Increased angiogenesis and enhanced bone formation in patients with IgM monoclonal gammopathy and urticarial skin rash: new insight into the biology of Schnitzler syndrome.
Schnitzler syndrome is a rare plasma cell disorder the pathogenesis of which is still not fully understood. We evaluated the circulating levels of four major angiogenic cytokines (VEGF, angiogenin, angiopoietin-1 and angiopoietin-2) and six bone remodeling markers (sRANKL, osteoprotegerin, dickkopf-1, CTX, osteocalcin and bone-specific alkaline phosphatase-bALP) in 13 patients with Schnitzler syndrome. At diagnosis, patients had elevated angiogenic cytokines. The mean VEGF levels were almost 3.5-fold higher in Schnitzler syndrome compared to controls, while 10 of 13 patients had higher VEGF than the upper control value. Successful treatment led to a significant reduction in VEGF. Patients with Schnitzler syndrome had increased bone formation (high bALP, osteocalcin and osteoprotegerin) which was not balanced by an increase in bone resorption (normal CTX and sRANKL). These data support a role for VEGF as a new minor criterion in the diagnosis and follow up of Schnitzler syndrome, while the uncoupling of bone remodeling in favor of bone formation justifies the presence of bone densification.
Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece. eterpos@med.uoa.gr/eterpos@hotmail.com
Evangelos
E
Terpos
Bouchra
B
Asli
Dimitrios
D
Christoulas
Jean-Claude
JC
Brouet
Efstathios
E
Kastritis
Michel
M
Rybojad
Djaouida
D
Bengoufa
Meletios A
MA
Dimopoulos
Jean Paul
JP
Fermand
D000328:Adult; D000368:Aged; D042501:Angiogenic Proteins / Q000097:blood*; D000943:Antigens, Differentiation / Q000097:blood*; D001862:Bone Resorption / Q000097:blood; D005260:Female; D006801:Humans; D007075:Immunoglobulin M; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D010012:Osteogenesis; D019873:Schnitzler Syndrome / Q000097:blood* / Q000150:complications / Q000473:pathology; D014581:Urticaria / Q000097:blood* / Q000150:complications / Q000473:pathology
D042501:Angiogenic Proteins; D000943:Antigens, Differentiation; D007075:Immunoglobulin M