Summary Background Pain is a prominent symptom of hidradenitis suppurativa (HS) and has been defined as a domain in the Core Outcome Set for the disease. Quality and intensity of pain is influenced by depression and anxiety, both of which are associated with HS. Objectives To describe HS‐related pain quantitatively and qualitatively; and to investigate how disease severity, depression and anxiety correlate with self‐reported pain quality. Methods Pain perception was investigated using the McGill Pain Questionnaire. Symptoms of depression and anxiety were examined using the Hospital Anxiety and Depression Scale. Statistical analyses investigated differences in number of words chosen (NWC) and pain‐rating index rank [PRI(R)] in patients with severe disease and in patients with depression/anxiety. Results A total of 138 patients with HS were recruited in an outpatient clinic (October 2017–March 2018). Patients presented a median NWC of 11·5 and a PRI(R) of 59·0%. Most common descriptors were ‘shooting’ (83%), ‘itchy’ (79%) and ‘blinding’ (75%). Patients with depression or anxiety presented significantly higher PRI(R)s [depressed 65% vs. non‐depressed 57% (P = 0·015); anxious 65% vs. nonanxious 57% (P = 0·004)]. Patients with involvement of three or more HS regions vs. those with fewer than three involved regions exhibited a significantly higher NWC (13 vs. 8; P = 0·048). Conclusions HS‐related pain includes nociceptive and neuropathic pain, and perception appears to be influenced by disease severity, anxiety and depression. A multimodal pain management strategy may be the most appropriate; however, more detailed studies are necessary to define recommendations on pain management. What's already known about this topic? Pain is a core outcome domain hidradenitis suppurativa. Few studies have addressed this significant clinical problem. What does this study add? This study suggests that HS pain comprises both nociceptive and neuropathic pain. Pain appears associated to depression, anxiety and severity of the disease.
P4 ATPase flippases translocate phospholipids across biomembranes, thus contributing to the establishment of transmembrane lipid asymmetry, a feature important for multiple cellular processes. The mechanism by which such phospholipid flipping occurs remains elusive as P4 ATPases transport a giant substrate very different from that of other P-type ATPases such as Na+/K+- and Ca2+-ATPases. Based on available crystal structures of cation-transporting P-type ATPases, we generated a structural model of the broad-specificity flippase ALA10. In this model, a cavity delimited by transmembrane segments TM3, TM4, and TM5 is present in the transmembrane domain at a similar position as the cation-binding region in related P-type ATPases. Docking of a phosphatidylcholine headgroup in silico showed that the cavity can accommodate a phospholipid headgroup, likely leaving the fatty acid tails in contact with the hydrophobic portion of the lipid bilayer. Mutagenesis data support this interpretation and suggests that two residues in TM4 (Y374 and F375) are important for coordination of the phospholipid headgroup. Our results point to a general mechanism of lipid translocation by P4 ATPases, which closely resembles that of cation-transporting pumps, through coordination of the hydrophilic portion of the substrate in a central membrane cavity.
Background Hidradenitis suppurativa (HS) is a chronic, inflammatory, and recurring disease mainly observed in adults. Obesity is considered an important independent factor in HS development and is associated with a higher prevalence of HS in children. We aimed to characterize the clinical presentation of HS in overweight and obese children and adolescents. Methods We performed a cross‐sectional observational study during January 2007–April 2015. Overweight and obese patients (5–17 years of age, BMI> 90th percentile) referred to The Children’s Obesity Clinic, Department of Paediatrics, Copenhagen University Hospital Holbæk, Denmark, underwent screening for dermatological conditions. A dermatologist ascertained the diagnosis of HS, and disease severity was assessed using Hurley staging and Sartorius score. Tobacco smoke exposure, body mass index (BMI) standard deviation score (SDS), and psychiatric comorbidities were recorded. Our cohort was compared with a reference cohort recruited in a previous study. Results A total of 195 children and adolescents underwent screening for dermatological conditions. Nine patients screened positive, and six of these patients were available for examination of whom five presented with HS. All HS cases were mild (median Sartorius score of 9). Four of the five patients (with varying constellations) reported tobacco exposure, a positive family history of HS, and exhibited psychiatric comorbidities. Conclusion Our findings support that the presence of pediatric HS is correlated with familial disposition to HS and psychiatric comorbidities.
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