Background: The impressive association of lung involvement and gastroesophageal reflux in scleroderma raises the possibility of a cause-effect relationship. Objectives: To determine clinical, radiological and histopathological features of systemic sclerosis (SSc) patients according the presence or absence of centrilobular fibrosis (CLF). Methods: Twenty-eight SSc patients with lung involvement were submitted to open lung biopsy and the specimens classified for the presence of CLF (bronchocentric distribution of the lesions and intraluminal matter according to the classification of idiopathic interstitial pneumonia). HRCT, pulmonary function tests and esophageal analysis were also performed. Subsequently, cyclophosphamide was introduced for the nonspecific interstitial pneumonia subgroup and antireflux treatment was intensified for isolated CLF patients. Results: Isolated CLF was found in 21% of the biopsies and also found associated to nonspecific interstitial pneumonia in 84% of these patients. The other 3 cases had usual interstitial pneumonia, pulmonary hypertension and respiratory bronchiolitis-associated interstitial lung disease. The histopathological analysis revealed that all 6 patients with isolated CLF had the bronchocentric distribution and intraluminal basophilic content, with foreign bodies detected in one third of them. The central distribution of lung involvement on HRCT was found in 67% of these patients with a consistent patchy distribution (100%). Ground glass (67%) and consolidation (33%) were the predominant patterns found. The constant clinical finding in all isolated CLF cases was dyspnea, esophageal abnormalities and a moderate lung impairment (FVC: 63.83 ± 16.31%; DLCO: 61.66 ± 18.84%). Lung function parameters in isolated CLF patients remained stable after 1 year of exclusively intensive antireflux treatment (FVC, p = 0.23; DLCO, p = 0.59). Conclusions: The novel description of CLF pattern in SSc lung disease with peculiar histological, tomographic and clinical features will certainly contribute to a more appropriate therapeutic approach.

Systemic sclerosis (SSc) is a disorder characterized by skin thickness and vasculopathy. The objective of the study was to evaluate the therapeutic effect and safety of the association of pentoxyphylline and vitamin E in SSc patients. Twelve SSc patients (American College of Rheumatology criteria) enrolled this 24-week open-label study. Patients received daily 800 mg of pentoxyphylline and 800 UI of vitamin E and were evaluated at 4-week interval. The primary efficacy endpoint was the change in Modified Rodnan Skin Score (MRSS) at week 24. Nine diffuse SSc patients treated 6 months with cyclophosphamide were used as a historical control group. The mean age of the treated group was 43.6 years, and ten of 12 (84%) patients were women. Their mean MRSS reduced from 25.7 to 18.7 (p = 0.03) at 16th week and remained significantly reduced throughout the study. In contrast, only a trend of MRSS reduction was observed in the historical control group (p = 0.06). Two patients started the study with active ischemic ulcers and ended with a complete healing of them. No serious side effects were reported. Pentoxyphylline and vitamin E might be an alternative therapeutic approach in SSc patients.

The aim of the study was to evaluate the expressions of adhesion molecules (AM) on peripheral blood mononuclear cells (PBMNC) from systemic sclerosis (SSc) patients. Thirty-one SSc patients (ACR) and 20 normal subjects were selected for the study. PBMNC were analyzed for LFA-1alpha, LFA-1beta, ICAM-3, ICAM-1, and L: -selectin expressions. ICAM-3 expression was decreased while ICAM-1 was increased on SSc PBMNC, compared to controls (p = 0.04 and 0.003, respectively). A positive association was found between LFA-1alpha (r = 0.37, p = 0.03), LFA-1beta (r = 0.38, p = 0.002), ICAM-3 (r = 0.42, p = 0.01), and L-selectin (r = 0.38, p = 0.03) expressions and greater number of immunosuppressive drugs taken by SSc patients. Also, anti-centromeric positive SSc patients had lower expressions of LFA-1alpha, LFA-1beta, ICAM-3, and L-selectin. Lower expression of ICAM-3 and higher expression of ICAM-1 suggest that AMs may be involved in the pathogenesis of scleroderma.

Introduction: Systemic sclerosis (SSc) is a rheumatologic disease characterized by autoimmune inflammation, vasculopathy and tissue fibrosis of skin and various organs. There are few effective treatments available for a severe cutaneous involvement of diffuse SSc. Therefore, we evaluated the efficacy of cyclophosphamide in the treatment of severe diffuse SSc. Patients and methods: Nine diffuse SSc (American College of Rheumatology [ACR] criteria) patients with a modified Rodnan skin score (MRSS) > 30 (0-51) were submitted to treatment with cyclophosphamide (CPM), at a monthly dose of 0.5 to 1.0 g/m 2 IV for 18 months. MRSS was performed every six months during 18 months. Laboratory evidence of inflammatory activity and adverse events were also retrospectively assessed. Patients with severe pulmonary and cardiac involvement were excluded. Results: Most patients were female (77%) with mean age of 41.7 years and duration of disease of 2.2 years. There was a significant reduction in the MRSS from 37.7 ± 4.08 to 29.1 ± 8.13 after 12 months of treatment (P = 0.009). Seven patients completed 18 months of CPM and had persistent reduction of the MRSS (mean MRSS = 26.4. P = 0.01). There was also a reduction of C-reactive protein (CRP) (initial mean CRP = 8.9 mg/dL) compared with values after 18 months of treatment (mean CRP = 3.09 mg/dL, P = 0.04). There were no infections, urinary disorders and/or important hematological problems throughout the treatment. Conclusion: The treatment with cyclophosphamide was effective and should be considered an alternative for the treatment of severe cutaneous involvement of SSc.

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