🔬 Overview

As the COVID-19 pandemic enters its fifth year, dermatological manifestations remain a key area of clinical and immunological inquiry. Among these, chilblains—also known as pernio—have emerged as a peculiar and persistent phenomenon, often dubbed “COVID toes” in early reports. Recent studies published in 2025 continue to refine our understanding of their pathogenesis, epidemiology, and diagnostic implications.

🧬 Pathophysiology: The Interferon Connection

One of the most compelling insights from recent literature is the role of type I interferon responses in COVID-associated chilblains. Histopathological studies have identified elevated levels of myxovirus resistance protein 1 (MxA), an interferon-induced GTPase, in both COVID-related chilblains and chilblain lupus. This suggests a shared immunologic pathway, where a robust innate response may suppress viral replication but trigger localized vascular inflammation.

Key mechanisms include:

• Interferon α overexpression: Linked to reduced PCR/antibody positivity, complicating diagnosis
• Endothelial dysfunction: SARS-CoV-2 may indirectly damage microvasculature, leading to pernio-like lesions
• ACE2 receptor modulation: Chilblains may reflect downstream effects of viral interaction with ACE2 and JAK-STAT pathways

📊 Epidemiological Trendsffff

A 2025 update in the British Journal of Dermatology highlights that pseudo-chilblains were among the earliest dermatologic signs observed during the pandemic, particularly in younger, otherwise asymptomatic individuals. However, longitudinal data show that:

• Chilblains were not strongly correlated with regional COVID-19 case surges (Spearman coefficient 0.18)
• Latinx populations had disproportionately fewer chilblain cases despite higher COVID-19 incidence, suggesting behavioral or genetic modifiers

🧪 Diagnostic Challenges

The interferon-driven nature of COVID-related chilblains presents a diagnostic paradox:

• Patients often test negative via PCR or serology due to suppressed viral replication
• Emerging biomarkers like lymphocyte activation assays may offer more sensitive detection, though they remain experimental

💉 Post-Vaccine and Long COVID Considerations

Cutaneous manifestations, including recurrent chilblains, have been reported post-vaccination and in long COVID syndromes. These may reflect lingering immune dysregulation or vaccine-triggered interferon responses.

🧠 Implications for Practice and Research

The chilblains-COVID link underscores the need for:

• Broader diagnostic criteria beyond PCR/antibody testing
• Continued exploration of interferon biology in viral and autoimmune dermatology
• Culturally sensitive epidemiologic modeling to account for behavioral and socioeconomic factors

🧬 Pathogenesis

• Type I Interferon Hyperactivation Triggered via TLR7 in plasmacytoid dendritic cells (pDCs), leading to sterilizing immunity and acral inflammation
• Endothelial Dysfunction Microvascular damage and inflammation contribute to lesion formation
• ACE2 Receptor Modulation Alters vascular tone and immune signaling, possibly amplifying pernio-like symptoms

📊 Epidemiology

• Chilblains surged during early COVID waves, especially in youth
• Often appeared in mild or asymptomatic cases
• Seasonal clustering observed, with lower incidence in Latinx populations despite higher COVID rates

🧪 Diagnostic Challenges

• Many patients show no seroconversion or PCR positivity
• Histopathology reveals MxA protein and pDC infiltration
• Chilblains may reflect strong innate immunity rather than active infection

🔍 Implications for Practice & Research

• Chilblains could serve as a biomarker for robust interferon response
• Calls for broader diagnostic criteria beyond PCR/antibody tests
• Future research should explore genetic predisposition and immune modulation strategies