1 / 27

MANAGEMENT OF BULLOUS PEMPHIGOID. What are the current problems ?

Pascal JOLY MD, PhD Rouen University Hospital France Coordinator of the French Study Group on autoimmune bullous skin diseases « Groupe Bulle ». MANAGEMENT OF BULLOUS PEMPHIGOID. What are the current problems ?. What should we take into account for optimal management of BP ?.

morrison
Télécharger la présentation

MANAGEMENT OF BULLOUS PEMPHIGOID. What are the current problems ?

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Pascal JOLY MD, PhD Rouen University Hospital France Coordinator of the French Study Group on autoimmune bullous skin diseases « Groupe Bulle » MANAGEMENT OF BULLOUS PEMPHIGOID.What are the current problems ?

  2. What should we take into account for optimal management of BP ? • main characteristics of patients (+++) • main characteristics of BP (localized, mild, extensive) • what is demonstrated from the literature ? • how data from the literature can help me to manage my patients ?

  3. Main characteristics of BP patients • elderly: mean age : 81 to 83 years-old incidence : 300 cases/M/year over 80 years • poor general condition : Karnowsky index : 60% 1/3 patients bed ridden • frequency of cardiovascular and Neurological disorders (dementia) with high functional impairment Neurological disorder in patients with bullous pemphigoidCordel N et al, Dermatology, 2007 French study on 341 BP patients : 40% neurological disorder(s) 20% severe dementia • 20% Parkinson’s disease, stroke

  4. Risk factors of Bullous Pemphigoid • prospective multicentre case- control study > 300 patients performed in France • major risk factors : -1 debilitating neurological disorders : • dementia (OR : 3.5) • Parkinson’s disease (OR : 2.0) • stroke (OR : 2.0) -2 major functionnal impairment, bed ridden patients (OR : 2.2) -3 chronic drug intake : diuretics : spironolactone (OR : 1.9), psycholeptics (OR : 2.1)

  5. Prognostic factors of BP Prediction of survival of patients with BP JOLY P et al – Arch Dermatol 2005;141:691-98 • deleterious prognostic factors - older age * - cardiac insufficiency - dementia - past history of stroke - poor general condition * NOT – extent of BP (+++), -number of daily new bullae * Multivariate analysis

  6. Prognostic factors of BP • POOR prognosis in European Countries one year mortality: -30 to 40% in France (probably overestimated (hospital-based series) -25-30% in Germany (hospital-based series) • -20% in the UK (probably underestimated: based exclusively on GP, excluding patients hospitalized in dermatotogy dept and in nursing homes • mortality rate 2 to 4 times higher than in the general population

  7. What should we take into account for optimal management of BP ? • main characteristics of patients (+++) • main characteristics of BP (localized, mild, extensive) • what is demonstrated from the literature ? • how data from the literature can help me to manage • my patients ?

  8. Oral corticosteroids • considered main stay of treatment for 20 years • Prednisone more effective than prednisolone (Lebrun-Vigne et al – Arch Dermatol 1999) - rate of disease control : 70 – 80 % 3 doses proposed : - high doses : 0.75 mg/kg/d to 1.25 mg/kg/d (no difference : Morel P et al – 1984) - medium doses : 0.5 mg/kg/d - low doses : 0.25 – 0.3 mg/kg/d

  9. It is clear from the literature, what we should not do… • use HIGH doses oral CS (especially in elderly patients) -Roujeau JC et al. Arch Dermatol 1998 - Rzani B et al. Arch Dematol 2OO2 - Joly P et al. N Engl J Med 2002 Mortality rate : 35% to 40% main causes of death : infections, stroke, acute cardiac failure,… • use LOW doses of oral CS for EXTENSIVE BP - Roujeau JC et al. Lancet 1984 0 of 15 BP patients controlled by: 0.3mg/kg/d oral prednisone

  10. It is clear from the literature, what we should not do… • Routine use of immunosuppressive drugs - Guillaume JC et al. Arch Dermatol 1993 NO BENEFIT (disease control, doses of CS), MORE SEVERE COMPLICATIONS • IV Ig - poorly convincing data: open series of «recalcitrant BP» (Do recalcitrant BP still exist ??) - decrease of CS doses (CS doses are always decreased) - very expensive - some adverse events: aseptic meningitis

  11. A comparison of oral methyl prednisolone plus azathioprine or mycophenolate mofetil for the treatment of Bullous pemphigoidBeissert S et al, Arch Dermatol, 2007 • 73 BP patients in Germany • Oral methylprednisolone+ azathioprine or MMF • Primary end-point: - cumulative dose of CS • - rate of remission • Complete remission: 38/38 (100%) CS+Aza • 35/35 (100%) CS+MMF • Median dose of CS: 4967g (Aza) vs 5754g (MMF) (NS) • Severe treatment side efect: 24% vs 17% (NS) • Conclusion: « MMF and aza demonstrate similar efficacy » +/- • « MMF: lower toxicity profile than Aza » Yes, but… • Infections more frequent in MMF group

  12. What is clearly demonstrated from the literature ? A comparison of oral and topical corticosteroids Joly P et al. N Engl J Med 2002;346:321-7 • To date, the only treatment regimen which has demonstrated a superiority as compared to oral CS is: High potency topical CS - better efficacy in controlling both localized andextensive BP - reduced morbidity and mortality as compared to 1mg/kg/d oral CS - diabetes melitus, bone fractures, infections (pneumoniae), psychiatric syndroms, myopathy..

  13. What is not clearly demonstrated, but could be interesting in the treatment of BP • medium doses of oral corticosteroids • combined treatment with topical CS and Methotrexate • antibiotics

  14. Are medium doses oral CS effective for the treatment of extensive BP ? • 0.75mg/d prednisolone:as effective as 1.25mg/d (Morel P et al.Ann Dermatol 1984) No major difference for treatment side effects • 0.3mg/d : not effective in controlling extensive BP(Roujeau JC et al. Lancet 1984) • 0.5mg/d : only one study in the literature My experience : - localized BP : topical CS easier, more effective - mild BP : often effective – well tolerated - extensive BP : 0.5mg/kg/d: only occasionally effective

  15. Medium doses of oral corticosteroidsPrednisone 0.5 mg/kg/d • poorly evaluated in the literature • one study in the literature (Joly P et al – N Engl J Med – 2002) - moderate BP :  10 new blisters daily  rate of complete remission by day 21 : 72/76 (95 %)  rate of relapse : 39/76 (40 %) • efficacy in extensive BP not evaluated Personal experience : 0.5 mg/kg/d : only occasionaly effective

  16. Methotrexate and topical CS Dereure O et al. Arch Dermatol 2002:138;1255-6 Bara C et al. Arch Dermatol 2003:139;1506-7 • 2 Single centre open studies in France • initial treatment with topical CS until control of BP lesions (15 days) • low doses MTX 10 - 15 mg/week • contra indications : - renal insufficiency - creatinine clearance (< 40 ml/min) - liver disfunction - anemia, neutropenia • seems effective, well tolerated,easy to use • to be confirmed by a controlled study

  17. Methotrexate and topical CS Kjelman P et al. Arch Dermatol 2008:144;612-16 • retrospective study 98 patients treated with : - MTX alone (n=61) 50 % mild disease - MTX + prednisone (n=37) 32 % mild disease • median dose MTX : 5 mg/w (2.5 – 10 mg) • doses of prednisone : 10 – 20 mg/d (initially or secondary added) • severe MTX side effect (stop treatment) : n=5 • rate of remission at 24 months : 43 % (MTX alone), 35 % (MTX + P) • median time to achieve CR remission : - 6 months mild BP - 17 months severe BP • « among to our groving clinical experience of MTX today, we usually increase the dose of MTX to 12.5 g/d»

  18. Tetracyclines and nicotinamide (Fivenson D et al. Arch Dermatol 1994) • single centre randomized study • suggested that tetracyclines and nicotinamide could be as effective as oral CS in the treatment of BP • very small number of patients: 6 vs 14 !!! • method of randomization not clear... • high rate of drop out patients • QUESTION: is the absence of difference due to efficacy of tetracyclines, or to a lack of statistical power of the study ? • data not confirmed by another study since 10 years

  19. What should we take into account for optimal management of BP ? • main characteristics of patients (+++) • main characteristics of BP (localized, mild, extensive) • what is demonstrated from the literature ? • how data from the literature can help me to manage • my patients ?

  20. How can I manage BP patients in view of the main data from literature 2) is hospitalization required for the treatment of BP patients ? • hospitalization is NOT responsible for a higher mortality rate in BP patients 1 year survival rate of BP out patients : 72 % (95 % CI 58 %-86 %) in patients : 67 % (95 % CI 62 %-73 %) COLBERT R et al. J Invest Dermato 2005;122:1091-95 JOLY P. et al. J Invest Dermatol 2005;124:664-5

  21. How can I manage BP patients in view of the main data from literature Hospitalization • not useful : - localized BP - « young » patients with mild BP • proposed for : - old patients in poor general condition (mild/extensive BP) - patients with associated disorders (cardiac insufficiency, diabete melitus…) - extensive BP

  22. Which treatment can we propose for our patients ? • localized BP : topical CS clobetasol propionate 10 g/day • mild BP (< 10 daily new blisters) - medium doses of oral CS ? (prednisone : 0,5 mg/kg/d) - medium doses of topical CS (clobetasol propionate 20-30 g/d) - initial topical cs + Methotrexate ?

  23. Treatment of mild forms of BP • patients with a good prognosis (« young » patients, good general condition) • both treatments can be proposed - prednisone 0,5 mg/kg/day - initial topical CS + Methotrexate - topical CS 2) patients with risk factors (old age, poor general condition) - topical cs (+++) - initial topical cs + MTX ?

  24. Patients with extensive BP Effective treatments - high doses of oral CS (prednisone 0,75-1 mg/kg/d) - high doses of topical CS (clobetasol propionate 30-40/d) - topical CS and MTX ? Patients with a good prognosis (young, good general condition) - both treatments Patients with risk factors (old age, poor general condition) - topical CS (+++) - topical CS + MTX ? - medium doses oral CS

  25. Conclusion • keep in mind : - the objective of treatment - the three deleterious predictors of BP: • high doses of oral CS • old age • poor general condition • be very cautious to treat elderly patients • avoid agressive treatments,especially if they have not been robustly evaluated

More Related