Practice Essentials
Pernio is an inflammatory skin condition presenting after exposure to cold as pruritic and/or painful erythematous-to-violaceous acral lesions. Pernio may be idiopathic or secondary to an underlying condition such as immune-mediated inflammatory disorders (IMIDs) with systemic lupus erythematosus (SLE) the most common.[1]
Pernio-like acral lesions in patients with COVID-19 infection (dubbed COVID toes/fingers) is the most common cutaneous manifestation of COVID-19.[2] It usually appears as a later symptom (75%) and is often encountered in children and young adults with milder or asymptomatic COVID-19 infection.[3]
Note the image below.
View Image | A 63-year-old man with pernio presenting as acral violaceous plaques with bullae. |
Pernio lesions can appear on 3% to 12% of the skin, most commonly on the hands, fingers, feet, and toes. There are over twenty clinical symptoms pernio that have been reported; papules, nodules, and itching are the most common.[4]
Pernio can often be diagnosed on the basis of clinical findings. Biopsy may be indicated to rule out other inflammatory processes in difficult chronic cases. Punch biopsy is adequate. The most common histologic findings are perivascular lymphocytic infiltrate (81% of patients), basal epidermal-cell layer vacuolation (67%), papillary dermal edema (66%), and perieccrine lymphocytic infiltrate (57%).[4]
Treatment of idiopathic pernio includes avoidance of exposure to cold, smoking cessation, calcium-channel blockers, and topical steroids.[5] Secondary pernio due to SLE (Chilblain lupus erythematosus [CHLE]) is treated with corticosteroids, immunosuppressive agents, and calcium-channel blockers. Refractory cases of CHLE have been successfully treated with anifrolumab, a monoclonal antibody.[6]
To prevent recurrence, patients should be advised to avoid exposure to cold, keep extremities warm and dry and cease smoking. For patient education resources see, Cold Hands and Feet.
Pathophysiology
Pernio is due to an abnormal vascular response to cold exposure,[7] and it is most frequent when damp or humid conditions coincide. Minor trauma also may predispose the acral parts to symptomatic pernio lesions in otherwise appropriate weather conditions. Hyperhidrosis and low lody mass index are suggested associations.[8] The response of pernio to vasodilator drugs varies. Keeping acral areas warm and dry best prevents pernio.
Etiology
The direct cause of pernio is cold exposure; specifically, exposure to both mild nonfreezing cold and humidity seems to be required.[9, 10] Chronic pernio may be secondary to various systemic diseases as follows:
Chronic myelomonocytic leukemia[11]
Anorexia nervosa[12] : Low body mass index may predispose to pernio.[9, 13]
Dysproteinemias
Macroglobulinemia
Cryoglobulinemia, cryofibrinogenemia, cold agglutinins
Antiphospholipid antibody syndrome
Raynaud disease[14]
Celiac disease[15]
Variants include the following:
Kibes (equestrian cold panniculitis): Erythrocyanotic plaques occur on the upper lateral thighs of women who ride horses. Histology is characterized by an intense perivascular infiltrate extending into subcutaneous fat.
Chilblain lupus erythematosus (CHLE) [16, 17] : Violaceous "pernio" plaques appear prominent over dorsal interphalangeal joints, often with positive antinuclear antibody (ANA) or rheumatoid factor (RF). Histologic and immunofluorescent evidence of lupus is present in the skin lesions. Half of the patients have associated facial discoid lupus lesions, and 15% develop systemic lupus.
Drug-induced pernio: Sulindac-induced cases have been reported.[18]
Posttraumatic unilateral perniosis[19]
Epidemiology
Frequency
United States
The true incidence of pernio is unknown because pernio frequently is unrecognized or misdiagnosed.
International
Rates of pernio vary with climate. England, with its cool damp climate, has an annual incidence rate of pernio of 10%. A clustering of pernio cases has been reported from Hong Kong during January and February, with resolution of most cases within a few weeks when the weather warmed.[20]
Sex
Women are affected by pernio more frequently than men.
Age
Pernio is most frequent in young and middle-aged women and in children. Note the image below.
View Image | Erythematous macules on distal toes of a 6-month-old girl with pernio. |
Prognosis
Prognosis is good. Recurrences may be observed annually with onset of cold weather.[13] Long-term follow-up of patients with chronic recurrent pernio is advised because this may reveal connective-tissue disease (lupus erythematosus). Most cases of pernio resolve without any adverse reactions. Pernio lesions that blister may become secondarily infected.
History
Most patients with pernio present with a history of recurrent painful and/or pruritic, erythematous, violaceous papules or nodules on the fingers and/or toes. Most cases of pernio resolve within 2-3 weeks. Elicit a history of cold exposure or repeated episodes of cold exposure.
Thin body habitus may be associated with heightened cutaneous vasoreactivity; the healthcare provider needs to be aware of this population at risk.
Physical Examination
Pertinent findings in pernio are limited to the skin. Cutaneous pernio lesions present 12-24 hours after cold exposure as red or violaceous macules, papules, nodules, or plaques, which may form vesicles or ulcerate. Pernio lesions occur on acral areas, are associated with burning or pruritus, and last 1-3 weeks. Note the images below.
View Image | Close-up of erythematous macules and plaques on distal plantar toes. |
View Image | Close-up of great toe bulla. |
Laboratory Studies
The following laboratory tests may be needed:
CBC count and sedimentation rate: These should be obtained to rule out associated leukemia.
Antiphospholipid antibody panel: Review of patients presenting with pernio shows an increased incidence of antiphospholipid antibody syndrome.
Cryoglobulins, cryofibrinogen, and cold agglutinin testing: These generally are absent but should be considered as part of the laboratory evaluation in a patient with chronic pernio. Because of occasional false-negative cryoprecipitate screening results, consider hepatitis C antibody screening or even rheumatoid factor (RF) as a marker for cryoglobulinemia in select cases.
Antinuclear antibody (ANA): Pernio lesions can occur in the setting of lupus erythematosus.
Serum protein electrophoresis (SPEP) and quantitative immunoglobulins: Dysproteinemias and macroglobulinemia, causing increased serum viscosity, may be associated with pernio.
Histologic Findings
Pernio can often be diagnosed on the basis of clinical findings. Biopsy may be indicated to rule out other inflammatory processes in difficult chronic cases. Punch biopsy is adequate. The most common histologic findings are perivascular lymphocytic infiltrate (81% of patients), basal epidermal-cell layer vacuolation (67%), papillary dermal edema (66%), and perieccrine lymphocytic infiltrate (57%).[4]
Approach Considerations
Treatment of idiopathic pernio includes avoidance of exposure to cold, smoking cessation, calcium-channel blockers, and topical steroids.[5]
Chilblain lupus erythematosus (CHLE) is treated with corticosteroids, immunosuppressive agents, and calcium-channel blockers. Refractory cases of CHLE have been successfully treated with anifrolumab, a monoclonal antibody.[6]
Consultations
Consult a dermatologist for diagnosis and evaluation of associated disease.
Prevention
Prophylactic warming of acral areas, achieved by heat and appropriate clothing, best prevents pernio.
Ultraviolet light, given at the beginning of the cold, damp season, has been touted as preventing outbreaks of pernio in prone individuals. Pathogenesis was loosely based on damaging the minute vessels and minimizing their ability to vasoconstrict with subsequent cold exposure. However, in at least one double-blind study, ultraviolet therapy was of no value in prophylaxis of pernio.[23]
Avoidance of nicotine may help alleviate pernio.[10]
Medication Summary
The use of topical and systemic steroids, vasodilators,[15, 24, 25, 26] intravenous calcium followed by intramuscular vitamin K, and ultraviolet B radiation have been anecdotally reported in the literature. In most cases of pernio, the value of these agents is at best questionable.
Nifedipine (Procardia)
Clinical Context:
Nifedipine relaxes coronary smooth muscle and produces coronary vasodilation, which, in turn, improves myocardial oxygen delivery. Small studies have shown this drug to be effective in reducing symptoms associated with severe recurrent pernio. Nifedipine is currently considered the drug of choice.
Class Summary
Peripheral arterial vasodilators may be effective in the treatment and prevention of pernio.
Author
Michele S Maroon, MD, Program Director, Department of Dermatology, Geisinger Medical Center
Disclosure: Nothing to disclose.
Coauthor(s)
David Hensley, MD, Mullanax Dermatology Associates, Arlington Memorial Hospital
Disclosure: Nothing to disclose.
Specialty Editors
Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA
Disclosure: Nothing to disclose.
Lester F Libow, MD, Dermatopathologist, South Texas Dermatopathology Laboratory
Disclosure: Nothing to disclose.
Chief Editor
William D James, MD, Emeritus Professor, Department of Dermatology, University of Pennsylvania School of Medicine
Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier<br/>Served as a speaker for various universities, dermatology societies, and dermatology departments.
Additional Contributors
Craig A Elmets, MD, Professor and Chair, Department of Dermatology, Director, Chemoprevention Program Director, Comprehensive Cancer Center, UAB Skin Diseases Research Center, University of Alabama at Birmingham School of Medicine
Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: University of Alabama at Birmingham; University of Alabama Health Services Foundation<br/>Serve(d) as a speaker or a member of a speakers bureau for: Ferndale Laboratories<br/>Received research grant from: NIH, Veterans Administration, California Grape Assn<br/>Received consulting fee from Astellas for review panel membership; Received salary from Massachusetts Medical Society for employment; Received salary from UpToDate for employment. for: Astellas.
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