Pernio

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 disease. Note the image below.

A 63-year-old man with pernio presenting as acral violaceous plaques with bullae.

Pernio is due to an abnormal vascular response to cold exposure,[1] 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.[2] The response of pernio to vasodilator drugs varies. Keeping acral areas warm and dry best prevents pernio.

The direct cause of pernio is cold exposure; specifically, exposure to both mild nonfreezing cold and humidity seems to be required.[3, 4] Chronic pernio may be secondary to various systemic diseases as follows:

• Chronic myelomonocytic leukemia[5]

• Anorexia nervosa[6] : Low body mass index may predispose to pernio.[3, 7]

• Dysproteinemias

• Macroglobulinemia

• Cryoglobulinemia, cryofibrinogenemia, cold agglutinins

• Antiphospholipid antibody syndrome

• Raynaud disease[8]

• Celiac disease[9]

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[10, 11] : 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.[12]

• Posttraumatic unilateral perniosis[13]

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.[14]

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.

Erythematous macules on distal toes of a 6-month-old girl with pernio.

Prognosis is good. Recurrences may be observed annually with onset of cold weather.[7] 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.

Avoid exposure to cold.

Keep extremities warm and dry.

Cease smoking.

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.

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.

Close-up of erythematous macules and plaques on distal plantar toes.

Close-up of great toe bulla.

Pernio lesions that blister may become secondarily infected.

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.

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. There is variable epidermal spongiosis or necrosis. Intense papillary dermal edema is present. A superficial and deep perivascular lymphocytic infiltrate is seen, with the described "fluffy edema" of vessel walls. Lymphocytic vasculitis may be present.

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.[15]

Avoidance of nicotine may help alleviate pernio.[4]

Consult a dermatologist for diagnosis and evaluation of associated disease.

Thin body habitus may be associated with heightened cutaneous vasoreactivity; the healthcare provider needs to be aware of this population at risk.

Prophylactic warming of acral areas with minimization of cold exposure may prevent disease recurrence.

Avoid exposure to cold.

Cease smoking.

The use of topical and systemic steroids, vasodilators,[9, 16, 17, 18] 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.

Class Summary

Peripheral arterial vasodilators may be effective in the treatment and prevention of pernio.

Nifedipine (Procardia)

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.