Decreased lymphatic vessel counts in patients with systemic sclerosis: association with fingertip ulcers.
OBJECTIVE
Systemic sclerosis (SSc) is a connective tissue disease that is characterized by microvascular disease and tissue fibrosis. Progressive loss and irregular architecture of the small blood vessels are well characterized, but the potential involvement of the lymphatic vessel system has not been analyzed directly in SSc. This study was undertaken to assess whether the lymphatic vascular system is affected in SSc, and whether changes to the lymphatic vessels are associated with dystrophic changes and tissue damage in patients with SSc.


METHODS
Lymphatic endothelial cells in skin biopsy samples from patients with SSc and age- and sex-matched healthy volunteers were identified by staining for podoplanin and prox-1, both of which are specifically expressed in lymphatic endothelial cells but not in blood vascular endothelial cells. CD31 was used as a pan-endothelial cell marker. Statistical analyses were performed using Kruskal-Wallis, Mann-Whitney U, and Spearman's rank correlation tests.


RESULTS
The numbers of podoplanin- and prox-1-positive lymphatic vessels were significantly reduced in patients with SSc as compared with healthy individuals. The number of podoplanin-positive lymphatic precollector vessels was significantly lower in SSc patients with fingertip ulcers than in SSc patients without ulcers. Moreover, the number of lymphatic vessels correlated inversely with the number of fingertip ulcers at the time of biopsy and with the number of fingertip ulcers per year. The inverse correlation between lymphatic precollector vessel counts and fingertip ulcers remained significant after statistical adjustment for the blood vessel count, age, and modified Rodnan skin thickness score.


CONCLUSIONS
These results demonstrate a severe reduction in the number of lymphatic capillaries and lymphatic precollector vessels in patients with SSc. Patients with decreased lymphatic vessel counts may be at particularly high risk of developing fingertip ulcers.
University of Erlangen-Nuremberg, Erlangen, Germany.
Alfiya
A
Akhmetshina
Jürgen
J
Beer
Karin
K
Zwerina
Matthias
M
Englbrecht
Katrin
K
Palumbo
Clara
C
Dees
Nicole
N
Reich
Jochen
J
Zwerina
Gabriella
G
Szucs
Johannes
J
Gusinde
Tatiana
T
Nevskaya
Oliver
O
Distler
Dontscho
D
Kerjaschki
Georg
G
Schett
Jörg H W
JH
Distler
D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005385:Fingers / Q000473:pathology*; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D008206:Lymphatic Diseases / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology; D042601:Lymphatic Vessels / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D015995:Prevalence; D012595:Scleroderma, Systemic / Q000453:epidemiology / Q000473:pathology*; D012883:Skin Ulcer / Q000453:epidemiology / Q000473:pathology*; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D055815:Young Adult; D000098551:Prospero-Related Homeobox 1 Protein; D000098853:Podoplanin
D018398:Homeodomain Proteins; D008562:Membrane Glycoproteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein; C117468:PDPN protein, human; D000098853:Podoplanin