Ulcers caused by bullous morphea: successful therapy with N-acetylcysteine and topical wound care.

Bullous morphea is an uncommon form of localized scleroderma. The pathogenesis is unknown and treatment of coexistent ulcers is difficult. The pathogenesis of bullae formation in morphea is multifactorial, but reactive oxygen species production appears to play a key role. We report a patient with bullous morphea with long-standing ulcers whom we successfully treated with N-acetylcysteine and topical wound care. N-acetylcysteine, an antioxidant sulfhydryl substance, promotes the healing of ulcers in patients with bullous morphea.

Long-term N-acetylcysteine therapy in systemic sclerosis interstitial lung disease: a retrospective study.

Systemic sclerosis (SSc) is associated with interstitial lung diseases. The primary endpoints of this study were changes between baseline and month 24 in single-breath carbon monoxide diffusing capacity (DLco). The secondary endpoints were: vital capacity (VC), forced expired volume in 1 sec (FEV1), total lung capacity (TLC), scores of high resolution computed tomography (HRCT) of the chest, number of adverse effects. In this study, we retrospectively investigated data from SSc patients who had undergone therapy with high-dose intravenous N-acetylcysteine (NAC) at a dosage of 15 mg/Kg/h for 5 consecutive hours every 14 days. After NAC therapy median values of DLco (69.5 vs 77.7%), VC (99 vs 101.3%) and TLC (93 vs 98.3%) significantly increased. We did not observe any significant changes from baseline in FEV1 value and HRTC score. The improvement in lung function was more evident in SSc patients without radiological signs of pulmonary fibrosis than in patients with pulmonary fibrosis. In SSc patients with mild-moderate pulmonary fibrosis intravenous NAC administration slows the rate of deterioration of DLco, VC and TLC. In conclusion, this retrospective study demonstrates that long-term therapy with intravenous NAC ameliorates pulmonary function tests in SSc patients.

Current strategies for the treatment of autoimmune diseases.

Autoimmune disease therapy may be considered a puzzle under construction. Current treatments for autoimmune diseases include physical therapy, non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, disease-modifying anti-inflammatory drugs (DMARDs), anticytokine therapies, inhibition of intracellular-signaling pathways, costimulation inhibition, biological inhibitors of T cell function, B-cell anergy and depletion, regulatory T cells, stem cell transplantion. New biologic drugs that target specific cells or cytokines involved in the early inflammatory response started because of their improved efficacy and limited toxicity. The hematopoietic stem cell transplantation represents a possible therapeutic strategy for autoimmune diseases resistant to available treatments.

N-acetylcysteine infusion improves hepatic perfusion in the early stages of systemic sclerosis.

The aim of our study is to evaluate portal and hepatic hemodynamic changes after N-acetylcysteine infusion in patients with systemic sclerosis. In an open-label study 40 patients with systemic sclerosis (SSc) were treated with 15 mg/kg/hour intravenous N-acetylcysteine for 5 consecutive hours in a single day. Hepatic flow volume, congestion index, portal flow volume, resistance index and pulse rate index were measured in each subject before and after infusion. In all patients mean hepatic flow volume (HFV) and mean portal flow volume (PFV) values after the five-hour infusion with NAC increased not significantly. In 22 selected patients with active capillaroscopic pattern, modified Rodnan Total Skin Score (mRTSS)<18 and mild-moderate score to vascular domain of disease severity scale (DSS), mean HFV increased significantly when compared with mean HFV of 18 SSc patients with late capillaroscopic pattern, mRTSS>18 and severe-end stage score to vascular domain of DSS. The results of our study demonstrate that NAC is able to increase HFV and total liver perfusion after a single infusion in SSc patients with low disease activity and severity scores.

Recurrent infections in patients with nickel allergic hypersensitivity.

Nickel (Ni) is the most common contact allergen among the general population in the industrialized world. Ni has been shown to exhibit immunomodulatory, if not immunotoxic, effects in several experiments conducted on humans and on rodents. This study tests the incidence of different infectious diseases in 100 patients with Ni hypersensitivity and compares it to data from 100 healthy volunteers. One hundred subjects with Ni hypersensitivity were enrolled. A group of 100 matched healthy volunteers with negative European standard patch test were enrolled as healthy controls. In patients with Ni hypersensitivity a higher incidence of recurrent herpes labialis (RHL), urinary tract infections (RUTI), genital candidiasis, and upper respiratory tract infections (RURTI) was detected. Fifteen patients with nickel allergic hypersensitivity (NAH) followed a Ni-poor diet. After a one-year diet a net reduction of incidence of RHL was found. Indeed, the number of episodes of RHL per year decreased from 6 +/- 2.75 to 2.4 +/- 1.2. Conversely, among the matched control group with NAH following a normal daily dietary nickel intake the RHL number did not show any statistically significant changes (6.1 +/- 1.7 vs 6 +/- 1.5 ). In conclusion, our study demonstrates a higher incidence of recurrent infections among patients with NAH. A low-Ni diet reduces the number of RHL episodes per year.

Significant changes of peripheral perfusion and plasma adrenomedullin levels in N-acetylcysteine long term treatment of patients with sclerodermic Raynauds phenomenon.

The unclear pathogenesis of scleroderma vascular lesions makes treatment of Raynaud's phenomenon (RP) in Systemic Sclerosis (SSc) patients very difficult and a new effective treatment is requested. Recently, a powerful antioxidant agent, the N-acetylcysteine (NAC) has been shown to decrease the frequency and severity of RP in SSc patients. Subsequently, using functional infrared imaging, we showed that a single 1-hour NAC infusion in these patients caused a significant increase of skin temperature. The aim of this study was to demonstrate the efficacy of long term therapy with NAC in an open clinical trial evaluating clinical, instrumental and laboratory parameters. Patients started the treatment receiving for two years, from October to May, intravenous NAC infusions of 15 mg/kg per hour each, for 5 consecutive hours, every two weeks. Before and after each infusion, patients underwent both Laser Doppler perfusion Imaging (LDPI) for the evaluation of the digital perfusion and a blood test to ascertain the plasma adrenomedullin (AM) levels. The NAC infusion increased global hands perfusion and induced a significant decreasing of plasma AM concentrations. Side effects were negligible, easy to control and reversible. Reduction of frequency and severity of RP attacks was recorded. In conclusion, NAC seems to act as an effective vasodilatator in the treatment of RP secondary to SSc and, in addition, it induced significant changes in plasma levels of AM, a potent vasodilator endothelial-derived peptide.

Immune effects of nickel.

Data on nickel immunomodulation are contradictory. The most consistent immune effects are suppression of immune responses. It has been shown that T-lymphocytes and NK cells are more susceptible to nickel toxicity than are B lymphocytes or macrophages. Data reported about cytokine production in human and nickel reactive T-cell clones are also conflicting. Some authors studied showed a higher synthesis of IL4, IL5 and IL13 but not of IFN gamma and TNFalpha in Ni allergic subjects. We found that the addiction on NiSo4 to the PBMC cultures of non sensitised subjects induces a reduction of release of IL5, IFN gamma and TNFalpha. Our studies demonstrate a clear difference in the NK cell activity between nickel-tolerant and intolerant individuals. In particular NK cell activity in reduced in sensitised patients respect to the normal subjects and the addition of Ni has immunotoxic potential. Researches are in progress in an Attempt to correlate the present data with other immune parameters and to measure the effects of a Ni Free diet on the immune system of subjects with Ni intolerance. The comprehension of the mechanisms inducing these changes requires further studies in the uptake and intracellular distribution and binding of the metal.