Chilblains (Perniosis): Cold-Triggered Skin Lesions

Table of Contents

1. What Chilblains Are
2. How They Differ From Frostbite and Raynaud's Phenomenon
3. How Often They Occur and in Whom
4. The Role of Damp Cold
5. What Skin Biopsies and Blood Tests Show
6. Chilblain Lupus and Other Linked Conditions
7. The Rise in Reports During the COVID-19 Pandemic
8. Later Studies Testing the COVID-19 Link
9. The Nifedipine Trials
10. Other Treatments as Reported
11. Course and Recurrence
12. Limits of the Evidence
13. Key Research Papers
14. Connections
15. Featured Videos

What Chilblains Are

Chilblains, also called perniosis or pernio, are sore or itchy red-to-purple skin lesions that appear after the skin has been in cool or cold, usually damp, conditions. A 2025 review describes them as an uncommon inflammatory condition whose cause remains poorly understood (Sharifzadeh 2025). A 2022 systematic review classes them as a non-freezing cold injury (Kapnia 2022). The skin does not have to freeze for them to appear.

The lesions form mostly on the toes and fingers. A 2021 systematic review adds that the heels, nose and ears are affected less often, and that the lesions tend to be symmetrical and can range from flat red-blue patches to blisters and ulcers (Pratt 2021). In a series of 104 patients at one US center, the toes were affected in 85 patients (82%) and the fingers in 31 (30%) (Cappel 2014). A pediatric report states that acute lesions may develop 12 to 24 hours after cold exposure, with intense pain, itching or burning (Simon 2005).

Doctors divide chilblains into two groups. Primary, or idiopathic, chilblains occur without any underlying disease. Secondary chilblains occur alongside another condition, such as an infection or an immune-mediated disease, with systemic lupus erythematosus the most common of those (Dubey 2022). Much of the research below separates the two.

Chilblains are also easy to mistake for something more serious. One review of 116 cases noted that their resemblance to blood vessel inflammation or to clots travelling to the fingers and toes can lead to an extensive and unnecessary work-up (Prakash 2009). A 1990 report of seven cases from San Francisco described unnecessary hospital admissions and, at times, hazardous treatment arising from unfamiliarity with the condition (Goette 1990).

The broader picture of cold fingers and toes, including causes other than chilblains, is on the Cold Hands and Feet page.

How They Differ From Frostbite and Raynaud's Phenomenon

Three conditions can follow cold exposure and affect the same body parts, but they involve different processes and last for different lengths of time.

• Frostbite is the freezing of tissue, with tissue death as the result (Simon 2005). Chilblains arise in temperatures above freezing, and the injury is inflammatory.
• Raynaud's phenomenon consists of sharply edged pallor and blueness of the skin followed by redness. It is far shorter, lasting hours rather than days (Simon 2005). The review literature names it as a main condition to tell apart from chilblains, along with cold panniculitis and chilblain lupus (Pratt 2021).
• Chilblains are raised or swollen inflamed lesions rather than a passing color change. Individual episodes last one to three weeks, according to the 2021 systematic review (Pratt 2021).

Narrowing of small blood vessels has also been measured in people with chilblains. In a small 2026 laboratory study, eight adults with a history of chilblains and eight without went through controlled cooling from 22°C to 10°C and then rewarming. Those with a history had significantly lower skin blood flow and lower oxygen delivery markers during the cold, and higher blood flow in the finger during rewarming. The authors read this as heightened cold-induced narrowing of the small vessels. No participant developed chilblains during the eight weeks of follow-up (Kapnia 2026). Treatment reviews also borrow from Raynaud's research, because direct chilblain trials are few (Sharifzadeh 2025).

How Often They Occur and in Whom

There is no agreed figure for how common chilblains are, and the papers describe the condition differently. A 2009 paper called chronic chilblains a common disease causing major restrictions in daily life (Souwer 2009), while a 2025 review calls perniosis uncommon (Sharifzadeh 2025). The figures below are counts from clinics and health systems, and they capture people who sought care and received the diagnosis.

• A Boston-area health system identified 1,478 patients with a recorded chilblains diagnosis from 2014 to 2021, reported as a registered prevalence of 0.02463%. Of these, 72.5% were female (Argobi 2025).
• A 2022 systematic review of 13 studies and 477 patients found that chilblains affected more women than men and most often involved the hands and fingers (Kapnia 2022).
• In the 104-patient US series, 82 (79%) were women and the mean age at diagnosis was 38.3 years (Cappel 2014).
• A retrospective series of 34 patients included 19 women and 15 men aged 15 to 57, and 16 were smokers. The authors noted the condition was more common in women and in people under 40 (Külcü Çakmak 2014).
• A series of 111 patients at a military hospital in northern Pakistan ran the other way, with 67 men (60.4%) and 44 women (39.6%) (Raza 2008). The setting of a study may shape who is counted.

Low body weight appears repeatedly. A review of 116 cases named female sex and low body mass index as risk factors (Prakash 2009). In a Colorado pediatric clinic, all five teenage girls seen over one winter were thin, below the 25th percentile for body mass index, and two reported wearing sandals in winter (Simon 2005). The 2021 systematic review also reports family clustering and cites a case-control series with a familial relative risk of 3.6, which suggests inherited susceptibility (Pratt 2021).

The Role of Damp Cold

Damp cold is the classic description. The 2021 systematic review states that idiopathic chilblains are triggered by damp-cold weather and are seen worldwide, more often in colder climates such as the UK and northwestern Europe (Pratt 2021). The seven San Francisco patients developed lesions after a cool or cold, damp environment (Goette 1990).

One study tested weather directly. Over a winter in Abbottabad, Pakistan, among 111 patients, onset was related to temperatures below 10°C in 89 patients (80.2%) and to relative humidity above 60% in 90 patients (81.1%). The authors concluded that susceptibility rises when temperature is below 10°C and humidity above 60% (Raza 2008). The study had no comparison group of people without chilblains, so it describes conditions at onset and cannot measure how much each factor raises risk.

Moisture also shows up in the skin findings. In meta-regression, smoking and frequent occupational exposure to water raised the likelihood of the characteristic microscopic changes (Kapnia 2022). Dampness is not an absolute requirement, though. The Colorado report notes that the cold there is quite dry, and the authors attributed their cases to a mix of cold climate, thin body build and cold exposure (Simon 2005).

Seasonal timing is described across the literature. Lesions usually begin in fall or winter and disappear in spring or early summer (Simon 2005).

What Skin Biopsies and Blood Tests Show

Under the microscope, primary chilblains show inflammation around blood vessels and sweat glands, together with fluid swelling in the upper skin. Pooled results from nine studies and 303 patients gave these frequencies (Kapnia 2022):

• Lymphocytes (a type of white blood cell) gathered around blood vessels: 81%
• Vacuole changes in the bottom layer of the epidermis: 67%
• Swelling of the upper dermis: 66%
• Lymphocytes gathered around sweat glands: 57%

A biopsy can help separate primary chilblains from lupus, though not with certainty. One study compared 17 thoroughly investigated idiopathic cases with 10 lupus biopsies from the hand. Spongy fluid changes in the epidermis (58% versus 0%), dermal swelling (70% versus 20%) and deep inflammation around sweat glands (76% versus 0%) were more frequent in chilblains, and vacuole changes in the basal layer (6% versus 60%) were more frequent in lupus. Staining for immune cell types did not help, since the same pattern of mostly T cells appeared in both (Cribier 2001).

A smaller comparison of 9 idiopathic and 11 autoimmune-associated cases agreed on one point. Inflammation around sweat glands was the only significant difference, seen in 66% of idiopathic and 27% of autoimmune cases (Boada 2010). A later series of 20 chilblain lupus and 39 idiopathic biopsies found that fibrin between the dermal fibers and increased mucin favored lupus, called the distinction still challenging, and found that the immune markers CD123 and CD30 did not separate the groups. The authors also pointed out that some patients counted as idiopathic might later develop lupus (Wang 2018). A study of 33 people with persistent chilblains found no features typical of lupus in any biopsy, including those from people who had the disease (Viguier 2001).

Blood tests in primary chilblains are often unremarkable, and they mainly serve to look for a linked condition. In the 104-patient series, 38 patients (37%) had at least one abnormal laboratory result. Cold agglutinins, antibodies that clump red blood cells in the cold, were positive in 11 of 20 people tested, while cryoglobulins, proteins that gel in the cold, were negative in all 53 tested (Cappel 2014). In the 34-patient series, antinuclear antibodies were positive in three people, and this finding was significantly more common in those with recurrent disease (Külcü Çakmak 2014). In the five Colorado teenagers, laboratory results were unremarkable (Simon 2005). The 2021 systematic review notes that chilblain-like lesions can be associated with cryoglobulins or cold agglutinins (Pratt 2021).

Chilblain Lupus and Other Linked Conditions

Chilblain lupus erythematosus is a rare, chronic form of cutaneous lupus. A 2022 review traces its first description to 1888, before the terms chilblains and perniosis were coined, and describes its biopsy pattern as interface dermatitis with lymphocytes around blood vessels and immune deposits along the junction of the two main skin layers (Dubey 2022).

Mayo Clinic authors proposed diagnostic criteria in 1994 from five cases, in a paper whose title also uses the name lupus pernio. That name is now mainly used for a skin sign of sarcoidosis, a different disease. The two major criteria are skin lesions on the extremities brought on by cold or a drop in temperature, and evidence of lupus in those lesions on biopsy or immunofluorescence. The three minor criteria are coexisting systemic lupus or discoid lesions, response to lupus treatment, and negative cryoglobulin and cold agglutinin tests (Su 1994).

The size of the link depends on who is studied:

• In the Boston-area health system, 169 of 1,478 patients with chilblains (11.43%) had an autoimmune disease, and systemic lupus erythematosus was the most frequent at 52.6% of those (Argobi 2025).
• Among 33 people whose chilblains lasted beyond one month, 22 had one or more abnormalities suggesting connective tissue disease, and 8 received a lupus diagnosis at first evaluation. Female sex and lesions persisting beyond the cold season were significantly associated with chilblain lupus. Two patients went on to severe systemic lupus during follow-up, needing oral steroids (Viguier 2001).
• A 2008 review states that up to 20% of people with chilblain lupus develop systemic lupus (Hedrich 2008).
• In the 104-patient US series, 4 (4%) had a non-lupus connective tissue disease and 3 (3%) had a blood cancer, and most had no underlying systemic association (Cappel 2014).

Inherited forms give the clearest window on the mechanism. Familial chilblain lupus begins in early childhood and is usually caused by a mutation in the TREX1 gene. In one family, lesions ranged from bluish-red swellings to necrotic ulcers that caused mutilation. All affected relatives had signs of systemic disease such as arthritis, low lymphocyte counts or antinuclear antibodies, with activation of type I interferon, an antiviral signaling pathway (Günther 2015). A 2024 study reported variants in a second gene, UNC93B1, that caused systemic lupus or chilblain lupus in five families, with the chilblain lupus variants showing a gain in activity of the virus-sensing receptor Toll-like receptor 8 in laboratory studies (David 2024).

Other reported links, most from small case series:

• Anorexia nervosa: three patients were described in 1994, with altered temperature regulation and an overactive small-vessel response to cold suggested as the explanation (White 1994). A 13-year-old boy who developed chilblain lupus after anorexia nervosa is described in the 2008 review (Hedrich 2008).
• Tumor necrosis factor inhibitor drugs: a 2021 report added three cases of chilblain lupus linked to these drugs, and counted eight earlier published cases (Shabeeb 2021).
• Cold-related blood proteins and antiphospholipid antibodies: listed as predisposing factors in the pediatric report, along with excessive cold exposure (Simon 2005).

The Rise in Reports During the COVID-19 Pandemic

From March 2020, case reports and series linked chilblain-like lesions, mostly in young people, with the pandemic of coronavirus disease 2019 (COVID-19). The lesions soon gained the popular name "COVID toes." These reports raised the question of whether the COVID-19 virus (SARS-CoV-2) was causing them, even though most patients had mild symptoms or none and their tests were usually negative.

The summaries of those early reports show the pattern:

• A 2021 systematic review summarized 31 papers and 813 cases, with a median age of 14. Nearly half (47%) had no symptoms beyond the skin, 15% tested positive for the virus, and 85% had partial or complete resolution within a mean of 13 days (Kashetsky 2021).
• A meta-analysis of 187 patients from case reports and 715 from 18 observational studies gave a mean age of 16.6 years. The feet were affected in 91.4%, and fewer than 15% were positive on a polymerase chain reaction test (Rocha 2021).
• A 2023 review of 69 pediatric studies counted 1,119 cases. Of these, 682 of 978 (70%) had no other symptoms, and 70 of 507 (14%) tested positive by polymerase chain reaction or antibody test. Resolution was reported in 355 of 415 cases (86%), and in 97 of 269 (36%) without any treatment (Starkey 2023).

Pandemic cases differed in some ways from the classic picture. The reviews above describe younger patients and a sex ratio close to equal, and many cases appeared during spring lockdowns (Kashetsky 2021; Starkey 2023; Poizeau 2022). In a French series of 40 consecutive patients with a median age of 22, 11 had lesions progress to blisters or tissue death and 24 (60%) had raised D-dimer levels. Polymerase chain reaction tests were negative in all, while antibody tests were positive in 12 (30%). Cryoglobulin and parvovirus B19 tests were negative in everyone tested (Hubiche 2021).

Under the microscope, pandemic and seasonal lesions look alike. A Paris study of 50 patients found similar biopsy patterns and overlapping gene activity in pandemic and seasonal chilblains, both with type I interferon activity. The pandemic cases showed more immunoglobulin A deposits in the skin, antibodies called immunoglobulin A antineutrophil cytoplasmic antibodies in 73% of patients, and blood markers of blood vessel lining damage (Frumholtz 2021).

Later Studies Testing the COVID-19 Link

Larger and better-controlled studies did not settle the question. They point in different directions, and the disagreement is still open.

Evidence against the virus as the direct cause:

• A northern California health plan study found that chilblains incidence rose during the pandemic, with 780 patients reported, but correlated only weakly with COVID-19 incidence across 207 location-months (Spearman coefficient 0.18). Only 17 of 456 people tested (3.7%) were positive for the virus, 9 of 456 (2.0%) within six weeks of the diagnosis, and 1 of 97 (1.0%) had antibodies. The authors named three possible explanations: a causal role of COVID-19, more care-seeking during the pandemic, and behavior changes during shelter in place (McCleskey 2021).
• A Connecticut study of 23 patients, 21 with pandemic chilblains, found prior infection in 9.5%, close to the 8.5% background rate of antibodies at the time. Staining of biopsies that seemed to show the virus may not have been from the virus. The authors stated that their results did not support the virus as the cause, while not excluding seronegative aborted infections (Gehlhausen 2022).
• A US single-center analysis reported a stronger association between chilblain cases and monthly temperature than between chilblain cases and COVID-19 incidence (Muser 2024).
• A Salt Lake County cohort of 29 patients had 0 positive results among 16 polymerase chain reaction tests and 2 positive results among 27 baseline antibody tests. Most presented during the strict quarantine period, when local case rates were low, and the usual seasonality was preserved (Sahni 2023).

Evidence for a link:

• A French case-control study compared 77 households of people with lockdown chilblains with 74 control households. After adjustment for age, the odds ratio for chilblains was 3.3 (95% confidence interval 1.4–7.3) with intermediate household exposure to the virus and 6.9 (2.5–19.5) with high exposure. Six of 57 case households tested (11%) had positive antibody results, compared with none of the 50 control households tested (Poizeau 2022). Exposure was estimated partly from reported symptoms and contacts, and the authors assessed the effect of possible misclassification in a bias analysis.
• A 2025 laboratory study proposed an explanation for the negative tests. White blood cells from patients produced abnormally high type I interferon when a virus-sensing receptor, Toll-like receptor 7, was stimulated, particularly by the COVID-19 virus. The authors suggested that predisposed people might clear the virus early, without making antibodies, with chilblains as the trade-off (Saidoune 2025). The French series above also found raised interferon-alpha production after laboratory stimulation (Hubiche 2021).

The idea of early immune clearance would account for negative antibody tests, and it is hard to test in an individual patient, since an aborted infection would leave little trace. The firmer findings are narrower: reports rose during the first waves, most patients tested were negative, and two of the studies above also found the usual link with cold weather.

Vaccination has been studied in very small numbers. A French questionnaire reached 54 people who had pandemic chilblains. Of those vaccinated, none reported a relapse of chilblains. Three reported erythromelalgia of the feet, a burning redness, lasting one week to one month. Reactions overall were similar to those in the vaccine trial used for comparison (Poizeau 2022 vaccination study).

The Nifedipine Trials

Nifedipine is a calcium channel blocker that widens blood vessels. It is widely prescribed for chilblains, and its evidence is mixed: the early placebo-controlled result came from a 10-patient trial, and a later placebo-controlled trial designed to follow it found no benefit (Pratt 2021; Souwer 2016). Where a figure below is not in a trial's own abstract, it comes from the table in the 2021 systematic review, which is named in the sentence.

• Placebo-controlled crossover trial from 1986, 10 patients. Enrolled people with severe disease lasting at least five months a year for the previous three years. According to the 2021 review's table, the trial gave nifedipine 20 mg three times daily for six weeks. Seven of 10 patients had lesions resolve within 10 days, against 20 to 28 days on placebo, and no new lesions appeared on treatment. Mild dizziness, flushing and occasional headaches were reported, and one patient needed a dose reduction for symptomatic low blood pressure (Dowd 1986, as tabulated in Pratt 2021).
• The same group's 1989 report of a pilot study, a double-blind placebo-controlled study and a long-term open trial. At 20 to 60 mg daily, nifedipine significantly shortened the time for existing lesions to clear, prevented new ones and reduced pain, soreness and irritation. Biopsies taken before and after treatment showed less swelling and less inflammation around blood vessels, and skin blood flow rose (Rustin 1989).
• Open comparison with diltiazem, 2003, 36 patients. Of 24 on nifedipine, 21 had 80 to 90% relief by day 14. Of 12 on diltiazem, 2 had complete relief at 7 days and 3 at about 21 days, while 7 had little or no response (Patra 2003). The 2021 review notes that statistical significance was not calculated.
• Comparison with glyceryl trinitrate 0.4% cream, 2014, 65 enrolled and 53 completing. Clearance averaged 10.9 days on nifedipine and 16.6 days on the cream (P = .05). Five of 26 patients stopped nifedipine because of severe headache (Khalid 2014, as tabulated in Pratt 2021).
• Comparisons with topical 5% minoxidil, 2010 and 2018. Both favored nifedipine. In the larger, 84-patient trial, 10 of 42 on nifedipine and 3 of 42 on minoxidil had very good improvement. In the earlier trial, flushing was reported in 54% on nifedipine, constipation in 9% and headache in 6% (Kubais 2010 and Jain 2018, as tabulated in Pratt 2021).
• Placebo-controlled, double-blind crossover trial from the Netherlands, 2016, 32 patients. The trial gave controlled-release nifedipine 30 mg twice daily and was designed to follow the older trial closely. After six weeks the difference in complaint scores on a 100 mm scale was 1.84 mm in favor of nifedipine (95% confidence interval reported as −6.67 to 2.99 mm, P = .44), and the difference in disability scores was 0.56 mm in favor of placebo (−2.97 to 4.09 mm, P = .75). Nifedipine lowered systolic blood pressure significantly and was linked to more swelling (edema). The authors concluded that nifedipine was not superior to placebo (Souwer 2016).

The two placebo-controlled trials enrolled different people. The 2021 review points out that the Dutch trial's participants had far shorter symptoms, three weeks against five months a year for three years, and that the Dutch trial started at a lower dose for the first two weeks. It also accounted for outdoor temperature, which the older trial did not, and this matters for a condition that clears when the weather warms. The 2021 review's overall verdict was moderate evidence supporting nifedipine in severe or refractory idiopathic chilblains (Pratt 2021). The Dutch authors reported that their findings do not support routine use (Souwer 2016). Reported harms across these trials include headache, flushing, swelling, dizziness and low blood pressure.

Other Treatments as Reported

A 2021 systematic review of eleven controlled trials, covering 576 people in total, found inadequate evidence or no significant effect for options beyond nifedipine and pentoxifylline (Pratt 2021). The reports below are given as published.

• Warming and drying: in the 104-patient series, conservative measures including warming, drying and stopping smoking gave a complete response in 23 of 28 patients with follow-up data (82%). There was no comparison group, and lesions clear on their own in many people (Cappel 2014).
• Pentoxifylline: a double-blind placebo-controlled trial in Iraq over four winters gave 400 mg three times daily for three weeks, with 110 patients completing. The very good response was significantly better than placebo, reported in the 2021 review's table as 40 of 55 (72.7%) against 11 of 55 (20%), and no side effects were recorded (Al-Sudany 2016; Pratt 2021). Temperature was not corrected for, according to the review. An earlier comparison with prednisolone and clobetasol lost half of its participants without explanation (Noaimi 2008, as tabulated in Pratt 2021).
• Tadalafil: in an open comparison, severity scores improved 50.65% on tadalafil 5 mg daily, 44.16% on pentoxifylline and 31.51% on prednisolone. Mild headache occurred in the first days in six people on tadalafil (Noaimi 2015, as tabulated in Pratt 2021).
• Topical betamethasone: a placebo-controlled crossover trial in 34 Dutch primary care patients found a difference of 0.56 mm on the 100 mm complaint scale in favor of placebo (P = .744). The betamethasone cream was not superior to placebo, despite its frequent use (Souwer 2017).
• Vitamin D3: 2,000 IU daily in 33 patients was no better than placebo, with 19% reporting fewer complaints and 6% less disability in both periods (Souwer 2009).
• Hydroxychloroquine: a retrospective report found symptom improvement in four of five patients, and its literature review counted 12 of 51 cases responding alone or in combination with other treatments (Yang 2010).
• Nitroglycerin, fluoxetine and botulinum toxin: a 2025 review reports that topical nitroglycerin improves peripheral blood flow, that fluoxetine and antimalarial drugs show promise particularly in secondary perniosis, and that botulinum toxin remains inconclusive for primary perniosis (Sharifzadeh 2025).

Treatment reports for chilblain lupus are separate, and they are almost all case-level:

• The 1994 Mayo Clinic cases benefited from antimalarial drugs, prednisone, pentoxifylline or dapsone (Su 1994). The 2008 review reports that lupus drugs had good effects on the systemic symptoms but not on the chilblains themselves (Hedrich 2008).
• Baricitinib, a Janus kinase inhibitor, 4 mg daily for three months in three patients with familial chilblain lupus from TREX1 mutations: all three had significant improvement of skin lesions with suppressed interferon activity in blood (Zimmermann 2019).
• Anifrolumab, an antibody that blocks the type I interferon receptor, given as 300 mg infusions every four weeks: a report describes two patients with disease that had not responded to other treatments as successfully treated. The first had marked improvement after four infusions, added to her existing treatments (Woodbury 2024).

Course and Recurrence

Primary chilblains usually clear on their own, then return. The 2021 systematic review describes episodes of one to three weeks, spontaneous resolution in spring and common annual recurrence, with a longer course in older people and in people with venous insufficiency (Pratt 2021). The pediatric report describes acute lesions as usually self-limited but capable of leading to recurrent disease, and notes that repeated cold exposure with persistent lesions is called chronic pernio (Simon 2005).

Detailed follow-up numbers come from the pandemic. In 82 French patients referred between March and May 2020 and surveyed in December 2020, 27 (33%) reported complete recovery, 33 (40%) had recurrences after their skin had returned to normal, and 22 (27%) developed persistent changes, mostly acrocyanosis (a lasting bluish color of the hands and feet). Most recurrences came in the following autumn and winter. A past history of chilblains did not predict them. Women had a higher risk of recurrence or persistent changes (odds ratio 1.30, 95% confidence interval 1.06–1.59) (Poizeau 2021). A smaller American cohort of 29 had no recurrences at six months (Sahni 2023), a difference that may reflect the shorter follow-up.

Some features are reported as signs that chilblains may not be the primary form. Persistence beyond the cold season was significantly associated with chilblain lupus (Viguier 2001). Antinuclear antibodies were more common in recurrent disease (Külcü Çakmak 2014). The authors of the 33-person study reported that chronic chilblains may reveal connective tissue disease, and that those with autoimmune abnormalities may develop severe systemic lupus (Viguier 2001). Lesions can also go beyond surface redness: blistering or tissue death was recorded in 11 of 40 patients in the French pandemic series (Hubiche 2021).

Limits of the Evidence

• Trials are few and small. A 2025 review states that there are no high-quality randomized controlled trials, and that treatment advice has come from case reports and studies of related conditions such as Raynaud's (Sharifzadeh 2025). The 2021 review could not perform a meta-analysis because the trials differed too much in design and data (Pratt 2021).
• Weather confounds treatment results. Chilblains clear as temperatures rise, so a drug given in late winter can look effective without a suitable control. The 2021 review lists no correction for ambient temperature as a limitation in most included trials (Pratt 2021).
• Many of the positive trials are open-label or have unclear baseline characteristics, according to the same review. One had a 50% dropout without explanation (Pratt 2021).
• Frequency figures come from people who reached clinics or health systems, so mild cases treated at home are not counted. Autoimmune rates may vary with the clinic, since a rheumatology referral group is likely to include more of those diseases than a primary care group.
• Definitions vary. Some series exclude chilblain lupus and others do not, and pandemic studies mix "chilblains," "pernio" and "chilblain-like lesions."
• COVID-19 studies depended on tests available at the time. Access to testing was uneven (Sahni 2023). Negative tests do not exclude an aborted infection, and increased care-seeking and lockdown behavior remain possible explanations for the rise in reports (McCleskey 2021; Gehlhausen 2022).
• Among the papers read for this page, long-term follow-up comes mostly from the pandemic cohorts and from small series of people with suspected connective tissue disease, leaving the long-term course of primary chilblains in the general population thinly documented.

Key Research Papers

1. Sharifzadeh A, Smith GP. An Evidence-Based Review of Perniosis (Chilblains): Therapeutic Strategies and Integration With Raynaud's Syndrome Management. Int J Dermatol. 2025;64(10):1781-1787. PubMed PMID: 40272049
2. Argobi Y. Trends and Associations of Chilblains Prevalence with Connective Tissue Diseases, Including COVID-19 Incidence. Clin Cosmet Investig Dermatol. 2025;18:339-344. PubMed PMID: 39911214
3. Cappel JA, Wetter DA. Clinical characteristics, etiologic associations, laboratory findings, treatment, and proposal of diagnostic criteria of pernio (chilblains) in a series of 104 patients at Mayo Clinic, 2000 to 2011. Mayo Clin Proc. 2014;89(2):207-15. PubMed PMID: 24485134
4. Külcü Çakmak S, Gönül M, Oğuz ID, Yayla D, Gül U, Köse K. Demographical, laboratory and associated findings in patients with perniosis. J Eur Acad Dermatol Venereol. 2014;28(7):891-4. PubMed PMID: 23763696
5. Kapnia AK, Ziaka S, Ioannou LG, Flouri I, Dinas PC, Flouris AD. Population Characteristics, Symptoms, and Risk Factors of Idiopathic Chilblains: A Systematic Review, Meta-Analysis, and Meta-Regression. Biology (Basel). 2022;11(11):1651. PubMed PMID: 36421364
6. Kapnia AK, Mantzios K, Karanika P, Angelopoulou-Athanatou EV, Tsaklis PV, Flouris AD. Physiological responses of individuals with idiopathic chilblains during cold exposure and rewarming: a nonrandomized clinical trial. Am J Physiol Regul Integr Comp Physiol. 2026;330(5):R530-R536. PubMed PMID: 41941353
7. Raza N, Sajid Mu, Suhail M, Haroon-ur-Rashid. Onset of chilblains in relation with weather conditions. J Ayub Med Coll Abbottabad. 2008;20(2):17-20. PubMed PMID: 19385449
8. Prakash S, Weisman MH. Idiopathic chilblains. Am J Med. 2009;122(12):1152-5. PubMed PMID: 19958897
9. Goette DK. Chilblains (perniosis). J Am Acad Dermatol. 1990;23(2 Pt 1):257-62. PubMed PMID: 2212122
10. Simon TD, Soep JB, Hollister JR. Pernio in pediatrics. Pediatrics. 2005;116(3):e472-5. PubMed PMID: 16140694
11. Cribier B, Djeridi N, Peltre B, Grosshans E. A histologic and immunohistochemical study of chilblains. J Am Acad Dermatol. 2001;45(6):924-9. PubMed PMID: 11712041
12. Boada A, Bielsa I, Fernández-Figueras MT, Ferrándiz C. Perniosis: clinical and histopathological analysis. Am J Dermatopathol. 2010;32(1):19-23. PubMed PMID: 20098080
13. Wang ML, Chan MP. Comparative Analysis of Chilblain Lupus Erythematosus and Idiopathic Perniosis: Histopathologic Features and Immunohistochemistry for CD123 and CD30. Am J Dermatopathol. 2018;40(4):265-271. PubMed PMID: 28719438
14. Viguier M, Pinquier L, Cavelier-Balloy B, de la Salmonière P, Cordoliani F, Flageul B, et al. Clinical and histopathologic features and immunologic variables in patients with severe chilblains. A study of the relationship to lupus erythematosus. Medicine (Baltimore). 2001;80(3):180-8. PubMed PMID: 11388094
15. Su WP, Perniciaro C, Rogers RS, White JW. Chilblain lupus erythematosus (lupus pernio): clinical review of the Mayo Clinic experience and proposal of diagnostic criteria. Cutis. 1994;54(6):395-9. PubMed PMID: 7867381
16. Hedrich CM, Fiebig B, Hauck FH, Sallmann S, Hahn G, Pfeiffer C, et al. Chilblain lupus erythematosus--a review of literature. Clin Rheumatol. 2008;27(8):949-54. PubMed PMID: 18543054
17. Dubey S, Joshi N, Stevenson O, Gordon C, Reynolds JA. Chilblains in immune-mediated inflammatory diseases: a review. Rheumatology (Oxford). 2022;61(12):4631-4642. PubMed PMID: 35412601
18. Günther C, Berndt N, Wolf C, Lee-Kirsch MA. Familial chilblain lupus due to a novel mutation in the exonuclease III domain of 3' repair exonuclease 1 (TREX1). JAMA Dermatol. 2015;151(4):426-31. PubMed PMID: 25517357
19. Zimmermann N, Wolf C, Schwenke R, Lüth A, Schmidt F, Engel K, et al. Assessment of Clinical Response to Janus Kinase Inhibition in Patients With Familial Chilblain Lupus and TREX1 Mutation. JAMA Dermatol. 2019;155(3):342-346. PubMed PMID: 30673078
20. David C, Arango-Franco CA, Badonyi M, Fouchet J, Rice GI, Didry-Barca B, et al. Gain-of-function human UNC93B1 variants cause systemic lupus erythematosus and chilblain lupus. J Exp Med. 2024;221(8):e20232066. PubMed PMID: 38869500
21. White KP, Rothe MJ, Milanese A, Grant-Kels JM. Perniosis in association with anorexia nervosa. Pediatr Dermatol. 1994;11(1):1-5. PubMed PMID: 8170840
22. Shabeeb N, Hinshaw M, Pei S, Craddock L, Keenan T, Endo J. Clinical features of tumor necrosis factor-α-inhibitor induced chilblain lupus: A case series. JAAD Case Rep. 2021;12:81-84. PubMed PMID: 34041339
23. McCleskey PE, Zimmerman B, Lieberman A, Liu L, Chen C, Gorouhi F, et al. Epidemiologic Analysis of Chilblains Cohorts Before and During the COVID-19 Pandemic. JAMA Dermatol. 2021;157(8):947-953. PubMed PMID: 34160569
24. Hubiche T, Cardot-Leccia N, Le Duff F, Seitz-Polski B, Giordana P, Chiaverini C, et al. Clinical, Laboratory, and Interferon-Alpha Response Characteristics of Patients With Chilblain-like Lesions During the COVID-19 Pandemic. JAMA Dermatol. 2021;157(2):202-206. PubMed PMID: 33237291
25. Frumholtz L, Bouaziz JD, Battistella M, Hadjadj J, Chocron R, Bengoufa D, et al. Type I interferon response and vascular alteration in chilblain-like lesions during the COVID-19 outbreak. Br J Dermatol. 2021;185(6):1176-1185. PubMed PMID: 34611893
26. Gehlhausen JR, Little AJ, Ko CJ, Emmenegger M, Lucas C, Wong P, et al. Lack of association between pandemic chilblains and SARS-CoV-2 infection. Proc Natl Acad Sci U S A. 2022;119(9):e2122090119. PubMed PMID: 35217624
27. Poizeau F, Oger E, Barbarot S, Le Corre Y, Samimi M, Brenaut E, et al. Chilblains during lockdown are associated with household exposure to SARS-CoV-2: a multicentre case-control study. Clin Microbiol Infect. 2022;28(2):285-291. PubMed PMID: 34619397
28. Poizeau F, Barbarot S, Le Corre Y, Brenaut E, Samimi M, Aubert H, et al. Long-term Outcome of Chilblains Associated with SARS-CoV-2. Acta Derm Venereol. 2021;101(12):adv00614. PubMed PMID: 34515805
29. Saidoune F, Lee D, Di Domizio J, Le Floc'h C, Jenelten R, Le Pen J, et al. Enhanced TLR7-dependent production of type I interferon by pDCs underlies pandemic chilblains. J Exp Med. 2025;222(7):e20231467. PubMed PMID: 40227192
30. Muser I, Gallop J, Narang J, Flatley EM, Tamburro J, Riegert M, et al. Development of chilblain lesions during the COVID-19 pandemic is strongly associated with cold weather: a retrospective analysis of patients from a single centre in the USA. Clin Exp Dermatol. 2024;49(3):284-286. PubMed PMID: 37966795
31. Sahni DR, Deacon DC, Madigan LM. The impact of seasonal temperature variation on the incidence of pernio during the COVID-19 pandemic. JAAD Int. 2023;10:3-5. PubMed PMID: 36164466
32. Kashetsky N, Mukovozov IM, Bergman J. Chilblain-Like Lesions (CLL) Associated With COVID-19 ("COVID Toes"): A Systematic Review. J Cutan Med Surg. 2021;25(6):627-633. PubMed PMID: 33849305
33. Starkey SY, Kashetsky N, Lam JM, Dutz J, Mukovozov IM. Chilblain-Like Lesions (CLL) Coinciding With the SARS-CoV-2 Pandemic in Children: A Systematic Review. J Cutan Med Surg. 2023;27(3):277-284. PubMed PMID: 37340564
34. Rocha KO, Zanuncio VV, Freitas BAC, Lima LM. "COVID toes": A meta-analysis of case and observational studies on clinical, histopathological, and laboratory findings. Pediatr Dermatol. 2021;38(5):1143-1149. PubMed PMID: 34515379
35. Poizeau F, Triquet L, Dupuy A. COVID-19 Vaccination Safety in Patients who have had SARS-CoV-2-induced Chilblains. Acta Derm Venereol. 2022;102:adv00728. PubMed PMID: 35506360
36. Rustin MH, Newton JA, Smith NP, Dowd PM. The treatment of chilblains with nifedipine: the results of a pilot study, a double-blind placebo-controlled randomized study and a long-term open trial. Br J Dermatol. 1989;120(2):267-75. PubMed PMID: 2647123
37. Dowd PM, Rustin MH, Lanigan S. Nifedipine in the treatment of chilblains. Br Med J (Clin Res Ed). 1986;293(6552):923-4. PubMed PMID: 3094717
38. Souwer IH, Bor JH, Smits P, Lagro-Janssen AL. Nifedipine vs Placebo for Treatment of Chronic Chilblains: A Randomized Controlled Trial. Ann Fam Med. 2016;14(5):453-9. PubMed PMID: 27621162
39. Patra AK, Das AL, Ramadasan P. Diltiazem vs. nifedipine in chilblains: a clinical trial. Indian J Dermatol Venereol Leprol. 2003;69(3):209-11. PubMed PMID: 17642888
40. Pratt M, Mahmood F, Kirchhof MG. Pharmacologic Treatment of Idiopathic Chilblains (Pernio): A Systematic Review. J Cutan Med Surg. 2021;25(5):530-542. PubMed PMID: 33653127
41. Al-Sudany NK. Treatment of primary perniosis with oral pentoxifylline (a double-blind placebo-controlled randomized therapeutic trial). Dermatol Ther. 2016;29(4):263-8. PubMed PMID: 26991468
42. Souwer IH, Bor JH, Smits P, Lagro-Janssen AL. Assessing the effectiveness of topical betamethasone to treat chronic chilblains: a randomised clinical trial in primary care. Br J Gen Pract. 2017;67(656):e187-e193. PubMed PMID: 28193616
43. Souwer IH, Lagro-Janssen AL. Vitamin D3 is not effective in the treatment of chronic chilblains. Int J Clin Pract. 2009;63(2):282-6. PubMed PMID: 19196366
44. Yang X, Perez OA, English JC. Successful treatment of perniosis with hydroxychloroquine. J Drugs Dermatol. 2010;9(10):1242-6. PubMed PMID: 20941949
45. Woodbury MJ, Smith KN, Smith JS, Merola JF. Anifrolumab for the treatment of refractory chilblain lupus erythematosus. JAAD Case Rep. 2024;48:69-71. PubMed PMID: 38778891

PubMed Topic Searches

1. PubMed: chilblains and perniosis
2. PubMed: nifedipine trials in chilblains
3. PubMed: chilblain lupus erythematosus
4. PubMed: chilblains and the COVID-19 virus
5. PubMed: familial chilblain lupus and interferon

Connections

• Dermatology — the skin conditions section this page belongs to
• Cold Hands and Feet — the wider symptom picture and its causes
• Raynaud's Phenomenon — the short color-change episodes often confused with chilblains
• Raynaud's Disease — the primary form of Raynaud's
• Lupus — the disease most often linked to secondary chilblains
• Cutaneous Lupus and Photoprotection — the skin forms of lupus
• Cryoglobulinemia — cold-sensitive blood proteins, tested for in chilblain workups
• Sarcoidosis: History — where the similar name lupus pernio comes from
• Anorexia Nervosa — a reported association through low body weight and temperature regulation

Back to Table of Contents

Featured Videos