COVID-19-associated dermatologic manifestations

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Nuha Al-Howthi, MD[2] Ogechukwu Hannah Nnabude, MD; Aditya Ganti M.B.B.S. [3]

Synonyms and Keywords: COVID-19-associated exanthematous rash; COVID-19-associated livedo reticularis; COVID-19-associated livedoid lesions; COVID-19-associated multisystem inflammatory syndrome in children; COVID-19-associated retiform purpura; COVID-19-associated urticaria; COVID-19-associated vasculitis; COVID-19-associated vesicular eruptions

Overview

COVID-19 infections is caused by the novel coronavirus or also known as SARS-2 virus. The disease is believed to incline towards respiratory organs due to the high expression of ACE receptors. However, skin rashes have been uncommonly described in patients with COVID-19 infection. Dermatologic manifestations of COVID-19 though rare include an erythematous exanthem, livedo reticularis, vasculitis, urticaria, vesicles. Common clinical features of covid-19 infection includes fever, dry cough, shortness of breath, myalgia and fatigue.

Historical Perspective

  • In 1937, coronavirus was first isolated from chickens.
  • In 1965, Tyrrell and Bynoe used cultures of human ciliated embryonal trachea to propagate the first human coronavirus (HCoV) in vitro.
  • The etiological agent, a novel coronavirus, SARS-CoV-2, is a virus identified as the cause of an outbreak of respiratory illness first detected in Wuhan, China.[1][2][3][4]
  • The outbreak was declared a Public Health Emergency of International Concern on 30 January 2020.
  • On March 12. 2020, the World Health Organization declared the COVID-19 outbreak a pandemic.

Classification

There is no established system for the classification of covid-19 induced cutaneous lesions.

Pathophysiology

Immune Response

Microscopic pathology

  • Histopathological studies and PCR investigation on skin biopsies are necessary to clarify the close relationship between skin and SARS-CoV-2 infection. On microscopy features
    • Classic dyskeratotic cells
    • Ballooning multinucleated cells
    • Sparse necrotic keratinocytes
    • Lymphocytic satellitosis.
    • Punch biopsy of the upper dermis demonstrated
      • Diffuse telangiectatic small blood vessels
      • Nests of Langerhans cells within the epidermis
    • Perivascular spongiotic dermatitis with exocytosis al
    • Dense perivascular lymphocytic infiltration
    • Eosinophilic rich around the swollen blood vessels
    • Extravasated erythrocytes.
    • Lymphocytic vasculitis.

Causes

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Differentiating COVID-19 Dermatologic manifestations with other Diseases

Disease Epidemiology Predisposing factors Clinical features[18][19][20] Lab abnormalities
Signs Symptoms
Toxic shock syndrome Occurs in both adults and children (9:1 female predominance)

(C. sordellii)[21][22][23][24][25]

Fever Hypotension Diffuse Rash Other signs
  • Diarrhea
  • Vomiting
  • Rash: Diffuse scarlantiform rash (red sunburn-like rash. It is flat and turns white if pressed)
  • Thick skin desquamation appears on the hands and feet at around 1-2 weeks of disease progression, and might be followed by hair desquamation or shedding of fingernails and toenails after 2-3 months[26]
+ + +
  • Nonpitting systemic edema
Meningococcemia Occurs in young adults living in close proximity (college dorms, military recruits)[30]
  • Close contact with a carrier
  • Intimate kissing and cigarette smoking are associated with increased risk of meningococcal carriage[31]
+ + +
  • Positive blood cultures (Neisseria meningitidis)
  • CSF findings typical of bacterial meningitis:[24]
    • Cells >300/uL
    • Predominantly granulocytes
    • Total protein 100-500mg/dl
    • Glucose ratio (CSF/plasma) <0.3
    • Lactate >2.1 mmol/L
    • CSF gram stain and culture may be positive
Stevens Johnson syndrome (SJS) HLA-B*1502 gene leads to increased susceptibility[35] Triggered by certain medications, most commonly: + + +
  • Histological work up of skin sections reveal widespread necrotic epidermis involving all layers
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome + + +
  • Multi-organ dysfunction:[42]
    • Pneumonitis
    • Hepatitis
    • Renal failure
    • Encephalitis
    • Cardiac failure
Red man syndrome Patients in whom the offending drug infusion is given over less than 1 hour and who are not pre-treated with diphenhydramine[45] Hypersensitivity to:[46] + + + No elevation in tryptase levels indicating that it is an anaphylactoid reaction[47]
Kawasaki

disease

Occurs in children, usually age 1-4 years

(autoimmune vasculitis)

+ + +
Scarlet fever Distributed equally among both genders. Most commonly affects children between five and fifteen years of age. Occurs after streptococcal pharyngitis/tonsillitis + +/- + Rash:
  • Characteristic sandpaper-like rash which appears days after the illness begins (although the rash can appear before illness or up to 7 days later), rash may first appear on the neck, underarm, and groin

For differentiating diseases presenting with rash and fever click here.

Epidemiology and Demographics

  • The incidence of dermatologic manifestations with COVID-19 infections increases with age; the median age at diagnosis is 53 years.
  • Males are more commonly affected than females.
  • Most of the patients were children (median 13 years) and young adults (median 31, average 36, range 18–91 years old).

Risk Factors

There are no established risk factors to determine what conditions or diseases predispose Covid-19 infection to manifest as cutaneous complications. However, similar to all viral illnesses, exposure is considered the most significant risk factor for infection with Coronavirus disease 2019 (COVID-19).

Screening

There is insufficient evidence to recommend routine for cutaneous manifestations related to covid-19.

Natural History, Complications and Prognosis

  • The skin lesions are initially reddish and papular resembling chilblains.
  • Subsequently, in the span of approximately 1 week they become more purpuric and flattened.
  • Finally, they seem to resolve by themselves without requiring any treatment.
  • Aggravation of previous skin diseases, such as rosacea, eczema, atopic dermatitis and neurodermatitis, was also observed in some Covid‐19 patients.

Diagnosis

Diagnostic studies

  • Diagnosis of COVID-19 infection was successfully confirmed by RT-PCR.
  • Histopathological studies and PCR investigation on skin biopsies are necessary to confirm infection of skin with SARS-CoV-2 infection.

History

  • History of patients infected with Coronavirus disease 2019 (COVID-19) can include international travel to where COVID-19 is highly prevalent.
  • History should also be focused on the possible exposure to a confirmed COVID-19 patient.

Symptoms

  • The timing of skin lesions depends on various factors and not really known but 3 days before diagnosis to 13 days after diagnosis.
  • The most common cutaneous manifestation of COVID-19 is a maculopapular exanthem (morbilliform).
  • The Majority of lesions were localized on the trunk, however, some patients experienced cutaneous manifestations in the hands and feet.
  • Skin lesion development occurred before the onset of respiratory symptoms or COVID-19 diagnosis in some of the patients, and lesions spontaneously healed in all patients within 10 days
  • The other cutaneous manifestations include:
Suspected COVID-19 rash Courtesy: Images in accordance with the licensing requirements of Creative Commons Attribution-NonCommercial-NoDerivs 3.0 (New Zealand).


Physical Examination

    • Acral eruption of erythemato‐violaceous papules and macules, with possible bullous evolution, or digital swelling.
    • Acute acro-ischemia in the child
    • Erythema multiforme-like lesions that might be another pattern of exanthem associated with COVID-19 infection.
    • Further studies are needed to evaluate whether these lesions are associated with the virus, the drug intake or any other conditions.
    • COVID-19 Toes.
      • Similar to the type of cold related changes we have seen in the feet of people for many years, but often occurring in places where the conditions are not cold and damp.
      • These seem to happen more commonly in younger patients.
    • Chilblain‐like lesions
      • The pseudo‐chilblain pattern frequently appears late in the evolution of the COVID‐19 disease.
      • The lesion was red–purple papules on the dorsal aspect of the fingers on both hands and diffused erythema in the subungual area of thumb.

Laboratory Findings

Electrocardiogram

There are no ECG findings associated with covid-19 rash.

X-ray

There are no x-ray findings associated with covid-19 rash.

Echocardiography or Ultrasound

There are no echocardiography/ultrasound findings associated with covid-19 rash.

CT scan

There are no CT scan findings associated with covid-19 rash.

MRI

There are no MRI findings associated with covid-19 rash..

Other Imaging Findings

There are no other imaging findings associated with covid-19 rash..

Treatment

  • Supportive care for patients is typically the standard protocol because no specific effective antiviral therapies have been identified.
  • Currently, infection prevention and control are considered urgent and critical due to the lack of specific treatment and heightened risk of spreading during the incubation period.

Primary Prevention

  • Effective measures for the primary prevention of COVID-19 include::[57]
    • Frequent handwashing with soap and water for at least 20 seconds or using a alcohol based hand sanitizer with at least 60% alcohol
    • Staying at least 6 feet (about 2 arms’ length) from other people who do not live with you
    • Covering your mouth and nose with a cloth face cover when around others and covering sneezes and coughs
    • Cleaning and disinfecting
  • There have been rigorous efforts in order to develop a vaccine for novel coronavirus and several vaccines are in the later phases of trials.[58]

Secondary prevention


References

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