Mediation of systemic vascular hyperpermeability in severe psoriasis by circulating vascular endothelial growth factor

Background: Severe forms of psoriasis can be complicated by systemic microvascular hyper-permeability. Vascular endothelial growth factor (VEGF) possesses potent vascular permeability activity. We suggest that VEGF enters the systemic circulation and acts on microvessels to mediate hyperpermeability. Objectives: To quantify renal microvascular permeability and circulating VEGF concentration in severe psoriasis, and to investigate the relationship between plasma VEGF concentration and skin and joint involvement. Design: Inception cohort studies of patients with generalized pustular psoriasis and plaque psoriasis. Setting: St John's Institute of Dermatology, London, England. Patients: Twenty-two patients (15 men and 7 women) with moderate and severe psoriasis were recruited (age range, 29-77 years; mean age, 47 years); 5 had generalized pustular psoriasis, 2 had erythrodermic psoriasis, and 15 had moderate-severe plaque psoriasis. An age- and sex-matched control group of 17 individuals (10 men and 7 women) was recruited (age range, 29-69 years; mean age, 42 years). Results: There was pathological proteinuria in patients with relapsing generalized pustular psoriasis, (4-fold increase in urinary protein excretion rate in relapse compared with remission). In patients with moderate and severe psoriasis, mean plasma VEGF concentration during relapse was approximately 2.5 times greater than during remission (mean VEGF(relapse)=257 pg/mL; mean VEGF(remission)=103 pg/mL; P<.01). There was a correlation between extent of skin involvement and plasma VEGF level (mean VEGF(severe) (psoriasis) = 365 pg/ml; mean VEGF(moderate psoriasis) = 149 pg/mL; P=.03). There was a correlation between presence of psoriatic arthritis and plasma VEGF level (mean relapse VEGF(arthritis)=277 pg/mL; mean relapse VEGF(nonarthritis),= 103.5 pg/mL; P=.03). Conclusions: Generalized pustular psoriasis is accompanied by pathological proteinuria and elevated plasma VEGF levels. Plasma VEGF concentration is significantly elevated in patients with extensive skin and joint involvement and may act on renal microvasculature to induce hyperpermeability.