COVID-19-associated dermatologic manifestations

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

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 include an erythematous exanthem (including a lacy pattern and a petechial, dengue-like rash), livedo reticularis, cutaneous vasculitis acute urticaria, chickenpox-like blisters.

Pathophysiology

• The exact mechanisms of COVID-19 induced cutaneous manifestations are not yet well known,
• The viral particles present in the cutaneous blood vessels could lead to a lymphocytic vasculitis.
• Keratinocytes may be a secondary target after Langerhans cells activation.
• Immune response to infection leads to Langerhans cells activation, resulting in a state of vasodilation and spongiosis.
• Microthrombosis and DIC originating in other organs results in livedo reticularis.
  • Hypoxia-related accumulation of deoxygenated blood in blood vessels.
  • Vasculopathy with deposition of C5b-9 and C4d.
  • Degeneration and necrosis of parenchymal cells and formation of hyaline thrombi in small vessels were observed in lung and other organs..

Histology

histopathological studies and PCR investigation on skin biopsies are necessary to clarify the close relationship between skin and SARS-CoV-2 infection,however histopathological study of skin dermatoses in patients affected by COVID-19 infection in the Northern part of Italy showed:.

• diffuse maculopapular eruption involving only the trunk, clinically suggestive for Grover disease showed, in addition to the classic dyskeratotic cells, ballooning multinucleated cells and sparse necrotic keratinocytes with lymphocytic satellitosis.
• punch biopsy showed in the upper dermis diffuse telangiectatic small blood vessels with no other peculiar features, and In a second punch nests of Langerhans cells within the epidermis was the unique clue in this stage.
• maculo-papulo-vesicular rash histological findings showed a perivascular spongiotic dermatitis with exocytosis along with a large nest of Langerhans cells and a dense perivascular lymphocytic infiltration eosinophilic rich around the swollen blood vessels with extravasated erythrocytes.
• papular erythematous exanthema showed edematous dermis with many eosinophils. Cuffs of lymphocytes around blood vessels in a lymphocytic vasculitis.

Differentiating COVID-19 Dermatologic manifestations with other Diseases

• COVID-19 can present with a rash and be mistaken for Dengue..
• maculopapular eruption involving only the trunk, clinically suggestive for Grover disease.

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.
• In Spain,Most of the patients were children (median 13 years) and young adults (median 31, average 36, range 18–91 years old)..

History and 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).
• 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 included:
  • morbilliform rash as the primary presenting symptoms..
  • Papulovesicular rash
  • Urticaria
  • Painful acral red purple papules
  • Livedo reticularis lesions
    • Livedo reticularis is caused by conditions, including disseminated intravascular coagulation (DIC), that reduce blood flow through the cutaneous microvasculature system leading to deoxygenated blood accumulation in the venous plexus..
  • petechial skin rash.
  • Acral eruption of erythemato‐violaceous papules and macules, with possible bullous evolution, or digital swelling.
  • Acute acro-ischemia in the child
    • the presentations of acro-ischemia including finger/toe cyanosis, skin bulla and dry gangrene..
    • they could be the expression of secondary microthrombosis due to endothelial damage and vascular disorders..
  • 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

Acute acro-ischemia in the child lab results:

• • D-dimer, fibrinogen and fibrinogen degradation product (FDP) were significantly elevated in most patients.
  • Prothrombin time was prolonged in 4 patients. D-dimer and FDP levels progressively elevated consistent with COVID-2019 exacerbation.
  • Four patients were diagnosed with disseminated intravascular coagulation (DIC) .
  • Low molecular weight heparin (LMWH) was administrated in 6 patients, which reduced D-dimer and FDP rather than improved clinical symptoms.

Treatment

Supportive care for patients is typically the standard protocol because no specific effective antiviral therapies have been identified.

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.