Nailfold capillary abnormalities in sclerodermatous chronic GVHD

Abstract

Chronic GVHD (cGVHD) complicating allo-SCT commonly presents as sclerotic skin changes resembling systemic sclerosis (SSc), suggesting a common pathophysiological pathway. Damage to capillaries is considered an early event in the pathogenesis of SSc, and is associated with characteristic nailfold capillary abnormalities. Whether such nailfold capillary abnormalities occur in sclerodermatous cGVHD is unknown. Nailfold videocapillaroscopy (NVC) was used to evaluate capillary morphology, density and loop dimensions in 14 patients with sclerodermatous cGVHD, 14 sex-and age-matched SSc patients, and 14 healthy controls. It was shown that none of the cGVHD patients and controls, whereas all SSc patients showed severe capillary abnormalities. cGVHD patients and controls showed no differences in capillary density (9.05 vs 9.16 loops/mm, respectively, P ¼ 0.84), and capillary loop dimensions (total loop width 44.36 vs 45.56 mm, respectively, P ¼ 0.84). Compared with cGVHD patients, SSc patients had a reduced capillary density (9.05 vs 5.25 loops/mm, respectively, Po0.001), and an increase in capillary loop dimensions (total loop width 44.36 vs 99.97 mm, respectively, P ¼ o0.001). In conclusion sclerodermatous cGVHD patients do not show the characteristic microvascular abnormalities seen in SSc, suggesting that capillary damage does not contribute to the pathophysiology of sclerodermatous cGVHD, and making NVC unsuitable for early identification.

NIH Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: II. The 2014 Pathology Working Group Report

“…They further showed that the endothelial microvasculature in chronic GVHD did not have the reduced VE cadherin and vWF expression observed in capillaries from patients with systemic sclerosis. Two related studies using capillaroscopy on nailfold capillaries confirmed the findings of Fleming et al that patients with PSS, but not chronic GVHD, had both morphologically abnormal capillaries and reduced density [100, 101]. …”

Optical coherence tomography angiography of normal skin and inflammatory dermatologic conditions

“…Cutaneous cGvHD occurs in approximately half of patients who undergo allogeneic hematopoietic stem cell transplantation [34] and is typically assessed using histopathology [35,36]. Non-invasive imaging modalities, such as capillaroscopy, have been used to investigate cutaneous GvHD, with conflicting results [37,38] deeming it unsuitable [39]. High frequency ultrasound technology has also been used, but results were mixed for skin thickness measurements [40,41].…”

“…Cutaneous manifestations of systemic sclerosis (SS or scleroderma) are commonly associated with microvascular changes in the skin, previously visualized with capillaroscopy [45,46]. Microvascular injury is thought to precede the development of fibrotic tissue in SS [39]. Figure 7 compares the proximal nail folds of a healthy individual and a patient with SS.…”

Animal Models of Systemic Sclerosis

“…The fibrosis of the skin and internal organs observed in mice with Scl-GVHD results from the action of TGF-, PDGF, CTGF, FGF-1, EGF, and VEGF [129][130][131][132]. A study using nailfold capillaroscopy revealed that patients with Scl-GVHD present symptoms of vasculopathy, but to date, no data has been reported on mice [133]. With regards to therapeutics, several immunomodulatory drugs have been tested in these mice.…”