Sex disparities in systemic sclerosis-associated pulmonary arterial hypertension: a cohort study.

BACKGROUND: The impact of male sex as a determinant of health outcomes in systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) is controversial. The primary objective of this study was to evaluate the effect of sex on survival in patients with SSc-PAH. The secondary objectives were to evaluate the effect of sex on age of PAH diagnosis, time from SSc diagnosis to PAH diagnosis, and SSc disease manifestations. METHODS: Sex-based disparities were evaluated in a cohort of SSc-PAH patients with a primary outcome of time from PAH diagnosis to all-cause mortality. Secondary outcomes were differences in age of diagnosis, disease duration, and SSc manifestations. Survival differences were evaluated using Kaplan-Meier and Cox proportional hazard models. RESULTS: We identified 378 SSc-PAH (58 males, 320 females) patients, with a female:male ratio of 5.5:1. Males had a shorter mean ± standard deviation time from SSc diagnosis to PAH diagnosis (1.7 ± 14 versus 5.5 ± 14.2 years); shorter PAH duration (3.5 ± 3.1 versus 4.7 ± 4.2 years), increased frequency of renal crisis (19 % versus 8 %, relative risk (RR) 2.33, 95 %CI 1.22, 4.46), interstitial lung disease (67 % versus 48 %, RR 1.41, 95 %CI 1.14, 1.74), and diffuse subtype (40 % versus 22 %, RR 1.84, 95 %CI 1.26, 2.69). Males appeared to have decreased 1-, 2-, 3-, and 5-year survival (83.2 %, 68.7 %, 53.2 %, 45.6 %) compared to females (85.7 %, 75.7 %, 66.4 %, 57.4 %). However, there was no difference in mortality between sexes (HR 1.43 (95 %CI 0.97, 2.13). CONCLUSIONS: Sex disparities appear to exist in the frequency of PAH, time to PAH diagnosis, PAH disease duration and SSc disease burden. However, male sex does not independently impact SSc-PAH survival.

Psoriatic Arthritis Mutilans: Clinical and Radiographic Criteria. A Systematic Review.

OBJECTIVE: Research on psoriatic arthritis mutilans (PAM), the most severe form of psoriatic arthritis, is impeded by the lack of an accepted classification criteria. We performed a systematic review of the literature to identify and synthesize clinical and radiographic features associated with the definition of PAM. METHODS: A systematic literature search limited to human studies was conducted without language restriction. Abstracts were independently screened by 2 investigators and studies that reported information on patients with PAM were included. A standardized form was used to independently collect clinical and radiographic items defining PAM, patient's demographics, disease characteristics, and outcomes. RESULTS: There were 8570 citations searched to identify 112 articles for full review and 58 articles for data abstraction. We identified 8 definitions of PAM that were used in 283 subjects with a mean age ± SD at diagnosis of PsA of 33.9 ± 8.2 years. Disease manifestations (prevalence) included dactylitis (29-64%), enthesitis (29-32%), axial disease (14-27%), and nail lesions (47%). PAM definitions include 1 (n = 2 studies) or more (n = 14 studies) joints involving interphalangeal, metacarpophalangeal, or metatarsophalangeal joints. The most prevalent PAM clinical features were digital telescoping (34%), digital shortening (33%), and flail joints (22%). The most prevalent PAM radiographic items were bone resorption (41%), pencil-in-cup change (16%), total joint erosions (14%), ankylosis (21%), and subluxation (7%). CONCLUSION: We have identified 8 definitions of PAM, and synthesized the clinical and radiographic items that are important for the classification of PAM. We have established the groundwork for future development classification criteria for PAM.

Effectiveness of phosphodiesterase-5 inhibitor therapy for portopulmonary hypertension.

BACKGROUND: Portopulmonary hypertension is associated with significant morbidity and mortality. Phosphodiesterase-5 inhibitor therapy is efficacious in other causes of WHO group I pulmonary arterial hypertension. OBJECTIVE: To evaluate the efficacy and safety of phosphodiesterase-5 inhibitor therapy in patients with portopulmonary hypertension. METHODS: A single-centre retrospective cohort study that included patients with a diagnosis of portopulmonary hypertension was performed. The primary outcome was change in pulmonary vascular resistance after six months of phosphodiesterase-5 inhibitor therapy. A secondary evaluation investigated the effect on other hemodynamic measurements, 6 min walk distance, functional class, safety outcomes and survival. RESULTS: Of 1385 patients screened, 25 patients with portopulmonary hypertension were identified, of whom 20 received a phosphodiesterase-5 inhibitor. After six months, there was a significant decrease in pulmonary vascular resistance (-236 dyn • s • cm(-5) [95% CI -343 dyn • s • cm(-5) to -130 dyn • s • cm(-5)]; P<0.001), mean pulmonary artery pressure (-8.9 mmHg [95% CI -13.7 mmHg to -4.2 mmHg]; P=0.001) and an increase in Fick cardiac output (0.9 L/min [95% CI 0.1 L/min to 1.6 L/min]; P=0.02). There was no change in 6 min walk distance. The proportion of subjects with a WHO functional class III or IV was significantly reduced at six months compared with baseline (18% versus 61%; P=0.002). Safety outcomes did not reveal any adverse events. CONCLUSIONS: Phosphodiesterase-5 inhibitor therapy improved hemodynamics and functional class at six months in a cohort of patients with portopulmonary hypertension.

The effect of male sex on survival in systemic sclerosis.

OBJECTIVE: Systemic sclerosis (SSc) has a female predominance, however, little is understood about the effect of sex on SSc manifestations and survival. The objectives of our study were to evaluate differences in disease manifestations, and survival rates between males and females with SSc. METHODS: A retrospective cohort study of the Toronto Scleroderma Program was conducted to evaluate sex-based differences in disease manifestations and survival. A relative survival analysis compared SSc survival to the general population. RESULTS: There were 959 patients (791 females, 168 males) identified, with a female:male ratio of 4.7:1. Males more frequently had diffuse SSc [45% vs 30%, relative risk (RR) 1.44, 95% CI 1.18-1.75] and interstitial lung disease (ILD; 41% vs 33%, RR 1.24, 95% CI 1.01-1.52). There were 324 deaths (65 males, 259 females). Males had increased unadjusted mortality compared to females (HR 1.57, 95% CI 1.19-2.06). In an adjusted model including immunosuppressive use, male sex (HR 1.40, 95% CI 1.06-1.85), ILD (HR 1.58, 95% CI 1.26-1.98), and older age at diagnosis (HR 1.05, 95% CI 1.04-1.06) were independently associated with increased mortality, whereas the limited subtype (HR 0.70, 95% CI 0.49-0.77) and anticentromere antibodies (HR 0.70, 95% CI 0.49-0.98) were independently associated with decreased mortality. Male sex was associated with increased risk of mortality (HR 1.16, p=0.003) in patients with SSc above that observed for males in the general population. CONCLUSION: The differential effect of disease between sexes is small, yet males have decreased survival compared to females with SSc.

Survival after lung transplantation in systemic sclerosis. A systematic review.

BACKGROUND: Lung transplantation is a life-saving option for systemic sclerosis (SSc)-associated pulmonary arterial hypertension (PAH) and interstitial lung disease (SSc-ILD) patients. However, some programs may be concerned about the possibility of excess post-transplantation mortality related to the extra-pulmonary manifestations of SSc. The objective of this study was to evaluate survival of SSc patients post-lung transplantation. We secondarily evaluated SSc lung transplant recipient characteristics (age, sex, and type of SSc lung disease), and discussed post-lung transplantation survival of SSc patients and non-SSc patients (idiopathic PAH, and ILD). METHODS: A systematic review of MEDLINE, EMBASE, Cochrane Central Registry of Controlled Trials and CINAHL (all inception to 2012) was performed to identify studies evaluating post-lung transplant survival in SSc compared to PAH and ILD patients. Two reviewers independently abstracted study and survival data. RESULTS: Two hundred twenty-six citations were screened to identify 7 observational studies reporting SSc patients who underwent single lung, double lung, or heart-lung transplantation. Mean age at transplantation ranged 46-53 years. SSc post-transplantation survival ranged 69%-91% at 30-days, 69%-85% at 6-months, 59%-93% at 1-year, 49%-80% at 2-years, and 46%-79% at 3-years. Causes of death included graft failure, infection, cardiac events, hemorrhagic stroke, respiratory failure, malignancy, pulmonary hypertension, complications of bronchiolitis obliterans syndrome, anesthetic complication, and scleroderma renal crisis. There were no reports of recurrence of SSc in the lung allograft. CONCLUSION: The short-term and intermediate-term survival post-lung transplantation are similar to IPAH and ILD patients requiring lung transplantation.