Decreased Arterial Vascular Tone in Small Arteries in Severe Hidradenitis Suppurativa - A Study Using Finger Photopulseplethysmography.

A previous study has found an association between chronic inflammatory disorders e.g. psoriasis, rheumatoid arthritis, and inflammatory bowel disease and increased vascular stiffness(1). Psoriasis and hidradenitis suppurativa (HS) are believed to have shared comorbidities and pathophysiology despite their morphologically different manifestations in the skin. In order to evaluate a putative association between the chronic inflammatory skin disease HS and arterial stiffness, an observational cross-sectional retrospective study was carried out as part of the Danish General Suburban Population Study (GESUS) (1), in which 430 patients with HS from the general population (representing mild HS; Table 1), 32 patients with HS from a hospital-based out-patient clinic (representing severe HS, Table 1), and 20,780 controls underwent measurements of arterial vascular tone and stiffness using photoplethysmography (Pulse Trace PCA2®; Micro Medical Ltd, Kent, UK). The method of Pulse Trace has been validated by correlation with intra-arterial sensing techniques, and is a simple cost-effective screening method[2]. All analyses were performed using SAS 9.3. This study was accepted by the ethics committee of Region Zealand (project number SJ-191, SJ-113, SJ-114) in Denmark (2,3). RESULTS Reflection index (RI) is an expression of arterial vascular tone and stiffness of small arteries. The raw data showed a significantly lower RI for both HS groups groups, compared to controls. The results remained significant when adjusting for confounders (age, sex, smoking and metabolic syndrome) in the out-patient clinic HS group (-11.26 (-17.75- -4.76), P=0.0002*), but not in the population HS group (Table 2). Stiffness index (SI) expresses arterial stiffness in large arteries. Both HS groups showed no significant difference in either SI or vascular age in multivariate analysis, when compared with controls (Table 2). DISCUSSION This study suggests that decreased vascular tone and stiffness of small arteries may be associated with severe HS, and at the same time found no difference in arterial stiffness in large arteries. The significance for the out-patient clinic HS group, but not the population HS group may reflect a dose-response relationship. Vascular tone in vascular smooth muscle cells of small arteries depends on competing vasodilators and vasoconstrictors. We speculate that the inflammation of HS may induce a dysfunctional balance e.g. through increased TNF-alpha with subsequent increase of the vasodilator nitric oxide resulting in the lower arterial vascular tone observed. Additionally, mast cells are increased in HS [4], possibly increasing levels of the vasodilator histamine. HS patients often suffer from stress which could increase sympathetic activity, thereby adrenalin/cortisol and subsequent vasodilation in e.g. muscles. The more peripheral an artery is, the more collagen it contains and the stiffer it is. The finding of lower vascular tone may also be suggestive of a different elastin:collagen ratio in small arteries in HS. The healing process of HS lesions is known to involve scarring formation of sinus tracts [5], which may suggest a hypothesis of altered connective tissue. This study found no difference in SI expressing arterial stiffness of large arteries between HS and controls. Our previous study found an association between HS and myocardial infarction, but no association with stroke, nor peripheral arterial stiffness of lower extremities in medium/large arteries [6], suggesting regional differences in vascular beds in HS. The major limitation of the study is the missing values of pulse trace measurement (Table 1) creating possible selection bias. Although unable to draw any clinical conclusions, we believe these results may contribute to the future research of the complexity of HS and cardiovascular risk profiling. This study suggests that decreased vascular tone and stiffness of small arteries may be associated with severe HS, and at the same time found no difference in arterial stiffness in large arteries. The significance for the out-patient clinic HS group, but not the population HS group may reflect a dose-response relationship. Vascular tone in vascular smooth muscle cells of small arteries depends on competing vasodilators and vasoconstrictors. We speculate that the inflammation of HS may induce a dysfunctional balance e.g. through increased TNF-alpha with subsequent increase of the vasodilator nitric oxide resulting in the lower arterial vascular tone observed. Additionally, mast cells are increased in HS [4], possibly increasing levels of the vasodilator histamine. HS patients often suffer from stress which could increase sympathetic activity, thereby adrenalin/cortisol and subsequent vasodilation in e.g. muscles. The more peripheral an artery is, the more collagen it contains and the stiffer it is. The finding of lower vascular tone may also be suggestive of a different elastin:collagen ratio in small arteries in HS. The healing process of HS lesions is known to involve scarring formation of sinus tracts [5], which may suggest a hypothesis of altered connective tissue. This study found no difference in SI expressing arterial stiffness of large arteries between HS and controls. Our previous study found an association between HS and myocardial infarction, but no association with stroke, nor peripheral arterial stiffness of lower extremities in medium/large arteries [6], suggesting regional differences in vascular beds in HS. The major limitation of the study is the missing values of pulse trace measurement (Table 1) creating possible selection bias. Although unable to draw any clinical conclusions, we believe these results may contribute to the future research of the complexity of HS and cardiovascular risk profiling.

Mast cells in hidradenitis suppurativa: a clinicopathological study.

Mast cells (MC) have been observed in hidradenitis suppurativa (HS) lesions. Their potential role in the pathogenesis of HS is unknown. The aim of this study was to assess the number and distribution MC in HS lesions, and its association with disease and itch severity. We studied biopsies from HS-lesions and perilesional skin from 34 HS patients. The samples were stained with CD117 and toluidine blue, and the number of MC determined semi-quantitatively (40 × magnification). The distribution of MC was also noted. The clinical features of the disease were extracted from patients' case records and a questionnaire-based database. MC were present to a greater degree in HS-lesions than in perilesional skin (P = 0.004). Disease severity (Sartorius score) was correlated to with MC count and itch when adjusted for sex and age (P = 0.042). Duration of the disease could not been significantly correlated with MC count. A positive correlation between MC count and HS activity was detected, suggesting a potential link between MC and HS.

Pain during topical photodynamic therapy - comparing methyl aminolevulinate (Metvix®) to aminolaevulinic acid (Ameluz®); an intra-individual clinical study.

BACKGROUND: Actinic keratoses are often treated by photodynamic therapy. However, the main side effect of this treatment is pain during and shortly after illumination. OBJECTIVES: To evaluate, in an intra-individual study, whether the pain response differ in treatment of actinic keratoses in scalp and forhead, using branded methyl aminolevulinate (MAL) and aminolaevulinic acid (ALA). MATERIALS AND METHODS: Patients with mild to moderate actinic keratoses on forehead and scalp were treated with methyl aminolaevulinate (MAL)-PDT and aminolaevulinic acid (ALA)-PDT on two similar areas of forehead and scalp. The pain response were measured using visual analogue scale ranging from 0 to 10 during the illumination and 30min after the treatment. RESULTS: Fourteen patients completed treatment to MAL and ALA-PDT. We found no significant difference in pain intensity between MAL and ALA-PDT, neither during the treatment (p-value=1) nor 30min after the treatment (p-value of 0.19). CONCLUSIONS: This intra-individual study demonstrate no significant difference between the pain response during PDT using methyl aminolevulinate and aminolaevulinic acid.

Ultrasound Evaluation as a Complementary Test in Hidradenitis Suppurativa: Proposal of a Standarized Report.

BACKGROUND: Staging and monitoring of patients with hidradenitis suppurativa (HS) have been traditionally based on clinical findings. However, the physical examination may show important limitations because of its poor sensitivity for differentiating between different lesion subtypes, and its low sensitivity to define the disease's activity. OBJECTIVE: To develop a consensus ultrasound (US) report that could summarize the relevant anatomical characteristics and staging of patients considering the experience of radiologists and dermatologists working on imaging of HS. METHODS: A questionnaire on different aspects related to US examination in HS was performed. A working group, called DERMUS, composed of doctors from 9 countries who have been working in dermatologic US applied in patients with HS on a regular basis were included to evaluate the different items provided. RESULTS: A consensus US report to evaluate HS patients was established. CONCLUSION: The authors present the first attempt to define a HS standardized sonographic report. This model would be the first effort to include this imaging technique as the first elective medical test for staging and monitoring patients, which can support therapeutic decisions by providing earlier, objective, deeper, anatomical, and comparative evaluations in this difficult to treat disease.

Validation of a Screening Questionnaire for Chronic Leg Ulcers.

The use of a validated screening questionnaire to identify individuals with chronic leg ulcers allows large-scale population-based studies to be conducted that measure and monitor the prevalence of the disease. The aim of this study was to design and validate such a screening questionnaire to identify patients with chronic leg ulcers. A simple 3-item questionnaire was developed at the Department of Dermatology, University Hospital of Zealand, Denmark. In total, 90 patients attending the department's outpatient clinic for dermatological diseases and chronic wounds were included in this study. All included participants completed the questionnaire and were subsequently examined by dermatologists. We found that the constructed 3-item questionnaire in this study had a sensitivity and specificity of 95% and 93% and a positive predictive value and negative predictive value of 78% and 95%, respectively. Moreover, we found that the use of the 3-item questionnaire, as compared with a single question, in which the participants were asked whether they currently have a leg ulcer, resulted in significantly higher positive predictive value (+11.6%, P = .035) and specificity (+5.6%, P = .046) of the diagnostic test. Future studies are merited to investigate the diagnostic accuracy of the questionnaire in other populations and settings.

Differences in Disease-specific Quality of Life in Patients with Actinic Keratosis in Australia and Denmark.

Actinic keratosis (AK) negatively influences patient quality of life as measured by the disease-specific Actinic Keratosis Quality of Life (AKQoL) questionnaire. The quality of life in Australian patients was significantly less affected than in Danish patients. We hypothesize that general factors such as public awareness and cultural connotations of AK, may influence the impact of AK on quality of life (QoL).

Self-reported skin morbidity in Denmark: a population-based cross-sectional study.

Skin diseases are thought to be common in the general population. In 2004, a cross-sectional study in Norway, using a validated questionnaire for 18,770 individuals, revealed a high prevalence of skin diseases in the general population. To describe the prevalence of self-reported skin morbidities and possible socio-demographic and economic associations in the Danish general population, and furthermore compare this data to that reported in Norway. A population-based cross-sectional study of the adult Danish suburban population was performed. Participants (n = 20,164) completed the Norwegian validated questionnaire. In total, 17.2% self-reported skin complaints. The most prominent self-reported skin complaint was itch with an overall prevalence of 6.5%. The skin morbidity most influenced by age was pimples. There was a uniform pattern showing fewer skin complaints with increasing education. Women reported skin morbidities more frequently than men. Participants in employment reported fewer skin morbidities compared to unemployed participants. Skin morbidities in Denmark are common, and the distribution of prevalence estimates in the Danish population parallel those of the Norwegian population, although the prevalence is generally higher in Norway. This difference may be attributed to climatic differences, and age, education, sex, and employment status may also be influential.

Guidelines for Performing Dermatologic Ultrasound Examinations by the DERMUS Group.

OBJECTIVES: To support standardization for performing dermatologic ultrasound examinations. METHODS: An international working group, called DERMUS (Dermatologic Ultrasound), was formed, composed of physicians who have been working on a regular basis and publishing in peer-reviewed articles on dermatologic ultrasound. A questionnaire on 5 critical issues about performance of the examinations was prepared and distributed by e-mail. The areas of discussion included technical aspects, main areas of application, minimum number of examinations per year required for assessing competence, qualifications of the personnel in charge of the examination, and organization of courses. Final recommendations were approved on the basis of the agreement of more than 50% of the members. RESULTS: The minimum frequency recommended for performing dermatologic examinations was 15 MHz. Routine use of color Doppler ultrasound and the performance of spectral curve analysis for assessing the main vascularity of lesions were suggested. Three-dimensional reconstructions were considered optional. The main dermatologic applications were benign tumors, skin cancer, vascular anomalies, cosmetic field, nail disorders, and inflammatory diseases. The minimum number of examinations per year suggested by the group for assessing competence was 300. A physician and not a sonographer was recommended to be the person in charge of performing the examination. On course organization, a minimum of 2 levels of complexity (basic and advanced) was suggested. CONCLUSIONS: There is a need to standardize the performance and quality of dermatologic ultrasound examinations. The present guidelines written by an international group of specialists in the field may support this objective.

Gallstones are associated with hidradenitis suppurativa: a population-based and hospital-based cross-sectional study from Denmark.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory dermatological disease that was recently linked to the metabolic syndrome (MetS). MetS has been associated with gallstones, and nonalcoholic fatty liver has been suggested to be the hepatic expression of MetS. OBJECTIVE: The objective of the study was to investigate whether there was an association of HS with gallstones as well as with hepatic dysfunction. PATIENTS AND METHODS: This was a cross-sectional study comparing a hospital-based HS group, a population-based HS group, and controls for self-reported gallstone and blood sample verified hepatic dysfunction. Blood samples were analyzed for alanine transaminase, bilirubin, alkaline phosphatase, albumin, thrombocytes, and the international normalized ratio. RESULTS: A total of 32 hospital HS patients, 430 population-based HS patients, and 20 780 non-HS controls were identified. The age-sex-smoking-adjusted analysis of gallstones revealed a significant OR of 1.72 (95% CI 1.23-2.42, P=0.0191) and a borderline significant OR of 3.28 (95% CI 1.24-8.74, P=0.0516) for the population HS group and hospital HS group versus controls, respectively. Furthermore, no clinically significant evidence was found with regard to hepatic dysfunction. CONCLUSION: This study demonstrates an association of HS with gallstones, but not with hepatic dysfunction. The association with gallstones may be partly explained by the comorbidity of hypertriglyceridemia and obesity as a part of MetS.

Coagulation Status in Hidradenitis Suppurativa: A Danish Population- and Hospital-Based Cross-Sectional Study.

BACKGROUND: Chronic inflammatory diseases other than hidradenitis suppurativa (HS) have been associated with prothrombotic/hypercoagulable status. OBJECTIVE: To investigate a possible association between the chronic inflammatory skin disease HS and prothrombotic/hypercoagulable state. METHODS: We performed a hospital- and population-based cross-sectional study investigating the coagulation status (thrombocytes, mean platelet volume [MPV], international normalized ratio [INR] and activated partial thromboplastin time [APTT]). RESULTS: 32 hospital HS subjects, 430 population HS subjects and 20,780 population non-HS control subjects were identified. The adjusted analyses showed no differences in the levels of thrombocytes, MPV, INR or APTT between the HS groups (hospital HS group, population HS group) when compared to controls (p = 0.089, p = 0.3078; p = 0.5499, p = 0.0659; p = 0.0932; p = 0.3432). CONCLUSION: We did not find an association between HS and prothrombotic/hypercoagulable status. Thus, thrombocytes may not be activated in HS. Furthermore, INR may not be affected in HS, suggesting that intrinsic and vitamin K-dependent coagulation factors appear unaffected.

Wound healing and all-cause mortality in 958 wound patients treated in home care.

Skin wounds are associated with significant morbidity and mortality. Data are, however, not readily available for benchmarking, to allow prognostic evaluation, and to suggest when involvement of wound-healing experts is indicated. We, therefore, conducted an observational cohort study to investigate wound healing and all-cause mortality associated with different types of skin wounds. Consecutive skin wound patients who received wound care by home-care nurses from January 2010 to December 2011 in a district in Eastern Denmark were included in this study. Patients were followed until wound healing, death, or the end of follow-up on December 2012. In total, 958 consecutive patients received wound care by home-care nurses, corresponding to a 1-year prevalence of 1.2% of the total population in the district. During the study, wound healing was achieved in 511 (53.3%), whereas 90 (9.4%) died. During the first 3 weeks of therapy, healing was most likely to occur in surgical wounds (surgical vs. other wounds: adjusted hazard ratio [AHR] 2.21, 95% confidence interval 1.50-3.23), while from 3 weeks to 3 months of therapy, cancer wounds, and pressure ulcers were least likely to heal (cancer vs. other wounds: AHR 0.12, 0.03-0.50; pressure vs. other wounds: AHR 0.44, 0.27-0.74). Cancer wounds and pressure ulcers were further associated with a three times increased probability of mortality compared with other wounds (cancer vs. other wounds: AHR 3.19, 1.35-7.50; pressure vs. other wounds: AHR 2.91, 1.56-5.42). In summary, the wound type was found to be a significant predictor of healing and mortality with cancer wounds and pressure ulcers being associated with poor prognosis.

Recurrence rate and patient satisfaction of CO2 laser evaporation of lesions in patients with hidradenitis suppurativa: a retrospective study.

BACKGROUND: Hidradenitis suppurativa (HS) is a debilitating disease and is difficult to treat. Validation of surgical techniques is therefore of great importance in the management of HS. Carbon dioxide (CO2) laser evaporation has been shown effective, but larger-scale studies are scarce. OBJECTIVE: To determine the recurrence rate, time to recurrence, and factors influencing disease recurrence in skin treated with CO2 laser evaporation, and healing by secondary intention; and patients' satisfaction with treatment. METHODS: Fifty-eight patients treated with CO2 laser evaporation were interviewed regarding recurrence and satisfaction after a mean of 25.7 months. RESULTS: Seventeen of 58 (29%) reported recurrence of HS lesions within the borders of the treated areas after a mean of 12.7 months. Obesity was a risk factor for recurrence with a hazard ratio of 4.53. Fifty-five patients (95%) reported some or great improvement, and 91% would recommend the CO2 laser surgery to other HS patients. CONCLUSION: This study supports the claim that CO2 laser treatment is an effective modality for recurrent HS lesions in a majority of patients. The authors identified obesity as a risk factor for recurrence. Self-reported satisfaction is high, and only 3 of 58 report no change in the condition. None reported a worsening.

Ingenol mebutate: from common weed to cancer cure.

Actinic keratosis, which is a potential precursor of squamous cell carcinoma, is a common skin condition in fair-skinned adults worldwide. Actinic keratosis may be treated with 'lesion-directed' approaches and/or 'field-directed' therapies, the latter of which include imiquimod, diclofenac and 5-fluorouracil. The topical formulation of ingenol mebutate, which is a protein kinase C inhibitor derived from the sap of the plant Euphorbia peplus, is the newest addition to the existing arsenal of field-directed treatments. Its mechanism of action primarily involves the induction of primary necrosis and initiation of an inflammatory response characterized by the migration of neutrophils to the treated area. The gel is available in two strengths: 150 micrograms/g to be applied to lesions on the face and scalp once daily for 3 consecutive days and 500 micrograms/g for application to lesions on the trunk and extremities for 2 consecutive days. Clinical studies have supported claims of the convenience of its application and efficacy; however, the literature provides scant information on comparative efficacy rates and side-effect profiles.

Expert advice provided through telemedicine improves healing of chronic wounds: prospective cluster controlled study.

Telemedicine is widely considered as an efficient approach to manage the growing problem of chronic wounds. However, to date, there is no convincing evidence to support the clinical efficacy of telemedicine in wound management. In this prospective cluster controlled study, we tested the hypothesis that advice on wound management provided by a team of wound-care specialists through telemedicine would significantly improve the likelihood of wound healing compared with the best available conventional practice. A total of 90 chronic wound patients in home care met all study criteria and were included: 50 in the telemedicine group and 40 in the conventional group. Patients with pressure ulcers, surgical wounds, and cancer wounds were excluded. During the 1-year follow-up, complete wound healing was achieved in 35 patients (70%) in the telemedicine group compared with 18 patients (45%) in the conventional group. After adjusting for important covariates, offering advice on wound management through telemedicine was associated with significantly increased healing compared with the best available conventional practice (telemedicine vs. conventional practice: adjusted hazard ratio 2.19; 95% confidence interval: 1.15-4.17; P=0.017). This study strongly supports the use of telemedicine to connect home-care nurses to a team of wound experts in order to improve the management of chronic wounds.