Efficacy of alprostadil in chilblain lupus erythematosus

Dear Editor, A 56-year-old woman presented with chronic pain in her digits. She had worked in the seafood frozen-packaging line of a food factory for many years. Physical examination revealed ulcerations on the pulps and knuckles of her digits, with hyperkeratosis and fissures [Figure 1a-d]. No similar lesions on toes were found. The lesions were worsened by exposure to a cold environment. Raynaud’s phenomenon and sclerodactyly were not observed. In addition, a patch of cicatricial alopecia was observed on the vertex of the scalp [Figure 1e]. Discoid lupus erythematosus was confirmed by skin biopsy.Figure 1: (a-d) Erythematous plaques with fissures and ulceration on the fingers and pulps of the digits. (e) A patch of cicatricial alopecia on the vertex of the scalp. (f and g) Bilateral hand magnetic resonance angiography showed patent distal radial arteries, ulnar to interdigital arteries, and postcontrast enhancement of soft tissue swelling over the 1st to 5th digits.Blood tests revealed high titers of anti-Ro/SSA antibodies (50.1 EliA U/mL) and low C4 levels (18.2 mg/dL). However, she tested negative for antinuclear antibodies (ANA), anticardiolipin antibodies, anti-Scl-70 antibodies, and anti-double-stranded DNA antibodies. The cryoglobulin and cold agglutinin tests were negative. A diagnosis of systemic lupus erythematosus (SLE) was not fulfilled. Bilateral hand magnetic resonance angiography showed patent distal radial arteries, ulnar to interdigital arteries, and postcontrast enhancement of soft-tissue swelling over the 1st to 5th digits [Figure 1f and g]. Based on her clinical symptoms and laboratory results, she was diagnosed with chilblain lupus erythematosus (CHLE). The proposed CHLE diagnostic criteria have not yet been validated, although the Mayo Clinic diagnostic criteria proposed by Su et al. include clinical presentation, laboratory findings, and histopathology.[1] She was treated with oral pentoxifylline and nifedipine for 5 months; however, only mild improvement was seen. We further administrated a 10-day regimen of intravenous alprostadil at a dose of 60 µg/day. Significant improvement in the digital ulcers was observed within 2 weeks [Figure 2a]. Laser Doppler flowmetry revealed increased microvascular perfusion in the digits of the left hand at 30°C and 44°C during the 8-week follow-up [Figure 2b].Figure 2: (a) The digital ulcers showed significant improvement within 2 weeks (left hand). (b) Laser Doppler flowmetry revealed an increase in microvascular perfusion in the middle digit of the left hand both at 30°C and 44°C after alprostadil treatment during an 8-week follow-up.CHLE is a rare form of cutaneous lupus erythematosus; based on previous studies, it coexists with SLE in 33%–88% of patients.[2,3] Moreover, SLE developed in these patients before or after the onset of CHLE.[2,3] CHLE lesions initially present as violaceous-erythematous papules and plaques on the toes, fingers, or face, and they worsen during exposure to cold stimuli or decreased temperature. As CHLE lesions progress, hyperkeratosis, ulceration, and dyspigmentation may occur. The antibody profile of CHLE is nonspecific.[4] Among patients with CHLE, 80% were ANA positive and 50% were anti-SSA positive, according to a retrospective study involving 30 patients.[3] The treatment for CHLE has not been standardized, although the protection from the cold is an integral part of its management. The current treatment options consist of topical or systemic corticosteroids, topical calcineurin inhibitors, antimalarials, or immunomodulators, such as mycophenolate mofetil, depending on the severity of the disease. Furthermore, calcium channel blockers are reportedly beneficial against vasoconstriction.[5] Prostaglandin E1, also known as alprostadil, has been used to treat peripheral circulatory insufficiency as it induces vasodilation and angiogenesis and inhibits platelet aggregation, leukocyte adhesion, and inflammation.[6,7] In the current study, alprostadil was the first used to treat digital ulcers in a patient with CHLE. Alprostadil (30 μg) was dissolved in 0.9% normal saline (500 mL) and administered intravenously over a 2-h period, twice daily for 10 days. Significant improvement in pain and ulceration was observed within 2 weeks. Laser Doppler flowmetry demonstrated increased microvascular perfusion of the digits during the 8-week follow-up period. Few studies have discussed CHLE, and this case report highlighted the efficacy of alprostadil in the treatment of CHLE. Further investigation and long-term follow-up will be conducted. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Data availability statement The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Financial support and sponsorship Nil. Conflicts of interest Prof. Chung-Hsing Chang, an editorial board member at Dermatologica Sinica, had no role in the peer review process of or decision to publish this article. The other authors declared no conflicts of interest in writing this paper.