Diagnostic and prognostic values of cutaneous manifestations in COVID‐19

Dear Editor,

Coronavirus disease 2019 (COVID‐19) has become a significant global concern owing to the widespread transmission and development of severe symptoms in a relatively high proportion of infected individuals. Patients with COVID‐19 manifest a clinical spectrum ranging from asymptomatic disease to acute respiratory distress syndrome. The disease also affects multiple organ systems owing to uncontrolled release of pro‐inflammatory cytokines and chemokines, resulting in clinical presentations other than respiratory symptoms. ¹

Skin is one of the organ systems involved in patients with COVID‐19. Different cutaneous lesions have been increasingly associated with the disease in the literature; however, their prevalence and clinical value remain inconclusive. Regarding classification of cutaneous presentations, Galván Casas et al categorized skin lesions of COVID‐19 based on their clinical patterns into five types: (a) acral areas of erythema with vesicles or pustules (pseudochilblain); (b) other vesicular eruptions; (c) urticarial lesions; (d) maculopapular eruptions; and (e) livedo or necrosis. ² Besides, Suchonwanit et al proposed that cutaneous manifestations in COVID‐19 may be classified into two major forms according to their pathomechanisms: (a) clinical features that indicate viral exanthems and (b) vasculopathy‐related skin lesions, especially vasculitis and thrombotic vasculopathy. ³ Both clinical and pathophysiologic classifications may elucidate the diagnostic and prognostic values of cutaneous eruptions occurring in patients with COVID‐19.

Exanthematous eruptions are commonly associated with viral infections. They are considered to be a hypersensitivity response to viral nucleotides. ⁴ Morbilliform eruptions, purpuric macules, petechial rash, urticaria, and varicella‐like vesicles have been reported as COVID‐19‐associated exanthems in several articles. ³ Besides, paraviral exanthems, including digitate papulosquamous eruption and pityriasis rosea, have been recently described. ⁵ , ⁶ However, none of the reported cases have so far revealed any correlation between the presence of exanthems and disease severity.

Vasculopathy‐related skin manifestations have been reported in patients with ranging severities of COVID‐19. Current evidence suggests that the multiple cytokines released could induce vasculitis and microangiopathy. Besides, activation of the coagulation cascade and complement‐mediated microvascular injury seen in severe disease could result in a variety of coagulation disorder‐associated skin manifestations. ⁷ Chilblain‐like (acro‐schemic, perniosis‐like, pseudochilblain) lesions have been reported in various countries in patients during the peak of the COVID‐19 pandemic. ² , ³ The released cytokines, especially type I interferons and/or microthrombi might induce microangiopathic changes resulting in chilblain‐like skin eruptions. ⁸ Considering that a majority of cases were asymptomatic or had mild clinical features, the presence of chilblain‐like lesions might help diagnose asymptomatic patients and might indicate a good prognosis. In contrast, livedo racemosa, retiform purpura, acrocyanosis, and dry gangrene in critically ill patients with a systemic hypercoagulable state may indicate a poor prognosis. ⁷ , ⁹ We postulate that the degree of thromboembolism may correlate with the disease severity. Patients having mild disease with low‐grade thrombosis might present with transient livedo reticularis, while those having severe disease with extensive thrombosis might present with livedo racemosa, retiform purpura, or limb ischemia. ³ , ⁹

Based on the current evidence, we may speculate that clinical features indicative of viral exanthems, including morbilliform, petechial, urticarial, and varicella‐like skin lesions in patients with COVID‐19, can be found in other diseases and therefore fail to provide specific clues for diagnosis and prognosis of COVID‐19; however, vasculopathy‐related skin manifestations, including chilblain‐like lesions, vasculitis, livedo reticularis/racemosa, retiform purpura, acrocyanosis, and dry gangrene, may provide prognostic values by indicating serious complications due to COVID‐19 and by monitoring disease severity. Early detection of cutaneous signs associated with severe disease is crucial to improve patient outcomes. However, there is still a lack of robust evidence to support this conclusion. Further studies regarding skin manifestations in COVID‐19 are required to validate our hypothesis, which that may provide a useful clue to predict disease outcomes in patients with COVID‐19.

CONFLICT OF INTEREST

The authors declare no potential conflict of interest.