ChilblainsMANAGEMENT

ENVIRONMENTAL AND EXPOSURE PRESENTATIONS · 12 SECTIONS

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682 items

☷ Legend

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Cardiovascular Presentations71▾

Respiratory Presentations52▾

Neurological Presentations83▾

Gastrointestinal Presentations74▾

Genitourinary and Reproductive Presentations48▾

Infectious Disease Presentations148▾

Trauma Presentations89▾

Toxicologic Presentations80▾

Psychiatric Presentations26▾

Musculoskeletal and Rheumatologic Presentations96▾

Dermatology Presentations23▾

Environmental and Exposure Presentations27▾

Acute Mountain Sickness Arterial Gas Embolism Bee-Wasp Sting (Anaphylaxis)Chilblains Ciguatera Fish Poisoning Coral Cut Decompression Sickness Electrical Burn Injury Envenomation (snake, spider, insect)High Altitude Cerebral Edema (HACE)High Altitude Pulmonary Edema (HAPE)High-altitude illness Hypothermia Hypothermia (Mild)Hypothermia (Severe)Immersion Foot Lightning Strike Injury Scombroid Fish Poisoning Scorpion Envenomation Sea Urchin Injury Shark Bite Snake Envenomation Spider Bite (Black Widow)Spider Bite (Brown Recluse)Stingray Spine Injury Tick paralysis White Phosphorus Burn

Hematologic and Oncologic Presentations36▾

Pediatric-Specific Presentations19▾

Endocrine and Metabolic Presentations45▾

ENT and Maxillofacial Presentations27▾

Ophthalmologic Presentations19▾

Obstetric Presentations23▾

Systemic and Miscellaneous Presentations17▾

01Approach to the Critical Patient/attcp42

Immediate priorities

›Recognition of severity and cold injury spectrum

›Chilblains is a nonfreezing cold injury (NFCI) — no tissue freezing

›Distinguish from frostbite (tissue freezing with necrosis)

›Distinguish from trench foot (prolonged days of cold-wet exposure)

›Most presentations are non-critical and self-limited

›Complete response to conservative care in approximately 82% of patients

›Typical resolution within 1 to 3 weeks

›Critical concern triggers

›Concurrent significant hypothermia

›Tissue necrosis or gangrene suggesting vascular emergency

›Bullous or deeply ulcerated lesions with superinfection

Alarm features requiring urgent evaluation

›Secondary pernio alarm features

›Lesions persisting beyond cold seasons

›Raises concern for SLE, connective tissue disease, or hematologic malignancy

›Secondary cause in approximately 3% of cases due to hematologic malignancy

›Constitutional symptoms

›Fever, weight loss, lymphadenopathy suggesting malignancy or autoimmune flare

›Arthralgias, malar rash, oral ulcers suggesting lupus

›Rapidly progressive tissue injury

›Expanding necrosis, new bullae, purulent drainage

›May require IV antibiotics or surgical consultation

›Immediate escalation triggers

›Concurrent hypothermia

›Core temperature monitoring

›Passive and active rewarming protocol

›Critical limb ischemia differentiation

02History/hx57

Presentation pattern

›Core symptoms

›Pruritus of affected acral areas

›Often burning quality

›Exacerbated by rewarming

›Pain and tenderness

›Throbbing or aching in lesions

›Worsens with temperature change

›Erythematous to violaceous discoloration

›Dorsal toes most common site (82% of cases)

›Fingers (30%), ears, nose, shins also affected

›Temporal relationship to cold exposure

›Lesion development 12 to 24 hours after cold exposure

›Nonfreezing temperatures 0 to 16 degrees C (32 to 60 degrees F)

›Cold-damp conditions more than dry cold

›Seasonal pattern

›Onset fall and winter

›Resolution spring and summer for primary pernio

›Persistence beyond cold season suggests secondary pernio

Risk factors and exposures

›Exposure history

›Cold exposure duration (typically 1 to 5 hours)

›Wet versus dry conditions

›Outdoor occupation (construction, military, agriculture)

›Protective clothing adequacy

›Sandals or open footwear in cold weather

›Wet socks or shoes

›Tight footwear restricting circulation

03Physical Exam/exam50

Skin and lesion assessment

›Lesion characteristics

›Morphology

›Erythematous to violaceous (purplish) papules or plaques

›Edematous, occasionally nodular

›May progress to vesicles, bullae, or superficial ulceration in severe cases

›Distribution

›Dorsal toes predominant

›Dorsal fingers

›Ears, nose, shins in some cases

›Tenderness

›Tender to palpation

›Burning or itching intensified by warming

›Lesion severity staging

›Mild

›Erythema and edema only

›No blistering or ulceration

›Moderate

›Vesicle or bulla formation

›Superficial erosion

›Severe

›Deep ulceration

›Necrosis raising concern for secondary infection or vascular compromise

Vascular and systemic exam

›Peripheral vascular assessment

›Peripheral pulses

›Should be intact in isolated chilblains

›Absent pulses suggest PAD, frostbite, or critical limb ischemia

04Differential Diagnosis/ddx48

Life-threatening mimics

›Critical limb ischemia

›ICD-10 I74.9 (arterial embolism) or I70.2 (PAD)

›Absent pulses, claudication, pallor, tissue loss

›Requires urgent vascular surgery consultation

›Thromboangiitis obliterans (Buerger disease)

›Young male smokers with digital ischemia

›ICD-10 I73.1

›Concurrent hypothermia

›May accompany severe cold exposure

›Core temperature less than 35 degrees C

›Requires active rewarming protocol

Primary cold injury differentials

›Frostbite

›ICD-10 T33 to T35 range

›Tissue freezing at temperatures below 0 degrees C

›White or grey discoloration, waxy texture, anesthesia

›Trench foot (immersion foot)

›Prolonged days of cold-wet exposure

›Deeper neurovascular damage than chilblains

›Raynaud phenomenon

›ICD-10 I73.0

›Sharply demarcated triphasic color change (pallor, cyanosis, erythema)

›Episodic, lasting hours not days

›No persistent papules or plaques

›Acrocyanosis

›Persistent symmetric cyanosis without papules

›Non-episodic baseline discoloration

05Laboratory Tests/lt47

Initial workup for secondary pernio concern

›Autoimmune and connective tissue screen

›Antinuclear antibody (ANA)

›Positive in approximately 22.5% of pandemic cohort at low titer

›Threshold for follow-up positive at 1:80 or higher

›Anti-dsDNA and anti-Smith antibodies

›If ANA positive, to evaluate for SLE

›Highly specific for SLE when positive

›Antiphospholipid antibodies

›Anticardiolipin antibody

›Anti-beta2-glycoprotein I

›Lupus anticoagulant

›Complement levels C3 and C4

›Low complement suggests active lupus

›Useful when SLE suspected

›Hematologic screen

›Complete blood count with differential

›Cytopenias may indicate lupus or hematologic malignancy

›Lymphocytosis may suggest lymphoproliferative disorder

›Cold agglutinins

›Positive in 55% of tested pernio patients in Mayo series

›Routine cryoglobulin testing may not be necessary

›Serum protein electrophoresis

›If hematologic malignancy suspected

›Hypergammaglobulinemia may distinguish secondary from idiopathic pernio

Inflammatory and nonspecific markers

›Inflammatory markers

›ESR and CRP

06Diagnostic Tests/dt65

Scoring Systems

›ARCTIC mnemonic for differential diagnosis

›Acrocyanosis

›Persistent symmetric cyanosis without papules

›No cold exposure trigger

›Raynaud phenomenon

›Triphasic episodic color change

›Duration hours not days

›Critical limb ischemia

›Absent pulses, tissue loss

›Urgent vascular consultation

›Thromboangiitis obliterans

›Young smoker with digital ischemia

›ICD-10 I73.1

›Idiopathic chilblains

›Seasonal, acral papules, cold exposure, primary pernio

›Self-limited

›COVID toes

›Pandemic context, without cold exposure, SARS-CoV-2 temporal association

›ANA low titer may be positive

›Severity classification (clinical)

›Primary (idiopathic) pernio

›Most common presentation

›Seasonal, self-limited, no underlying systemic disease

›Secondary pernio

›Associated with SLE, antiphospholipid syndrome, hematologic malignancy, or viral infection

›Key distinguishing features: persistence beyond cold seasons, older age, male sex, hypergammaglobulinemia

›Acute versus chronic pernio

›Acute: develops 12 to 24 hours post-exposure, resolves within 1 to 3 weeks

›Chronic: recurrent with repeated cold exposure, lesions persist seasonally

MRI

›MRI role in chilblains

›Not routinely indicated for typical chilblains

›Clinical diagnosis in most cases

›Imaging rarely changes initial management

›Specific indication: suspected inflammatory arthritis with chilblains

›MRI of digits may show phalangeal bone marrow edema in secondary chilblains with inflammatory arthritis

›Reported in case series of novel association between chilblains and inflammatory arthritis

›Contraindications and limitations

›Not appropriate for unstable patient

›Incompatible implants

›Limited availability in emergency setting

›CT role in chilblains

›Generally not indicated for isolated primary chilblains

›No CT findings specific to chilblains

›Radiation exposure not justified for benign dermatologic condition

›Potential indications for secondary cause evaluation

›CT chest, abdomen, pelvis if lymphoproliferative disorder or malignancy suspected

›CT angiography if vascular occlusion or PAD in differential

›COVID-19 associated pernio context

›CT chest findings of COVID-19 may be present in pandemic pernio cohort

›Not routine unless respiratory symptoms present

Ultrasound

›Doppler ultrasound indications

›Arterial Doppler of affected extremity

›To exclude PAD or critical limb ischemia when pulses absent or diminished

›Ankle-brachial index (ABI) calculation

›Normal result supports benign diagnosis when exam uncertain

›Not routinely required in classic chilblains with intact pulses

›Clinical vascular exam usually sufficient

›Reserve for atypical presentations

›Nailfold capillaroscopy

›Role in Raynaud and connective tissue disease evaluation

›Scleroderma pattern: capillary drop-out, giant capillaries, hemorrhages

›Normal pattern more consistent with primary Raynaud or chilblains

›Not emergency department test

›Outpatient rheumatology referral for formal capillaroscopy

›Results modify secondary workup

07Disposition/dispo43

Discharge criteria

›Outpatient management appropriate for most chilblains

›Vitals normal

›No hypothermia

›No hemodynamic instability

›Diagnosis established clinically

›Classic presentation with cold exposure

›No alarming secondary features requiring urgent workup

›Able to self-care and follow precautions

›Understands rewarming instructions

›Can avoid cold re-exposure

›Follow-up plan at discharge

›Primary care or dermatology within 2 to 3 weeks

›Assess lesion resolution

›Evaluate for secondary workup need if not resolved

›Rheumatology referral if ANA positive at 1:80 or higher

›Or features of connective tissue disease on exam or history

›Dermatology referral for biopsy consideration or refractory cases

Admission indications

›Rare indications for hospital admission

›Concurrent significant hypothermia

›Core temperature monitoring

›Active rewarming protocol

›Severe tissue injury with superinfection

›Deep ulceration with cellulitis

›IV antibiotic requirement

›Secondary pernio with systemic disease flare

›Active SLE with organ involvement

08Treatment/t105

Conservative care (all patients)

›Rewarming and protection

›Gentle passive rewarming

›Move patient to warm environment

›Avoid rapid active rewarming (worsens burning and pain)

›Skin care of lesions

›Clean and dry affected areas

›Elevate affected limb to reduce edema

›Protection from further exposure

›Warm, insulated, moisture-wicking socks and gloves

›Avoid tight footwear

›Waterproofing of footwear in wet conditions

›Smoking cessation

›Priority lifestyle modification

›Nicotine causes vasoconstriction aggravating chilblains

›Counseling and pharmacotherapy referral at visit

›Behavioral and pharmacologic support

›Nicotine replacement therapy

›Varenicline or bupropion as options

Analgesics and topical therapy

›Pain and inflammation relief

›NSAIDs for mild pain

›Ibuprofen 400 to 600 mg PO every 6 to 8 hours with food

›Maximum 2400 mg per day in adults

›Acetaminophen

›500 to 1000 mg PO every 4 to 6 hours as alternative

›Maximum 3000 to 4000 mg per day

›Topical corticosteroids

›Symptomatic relief of inflammation acutely

›Mid-potency topical steroid to affected areas

›Use twice daily for up to 2 weeks

›Evidence limited but commonly used

›May reduce swelling, pruritus, and burning

›No systemic side effects at short-term topical use

Vasodilator therapy

›Nifedipine (first-line pharmacologic for moderate to severe or recurrent)

›Dose

›Nifedipine extended-release 20 to 60 mg per day

›Start at lower dose and titrate based on response and tolerance

›Evidence

›Older RCT (Rustin 1989) showed reduction in pain, facilitation of healing, and prevention of new lesions

›More recent RCT (Souwer 2016) found no superiority over placebo for chronic chilblains

›Use when benefits outweigh uncertain evidence

›Monitoring and adverse effects

›Monitor blood pressure for hypotension

›Peripheral edema as side effect

›Reflex tachycardia possible

›Contraindications

›Hypotension (SBP less than 90 mmHg)

›Concurrent use of strong CYP3A4 inhibitors

›Topical nitroglycerin

›May improve peripheral perfusion

›Apply 2% nitroglycerin ointment to affected areas

›Limited evidence; adjunct option

›Avoid if hypotension or concurrent phosphodiesterase inhibitor use

›Headache as common side effect

›Short duration of action

Neuropathic pain management

›Amitriptyline

›Dose

›Amitriptyline 50 to 100 mg at bedtime

›Start at 25 mg and titrate over 1 to 2 weeks

›Indications

›Neuropathic or refractory pain component

›Burning, allodynia, dysesthesia

›Monitoring

›QT prolongation risk

›Anticholinergic side effects (urinary retention, constipation)

›Gabapentin

›Adjunct for refractory neuropathic pain

›Gabapentin 300 mg at bedtime initially

›Titrate up to 300 to 900 mg three times daily as tolerated

›Monitoring

›Sedation, dizziness, peripheral edema

›Renal dose adjustment required if eGFR reduced

Secondary pernio directed therapy

›Chilblain lupus (SLE-associated)

›Hydroxychloroquine

›200 to 400 mg per day

›Baseline ophthalmologic screening required

›Long-term use for lupus management

›Immunosuppression per rheumatology guidance

›Based on overall lupus disease activity

›Oral corticosteroids for acute flares

›Other secondary pernio agents (limited evidence)

›Fluoxetine

›20 to 40 mg per day

›Shows promise particularly for secondary pernio

›Serotonin effect on peripheral vasomotor tone

›Pentoxifylline

›Improves erythrocyte flexibility and microcirculatory flow

›400 mg PO three times daily

›Tadalafil

›PDE5 inhibitor with vasodilatory effect

›May be superior to corticosteroids for primary pernio

›10 to 20 mg daily

Superinfection treatment

›Wound care for ulcerated or blistered lesions

›Gentle cleansing and non-adherent dressings

›Avoid rupturing intact bullae

›Topical antiseptic for open lesions

›Topical antibiotic for infected erosions

›Mupirocin 2% ointment applied three times daily

›Bacitracin ointment as alternative

›Systemic antibiotics for cellulitis complication

›Cephalexin 500 mg PO four times daily for 5 to 7 days

›Covers Staphylococcus and Streptococcus species

›First-line for mild to moderate cellulitis

›Trimethoprim-sulfamethoxazole DS one tablet PO twice daily

›If MRSA skin infection concern

›Renal dose adjustment as needed

09Special Populations/sp79

Pregnancy

›Pregnancy-specific considerations

›Increased cold sensitivity due to peripheral vasomotor changes

›Altered thermoregulatory physiology

›Vasoconstriction as normal response to cold may be accentuated

›Conservative management preferred

›Passive rewarming, elevation, protective clothing

›Smoking cessation strongly recommended

›Drug safety in pregnancy

›Nifedipine

›FDA category C (former classification); use with caution

›Actually used in obstetrics for tocolysis and preterm labor

›Short-term low-dose use for severe symptoms may be acceptable

›Discuss risk-benefit with obstetrics team

›Avoid or use with caution

›NSAIDs: avoid in third trimester (ductal constriction risk)

›Amitriptyline: limited data, avoid in first trimester if possible

›Hydroxychloroquine: may be continued if patient on it for lupus

›Acetaminophen preferred analgesic

›500 to 1000 mg PO every 4 to 6 hours

›Safe in all trimesters at recommended doses

›Secondary pernio and pregnancy

›SLE in pregnancy requires obstetric rheumatology co-management

›Higher risk of flare

›Fetal and maternal monitoring

›COVID-19 associated pernio in pregnancy

›Obstetric involvement for COVID-19 management

›Chilblain-like lesions typically self-limited

Geriatric

›Atypical presentation in older adults

›Increased risk of secondary pernio

›Prevalence of autoimmune and hematologic disease higher with age

›Atypical demographics (older male) warrant secondary workup

›Comorbidities complicating management

›Peripheral arterial disease may coexist

›Pulse examination critical to exclude vascular emergency

›Drug considerations in older adults

›Nifedipine

›Higher hypotension risk

›Fall risk from vasodilation

›Start at lower dose (20 mg daily) and titrate slowly

›Monitor orthostatic blood pressure

›Amitriptyline

›Avoid due to high anticholinergic burden (Beers Criteria)

›Prefer gabapentin or topical agents for neuropathic pain

›NSAIDs

›Avoid prolonged use due to renal impairment risk and GI bleeding

›Acetaminophen preferred analgesic

›Wound healing impairment

›Slower resolution of ulcerated lesions

›Higher superinfection risk

›More frequent wound care follow-up needed

›Nutritional status impacts healing

›Adequate protein and caloric intake

›Vitamin C and zinc repletion if deficient

Pediatrics

›Epidemiology in children

›Chilblains occurs in children and adolescents

›Anorexia nervosa in adolescents is a specific risk factor

›Low BMI contributes to cutaneous vasoreactivity

›Secondary causes in pediatrics

›SLE can present in adolescents

›Hematologic malignancy rare but possible

›COVID toes during pandemic more common in younger patients

›Pediatric treatment approach

›Conservative measures first line

›Passive rewarming and warm protective clothing

›Education of parents and child

›Nutritional assessment if eating disorder suspected

›Nifedipine in pediatric use

›Off-label use in children for severe or recurrent chilblains

›Dosing: 0.25 to 0.5 mg/kg per day divided in 2 to 3 doses

›Monitor blood pressure closely

›Anorexia nervosa management

›Multidisciplinary team involvement

›Chilblains may resolve with nutritional rehabilitation and weight restoration

›Eating disorder referral

›Child protection considerations

›Recurrent chilblains without adequate prevention

›Home environment assessment (inadequate heating)

›Social services involvement if neglect concern

›Housing vulnerability in homeless youth

10Background/b71

Epidemiology

›Incidence and prevalence

›Uncommon condition; exact incidence not well established

›Predominantly affects young women (79% female in Mayo series)

›Mean age of onset approximately 38 years

›Seasonal variation

›Peak incidence in fall and winter months

›May increase with climate variability in cold-humid regions

›COVID-19 pandemic surge

›Marked increase in pernio-like acral lesions during SARS-CoV-2 pandemic

›Pandemic cohorts show different demographics including younger patients

›Secondary pernio burden

›Underlying conditions in 3% to 11% of pernio series

›Hematologic malignancy in approximately 3% of cases (Mayo series)

›SLE and connective tissue disease more common secondary cause

›Recurrence

›Chronic pernio recurs with each cold season

›Primary pernio may resolve permanently with lifestyle modification

Pathophysiology

›Core mechanism

›Abnormal vasospastic response to nonfreezing cold and damp exposure

›Sustained vasoconstriction of arterioles and venules in acral skin

›Subsequent reactive vasodilation causes inflammatory cascade

›Hypersensitivity of dermal vessels

›Low BMI associated with increased cutaneous vasoreactivity

›Hormonal influences may explain female predominance

›Inflammatory response

›Lymphocytic perivasculitis

›Superficial and deep perivascular lymphocytic infiltrate on histology

›Dermal edema, necrotic keratinocytes, perieccrine inflammation

›Endothelialitis and microthromboses (especially COVID-associated)

›Interferon-alpha upregulation in COVID toes

›Granular C3 and IgM deposition in vessel walls on immunofluorescence

›Secondary pernio mechanisms

›SLE: immune complex deposition and complement activation

›Lupus band test may be positive on direct immunofluorescence

›Anti-dsDNA and complement consumption markers

›Antiphospholipid syndrome: thrombotic microangiopathy

›Lupus anticoagulant and anticardiolipin antibody-mediated

›Thrombotic occlusion contributes to ischemic changes

›Cryoproteins: cold-precipitated proteins occlude vessels

›Cryoglobulins and cold agglutinins cause microvascular occlusion

›Reversible with rewarming

Therapeutic Considerations

›Evidence base for treatment

›Conservative therapy produces complete response in approximately 82% of patients

›Passive rewarming, protection, smoking cessation most effective interventions

›Primary pernio typically resolves within 1 to 3 weeks

›Nifedipine evidence

›Older RCT by Rustin 1989 demonstrated benefit for pain reduction and healing

›Newer RCT by Souwer 2016 found no superiority over placebo for chronic chilblains

›Net clinical recommendation: reasonable to offer for moderate to severe or recurrent cases when benefits outweigh uncertain evidence

›Emerging evidence for secondary pernio management

›Tadalafil and fluoxetine show promise with limited study

›Hydroxychloroquine established for chilblain lupus

›Prevention strategy

›Protective clothing and footwear

›Insulated, moisture-wicking socks

›Waterproof footwear in wet conditions

›Avoid tight footwear that restricts circulation

›Lifestyle modification

›Smoking cessation primary recommendation

›Adequate caloric intake and healthy body weight

›Minimize prolonged cold-wet exposure

›Prophylactic vasodilator therapy for recurrent primary pernio

›Seasonal prophylaxis with nifedipine in high-frequency recurrence

›Begin prior to cold season onset

›Prognosis

›Primary pernio: excellent prognosis with appropriate management

›Resolution expected within 1 to 3 weeks

›Recurrence with each cold season is common

›Secondary pernio prognosis tied to underlying disease

›Chilblain lupus may follow relapsing-remitting course

›Hematologic malignancy prognosis dependent on type and stage

11Patient Discharge Instructions/pdi38

copy discharge instructions

›What are chilblains

›Chilblains (pernio) are small, itchy, painful inflammatory spots on the skin

›Caused by an abnormal reaction to cold and damp weather

›Not frostbite — skin does not freeze

›Most cases heal completely within 1 to 3 weeks

›Affected areas

›Typically toes and fingers

›Can also affect ears, nose, or shins

›Home care instructions

›Warming and skin care

›Warm the affected area slowly — avoid sudden heat (hot water bottles, heating pads directly on skin)

›Keep skin clean, dry, and covered

›Elevate affected feet or hands to reduce swelling

›Medications at home

›Take pain medicine as prescribed (ibuprofen or acetaminophen)

›Apply prescribed topical cream to affected areas as directed

›Take any prescribed blood pressure or other medications exactly as directed

›Prevention

›Wear warm, insulated, waterproof socks, gloves, and footwear in cold or wet weather

›Avoid tight footwear that restricts blood flow

›Stay warm and dry — limit time outdoors in cold, wet conditions

›Stop smoking — smoking makes chilblains worse by reducing blood flow

›Maintain healthy nutrition and body weight

›What to expect

›Healing timeline

›Most chilblains heal within 1 to 3 weeks with proper care

›Itching and burning may worsen briefly when skin warms up — this is normal

12References/r37

Guidelines and key sources

›Primary clinical references

›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 Clinic Proceedings. 2014

›PMID 24485134

›Foundational epidemiologic and diagnostic reference

›Rustin MH, Newton JA, Smith NP, Dowd PM. The Treatment of Chilblains With Nifedipine. British Journal of Dermatology. 1989

›PMID 2647123

›Older RCT supporting nifedipine efficacy

›Souwer IH, Bor JH, Smits P, Lagro-Janssen AL. Nifedipine vs Placebo for Treatment of Chronic Chilblains: A Randomized Controlled Trial. Annals of Family Medicine. 2016

›PMID 27621162

›Newer RCT showing no superiority of nifedipine over placebo

›Cold injury and wilderness medicine

›Zafren K et al. Prevention and Treatment of Nonfreezing Cold Injuries and Warm Water Immersion Tissue Injuries: A Supplement to the Wilderness Medical Society Clinical Practice Guidelines. Wilderness and Environmental Medicine. 2023

›Comprehensive nonfreezing cold injury management reference

›Conservative rewarming and supportive care protocols

›CDC Yellow Book. Heat and Cold Illness in Travelers. Howard D. Backer and Luanne Freer. 2025

›Traveler context cold injury classification and management

›COVID-19 associated pernio

›Hubiche T et al. Clinical, Laboratory, and Interferon-Alpha Response Characteristics of Patients With Chilblain-like Lesions During the COVID-19 Pandemic. JAMA Dermatology. 2021

›Pathophysiology and interferon-alpha mechanism

›McCleskey PE et al. Epidemiologic Analysis of Chilblains Cohorts Before and During the COVID-19 Pandemic. JAMA Dermatology. 2021

›Pandemic surge epidemiology

›Cappel MA, Cappel JA, Wetter DA. Pernio (Chilblains), SARS-CoV-2, and COVID Toes Unified Through Cutaneous and Systemic Mechanisms. Mayo Clinic Proceedings. 2021

›PMID 33714595

›Unifying mechanistic framework for COVID toes

›Secondary pernio and autoimmune references

›Sharifzadeh A, Smith GP. An Evidence-Based Review of Perniosis (Chilblains): Therapeutic Strategies and Integration With Raynaud's Syndrome Management. International Journal of Dermatology. 2025

›PMID 40272049

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Reviewed by SymptomDx Medical Team · Last reviewed August 18, 2026

SymptomDx is an educational tool for medical professionals. It does not replace clinical judgment. Verify all clinical data and drug dosages with authoritative sources.