Haptoglobin is an independent marker for disease severity and risk for metabolic complications in hidradenitis suppurativa: A prospective study.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease that is highly correlated with obesity. Haptoglobin serum levels have recently been recognized as an important biomarker linking obesity with chronic inflammation. OBJECTIVE: To compare haptoglobin with previously proposed serum biomarkers for the determination of disease severity in HS patients. For this purpose, disease severity of HS patients was determined by a panel of clinical scores as well as several risk factors, such as weight and smoking habits. METHODS: A prospective, diagnostic accuracy study was performed at the International Centre for Hidradenitis suppurativa/Acne inversa Bochum (ICH). The study included a total of 263 patients, including 131 who had a confirmed diagnosis of HS in Hurley I (n = 16), II (n = 56) and III (n = 59) HS, and 132 healthy controls. The main outcome was to identify serological inflammatory markers for HS disease severity [severe (III) vs. moderate/mild (II/I)] as assessed by Hurley classification. RESULTS: The serum levels of acute phase proteins haptoglobin and CRP, as well as the number of neutrophils in peripheral blood, number of monocytes, the systemic immune-inflammation index and the pan-immune-inflammatory value correlated with disease severity according to established clinical scores (mHSS, SAHS, Hurley, DLQI). HS patients had significantly higher haptologlobin levels compared to healthy controls. Logistic regression analysis revealed haptoglobin as the only independent marker predicting severe HS. CONCLUSION: In this prospective study, we discovered that the serum levels of the acute phase protein haptoglobin levels serve as an independent marker of disease severity in HS. While this presents the first study in the context of HS. Thus, the present data not only yield a highly promising serum marker to be further validated.

Complete blood collection-based systemic inflammation biomarkers for patients with hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a relatively common chronic inflammatory condition of intertriginous skin. In recent years, the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR) and platelet/neutrophil ratio (PLR) have been shown to be indicators of systemic inflammation correlating with severity of inflammatory conditions. OBJECTIVES: We aimed to analyse for the first time the systemic inflammation biomarkers also including the pan-immune-inflammation value (PIV) and the systemic immune-inflammation index (SII) in HS patients and controls. METHODS: This study retrospectively investigated clinical and laboratory data of 142 patients with HS. Moreover, a sex-age-matched healthy control group was included. The severity of HS was routinely assessed by the Hurley staging, the mHSS and the SAHS score. All inflammation-based biomarkers were calculated from absolute values of complete blood counts. Receiver-operating characteristics analyses, including the Youden index, were performed in order to determine optimal cut-off values and test performance. RESULTS: Whereas PIV and SII were significantly higher in HS patients, PLR, MLR and PNR were significantly lower in HS patients when compared to controls. Almost all inflammation-based biomarkers significantly correlated with disease severity. However, PIV was the only test that was significantly associated with HS severity as indicated by a Youden index of 0.56 (associated criterion: 756.4; AUC: 0.79, P < 0.0001). CONCLUSIONS: Although all systemic inflammation-based biomarkers investigated are more or less associated with HS severity, the PIV appears to have the best performance in this regard. It may be employed in adjunction with the clinical scores for treatment decision making or clinical trial assessments.

[Hidradenitis suppurativa /acne inversa-surgical options, reconstruction and combinations with drug therapies-an update]. / Hidradenitis suppurativa/Acne inversa ­ operative Optionen, Rekonstruktionen und Kombinationen mit medikamentösen Therapien ­ Ein Update.

Hidradenitis suppurativa/acne inversa (HS/AI) is a chronic inflammatory skin disease whose treatment includes both conservative and surgical treatment options. In Hurley stages II and III, surgical resection of irreversibly destroyed tissue should be the objective. For this purpose several resection techniques exist, which differ primarily with regard to their invasiveness and tendency to recur. To date, there is no generally accepted consensus on the use of different resection and reconstruction techniques or the inclusion of drug therapies in the overall therapeutic concept.

NOD2 signalling in hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is associated with dysregulated immune responses including altered expression of cytokines, chemokines, and antimicrobial peptides and proteins (AMPs). AIMS: To evaluate the expression of nucleotide-binding oligomerization domain-containing (NOD)2 and related factors in HS skin samples and keratinocyte cultures. METHODS: We performed real-time PCR for NOD2, receptor-interacting serine/threonine-protein kinase (RIP)2, cyclic amine resistance locus (CARL), skin-derived antileukoproteinase (SKALP)/elafin, human ß-defensin (hBD)2, LL37, psoriasin and RNAse7 in lesional and nonlesional skin of 19 patients with HS and in keratinocyte cultures [unstimulated, muramyl dipeptide (MDP)-stimulated or Pam2CSK4 (Pam2)-stimulated] from and nonlesional skin. RESULTS: We observed significantly elevated mRNA expression for NOD2 (P < 0.01), hBD2 (P = 0.02), RNase7 (P < 0.001), psoriasin (P < 0.01) and SKALP/elafin (P = 0.02) in lesional compared with nonlesional skin. We found a significant correlation between NOD2 mRNA and hBD2 (r = 46; P = 0.04), psoriasin (r = 0.67; P < 0.01) and SKALP/elafin (r = 0.65; P < 0.01). In unstimulated, Pam2-stimulated and MDP-stimulated normal keratinocytes, NOD2, RIP2, CARL and SKALP/elafin expression significantly (P < 0.05) increased from 6 to 48 h, whereas in unstimulated, Pam2-stimulated and MDP-stimulated HS keratinocytes, RIP2, CARL and SKALP/elafin expression significantly (P < 0.05) declined from 6 to 48 h. mRNA expression of NOD2 (unstimulated, Pam2-stimulated, MDP-stimulated), CARL (unstimulated, Pam2-stimulated, MDP-stimulated) and SKALP/elafin (unstimulated, Pam2-stimulated) at 6 h was significantly increased in HS compared with normal keratinocytes. CONCLUSION: We have shown for the first time that NOD2 signalling is activated in HS and might contribute to the pathogenesis via induction of AMPs and activation of other pathways such as nuclear factor κB signalling.

Multivariate analysis of prognostic factors in patients with nodular melanoma.

PURPOSE: Nodular melanoma (NM) is associated with worse disease outcome when compared to superficial spreading melanoma (SSM). We aimed to perform a single-center analysis of prognostic factors in patients with NM and compare the data with SSM patients. METHODS: We studied 228 patients with NN and 396 patients with SSM. Patients with in situ melanomas or stage IV at diagnosis were not included in the study. Data were analyzed using the Mann-Whitney test, Chi-square test, Kaplan-Meier curves including the log-rank test, and logistic regression model. RESULTS: When compared to patients with SSM, patients with NM had less likely lower Clark level, higher tumor thickness, less likely tumor regression, more often ulcerated tumors, and less likely a history of precursor lesions such as a nevus. Within a 5-year follow-up we observed significantly more disease relapses and deaths in NM patients than in SSM patients. On multivariate analysis, disease relapse in NM patients was independently predicted by tumor thickness and positive SLNB, whereas melanoma-specific death of NM patients was independently predicted by male sex and tumor thickness. Histologic regression also remained in the logistic regression model as a significant independent negative predictor of NM death. CONCLUSIONS: We did not observe that NM subtype was per se a significant independent predictor for disease relapse or melanoma-specific death. Among the well-known prognostic factors such as tumor thickness and male sex, NM is also associated with other unfavorable factors such as absence of regression.

Increased expression profile of NCSTN, Notch and PI3K/AKT3 in hidradenitis suppurativa.

BACKGROUND: In a small number of kindreds with familial hidradenitis suppurativa (HS) different mutations of NCSTN (nicastrin) have been identified. Blocking of NCSTN leads to impairment of the Notch and PI3K/AKT signalling pathway, which is assumed to play a pathogenic role in HS. However, very limited data are available concerning expression levels of these pathway components in HS skin. OBJECTIVES: To analyse the mRNA and protein expression of NCSTN, Notch1-3, PIK3R3 and AKT3 in HS. METHODS: Skin samples from healthy controls, lesional and perilesional skin of HS patients with and without a positive family history were analysed by quantitative real-time RT-PCR and immunohistochemistry. Univariate statistical analyses were conducted regarding association between expression levels and patient's characteristics. RESULTS: Expression levels of all investigated genes showed significantly higher levels in lesional HS skin compared with healthy controls. Univariate analysis showed no association between a positive family history and mRNA expression levels. Perilesional HS skin of patients with mild disease severity (Hurley I) showed significant higher mRNA expression levels of the investigated pathway components compared to moderate (Hurley II) and severe disease (Hurley III). CONCLUSION: We found no evidence for diminished expression levels of the Notch signalling. In contrast, the NCSTN, Notch and PI3K/AKT signalling components are overexpressed in HS. Future research is needed to investigate a possible pathogenetic role or to reveal a coactivation of these overexpressed components during inflammatory response in HS.

Electrochemotherapy in the treatment of cutaneous malignancy: Outcomes and subgroup analysis from the cumulative results from the pan-European International Network for Sharing Practice in Electrochemotherapy database for 2482 lesions in 987 patients (2008-2019).

BACKGROUND: Electrochemotherapy (ECT) is a treatment for both primary and secondary cutaneous tumours. The international Network for sharing practices on ECT group investigates treatment outcomes after ECT using a common database with defined parameters. METHODS: Twenty-eight centres across Europe prospectively uploaded data over an 11-year period. Response rates were investigated in relation to primary diagnosis, tumour size, choice of electrode type, route of bleomycin administration, electrical parameters recorded and previous irradiation in the treated field. RESULTS: Nine hundred eighty-seven patients, with 2482 tumour lesions were included in analysis. The overall response (OR) rate was 85% (complete response [CR]: 70%, partial response rate: 15%, stable disease: 11%, and progressive disease: 2%). For different histologies, OR and CR rates for metastases of malignant melanoma were 82% and 64%, basal cell carcinoma were 96% and 85%, breast cancer metastases were 77% and 62%, squamous cell carcinoma were 80% and 63% as well as Kaposi's sarcoma were 98% and 91%, respectively. Variance was demonstrated across histotypes (p < 0.0001) and in accordance with size of lesion treated (dichotomised at diameter of 3 cm (p < 0.0001). Hexagonal electrodes were generally used for larger tumours, but for tumours up to 3 cm, linear array electrodes provided better tumour control than hexagonal electrodes (80%:74%, p < 0.003). For tumours more than 2 cm, intravenous administration was superior to intratumoural (IT) administration (p < 0.05). Current recorded varied across tumour histologies and size but did not influence response rate. In previously irradiated areas, responses were selectively lower for IT administration. CONCLUSIONS: These cumulative data endorse efficiency of ECT across a broad range of histotypes. Analysis of 2482 lesions details subgroup analysis on treatment response informing future treatment choices.

Does very early timing of lymph node surgery after resection of the primary tumour improve the clinical outcome of patients with melanoma?

BACKGROUND: In patients with cutaneous melanoma (CM), the time span between resection of the primary tumour and sentinel lymph node biopsy (SLNB) as well as the subsequent interval between SLNB and complete lymph node dissection (CLND) varies greatly. AIM: To determine whether very early timing of SLNB after resection of the primary tumour, or timing of CLND after SLNB affect the clinical outcome of patients with CM, compared with longer time intervals. METHODS: We compared the time spans between complete resection of the primary tumour and SLNB, and the interval between SLNB and CLND in a cohort of 896 patients with melanoma who had undergone SLNB. An interval between primary resection and SLNB or between SLNB and CLND of up to 7 days was classified as very early (VE-SLNB and VE-CLND, respectively). This time span was compared with intervals of > 7 days. Univariate and multivariate statistics were performed. RESULTS: VE-SLNB was significantly associated with the presence of micrometastases. However, this was probably due to tumour thickness being significantly higher in patients with VE-SLNB compared with patients with later SLNB. Importantly, VE-SLNB was not significantly associated with disease relapse and VE-CLND was not associated with melanoma-specific death. CONCLUSIONS: VE-SLNB and VE-CLND neither improved nor worsened the clinical outcome of patients. Thus, timing of SLNB and CLND has no influence on the overall clinical outcome of patients with melanoma. Our findings support the rational planning of lymph node surgery after resection of the primary tumour and provide help for effective patient counselling.

[Hidradenitis suppurativa/acne inversa in the genitoanal region]. / Hidradenitis suppurativa/Acne inversa in der Genitoanalregion.

Hidradenitis suppurativa/acne inversa (HS/AI) is a chronic inflammatory skin disease. Several studies showed that perianal, perineal and gluteal involvement is more common in men. Axillary, submammary and inguinal localizations seem to be more prevalent in women. Involvement of the genitoanal region is associated with a higher reduced quality of live and sexual health compared to other locations. Moreover HS/AI in the genitoanal region can lead to serious complications. The knowledge of perianal fistula formation, pubogenital lymphedema and squamous cell carcinoma, which are three of the most severe complications, is critical for adequate treatment.

Frequency of circulating subpopulations of T-regulatory cells in patients with hidradenitis suppurativa.

BACKGROUND: Decreased number of T-regulatory cells (Tregs) and/or their loss of function potentially lead to uncontrolled immune-mediated inflammatory responses. There are only few data available on Tregs in hidradenitis suppurativa (HS) - a disease in which it has been suggested that host immune factors and an overactive immune system of the follicular epithelium play a pathogenetic role. OBJECTIVES: To analyse frequencies of Tregs subpopulations in blood of HS patients in comparison with a healthy control group. MATERIALS & METHODS: Blood samples obtained from HS patients and healthy controls were evaluated by flow cytometry and enzyme-linked immunosorbent assay. RESULTS: The frequency of natural Tregs among CD4+ T lymphocytes were significantly reduced in the HS group compared to the healthy controls. The proportion of activated Tregs, non-suppressive Tregs and proliferating Tregs showed no significant difference when compared to controls. Regarding Tregs frequencies, there was no significant difference between the three Hurley stages. Serum concentrations of IL-10, TGF-ß1 and IL-17A did not show significant differences between the HS and control group. CONCLUSION: The reduction of natural Tregs observed in blood of HS patients could be the result of Tregs homing to sites of inflammatory hot spots in HS skin. Further studies are justified evaluating the role of circulating Tregs during the evolution of HS lesions and as a biomarker for treatment response.

Hidradenitis suppurativa/acne inversa: a practical framework for treatment optimization - systematic review and recommendations from the HS ALLIANCE working group.

Hidradenitis suppurativa (HS)/acne inversa is a debilitating chronic disease that remains poorly understood and difficult to manage. Clinical practice is variable, and there is a need for international, evidence-based and easily applicable consensus on HS management. We report here the findings of a systematic literature review, which were subsequently used as a basis for the development of international consensus recommendations for the management of patients with HS. A systematic literature review was performed for each of nine clinical questions in HS (defined by an expert steering committee), covering comorbidity assessment, therapy (medical, surgical and combinations) and response to treatment. Included articles underwent data extraction and were graded according to the Oxford Centre for Evidence-based Medicine criteria. Evidence-based recommendations were then drafted, refined and voted upon, using a modified Delphi process. Overall, 5310 articles were screened, 171 articles were analysed, and 65 were used to derive recommendations. These articles included six randomized controlled trials plus cohort studies and case series. The highest level of evidence concerned dosing recommendations for topical clindamycin in mild disease (with systemic tetracyclines for more frequent/widespread lesions) and biologic therapy (especially adalimumab) as second-line agents (following conventional therapy failure). Good-quality evidence was available for the hidradenitis suppurativa clinical response (HiSCR) as a dichotomous outcome measure in inflammatory areas under treatment. Lower-level evidence supported recommendations for topical triclosan and oral zinc in mild-to-moderate HS, systemic clindamycin and rifampicin in moderate HS and intravenous ertapenem in selected patients with more severe disease. Intralesional or systemic steroids may also be considered. Local surgical excision is suggested for mild-to-moderate HS, with wide excision for more extensive disease. Despite a paucity of good-quality data on management decisions in HS, this systematic review has enabled the development of robust and easily applicable clinical recommendations for international physicians based on graded evidence.

Melanocytic soluble adenylyl cyclase protein expression around lentigo maligna and in contralateral control skin.

Recurrence rates of both lentigo maligna (LM) and lentigo maligna melanoma (LMM) following conventional surgery are usually relatively high. We aimed to assess the frequencies of melanocytes in tumour-free margins around LM/LMM using soluble adenylyl cyclase (sAC) immunohistochemistry, and to compare these with those of matched healthy contralateral skin. Using the primary mouse-anti-human sAC antibody R21, we evaluated pan-nuclear melanocytic R21 immunostaining, and found that it was significantly (P < 0.001) higher in peritumoural melanocytes (median 20%; range 0-100%) than in contralateral healthy skin (mean 0%; range 0-20%). Accordingly, there was no correlation between peritumoural and contralateral R21 immunoreactivity (r = 0.12; P = 0.18). In conclusion, melanocytic R21 immunoreactivity in melanocytes is higher in tumour-free margins around LM/LMM than in site-matched contralateral skin. This observation may indicate that the biology of 'healthy'-appearing melanocytes around LM/LMM might be different from that of truly benign melanocytes.

Altered epigenetic pathways and cell cycle dysregulation in healthy appearing skin of patients with koebnerized squamous cell carcinomas following skin surgery.

BACKGROUND: Koebnerized non-melanoma skin cancer following skin trauma represents a rare and obscure event. OBJECTIVES: To study molecular pathological parameters in koebnerized squamous cell carcinomas (K-SCCs) occurring after complete tumour removal. METHODS: We assessed two patients with multiple sclerosis who were on treatment with dimethylfumarate (DMF) preceded by long-term azathioprine therapy. Both patients rapidly developed several K-SCCs following histopathologically proven complete excision of cutaneous SCCs. We performed immunohistochemistry for p53, p16, Ki-67, TET-2, IDH-2, 5-hmc and 5-mc. PCR was carried out for the detection of human papilloma viruses. Mutation analysis was performed for BRAF, K-RAS and EGFR. RESULTS: All lesions investigated were negative for HPV DNA. Mutations were not detected. Healthy appearing skin of both patients showed relatively high Ki-67, p16 and p53 expression which was comparable to the expression observed in primary SCCs as well as K-SCCs. Protein expression of Ki-67, p16 and mutant p53 was barely detected in the specimens of the healthy controls. A decreased protein expression of TET-2 enzyme was seen in all tumours and healthy appearing skin when compared to the skin of healthy controls. CONCLUSIONS: We observed two patients with K-SCCs developing under DMF treatment. In healthy appearing skin of patients with K-SCCs, wound healing processes, including induction of proliferation and growth factor release, might promote the growth of preneoplastic keratinocytes and cancer formation on the basis of pre-existing altered epigenetic pathways and cell cycle dysregulation. Although fumarates can reduce TET-2 expression, the role of DMF intake in the development of K-SCCs remains unclear.

[Surgical treatment options for hidradenitis suppurativa/acne inversa]. / Operative Behandlungsoptionen bei Hidradenitis suppurativa/Acne inversa.

Hidradenitis suppurativa/acne inversa (HS/AI) is a chronic inflammatory skin disease. Therapy consists of conservative and surgical treatment options. In Hurley stages II and III, surgical intervention is regarded as the method of choice for areas with irreversible tissue destruction. Resection techniques with different grades of invasiveness are described in the literature. Nevertheless, there is no generally accepted concept regarding resection and reconstruction techniques or specific postoperative care. Due to lack of definitions of recurrence after surgery and poor study quality, recurrence rates are difficult to determine.

Histological findings after argon plasma coagulation: an ex-vivo study revealing a possible role in superficial ablative treatment of the skin.

Argon plasma coagulation (APC) is an electrosurgical technique which can be used to ablate skin lesions with limited invasion depth into dermal tissue. Hence, APC might be well suited for the removal of epithelial tumours. However, there are no data on the effects of APC on human skin tissue. Thus, the aim of this study was to determine the extent of epidermal and dermal damage after APC of human skin. We performed APC ex-vivo on 91 freshly resected human skin samples, which were obtained after reconstructive surgical closures in actinically damaged areas. Tissue effects were evaluated histologically and compared across different power settings. Using 15, 30, and 45 W, median (interquartile range; IQR) coagulation depths were 110.0 µm (91.7-130.0), 113.3 µm (85.8-135.0), and 130.0 µm (100.0-153.3.0), respectively. Median (IQR) thickness of necrosis zone was 30.0 µm (23.3-40.0) at 15 W, 26.7 µm (20.0-41.6) at 30 W, and 43.3 µm (30.8-57.5) at 45 W. The Kruskal-Wallis test showed significant differences between 15 and 30 W versus 45 W for coagulation depth (P = 0.0414), necrosis zone (P = 0.0017), and necrosis according to overlaying epidermal thickness (P = 0.0467). In summary, APC is a simple and controllable electrosurgical technique to remove epidermal tissue with limited penetration to the dermis. Thus, APC is particularly suited for the ablation of epithelial skin lesions and, therefore, may serve as possible treatment approach for intraepithelial neoplasms such as actinic keratosis.

Towards global consensus on core outcomes for hidradenitis suppurativa research: an update from the HISTORIC consensus meetings I and II.

BACKGROUND: A core outcomes set (COS) is an agreed minimum set of outcomes that should be measured and reported in all clinical trials for a specific condition. Hidradenitis suppurativa (HS) has no agreed-upon COS. A central aspect in the COS development process is to identify a set of candidate outcome domains from a long list of items. Our long list had been developed from patient interviews, a systematic review of the literature and a healthcare professional survey, and initial votes had been cast in two e-Delphi surveys. In this manuscript, we describe two in-person consensus meetings of Delphi participants designed to ensure an inclusive approach to generation of domains from related items. OBJECTIVES: To consider which items from a long list of candidate items to exclude and which to cluster into outcome domains. METHODS: The study used an international and multistakeholder approach, involving patients, dermatologists, surgeons, the pharmaceutical industry and medical regulators. The study format was a combination of formal presentations, small group work based on nominal group theory and a subsequent online confirmation survey. RESULTS: Forty-one individuals from 13 countries and four continents participated. Nine items were excluded and there was consensus to propose seven domains: disease course, physical signs, HS-specific quality of life, satisfaction, symptoms, pain and global assessments. CONCLUSIONS: The HISTORIC consensus meetings I and II will be followed by further e-Delphi rounds to finalize the core domain set, building on the work of the in-person consensus meetings.

Interleukin-36 in hidradenitis suppurativa: evidence for a distinctive proinflammatory role and a key factor in the development of an inflammatory loop.

BACKGROUND: Possible regulatory involvement of the interleukin (IL)-36 family in inflammatory diseases has been suggested. OBJECTIVES: To analyse the expression of IL-36α, IL-36ß, IL-36γ and the antagonistic cytokines IL-36 receptor agonist (IL-36Ra), IL-37 and IL-38 in the skin of patients with hidradenitis suppurativa (HS). METHODS: Skin samples from lesional and corresponding perilesional HS skin, and from healthy controls were included in this study and analysed by quantitative real-time reverse-transcriptase polymerase chain reaction (PCR). To evaluate the PCR results of IL-36α, IL-36ß and IL-36γ, a subset of skin samples was studied by immunohistochemistry. RESULTS: Expression levels of IL-36α, IL-36ß, IL-36γ and IL-36Ra were all significantly higher in lesional HS skin than in healthy controls. IL-37 and IL-38 levels were significantly higher in perilesional HS skin than in healthy controls and were decreased in lesional HS skin. Limitations of the study are its descriptive nature and the small sample size. CONCLUSIONS: Our results showed a possible involvement of IL-36 cytokines in the inflammatory network of HS and a dysbalance between the agonistic and antagonistic cytokines in HS skin.

Development and validation of the International Hidradenitis Suppurativa Severity Score System (IHS4), a novel dynamic scoring system to assess HS severity.

BACKGROUND: A validated tool for the dynamic severity assessment of hidradenitis suppurativa/acne inversa (HS) is lacking. OBJECTIVES: To develop and validate a novel dynamic scoring system to assess the severity of HS. METHODS: A Delphi voting procedure was conducted among the members of the European Hidradenitis Suppurativa Foundation (EHSF) to achieve consensus towards an initial HS Severity Score System (HS4). Strengths and weaknesses of HS4 were examined by a multicentre prospective study. Multivariate logistic regression, discriminant analysis and receiver operating characteristic curves, as well as examination for correlation (Spearman's rho) and agreement (Cohen's kappa) with existing scores, were engaged to recognize the variables for a new International HS4 (IHS4) that was established by a second Delphi round. RESULTS: Consensus HS4 was based on number of skin lesions, number of skin areas involved and Dermatology Life Quality Index (DLQI), and was evaluated by a sample of 236 patients from 11 centres. Subsequently, a multivariate regression model calculated adjusted odds ratios for several clinical signs. Nodules, abscesses and draining tunnels resulted as the scoring variables. Three candidate scores were presented to the second Delphi round. The resulting IHS4 score is arrived at by the number of nodules (multiplied by 1) plus the number of abscesses (multiplied by 2) plus the number of draining tunnels (multiplied by 4). A total score of 3 or less signifies mild, 4-10 signifies moderate and 11 or higher signifies severe disease. Cohen's kappa was fair (κ = 0·32) compared with Hurley classification, and moderate (κ = 0·49) compared with Expert Opinion. Correlation was good (ρ > 0·6) with Hurley classification, Expert Opinion, Physician's Global Assessment and Modified Sartorius score, and moderate for DLQI (ρ = 0·36). CONCLUSIONS: The novel IHS4 is a validated tool to dynamically assess HS severity and can be used both in real-life and the clinical trials setting.

A case series of verrucae vulgares mimicking hyperkeratosis in individuals with diabetic foot ulcers.

BACKGROUND: Diabetic foot ulcers are a common complication in the advanced stages of diabetes mellitus. Certain lesions may be refractory to usual treatments with prolonged healing. In these cases, differential diagnoses to classical ulcers should be considered. Although plantar warts are a common and easy-to-diagnose finding in the general population, diagnosis can be challenging in people with diabetic foot ulcers, as they mimic hyperkeratosis in these people. CASE REPORT: We report seven cases of people with diabetic foot ulcers and verrucae vulgares mimicking treatment-refractory hyperkeratosis, presenting to our centre between 2014 and 2016. Diagnosis was aided by the clinical presentation, followed by dermoscopy and punch biopsy. Treatment included topical application of 5-fluoruracil and salicylic acid (four people), cryotherapy (three people) and surgical excision (three people), all in combination with local pressure offloading. In five people, the verrucae were completely removed after a mean treatment period of 9.4 months; two individuals were lost to follow-up. CONCLUSION: Verrucae may be more common in people with diabetic foot lesions and polyneuropathy than generally assumed. Typical findings include small, pinhead-sized bleedings within and surrounding hyperkeratous lesions. These findings should alert the clinician for the potential presence of a verruca. In such cases, biopsy should be performed to enable specific diagnosis and treatment.