A punch biopsy from one of the lesions on the feet showed subtle basal vacuolar interface inflammation on the epidermis and rare apoptotic keratinocytes. There was an underlying dermal lymphocytic inflammatory infiltrate around the vascular plexus. Dermal mucin appeared slightly increased. The histologic findings are consistent with pernio. He had a negative direct immunofluorescence study.
Dr. Catalina Matiz
Laboratory work-up showed an elevated antinuclear antibody (ANA) of 1:620; positive anticardiolipin IgM was at 15.2. A complete blood count showed no anemia or lymphopenia, he had normal complement C3 and C4 levels, normal urinalysis, negative cryoglobulins and cold agglutinins, and a normal protein electrophoresis.
Given the chronicity of his lesions, the lack of improvement with weather changes, the histopathologic findings of a vacuolar interface dermatitis and the positive ANA titer he was diagnosed with chilblain lupus.
Chilblain lupus erythematosus (CLE) is an uncommon form of chronic cutaneous lupus erythematosus that presents with tender pink to violaceous macules, papules, and/or nodules that sometimes can ulcerate and are present on the fingers, toes, and sometimes the nose and ears. The lesions are usually triggered by cold exposure.1 These patients also have clinical and laboratory findings consistent with lupus erythematosus.
Even though more studies are needed to clarify the clinical and histopathologic features of chilblain lupus, compared with idiopathic pernio, some authors suggest several characteristics: CLE lesions tend to persist in summer months, as occurred in our patient, and histopathologic evaluation usually shows vacuolar and interface inflammation on the basal cell layer and may also have a positive lupus band on direct immunofluorescence.2 About 20% of patient with CLE may later develop systemic lupus erythematosus.3
There is also a familial form of CLE which is usually inherited as an autosomal-dominant trait. Mutations in TREX1, SAMHD1, and STING have been described in these patients.4 Affected children present with skin lesions at a young age and those with TREX1 mutations are at a higher risk to develop systemic lupus erythematosus.
The differential diagnosis of chilblain lupus includes idiopathic pernio or pernio secondary to other conditions. Other conditions that are thought to be associated with pernio, besides lupus erythematosus, include infectious causes (hepatitis B, COVID-19 infection),5 autoimmune conditions, malignancy and hematologic disorders (paraproteinemia).6 In histopathology, pernio lesions present with dermal edema and superficial and deep lymphocytic infiltrate.
The pathogenesis of pernio is not fully understood but is thought be related to vasospasm with secondary poor perfusion and ischemia and type I interferon (INF1) immune response. A recent review of the published studies trying to explain the causality between COVID 19 and pernio-like lesions, from January 2020 to December 2020, speculate several possible mechanisms: an increase in the vasoconstrictive, prothrombotic, and proinflammatory effects of the angiotensin II pathway through activation of the ACE2 by the virus; COVID-19 triggers a robust INF1 immune response in predisposed patients; pernio as a sign of mild disease, may be explained by genetic and hormonal differences in the patients affected.7
Another condition that can be confused with CLE is Raynaud phenomenon, were patients present with white to purple to red patches on the fingers and toes after exposure to cold, but in comparison with pernio, the lesions improve within minutes to hours after rewarming. Secondary Raynaud phenomenon can be seen in patients with systemic lupus erythematosus and in patients with other connective tissue disorders. The skin lesions in our patient were persistent and were not triggered by cold exposure, making Raynaud phenomenon less likely. Children with vasculitis can present with painful red, violaceous, or necrotic lesions on the extremities, which can mimic pernio. Vasculitis lesions tend to be more purpuric and angulated, compared with pernio lesions, though in severe cases of pernio with ulceration it may be difficult to distinguish between the two entities and a skin biopsy may be needed.
Sweet syndrome, also known as acute febrile neutrophilic dermatosis, is a rare skin condition in which children present with edematous tender nodules on the hands and with less frequency in other parts of the body with associated fever, malaise, conjunctivitis, or joint pain and it is usually associated with infection or malignancy. Our patient denied any systemic symptoms and had no conjunctivitis nor arthritis.
Most patients with idiopathic pernio do not require a biopsy or further laboratory evaluation unless the lesions are atypical, chronic, or there is a suspected associated condition. The workup for patients with prolonged or atypical pernio-like lesions include a skin biopsy with direct immunofluorescence, ANA, complete blood count, complement levels, antiphospholipid antibodies, cold agglutinins, and cryoglobulins.
Treatment of mild CLE is with moderate- to high-potency topical corticosteroids. In those patients not responding to topical measures and keeping the extremities warm, the use of hydroxychloroquine has been reported to be beneficial in some patients as well as the use of calcium-channel blockers.
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.
References
1. Su WP et al. Cutis. 1994 Dec;54(6):395-9.
2. Boada A et al. Am J Dermatopathol. 2010 Feb;32(1):19-23.
3. Patel et al. SBMJ Case Rep. 2013;2013:bcr2013201165.
4. Genes Yi et al. BMC. 2020 Apr 15;18(1):32.
5. Battesti G et al. J Am Acad Dermatol. 2020;83(4):1219-22.
6. Cappel JA et al. Mayo Clin Proc. 2014 Feb;89(2):207-15.
7. Cappel MA et al. Mayo Clin Proc. 2021;96(4):989-1005.