D.M. Saunte

Diagnostic delay in hidradenitis suppurativa is a global problem.

DEAR EDITOR, Hidradenitis suppurativa (HS) is clinically defined with recognized diagnostic criteria and recognizable physical characteristics. Untreated, the disease causes significant morbidity. The prevalence varies between 0 0003% and 4% depending on the study population. Estimates from insurance databases suggest a prevalence of < 0 1%. This variation strongly suggests a significant selection bias or misclassification, and it may be speculated that not all patients present for care. This is reinforced by clinical experience and published evidence indicating a significant delay in diagnosis. This study explores the delay in diagnosis for patients with HS on an international level. The study (survey) was conducted in 2013. Observational data were collected during routine visits or extracted from case records. Because of the simple and obvious symptomatology of recurrent painful lesions present in restricted welldefined areas of the body, patients’ self-reported history was considered valid regarding onset of symptoms. Consecutive patients with HS and psoriasis were included from each participating centre during a period of 4 months or less. The data were anonymized by removing any names, addresses and social security numbers, and included age, sex, age at disease onset, age at diagnosis, delay in diagnosis, time from onset of symptoms to first physician contact, age at first medical contact, number of physicians seen prior to the diagnosis, family history and disease severity. If the diagnosis was made by a primary care physician or by a specialist other than a dermatologist prior to seeing a dermatologist, this was recorded as the date of the diagnosis. Individual centres were responsible for and obtained any locally required permissions and signed informed consent forms, for example ethics committee approval, in accordance with national registry and data protection rules. Patients diagnosed with HS or psoriasis (and confirmed by the investigator) were included. The primary outcome was quantification of the delay in diagnosis. Additionally, documentation was made of both the delay in visiting a physician (and so gaining access to specialist treatment) and the relative delay in diagnosis of HS compared with psoriasis with/without a family history. The severity of HS was determined by Hurley’s staging criteria: stage I, mild; stage II, moderate and stage III, severe. In patients with psoriasis, severity was evaluated by the Psoriasis Area and Severity Index: score < 7, mild; 7–12, moderate and > 12, severe. The t-test, Wilcoxon rank sum test and v-test were used where appropriate. Univariate and multivariate logistic regression analyses were used to identify factors predictive of significant diagnostic delay. Diagnostic delay > 2 years was defined as significant. Diagnosis, sex, age of onset, family history and disease severity were selected as potentially important

Tumor Cell Adhesion As a Risk Factor for Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma

PURPOSE Less than 20% of patients with melanoma who undergo sentinel lymph node (SLN) biopsy based on American Society of Clinical Oncology/Society of Surgical Oncology recommendations are SLN positive. We present a multi-institutional study to discover new molecular risk factors associated with SLN positivity in thin and intermediate-thickness melanoma. PATIENTS AND METHODS Gene clusters with functional roles in melanoma metastasis were discovered by next-generation sequencing and validated by quantitative polymerase chain reaction using a discovery set of 73 benign nevi, 76 primary cutaneous melanoma, and 11 in-transit melanoma metastases. We then used polymerase chain reaction to quantify gene expression in a model development cohort of 360 consecutive thin and intermediate-thickness melanomas and a validation cohort of 146 melanomas. Outcome of interest was SLN biopsy metastasis within 90 days of melanoma diagnosis. Logic and logistic regression analyses were used to develop a model for the likelihood of SLN metastasis from molecular, clinical, and histologic variables. RESULTS ITGB3, LAMB1, PLAT, and TP53 expression were associated with SLN metastasis. The predictive ability of a model that included these molecular variables in combination with clinicopathologic variables (patient age, Breslow depth, and tumor ulceration) was significantly greater than a model that only considered clinicopathologic variables and also performed well in the validation cohort (area under the curve, 0.93; 95% CI, 0.87 to 0.97; false-positive and false-negative rates of 22% and 0%, respectively, using a 10% cutoff for predicted SLN metastasis risk). CONCLUSION The addition of cell adhesion-linked gene expression variables to clinicopathologic variables improves the identification of patients with SLN metastases within 90 days of melanoma diagnosis.

The bacteriology of hidradenitis suppurativa: a systematic review

Hidradenitis suppurativa (HS) is a chronic inflammatory disabling skin disease consisting of recurrent nodules, sinuses, fistulas and scarring involving the intertriginous regions. HS is often a therapeutic challenge and most treatments are off‐label. A better understanding of aetiology and pathogenesis of HS may facilitate the development of effective treatment. Although the clinical presentation is strongly reminiscent of bacterial infection, the role of bacteria remains controversial. Studies have isolated an array of different bacteria specimens. Consistent findings of Gram‐positive cocci and Gram‐positive rods including Staphylococus aureus, coagulase‐negative staphylococci (CoNS) and Corynebacterium species in deep tissue samples have been demonstrated in HS and may constitute a central target for the immune system. Efficacy of antibiotics, that is rifampicin, clindamycin or tetracycline, supports a microbial role in disease pathogenesis. However, these antibiotics also work as immunomodulators of especially T cells, and the underlying mechanisms may therefore be more complex. We performed a systematic review of previous studies investigating the bacterial flora in hidradenitis suppurativa. We searched PubMed, EMBASE, Royal Danish Library and Cochrane library (search date 11 December 2014). A total of 66 papers were identified and nine papers published between 1988 and 2014 matched our inclusion criteria, yielding bacteriological data of a total of 324 patients with HS (mean age 36.8 years and female/male ratio 215/109). This overview of the bacteriology may aid researchers and physicians exploring the potential role of bacteria in HS. Furthermore, to stimulate a broader debate, we also present different viewpoints on the possible role of bacteria in HS.

The Follicular Skin Microbiome in Patients With Hidradenitis Suppurativa and Healthy Controls

Importance Although the pathogenesis of hidradenitis suppurativa (HS) remains enigmatic, several factors point to potential involvement of the cutaneous microbiome. Insight into the cutaneous microbiome in HS using next-generation sequencing may provide novel data on the microbiological diversity of the skin. Objective To investigate the follicular skin microbiome in patients with HS and in healthy controls. Design, Setting, and Participants This case-control study obtained punch biopsy specimens from patients with HS (lesional and nonlesional) and healthy controls between October 1, 2014, and August 1, 2016. Data were analyzed from March to November 2016. Patients with HS were recruited from the Department of Dermatology, Zealand University Hospital, Roskilde, Denmark. Biopsy specimens were analyzed at the Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark. None of the participants received any antibiotics (systemic or topical therapy) within 1 month before the study. In patients with HS, biopsy specimens were obtained from lesional skin (axilla or groin) and nonlesional skin. Only nodules containing at least 1 visible hair follicle were biopsied. Biopsy specimens from healthy controls were obtained from the axilla only. Main Outcomes and Measures The different microbiomes were investigated using next-generation sequencing targeting 16S and 18S ribosomal RNA. Results The skin microbiome was characterized in 30 patients with HS (mean [SD] age, 46.9 [14.0] years; 19 [63% female]) and 24 healthy controls (mean [SD] age, 32.2 [12.0] years; 13 [54% female]). The next-generation sequencing data provided a previously unreported (to our knowledge) characterization of the skin microbiome in HS. The study demonstrated that the microbiome in HS differs significantly from that in healthy controls in lesional and nonlesional skin. Overall, the following 5 microbiome types were identified: Corynebacterium species (type I), Acinetobacter and Moraxella species (type II), Staphylococcus epidermidis (type III), Porphyromonas and Peptoniphilus species (type IV), and Propionibacterium acnes (type V). In lesional skin, microbiome types consisted predominantly of type I or type IV. Microbiome type IV was not detected in healthy controls. Several taxa, including Propionibacterium, showed a significantly higher relative abundance in healthy controls vs HS skin, indicating that Propionibacterium may be part of the pathogenesis in HS. Conclusions and Relevance The study findings suggest a link between a dysbiotic cutaneous microbiome and HS.

Bacterial Biofilm in Chronic Lesions of Hidradenitis Suppurativa

Chronic nonhealing or recurrent inflammatory lesions, reminiscent of infection but recalcitrant to antibiotic therapy, generally characterize biofilm‐driven diseases. Chronic lesions of hidradenitis suppurativa (HS) exhibit several characteristics, which are compatible with well‐known biofilm infections.

Hidradenitis Suppurativa: Advances in Diagnosis and Treatment

Importance Hidradenitis suppurativa (HS) is relatively common, with the prevalence of 0.05% to 4.10%, yet many patients receive inadequate treatment. Objective To review the diagnosis, epidemiology, and treatment of HS with an emphasis on advances in the last 5 years. Evidence Review A literature search was conducted using PubMed, MEDLINE (Medical Subject Headings [MeSH]), and EMBASE to include recently published treatment studies (searched from September 1, 2011, to May 1, 2017). Reviews, guidelines, conference abstracts, and studies with less than 10 patients were excluded. Furthermore, internet searches for guidelines on hidradenitis suppurativa using Baidu, Bing, Google, and Qwant browsers were performed. Findings The diagnosis of HS is made by lesion morphology (nodules, abscesses, tunnels, and scars), location (axillae, inframammary folds, groin, perigenital, or perineal), and lesion progression (2 recurrences within 6 months or chronic or persistent lesions for ≥3 months). HS is more common than was previously thought based on epidemiological analysis (0.05%-4.10%). Disability from HS can be significant. Patients with HS may have significant comorbidities (eg, obesity, metabolic syndrome, diabetes, and arthritis) and increased all-cause mortality (incidence rate ratio, 1.35 [95% CI, 1.15-1.59]). Antibiotic treatment with combinations of clindamycin and rifampicin, or ertapenem followed by combination rifampicin, moxifloxacin, and metronidazole for 6 months is effective. Adalimumab is effective in a significant proportion of patients and treatment with IL-1 and IL-12 receptor subunit beta 1 (Rb1) antibodies may also be useful. Tissue-sparing surgical techniques and carbon dioxide laser treatments also are available, but the evidence on clinical outcomes with these approaches is limited. Conclusions and Relevance Hidradenitis suppurativa is more common than previously thought and may be treated by an array of pharmacological and surgical techniques. Hidradenitis suppurativa should be considered in the differential diagnosis of nodular lesions or sinus tracts present in the axillae, groin, perineal, and mammillary fold regions.

Normal Skin Microbiota is Altered in Pre-clinical Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease defined by recurrent nodules, tunnels (sinus tracts) and scarring involving the intertriginous regions. The clinical course of HS is compatible with a biofilm-driven disease, and biofilm has been described in lesional HS skin. We therefore hypothesized that clinically unaffected HS skin would also have an increased presence of biofilm compared with that of healthy controls. We conducted a case-control study, investigating the morphology of the axillary skin microbiota. Peptide nucleic acid - fluorescence in situ hybridization probes were used in combination with confocal laser scanning microscopy. Significant differences were found in both distribution and quantity of the cutaneous microbiota in clinically non-affected axillary skin of patients with HS compared with healthy controls. Surprisingly, we detected fewer bacteria and less biofilm in patients with HS. The reduced microbiota in patients with HS may play an important role in the early course of the disease.

Pain in Hidradenitis Suppurativa: A Pilot Study.

Hidradenitis suppurativa (HS) is a chronic, inflammatory and often painful, skin disease presenting as recurrent nodules and tunnels (sinus tracts) with subsequent scarring predominantly involving the intertriginous regions. The nodules progress from non-inflamed, through inflamed nodules, to abscesses that may rupture causing suppuration and severe malodorous discharge (1). Estimates of the prevalence of HS range from 0.05% to 4% (2). Although it has been shown that the hair follicle is central to the pathogenesis of the disease the exact aetiology of HS is unknown (3, 4). Adjuvant measures may alleviate the symptoms; however, many patients require surgery to manage chronic predisposing anatomical changes. Pain is an important aspect of HS. Several studies have previously demonstrated a significant reduction in quality of life (QoL), using Dermatology Life Quality Index (DLQI), among patients with HS (5, 6). In fact, a study found that the mean DLQI scores for patients with HS (8.9) were higher than previously reported for other skin diseases, such as alopecia (8.3), acne (7.5) and psoriasis (7.0) (6). The highest DLQI scores attained were predominantly attributed to soreness, embarrassment and level of HS-related pain, highlighting the role of HS-related pain in the everyday life of patients with HS. The body of literature describing HS-related pain is small. Increased understanding of HS-related pain would aid dermatologists and other physicians in managing all aspects of HS, from the perspectives of both patients and physicians.

Low and high body mass index in hidradenitis suppurativa patients-different subtypes?

Overweight is a well‐established risk factor for hidradenitis suppurativa (HS). In this cross‐sectional study, we compare HS patients with a high body mass index (BMI) with HS patients with a low BMI to investigate differences in disease characteristics.

Prodromal symptoms in hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease, which presents as recurrent nodules and sinus tracts (tunnels) with subsequent scarring, predominantly involving the intertriginous regions. Although prodromal symptoms (i.e. various symptoms preceding the eruption of the HS lesions) are often mentioned, there have been no formal investigations into this aspect. Insight into prodromal symptoms may enable patients with HS or dermatologists in choosing a more targeted treatment at a much earlier stage, potentially increasing treatment efficacy and quality of life.