphocytes.