Cutaneous ulceration is a well-established manifestation of antiphospholipid syndrome (APLS) and is often painful for patients and difficult to control despite appropriate anticoagulation therapy. The immunomodulatory agent hydroxychloroquine (HCQ) has been known to exert anti-thrombotic effects in APLS through down-regulation of several pro-inflammatory pathways associated with endothelial activation. We observed two cases of APLS, one primary (occurring without a diagnosed connective tissue disorder) and one secondary, where commencement of hydroxychloroquine led to marked improvement in previously poorly controlled cutaneous ulcers.
Clinical cases were reviewed retrospectively through the electronic medical record. Both patients had been diagnosed with anti-phospholipid syndrome without an associated connective tissue disease diagnosis. Both were commenced on a trial of HCQ 200 mg daily, and comparison was made before and after this trial in terms of ulcer size, appearance, and associated symptoms. Clinical photos were utilised with verbal permission from each patient. Ongoing therapeutic anticoagulation was continued for both patients throughout this period.
Patient A: A 65-year-old female developed two adjacent ulcers at the left breast, 7 years post mastectomy and localized radiotherapy at the same site for breast carcinoma in situ. Breast MRI performed at this time demonstrated fat necrosis with surrounding area of enhancing tissue in this region. Core biopsy revealed a sclerotic fibrotic process compatible with post-radiation morphea. She had previously trialed multiple courses of oral antibiotics (cephalexin, clindamycin, augmentin), which did not elicit any meaningful improvement. These ulcers persisted for approximately 6 months. After a trial of 200 mg daily HCQ, they began to improve from 3 weeks, with reduced nipple retraction, ulcer depth, and extent of surrounding inflammation. A repeat breast MRI demonstrated reduced enhancement surrounding the left breast. She remained on a therapeutic dose of warfarin (International Normalised Ratio 2.2 to 3.0) throughout this period.
A 46-year-old lady presented with recurrent left lower limb ulcers over approximately 2 years, which were painful and would frequently wake her at night. Previous biopsy demonstrated nil malignant features. On examination, there were separate 3 x 2-cm and 1 x 2-cm ulcers along the medial left lower leg with irregular borders, with surrounding features of thrombophlebitis. After a trial of HCQ, we observed a reduction in pain and improvement in healing of these ulcers from 2 months. Anticoagulation was with therapeutic low-molecular-weight heparin.
Both patients demonstrated a significant reduction in extent of cutaneous ulceration, as well as associated symptoms, as early as 3 weeks after commencement of HCQ. At the time of the HCQ trial, neither patient had been diagnosed with an associated connective tissue disease (SLE) for which HCQ is typically indicated. This suggests that HCQ may exert beneficial effects in both primary and secondary APLS, potentially as an adjunct antithrombotic agent.
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