Systematic administration of chloroquine in discoid lupus erythematosus reduces skin lesions via inhibition of angiogenesis

Abstract

Background. Discoid lupus erythematosus (DLE) is a chronic cutaneous form of lupus erythematosus, characterized by inflammation and scarring skin lesions, with lymphocyte infiltration and vasodilation. Antimalarial drugs have beneficial therapeutic effects in DLE, partially resulting from their immunomodulating and photoprotective properties. The possible influence of these drugs on angiogenesis has not been previously evaluated. Aims. To investigate the impact of chloroquine (CQ) treatment on the expression of vascular endothelial growth factor (VEGF, a major regulator of angiogenesis) and CD34 (a transmembrane glycoprotein expressed on endothelial cells and involved in tethering lymphocytes) in patients with DLE. Methods. A 3-mm skin biopsy was taken from typical skin lesions in 10 people with DLE. Another biopsy was taken from the same area after 3 months of treatment with CQ (250 mg ⁄ day). Skin sections were stained with monoclonal antibodies directed against VEGF and CD34. The intensity of epidermal VEGF expression, and the number and area of CD34-positive dermal blood vessels were assessed. Results. CQ treatment induced a reduction in epidermal VEGF expression. It also resulted in a significant decrease in the median number of CD34+ dermal blood vessels (from 219 to 125 vessels per mm 2 ). Furthermore the median vessel area was significantly lowered from 9.76 · 10 6 to 6.92 · 10 6 mm 2 per mm 2 of the dermis. Conclusions. These results indicate that one beneficial effect of CQ treatment in DLE may be due to its antiangiogenic properties.

Assessment of chloroquine as a modulator of immune activation to improve CD4 recovery in immune nonresponding HIV‐infected patients receiving antiretroviral therapy

“…However, its role in HIV infection remains controversial. In the present study, CQ was administrated at a single oral dose of 250 mg once daily for 24 weeks, a similar dosage to that used in autoimmune diseases [13][14][15]. In our study population, CQ was well tolerated and no grade 3 or 4 side effects were observed during the study.…”

Impairment of Angiogenesis in Patients with Granuloma Annulare and Necrobiosis Lipoidica

“…VEGF is a multifunctional peptide that is capable of inducing endothelial cell proliferation and angiogenesis both in vivo and in vitro. VEGF induces microvascular hyperpermeability, and its angiogenic effect plays a role in a variety of physiological and pathological conditions-including wound healing, blister formation, and skin neoplasia [15][16][17][18]. The raised plasma levels of VEGF have been noted not only in vascular tumors of the skin (such as Kaposi's sarcoma) but also in chronic inflammatory and autoimmune diseases.…”

Experience with the use of hydroxychloroquine for the treatment of lupus erythematosus

“…Chloroquine and HCQ possess activity that inhibits angiogenesis, and there is a report of a decrease in vessels in the dermis. 9 HCQ was effective against erythema and telangiectasia, but that may have reflected the fact that there was very little change in the atrophy or scarring. The considerable improvement in the telangiectasia in case 3 may have been attributable to the activity of HCQ that inhibits angiogenesis.…”