Quality of life in patients with early- and late-onset hidradenitis suppurativa.

Hidradenitis suppurativa (HS) usually has an early onset, however, also onset in the mid-40 s may occur. Recently, the threshold of 28 years to distinguish patients with early and late onset has been proposed. The objective of our study was to compare the quality of life (QoL) and psychological distress in early- and late-onset HS patients. In this cross-sectional, observational study, consecutive patients diagnosed with HS aged ≥ 16 years were recruited. Dermatology-specific QoL was evaluated using the Skindex-17 questionnaire, and psychological distress using the 12-item General Health Questionnaire (GHQ-12). Patients were categorized into "early onset" (< 28 years) and "late onset" (≥ 28 years). Data were collected on 467 patients. Mean age at diagnosis was 21.6 years, with 22.0% of patients presenting with late disease onset. Patients with late onset reported worse psychosocial QoL and higher psychological distress compared to early onset. No differences between the two groups were observed for clinical severity. In the final multivariate model lower diagnostic delay, higher number of fistulae, higher BMI, ex-smoker, no localization on axillae, no localization on mammary region, presence of psoriasis, and higher scores on the psychosocial scale of Skindex-17 were statistically significantly associated with late onset. In conclusion, the psychosocial impact of HS is higher in patients with late onset compared to those with early onset. Differences between these two groups should be further investigated.

Evidence for a 'window of opportunity' in hidradenitis suppurativa treated with adalimumab: a retrospective, real-life multicentre cohort study.

BACKGROUND: The anti-tumour necrosis factor (TNF)-α adalimumab is the only licenced biologic for moderate-to-severe hidradenitis suppurativa (HS). No predictors of response have been identified so far. OBJECTIVES: To identify clinical parameters predicting response to adalimumab and confirm its efficacy/safety. METHODS: The data of 389 patients with HS treated with adalimumab in 21 Italian centres were reviewed. Sex, age at onset/diagnosis/baseline, body mass index, smoking, phenotype, previous treatments, concomitant antibiotics and 'therapeutic delay', defined as the time from HS onset to adalimumab initiation, were assessed. Response to adalimumab and its impact on quality of life (QoL) were evaluated using the Hidradenitis Suppurativa Clinical Response (HiSCR) and the Dermatology Life Quality Index (DLQI) or the Visual Analogue Scale for pain (VAS pain), respectively. Logistic regression analysis was performed. RESULTS: The therapeutic delay correlated to lack of response to adalimumab at week 16 [odds ratio (OR) 1·92 for therapeutic delay > 10 years; 95% confidence interval (CI) 1·28-2·89; P = 0·0016). HiSCR was achieved in 43·7% and 53·9% patients at week 16 and 52, respectively. Significant reductions in both DLQI and VAS pain were found between week 16 vs. baseline (P < 0·0001 for both) and week 52 vs. baseline (P < 0·0001 for both). Previous immunosuppressants inversely correlated to HiSCR at week 52 (OR = 1·74, 95% CI 1·04-2·91, P = 0·0342). CONCLUSIONS: Inverse correlation between therapeutic delay and clinical response was found, supporting early adalimumab use and providing evidence for a 'window of opportunity' in HS treatment. Adalimumab efficacy and safety were confirmed, along with patients' QoL improvement. Immunosuppressants could negatively influence the response to adalimumab inducing a switch to non-TNF-α-driven pathways.

Involvement of transcribed lncRNA uc.291 and SWI/SNF complex in cutaneous squamous cell carcinoma.

While non-melanoma skin cancers (NMSCs) are the most common tumours in humans, only the sub-type cutaneous squamous cell carcinoma (cSCC), might become metastatic with high lethality. We have recently identified a regulatory pathway involving the lncRNA transcript uc.291 in controlling the expression of epidermal differentiation complex genes via the interaction with ACTL6A, a component of the chromatin remodelling complex SWI/SNF. Since transcribed ultra-conserved regions (T-UCRs) are expressed in normal tissues and are deregulated in tumorigenesis, here we hypothesize a potential role for dysregulation of this axis in cSCC, accounting for the de-differentiation process observed in aggressive poorly differentiated cutaneous carcinomas. We therefore analysed their expression patterns in human tumour biopsies at mRNA and protein levels. The results suggest that by altering chromatin accessibility of the epidermal differentiation complex genes, down-regulation of uc.291 and BRG1 expression contribute to the de-differentiation process seen in keratinocyte malignancy. This provides future direction for the identification of clinical biomarkers in cutaneous SCC. Analysis of publicly available data sets indicates that the above may also be a general feature for SCCs of different origins.

Sex- and gender-associated clinical and psychosocial characteristics of patients with psoriasis.

BACKGROUND: Sex and gender may affect disease prevalence, adverse effects and response to therapy. AIM: To analyse sex and gender differences in outpatients with psoriasis. METHODS: A cross-sectional study was conducted at IDI-IRCCS, Rome, over a 3-year period. In total, 3023 patients with psoriasis were enrolled. Anthropometric and demographic characteristics were recorded, and a dermatologist evaluated the clinical severity of disease. Quality of life (QoL) questionnaires were collected. Univariate and multivariate analyses were performed to examine factors associated with sex. RESULTS: We found sex- and gender-associated differences in clinical characteristics, disease severity, psychological distress and quality of life. Male sex was associated with body mass index, smoking, alcohol consumption, Psoriasis Area Severity Index ≥ 10 and age at onset ≥ 20 years. Female sex was associated with family history of diabetes, joint involvement, clinical type other than diffuse plaque psoriasis, higher psychological distress and a greater effect on QoL. CONCLUSION: Our study identified sex and gender differences of potential clinical relevance in psoriasis.

Mutation identification of Fabry disease in families with other lysosomal storage disorders.

Fabry disease (FD) is an X-linked lysosomal storage disorder (LSD) caused by the deficiency of the enzyme α-galactosidase. It exhibits a wide clinical spectrum that may lead to a delayed or even missed diagnosis and the real incidence can be underestimated. We report the cases of two unrelated Italian families in whom FD was incidentally diagnosed in two females. In both families, the risk for other lysosomal disorders was known from other members affected by fucosidosis or mucopolysaccharidosis I Hurler/Scheie. Some subjects were simultaneously heterozygous for Fabry and the other lysosomal deficiency. Our study shows that the risk for more than one LSDs can occur in a family pedigree. The diagnosis of Fabry in female probands represents a diagnostic challenge, as symptoms and signs can be variably present because of the random X-chromosome inactivation.

Selective use of amiodarone and early cardioversion for postoperative atrial fibrillation.

BACKGROUND: Postoperative atrial fibrillation (AF) occurs in 20%-40% of patients undergoing open-heart surgery. Numerous pharmacological and electrical therapies have been used as a prophylaxis to prevent this dysrhythmia. The purpose of this study was to examine the selective use of amiodarone and early cardioversion (CVN) postoperatively to restore normal sinus rhythm (NSR). METHODS: A retrospective nonrandomized review of patients who received amiodarone and early electrical CVN (study group) for postoperative AF after coronary artery bypass grafting (CABG) were compared with patients who received nonamiodarone therapies (control group). The study group received 150 mg of amiodarone bolus intravenously and thereafter received an infusion of 1 g over a 24-hour period. If NSR was established within 24 hours, then the intravenous (IV) infusion was continued for another 24 hours with concomitant oral amiodarone overlap. If NSR was not established within 24 hours, then external electrical CVN was performed. After 48 hours, the IV infusion was discontinued and the oral regimen maintained through discharge. Control group patients received either combination digoxin and procainamide or diltiazem. Postoperative beta-blocker administration was instituted in all patients. RESULTS: Six-hundred forty consecutive CABG patients were examined between July 1995 and June 2003. Postoperative AF developed in 160 of these patients (25%). One-hundred patients constituted the study group and 60 patients represented the control group. Restoration of NSR within 24 and 48 hours occurred in 79 (79%) and 90 patients (90%) for the study group, respectively, compared with 38 (64%) and 44 patients (73%) for the control group, respectively. The presence of NSR at discharge was achieved in 98 study patients (98%) and 50 control patients (83%). The length of stay (LOS) for the study and control patients was 7.4 and 9.1 days, respectively. There was no mortality in either group. CONCLUSIONS: Amiodarone and early CVN was more effective than nonamiodarone therapies with regard to restoring NSR for patients in whom AF developed after elective CABG. A trend toward a decrease in LOS was observed in the study group, but was not statistically significant. The overall LOS using amiodarone therapy with early CVN was similar to postoperative AF for patients in whom the condition did not develop.

Ventricular assist device support for management of sustained ventricular arrhythmias.

We describe herein the cases of 2 patients who had ventricular arrhythmias. In one, a short-term biventricular assist device, the ABIOMED BVS 5000, was placed because the patient had sustained ventricular tachycardia and could not be weaned from cardiopulmonary bypass. Excellent hemodynamic support was maintained for several days while the antiarrhythmic therapy was maximized. Sinus rhythm was restored, and the patient was successfully weaned from the ventricular assist device. However, the substrate for the arrhythmia persisted, and a recurrence, 1 week later, resulted in the patient's death. In the 2nd patient, the use of an implantable left ventricular assist device was successful in temporarily alleviating the ventricular tachycardia associated with ischemic cardiomyopathy. However, after 2 days of device assistance, the patient experienced a recurrence of the tachycardia, which degenerated into ventricular fibrillation with a marked deterioration in the patient's hemodynamics. The arrhythmia persisted despite multiple attempts at external cardioversion, and internal cardioversion and placement of an automatic implantable cardioverter-defibrillator were necessary. This treatment, along with repeated boluses of amiodarone, led to successful suppression of the arrhythmias, and the patient eventually underwent transplantation. The mechanical hemodynamic support of the circulation by ventricular assist devices was effective in supporting these 2 patients who had sustained ventricular arrhythmias.