Subjects:
Acne & HS
Synopsis:
Acne and hidradenitis suppurativa (HS) both centre on hair follicles. They often occur together as part of the acne tetrad, but are found in distinct localizations. Acne is primarily defined by the presence of comedones and inflammatory lesions. However, in HS the intertriginous localization and chronicity play equally important roles for the diagnosis to the inflammatory lesions. Genetics, bacteria, environmental factors and innate inflammation have all been found to play a role in acne and/or HS. Surprisingly, there is little overlap between the findings so far. The genetics of acne and HS are distinct, bacteria have not been shown convincingly to play a role in HS, and the important risk factors obesity and smoking in HS cannot be easily translated to acne. The one driving factor central to both diseases is innate inflammation, most strikingly involving interleukin-1. Hence the interleukin-1 family, as already shown in autoinflammatory conditions associated with acne, could represent attractive treatment targets.
Full Research Link:
https://www.ncbi.nlm.nih.gov/m/pubmed/29380349/?i=14&from=autoinflammatory%20hidradenitis
Adolescent-Onset Prevalence, Risk Factors and Disease Features
Synopsis:
Background/aims: Hidradenitis suppurativa (HS) is a chronic inflammatory and destructive skin disorder. Early diagnosis and treatment are critical to stop its progression. Data concerning adolescent-onset HS are scarce. The aims of this study are to describe the prevalence of adolescent-onset HS and to explore potential risk factors and the disease features of these patients.
Patients and methods: A cross-sectional study including 134 patients was performed.
Results: Adolescent-onset HS occurred in 51.5% (69/134) of patients. Adolescent-onset HS was associated with female sex, positive family history, presence of pilonidal sinus, acne conglobata, longer disease duration and a worse perception of disease severity.
Conclusion: Adolescent-onset HS might be more frequent than previously reported. Female sex, positive family history and the presence of elements of the follicular occlusion tetrad identify individuals with a higher risk of early onset. These patients experience a longer disease duration and perceive their disease as severer.
Full Research Link: https://www.ncbi.nlm.nih.gov/pubmed/30368494
Amyloidosis in HS
Amyloidosis in hidradenitis suppurativa:
A cross-sectional study and review of literature.
Synopsis:
Background: Coexistence of hidradenitis suppurativa (HS) and amyloidosis has been anecdotally described, but the association between these conditions is yet to be firmly established.
Aim: To study the association between HS and amyloidosis using a large-scale computerized database, and to perform a literature review to characterize all reported patients with coexistent HS and amyloidosis.
Methods: A cross-sectional study was conducted comparing the prevalence of amyloidosis among patients with HS and age-, sex- and ethnicity-matched healthy controls (HCs). Additionally, a review of literature was performed to summarize all reported cases with a dual diagnosis of both conditions.
Results: In total, 4417 patients with HS and 22 085 controls were included in the study. The prevalence of amyloidosis was increased in patients with HS compared with the HC group [n = 7 (0.2%) vs. n = 2 (0.0%), respectively; OR = 17.5; 95% CI 3.6-84.4; P < 0.001]. In a multivariate analysis, HS was still associated with amyloidosis (OR = 11.2; 95% CI 1.3-94.5; P = 0.03). The literature review identified nine patients who developed amyloidosis during the course of HS, with 44.4% eventually having renal failure. Favourable outcomes were reported in patients managed by tumour necrosis factor (TNF)-α inhibitors.
Conclusion: This study establishes the association between HS and amyloidosis. Screening for amyloidosis may be considered in patients with HS with a relevant clinical picture, mainly proteinuria. TNF-α inhibitors may be preferred in patients with a dual diagnosis of these conditions.
Full Research Link:
https://www.ncbi.nlm.nih.gov/m/pubmed/31989656/?i=1&from=hidradenitis%20suppurativa
Assessment of Overall and Specific Cancer Risks in Patients With HS
Chron’s Disease
The Association Between Crohn’s Disease and HS
Hidradenitis suppurativa is a chronic, autoinflammatory skin disease. Shalom et al. demonstrate in a large cross-sectional study an association between Crohn’s disease and hidradenitis suppurativa, but not with ulcerative colitis. This association supports the hypothesis that a similar pathogenic mechanism contributes to both diseases, providing new possibilities for functional studies and therapy development. Patients with hidradenitis suppurativa may have undiagnosed Crohn’s disease.
Hidradenitis suppurativa (HS) is a chronic, autoinflammatory disease, recurrent, debilitating affecting the hair follicles that usually presents after puberty with painful, deep-seated, inflamed lesions, most commonly in the axillary, inguinal, and anogenital regions. But can affect other areas of the body (Zouboulis et al., 2015). An association between HS and inflammatory bowel disease, comprising Crohn’s disease (CD) and ulcerative colitis, has long been suspected, but never validated. Shalom et al. (2016) provide epidemiological evidence for this association.
Hidradenitis suppurativa is associated with Crohn’s disease but not with ulcerative colitis
Shalom et al. (2016) report the results of a large cross-sectional study of 3,207 patients with HS and 6,412 age- and gender-matched controls in a population-based database in Israel of more than 4,300,000 enrollees. The inflammatory bowel disease diagnoses were made by gastroenterologists, and all files of patients with inflammatory bowel disease were reviewed manually by a dermatologist to confirm the HS diagnoses. The investigators demonstrate a significant association between HS and CD (odds ratio = 2.03, 95% confidence interval: 1.14–3.62, P = 0.01) but not ulcerative colitis (odds ratio = 1.82, 95% confidence interval: 0.81–4.05, P = 0.15), both in univariate and adjusted multivariate analyses.
An immunopathogenic link between hidradenitis suppurativa and Crohn’s disease HS and CD share interesting clinical and pathogenic similarities. Clinically, both diseases present with sterile abscesses in perineal and inguinal areas, sinus tracts, and associated arthritis, and both respond well to tumor necrosis factor alpha inhibitors. Pathogenically, an aberrant immune response is thought to play important roles in both of these chronic inflammatory diseases.
Contemporary evidence suggests that CD is associated with disrupted immune tolerance that accompanies shifts in common gut flora (dysbiosis), and it has been hypothesized that chronic gut inflammation is the result of abnormal immune responses in genetically susceptible individuals to microorganisms that reside in the gut (Maloy and Powrie, 2011). This hypothesis is supported by the finding that several risk loci are associated with regulation of the innate immunity and intracellular processing and killing of bacteria in CD (e.g., NOD2, ATG16L1, IRGM) (Ventham et al., 2013). For example, NOD2-deficient mice display increased loads of commensal microbiota and altered ratios of microbiota (Rehman et al., 2011).
Specific microorganisms may also play a role in maintaining homeostasis or inducing pathology, and they have been studied extensively in vitro and in vivo. For example, Faecalibacterium prausnitzii appears to have anti-inflammatory properties in the gut. Stimulation of peripheral blood mononuclear cells with this bacterium induced very low levels of the proinflammatory cytokines IFN-γ and IL-12, and this was paralleled by high levels of IL-10. F. prausnitzii is therefore considered important for maintaining gut homeostasis. As a consequence of dysbiosis, pathological strains may arise in microbiota. For example, the gut adherent-invasive Escherichia coli are capable of adhering to epithelial cells and are able to invade and replicate intracellularly. These E. coli strains even survive and replicate within macrophages, without triggering host cell death, leading to the release of large amounts of tumor necrosis factor-α (Barnich and Darfeuille-Michaud, 2007). It, therefore, remains unclear whether dysbiosis precedes the disease or is the consequence of the inflammatory milieu.
It is tempting to speculate that HS, in a fashion similar to CD, is initiated by an abnormal response to bacteria in the skin of genetically predisposed individuals, although a genetic association with NOD2 has not been demonstrated in patients with HS (Schneider-Burrus et al., 2008). Moreover, patients with HS display normal quantities of F. prausnitzii in their gut, whereas patients with psoriasis and patients with CD have a decreased presence of F. prausnitzii (Eppinga et al., 2016).
The skin microbiome is, however, also driven by environmental factors, and the responses vary, depending on body site characteristics such as sebaceous gland density, moisture content, temperature, and endogenous (e.g., host genetics) factors. In turn, the skin innate immune system is an important host factor regulating the composition and balance of the skin microbiota. The microorganisms on the skin and the immune system interact continuously, and imbalances in the commensal ecosystem may cause skin pathology, such as HS, via changes in skin immunity, epithelial dysfunction, or overgrowth by pathogenic species. On the other hand, little is known about the skin microbiota in HS. Swabs from abscess discharges and HS-affected skin lesions are mostly negative, and in cases where bacteria were cultured, only skin commensals were identified (Ring et al., 2015). Preliminary evidence, however, suggests that the skin microbiota may contribute to HS in several ways (Guet-Revillet et al., 2014). First, overgrowth of commensal bacteria may aggravate the disease by causing a chronic infection or by triggering innate inflammatory pathways by engaging with Toll-like receptors, NOD-like receptors, or inflammasomes. DNA and RNA from dead commensal bacteria are capable of activating the innate immune system in conjunction with proinflammatory signals generated by scattered dermal keratin filaments. Secondly, the immune response to skin commensal bacteria may be altered and the triggering threshold lowered, which resembles the pathogenic concept of CD as a response to the gut microbiota. Robust data on the skin microbiota in HS are however currently lacking. Thirdly, and less likely, the composition of the skin microbiota in HS may be altered toward containing more pathogenic species.
HS might be misdiagnosed as cutaneous Crohn’s disease in daily clinical practice HS and CD occur together more often than thought previously. Perianal HS and perianal CD are clinically quite similar, and both can form inflammatory draining tunnels in the skin. To differentiate between these diseases, especially in the perianal area, can therefore be challenging. Moreover, histology is not always helpful because in both diseases granuloma formation and lymphoid follicles can be present. We argue that in patients with CD, inflammatory lesions in the inguinal region are likely to be misdiagnosed as cutaneous Crohn’s even though true cutaneous CD (metastatic CD) is very rare. To differentiate between HS and CD, we recommend imaging techniques such as magnetic resonance imaging. We argue that in true CD, fistulas originate from the bowel in the anogenital region, although, in contrast to HS, sinus tracts do not penetrate the anal sphincter. We furthermore propose that histological staining with pan-keratin antibodies may help to differentiate between the two diseases, because keratin remnants derived from ruptured cysts are often present in the dermis of HS-affected skin.
Shalom et al. (2016) are to be commended for providing useful data that may help to unravel HS pathogenesis and alert dermatologist as well as gastroenterologists of their possible coexistence.
Comorbid Conditions Burdening HS
Characterization of comorbid conditions burdening
hidradenitis suppurativa: a multicentric observational study
Synopsis:
Background: Hidradenitis suppurativa (HS) is a chronic, disabling, inflammatory skin disorder that primarily affects the hair follicle localized at the apocrine-gland-bearing areas of the body, including axillary, inguinal, buttocks, and anogenital areas, and it may be associated with a wide array of comorbid conditions. This study aimed to described comorbid conditions affecting HS patients and to detect any correlation with disease severity.
Methods: Analyzing clinic database, we included all charts of patients visited at the HS outpatient clinic of three University Dermatologic Departments in order to describe demographic data, anthropometric measures, disease features, personal habits, clinical history, and presence of comorbidities.
Results: Two hundred thirty-four patients, mostly females (62%), were enrolled in this study. Based on Hurley staging classification 41% of patients were classified as Hurley Stage I, 43.0% as Hurley II, and 16% Hurley III, with a mean mSartorius Score value of 24.7 (SD: ±19.39) and a mean AISI score value of 12.5 (SD: ±11.93). The most frequently observed comorbidities were: obesity (26.1%), polycystic ovary syndrome (PCOS) (13.8% of the overall study population and 22.3% of females), hypertension (11.9%), dyslipidemia (9.9%), type II diabetes (9.5%), thyroid disorders (9.1%), nervous system disorders (7.1%), acne (6.7%), metabolic syndrome (4.4%), and Crohn’s disease (3.6%). Obesity represented a key-comorbid condition increasing the likelihood of having more severe HS and PCOS (odds ratio 3.35 and 3.74, respectively).
Conclusions: HS is associated with a variety of comorbid conditions that should be considered to perform targeted routine screening and to improve HS management.
Full Research Link:
https://www.ncbi.nlm.nih.gov/m/pubmed/30295448/?i=11&from=hidradenitis%20follicle
Comorbidity screening in HS: Evidence-based recommendations from the US & Canadian HS Foundations
Comorbidity screening in hidradenitis suppurativa:
Evidence-based recommendations from the US and Canadian HS Foundations
Synopsis:
A number of comorbid conditions affect patients with HS and contribute to poor health and impaired quality of life, beyond the significant impact of the disease itself. These screening guidelines are intended to support health advocacy efforts along with comprehensive care strategies for patients with HS.
Please refer to research below complete comorbidity list.
Full research circulation link:
https://www.sciencedirect.com/science/article/pii/S0190962221002139
Comparison of Morphologic Characteristics Between Pilonidal Cysts and HS
Sonographic Comparison of Morphologic Characteristics
Between Pilonidal Cysts and Hidradenitis Suppurativa
https://www.ncbi.nlm.nih.gov/m/pubmed/28649748
Link below for full research circulation for this
https://drive.google.com/file/d/1jQxYAkAJulXYH6QHrVMal_6o4opeAvDB/view?usp=drivesdk
Disease trajectories for HS in the Danish population
Disease trajectories for hidradenitis suppurativa in the Danish population
RESEARCH SUMMARY
Who?
Researchers from Zealand University and University of Copenhagen
Aim?
Most of the studies looking at diseases co-occurring with HS have been cross-sectional designs. What does that mean? Cross-sectional research designs provide a snapshot of the status of the population at one point in time. The goal of this study specifically is to look at temporal association of HS with multiple co-occurring diseases. What does that mean? They want to look at what is the relationship between HS and the time of onset of other conditions.
How was it done?
Backward-looking cohort study that looked at the entire Danish population from January 1, 1994 – Aug 10, 2018. Among the cohort 14488 Danish people were diagnosed with HS based on surgical procedure code data or ICD-10 data.
What did they find out?
Before HS diagnosis, disease such as depression, type 1 diabetes, asthma, inflammatory diseases of vagina and vulva, and severe stress adjustment disorder were more likely
After the diagnosis of HS, chronic obstructive pulmonary disease (COPD), pneumonia, and myocardial infraction (heart attack), chronic ischemic heart disease was more likely to develop
The average time of serious conditions (heart attack or chronic ischemic heart disease) to occur after HS diagnosis was fewer than 5 years
What does it all mean?
The work of these researchers highlights some important aspects of patient care. The findings suggest that before a person is diagnosed with HS they are more likely to be experiencing other disease such as diabetes and inflammatory conditions and are at risk in the future for the development of serious conditions like COPD and heart disease.
These association can help physicians and care teams make better guidelines for care and be better prepared for how HS evolved with time for each patient. Therefore, it is important that once an HS diagnosis is made we can anticipate possible complications in the future.
This study further demonstrates how important time of HS diagnosis is and how any delay in diagnosis has increased disease burden not just of HS but other conditions that are associated with it.
References:
Kjærsgaard Andersen R, Jørgensen IF, Reguant R, Jemec GBE, Brunak S. Disease Trajectories for Hidradenitis Suppurativa in the Danish Population. JAMA Dermatol. 2020;156(7):780–786. doi:10.1001/jamadermatol.2020.1281
Link to Full Research: https://jamanetwork.com/journals/jamadermatology/article-abstract/2766277
Disclaimer
Summary written by Ghazal Ghafari and reviewed with Denise Panter-Fixsen. This research summary is meant for educational and informational purposes only. Neither this summary nor any information contained within it are a substitute for professional care by a doctor or other qualified medical professional. This research summary does not constitute medical or other professional advice or services. If you have a medical concern, please consult with your physician.
Eye Problems
Synopsis:
Characteristics of inflammatory eye disease associated with hidradenitis suppurativa: There is one small study with 20 participants, which may indicate a “potential” association.
NOTE: Thirteen out of 20 patients (65%) had multiple autoimmune and/or inflammatory comorbidities. That could have contributed to the eye problems. Leaving seven participants only having hidradenitis. The study is way too small to be able to say HS and eye problems are definitely associated.
Until there are further studies with several HS participants (a large study). With no other contributing factors (illnesses). This answer will remain unclear.
Full Research Link:
High prevalence of HS in Patients with Perianal Fistula
Synopsis:
In 6.6% (8/122) of patients, HS was diagnosed outside the perianal region. Four of these patients were newly diagnosed. The fistulas in HS patients were classified as a superficial fistula (three), a blind ending fistula (two), and a transsphincteric fistula (two). One patient had more than one type of fistula.
Conclusion: The prevalence of HS in patients with a perianal fistula is at least 6.6%. This is higher than the prevalence reported in the general European population (1%) suggesting an association between perianal fistulas and HS. We stress the importance to screen for HS in patients with perianal fistulas in order to start appropriate anti-inflammatory treatment to reduce symptoms and disease progression.
Full circulation research link:
https://link.springer.com/article/10.1007/s00384-019-03313-2
HS and pemphigus
Hidradenitis suppurativa and pemphigus: a cross-sectional study
Synopsis:
A recent study of comorbidities in hospitalized pemphigus patients in the United States has demonstrated a significant association of hidradenitis suppurativa (HS) and pemphigus, but this association has not been firmly established in other populations. A retrospective, cross-sectional study was undertaken to determine the prevalence of HS in patients with pemphigus and compare with control subjects. Regression analysis was performed to obtain ORs, and 95% CIs, to evaluate the prevalence between pemphigus patients and controls matched by age, sex, and ethnicity. Among the patients included in the study, 1985 patients had pemphigus and 9874 were control subjects. The average age of presentation of pemphigus was 72.1 ± 18.5 and the group was comprised of 59.8% females. Overall, the pemphigus group had lower rates of smoking (25.7% vs. 27.9%; P = 0.045). The prevalence of HS was greater in patients with pemphigus than in control subjects (OR 4.98; 95% CI 1.01-24.69; P < 0.001), with an even more prominent association among patients who have been prescribed “pemphigus-related treatments” (OR 6.30; 95% CI 1.27-31.22; P < 0.001). The study detected a significant association between HS and pemphigus in an Israeli population. Future prospective studies are needed to establish a temporal order of appearance and the mechanistic relationship between these entities.
Full Research Link:
https://www.ncbi.nlm.nih.gov/m/pubmed/32034471/?i=11&from=hidradenitis
HS Associated with Spondylarthritis
Hidradenitis Suppurativa Associated with Spondyloarthritis —
Results from a Multicenter National Prospective Study
Synopsis:
Objective: To determine the prevalence and characterize the inflammatory musculoskeletal symptoms of hidradenitis suppurativa (HS), a chronic inflammatory disease of skin appendages.
Methods: Patients with HS referred to 3 dermatology university hospital centers were systematically screened for peripheral arthritis, dactylitis, inflammatory back pain, or enthesitis. After careful clinical examination, patients were further classified according to clinical and imaging criteria for spondyloarthritis (SpA) using the Amor, European Spondyloarthropathy Study Group (ESSG), and Assessment in ankylosing spondylitis (ASAS).
Results: We screened 640 patients with HS; 184 had musculoskeletal symptoms. In all, 43 (mean age 39.4 yrs, ± 8.3; 80% women) had arthritis, inflammatory back pain, or enthesitis and were investigated further. Signs of HS preceded the onset of articular symptoms in 39 patients (90%), at a mean interval of 3.6 years. A total of 18 (41%), 24 (55%), and 15 (34%) patients fulfilled the Amor, ESSG, and ASAS criteria, respectively, while synovitis, acne, pustolosis, hyperostosis, and osteitis (SAPHO) syndrome was established in 4 patients. The crude prevalence of SpA in all 640 patients with HS was 3.7% by the ESSG criteria.
Conclusion: SpA may occur in patients with HS, with the prevalence in this group exceeding that in the general population. The very short time between skin and joint symptom onset in some cases suggests common pathogenic mechanisms underlying HS and SpA.
Full Research Link:
HS Increases Alopecia Risk
Hidradenitis Suppurativa Increases Alopecia Risk
Synopsis:
Our findings are consistent with those of Lee et al3 and showed an increased risk of AA in a US-based HS sample. As currently understood, AA is caused by the loss of immune privilege at the hair follicle either because of local hair follicle epithelium disruption or a dysregulated immune response.2 HS pathogenesis involves hair follicle disruption and a sustained dysregulated immune response.4 Both AA and HS likely involve an inciting event at the hair follicle that leads to subsequent inflammation. In support of this hypothesis, the lesions of patients with HS and AA have considerable overlap in the expression of key inflammatory cytokines, including tumor necrosis factor α, interleukin 17, interferons, chemokine ligands 9 and 10, granzyme B, and others.4, 5 The similarities in the gene expression profiles of patients with HS and AA may explain why AA is more common in patients with HS. The results of this study encourage more research to investigate the molecular, genetic, and environmental factors contributing to this increased risk relationship between AA and HS. Clinicians should also be aware of the increased risk of AA in people with HS.
Full Research Link:
HS May Precede Inflammatory Arthritis
Synopsis:
Risk of Inflammatory Arthritis After a New Diagnosis of Hidradenitis Suppurativa
Hidradenitis suppurativa (HS) has been associated with a high prevalence of spondyloarthritis; however, the population-based risk of developing inflammatory arthritis remains unclear.1 This population-based cohort study sought to evaluate the risk of developing inflammatory arthritis among patients with HS compared with matched patients without HS.
Methods
Patients
We used longitudinal claims data from commercially insured patients, including those with Medicaid and Medicare, covering 185 million lives in the United States between January 1, 2003, and January 1, 2016. We identified patients of all ages who received a diagnosis of HS (International Classification of Diseases, Ninth Revision code 705.83 or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code L73.2), defined as 1 diagnosis by a dermatologist or 3 diagnoses by any health care professional.2 The cohort entry date for the HS group was the first recorded diagnosis date of HS after at least 180 days of continuous enrollment (eFigure in the Supplement). For the non-HS group, we risk-set sampled 2 patients without HS from all plan enrollees who did not have a diagnosis of HS matched on the date the patient with HS entered the cohort. We excluded patients who had less than 180 days of continuous enrollment before cohort entry or had preexisting inflammatory arthritis, including ankylosing spondylitis, psoriatic arthritis, other spondyloarthritis, or rheumatoid arthritis (eAppendix in the Supplement). The Brigham and Women’s Hospital’s Institutional Review Board approved this study. All patient information was deidentified.
Outcomes
We used validated algorithms using hospital discharge diagnoses or physician visit claims to identify the following outcomes: ankylosing spondylitis, psoriatic arthritis, other spondyloarthritis (reactive arthropathy, spinal enthesopathy, sacroiliitis, or unspecified inflammatory spondylopathies), and rheumatoid arthritis (eTable 1 in the Supplement).3,4 Follow-up started the day after cohort entry and lasted until one of the following events occurred: outcome, death, disenrollment, or end of data stream, whichever came first (eTable 3 in the Supplement).
Baseline Patient Characteristics
All the characteristics of the patients were assessed during the 180 days before or on the cohort entry date: age, sex, region, number of outpatient visits, number of unique medications, use of systemic biologic or nonbiologic immunomodulatory agents, comorbidities (ie, psoriasis or inflammatory bowel disease), and combined comorbidity score (eTable 2 in the Supplement).5
Statistical Analysis
Statistical analysis was performed from January 1, 2003, to January 1, 2016. We estimated hazard ratios (HRs) of the outcomes with 95% CIs by fitting Cox proportional hazards regression models, adjusting for all 10 baseline characteristics. To further account for confounding, HRs of developing inflammatory arthritis were computed after 1:1 propensity score matching.6 Patients’ propensity scores were estimated using the multivariable logistic regression that included all aforementioned patient characteristics.
Results
We identified 70 697 patients with HS (mean [SD] age, 36.5 [14.7] years) and 141 412 risk-set sampled patients without HS (mean [SD] age, 38.3 [21.1] years). Before matching, patients with HS were more often female (78.0% vs 52.0%) and had an increased comorbidity burden (Table 1). Median follow-up was 1.5 years (interquartile range, 0.6-3.1 years), with a maximum of 11 years. Both groups were free of arthritis prior to the cohort entry. After propensity score matching, patients with HS had an increased risk for developing ankylosing spondylitis compared with those without HS (incidence rate, 0.60 vs 0.36 per 1000; HR, 1.65 [95% CI, 1.15-2.35]), psoriatic arthritis (incidence rate, 0.84 vs 0.58 per 1000; HR, 1.44 [95% CI, 1.08-1.93]), and rheumatoid arthritis (incidence rate, 4.54 vs 3.86 per 1000; HR, 1.16 [95% CI, 1.03-1.31]) (Table 2). We did not observe an increased risk of other spondyloarthritis among patients with HS vs those without HS (incidence rate, 3.07 vs 3.00 per 1000; HR, 1.02 [95% CI, 0.89-1.17]).
Discussion
This large cohort study provides population-based rates of newly recorded inflammatory arthritis after a diagnosis of HS. We observed increased risks of developing ankylosing spondylitis, psoriatic arthritis, and rheumatoid arthritis among patients with HS compared with those without HS. Generally, the incidence of arthritis was low, resulting in only between 2 and 6 additional cases per 10 000 patients with HS per 1.5 years. Although the data support a systematic association between HS and subsequent newly diagnosed inflammatory joint disease, the low incremental risk is reassuring. Nevertheless, physicians treating patients with HS should be aware of symptoms suggestive of inflammatory arthritis, including morning stiffness and joint pain or swelling. This study cannot prove a causal relationship between HS and inflammatory arthritis, and further work is needed to elucidate the underlying potential shared pathogenesis of these disorders.
Accepted for Publication: November 26, 2019.
Corresponding Author: Maria C. Schneeweiss, MD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, 1620 Tremont St, Ste 3030, Boston, MA 02120 (mschneeweiss@partners.org).
Published Online: January 22, 2020. doi:10.1001/jamadermatol.2019.4590
Author Contributions: Dr M.C. Schneeweiss had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Rosmarin and Merola were co–senior authors.
Concept and design: M. C. Schneeweiss, S. Schneeweiss, Rosmarin, Merola.
Acquisition, analysis, or interpretation of data: M. C. Schneeweiss, Kim, S. Schneeweiss, Rosmarin.
Drafting of the manuscript: M. C. Schneeweiss, Merola.
Critical revision of the manuscript for important intellectual content: M. C. Schneeweiss, Kim, S. Schneeweiss, Rosmarin.
Statistical analysis: M. C. Schneeweiss, Kim.
Administrative, technical, or material support: M. C. Schneeweiss.
Supervision: Kim, Rosmarin, Merola.
Conflict of Interest Disclosures: Dr Kim reported receiving research grants to the Brigham and Women’s Hospital from Pfizer, Roche, AbbVie, and Bristol-Myers Squibb for unrelated topics. Dr Rosmarin reported serving as a paid consultant for AbbVie, Celgene, Dermavant, Janssen, Lilly, Novartis, Pfizer, and Regeneron Pharmaceuticals Inc; receiving research support from AbbVie, Celgene, Dermira, Incyte, Janssen, Lilly, Merck, Novartis, Pfizer, and Regeneron Pharmaceuticals Inc; and serving as a paid speaker for AbbVie, Celgene, Janssen, Lilly, Novartis, Pfizer, Regeneron Pharmaceuticals Inc, and Sanofi. Dr S. Schneeweiss reported being the principal investigator of investigator-initiated grants to the Brigham and Women’s Hospital from Bayer, Vertex, and Boehringer Ingelheim unrelated to the topic of this study; and serving as a consultant to WHISCON and to Aetion, a software manufacturer for which he owns equity. Dr Merola reported serving as a consultant and/or investigator for Merck Research Laboratories, AbbVie, Dermavant, Eli Lilly and Co, Novartis, Janssen, UCB, Samumed, Celgene, Sanofi Regeneron, GSK, Almirall, Sun Pharma, Biogen, Pfizer, Incyte, Aclaris, and Leo Pharma. No other disclosures were reported.
Funding/Support: This study was supported by the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, and the Department of Dermatology, Brigham and Women’s Hospital. This project was partially funded by the Pfizer fellowship for dermatology-pharmacoepidemiology research.
Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
References
1.
Rondags A, Arends S, Wink FR, Horváth B, Spoorenberg A. High prevalence of hidradenitis suppurativa symptoms in axial spondyloarthritis patients: a possible new extra-articular manifestation. Semin Arthritis Rheum. 2019;48(4):611-617. doi:10.1016/j.semarthrit.2018.03.010PubMedGoogle ScholarCrossref
2.
Kim GE, Shlyankevich J, Kimball AB. The validity of the diagnostic code for hidradenitis suppurativa in an electronic database. Br J Dermatol. 2014;171(2):338-342. doi:10.1111/bjd.13041PubMedGoogle ScholarCrossref
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Curtis JR, Harrold LR, Asgari MM, et al. Diagnostic prevalence of ankylosing spondylitis using computerized health care data, 1996 to 2009: underrecognition in a US health care setting. Perm J. 2016;20(4):15-151. doi:10.7812/TPP/15-151PubMedGoogle Scholar
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Hanly JG, Thompson K, Skedgel C. The use of administrative health care databases to identify patients with rheumatoid arthritis. Open Access Rheumatol. 2015;7:69-75. doi:10.2147/OARRR.S92630PubMedGoogle ScholarCrossref
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Gagne JJ, Glynn RJ, Avorn J, Levin R, Schneeweiss S. A combined comorbidity score predicted mortality in elderly patients better than existing scores. J Clin Epidemiol. 2011;64(7):749-759. doi:10.1016/j.jclinepi.2010.10.004PubMedGoogle ScholarCrossref
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Rosenbaum PR, Rubin DB. The central role of the propensity score in observational studies for causal effects. Biometrika. 1983;70:41-55. doi:10.1093/biomet/70.1.41Google ScholarCrossref
JAMA Dermatology
Article Research Link: https://www.rheumatologynetwork.com/news/hidradenitis-suppurativa-may-precede-inflammatory-arthritis
Synopsis research link: https://jamanetwork.com/journals/jamadermatology/article-abstract/2759138
Full research circulation: https://pubmed.ncbi.nlm.nih.gov/31968066/
Menses and pregnancy
Menses and pregnancy affect symptoms in Hidradenitis Suppurativa:
A cross-sectional study
Synopsis:
The results of the previous smaller studies investigating the prevalence of perimenstrual flares and change of symptoms during pregnancy are in line with our findings. A flare of HS symptoms around menses was most frequently reported, by 44% to 63% of women.3, 4 An amelioration of symptoms during pregnancy was most often described, namely in 20% to 83% of subjects.3, 4 A major strength of our study is the relatively large sample size compared with previous studies. However, our survey-based study is limited by recall bias and a lack of information on the influence of reproductive elements (eg, menarche, menopause) or the use of hormonal contraceptives on the course of HS symptoms. Notwithstanding, the results provide additional clinical relevant insight into the course of symptoms in women with HS.
In conclusion, this study suggests a significant correlation between perimenstrual deterioration of HS symptoms and amelioration during pregnancy. This correlation could be explained from a hormonal perspective in that estrogen has been shown to inhibit proinflammatory Th1 and Th17 cytokines and thus favors an immunosuppressive environment.5 Nonetheless, a substantial subset of women have no alteration of HS disease course perimenstrually or during pregnancy.
Full circulation research study link:
https://www.jaad.org/article/S0190-9622(16)30502-3/fulltext
Full circulation research study PDF:
https://drive.google.com/file/d/1E7qWWPDySMZxO8IL2c0gyecidn1UhYSf/view?usp=drivesdk
Myocardial Infarction and Cerebrovascular Accident in Patients with HS
Synopsis:
Importance: Although hidradenitis suppurativa (HS) is associated with several cardiovascular risk mediators, information on the risk of myocardial infarction (MI) and cerebrovascular accident (CVA) in this population is sparse.
Objective: To compare risk of MI, CVA, and composite disease (MI or CVA) in patients with HS, stratified by use of biologic agents, with controls without HS.
Design, setting, and participants: A retrospective cohort analysis was conducted between January 1, 1999, and April 1, 2019, using a demographically heterogeneous population-based sample of over 56 million unique patients. Individuals with HS (n = 49 862) and without HS (n = 1 421 223) were identified using electronic health records data.
Main outcomes and measures: The primary outcome was incidence of composite MI or CVA.
Results: Of the 49 862 patients with HS, 37 981 were women (76.2%), 29 711 were white (59.6%), and mean (SD) age was 38.3 (13.3) years. Crude incidence rate of composite disease was 6.6 (95% CI, 6.3-7.0) per 1000 person-years in patients with HS compared with 6.8 (95% CI, 6.7-6.8) per 1000 person-years in controls. In patients with HS, crude incidence rates were 2.9 (95% CI, 2.6-3.1) per 1000 person-years for MI alone and 4.1 (95% CI, 3.9-4.4) per 1000 person-years for CVA alone compared with 3.2 (95% CI, 3.18-3.25) per 1000 person-years for MI alone in control patients and 4.1 (95% CI, 4.0-4.1) per 1000 person-years for CVA alone in control patients. In adjusted analysis, patients with HS had a 23% increased risk of composite disease (hazard ratio [HR], 1.23; 95% CI, 1.17-1.30; P < .001) and a similar increase in the risk of MI alone (HR, 1.21; 95% CI, 1.12-1.32; P < .001) and CVA alone (HR, 1.22; 95% CI, 1.14-1.31; P < .001) compared with control patients. The relative difference in composite MI or CVA risk between patients with HS and controls was highest among younger patients HR in subgroup aged 18-29 years: 1.67; 95% CI, 1.37-2.03).
Conclusions and relevance: Patients with HS appear to have an increased risk of MI and CVA. Early management of modifiable cardiovascular risk mediators may be warranted in patients with HS.
Synopsis research link:
Full circulation research link:
https://jamanetwork.com/journals/jamadermatology/fullarticle/2754717
Pilonidal sinus disease
Pilonidal sinus disease:
an intergluteal localization of hidradenitis suppurativa/acne inversa:
a cross-sectional study among 2465 patients
Synopsis:
Background: Hidradenitis suppurativa (HS), also referred to as acne inversa, is a debilitating skin disease characterized by inflammatory nodules, chronic abscesses and tunnels (fistulae and sinuses). The association with pilonidal sinus disease (PSD) is frequently reported but not well documented.
Objectives: To determine the prevalence and characteristics of inflammatory skin lesions located in the intergluteal fold (IGF) of patients with HS.
Methods: This was an international multicentre retrospective cross-sectional study based on data collection from a large cohort of patients with HS with and without histopathology. Results From a total of 2465 patients with HS included in the study, 661 (27%) reported lesions in the IGF. These patients were significantly more often smokers and had more severe HS. Of the 238 patients with an available clinical diagnosis, intergluteal-HS (IG-HS) was diagnosed in 52 patients (22%) and PSD was diagnosed in 186 patients (78%). IG-HS was associated with the localization of HS in the proximity of the IGF, including the buttocks, genitals and the anus. There was a possibility of misclassification bias in this study as a clinical/image-based diagnosis or histopathology of the IGF lesions was not always available.
Conclusions: The high prevalence of PSD suggests a strong link between both entities. Therefore, it may be useful to identify common pathophysiological mechanisms and develop common therapeutic strategies. What’s already known about this topic? The occurrence of pilonidal sinus disease has not been clearly reported among patients with hidradenitis suppurativa/acne inversa. What does this study add? This is the first study that investigated the prevalence of pilonidal sinus disease among a large cohort of patients and identified the patient characteristics. Risk factors that might help to improve the management of patients were identified.
Full Research Link:
Polycystic Ovary Syndrome (PCOS)
Hidradenitis Suppurativa Is Associated with Polycystic Ovary Syndrome:
A Population-Based Analysis in the United States
Prevalence and Risk of Inflammatory Bowel Disease (IBD)
Synopsis:
In conclusion, we found an increased prevalence and risk of new-onset CD and UC in patients with HS. The link may be due to a shared immunopathogenesis, as well as modifiable lifestyle factors. In patients with HS presenting with gastrointestinal complaints, timely referral for gastroenterological evaluation of IBD may be appropriate.
Full Research Link:
Prevalence of Anal Fistula in the UK
Synopsis:
Background: Anal fistula is a pathological connection between the anal canal and perianal skin, which most commonly develops from an infected anal crypt. While the majority of anal fistulas are idiopathic, they are also associated with Crohn’s disease (CD) and other inflammatory conditions. The prevalence of anal fistula is estimated to be 1-2 per 10000 patients, but population-based studies on anal fistula epidemiology are limited and outdated.
Aim: To assess the prevalence of anal fistula and relevant comorbidities, with and without CD in the United Kingdom and Europe.
Methods: A retrospective population-representative observational cohort study was performed in The Health Improvement Network (THIN), a United Kingdom primary care database. Mid-year point prevalence of anal fistula was calculated on the first of July for each year between 2014 and 2017. Estimates were calculated for anal fistula overall and by CD status and standardized to the United Kingdom and European population. Prevalence of relevant comorbidities including lymphogranuloma venereum, hidradenitis suppurativa, anal presentation of sexually transmitted diseases, diabetes mellitus, and radiation in the pelvic area was reported.
Results: The United Kingdom-standardized overall point prevalence of anal fistula was 1.80 (95%CI: 1.65-1.94) per 10000 patients in 2017, while the Europe standardized estimate was 1.83 (95%CI: 1.68-1.98) per 10000 patients. Both these standardized point prevalence estimates ranged from 1.89 to 2.36 between 2014-2016. The United Kingdom-standardized point prevalence of anal fistula without CD was 1.35 (95%CI: 1.23-1.48) per 10000 patients, while the Europe-standardized estimate was 1.39 (95%CI: 1.26-1.52) per 10000 patients. In contrast, the standardized point prevalence estimate of anal fistula with CD was lower for both United Kingdom and Europe (0.44; 95%CI United Kingdom: 0.37-0.52, 95%CI Europe: 0.37-0.51) per 10000 patients in 2017. In 2017, 19% of anal fistula patients without CD and 13% of anal fistula patients with CD had at least one relevant comorbidity. These results show that anal fistulas are infrequent in the general population. 24.5% of prevalent anal fistulas are associated with CD, but other potentially etiological comorbidities are rare.
Conclusion: This real-world evidence study estimated the United Kingdom-standardized prevalence of anal fistula was 1.80 per 10000 patients in 2017. Approximately 25% of cases may be associated with CD, while other comorbidities are rare.
Full Research Link:
https://www.ncbi.nlm.nih.gov/m/pubmed/31417925/?i=6&from=hidradenitis%20global%20population
Pruritus (itching)
Assessing Pruritus in Hidradenitis Suppurativa: A Cross-Sectional Study
Pruritus (itching) is still a forgotten aspect of hidradenitis suppurativa (HS) and, to date, has never been adequately studied. The prevalence rate of pruritus in 211 HS patients was 57.3%.
Conclusion:
Pruritus is a frequent but under-reported symptom in patients with HS. Its moderate to severe intensity and significant impact on daily activities have great potential to impair patients’ quality of life.
Psoriasis
Psoriasis and Hidradenitis Suppurativa: A Large-scale Population-based Study
Synopsis:
Background: The coexistence of psoriasis and hidradenitis suppurativa (HS) has been described, but the association between these conditions is yet to be firmly established.
Objectives: To study the association between psoriasis and HS using a large-scale real-life computerized database.
Methods: A cross-sectional study was conducted comparing the prevalence of HS among patients with psoriasis and among age-, sex- and ethnicity-matched control subjects.
Results: A total of 68,836 patients with psoriasis and 68,836 controls were included in the study. The prevalence of HS was increased in patients with psoriasis as compared to the control group (0.3% vs. 0.2%, respectively; OR, 1.8; 95% CI, 1.5-2.3; P<0.001). In a multivariate analysis adjusting for smoking, obesity, and other comorbidities, psoriasis was still associated with HS (OR, 1.8; 95% CI, 1.4-2.2; P<0.001). Patients with coexistent psoriasis and HS were significantly younger (39.0±15.7 vs. 42.6±21.2 years; P=0.015) and had a higher prevalence of obesity (35.1% vs. 25.3%; P=0.001) and smoking (58.5% vs. 37.3%; P<0.001) as compared to patients with psoriasis alone.
Limitations: Retrospective data collection.
Conclusions: A positive association was observed between HS and psoriasis. Further longitudinal observational studies are necessary to establish these findings in other study populations.
Full Research Link:
Spondyloarthritis
Hidradenitis Suppurativa Associated with Spondyloarthritis —
Results from a Multicenter National Prospective Study
Synopsis:
Objective: To determine the prevalence and characterize the inflammatory musculoskeletal symptoms of hidradenitis suppurativa (HS), a chronic inflammatory disease of skin appendages.
Methods: Patients with HS referred to 3 dermatology university hospital centers were systematically screened for peripheral arthritis, dactylitis, inflammatory back pain, or enthesitis. After careful clinical examination, patients were further classified according to clinical and imaging criteria for spondyloarthritis (SpA) using the Amor, European Spondyloarthropathy Study Group (ESSG), and Assessment in ankylosing spondylitis (ASAS).
Results: We screened 640 patients with HS; 184 had musculoskeletal symptoms. In all, 43 (mean age 39.4 yrs, ± 8.3; 80% women) had arthritis, inflammatory back pain, or enthesitis and were investigated further. Signs of HS preceded the onset of articular symptoms in 39 patients (90%), at a mean interval of 3.6 years. A total of 18 (41%), 24 (55%), and 15 (34%) patients fulfilled the Amor, ESSG, and ASAS criteria, respectively, while synovitis, acne, pustolosis, hyperostosis, and osteitis (SAPHO) syndrome was established in 4 patients. The crude prevalence of SpA in all 640 patients with HS was 3.7% by the ESSG criteria.
Conclusion: SpA may occur in patients with HS, with the prevalence in this group exceeding that in the general population. The very short time between skin and joint symptom onset in some cases suggests common pathogenic mechanisms underlying HS and SpA.
Full Research Link:
Thyroid Function in HS
Thyroid Function in Hidradenitis Suppurativa:
A Population-Based Cross-Sectional Study from Denmark
Synopsis:
A significantly higher prevalence of thyroid disorders was found among patients with hidradenitis suppurativa, and additional study to increase the strength of the association was encouraged in a research letter published in Journal of the American Academy of Dermatology.
“Although HS is thought to be an autoinflammatory disease in contrast to the autoimmune nature of the thyroid disorders, production of inflammatory cytokines such as [tumor necrosis factor]-alpha and [interleukin]-1 beta in HS could trigger the autoimmune process of thyroid disorders in susceptible individuals,” wrote Prakash Acharya, MBBS, MD, and Mahesh Mathur, MD, DCP, both from the department of dermatology, College of Medical Sciences in Bharatpur, Nepal.
A search of PubMed, Scopus and Cochrane databases was employed using various terms associated with thyroid disorder and hidradenitis suppurativa (HS) to assess a possible association between the two. Case reports, reviews and studies without controls were excluded.
Six studies encompassing 39,748 patients with HS and 206,967 controls were included.
All studies showed a higher prevalence for thyroid disorders in patients with HS; however, the results were statistically significant in only three studies, according to researchers. Heterogeneity was determined significant. Using funnel plot examination, researchers did not reveal any publication bias.
The researchers found a significantly higher prevalence of thyroid disorders among patients with HS (OR = 1.88; 95% CI, 1.25-2.81).
The study lacked subgroup analysis based on severity and duration of HS, due to insufficient data, according to the researchers. Separate analyses according to the type of thyroid disorder were not performed and represents another limitation. – by Abigail Sutton
Acharya P, et al. J Am Acad Dermatol. 2019;doi:10.1016/j.jaad.2019.07.025.
Full Research Link:
https://www.ncbi.nlm.nih.gov/m/pubmed/29785760
Hidradenitis suppurativa linked with thyroid disorders study: