52 e CONGRES DE L A.M.U.B.

Transcription

1 52 e CONGRES DE L A.M.U.B. Session Actualités thérapeutiques et diagnostiques Samedi 8 septembre 2018 Modérateurs : F. FELGUEROSO-BUENO Th. PEPERSACK B. VAN BENEDEN Dr. BENHADOU Farida Dermatologie Service de Dermatologie Hôpital Universitaire Erasme La maladie de Verneuil, ce qu il faut savoir! Association des Médecins anciens étudiants de l Université libre de Bruxelles

2 Conflits d intérêt en rapport avec la présentation Consultance pour ABBVIE

3 Introduction Hidradentis suppurativa (HS) General prevalence : 1-3% Maladie de Verneuil Acne inversa. Belgium: > patients Sex ratio: 3F/1M

4 Diagnostic criteria

5 Nodule

6 Abcess

7 Comedo

8 Hypertrophic scars and fistulae

9 Severity score: Hurley stages Hurley I Hurley II Hurley III

10 HS: A complex inflammatory disease Sudoral glands (Verneuil) Apocrin glands (Shelley) Follicular occlusion (Yu) Plewig/Kligman : «Acne inversa» and association with acne conglobata and dissequant folliculitis from the scalp (associated later with pilonidal sinus) Follicular tetrad Follicular occlusion definitively recognised as pathognomonic sign Yu CC, Cook MG Br J Derm, 1990 Plewig G, Kligman AM, Acne, morphogenesis and treatment, Berlin, Springer, 1975 Revuz J, Hidradenite Suppurée, EMC dermatologie, 2014, 49(4):1-15

11 Pathophysiology M. Nazary et al. / European Journal of Pharmacology 672 (2011) 1 8

12 HS lesions development Van der Zee HH et al. Exp Dermatol 21:735 9, 2012

13 Pathophysiology M. Nazary et al. / European Journal of Pharmacology 672 (2011) 1 8

14 HS and inflammatory diseases Inflammatory bowel disease Rheumatologic disorder HS Skin inflammatory conditions

15 Management of HS patients Surgery? Topical treatment? Systemic therapy?

16 TREATMENT FLOW CHART Mild Moderate - Severe GENERAL MEASURES* Smoking cessation Weight loss Discuss oral contraceptives Pain management Local wound care / Antiseptic wash HS SYSTEMIC TREATMENT* Topical/Intralesional treatment AND/OR Tetracyclines PO** Clindamycin +Rifampicin** Adalimumab** NO NO Improvement? Improvement? YES YES YES Improvement? NO Zinc gluconate AND/OR Metformin*** Acitretin or Tetracyclines AND/OR Metformin AND/OR Zinc gluconate*** Maintain Alternative therapy*** Based on EDF guidelines* (Zouboulis 2015), suggested flow chart** (Gulliver, 2016) and Belgian HS expert board discussions***

17 TREATMENT FLOW CHART Mild Moderate - Severe GENERAL MEASURES* Smoking cessation Weight loss Discuss oral contraceptives Pain management Local wound care / Antiseptic wash Based on EDF guidelines* (Zouboulis 2015), suggested flow chart** (Gulliver, 2016) and Belgian HS expert board discussions***

18 TREATMENT FLOW CHART Smoking cessation Rx: Nicotine substitutes REFERRAL? Tobaccologists For more information about smoke cessation: or - Contact details tobaccologists - Online coaching - Phone coaching: Groups sessions - Based on EDF guidelines* (Zouboulis 2015), suggested flow chart** (Gulliver, 2016) and Belgian HS expert board discussions***

19 TREATMENT FLOW CHART WEIGHT LOSS REFERRAL? Nutritionist, dietician, psychologist Choose your battle: smoke stop or weight loss? Based on EDF guidelines* (Zouboulis 2015), suggested flow chart** (Gulliver, 2016) and Belgian HS expert board discussions***

20 TREATMENT FLOW CHART ORAL CONTRACEPTIVES with anti-androgen activity WHEN? pre-menstrual flares (cfr. for acne) androgenic profile disturbances ( polycystic ovarian syndrome, Down Syndrome, ) Rx 1. DIANE (CYPROTERONCE ACETATE) 2. LOUISE (DIENOGEST) 3. BELLINA (CHLORMADINON) 4. YASMINE /YASMINELLE (DROSPIRENON) ASSESSMENT PERIOD: a minimum of 3 months of treatment in order to assess impact RISK FACTORS: thrombosis, considered as (relative) contra-indication for these types of OAC REFERRAL? gynaecologist or general practitioner Based on EDF guidelines* (Zouboulis 2015), suggested flow chart** (Gulliver, 2016) and Belgian HS expert board discussions***

21 TREATMENT FLOW CHART PAIN MANAGEMENT Rx No specific HS protocol use existing hospital-based analgesics flow charts as a basis 1. PARACETAMOL 2. NSAIDs! number of contra-indications is rising, e.g. gastritis/gastric ulcers, cardiovascular comorbidities; 3. OPIOÏD-LIKE ANALGESICS: MORPHINE, TRAMADOL (Domperidone to counter sickness during the first few days) Based on EDF guidelines* (Zouboulis 2015), suggested flow chart** (Gulliver, 2016) and Belgian HS expert board discussions***

22 TREATMENT FLOW CHART WOUND CARE Rx ANTISEPTIC WASH e.g. Povidone iodine (Isobetadine liquid soap ) max 3x/week (although no evidence exists) ANTISEPTIC CREAM e.p. Chlorhexidine cream Based on EDF guidelines* (Zouboulis 2015), suggested flow chart** (Gulliver, 2016) and Belgian HS expert board discussions***

23 TREATMENT FLOW CHART Mild Moderate - Severe GENERAL MEASURES* Smoking cessation Weight loss Discuss oral contraceptives Pain management Local wound care / Antiseptic wash HS SYSTEMIC TREATMENT* Topical/Intralesional treatment AND/OR Tetracyclines PO** Clindamycin +Rifampicin** Adalimumab** NO NO Improvement? Improvement? YES YES YES Improvement? NO Zinc gluconate AND/OR Metformin*** Acitretin or Tetracyclines AND/OR Metformin AND/OR Zinc gluconate*** Maintain Alternative therapy*** Based on EDF guidelines* (Zouboulis 2015), suggested flow chart** (Gulliver, 2016) and Belgian HS expert board discussions***

24 TREATMENT FLOW CHART Mild TOPICAL TREATMENT Rx CLINDAMYCIN (ZINDACLIN GEL OR DALACIN LOTION) ERYTHROMYCIN (INDERM LOTION OR ERYCINE LOTION) WHEN? superficial lesions - less tolerated on open lesions (alcoholic formulations) - limited package size - preparations combined with corticosteroids : less stability! Avoid topical antibiotics when systemic antibiotics are used; only antiseptic washes and/or topical resorcinol. ( Resorcinol to be prescribed in 15% Lanette cream II <> not stable in cetomacrogol cream base.) Resorcinol 15% dans NOURIVAN ANTIOX CREAM 500g ( Fagron ). Based on EDF guidelines* (Zouboulis 2015), suggested flow chart** (Gulliver, 2016) and Belgian HS expert board discussions***

25 TREATMENT FLOW CHART Mild INTRALESIONAL TREATMENT Rx Corticosteroid injection E.g. KENACORT OR CELESTONE, INJECT ML (< 1.0 ML) +/- LIDOCAINE. HOW? light aspiration of the lesion prior to CS injection less pressure / less pain within a few hours to be expected WHEN? single location and/or few flares/year - Painful Based on EDF guidelines* (Zouboulis 2015), suggested flow chart** (Gulliver, 2016) and Belgian HS expert board discussions***

26 TREATMENT FLOW CHART Mild TETRACYCLIN PER OS Rx MINOCYCLIN: mg/d dose to be decreased when disease is stabilized E.g. in obese patients start mg/d and taper down to 100 mg/d (note: no evidence exists regarding this dosing schedule, it is purely experienced-based) in case minocyclin is not tolerated (e.g. auto-immune background) DOXYCYCLIN 2x100 OR 2x200 mg/d or ALTERNATIVE TETRACYCLINE - photo toxicity <> e.g. pregnancy: MACROLIDE ANTIBIOTICS: ERYTHROMYCIN: 3x500 mg/d, may be tapered to 2x500 mg AZITHROMYCIN: 500 mg/d Based on EDF guidelines* (Zouboulis 2015), suggested flow chart** (Gulliver, 2016) and Belgian HS expert board discussions***

27 TREATMENT FLOW CHART Mild Moderate - Severe GENERAL MEASURES* Smoking cessation Weight loss Discuss oral contraceptives Pain management Local wound care / Antiseptic wash HS SYSTEMIC TREATMENT* Topical/Intralesional treatment AND/OR Tetracyclines PO** Clindamycin +Rifampicin** Adalimumab** NO NO Improvement? Improvement? YES YES YES Improvement? NO Zinc gluconate AND/OR Metformin*** Acitretin or Tetracyclines AND/OR Metformin AND/OR Zinc gluconate*** Maintain Alternative therapy*** Based on EDF guidelines* (Zouboulis 2015), suggested flow chart** (Gulliver, 2016) and Belgian HS expert board discussions***

28 TREATMENT FLOW CHART Mild ZINC GLUCONATE and/or METFORMIN Rx ZINC GLUCONATE 90 mg/d (= 4 tabs of ZINCOTABS) ZINC SULFATE mg/d METFORMIN 1x500 mg/d after 1 week 2x500 mg/d and if possible up to 3x500 mg/d; one might try 2x850 mg/d in obese patients anti-androgenic effect in addition to lowered insulin resistance ASSESSMENT PERIOD 6 months manage patient expectations - gastro-intestinal side-effects; usually transient! Use a sequential approach to start Zinc and Metformin <> gastro-intestinal side-effects of both! Discuss metformin prescription with GP Based on EDF guidelines* (Zouboulis 2015), suggested flow chart** (Gulliver, 2016) and Belgian HS expert board discussions***

29 TREATMENT FLOW CHART Mild Moderate - Severe GENERAL MEASURES* Smoking cessation Weight loss Discuss oral contraceptives Pain management Local wound care / Antiseptic wash HS SYSTEMIC TREATMENT* Topical/Intralesional treatment AND/OR Tetracyclines PO** Clindamycin +Rifampicin** Adalimumab** NO NO Improvement? Improvement? YES YES YES Improvement? NO Zinc gluconate AND/OR Metformin*** Acitretin or Tetracyclines AND/OR Metformin AND/OR Zinc gluconate*** Maintain Alternative therapy*** Based on EDF guidelines* (Zouboulis 2015), suggested flow chart** (Gulliver, 2016) and Belgian HS expert board discussions***

30 TREATMENT FLOW CHART Moderate - Severe CLINDAMYCIN + RIFAMPICIN Rx 2x300 mg/d for WEEKS (MAX!) CLINDAMYCIN! Clostridium difficile limit in time. Rifampicin is counterbalancing the risk. RIFAMPICIN! never in monotherapy due to the risk of resistance (tuberculosis!). <> Pregnancy use mechanic contraceptive methods because of interaction of Rifampicin with oral contraceptives - gastro-intestinal side effects ENTEROL - Rifampicin not reimbursed (only for TBC)! Liver function tests at week 0, 4 and 10! Discuss Rifampicin prescription with GP Based on EDF guidelines* (Zouboulis 2015), suggested flow chart** (Gulliver, 2016) and Belgian HS expert board discussions***

31 TREATMENT FLOW CHART Mild Moderate - Severe GENERAL MEASURES* Smoking cessation Weight loss Discuss oral contraceptives Pain management Local wound care / Antiseptic wash HS SYSTEMIC TREATMENT* Topical/Intralesional treatment AND/OR Tetracyclines PO** Clindamycin +Rifampicin** Adalimumab** NO NO Improvement? Improvement? YES YES YES Improvement? NO Zinc gluconate AND/OR Metformin*** Acitretin or Tetracyclines AND/OR Metformin AND/OR Zinc gluconate*** Maintain Alternative therapy*** Based on EDF guidelines* (Zouboulis 2015), suggested flow chart** (Gulliver, 2016) and Belgian HS expert board discussions***

32 TREATMENT FLOW CHART Moderate - Severe Rx ACITRETIN mg/d, usually 25 mg/d if obese.! NEVER in woman of childbearing age! Not to be used when important number of inflammatory AN, because the skin barrier is too vulnerable HS flare-up! ( Rx Medrol +/- antibiotics) ACITRETIN OR TETRACYCLINE <> Acitretin (risk = pseudotumor cerebri) OR ERYTHROMYCIN 2-3x500 mg/d (! Liver function) AND/OR METFORMIN AND/OR ZINC GLUCONATE Based on EDF guidelines* (Zouboulis 2015), suggested flow chart** (Gulliver, 2016) and Belgian HS expert board discussions***

33 TREATMENT FLOW CHART Mild Moderate - Severe GENERAL MEASURES* Smoking cessation Weight loss Discuss oral contraceptives Pain management Local wound care / Antiseptic wash HS SYSTEMIC TREATMENT* Topical/Intralesional treatment AND/OR Tetracyclines PO** Clindamycin +Rifampicin** Adalimumab** NO NO Improvement? Improvement? YES YES YES Improvement? NO Zinc gluconate AND/OR Metformin*** Acitretin or Tetracyclines AND/OR Metformin AND/OR Zinc gluconate*** Maintain Alternative therapy*** Based on EDF guidelines* (Zouboulis 2015), suggested flow chart** (Gulliver, 2016) and Belgian HS expert board discussions***

34 TREATMENT FLOW CHART Moderate - Severe ADALIMUMAB (Humira ) Rx HUMIRA : week 0: 160mg; week 2: 80 mg; as of week 4: 40mg on a weekly basis WHY? TNF-α levels are significantly increased in HS patients! PRE-TESTS : TB: Mantoux test + chest X-ray - if negative Mantoux (ok); - if positive (beware of false-positives => do Quantiferon test/igra test). - If Quantiferon test also postive Check CXR and consult pneumology for risk active TB - Adequate prophylaxis in case of latent TB To add? antibiotics (tetracycline, Rifampicin Clindamycin)! Bacterial swab at baseline, after 3 months and in case of sudden flares, strong suppuration, sick patient/fever or strongly elevated inflammatory parameters, especially in extensive Hurley II or Hurley III Based on EDF guidelines* (Zouboulis 2015), suggested flow chart** (Gulliver, 2016) and Belgian HS expert board discussions***

35 TREATMENT FLOW CHART Mild Moderate - Severe GENERAL MEASURES* Smoking cessation Weight loss Discuss oral contraceptives Pain management Local wound care / Antiseptic wash HS SYSTEMIC TREATMENT* Topical/Intralesional treatment AND/OR Tetracyclines PO** Clindamycin +Rifampicin** Adalimumab** NO NO Improvement? Improvement? YES YES YES Improvement? NO Zinc gluconate AND/OR Metformin*** Acitretin or Tetracyclines AND/OR Metformin AND/OR Zinc gluconate*** Maintain Alternative therapy*** Based on EDF guidelines* (Zouboulis 2015), suggested flow chart** (Gulliver, 2016) and Belgian HS expert board discussions***

36 TREATMENT FLOW CHART Moderate - Severe ALTERNATIVE THERAPY ANTIBIOTICS Bactrim in pulse treatments Oral metronidazol (Flagyl ) monotherapy (for 6 weeks, no longer due to risk of neurologic complications) Rifampicin 2x300 mg/d + oral Metronidazol 3x500 mg/d (max. 6 weeks cfr. supra) + Moxifloxacin 400 mg/d DAPSON mg/d Multiple side effects and drug interactions, frequent blood analysis necessary. Blood tests: Check for glucose-6-phosphate dehydrogenase insufficiency before start, first month weekly, second month bi-weekly, and then 1x/month up to 1x/3-6 months. COLCHICIN (2x 0.5 mg 2 x 1 mg/d) as alternative treatment: disappointing; the evidence is very weak; might consider combining with Dapson. INFLIXIMAB, ANAKINRA* (not approved for HS, only limited data available) *not available in Belgium Based on EDF guidelines* (Zouboulis 2015), suggested flow chart** (Gulliver, 2016) and Belgian HS expert board discussions***

37 TREATMENT IN CASE OF ACUTE FLARES AMOXICILLIN + CLAVULANATE Rx IV Augmentin 4 g/d for 3-5 days (hospitalized), followed by oral Augmentin 3x875mg/d OR oral Augmentin 2x2 gr (1 gr retard formulation) for 5-10 days Do not use Augmentin longer than 2 weeks (resistance!) METHYLPREDNISOLON (MEDROL ))) Rx 32 mg/d taper rapidly (e.g. to 8 mg/5 d) Only for short terms for extreme flare-ups; can be combined with Augmentin Topical corticosteroids (e.p. betamethasonedipropionate) can be considered for larger patches of very inflammatory regions FOR A SHORT PERIOD Based on EDF guidelines (Zouboulis 2015), suggested guideline flow chart (Gulliver, 2016) and Belgian HS expert board discussions.

38 The use of adalimumab in HS

39 EMA approval 25 Jun 2015

40 Posology Induction dose Weekly treatment

41 First request Diagnosis : 18 y Active moderate to severe HS Hurley II of III* 5 inflammatory lesions HS-PGA score moderate (3, 4 of 5)* 6 months Insufficient response, documented intolerance or contra-indication to Oral tetracyclins 4 months AND Oral clindamycin (300mg 2x/d) + rifampicin (600mg/d) 10 weeks No active TB

42 Patients (%) Patients (%) PIONEER I 1 PIONEER II 2 70% 60% ADA weekly (N=153) 70% PBO (N=154) 58,9% ** 60% ADA weekly (N=163) PBO (N=163) 50% 41,8% * 50% 40% 40% 30% 26,0% 30% 96/163 27,6% 20% 64/153 20% 10% 40/154 10% 45/163 0% Week 12 0% Week 12 NRI analysis. * Statistically significant with P value 0.01; ** P < Kimball AB et al. Safety and Efficacy of Adalimumab in Moderate to Severe Hidradenitis Suppurativa: Results from first 12 Weeks of PIONEER I, a Phase 3, Randomized, Placebo-Controlled Trial. Poster presented at: 73rd Annual meeting of the American Academy of Dermatology, San Francisco, CA, March 20-24, Jemec GBE et al. Efficacy and Safety of Adalimumab in Patients With Moderate to Severe Hidradenitis Suppurativa: Results From PIONEER II, a Phase 3 Randomized Placebo-controlled Trial Poster Presented at the 73rd Annual Meeting of the American Academy of Dermatology, San Francisco,

43 PIONEER I: Improvement in QOL PIONEER I Percent reduction in skin pain Reduction in DLQI 0,00% 0.00% 0-5,00% 5.00% 6.5% ,00% 10.00% 19.6% ,00% 15.00% ,00% 20.00% ,00% 25.00% Placebo ADA weekly -6 6 Armstrong A et al. Adalimumab Improves Health-related Quality of Life (HRQoL) in Patients With Moderate to Severe Hidradenitis Suppurativa (HS): Results From the First 12 Weeks of PIONEER I. Poster 197 Presented at the 44th Annual European Society for Dermatological Research Meeting, September 2014, Copenhagen, Denmark.

44 Mean ± SD PIONEER II: Improvement in QOL PIONEER II Reduction in DLQI from baseline to Week 12* PBO ADA weekly 0 Week 4 Week ± ± ± ± 0.53 *Week 12 imputation method used was last observation carried forward (LOCF). P values were calculated from ANCOVA with stratum (baseline Hurley Stage and antibiotics use), baseline value, and treatment in the model. P< ADA=adalimumab; DLQI=dermatology life quality index; PBO=placebo; SD=standard deviation. Armstrong A et al. Adalimumab Improves Health-Related Quality of Life (HRQoL) in Patients with Moderate to Severe Hidradenitis Suppurativa (HS): Results from the First 12 Weeks of PIONEER II: Poster Presented at the 73rd Annual Meeting of the American Academy of Dermatology, San Francisco, California, March 20 24, 2015.

45 Take home message