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Systemic sclerosis (SSc) and mixed connective tissue disease (MCTD) are both associated with microvascular pathology. The most striking early clinical manifestation is Raynaud phenomenon (RP), which is only partly caused by functional narrowing of small vessels. Moreover, alteration of endothelial function1 and impairment of endothelial progenitor cell function in these patients have been previously described.2 This may have an important impact on capillary pathology. The resulting morphological changes can be observed by nailfold capillaroscopy (NFC). Haemorrhages, giant capillaries and avascular regions are typical findings that cannot only be detected by NFC, but also, at least in part, with moderate to substantial reliability using simpler methods such as ophthalmoscopes or dermatoscopes.3 These findings may change with disease duration. Early in the disease course haemorrhages and giant capillaries are prevalent; later, capillaries begin to disappear and avascular regions become apparent.4 5
Autologous haematopoietic stem cell transplantation (HSCT) is an intense immunosuppressive procedure and seems to be of benefit in patients with SSc.6 Whether HSCT is able to halt natural progression of capillary pathology in SSc and MCTD, or could lead to a reversal or normalisation of capillary pathology is unknown. A combined therapy with iloprost and cyclosporine has been shown to positively influence NFC over a 1-year period.7 We report on sequential NFC in two patients who underwent HSCT for SSc and MCTD.
Patient 1 (fig 1A), a male who was 31 years old at diagnosis, experienced the first symptoms of diffuse SSc in the beginning of 2005. At diagnosis he had skin and lung involvement. In January 2007, 3 months after mobilisation, HSCT was performed. Patient 2 (fig 1B) was a 29-year-old female suffering from MCTD diagnosed in 1999 and associated with pulmonary arterial hypertension and arthritis. She had previous ineffective treatments with azathioprine, cyclosporine and cyclophosphamide. HSCT was performed in April 2007, with mobilisation 3 months earlier. Both suffered from severe RP. Mobilisation of stem cells was performed using cyclophosphamide, 4 g/m2, followed by granulocyte colony stimulating factor, 5 μg/kg bodyweight daily subcutaneously until granulocyte counts normalised. Stem cells were then harvested and positively selected for CD34+ cells. Conditioning consisted of 200 mg/kg bodyweight cyclophosphamide and 7.5 mg/kg bodyweight rabbit anti-thymocyte globulin followed by re-infusion of at least 2×106 stem cells/kg bodyweight.
Both patients underwent NFC before mobilisation (fig 1, A1 and B1), after mobilisation (fig 1, A2 and B2) and 1 month (fig 1, B3) or 5 months after HSCT (fig 1, A3). In both, a striking change from a severely pathologic scleroderma like pattern to an almost normal (patient 1) or only slightly pathologic morphology (patient 2) could be observed. To compensate for the known fact of non-homogeneous distribution of morphological changes even in the same finger (fig 2) and to underline our observation, the presented fingers offer a relatively large field of view. In all but one finger an amelioration of NFC morphology was noted. This could already be observed shortly after stem cell mobilisation. Paralleled by the improvement of NFC, the patients reported amelioration of RP (no objective measurement performed).
Our findings support the reversibility of the microvascular changes in patients with SSc and MCTD on a short time interval. Intense immunosuppression seems to have an impact on vascular remodelling in patients with SSc and MCTD.