Perniosis
Salient features
·
Cold-sensitive inflammatory disorder in which
erythrocyanotic discoloration of acral skin is accompanied by a sensation of
itching, burning or pain
·
Common trigger is exposure to cold, wet,
non-freezing conditions
·
Must be distinguished from chilblain lupus
and cold-sensitive blood dyscrasias
·
Nifedipine can be used to treat moderate to
severe pernio
Introduction
Perniosis is a benign localized
inflammatory lesion on the acral skin with erythema and swelling caused by abnormal (exaggerated) reaction to
cool temperatures (above freezing) and dampness in genetically susceptible
person, typically presenting during winter climate. Pernio
may be idiopathic or secondary to an underlying disease. In people predisposed by poor peripheral circulation, even moderate
exposure to cold may produce chilblains. Hyperhidrosis
and low body mass index are suggested associations.
Epidemiology
Women, children and the elderly
and persons with low body mass index are most commonly affected. Elderly patients
may have a prolonged course, while younger patients improve spontaneously.
Environmental
factors
Perniosis occurs in susceptible individuals during the
autumn or winter in a climate that is both cold and damp.
Spontaneous remission is common when spring arrives, and relapse is frequent during the
following winters. However, chilblains do not always occur at the time of
maximum cold.
Aetiology
The direct cause of
pernio is
persistent cold exposure; specifically, exposure to
both mild non freezing cold and humidity seems to be required. Chronic
pernio may be secondary to various systemic diseases as follows:
·
Chronic
myelomonocytic leukemia
·
Anorexia
nervosa : Low body mass index
may predispose to pernio.
·
Dysproteinemias
·
Macroglobulinemia
·
Cryoglobulinemia, cryofibrinogenemia,
cold agglutinins
·
Antiphospholipid
antibody syndrome
Pathophysiology
The
precise pathogenesis of pernio is unknown, but the condition is thought to
represent an abnormal inflammatory response to vascular ischemia caused by
prolonged vasoconstriction in the setting of extended cold exposure. In perniosis there is
a persistent cold-induced vasoconstriction of the deep cutaneous arterioles
with concomitant dilatation of the smaller, superficial vessels. This is in
contrast with normal subjects, in whom cold exposure induces cutaneous
vasoconstriction succeeded by vasodilatation, a homeostatic mechanism necessary
for the maintenance of reperfusion. In children, it may be
associated with cryoproteins.
Clinical features
Patients with
chilblains are often unaware of the cold injury when it is occurring, but later
burning, pain, itching, and redness call it to their attention. Pernio develop acutely with
single or multiple bluish red macules, oedematous papules, plaques or nodules, that
appear 12 to 24 hours after prolonged
exposure to cool, damp air, the color partially
or totally disappearing on pressure, and are decidedly cool to the touch.
Sometimes the extremities are clammy because of excessive sweating. In severe
cases, blistering and ulceration may be seen. Lesions are more common on the dorsal aspects of the digits.
Involvement of the feet is most common, followed by the hands. Lesions
are often symmetrically distributed on acral skin, in particular the distal toes and fingers, and less
often on the heels, nose, and ears. Overlying scale can also develop. Deep pernio may be seen on the thighs, calves, and
buttocks as blue-erythrocyanotic plaques. As long as the
damp/ cold exposure continues, new lesions will continue to appear. Each
lesion tends to undergo spontaneous resolution after 2–3 weeks but may become
chronic in elderly
people with venous stasis.
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: Chilblain LE (also
known as Hutchinson lupus) is a form of cutaneous LE that presents in a similar
way to idiopathic perniosis. Erythrocyanotic papules and plaques appear prominent over dorsal interphalangeal joints
of the fingers and toes, develop in cold weather and tend to persist, in some
cases becoming ulcerated, 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.
Pathology
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. Idiopathic perniosis is
characterized histologically by intense oedema of the papillary dermis
and by the presence of superficial and deep perivascular lymphocytic
infiltrates, with
peri-eccrine accentuation. The infiltrate is composed
predominantly of T lymphocytes. Necrotic keratinocytes and
lymphocytic vasculitis may also be present. Thickening of blood vessel walls
with intimal proliferation may lead to obliteration of the vascular lumen.
Prognosis
Prognosis is good. Recurrences may be
observed annually with onset of cold weather. 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 when steps are taken to prevent cold
exposure. Idiopathic chilblains are rarely associated with joint inflammation,
and the presence of arthritis should prompt consideration for multisystem
disease.
Investigations
All patients with perniosis should undergo a detailed
history, review of systems, and physical examination with or without a skin
biopsy based on the degree of clinical certainty. Laboratory workup should be
conducted only if the clinical presentations suggest a possible underlying systemic
disease. Pernio demonstrating a chronic course (continuous for at least 4 weeks
and, in some cases, 8 weeks or longer, or episodic in nature), persistence into
warm weather months, and onset in the elderly may be suggestive of an
associated connective tissue disease, haematological malignancy, or other
systemic condition.
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.
Treatment
The most
important point in management is prophylaxis through the use of adequate,
loose, insulating clothing and appropriate warm housing and workplace. The affected parts should be protected against further exposureto cold
and dampness. If the feet are affected, woolen socks should be worn at all
times during the cold months. Keep feet dry. Moisture enhances cold injury. For
perniosis of the hands, gloves are recommended. Use electrical or other hand
warmers. Tight garments, such as s gloves, stockings, and shoes, are especially
to be avoided in cases in which there is concomitant peripheral vascular
disease. Maintaining the blood
circulation by avoiding immobility is also helpful. Because patients are often not conscious of the cold exposure that
triggersthe lesions, appropriate dress must be stressed, even if patients say
they do not sense being cold. Since central cooling triggers peripheral
vasoconstriction, keeping the whole body (not just the affected extremity) warm
is critical. Heating pads may be used judiciously to warm the parts.
Once
chilblains occur, treatment is symptomatic with rest and warmth. Other
conservative measures include smoking cessation and application of mid potency
topical steroid twice daily until the lesions heal. Associated systemic
disease, if present, should be treated.
Second line
therapy of pernio consists of the addition of a calcium channel blocker, such
as nifedipine 20-60 mg daily or diltiazem 60-120mg three times daily. It
is effective in about 70% of patients, in both clearing existing pernio lesions and in
preventing the development of new lesions. This efficacy is due to the
vasodilatory effect of this medication. While mild symptoms of peripheral oedema
and hypotension may occur, these symptoms rarely require discontinuation of the
medication when used at low doses. Monitor blood pressure at the start of
treatment and at return visits.
Amlodipine
2.5–5 mg once daily may be used as an alternative calcium channel blocker. The
long half-life and consequent once daily dosing of this drug is beneficial when
chronic therapy is required.
Third line and
alternative management options include vasodilators such as nicotinamide, 500
mg three times a day, or dipyridamole, 25 mg three times a day, or the
phosphodiesterase inhibitor sildenafil, 50 mg twice daily, may be used to
improve circulation. Pentoxifylline 400mg bid or tid is probably the safest
approach. Topical minoxidil, topical 0.2% nitroglycerin and topical tacrolimus
are also used.
Systemic
corticoid therapy is useful in chilblain lupus erythematosus.
Preventing
chilblains
The following advice may help prevent
chilblains:
·
Stop smoking. Nicotine causes
the blood vessels to constrict (get narrower), which can make chilblains worse.
·
Avoid medicines that may
constrict blood vessels, such as caffeine and decongestants.
·
Keep active. This helps improve
your circulation.
·
Wear warm clothes and insulate
your hands, feet, and legs. Wearing long johns, long boots, tights, leg warmers
or long socks will help. If you get cold feet in bed, wear a pair of clean
socks.
·
Avoid tight shoes and boots as
these can restrict the circulation to toes and feet.
·
Moisturize your feet regularly.
This stops them from drying out and the skin cracking.
·
In cold weather, eat at least
one hot meal during the day. This will help warm your whole body.
·
Warm your shoes on the radiator
before you put them on. Make sure damp shoes are dry before wearing them.
·
Warm your hands before going
outdoors by soaking them in warm water for several minutes and drying them
thoroughly. Wear cotton-lined waterproof gloves if necessary.
·
Turn up the central heating.
Try to keep one room in the house warm and avoid drafts.
