Hidradenitis Suppurativa
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1 Disclosures Hidradenitis Suppurativa I have no conflicts of interest Will discuss off-label uses of medications Jennifer Hsiao, MD UCLA Dermatology Background information Clinical features Treatments Lifestyle modifications Medical therapeutics Procedural management Comorbidities and Complications Outline Epidemiology The estimated prevalence of HS varies from 0.05% to 4.1% Recent retrospective analysis of a heterogenous populations-based sample of more than 48 million patients across the United States Overall HS prevalence found to be 0.1% Prevalence in women more than twice that of men Prevalence of HS highest among patients aged 30 to 39 years HS prevalences among African American and biracial patients were more than 3-fold and 2-fold greater than that among white patients Surveys show that the mean delay in establishing a diagnosis of HS is seven years Saunte et al. JAMA Garg et al. JAMA Dermatol Burden of Disease Patients with HS have an increased utilization of high-cost settings, such as the emergency department and inpatient care, compared to patients with psoriasis Follicular Occlusion HS is an inflammatory disorder originating from the hair follicle Follicular occlusion leads to perifollicular cyst development and then rupture of cyst contents (including bacteria) into the dermis Patients with HS have been found to have a higher health-related quality of life impairment compared to patients with psoriasis Khalsa et al. J Am Acad Dermatol Hamzavi et al. J Am Acad Dermatol
2 Genetics Microbiome There is a familial form of HS with AD inheritance Mutations in genes that make up the gamma-secretase protein complex have been found in patients with familial HS Gamma-secretase protein catalyzes cleavage of transmembrane proteins including Notch Mice deficient in Notch mimic mice deficient in gamma-secretase, with cyst formation and epidermal and follicular defects Defective Notch signaling could play a role in HS pathogenesis, but there could be other gamma-secretase substrates to consider Hoffman et al. Semin Cutan Med Surg Role of bacteria remains controversial A systematic review of 9 studies with a total of 324 patients investigating bacterial flora in HS found that the most frequently encountered types of bacteria included coagulase negative staph and mixed anaerobic bacteria Case control study reviewing punch biopsy specimens found that the microbiome in HS patients (lesional and non-lesional skin) differed significantly from that in healthy controls; in HS patients there was an abundance of Corynebacterium and anaerobes at HS affected sites and sites of HS predilection Bacterial biofilms have been found in acute HS lesions and HS sinus tracts Ring et al. Exp Dermatol Ring et al. JAMA Dermatol Okoye et al. Br J Dermatol Hormones Majority of HS patients have normal androgen profiles In one survey of patients with HS, 20% (out of 85 women) reported amelioration of HS symptoms with pregnancy In another survey of women with HS: 43% (out of 186 patients) reported a deterioration of HS around menses 30% (out of 96 patients) reported amelioration of HS during pregnancy Amelioration during pregnancy more frequently reported by patients who experienced a deterioration during menses Immune Dysregulation Increased TNF-α, IL-1β, IL-10, IL-17, IL-12, IL-23, IL-22, IL-20 found in lesional HS skin compared to healthy control skin Therapeutic response to anti-tnf-α, anti-il-1, and anti-il-12/23 agents in some studies Kromann et al. Br J Dermatol Vossen et al. J Am Acad Dermatol Kelly et al. Int J Dermatol Clinical Presentation Criteria for diagnosis 1. Typical lesions present: nodule, abscess, sinus tract, scar 2. Typical locations involved: axillae, groin, perineum, buttocks, infra- and intermammary folds 3. History of chronicity and recurrence (2x/6 months) Hurley Stages Hurley Stage I: Abscess formation, single or multiple, without sinus tracts and scarring Hurley Stage II: Recurrent abscesses with tract formation and scarring, single or multiple, and widely separated lesions Hurley Stage III: Diffuse or near-diffuse involvement of multiple interconnected tracts and abscesses across the entire area Van der Zee et al. J Am Acad Dermatol
3 Other Scoring Systems Sartorius score Incorporates the involved anatomic regions, number and types of lesions, distance between lesions, and the presence of normal skin in between lesions Hidradenitis Suppurativa Clinical Response (HiSCR) At least a 50% reduction from baseline in the total abscess and inflammatory-nodule count, with no increase in the abscess or draining-fistula count Hidradenitis Suppurativa - Physician Global Assessment (HS - PGA) 6 point score ranging from clear to very severe, based on number of inflammatory and noninflammatory nodules, abscesses, and draining fistulas Dermatology Life Quality Index (DLQI) 10 questions (score of 0-30) Hidradenitis Suppurativa Severity Index (HSSI) Incorporates number of anatomic sites and body surface area involved, number of lesions, pain severity (determined through a visual analogue scale), and drainage HS Phenotypes Axillary-Mammary phenotype: High probabilities for breast and axillae involvement, and for hypertrophic scars. Follicular phenotype: High probabilities for breasts, axillae, and also ears, chest, back, or legs involvement. Higher probabilities than patients in the other two classes for follicular lesions (epidermal cysts, pilonidal sinus, and comedones) and for a present or past history of severe acne. Higher proportion of men, current/former smokers, greater disease severity. Gluteal phenotype: Gluteal involvement, papules, and folliculitis. More often smokers, lower BMI values, less severe disease. Canoui-Poitrine et al. J Invest Dermatol Lifestyle Modifications Smoking cessation Weight loss Avoid tight fitting clothing Medical Therapeutics Topical Antibiotics Clindamycin 1% topical (gel, lotion, or solution) Dapsone 5% gel Gentamicin 0.1% topical Metronidazole 0.75% topical Can combine with antiseptic washes: Chlorhexidine (hibiclens) wash Benzoyl peroxide wash Topical Resorcinol Study of 32 patients with Hurley Stage I and II: Resorcinol 15% topical BID for 30 days led to reductions in pain and size (a significant difference already seen by day 7) Resorcinol is a phenol derivate, used in dermatology mainly because of its keratolytic properties, though it also has effects on controlling inflammation as well Peeling effect starts at concentrations of 10% No pregnancy category assigned Scheinfeld. Dermatol Online J Pascual et al. J Am Acad Dermatol Boer et al. Clin Exp Dermatol
4 Systemic Antibiotics - Monotherapy** Systemic Antibiotics - Combined Therapy Doxycycline 100mg PO BID or Minocycline 100mg PO BID (or extended release minocycline at weight adjusted dose once a day) for 8-12 weeks Dapsone 50mg to 200mg PO daily Check CBC, CMP, G6PD **Appropriate for Hurley Stage I and II patients Jemec et al. J Am Acad Dermatol Kaur et al. J Dermatolog Treat Yazdanyar et al. Dermatology Clindamycin 300mg PO BID and Rifampin 300mg PO BID for weeks Rifampin (10mg/kg/day) + moxifloxacin 400mg/day + metronidazole 500mg TID for 12 weeks (metronidazole for first six weeks only) Can also trial rifampin + levofloxacin + metronidazole For severe HS patients, can start with induction treatment with IV ertapenem (1g daily) for 6 weeks before consolidation treatment with combination oral antibiotics Induction treatment with IV ceftriaxone (1g daily) + oral metronidazole (500mg TID) for 3-4 weeks has also been reported Gener et al. Dermatology Join-Lambert et al. Dermatology Join-Lambert et al. J Antimicrob Chemother Oral Retinoids Acitretin 0.5mg/kg/day may be beneficial, although given side effects, dose may be limited to 25mg daily 1 Isotretinoin mixed results in the literature Study of 68 HS patients found that 23.5% had clearance (treatment was more successful in milder forms of HS) 2 A retrospective study of 358 patients found 16% reporting an improvement with previous treatment with oral isotretinoin 3 A retrospective chart review of 25 patients on isotretinoin 0.45mg/kg/day for average of 6.8 months found that 32% showed PR and 36% showed CR (only seen in Hurley stage I and II patients) 4 Key point: at this time, isotretinoin is not a primary therapy for HS. More research needed to see if it could be helpful in certain subtypes of HS (for example, in patients with migratory furunculoid lesions) 5 Hormonal Therapy For women: Spironolactone 100 to 150mg daily OCP (with increased estrogen and with anti-androgenic progestin, like drospirenone) For men: Finasteride 5 to 10mg daily Leuprolide acetate For both: Metformin 500mg to 1500mg daily (especially in patients who are obese or who have diabetes) 1. Matusiak et al. Br J Dermatol. 2014; 2. Boer et al. J Am Acad Dermatol. 1999; 3. Soria et al. Dermatology. 2009; 4. Huang et al. Dermatology. 2017; 5. Boer. Dermatology Scheinfeld. Dermatol Online J Verdolini et al. J Eur Acad Dermatol Venereol Biologics Adalimumab Most evidence behind: Adalimumab (FDA approved) Infliximab Other biologics to consider: Ustekinumab Anakinra Fully human monoclonal antibody against TNF-alpha Dosing schedule Day 1: 160mg SC x 1 Day 15: 80mg SC x 1 Day 29: 40mg SC weekly Kimball et al. NEJM
5 Infliximab Chimeric (mouse/human) monoclonal antibody against TNF-alpha Dosing: 5mg/kg infusion at weeks 0, 2, and 6, then q4-8 weeks Can consider adding low dose methotrexate to prevent anti-drug antibodies (ADA) Report in literature of a 47 yo man with severe familial HS, took three courses of infliximab, each followed by surgical debridement of the perineal and anal areas after 3 rd surgical debridement his physician noted presence of SCC. Infliximab was stopped. Had scans done soon afterwards that showed the SCC had metastasized and he passed away within a year later. Kimball et al. NEJM Grant et al. J Am Acad Dermatol. 2010; Lesage et al. Eur J Dermatol. 2012; Paradela et al. J Dermatol Treat. 2012; Scheinfeld. Dermatol Online J Ustekinumab Human monoclonal antibody against IL-12 and IL-23 Dosing: 45mg (<100kg) or 90mg (>100kg) at weeks 0, 4, then q12 weeks Study of 17 patients in open-label study treated with above regimen Week 40: 82% (14/17) of patients had moderate to marked improvement of the modified Sartorius score 47% (8/17) achieved the Hidradenitis Suppurativa Clinical Response (HiSCR) Case report: 39 yo woman with Behcet s disease, psoriasis, HS with improvement of all three diseases with ustekinumab Case report: 55 yo man with psoriasis and HS, failed methotrexate, adalimumab, mycophenolate, had modest response to ustekinumab 45mg on weeks 0, 4, and 12 so dose was increased to 90mg q8 weeks Blok et al. Br J Dermatol. 2016; Baerveldt et al. Ann Rheum Dis. 2013; Sharon. Acta Derm Venereol IL-1 receptor antagonist Dosing: 100mg SC daily Anakinra RCT with 20 patients with HS II or HS III 10 received anakinra, 10 received placebo for 12 weeks At week 12: HiSCR achieved in 78% (7/9) of the anakinra arm (1 patient lost to follow-up) and 30% (3/10) of placebo arm Change in overall DLQI at weeks 12 and 24 from baseline at week 0 was not different between the study arms Open-label study with 6 patients receiving anakinra for 8 weeks 5 patients completed 8 week therapy, all showed significant mean decrease in their modified Sartorius score. DLQI also showed reduction in mean scores. HS disease activity rebounded rapidly when off therapy Tzanetakou et al. JAMA Dermatol Leslie et al. J Am Acad Dermatol Anakinra Case report: 37 yo woman (119kg) receiving anakinra 200mg SC daily with considerable improvement, at time of publication had continued on anakinra for over a year. Three episodes of pustular folliculitis due to Staphylococcus aureus treated with short-term oral antibiotics. No other adverse effects reported. Of note, there are also case reports in the literature of failure of anakinra therapy for HS A Phase 2 trial of MEDI8968 (fully human anti-il-1 receptor 1 monoclonal antibody) was terminated because no evidence of reduction in HS severity or pain over placebo Other Therapeutics Cyclosporine (3-5mg/kg/day) has shown benefit in some reports 1,2 Colchicine: mixed reviews Open prospective study: 8 HS patients (HS I-III) treated with colchicine 0.5mg PO BID for up to 4 months (with two patients receiving 0.5mg PO TID after the 1 st month) --> no significant clinical improvement in any patient s HS disease 6 patients completed 2 months of treatment, only 2 patients were treated for 4 months Open prospective study: 20 HS patients (HS I-III) treated with 100mg minocycline daily + 0.5mg colchicine BID for 6 months, then maintenance regimen of 0.5mg colchicine BID for 3 months. All patients showed signs of marked or moderate improvement within the first 3 months of therapy and continued to improve throughout the next 6 months. 25 yo man, a UCLA HS clinic patient, took minocycline and colchicine x 6 months, then colchicine alone, and within two months of stopping minocycline, his condition started to flare Zarchi et al. JAMA Dermatol Menis et al. Br J Dermatol Anderson et al. J Dermatolog Treat. 2016; 2. Rose et al. Clin Exp Dermatol. 2006; 3. Van der Zee et al. Dermatology. 2011; 4. Armyra et al. Int J Dermatol
6 Other Therapeutics Emerging Therapies Zinc gluconate 90mg PO daily Pilot study: 22 patients with HS (11 Hurley Stage I, 10 Hurley Stage II, 1 Hurley Stage III) 8/22 (36%) had a complete remission (disappearance of cutaneous lesions or no new lesions during 6 months or more) most were Hurley Stage I 14/22 (63.6%) had partial remission (reduction of 50% or more of the number of nodules and/or a shorter cycle of each inflammatory lesion) Main side effect: GI distress Excess zinc supplementation may lead to copper deficiency Brocard et al. Dermatology Liraglutide (glucagon-like peptide-1 agonist) 1 0.6mg SC daily titrated up to 1.8mg SC daily Case report of 1 patient whose HS improved (had 6.5kg weight loss over 8 weeks) Aprelimast (phosphodiesterase 4 inhibitor) 2 30mg BID Case series of 9 patients (Hurley stage II-III), 3 dropped out, 5/6 improved Canakinumab (anti-il-1beta antibody) 3,4 150mg SC monthly (1 patient received 150mg day 1, day 15, then monthly) Case reports of 3 patients (2 improved, 1 flared) Jennings et al. Br J Dermatol. 2017; 2. Weber et al. J Am Acad Dermatol. 2017; Houriet et al. JAMA Dermatol. 2017; 4. Tekin et al. Indian J Dermatol Venereol Leprol Emerging Therapies Secukinumab (anti-il-17a antibody) 300mg weekly for 1 month, then q4 weeks Case reports of 2 patients, both improved IFX-1 (anti-c5a antibody) Weekly IV infusion Phase II trial, 12 Hurley stage III patients, HiSCR 83% at 12 weeks Management of Severe HS patients Biologic + oral antibiotics + either acitretin or dapsone or colchicine or other disease modifying treatment +/- hormonal agent For acute flares, consider short courses of prednisone If disease is very severe, consider recommending hospitalization and starting IV steroids and/or IV antibiotics Schuch et al. Acta Derm Venereol Thorlacius et al. Br J Dermatol Riis et al. Expert Opin Investig Drug Case Study REMINDER: Do NOT give Methotrexate and Dapsone together (hematologic toxicity) 54 yo woman with history of PCOS, DM type 2, obesity (110kg), undifferentiated connective tissue disease, fibromyalgia, depression, anxiety, and smoking (1-2 e-cigarettes/day, formerly 1ppd cigarettes) 10 year history of HS: diffusely scattered open comedones, erythematous papules and nodules, and scarring in the bilateral axillae, mammary region, groin folds, on the buttocks, and under the abdominal pannus (diffuse Hurley stage II) 6
7 Case Study HS Regimen: Adalimumab 40mg SC weekly Acitretin 25mg daily (cleared by patient s psychiatrist to start) Spironolactone 100mg daily Metformin ER 1000mg daily Liraglutide 1.8mg SC daily BP wash daily Clindamycin 1% solution BID ILK injections After starting adalimumab, patient also took a two month course of oral clindamycin 300mg PO BID (rifampin had too many medication interactions) Patient s Care Team Internist (PCP) Endocrinologist Rheumatologist Nutritionist General surgeon (patient s/p gastric sleeve surgery) Psychiatrist Therapist Acupuncturist (East West medicine) Dermatologist Procedural Management Intralesional Steroid Intralesional triamcinolone (10mg/ml) helps to reduce pain and inflammation Riis et al. J Am Acad Dermatol Laser Therapy Laser hair removal (1064-nm Nd:YAG laser, 800-nm diode laser, non- Q-switched ruby laser) Photodynamic therapy Intralesional photodynamic therapy: intralesional photosensitizer (5- aminolevulinic acid 5% gel or 1% solution) administered into sinus tracts and nodules, and then after incubation period, a 630-nm laser introduced into the lesion through a fiber optic probe CO2 laser surgery (tissue debulking) Hamzavi et al. J Am Acad Dermatol Suarez Valladares et al. J Dermatol Sci Wide Local Excision Retrospective study of 74 patients with Hurley stage III HS who underwent wide local excision and secondary intention healing DLQI scores went from to 5.31 after surgery 70.3% of patients were satisfied with the cosmetic results. 84 patients (most with Hurley stage II or III) who underwent wide local excision and secondary intention healing, answered questionnaire Recurrence in 37.6% of the procedures within a mean follow-up period of 3 years Total remission of an anatomical area achieved in 49% of procedures 92% of patients were glad they had the operation Posch et al. J Am Acad Dermatol Deckers et al. J Eur Acad Dermatol Venereol
8 HS Comorbidities Cardiovascular: obesity, diabetes type 2, dyslipidemia, hypertension, metabolic syndrome, smoking Inflammatory disease: acne, follicular occlusion tetrad, pyoderma gangrenosum, inflammatory bowel disease, arthritis Hormonal: polycystic ovary syndrome Psychological: anxiety, depression, decreased work productivity, social isolation, impaired sexual health HS Complications Cutaneous complications Anal, urethral, and rectal strictures and fistulas Lymphedema Contractures and limb mobility limitations Cutaneous squamous cell carcinoma Systemic complications Anemia Systemic amyloidosis Serious infection Vekic et al. Australas J Dermatol. 2018; Dauden et al. J Eur Acad Dermatol Venereol. 2018; Patel et al. Curr Pain Headache Rep. 2017; Janse et al. Br J Dermatol Alikhan et al. J Am Acad Dermatol SCC in Chronic HS Multidisciplinary Approach Human papilloma virus and smoking may be risk factors associated with SCC in HS SCC arising from chronic HS is very aggressive, and has a high likelihood for rapid progression, recurrence, metastasis, and mortality Recommend aggressive approach to management at the time of SCC diagnosis (consult with surgery, radiation oncology, and either gynecologic oncology, urologic oncology, or hematology/oncology) Primary care Plastic surgery General surgery Obstetrics/Gynecology Urology Gastroenterology Nutrition Bariatric surgery Endocrinology Cardiology Rheumatology Psychiatry Psychology Pain management Jourabchi et al. Int Wound J Thank you! UCLA Hidradenitis Suppurativa Specialty Clinic Director: Jennifer Hsiao, MD jhsiao@mednet.ucla.edu Referrals: Special thank you to our HS patients, to our UCLA dermatology residents, and to Dr. Richard Bennett 8
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