Nail disorders. Prof. MUDr. Petr Arenberger, DrSc, MBA

Transcription

1 Nail disorders Prof. MUDr. Petr Arenberger, DrSc, MBA

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3 Baseline Nail Disease in Patients with Moderate-to-Severe Psoriasis and Response to Treatment with Infliximab over One Year Phoebe Rich, Christopher E. M. Griffiths, Kristian Reich, Frank O. Nestle, Richard K. Scher, Shu Li, Stephen Xu, Ming-Chun Hsu, Cynthia Guzzo J Am Acad Dermatol Feb;58(2): Epub 2007 Dec 20.

4 Content Back to basics Nail anatomy Nail pathology Key clinical features of nail psoriasis Epidemiology Impact and consequences of disease Assessment tools Is the nail a window to something more? Management of nail disease

5 The Nail as a Musculoskeletal Appendage The nail as a skin appendage Developmentally, it arises as an in-growth from the epidermis 1 However, recent histological studies showed The nail is integrated with the musculoskeletal system Functionally linked to the distal phalanx and distal interphalangeal (DIP) joint structures 2 1 Dawber RPR, et al. Science of the nail apparatus. In: Diseases of the Nails and Their Management. Blackwell Science; pp 1-47; 2 McGonagle D, et al. Dermatology 2009;218(2):

6 Anatomy of the Nail Eponychium Lunula Onychondermal band Proximal nail fold Nail plate Nail bed Dorsal proximal nail fold Ventral proximal nail fold Proximal nail fold sub-divisions Eponychium Nail bed Matrix Nail plate Hyponichium Distal groove Distal phalanx Adapted from: Jiaravuthisan MM, et al. JAAD. 2007;57:1-27.

7 Key Clinical Features: Pit Formation Dorsal proximal nail fold Pit Nail plate Ventral proximal nail fold Matrix Nail bed Adapted from: Jiaravuthisan MM, et al. JAAD 2007;57:1-27.

8 Clinical manifestation nail matrix Pits Dystrophy Erythema of the Lunula Clinical pictures from Kristian Reich, Hamburg and Robert Baran, Cannes (France) Leukonychia

9 Hyperparakeratosis of the nail matrix Clinical pictures from Kristian Reich, Hamburg and Robert Baran, Cannes (France)

10 Clinical manifestation nail bed Splinter hemorrhage Oil drop Onycholysis Clinical picture from Kristian Reich, Hamburg Subungual Hyperkeratosis

11 Clinical manifestation nail bed Splinter hemorrage/bleeding Clinical picture from Kristian Reich, Hamburg

12 Clinical spectrum of nail psoriasis Psoriatic Onychopachydermoperiostitis (POPP Syndrome) Clinical pictures from Robert Baran, Cannes (France)

13 Pathology of Nail Psoriasis Current concept Genetic factors Mechanical stress Environmental factors Pattern of immunopathology Jiaravuthisan MM, et al. JAAD. 2007;57:1-27. Photographs courtesy of Robert Baran, MD, Cannes (France).

14 Key Clinical Manifestations Leukonychia Red Spots Pitting Nail Bed Nail Matrix Oil Drop Discoloration Splinter Haemorrhages Subungual Hyperkeratosis Crumbling Onycholysis Jiaravuthisan MM, et al. JAAD. 2007;57:1-27. Photograph from Rich P, et al. JAAD 2008;58(2):

15 Clinical Manifestations: Nail Matrix Pitting Dystrophy (transverse grooves) (crumbling) Leukonychia Photographs courtesy of Robert Baran, MD, Cannes (France) and Kristian Reich, Hamburg.

16 Clinical Manifestations: Nail Bed Subungual hyperkeratosis Oil Spot Splinter haemorrhage Onycholysis Photographs courtesy of Robert Baran, MD, Cannes (France) and Kristian Reich, Hamburg.

17 Clinical Spectrum of Nail Psoriasis Psoriatic Paronychia Photographs courtesy of Robert Baran, MD, Cannes (France).

18 Clinical Spectrum of Nail Psoriasis Psoriatic Onychopachydermoperiostitis (POPP syndrome) Photograph courtesy of Robert Baran, MD, Cannes (France).

19 Frequency of Nail Psoriasis in PsA Parameter Patients with PsA (n = 312) Patients without PsA (n = 1,055) Mean age [years] (SD) 49.4 (14.0) 50.9 (15.4) Gender [%] (n) Positive family history of psoriasis n (%) Male 57.7 (180) 58.5 (617) Female 42.3 (132) 41.5 (438) 145 (46,5) 388 (36.8) Nail psoriasis n (%) 214 (68.6) 427 (40.5) PASI (mean) DLQI (mean) n =1,511 Reich K, et al. Br J Dermatol. 2009

20 Extensor Tendon Enthesis Sagittal section of distal interphalangeal (DIP) joint (Masson s trichrome stain) shows extensor tendon enthesis fibrous tissue enveloping the nail root Superficial Lamina Extensor Tendon Nail Root Deep Lamina Fat Adapted from: Tan, et al. Rheumatology. 2007;46(2): Distal Phalanx

21 Anchored by Entheses Extensor Tendon Superficial and Deep Lamina Nail Flexor Tendon Lateral Lamina Adapted from: McGonagle D, et al. Dermatology 2009;218(2):

22 Linear manifestation of nail changes

23 Frequency of Symptoms of Nail Psoriasis Survey sent to Dutch union of psoriasis patients; 7000 questionnaires sent, 1728 were returned Baseline Characteristics Age (yrs), mean (SD) 47 (14) Patients with skin lesions present 100% Disease duration, mean (SD) 12 (10) Patients with joint complaints 48.5% Nail psoriasis present,* n(%) 1369 (79.2%) Pitting (%) 75.3% Deformation (%) 65.9% Upward lifting (%) 49.3% Onycholysis (%) 46.2% Discoloration (%) 29.2% * 62.6% of pts had both fingers and feet involved; 26.8 only fingers and 8.6% only feet. de Jong EM, et al. Dermatology. 1996;193:

24 Frequency of Symptoms of Nail Psoriasis EXPRESS: Summary of target manifestations at baseline Randomised patients with nails involved at baseline Target nail feature Nail matrix psoriasis Pitting, n (%) Leukonychia, n (%) Nail plate crumbling, n (%) Red spots in lunula, n (%) Target nail feature Nail bed psoriasis Onycholysis, n (%) Oil drop discoloration, n (%) Nail bed hyperkeratosis, n (%) Splinter haemorrhages, n (%) Placebo Infliximab (5 mg/kg)* * Patients in the placebo group crossed over to infliximab (5 mg/kg) at week 24. Infliximab (5 mg/kg) (72.3) 24 (36.9) 21 (32.3) 4 (6.2) 48 (73.8) 34 (52.3) 28 (43.1) 11 (16.9) 170 (70.8) 111 (46.3) 81 (33.8) 27 (11.3) 159 (66.3) 110 (45.8) 102 (42.5) 60 (25.0) Rich P, et al. JAAD. 2008;58(2):

25 Prevalence of Nail Psoriasis Approx. 30% (15% 50%) of psoriasis patients have nail involvement 1 (Europe: 1.5 million; USA: 2 million) Approx. 50% of patients attending a dermatologist for psoriasis have nail psoriasis 2 The lifetime incidence of nail psoriasis among patients with psoriasis is 80% 90% 1 Only 1% 5% of patients have nail involvement without other cutaneous findings 3 Approximately 70% to 80% of patients with psoriatic arthritis (PsA) have nail involvement 6 1 Jiaravuthisan MM et al. J Am Acad Dermatol 2007; 57: 1-27; 2 Augustin M et al. Dermatology 2008; 216(4): ; 3 Van Laborde S, Scher RK. Dermatol Clin 2000; 18: 37-46; 4 Lawry M. Dermatol Ther 2007: 20; 60-67

26 Frequency of Nail Psoriasis and Severity of Skin Symptoms* Number of patients Pts with nail pso Pts without nail pso % 54.2% 61.2% Mild (PASI <10) Moderate (PASI >10; 20) Severe (PASI >20) Severity of Skin Symptoms Augustin M, et al. Dermatology. 2008;216(4): * n =1,511; 48.1% with nail psoriasis

28 Impact of Disease Skin Joints Quality of Life Function Treatment decision Nails

29 Dutch Survey: Complaints Related to Nail Psoriasis* Restricted in Daily Activities 58.9 Restricted in Housekeeping 56.1 Restricted in Profession Percentage of Patients (%) 52% of all respondents suffer from pain caused by the nail changes 93% of all respondents are concerned about the cosmetic appearance of their nails 77% of patients with nail lesions would like to undergo treatment de Jong EM, et al. Dermatology. 1996;193: * n =1,728

30 Dutch Survey: Treatment of Nail Psoriasis* Improvement with previous treatments for nail psoriasis Marked Improvement Little Improvement No Improvement * N= % of patients reported little to no improvement with previous therapies for nail psoriasis de Jong EM, et al. Dermatology 1996;193:

31 Significance of Nail Psoriasis Restricts patients in daily activities and causes social embarrassment 1 >50% of patients suffer from pain 1 Difficult to treat 2-4 Slow to respond Conventional treatments are generally difficult to administer and often ineffective Removal of nail may be necessary for refractory cases 1 de Jong EM, et al. Dermatology 1996;193: ; 2 Scher RK. Dermatol Clin. 1985;3: ; 3 de Berker D. Clin Exp Dermatol. 2000;25: ; 4 Farber EM. Cutis 1992;50: Photograph courtesy of Robert Baran, MD, Cannes (France).

33 Nail Psoriasis Severity Index (NAPSI) Nail is divided into four quadrants In each quadrant the presence of nails matrix and/or nail bed is assessed 0 = absent, 1 = present Nail bed psoriasis (onycholysis, splinter haemorrhages, oil drop discoloration and nail bed hyperkeratosis): 0 4 Nail matrix psoriasis (pitting, leukonychia, red spots in the lunula and nail plate crumbling): 0 4 NAPSI scores ranges from 0 8 (target nail) 10 nails (0 80); 20 nails (0 160) Rich, Scher, JAAD. 2003;49:

34 Determining the NAPSI Matrix Bed Pitting Leuconychia Onycholysis Splinter haemorrhages Lunulaerythema Onychodystrophy Oil drop Subungual hyperkeratosis NAPSI = 5

35 Assessment Tools and Nail Involvement Assessment Tool PASI Baran s nail psoriasis severity index 3 Cannavò s scoring system 4 NAPSI 2 DLQI 1 Involvement of Nails Does not take the severity of nail involvement into account Yes, but does not focus on function, pain or QoL Yes, but only little focus on function, pain or QoL (3 items, no validation) Yes, but does not focus on function, pain or QoL Does not focus on nails, only mentions skin 1 Finlay AY, Khan GK. Clin Exp Dermatol. 1994;19: ; 2 Rich P, Scher R. J Am Acad Dermatol. 2003;49: ; 3 Baran RL. Br J Dermatol. 2004;150: ; 4 Cannavò SP, et al. Dermatology. 2003;206:

37 Nail psoriassis a window to more? A window to the joint? Enthesitis DIP involvement; PsA Nail psoriasis early marker? 1 de Jong EM, et al. Dermatology. 1996;193: ; 2 Lawry M. Dermatol Ther. 2007:20;60-67; 3 McGonagle D, et al. Dermatology. 2009;218(2):97-102; 4 Tan AL, et al. Arthritis Rheum. 2006:54(4):

38 Nail Psoriasis May Be Sign of Joint Involvement 2 studies have assessed relationship between nail involvement and DIP joint manifestations Patients with psoriasis without symptomatic PsA 1 Prevalence of DIP bone involvement was higher in patients with fingernail and toenail involvement (P=0.039 and P=0.021, respectively) Positive correlation of fingernail and toenail psoriasis severity and bone involvement severity Patients with PsA with or without onychopathy 2 MRI distal phalanx abnormalities were higher in patients with onychopathy MRI DIP joint involvement was almost exclusively associated with patients with nail involvement and distal phalanx changes 1 Serarslan G, et al. Clin Rheumatol. 2007;26: ; 2 Scarpa R, et al. J Rheumatol. 2006;33:

39 Clinical Predictors of PsA Of 1593 patients with psoriasis, <10% developed PsA Psoriasis features associated with significantly higher risk for PsA Scalp lesions Nail dystrophy Intergluteal/ perianal lesions Wilson FC, et al. Arthritis Rheum. 2009;61(2);

40 The Importance of the Nail in Psoriasis A window to disease severity? Nail psoriasis Systemic inflammation Severe disease course of PsA 1 de Jong EM, et al. Dermatology. 1996;193: ; 2 Lawry M. Dermatol Ther. 2007:20;60-67; 3 McGonagle D, et al. Dermatology. 2009;218(2):97-102; 4 Tan AL, et al. Arthritis Rheum. 2006:54(4):

41 Link Between Nail Disease Severity and PsA Study examined the relationship between severity of nail disease and PsA in 69 patients 2 83% of patients had clinically detectable nail disease More severe nail disease More severe skin disease Increased rates of unremitting PsA with functional impairment Williamson L, et al. Rheumatology. 2004;43:

42 Nail Psoriasis: A Window to Something More? Two studies; n = 1,511 (2005) and n = 2,009 (2007) Nail psoriasis Is more frequent in males (approx. 10% difference) Correlates with high disease activity (PASI, BSA, hospitalisation, disease duration) Correlates with higher body weight A Marker of systemic inflammation? Augustin M, Reich K, et al. Unpublished.

43 PsA Underdiagnosis by Dermatologist? N = 1,511 patients with plaque-type psoriasis Screened for PASI, DLQI, etc Results 20.6% had PsA* 85% of cases with new PsA diagnosis 95% with active arthritis and 53% had >5 joints affected 41% DIP involvement and 23.7% dactylitis PsA patients had higher PASI and DLQI * Patients with joint symptoms were referred to a rheumatologist for diagnosis. Reich K, et al. Br J Dermatol. 2009

44 Dermatologists Opportunity dermatologists are in the vanguard of diagnosing early psoriatic arthritis and have the opportunity, perhaps even responsibility, to prevent joint destruction by timely intervention Saraceno R, et al. JAAD. 2006;54:S81-S84.

46 Psoriasis manifestation and treatment decision Primary basis of treatment decision Visible indicators Skin Influences treatment decision Joints Quality of life Should influence treatment decision Nails

47 Treatment Options for Nail Psoriasis Topical Corticosteroids Vitamin D analogues Intralesional injections Corticosteroids Systemic MTX Cyclosporine Retinoids Biologic Adalimumab Etanercept Infliximab Ustekinumab

48 Treatment Goals With Biologics for Nail Psoriasis Significant improvement of nail disease should be achieved NAPSI score of 0 Treatment strategies Effects typically later than reduction of skin symptoms; e.g. 24 weeks Improved treatment options with the availability with biologics Long lasting Bianchi L, et al. JAAD. 2008;58(2):

49 Efficacy in Nail Psoriasis of Different Biologics Trial ETA 1 PsO pts., n=708 (nail at BL 564) Open-label study: ETA 25 mg BIW cont. NAPSI 0 8 ADA 2 UST 3 PsA pts., n=442 (nail at BL n/a) Open-label study: ADA 40 mg EOW NAPSI 0-80 PsO pts., n=766 (nail at BL 545) DB-PBO ctrl, RCT: 45 mg and 90 mg NAPSI 0 8 Outcome Mean NAPSI reduction: 57,5% at wk 54 (cont. ETA) 32,1% nail clearance at wk 54 Mean NAPSI reduction: 65% at wk 20 Data on nail clearance: n/a Data on mean NAPSI reduction and nail clearance: N/A Median percent improvement from BL in NAPSI wk 24 (50%) after 3 doses 1 Gianetti A, et al. EADV 2008 Abstract FC08-7. Spring EADV 2008 (CRYSTEL); 2 Van den Bosch F, et al. EULAR Poster FRI0472.; 3 Rich P, et al. EADV Abstract FP1007.

50 Efficacy in Nail Psoriasis of Different Biologics IFX Trial PsO pts., n=373 (nail at BL 305) DB-PBO ctrl RCT: IFX 5 mg/kg NAPSI 0 8 Outcome Mean percent improvement from BL in NAPSI at wk 24 (56.3%) Complete clearance in almost 50% at 1 yr (EXPRESS) Rich P, et al. JAAD. 2008;58:

51 Effectiveness of Infliximab in Nail Psoriasis Results of the Phase III Study EXPRESS Nail psoriasis present in 82% of 373 patients at baseline Mean NAPSI target nail (0 8): 4,3 ± 1,9 (Placebo) 4,6 ± 2,0 (Infliximab) Rich P, Griffiths CE, Reich K et al. J Am Acad Dermatol 2008; 58(2):

52 EXPRESS: Mean Percent Improvement of NAPSI Through Week *P< vs placebo 72.5* Mean Improvement of NAPSI (%) * -5.9* 56.3* -3.2* 56.3* Weeks Placebo --> Infliximab 5 mg/kg Infliximab 5 mg/kg Placebo (n=65 at BL, n=58 at wk 50) and IFX (n=240 at BL, n=223 at wk 50). Reich K, et al. Lancet. 2005;366:

53 EXPRESS: Full Nail Clearance with Infliximab Over Time Proportion of patients with nail psoriasis at baseline but no residual nail psoriasis over time Percentage of Patients (%) Rich P, et al. JAAD. 2008;58(2): *P< * Weeks PBO -> IFX (5 mg/kg) wk 24 IFX (5 mg/kg) Based on subjects with nail psoriasis at baseline (81.8% of subjects). Mean NAPSI at BL: 4.6 (IFX), 4.3 (PBO)

54 EXPRESS: Complete nail clearance during treatment with infliximab Baseline Week 24 Reich K, et al. Lancet 2005; 366:

55 EXPRESS: Effect of Infliximab on Nail Psoriasis Infliximab shows rapid and significant improvement of different types of nail psoriasis Week 0 Week 24 Photographs from Rich P, et al. JAAD. 2008;58(2): with permission from Elsevier.

56 Mean NAPSI Score Efficacy of Anti-TNFα Agents in Nail Psoriasis* Improvement (%) of NAPSI scores of different biologics 22.6 BL 8.4*** 2.4*** ** *** Infliximab (n=14) Etanercept (n=14) Adalimumab (n=14) * n = 42 (20 only psoriasis, 22 PsA) ** P<0.005; *** P< Saraceno R, et al. G2C2008. Abstract P % % % Wk6 Wk22 BL Wk6 Wk22 BL Wk6 Wk22

57 Infliximab Seems to Improve Enthesitis and Dactylitis in PsA (No head-to-head trials) Placebo n=100 IMPACT 2 1 Infliximab 5 mg/kg n=100 Enthesitis baseline 35% 42% Enthesitis 24 weeks 37% 20% P value vs Placebo Placebo n=162 NS* ADEPT (38%) Adalimumab 40 mg EOW n=151 NS* Dactylitis baseline 40% 41% Dactylitis 24 weeks 34% 12% <0.001 NS* 117 (37%) NS* * Mean improvement in enthesitis and dactylitis in patients treated with adalimumab not significant versus baseline. 1 Antoni C, et al. Ann Rheum Dis. 2005;64: ; 2 Mease P, et al. Arthritis Rheum. 2005;52:

58 Treatment Recommendations: GRAPPA* Based on literature reviews and from consensus opinion in areas lacking sufficient evidence, these recommendations may serve as a basis for treatment guidelines Domain Peripheral arthritis Axial disease Skin Enthesitis Dactylitis Therapy and Level of Recommendation (Graded From A D) A- NSAIDs; TNF inhib.; SSZ; Leflunomide B- MTX; Cyclosporine D- Intra-articular steroids A- NSAIDs; TNF inhib.; physical therapy; sacroiliac joint injection 1st line: A- UVA; PUVA +/-acitretin; MTX; fumaric acid esters; TNF inhibitors; efalizumab; cyclosporine 2nd line: A- acitretin; alefacept 3rd line: A- SSZ; Leflunomide. C-hydroxyurea, mycophenolate mofetil; thioguanine A- Infliximab; D- NSAIDs; physical therapy; DMARDs; injections A- Infliximab; D-NSAIDs; physical therapy; DMARDs; injections * GRAPPA = Group for Research and Assessment of PsA. Ritchlin, et al. Ann Rheum Dis Epub 24OCT08.

59 Nail Psoriasis 2010 Conclusions and Outlook Nail involvement is highly prevalent in psoriasis and PsA 1-3 May be predictive of more severe disease and a precursor to joint involvement Nail disease is associated with a significant functional and emotional impairment of affected patients 1,3 Nail disease should be integrated into the management of moderate to severe psoriasis (treatment goals and algorithms) Infliximab demonstrates rapid and complete clearing of nails in almost half of the patients 4 and appears to be one of the most effective treatment for nail psoriasis to date 6 1 Jiaravuthisan MM, et al. JAAD. 2007;57:1-27; 2 Williamson L, et al. Rheumatology. 2004;43: ; 3 Lawry M. Dermatol Ther. 2007:20;60-67; 4 Rich P, et al. JAAD. 2008;58(2): ; 5 Noiles K, et al. J Cutaneous Med Surg. 2009:13(1);1-5.

60 Current Problems in Nail Psoriasis Significant impact on life of affected patients No established scores for assessing severity No specific evaluation of disease burden No established treatment goals and algorithms Correlation between response of skin, nails and joints unclear