Sexual distress, sexual dysfunction and relationship quality in women with systemic sclerosis: correlation with clinical variables.

To assess the rate of sexual distress, sexual dysfunction and relationship quality and their association with clinical variables in women with systemic sclerosis (SSc), 102 sexually active women with SSc were recruited. Sexual distress, sexual dysfunction and dissatisfaction with relationship quality were investigated by Female Sexual Distress Scale Revised (FSDS-R), Female Sexual Function Index (FSFI) and Dyadic Adjustment Scale (DAS), respectively. The patients underwent medical examinations and nailfold videocapillaroscopy (NVC). Of the 102 patients, 37 (36%) reported sexual distress with FSDS-R score >11, 45 (44%) had sexual dysfunction with FSFI score <19 and 49 (48%) were not satisfied with relationship quality with DAS score <100. There was a negative correlation (p<0.001, R= -0.30) between FSDS-R and FSFI. No correlation was found between FSDS-R and DAS. FSFI showed a positive correlation with DAS (p<0.0001, R= 0.36). Age correlated negatively (p<0.05, R= -0.26) with FSFI, while FSDS-R and DAS did not correlate (p>0.05) with age. SSc women with digital ulcers (DU) had a reduction of FSFI and DAS compared with women without DU. In patients with late capillaroscopic pattern, mean value of FSFI was significantly lower than the other two capillaroscopic patterns. DAS decreased with progression of capillaroscopic damage. In a high percentage of women with SSc FSDS-R was increased, while FSFI and DAS were reduced. Age correlated negatively with FSFI, while skin score showed a negative correlation with DAS. Digital vascular damage negatively influenced FSFI and DAS.

Doppler ultrasound study of penis in men with systemic sclerosis: a correlation with Doppler indices of renal and digital arteries.

Erectile dysfunction (ED) prevalence in male systemic sclerosis (SSc) is high and its pathogenesis is unclear. The aim of the study is to assess correlation between Doppler ultrasound indices of penis and kidneys or digital arteries in male systemic sclerosis. Fourteen men with systemic sclerosis were enrolled in this study. Erectile function was investigated by the International Index of Erectile Function-5. Peak systolic velocity, end diastolic velocity, resistive index, pulsative index, and systolic/diastolic ratio were measured on the cavernous arteries at the peno-scrotal junction in the flaccid state, on the interlobar artery of both kidneys and all ten proper palmar digital arteries. Ten (71 percent) patients have an International Index of Erectile Function-5 less than 21. Reduction of penis peak systolic velocity was observed in all SSc subjects. Doppler indices of cavernous arteries correlate with the International Index of Erectile Function-5. The renal and digital arteries resistive index demonstrated a good correlation (p less than 0.0001) with International Index of Erectile Function-5. A positive correlation exists between penis and kidney arteries Doppler indices: end diastolic velocity (p less than 0.05, r=0.54), resistive index (p less than 0.0001, r=0.90), systolic/diastolic ratio (p less than 0.01, r=0.69). A positive correlation was observed between penis and digital arteries Doppler indices: peak systolic velocity (p less than 0.01, r=0.68), end diastolic velocity (p less than 0.01, r=0.75), resistive index (p less than 0.001, r=0.79), systolic/diastolic ratio (p less than 0.05, r=0.59). A correlation exists between arterial impairment of penis and renal or digital arteries.

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.

The combination of laser Doppler perfusion imaging and photoplethysmography is useful in the characterization of scleroderma and primary Raynaud's phenomenon.

OBJECTIVE: To investigate simultaneously skin perfusion and digital artery pulsatility of hands in patients with primary Raynaud's phenomenon (PRP) and systemic sclerosis (SSc). METHODS: In 100 SSc patients, 92 PRP patients, and 80 healthy controls, perfusion and digital artery pulsatility of the hands were investigated by laser Doppler perfusion imaging (LDPI) and photoplethysmography (PPG), respectively. RESULTS: Both the mean value of mean perfusion and the mean value of sphygmic wave amplitude were lower (p < 0.0001) in the PRP group than in the SSc group, and also in the SSc group compared with the healthy controls. A positive correlation (r = 0.95) was found between the mean value of mean perfusion and the mean value of sphygmic wave amplitude. A homogeneous perfusion distribution pattern was present in 95% of the healthy controls, 93% of the PRP patients, and 4% of the SSc patients. PPG shows a homogeneous pattern in 95% of the healthy controls, 93% of the PRP patients, and 28% of the SSc patients. LDPI and PPG showed a positive concordance (p < 0.05) in homogeneous pattern evaluation. In the SSc patients, no correlation (r = 0.38) was observed between the mean value of sphygmic wave amplitude and the mean value of mean perfusion of each finger. CONCLUSION: LDPI and PPG can provide useful information in distinguishing patients with PRP and SSc, although nailfold videocapillaroscopy (NVC) is the best method for analysing microvascular damage in rheumatic diseases.

Subcutaneous immunoglobulin therapy in a patient with myopathic dropped head syndrome and common variable immunodeficiency.

Prominent neck extension weakness is an uncommon clinical entity, also termed dropped-head syndrome, that may be part of a generalized neuromuscular disorder. We report here the case of a woman with dropped-head syndrome and pulmonary arterial hypertension secondary to systemic sclerosis. Subsequently, she developed common variable immunodeficiency and subcutaneous immunoglobulin therapy was started. After two months from the start of therapy we did not observe any improvement in the degree of flexion of the head, although the clinical examination shows an improvement in neck extensor muscle strength. Subcutaneous immunoglobulin therapy could be a possible therapeutic option for the treatment of myopathic neck extensor weakness.

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.

Digital ischemic necrosis in a patient with systemic sclerosis: the role of laser Doppler perfusion imaging.

The impairment of microcirculation is a cardinal feature of systemic sclerosis (SSc). Raynaud's phenomenon and SSc can cause painful digital ulcers on the fingers or toes, with resulting complications such as serious infections, gangrene or possible amputation. This case report shows the possible role laser Doppler perfusion imaging (LDPI) could play in diagnosis and follow-up of digital arterial obstructions in SSc patients. LDPI is a non-invasive microvascular imaging technique able to provide maps of the cutaneous blood flow (CBF). We describe here the case of a woman affected by SSc who suddenly presented with pallor and pain; afterwards an area of necrosis became clearly visible at the distal phalanx of the third right finger. The LDPI of the dorsal surface of that finger showed a reduction of CBF. Selective arteriography was performed in order to assess the degree and location of the obstruction before proceeding with adventitiectomy. Following this procedure LDPI showed a normal CBF in the distal phalanx and complete healing of the necrotic area. Consequently, we can state that LDPI alone provides an indirect functional estimation of possible digital artery obstruction. Further, we can assert that the overall effect of the adventitiectomy resulted in an increase of the CBF.

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.

Plasma adrenomedullin and endothelin-1 levels are reduced and Raynaud's phenomenon improved by daily tadalafil administration in male patients with systemic sclerosis.

The aim of our study is to evaluate in Systemic Sclerosis (SSc) male patients the tadalafil effects on Raynaud's phenomenon and on AM and ET-1 plasma levels. In an open-label study 20 consecutive male patients with SSc were enrolled and received 10 mg of tadalafil daily for 12 weeks. The primary endpoint was the subjective reduction of frequency and duration of Raynaud's attacks measured with a 10-point Raynaud's Condition Score; the secondary aim was to modify Adrenomedullin (AM) and Endothelin-1 (ET-1) plasma levels. After the treatment Raynaud's phenomenon was improved by once-daily tadalafil (decrease of mean number of Raynaud's attacks and of Raynaud's Condition Score) and plasma AM and ET-1 levels decreased. The results of our study lead us to postulate the beneficial effect of adding long term inhibition of Phosphodiesterase type 5 to Systemic Sclerosis' therapy.

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.

Raynaud's phenomenon: Infrared functional imaging applied to diagnosis and drug effects.

A non-invasive, innovative approach to the study of Raynaud's Phenomenon is proposed. A group of patients, with respect of a control group, underwent a simultaneous assessment of thermal properties of all ten fingers using infrared functional imaging (IRFI). The assessment highlighted a quite different behaviour between patients with Primary- (PRP) and those with scleroderma - Raynaud's Phenomenon (SSc) and, compared with other existing techniques, seems to be an objective and effective tool to discriminate between PRP and RP secondary to SSc. 18 healthy volunteers (Norm), 20 Primary Raynaud's Phenomenon (PRP) and 20 Secondary Scleroderma (SSc) patients were studied subsequently to clinical evaluation and nail fold capillaroscopy. High-resolution infrared imaging of finger re-warming processes, immediately after a 2 min cold stress, allowed to identify objective parameters. Temperature integral Q (the temperature evaluation of the area under the time-temperature curve along the re-warming period) provided particularly effective figures in describing thermal properties of the fingers. Grand average Q values were (383.4 ∓ 12.5) °C×min, (502.9 ± 88.1) °C×min and (1022.0 ± 110.2) °C×min for the PRP, SSc and Normal groups, respectively. Separate evaluation of the temperature integral for each finger leads to very similar results for the fingers of all the PRP patients; a different thermoregulatory response was observed in SSc patients. The sensitivity of the method in order to distinguish healthy from ill fingers was 100%. The specificity in distinguishing SSc from PRP was 95%. In addition, IRFI parameters provided a better understanding of the impaired control of the finger's temperature in PRP and SSc with respect to the Normal group. This pilot study also applied IRFI for the measurement of drug effects in patients with Raynaud's Phenomenon. Sixteen out of twenty SSc patients were tested in a single 1-hour session of N-acetylcysteine infusion. IRFI clearly documented a significant increase of face and hands temperature during the drug administration. The grand average value of the finger's temperature after the 1 hour NAC administration was (29.6 ± 3.7) °C, while its value before was (27.9 ± 3.7) °C (p<0.001). N-acetylcysteine seems to act as a vasodilator in patients with Raynaud's phenomenon secondary to systemic sclerosis (scleroderma).

High incidence of Helicobacter pylori infection in patients with systemic sclerosis: association with Sicca Syndrome.

To test the incidence of Helicobacter pylori (HP) infection in patients affected by Systemic Sclerosis (SSc) a swift urease test, followed by histologic confirmation for the presence of HP was verified in 35 SSc patients. Serum samples from 46 patients were tested for HP IgG antibodies by an enzyme-linked immunosorbent assay. Urease test demonstrated the presence of HP in 23 patients out of 35 (66%); 12 of them were negative to colonization. A Sicca syndrome, with abnormal Schirmer’s test and dry mouth was detected in 66% of the patients. 78% of the patients with Sicca syndrome had a concomitant HP infection, compared to 42% of those without the syndrome (p=0,029). Altered peristalsis and reduced salivary clearance usually encourage HP infection. In patients with Systemic Sclerosis we found an enhanced frequency of HP infection.