Initial steps towards developing a predictive algorithm of disease progression for hidradenitis suppurativa (HS): results from a Cox proportional hazard regression analysis on disease progression among a cohort of 335 Danish patients with HS.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory and scarring disease with a wide spectrum of disease severity. The amount of scarring is proportional to the preceding tissue damage and poses a challenge to patients. Severe HS is most often treatment recalcitrant, but hypothetically avoidable through early biologic treatment. Early prediction of individual risk of disease progression is therefore essential for patient management. OBJECTIVES: To investigate risk factors associated with disease progression and to design an algorithm capable of predicting disease -progression. METHODS: A prospective cohort study of 335 Hurley III-naïve patients with HS, not treated with biologics, was followed for a median of 2 years. Potential risk factors covered basic demographics, HS anamnestic factors and clinical HS factors collected during physical examination. Two separate Cox proportional hazard regression (CPHR) analyses were conducted. A summated 'progression score' was calculated and used in the predictive algorithm of severe disease. Subsequent bootstrap sampling was used to validate the predictability of the predictive algorithm. RESULTS: The CPHR analysis of Transition to severe disease found that active smoking [hazard ratio (HR) 4.01, 95% confidence interval (CI) 1.71-9.40, P = 0.001]; body mass index (BMI) points > 25 at baseline (each point: HR 1.06, 95% CI 1.02-1.09, P < 0.001); active disease in 2 (HR 4.26, 95% CI 1.23-14.84, P = 0.02) and ≥ 3 areas (HR 6.54, 95% CI 1.89-22.72, P = 0.003) all constituted substantial risk factors. Conversely, the CPHR analysis of Disease progression did not yield results of clinical relevance. A 'progression score' of 3.04 was used as a threshold in the predictive algorithm of Transition to severe disease and achieved the following test specifics: sensitivity = 0.51, specificity = 0.86, positive predictive value = 0.50, negative predictive value = 0.86. CONCLUSIONS: We found a disparity between factors increasing the risk of simple Disease progression and those increasing the risk of Transition to severe disease. For the latter, active smoking, BMI points > 25, active disease in 2 or ≥ 3 areas were all shown to be the clinically relevant factors that could be used to construct an algorithm that correctly predicted progression to severe HS in more than half of all instances.

Bacterial biofilm is associated with higher levels of regulatory T cells in unaffected hidradenitis suppurativa skin.

BACKGROUND: The role of bacterial biofilm in hidradenitis suppurativa (HS) is highly debated. Less biofilm is found in clinically unaffected axillary perilesional skin of HS patients compared with healthy controls. OBJECTIVE: To study the correlation between biofilm and the phenotypical characterization of the preclinical inflammatory infiltrate. MATERIALS AND METHODS: An exploratory comparative study of punch biopsies from unaffected axillary HS skin compared to similarly biopsies from healthy controls underwent standard staining procedures for CD4, CD8, CD25, FoxP3 and IL17. Standard-sized inflammatory histological hotspots were identified manually. Slides were scanned into Leica Biosystems' Digital Image Hub. Number of stained cells per slide and hotspot was found using an algorithm. RESULTS: 12.5% of HS had biofilm compared to 85% of controls. For full slides, HS patients had more CD4+ cells than controls; HS patients with biofilm had higher CD4+ cell number than controls with or without biofilm and HS patients without biofilm. For hotspots, HS patients with biofilm had higher number of CD4+FoxP3+ cells than HS patients without biofilm and controls with biofilm. CONCLUSION: The association between biofilm and the number of regulatory T cells in HS patients supports the concept of dysbiosis as a factor in the preclinical HS lesions.

Serum Anticytokine Autoantibody Levels Are Not Increased in Hidradenitis Suppurativa: A Case-Control Pilot Study.

BACKGROUND: Hidradenitis suppurativa is a skin disease of recurrent episodes of inflammatory nodules, abscesses, and scarring of the intertriginous regions, e.g. the axillae and groin. A dysregulated immune response to one or more unknown antigens in hidradenitis suppurativa has been suggested. One hypothetical element of this dysregulation may be the functionality of the cytokines. This study examines the serum level of anticytokine autoantibodies for interleukin (IL)-1α, IL-6, IL-10, IL-17A, IL-17E, IL-17F, and interferon-α. METHOD: Recombinant, carrier-free cytokines were coupled to microspheres. The coupled beads were incubated for 1 h in the dark with assay buffer-diluted sera, and subsequently for 30 min with polyclonal goat F(ab')2 anti-human IgG phycoerythrin-conjugated antibody. Data are presented as the median fluorescence intensity of samples. RESULTS: No difference in levels of anticytokine autoantibodies was demonstrated for any of the autoantibodies studied. DISCUSSION: The data suggest that endogenously produced autoantibodies only play a minor role, if any, in hidradenitis suppurativa.

Primary skin abscess microbiota a systematic review.

An abscess is a collection of pus forming a cavity in the tissue, for example, the skin. They are generally perceived as the result of infection but infection is not mandatory for the diagnosis. Skin abscesses may occur independently (primary) or be part of other diseases such as the recurrent inflammatory skin disease hidradenitis suppurativa (HS). HS is noninfectious but nevertheless abscesses are a common differential diagnosis. The purpose of this study is to review the microbiome of bacteria positive primary skin abscesses in order to explore the reported microbiota. EMBASE, MEDLINER, and COCHRANE LIBRABRY were searched on 9th of October 2021 for microbiome, skin, and abscesses. Studies with more than 10 patients reporting the microbiome in human skin-abscesses were included and studies with abscess microbiota sampled from HS patients, microbiota not sampled from skin-abscesses, missing information on microbiome data, sampling bias, studies in other language than English or Danish, reviews and meta-analyses were excluded. In total 11 studies were included for further analysis. S. aureus is likely to dominate the microbiome of bacteria positive primary skin abscesses in contrast to the polymicrobial microbiome of HS.

Mammary Hidradenitis Suppurativa Lesions - A Suggestion for Phenotyping.

BACKGROUND: Hidradenitis suppurativa (HS) is an under-diagnosed chronic inflammatory skin disease of the pilosebaceous unit of apocrine gland-rich parts of the body. The mammary area is the fourth most HS-affected area and, as typical lesions include non-fluctuating nodules, abscesses, and tunnels/sinus tracts, mammary HS is often mistaken for other mammary "boils", such as sub-areolar and granulomatous non-lactating breast abscesses. Our objective was to present a spectrum of mammary HS lesions, explore a possible classification, and expose mammary HS as a possible differential diagnosis to non-lactational breast abscesses. METHODS: A cross-sectional study on current and newly-referred patients treated for HS affecting the mammary area. Anamnestic information, subjective outcome measures, and lesion counts including anatomical location were collected. Patients with similar morphologies were grouped, and characteristics for the groups were investigated. LIMITATIONS: We were not aware of the number of morphologies we would find, and as a result the study did not have sufficient power to show significant differences after correction for multiple testing. RESULTS: We found three morphologically different subtypes of mammary HS; the Sternal, the Frictional, and the Nodule types. These groups differed in anatomical lesion characteristics and other patient characteristics. Furthermore, we found a fourth Mixed type - a combination of the other three. CONCLUSION: Differential diagnosis between mammary HS and sub-areolar or granulomatous non-fluctuating non-lactating breast abscess is most easily performed by assessing the precise anatomical location of the lesion and determining if the mammary lesion is the only lesion present or if similar lesions exist in other HS-specific areas.

The effect of age on self-rated skin pain in patients with hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a recalcitrant chronic inflammatory skin disease characterized by recurrent and painful nodules that negatively affect health-related quality of life. Pain is the most disabling symptom of HS, but data on HS pain remain limited. We previously observed a dissociation between pain and number of HS lesions with regards to increasing age. OBJECTIVES: To further explore this observation, we investigated the relationship between experienced HS pain and age, adjusting for other relevant factors that might affect pain assessment. MATERIALS & METHODS: We conducted a retrospective cohort study (n = 342) using data from the Registry for Hidradenitis Suppurativa database. Multiple linear regression analysis was performed for self-evaluated pain (measured on a 0-10 numerical rating scale [NRS]) as an outcome with age and adjusted for the effects of sex, BMI, smoking status, lesion count and percentage of lifetime spent with HS symptoms. RESULTS: The multiple linear regression showed that age was associated with a decreased pain level of 0.31 NRS points/year (95% CI: -0.062; -0.0088; p = 0.044) and number of nodules was associated with an increased pain level of 0.081 NRS points/nodule (95% CI: 0.00077; 0.16; p = 0.048). Percentage of lifetime spent with HS symptoms was not found to significantly affect pain levels. CONCLUSION: This study supports our hypothesis that older HS patients report decreased levels of pain, independent of disease severity, which may be due to factors such as demyelination of nerve fibres, reduced painful physical activity, improved coping, or associated co-morbidities that distract from HS-related pain.

Umbilical hidradenitis suppurativa symptoms: a case series and review of the literature.

INTRODUCTION: Umbilical erythema, itching, pain, and suppuration among hidradenitis suppurativa (HS) patients form a group of symptoms that is not described in the medical literature. METHODS: A review of the medical literature combined with a case series of patients experiencing umbilical symptoms in relation to HS. These were collected among 348 HS patients connected to the Department of Dermatology at Zealand University Hospital, Roskilde, Denmark, and members of the Danish HS Association's Facebook page (Patientforeningen HS Danmark), who were asked to complete a questionnaire to better describe their symptoms. RESULTS: Umbilical symptoms among HS patients are previously undescribed in the medical literature. Among the outpatient clinic's patients, 7.1% (24/348) experienced umbilical symptoms, and for the Facebook group the number was 10.3% (28/272). Twenty-eight patients agreed to answer the questionnaire. Three-quarters of them experienced not only itching and erythema, but also malodorous and/or bloody umbilical discharge. CONCLUSIONS: The description of discharge symptoms experienced by many patients is similar to the description of symptoms of an umbilical pilonidal sinus (UPS). This is a condition with a morphology reminiscent to that of HS because it is defined by sinus tract formation triggered by hair penetrating the umbilical skin. UPS could be an explanation for umbilical HS symptom.

Disease Trajectories for Hidradenitis Suppurativa in the Danish Population.

Importance: Hidradenitis suppurativa (HS) is a chronic skin disease characterized by recurrent inflamed nodular lesions and is associated with multiple comorbidities; previous studies have been of cross-sectional design, and the temporal association of HS with multiple comorbidities remains undetermined. Objective: To evaluate and characterize disease trajectories in patients with HS using population-wide disease registry data. Design, Setting, and Participants: This retrospective registry-based cohort study included the entire Danish population alive between January 1, 1994, and April 10, 2018 (7 191 519 unique individuals). Among these, 14 488 Danish inhabitants were diagnosed with HS or fulfilled diagnostic criteria identified through surgical procedure codes. Exposures: Citizens of Denmark with a diagnosis code of HS as defined by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) or as identified through surgical procedures. Main Outcomes and Measures: Disease trajectories experienced more frequently by patients with HS than by the overall Danish population. Strength of associations between disease co-occurrences was evaluated using relative risk (RR). All significant disease pairs were tested for directionality using a binomial test, and pairs with directionality were merged into disease trajectories of 3 consecutive diseases. Numerous disease trajectories were combined into a disease progression network showing the most frequent disease paths over time for patients with HS. Results: A total of 11 929 individuals were identified by ICD-10 diagnosis codes (8392 [70.3%] female; mean [SD] age, 37.72 [13.01] years), and 2791 were identified by procedural codes (1686 [60.4%] female; mean [SD] age, 37.38 [15.83]). The set of most common temporal disease trajectories included 25 diagnoses and had a characteristic appearance in which genitourinary, respiratory, or mental and behavioral disorders preceded the diagnosis of HS and chronic obstructive pulmonary disease (604 cases [4.2%]; RR, 1.57; 95% CI, 1.55-1.59; P < .001), pneumonia (827 [5.7%]; RR, 1.18; 95% CI, 1.15-1.20; P < .001), and acute myocardial infarction (293 [2.0%]; RR, 1.37; 95% CI, 1.35-1.39; P < .001) developed after the diagnosis. Conclusions and Relevance: The findings suggest that patients with newly diagnosed HS may have a high frequency of manifest type 1 diabetes and subsequent high risk of acute myocardial infarction, pneumonia, and chronic obstructive pulmonary disease.

Psoriasis as a comorbidity of hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) and psoriasis (PSO) appear to share important pathogenic elements; in spite of this, the co-occurrence of the two has been widely unexplored. METHODS: To explore the co-occurrence of HS and PSO, we recorded the number of patients attending the outpatient clinic at the Department of Dermatology, Zealand University Hospital, Roskilde, Denmark, for the ICD10 diagnosis HS (DL73.2) or PSO (DL40.0, DL40.3, DL40.4, DL40.8, and DL40.9). Data were further compared with previously reported Danish national prevalence rates for HS and PSO. RESULTS: A total of 1,036 patients were included from the outpatient clinic: 440 HS, 624 PSO, and 28 with both diagnoses. In total 6.4% of HS patients had PSO, and 4.5% of PSO patients had HS. HS patients had OR = 2.99 (95% CI 2.04-4.38) of having PSO as compared to the background population. For PSO patients, they had OR = 2.56 (95% CI 1.74-3.77). DISCUSSION: We found a strong association between HS and PSO, which implies a possible comorbidity between PSO and HS that has not previously been properly elucidated. Such a connection could be a common inflammatory pathway driven by the increased secretion of IL-12/23 and TNFα that is a hallmark of both diseases.

Teledermatology management of difficult-to-treat dermatoses in the Faroe Islands.

INTRODUCTION: Teledermatology is a useful tool for underserved areas. However, because it is not without costs, knowledge of the burdens incurred by teledermatology treatment would be valuable for future types of management. METHODS: All specialist dermatology services in the Faroe Islands have been provided by our department through a mix of standard and teledermatology consultations. We performed a retrospective review of the teledermatology database from its inauguration in 2003 to November 2018. The ratio of consultations per patient (CPP) was calculated as a way to investigate any disproportionate teledermatology burden per patient with a specific disease. RESULTS: The most common diagnoses were psoriasis, dermatitis, atopic dermatitis, and acne. Among the most frequent CPP diagnoses were bullous pemphigoid, hidradenitis suppurativa, lichen sclerosus, and granuloma annulare. DISCUSSION: Dermatological conditions that require paraclinical assistance for diagnosis, hands-on examination, or treatment with either biologics or surgery will all result in high CPP. However, teledermatology still has a place in the treatment of high-CPP dermatoses in rural areas because there is no other alternative. For non-rural areas, CPP can be used as a way to identify those dermatoses that are not advantageous to treat using telemedicine, but instead best benefit from standard face-to-face consultation.