Pseudo-Chilblains in Adult Patients with Confirmed COVID-19: A Systematic Review

Background: Pseudo-chilblains have been associated with COVID-19. Many reports, however, lack confirmation of COVID-19 infection. While likely associated, all chilblains/chilblain-like lesions during this time should not be assumed to be COVID-19 related. This study examines the characteristics of adults with pseudo-chilblains and confirmed COVID-19. Methods: A systematic review of PubMed/MEDLINE database was performed using the PRISMA guidelines. Adults (>18 years) with confirmed COVID-19 were included. De-identified registries were excluded to avoid duplication. We extracted study design, age, sex, race, geographic location, relationship of COVID-19 diagnosis to chilblains onset, confirmatory testing, hospitalization status, anatomical location, cold/damp exposure, presence/absence/description of pseudo-chilblains symptoms, presence/absence of biopsies/histopathologic findings, tissue IHC/PCR, presence/absence/details of extracutaneous COVID-19 disease, pre-existing chilblains, treatment and resolution timeline. The search was completed in July 2022. Results: We identified 13 studies (29 patients). In COVID-19-infected adults, pseudo-chilblains were reported primarily from North America and Europe, occurring in both sexes over a wide age-range, affected well and ill patients, favored the hands and feet and could be symptomatic or asymptomatic. Most patients had extracutaneous symptoms. Resolution time ranged from 50 days. There was marked variation in treatment strategies and appearance of pseudo-chilblains relative to entire disease course. Biopsies were infrequently performed but findings similar to classical chilblains were described. Conclusions: Many patients reported as pseudo-chilblains of COVID-19 lack confirmed infection. Infection confirmation, photographic documentation and histopathology are critical to establish homogeneity in reported pseudo-chilblains during this global pandemic. Further work clarifying the relationship of acral eruptions and COVID-19 is necessary

The autonomic nervous system

The autonomic nervous system innervates the visceral organs, the glands and the blood vessels. It regulates the internal environment, and it is largely responsible for maintaining normal bodily functions such as respiration, blood pressure and micturition. The peripheral autonomic nervous system consists of two parts, a thoracolumbar or sympathetic and a craniosacral or parasympathetic division, which usually have antagonistic effects (Sect. 12.2). The sympathetic system is organized to mobilize the body for activities, especially in stressful situations (Cannon’s fight or flight), whereas the parasympathetic system in particular stimulates the peristaltic and secretory activities of the gastrointestinal tract (also known as rest and digest response). The peripheral part of the autonomic nervous system includes neurons in the viscera and peripheral ganglia, which are innervated by the lateral horn of the spinal cord and certain brain stem nuclei. Neuronal plexuses in the gastrointestinal tract form the enteric nervous system, which is often viewed as the third component of the autonomic nervous system. Tonically active bulbar centres control vital functions such as blood pressure and respiration. The autonomic centres in the brain stem and spinal cord are reciprocally connected with the central autonomic network (Sect. 12.3), which includes the hypothalamus and several other forebrain (in particular the extended amygdala and the insula) and brain stem structures such as the periaqueductal grey and the parabrachial nucleus. This network is essential for the integration of autonomic, endocrine and somatomotor functions. The peripheral and central autonomic pathways may be affected by many diseases, which cause derangement of autonomic functions as exemplified in several Clinical Cases on disorders of the neural control of blood pressure, breathing and micturition. The English terms of the Terminologia Neuroanatomica are used throughout