Chilblains

Chilblains, also known as pernio and chill burns,[2] are a medical condition in which damage occurs to capillary beds in the skin, most often in the hands or feet, when blood perfuses into the nearby tissue resulting in redness, itching, inflammation, and possibly blisters.[3] It occurs most frequently when predisposed individuals, predominantly women, [4] are exposed to cold and humidity. Ulcerated chilblains are referred to as kibes. Temperature-related chilblains can be prevented by keeping the feet and hands warm in cold weather and avoiding exposing these areas to extreme temperature changes. Once the diagnosis of chilblains is made, first-line treatment includes avoiding cold, damp environments and wearing gloves and warm socks.[5]

Chilblain
Other names	Pernio, chill burn, perniones, perniosis[1]
Toes inflamed by chilblains
Pronunciation	/ˈtʃɪlbleɪnz/
Specialty	Emergency medicine

Chilblains can be idiopathic (spontaneous and unrelated to another disease), but similar symptoms may also be a manifestation of another serious medical condition that must be investigated. Related medical conditions include Raynaud's disease, erythromelalgia, frostbite, and trench foot, as well as connective tissue diseases such as lupus or vasculitis. In infants affected by Aicardi–Goutières syndrome (a rare inherited condition which affects the nervous system) chilblain-like symptoms occur together with severe neurologic disturbances and unexplained fevers.

Chilblain-like symptoms have also been linked to COVID-19.[6][7][8] COVID toes, as they are commonly known,[9][10] have mostly been reported in older children and adolescents,[11] who often have not had other symptoms of COVID-19.[12] The symptoms are usually mild and disappear without treatment.[11] Their cause is debated: it is uncertain whether COVID toes are a delayed consequence of the viral infection itself (or at least partially connected to environmental factors during the COVID-19 pandemic).[9][10][13] The occurrence of such lesions has been attributed to the similar interferon-1 mediated immune response in both COVID-19 and systemic lupus erythematosus, another possible explanation is based on a common genetic background.[14] In a recent genome-wide association study, the 3p21.31 region was found to be associated with COVID-19 severity.[15] This region also contains the TREX1 gene. Missense mutations of the TREX1 gene are responsible for familial chilblain lupus and its genetic polymorphisms have been implicated in the pathogenesis of systemic lupus erythematosus. The TREX1 mutation significantly reduces its exonucleolytic activity which results in the accumulation of nucleic acids that can stimulate type-I interferon responses and trigger autoimmunity. Thus an alteration in TREX1 activity, perhaps due to a promoter/enhancer modulation, may be responsible for the coincidence of both viral infection and an autoimmune phenomenon such as chilblain.[16] They may share some of the microscopic features of chilblains caused by lupus.[12] It has been suggested that in the absence of exposure to cold and damp, COVID-19 should be considered as a possible cause of chilblains.[12]