Nail disorders
Prof. MUDr. Petr Arenberger, DrSc, MBA
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. 2008 Feb;58(2):224-31. Epub 2007 Dec 20.
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
The Nail as a Musculoskeletal Appendage
• The nail as a skin appendage
–
Developmentally, it arises as an in-growth from
the epidermis1
However, recent histological studies showed
• The nail is integrated with the musculoskeletal
system
–
Functionally linked to the distal phalanx and distal
interphalangeal (DIP) joint structures2
1Dawber
RPR, et al. Science of the nail apparatus. In: Diseases of the Nails and Their Management. Blackwell Science; 2001.
pp 1-47;
D, et al. Dermatology 2009;218(2):97-102.
2McGonagle
Anatomy of the Nail
Lunula
Eponychium
Onychondermal band
Proximal nail fold
Nail plate
Nail bed
Nail bed
Eponychium
Dorsal proximal nail fold
Ventral proximal nail fold
Hyponichium
Distal groove
Distal phalanx
Proximal nail fold
sub-divisions
Matrix
Adapted from: Jiaravuthisan MM, et al. JAAD. 2007;57:1-27.
Nail plate
Key Clinical Features: Pit Formation
Dorsal proximal nail fold
Nail plate
Pit
Ventral
proximal
nail fold
Nail bed
Matrix
Adapted from: Jiaravuthisan MM, et al. JAAD 2007;57:1-27.
Clinical manifestation nail matrix
Pits
Dystrophy
Erythema of the Lunula
Leukonychia
Clinical pictures from Kristian Reich, Hamburg and Robert Baran, Cannes (France)
Hyperparakeratosis of the nail matrix
Clinical pictures from Kristian Reich, Hamburg and Robert Baran, Cannes (France)
Clinical manifestation nail bed
Splinter hemorrhage
Oil drop
Onycholysis
Clinical picture from Kristian Reich, Hamburg
Subungual Hyperkeratosis
Clinical manifestation nail bed
Splinter hemorrage/bleeding
Clinical picture from Kristian Reich, Hamburg
Clinical spectrum of nail psoriasis
Psoriatic Onychopachydermoperiostitis (POPP Syndrome)
Clinical pictures from Robert Baran, Cannes (France)
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).
Key Clinical Manifestations
Oil Drop
Discoloration
Leukonychia
Nail Bed
Splinter
Haemorrhages
Red Spots
Nail Matrix
Pitting
Crumbling
Jiaravuthisan MM, et al. JAAD. 2007;57:1-27.
Photograph from Rich P, et al. JAAD 2008;58(2):224-231.
Subungual
Hyperkeratosis
Onycholysis
Clinical Manifestations: Nail Matrix
Pitting
Dystrophy
(transverse grooves)
Leukonychia
(crumbling)
Photographs courtesy of Robert Baran, MD, Cannes (France) and Kristian Reich, Hamburg.
Clinical Manifestations: Nail Bed
Subungual hyperkeratosis
Oil Spot
Splinter haemorrhage
Onycholysis
Photographs courtesy of Robert Baran, MD, Cannes (France) and Kristian Reich, Hamburg.
Clinical Spectrum of Nail Psoriasis
Psoriatic Paronychia
Photographs courtesy of Robert Baran, MD, Cannes (France).
Clinical Spectrum of Nail Psoriasis
Psoriatic Onychopachydermoperiostitis (POPP syndrome)
Photograph courtesy of Robert Baran, MD, Cannes (France).
Frequency of Nail Psoriasis in PsA
Parameter
Patients with PsA
(n = 312)
Patients without
PsA
(n = 1,055)
49.4 (14.0)
50.9 (15.4)
Male
57.7 (180)
58.5 (617)
Female
42.3 (132)
41.5 (438)
Positive family history of
psoriasis n (%)
145 (46,5)
388 (36.8)
Nail psoriasis n (%)
214 (68.6)
427 (40.5)
PASI (mean)
14.3
11.5
DLQI (mean)
11.6
7.7
Mean age [years] (SD)
Gender
[%] (n)
n =1,511
Reich K, et al. Br J Dermatol. 2009
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
Nail Root
Extensor
Tendon
Deep Lamina
Fat
Distal Phalanx
Adapted from: Tan, et al. Rheumatology. 2007;46(2):253-256.
Anchored by Entheses
Extensor Tendon
Flexor Tendon
Adapted from: McGonagle D, et al. Dermatology 2009;218(2):97-102.
Superficial and
Deep Lamina
Nail
Lateral Lamina
Linear manifestation of nail changes
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;193:300-303.
Frequency of Symptoms of Nail Psoriasis
EXPRESS: Summary of target manifestations at baseline
Randomised patients with nails involved
at baseline
Placebo →
Infliximab
(5 mg/kg)*
Infliximab
(5 mg/kg)
65
240
Target nail feature—Nail matrix psoriasis
Pitting, n (%)
Leukonychia, n (%)
Nail plate crumbling, n (%)
Red spots in lunula, n (%)
47 (72.3)
24 (36.9)
21 (32.3)
4 (6.2)
170 (70.8)
111 (46.3)
81 (33.8)
27 (11.3)
Target nail feature—Nail bed psoriasis
Onycholysis, n (%)
Oil drop discoloration, n (%)
Nail bed hyperkeratosis, n (%)
Splinter haemorrhages, n (%)
48 (73.8)
34 (52.3)
28 (43.1)
11 (16.9)
159 (66.3)
110 (45.8)
102 (42.5)
60 (25.0)
* Patients in the placebo group crossed over to infliximab (5 mg/kg) at week 24.
Rich P, et al. JAAD. 2008;58(2):224-231.
Prevalence of Nail Psoriasis
• Approx. 30% (15%–50%) of psoriasis patients have nail
involvement1 (Europe: 1.5 million; USA: 2 million)
• Approx. 50% of patients attending a dermatologist for
psoriasis have nail psoriasis2
• 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 findings3
• Approximately 70% to 80% of patients with psoriatic
arthritis (PsA) have nail involvement6
1Jiaravuthisan
MM et al. J Am Acad Dermatol 2007; 57: 1-27; 2 Augustin M et al. Dermatology 2008; 216(4):
366-372; 3 Van Laborde S, Scher RK. Dermatol Clin 2000; 18: 37-46; 4Lawry M. Dermatol Ther 2007: 20; 60-67
Frequency of Nail Psoriasis and Severity of
Skin Symptoms*
Number of patients
700
Pts with nail pso
600
500
Pts without nail pso
403
400
181
300
101
200
100
283
54.2%
41.1%
61.2%
214
159
0
Mild (PASI <10)
Moderate (PASI >10; ≤20)
Severe (PASI >20)
Severity of Skin Symptoms
* n =1,511; 48.1% with nail psoriasis
Augustin M , et al. Dermatology. 2008;216(4):366-372.
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
Impact of Disease
Skin
Quality
of Life
Treatment
decision
Function
Joints
Nails
Dutch Survey: Complaints Related to
Nail Psoriasis*
Restricted in
Daily Activities
58.9
Restricted in
Housekeeping
56.1
Restricted in
Profession
47.9
0
10
20
30
40
Percentage of Patients (%)
50
60
70
* n =1,728
• 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;193:300-303.
Dutch Survey: Treatment of
Nail Psoriasis*
Improvement with previous treatments for nail psoriasis
100
80
60
45.7
35
40
19.3
20
0
Marked
Improvement
Little Improvement No Improvement
81% of patients reported little to no improvement with
previous therapies for nail psoriasis
de Jong EM, et al. Dermatology 1996;193:300-303.
* N=1728
Significance of Nail Psoriasis
• Restricts patients in daily activities
and causes social embarrassment1
• >50% of patients suffer from pain1
• Difficult to treat2-4
–
–
–
Slow to respond
Conventional treatments are generally difficult to
administer and often ineffective
Removal of nail may be necessary for refractory
cases
1de
Jong EM, et al. Dermatology 1996;193:300-303; 2Scher RK. Dermatol Clin. 1985;3:387-394; 3de Berker D. Clin Exp Dermatol.
2000;25:357-362; 4Farber EM. Cutis 1992;50:174-178.
Photograph courtesy of Robert Baran, MD, Cannes (France).
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
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;49:206-212.
Determining the NAPSI
Matrix
• Pitting
• Leuconychia
• Lunulaerythema
• Onychodystrophy
Bed
0
1
1
0
• Onycholysis
• Splinter
haemorrhages
• Oil drop
• Subungual
hyperkeratosis
1
1
1
0
NAPSI = 5
Assessment Tools and Nail
Involvement
Assessment Tool Involvement of Nails
PASI
Does not take the severity of nail involvement
into account
Baran’s nail psoriasis
severity index3
Yes, but does not focus on function, pain or
QoL
Cannavò’s scoring
system4
Yes, but only little focus on function, pain or
QoL (3 items, no validation)
NAPSI2
Yes, but does not focus on function, pain or
QoL
DLQI1
Does not focus on nails, only mentions skin
1Finlay AY,
Khan GK. Clin Exp Dermatol. 1994;19:210-216; 2Rich P, Scher R. J Am Acad Dermatol. 2003;49:206-212;
3Baran RL. Br J Dermatol. 2004;150:568-569; 4Cannavò SP, et al. Dermatology. 2003;206:153-156.
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
Nail psoriassis – a window to more ?
A window to the joint?
Enthesitis
DIP
involvement;
PsA
Nail
psoriasis
1de
early marker?
Jong EM, et al. Dermatology. 1996;193:300-303; 2Lawry M. Dermatol Ther. 2007:20;60-67; 3McGonagle D, et al.
Dermatology. 2009;218(2):97-102; 4Tan AL, et al. Arthritis Rheum. 2006:54(4):1328-1333.
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 PsA1
• 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
1Serarslan
Patients with PsA with or without
onychopathy2
• 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
G, et al. Clin Rheumatol. 2007;26:1245-1247;2Scarpa R, et al. J Rheumatol. 2006;33:1315-1319.
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
Wilson FC, et al. Arthritis Rheum. 2009;61(2);233-239.
Intergluteal/
perianal
lesions
The Importance of the Nail in Psoriasis
A window to disease severity?
Nail psoriasis
Systemic
inflammation
Severe
disease
course of PsA
1de
Jong EM, et al. Dermatology. 1996;193:300-303; 2Lawry M. Dermatol Ther. 2007:20;60-67; 3McGonagle D, et al.
Dermatology. 2009;218(2):97-102; 4Tan AL, et al. Arthritis Rheum. 2006:54(4):1328-1333.
Link Between Nail Disease Severity
and PsA
• Study examined the relationship between
severity of nail disease and PsA in
69 patients2
–
83% of patients had clinically detectable nail
disease
More severe
nail disease
Williamson L, et al. Rheumatology. 2004;43:790-794.
More severe
skin disease
Increased
rates of
unremitting
PsA with
functional
impairment
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.
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
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.
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
Psoriasis manifestation and treatment
decision
Visible indicators
Primary basis of
treatment
decision
Influences
treatment
decision
Joints
Skin
Quality
of life
Should
influence
treatment
decision
Nails
Treatment Options for Nail Psoriasis
• Topical
–Corticosteroids
–Vitamin D analogues
• Intralesional injections
– Corticosteroids
• Systemic
–MTX
–Cyclosporine
–Retinoids
• Biologic
–Adalimumab
–Etanercept
–Infliximab
–Ustekinumab
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):224-231.
Efficacy in Nail Psoriasis of
Different Biologics
Trial
ETA1
ADA2
UST3
1Gianetti A,
• PsO pts., n=708 (nail at BL 564)
• Open-label study:
ETA 25 mg BIW cont.
• NAPSI 0–8
• 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
et al. EADV 2008 Abstract FC08-7. Spring EADV 2008 (CRYSTEL); 2Van den Bosch F, et al. EULAR 2007. Poster
FRI0472.;
P, et al. EADV 2008. Abstract FP1007.
3Rich
Efficacy in Nail Psoriasis of Different
Biologics
Trial
IFX
• PsO pts., n=373 (nail at BL
305)
• DB-PBO ctrl RCT:
IFX 5 mg/kg
• NAPSI 0–8
(EXPRESS) Rich P, et al. JAAD. 2008;58:224-231.
Outcome
•Mean percent improvement from
BL in NAPSI at wk 24 (56.3%)
•Complete clearance in
almost 50% at 1 yr
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): 224-231
EXPRESS: Mean Percent Improvement
of NAPSI Through Week 50
90
72.5*
Mean Improvement
of NAPSI (%)
*P<0.0001 vs placebo
70
56.3*
56.3*
50
26.0*
30
10
-10
-5.9*
0
10
-3.2*
24
50
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;366:1367-1374.
EXPRESS: Full Nail Clearance with
Infliximab Over Time
Percentage of Patients (%)
Proportion of patients with nail psoriasis at baseline but
no residual nail psoriasis over time
50
48.2
42
*P<0.001
44.7
40
*
26.4
30
34.5
20
6.9
10
5.1
1.7
0
10
14
18
22
26
30 34
Weeks
PBO-> IFX (5 mg/kg) wk 24
38
42
46
50
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)
Rich P, et al. JAAD. 2008;58(2):224-231.
EXPRESS: Complete nail clearance
during treatment with infliximab
Baseline
Reich K, et al. Lancet 2005; 366: 1367-1374
Week 24
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):224-231 with permission from Elsevier.
Efficacy of Anti-TNFa Agents in Nail
Psoriasis*
Improvement (%) of NAPSI scores of different biologics
Mean NAPSI Score
60
- 89.2%
50
- 63.7%
40
30
- 65.0%
37.1
26.0
22.6
26.6
20
11.4
8.4***
2.4***
10
13.0***
9.4**
0
BL
Wk6
Wk22
Infliximab (n=14)
BL
Wk22
Etanercept (n=14)
* n = 42 (20 only psoriasis, 22 PsA)
** P<0.005; *** P<0.001.
Saraceno R, et al. G2C2008. Abstract P47.
Wk6
BL
Wk6
Wk22
Adalimumab (n=14)
Infliximab Seems to Improve Enthesitis
and Dactylitis in PsA
(No head-to-head trials)
IMPACT 21
ADEPT2
Placebo Infliximab P value
n=100
5 mg/kg
vs
n=100
Placebo
Enthesitis baseline
35%
42%
Enthesitis 24 weeks
37%
20%
Dactylitis baseline
40%
41%
Dactylitis 24 weeks
34%
12%
Placebo
n=162
Adalimumab
40 mg EOW
n=151
118 (38%)
0.002
NS*
NS*
117 (37%)
<0.001
NS*
NS*
* Mean improvement in enthesitis
and dactylitis in patients treated
with adalimumab not significant
versus baseline.
1Antoni
C, et al. Ann Rheum Dis. 2005;64:1150-1157; 2Mease P, et al. Arthritis Rheum. 2005;52:3279-3289.
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
Therapy and Level of Recommendation
(Graded From A–D)
Peripheral
arthritis
A- NSAIDs; TNF inhib.; SSZ; Leflunomide
B- MTX; Cyclosporine
D- Intra-articular steroids
Axial disease
A- NSAIDs; TNF inhib.; physical therapy; sacroiliac joint injection
Skin
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
Enthesitis
A- Infliximab; D- NSAIDs; physical therapy; DMARDs; injections
Dactylitis
A- Infliximab; D-NSAIDs; physical therapy; DMARDs; injections
* GRAPPA = Group for Research and Assessment of PsA.
Ritchlin, et al. Ann Rheum Dis. 2008. Epub 24OCT08.
Nail Psoriasis 2010–Conclusions and
Outlook
• Nail involvement is highly prevalent in psoriasis
and PsA1-3
–
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 patients1,3
• 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 patients4 and appears to be one
of the most effective treatment for nail psoriasis to date6
1Jiaravuthisan
MM, et al. JAAD. 2007;57:1-27; 2Williamson L, et al. Rheumatology. 2004;43:790-794; 3Lawry M. Dermatol Ther.
2007:20;60-67;4Rich P, et al. JAAD. 2008;58(2):224-231; 5Noiles K, et al. J Cutaneous Med Surg. 2009:13(1);1-5.
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