The global impact of COVID-19 has extended far beyond its respiratory origins, revealing a complex spectrum of systemic manifestations. Among these, dermatologic involvement has emerged as both a diagnostic clue and a prognostic marker. Skin breakdown—encompassing inflammatory eruptions, ischemic lesions, and necrosis—has become a subject of increasing clinical interest. This article explores the multifactorial etiology of COVID-19-related skin breakdown, examining the genomic mechanisms, physical diagnosis, phenotypic variations, therapeutic strategies, and clinical outcomes associated with these cutaneous manifestations.
At the genomic level, the pathogenesis of skin breakdown in COVID-19 begins with the virus’s entry into host cells via the angiotensin-converting enzyme 2 (ACE2) receptor. This receptor is expressed not only in pulmonary tissue but also in keratinocytes, endothelial cells, and eccrine glands, making the skin a potential target for direct viral insult. Once inside the host, SARS-CoV-2 initiates a cascade of immune responses that can culminate in a cytokine storm. Genomic studies have identified polymorphisms in key inflammatory mediators—such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interferon signaling pathways—that correlate with severe disease and cutaneous involvement. These genetic variations contribute to immune dysregulation, endothelial damage, and complement activation, all of which are central to the development of skin lesions.
In addition to immune-mediated injury, COVID-19 is associated with a hypercoagulable state. Genetic predispositions, including variants in coagulation-related genes like Factor V Leiden and plasminogen activator inhibitor-1 (PAI-1), may increase susceptibility to thrombotic skin lesions. These lesions, such as retiform purpura and livedo racemosa, often reflect underlying microvascular thrombosis and signal a poor prognosis. The interplay between viral genomics and host susceptibility underscores the importance of personalized medicine in managing COVID-19-related dermatologic complications.
Clinically, the dermatologic manifestations of COVID-19 are diverse and can be categorized into five primary types: pernio-like lesions, urticarial eruptions, maculopapular rashes, vesicular eruptions, and livedoid or necrotic lesions. Pernio-like lesions, colloquially known as “COVID toes,” typically present as acral erythema and are often observed in younger patients with mild or asymptomatic disease. Urticarial eruptions, characterized by transient wheals and intense pruritus, may precede systemic symptoms and serve as an early warning sign. Maculopapular rashes, resembling morbilliform eruptions, are among the most common but nonspecific findings. Vesicular eruptions, which mimic varicella, tend to appear early in the disease course and may indicate moderate severity. The most concerning are livedoid and necrotic lesions, which result from vascular occlusion and are strongly associated with severe disease and increased mortality.
Diagnosis of these dermatologic manifestations relies on a combination of clinical observation and ancillary testing. Dermoscopy can aid in distinguishing vascular from inflammatory lesions, while skin biopsy provides histopathological insights. Common findings include lymphocytic vasculitis, thrombotic microangiopathy, and viral cytopathic changes. In select cases, polymerase chain reaction (PCR) and immunohistochemistry may detect viral RNA or spike protein within skin samples, although sensitivity remains variable.
The presentation of COVID-19-related skin breakdown varies across populations. Pediatric patients often exhibit erythema multiforme, papular acrodermatitis, and acute hemorrhagic edema of infancy, particularly in the context of multisystem inflammatory syndrome in children (MIS-C). These findings reflect a robust immune response and require careful monitoring. Racial and ethnic differences also influence dermatologic presentation. In individuals with skin of color, erythema may be less apparent, leading to underdiagnosis. Moreover, post-inflammatory hyperpigmentation, keloid formation, and scarring are more prevalent in darker phototypes, necessitating tailored therapeutic approaches.
The advent of COVID-19 vaccines introduced a new dimension to dermatologic manifestations. Both mRNA and adenoviral vector vaccines have been associated with cutaneous reactions, including urticaria, morbilliform eruptions, and delayed hypersensitivity responses. In rare cases, vaccine-induced thrombotic thrombocytopenia has resulted in skin necrosis, highlighting the need for vigilance in post-vaccination monitoring.
Treatment of COVID-19-related skin breakdown is guided by the underlying pathophysiology and severity of the lesions. Supportive care remains the cornerstone for mild to moderate presentations. Topical corticosteroids are effective for inflammatory lesions, while antihistamines provide symptomatic relief from pruritus. Emollients play a crucial role in restoring the skin barrier, particularly in xerotic or eczematous conditions. For more severe manifestations, systemic therapies may be warranted. Anticoagulation is indicated in cases of livedoid or thrombotic lesions, and immunomodulatory agents—such as intravenous immunoglobulin (IVIG), systemic corticosteroids, or biologics—are employed in MIS-C and severe vasculitis. Antiviral therapy, while not directly targeting cutaneous disease, may reduce systemic viral load and mitigate skin involvement.
Management of necrotic or ulcerated lesions requires a multidisciplinary approach. Surgical debridement, negative pressure wound therapy, and skin grafting may be necessary in refractory cases. These interventions aim to preserve tissue integrity, prevent secondary infection, and promote healing.
Outcomes associated with COVID-19-related skin breakdown vary widely. Certain cutaneous signs serve as prognostic indicators. Livedoid and necrotic lesions are often associated with intensive care unit (ICU) admission and increased mortality, whereas pernio-like lesions may reflect a robust immune response and portend a favorable outcome. Persistent dermatologic symptoms, such as chronic urticaria or telogen effluvium, have been linked to long COVID and ongoing systemic inflammation. Long-term sequelae include post-inflammatory hyperpigmentation, scarring, and psychosocial distress due to visible skin changes.
Incorporating dermatologic assessment into COVID-19 triage protocols can enhance early detection and risk stratification. This is particularly valuable in resource-limited settings, where skin signs may precede respiratory symptoms. Teledermatology has emerged as a vital tool for remote diagnosis and monitoring, expanding access to care and reducing exposure risk.
In conclusion, skin breakdown in the context of COVID-19 reflects a multifaceted etiology rooted in viral genomics, immune dysregulation, and vascular compromise. Dermatologic manifestations offer critical insights into disease progression and prognosis. As the pandemic continues to evolve, ongoing research into genetic susceptibility, therapeutic efficacy, and long-term outcomes will refine our understanding and improve patient care. Recognizing the skin as both a mirror and a messenger of systemic disease underscores its importance in the holistic management of COVID-19.
Genomic Mechanisms and Pathophysiology
Viral Entry and ACE2 Expression
SARS-CoV-2 enters host cells via the ACE2 receptor, which is expressed in keratinocytes, endothelial cells, and eccrine glands. This tropism facilitates direct viral insult to skin structures, contributing to inflammatory and ischemic lesions.
Cytokine Storm and Immune Dysregulation
Genomic studies have identified polymorphisms in IL-6, TNF-α, and interferon pathways that correlate with severe COVID-19 and cutaneous involvement. The cytokine storm induces endothelial damage, complement activation, and microvascular thrombosis—hallmarks of skin breakdown in severe cases.
Coagulopathy and Genetic Susceptibility
Variants in coagulation-related genes (e.g., Factor V Leiden, PAI-1) may predispose individuals to thrombotic skin lesions such as retiform purpura and livedo racemosa. These lesions often signal systemic coagulopathy and poor prognosis.
Physical Diagnosis and Dermatologic Classification
Common Presentations
Dermatologic manifestations of COVID-19 can be broadly classified into five categories:
| Type | Description | Prognostic Implication |
|---|---|---|
| Pernio-like lesions | Chilblain-like, acral erythema | Often benign, late onset |
| Urticarial eruptions | Transient wheals, pruritic | May precede systemic symptoms |
| Maculopapular rashes | Morbilliform, widespread | Common, nonspecific |
| Vesicular eruptions | Varicella-like blisters | Early onset, moderate severity |
| Livedoid/necrotic lesions | Retiform purpura, ischemic necrosis | Severe, high mortality |
Diagnostic Tools
- Dermoscopy: Useful for differentiating vascular from inflammatory lesions.
- Skin biopsy: Reveals lymphocytic vasculitis, thrombotic microangiopathy, or viral cytopathic changes.
- PCR and immunohistochemistry: Detect viral RNA or spike protein in skin samples, though sensitivity varies.
Variations Across Populations
Pediatric Manifestations
Children often present with erythema multiforme, papular acrodermatitis, and acute hemorrhagic edema of infancy. These are frequently associated with multisystem inflammatory syndrome in children (MIS-C).
Racial and Ethnic Differences
Skin of color may mask erythema, leading to underdiagnosis. Hyperpigmentation, keloid formation, and post-inflammatory changes are more common in darker phototypes.
Vaccine-Related Cutaneous Reactions
mRNA and adenoviral vector vaccines have triggered urticaria, morbilliform eruptions, and delayed hypersensitivity reactions. Rarely, vaccine-induced thrombotic thrombocytopenia presents with skin necrosis.
Treatment Strategies
Supportive Care
- Topical corticosteroids: For inflammatory lesions such as urticaria and maculopapular rashes.
- Antihistamines: Symptomatic relief for pruritus.
- Emollients: Barrier restoration in xerotic or eczematous skin.
Systemic Therapies
- Anticoagulation: Indicated for livedoid or thrombotic lesions.
- Immunomodulators: IVIG, corticosteroids, or biologics in MIS-C or severe vasculitis.
- Antivirals: Limited role in cutaneous disease but may reduce systemic viral load.
Wound Management
For necrotic or ulcerated lesions:
- Debridement
- Negative pressure wound therapy
- Skin grafting in refractory cases
Outcomes and Prognostic Value
Cutaneous Signs as Prognostic Indicators
- Livedoid and necrotic lesions: Associated with ICU admission and mortality.
- COVID toes: Typically benign, may indicate robust immune response.
- Persistent urticaria or telogen effluvium: Linked to long COVID and chronic inflammation.
Long-Term Sequelae
- Post-inflammatory hyperpigmentation
- Scarring and keloid formation
- Psychosocial impact due to visible skin changes
Integration into Clinical Practice
Dermatologic assessment should be part of COVID-19 triage, especially in resource-limited settings where skin signs may precede respiratory symptoms. Teledermatology has emerged as a valuable tool for remote diagnosis and monitoring.
Conclusion
COVID-19-related skin breakdown reflects a multifactorial etiology rooted in viral genomics, immune dysregulation, and vascular compromise. Dermatologic manifestations offer diagnostic and prognostic insights, especially when integrated with systemic evaluation. As the pandemic evolves, continued research into genetic susceptibility, treatment efficacy, and long-term outcomes will refine our understanding and improve patient care.
References
- Polly S, Muser I, Fernandez A. Update in cutaneous manifestations of COVID-19: Special populations. Cleveland Clinic Journal of Medicine. 2023;90(1):43–52. View article
- Freeman E, Garcia-Doval I, Naldi L, Hay R. COVID-19 and the skin: long-term impacts and clinical practice. British Journal of Dermatology. 2023;189(1):1–3. View article
- Munarov V, Munarov J, Naeem A, et al. Dermatological Manifestations of COVID-19: A Comprehensive Review. Physician’s Journal of Medicine. 2024;3:12–27. View article