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 hyperpermeability. 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.


OBJECTIVE
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.


METHODS
Inception cohort studies of patients with generalized pustular psoriasis and plaque psoriasis.


METHODS
St John's Institute of Dermatology, London, England.


METHODS
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.
Creamer
Daniel
D
St Johns Institute of Dermatology, St Thomas Hospital, King's College Hospital, London, England. daniel.creamer@kingshc.nhs.uk
Allen
Michael
M
Jaggar
Rhys
R
Stevens
Richard
R
Bicknell
Roy
R
Barker
Jonathan
J
D000328:Adult; D000368:Aged; D015535:Arthritis, Psoriatic / Q000175:diagnosis / Q000378:metabolism; D015415:Biomarkers; D016022:Case-Control Studies; D002463:Cell Membrane Permeability; D015331:Cohort Studies; D016228:Endothelial Growth Factors / Q000032:analysis* / Q000097:blood* / Q000652:urine*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008222:Lymphokines / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D011336:Probability; D011565:Psoriasis / Q000175:diagnosis / Q000378:metabolism*; D012016:Reference Values; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013582:Synovial Fluid / Q000378:metabolism; D016482:Urinalysis; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D015415:Biomarkers; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors