Hessel H. van der Zee

Adalimumab for the Treatment of Moderate to Severe Hidradenitis Suppurativa: A Parallel Randomized Trial

BACKGROUND Hidradenitis suppurativa (HS) is a chronic, painful skin disease characterized by abscesses, nodules, and draining fistulas in the axilla and groin of young adults. OBJECTIVE To evaluate the efficacy and safety of adalimumab, an anti-tumor necrosis factor-α antibody, in patients with moderate to severe HS. DESIGN Phase 2, parallel, randomized, placebo-controlled trial consisting of a blinded 16-week period (period 1) and an open-label 36-week period (period 2). All study personnel, investigators, and patients remained blinded to treatment group throughout the study. (ClinicalTrials.gov: NCT00918255) SETTING 26 academic and private practice medical centers in the United States and Europe. PATIENTS 154 adult patients with moderate to severe HS who were unresponsive or intolerant to oral antibiotics. INTERVENTION Patients were assigned in a 1:1:1 ratio to adalimumab, 40 mg/wk; adalimumab, 40 mg every other week (EOW); or placebo. All patients received adalimumab, 40 mg EOW, at the beginning of period 2 but switched to weekly dosing if the response was suboptimal (HS Physicians Global Assessment [PGA] score of moderate or worse) at weeks 28 or 31. MEASUREMENTS The primary outcome measure (clinical response) was the proportion of patients achieving an HS-PGA score of clear, minimal, or mild with at least a 2-grade improvement relative to baseline at week 16. RESULTS At week 16, 3.9% of placebo patients (2 of 51), 9.6% of EOW patients (5 of 52), and 17.6% of weekly patients (9 of 51) achieved clinical response (EOW vs. placebo strata-adjusted difference, 5.6% [95% CI, -4.0% to 15.3%]; P = 0.25; weekly vs. placebo strata-adjusted difference, 13.7% [CI, 1.7% to 25.7%]; P = 0.025). Serious adverse event rates were 3.9%, 5.8%, and 7.8% for placebo, EOW, and weekly patients, respectively (EOW vs. placebo difference, 1.8% [CI, -6.4% to 10.1%]; weekly vs. placebo difference, 3.9% [CI, -5.2% to 13.0%]). Significantly greater improvements in patient-reported outcomes and pain were seen in the weekly dosing group than in the placebo group. A decrease in response was seen after the switch from weekly to EOW dosing in period 2. LIMITATIONS Weeks 16 to 52 of the study were open-label. The study was not powered to assess the risk for known serious adverse effects of adalimumab, such as tuberculosis, other serious infections, and demyelinating disorders. CONCLUSION Adalimumab dosed once per week alleviates moderate to severe HS. PRIMARY FUNDING SOURCE Abbott Laboratories.

The Effect of Combined Treatment with Oral Clindamycin and Oral Rifampicin in Patients with Hidradenitis Suppurativa

Background: A previous limited study showed promising results of combined oral treatment with rifampicin 600 mg and clindamycin 600 mg for 10 weeks. Objective: To expand and to validate the basis for this therapy, we reviewed the response to different treatment durations. Method: A retrospective study in 34 patients. Results: Twenty-eight of 34 patients (82%) experienced at least partial improvement, and 16 (47%) showed a total remission. The maximum effect of treatment appeared within 10 weeks. Following total remission, 8 of 13 (61.5%) patients treated as mentioned above experienced a relapse after a mean period of 5.0 months. Nonresponders were predominantly patients with severe disease. Conclusion: Combination treatment with oral rifampicin and clindamycin is a promising treatment option for hidradenitis suppurativa, despite the frequent occurrence of diarrhea as a side effect. The length and the dosage of treatment are not yet firmly established.

Hidradenitis suppurativa: viewpoint on clinical phenotyping, pathogenesis and novel treatments

Hidradenitis suppurativa (HS) is an inflammatory, debilitating follicular skin disease with recurring flare‐ups. The painful, deep‐seated, inflamed lesions in the inverse areas of the body cause severe discomfort, and hence, serious psycho‐social and economic costs. HS is common, but often misdiagnosed and mechanistically poorly understood. Furthermore, HS is notoriously difficult to treat resulting in a high unmet medical need. To provoke debate, rational experimentation and initiate strategic studies, we here present a concise viewpoint on seven topics: the diagnosis of HS, the role of mechanical friction, the critical importance of accurate clinical subgrouping, smoking and obesity, the role of bacteria, and our comprehensive view on HS pathogenesis with a central role for keratin clearance, and novel treatment approaches.

Correlation of early-onset hidradenitis suppurativa with stronger genetic susceptibility and more widespread involvement

BACKGROUND The reported mean age of onset of hidradenitis suppurativa (HS) is between 20 and 24 years. Prepubertal onset is thought to be rare. OBJECTIVE We sought to determine the prevalence of early-onset HS and to compare clinical characteristics between early-onset and normal-onset HS in a retrospective study. METHODS Data were collected from 855 patients with HS. Early-onset HS was defined as onset before the thirteenth birthday. Clinical characteristics were analyzed in relation to the age of onset. RESULTS In all, 66 patients (7.7%) reported early-onset HS. A family history for HS was significantly higher in early-onset patients (55.6% vs 34.2%; odds ratio 2.1, 95% confidence interval 1.2-3.6, P = .006). They developed inflammatory lesions at more body sites than patients with normal-onset HS (odds ratio 3.0, 95% confidence interval 1.8-4.9, P < .001). Distribution of the Hurley stages of severity showed no differences between the 2 groups (odds ratio 1.1, 95% confidence interval 0.7-1.8, P = .72). LIMITATIONS Some data were based on patient-reported information. CONCLUSION Early-onset HS occurs more frequently than previously believed. Patients with early-onset HS often report a family history for HS and develop lesions at more body sites.

New insights into the diagnosis of hidradenitis suppurativa: Clinical presentations and phenotypes

Current classifications for hidradenitis suppurativa (HS), such as the Hurley staging system, are not very specific. The absence of rigorous classifications is incongruous with the clinical variability of the condition. There is no pathognomonic sign for HS that leads to a diagnosis that is unquestionable. Consequently, diagnosis is made largely through clinical presentation of the condition. The use of several validated tools assists in confirming the diagnosis and the severity of the disease. In future investigations, the identification of phenotypes and clinical subtypes--taking into account genetic variants--will serve to identify subpopulations of patients who are responsive to particular therapies, thereby improving the overall therapeutic picture for patients with HS. There is a potential for personalized, tailored delivery of therapy in the HS setting.

Is mechanical stress an important pathogenic factor in hidradenitis suppurativa

Abstract:  Hidradenitis suppurativa (HS) is a chronic of recurrent, inflammatory, follicular disease that usually presents after puberty with painful deep‐seated, inflamed lesions in the inverse skin areas of the body. It has been hypothesized that mechanical pressure or friction is a risk factor for HS. We describe the case of a man with a lower leg amputation who presented HS‐like lesions on his leg stump after wearing a leg prosthesis. Although pilonidal sinus‐like disease could not be excluded, we diagnosed him with HS‐like lesions, induced by prosthesis‐related friction. We argue that this case supports the concept that mechanical friction and a warm humid microclimate by occlusion contribute to HS development.

Inflammatory bowel disease is associated with hidradenitis suppurativa: Results from a multicenter cross-sectional study

Background: Hidradenitis suppurativa (HS) is often associated with inflammatory bowel disease (IBD; Crohns disease or ulcerative colitis). However, the prevalence of IBD in HS patients is unknown. Objective: To determine the prevalence of IBD in HS patients, and determine if patients with HS and IBD have a distinct HS phenotype. Methods: For this multicenter, cross‐sectional study, HS patients were asked during their first consultation if they had IBD. The diagnosis of IBD was checked in the medical files, and clinical characteristics were collected. Results: IBD had a prevalence of 3.3% (95% CI 2.3‐4.4) in 1076 HS patients. The prevalence of Crohns disease was 2.5% (95% CI 1.6‐3.4) and the prevalence of ulcerative colitis was 0.8% (95% CI 0.3‐1.4). HS‐IBD patients were less frequently obese (13.9% vs 31.2%, P = .04) than HS‐only patients, but there were no differences in gender, family history of HS, disease severity, body areas affected by HS, or smoking status. Limitations: The prevalence might be underestimated since HS patients might still develop IBD. Conclusion: The prevalence of IBD in HS patients (3.3%) is 4‐8 times higher than the prevalence in the general northern European population (0.41%‐0.74%), however HS‐IBD patients do not have a distinct HS phenotype.

Fumarates, a new treatment option for therapy-resistant hidradenitis suppurativa: a prospective open-label pilot study

Dermatology and are currently being edited and typeset. Readers should note that articles published below have been fully refereed, but have not been through the copy-editing and proof correction process. Wiley-Blackwell and the British Association of Dermatologists cannot be held responsible for errors or consequences arising from the use of information contained in these articles; nor do the views and opinions expressed necessarily reflect those of Wiley-Blackwell or the British Association of Dermatologists This article is protected by copyright. All rights reserved.

Severe fatigue based on anaemia in patients with hidradenitis suppurativa: report of two cases and a review of the literature.

Editor Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease. Patients often report fatigue, which is generally attributed to the debilitating psychosocial impact of HS. However, sometimes severe anaemia causes the fatigue. The co-occurrence of HS and anaemia is mentioned in reviews on the disease, but they refer to a single case series from 1968. Since, no studies have been published on this subject. Therefore, we present two representative cases of severe HS with fatigue, based on chronic marked anaemia. The first case is a 46-year-old, otherwise healthy, man with a 6-year history of HS, Hurley stage III, on his buttocks, groin and peri-genital area. He presented with purulent blood loss from his HS lesions and intense fatigue (Fig. 1a). Previous treatments with isotretinoin and multiple antibiotics were ineffective. Laboratory tests revealed a microcytic anaemia (haemoglobin (Hb): 4.5 mmol/L) (Table 1), for which he received three packed cells and was referred to internal medicine. Colonoscopy revealed no abnormalities, gastroscopy was discontinued because of patient’s anxiety. Helicobacter Pylori-breathing test was negative. Iron supplementation was started, temporarily improving his haemoglobin level. Clindamycin 3dd200 mg yielded minor effect on his HS. Extensive wide excision was performed of all HS affected skin with closure by split-skin grafting. Six months postoperatively the wounds were healed (Fig. 1b), his fatigue resolved and his haemoglobin level normalized (Hb: 9.4 mmol/L) (Table 1). The second case is a 61-year-old woman, suffering from HS since the age of 14, Hurley stage III, located in the axillae, groin, pubic and gluteal area. She had a medical history of fatigue, diabetes and hypertension. Previous treatments with antibiotics were ineffective. Laboratory testing revealed normocytic anaemia (Hb: 5.0 mmol/L) (Table 1). She was referred to internal medicine who concluded that her anaemia was caused by iron deficiency and chronic disease, since no other cause was found. She received multiple blood transfusions, temporarily increasing her haemoglobin. Adalimumab was started for her HS, with modest efficacy. Multiple extensive surgical excisions were performed on her axillae, groin and gluteal area, with subsequent blood loss requiring blood transfusions. Hereafter infliximab infusions were started. The remaining HS lesions improved and the haemoglobin level normalized (Hb 8.5 mmol/L) (Table 1). HS patients often report fatigue, which is attributed to the debilitating course and great psychological impact of HS. However, a more general underlying cause, chronic marked anaemia, is sometimes overlooked. In 1968, Tennant et al. reported on anaemia associated with HS. In their population, 10 of 42 (24%) patients with severe HS had marked anaemia (Hb < 6.3 mmol/L). They concluded that anaemia was probably caused by chronic inflammatory processes. Anaemia as consequence of chronic disease is believed to be caused by the effects of elevated levels of pro-inflammatory cytokines. Interferon-c, interleukin (IL)1 and tumour necrosis factor alpha (TNF-a) can inhibit renal production of erythropoietin and reduce its physiological effect on the bone marrow. In addition, these (a)

Medical Treatments of Hidradenitis Suppurativa: More Options, Less Evidence

Hidradenitis suppurativa is a common debilitating skin disease that has been neglected by science. The disease is getting more and more attention, reflected by the rising number of scientific publications. There is a clear need for effective treatment. We are still at the beginning of improving care for these patients as demonstrated by the low levels of evidence for the medical treatments. Many of these therapies showed promising results, but are still waiting to be validated in randomized, controlled trials. Much more research is needed to strengthen the Level of Evidence for these therapies and thus improve patient care.