Chilblains in Southern California: two case reports and a review of the literature

Chilblains or perniosis is an acrally located eruption that occurs with exposure to cold. The lesions may be erythematous or purplish in color and may be either macular or papular. Chilblains may be primary or idiopathic, or secondary to an underlying connective tissue disease (CTD), monoclonal gammopathy or cryoglobulinemia. The differential diagnosis includes vasculitis, acrally located lesions of systemic lupus erythematosus (SLE), and emboli. A skin biopsy can help exclude these other diagnoses, but the histopathology of chilblains is nonspecific. The histopathologic findings include an inflammatory infiltrate usually extending through the dermis with associated edema, and may be concentrated in a perieccrine distribution. The epidermis may show necrotic keratinocytes. Cribier et al. studied biopsy specimens from patients with chilblains to determine if there are characteristic histopathologic features that distinguish primary chilblains from lupus erythematosus [1]. They concluded that it is not always possible to distinguish between idiopathic chilblains and lupus erythematosus based on histopathologic findings alone. However, lack of edema and the presence of vacuolation were more characteristic of lupus erythematosus [1].

We present two cases of chilblains from Southern California and a review of the literature. The first case is an example of secondary chilblains. The second case is an example of idiopathic chilblains.

Chilblains, or perniosis, manifests as cold-induced inflammatory cutaneous lesions. It can easily be mistaken for vasculitis or an embolic event; and, as illustrated by our two cases, can be idiopathic or a secondary phenomenon related to an underlying CTD, typically SLE. A form of familial lupus chilblains exists, associated with a TREX1 gene mutation, mostly in Asian populations [2‐4].

The exact pathogenesis of chilblains is unknown. The process is generally described as a vasculopathy whereby there is disruption of normal neurovascular responses to dermal temperature changes. It has been suggested that patients with chilblains have persistent or prolonged cold-induced vasoconstriction leading to hypoxemia and a subsequent secondary inflammatory reaction [5].

There are no pathognomonic histological findings for idiopathic chilblains, but many studies describe superficial and deep perivascular lymphocytic infiltrates, with vessel wall and papillary dermal edema [1, 5‐7]. It has been suggested that idiopathic chilblains may be distinguished from secondary lesions seen in lupus by the presence of spongiosis, perieccrine inflammation, and dermal edema [1] in idiopathic lesions, whereas vacuolation of basal cells is more commonly seen in lupus erythematosus lesions.

Idiopathic chilblains is frequently seen in cold, damp areas of Western Europe (air humidity appears to enhance air conductivity of cold); however, an increasing number of cases are being reported in coastal areas of North America [5]. Cases typically present during the cold season of late winter to early spring. Attacks can, however, be precipitated by other types of cold exposure. Cases have been reported with use of cold therapy systems, which are used after some orthopedic procedures [8]. Lesions are almost always seen within a few hours of exposure to nonfreezing, damp conditions. Typically, they manifest as painful erythematous or purple lesions with associated swelling or itching. Overlaying erosions, ulcerations, or blisters may also be seen. Chilblain lesions are typically present symmetrically on the hands and feet. Other locations include the ear, nose, thighs, and buttocks [5]. In general, a female predominance is seen and may be associated with a low body mass index, although lesions are not uncommonly observed in men and children. Female gender is strongly associated with underlying CTD, especially SLE. The results of laboratory evaluation of idiopathic chilblains are usually normal, although an elevated ESR has been observed in some cases [5].

Secondary chilblains can present as a cutaneous feature of many conditions such as lupus (most commonly), Behcet's disease, monoclonal gammopathy, cryoglobulinemia, chronic myelomonocytic leukemia, antiphospholipid syndrome, and other CTDs. There have even been cases of tumor necrosis factor inhibitor-induced lupus chilblains [7, 9]. Lesions present similarly to idiopathic chilblains, although persistence of lesions beyond the cold seasons is more common with secondary chilblains [10]. Pathogenesis is probably similar to that of idiopathic chilblains, involving an exaggerated vasoconstrictive response with subsequent hypoxemia and inflammation. However, hyperviscosity may play more of a role in the development of secondary lesions. Hypergammaglobulinemia and autoantibodies, frequently seen with CTD, may play a role in the development of these lesions, but their exact pathophysiological relevance is not known [11]. One epidemiologic study of chilblains suggests advanced age, female gender, persistence of the disorder beyond the cold season, hypergammaglobulinemia, and autoantibody positivity are suggestive of secondary chilblains [10].

The diagnosis can usually be made clinically by the appearance of typical lesions during the cold damp seasons. Idiopathic chilblains is, however, a diagnosis of exclusion, and an underlying CTD, or a mimic, such as vasculitis or cutaneous leukemia [12], must be considered. A thorough history and physical examination should be performed to evaluate for the presence of systemic disease. Initial laboratory evaluation should include: a complete blood count, ANA and antiphospholipid antibody profiles, cryoglobulins, and serum protein electrophoresis. Biopsy should be considered for treatment-resistant cases. Typical lesions in a person with a known CTD or Raynaud’s can help to make the diagnosis of secondary chilblains. Again, a biopsy may need to be considered for lesions resistant to warming measures because it is important to distinguish chilblains from vasculitis, which requires immunosuppressive therapy.

Treatment of chilblains is focused on keeping the affected area warm, and occasionally using vasodilator agents such as calcium-channel blockers. At least two small placebo-controlled studies showed rapid improvement of symptoms with use of extended-release nifedipine 20mg, taken three times daily [13, 14]. Calcium-channel blockers may also play a role in prevention of recurrent or chronic lesions [7, 11]. Regardless of therapy, symptoms generally resolve within days to months, although chronic, waxing and waning lesions can develop with persistent cold exposure. Secondary chilblains may have a more chronic course, and there have been cases of response to corticosteroids (systemic and topical) and mycophenolate mofetil [5, 11]. Data on the use of anti-malarial medications, such as hydroxychloroquine, for both idiopathic and secondary lesions are relatively limited. Results from small retrospective studies are conflicting [15]. Some studies suggest that while hydroxychloroquine is helpful for many symptoms of CTD, it is not necessarily helpful in treating chilblain lesions [5, 11].

In this series, we present two cases of chilblains seen in the winter months in Southern California. One case is purely idiopathic, whereas the other is more consistent with a secondary phenomenon related to the patient’s history of Raynaud’s and an underlying undifferentiated CTD. In both cases, lesions responded well to warming measures alone. This condition needs to be recognized even in typically warmer climates, and screening for an underlying systemic disease should be done, especially in treatment-resistant cases.

Written informed consent was obtained from the patients for publication of this case report and accompanying images. Copies of the written consents are available for review by the Editor-in-Chief of this journal.