Scand J Rheumatol 2010;39:299–302 299

© 2010 Taylor & Francis on license from Scandinavian Rheumatology Research Foundation

DOI: 10.3109/03009741003604559 www.scandjrheumatol.dk

SRHESmall joint involvement in psoriatic arthritis is associated with onycholysis: the Reykjavik Psoriatic Arthritis Study

TJ Love et alTJ Love1,2, JE Gudjonsson3, H Valdimarsson4,5, B Gudbjornsson2,5

1Brigham and Women’s Hospital, Harvard Medical School, Boston, USA, 2Centre for Rheumatology Research, Landspitali UniversityHospital, Reykjavik, Iceland, 3Department of Dermatology, University of Michigan, USA, 4Department of Immunology, LandspitaliUniversity Hospital, Reykjavik, and 5Faculty of Medicine, University of Iceland, Iceland

Objectives: Psoriasis and psoriatic arthritis (PsA) are associated with nail changes. Recent reports suggest that nailchanges may be a part of the enthesitis of PsA and that they predict the onset of arthritis among patients with psoriasis,but they have not reported on subclasses of nail changes. However, earlier reports suggested that onycholysis is the nailchange most strongly associated with PsA. If nail changes in PsA are a sign of enthesitis, they might be associated withsmall joint disease in general and the objective of this study was to test this hypothesis.Methods: A total of 154 patients recruited through the Reykjavik Psoriatic Arthritis Study had a joint, skin, and nailevaluation. Associations with small joint disease were tested using univariate analysis, and confirmed in a multivariatemodel.Results: Onycholysis had a strong association with small joint involvement [odds ratio (OR) 3.42, 95% confidenceinterval (CI) 1.41–8.92], while other types of nail changes did not. The number of swollen joints and shorter diseaseduration were also associated with small joint disease.Conclusions: Onycholysis is associated with small joint disease in PsA. Future studies of PsA should report thesubtypes of nail changes. Longitudinal studies are needed to determine whether onycholysis predicts PsA.

Psoriatic arthritis (PsA) is an inflammatory arthritis asso-ciated with the skin disease psoriasis. Although mostpatients with PsA will eventually develop skin findings,up to 20% of patients present with arthritis without skindisease, or PsA ‘sine psoriasis’ (1). In addition to skinfindings, psoriasis has been associated with a number ofnail changes, including oil spots, pitting, onycholysis, andsubungual hyperkeratosis (2), and nail changes have beenassociated with longer disease duration and more severeskin disease (3). Reports suggest that while 15–50% ofpatients with psoriasis have nail changes, the same is trueof up to 85% of patients with PsA (2, 4–6). A recent pro-spective study suggests that nail changes predict the onsetof PsA in psoriasis patients with a hazard ratio of 2.24 onmultivariate analysis (7).

Recent reports have suggested that there may be adirect link between inflammation in distal interphalan-geal (DIP) joints and nail changes (8, 9). The anatomi-cal relationship between the fingernail and the DIPjoint has been identified as a potential explanation, and

this has led to the suggestion that nail findings in PsAare an extension of entheseal changes and are a part ofthe arthritis (8, 9). If some types of nail changes areindeed related to enthesopathy, the associationbetween those nail changes and arthritis might extendbeyond the DIP joints to other small joints, but this hasnot been studied.

This study describes the relationship between nailchanges and small joint involvement in patients withPsA in the Reykjavik Study of Psoriatic Arthritis (6),adjusting for other predictors of small joint involvementfound in the dataset.

Methods

Patients

This was a cross-sectional study of individuals previouslydiagnosed with PsA by rheumatologists. Potential cases ofPsA were located in hospital records and a community-based database of patients with psoriasis using methodsdescribed in detail in a previous report (6), but in thepresent study expanded to include the entire country of Ice-land. An attempt was made to contact all patients by tele-phone and mail and invite them to participate in the study.

Thorvardur Jon Love, 1723 Washington Street, #301, Boston,MA 02118, USA.E-mail: thorvardur@gmail.com

Accepted 8 January 2010

Scan

d J

Rhe

umat

ol D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y SU

NY

Sta

te U

nive

rsity

of

New

Yor

k at

Sto

ny B

rook

on

10/3

0/14

For

pers

onal

use

onl

y.

300 TJ Love et al

www.scandjrheumatol.dk

Ascertainment of disease

The inclusion criteria used for this study are derivedfrom those of the Swedish Psoriatic Arthritis Registry(SwePsA) (10). Patients who reported a diagnosis of arheumatic disease other than PsA when interviewed, orwho were observed to have another rheumatic condi-tion when examined, were excluded. The Classifica-tion of Psoriatic Arthritis (CASPAR) criteria for PsA(11) were not available at the time these data werecollected, and therefore insufficient data points weregathered to fully assess for these criteria. However,based on the limited data available, 80% meet theCASPAR criteria.

Data collection

Joints, skin, and fingernails were evaluated by a med-ical doctor (TJL) trained by a rheumatologist (BG) anda dermatologist (JEG) for the task. Skin was evaluatedusing the psoriasis area and severity index (PASI)score (12), and arthritis activity was measured usingthe 66 swollen joint count (13). Nails were examinedand oil spots, onycholysis, subungual hyperkeratosis,and pitting were noted; examples of these changes areprovided in Figure 1A–D. Only fingernails were evalu-ated to reduce the risk of misclassification due to fun-gal toe nail disease. Small joints were defined as theDIP, proximal interphalangeal (PIP), and metacarpo-phalangeal (MCP) joints of the hands, as well as thePIP and metatarsophalangeal (MTP) joints of the feet,so that 48 joints were included in the definition ofsmall joints.

Statistical analysis

The association between small joint involvement andnail disease was evaluated using the c2 test. Statisticallysignificant associations defined by a p-value of 0.05 orless were evaluated further in a multivariate logisticregression model. Age and gender were included ascovariates in all multivariate analyses. Other potentialcovariates were identified based on clinical experienceand information in the literature, and then tested for aunivariate association with small joint disease, using thec2 test for categorical variables and univariate logisticregression for continuous variables. Odds ratios (ORs)were calculated with 95% confidence intervals (CIs).Those variables that were significantly associated withthe main outcome of small joint disease on univariateanalysis at a p-value of 0.05 or less were included in themultivariate analysis as covariates. Statistical analysiswas performed using JMP version 7 from SAS.

Results

Using the methods described above, a group of 301patients living in Iceland with a self-reported or ICD-9-coded rheumatologist diagnosis of PsA was identified.After attempting to contact all of these patients, 187(62%) were examined and interviewed. PsA accordingto the SwePsA criteria (10) was confirmed in 154patients (82%), who constituted the study group. Ofthese 154 patients, 144 had evidence of inflammatoryjoint disease on the day of their visit, and the remaining10 gave a clear history of both inflammatory arthritisand dactylitis. Because of the cross-sectional design of

A

B C D

Figure 1. Nail changes in psoriatic arthritis(PsA): (A) onycholysis; (B) dystrophy withoil spots; (C) subungual hyperkeratosis;(D) pitting.

Scan

d J

Rhe

umat

ol D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y SU

NY

Sta

te U

nive

rsity

of

New

Yor

k at

Sto

ny B

rook

on

10/3

0/14

For

pers

onal

use

onl

y.

Onycholysis and small joint involvement 301

www.scandjrheumatol.dk

the study and the fluctuating nature of PsA, these 10patients were included in the PsA group.

The mean age ± SD of all patients at the time of enter-ing the study was 54 ± 14 years and the mean durationof their arthritis was 20 ± 12 years (Table 1). Mostpatients (78%) had onset of arthritis after their psoriasiswas diagnosed, 11% had joint symptoms first, and 11%had onset of joint and skin symptoms simultaneously.The mean number of swollen joints was 3.5 ± 4.0, andthe mean PASI score was also 3.5 ± 4.0. At the time ofthe study 39% had active small joint involvement, and79% had some form of nail changes.

The results of the univariate analysis of potential pre-dictors of small joint involvement are shown in Table 2.There was no significant association between nail changesin general and small joint involvement. However, uni-variate analysis of each of the subtypes of nail changesrevealed that onycholysis was associated with small jointdisease with an OR of 2.80 (95% CI 1.34–5.85). In addi-tion to onycholysis, an increasing number of swollenjoints and shorter disease duration were significantlyassociated with the presence of small joint disease.

A multivariate model was created to adjust forvariables other than nail changes associated with smalljoint disease on univariate analysis. After the covariatesidentified as significant through univariate analysis hadbeen added to the multivariate logistic regression model,onycholysis remained statistically significantly associ-ated with small joint disease at an OR of 3.42 (95% CI1.41–8.92), compared to 2.80 on univariate analysis.Table 2 shows the results of the multivariate analysis.

Discussion

This study demonstrates a relationship between ony-cholysis and small joint involvement in a population-based cohort of patients with PsA. The associationremains strong after adjusting for other predictors ofsmall joint involvement in a multivariate model. Mean-while, no association could be confirmed betweensmall joint arthritis and pitting, oil spots, or subungualhyperkeratosis.

Nail changes have long been recognized as a part ofpsoriasis and PsA, but have been considered part of theskin disease. Previous reports suggest that nail changesare more common in PsA (2, 4, 6), that onycholysis isassociated with PsA in general and DIP arthritis inparticular (14, 15), and that nail changes predict theonset of arthritis in patients with psoriasis (7). The find-ing presented here of an association between onycholy-sis and small joint involvement adds to the literaturesuggesting that nail changes are closely associated withPsA (8, 9). The association with onycholysis in particu-lar supports earlier findings where subclasses of nailchanges were examined (12, 15), but the more recentstudies cited here have not reported on subclasses of nailinvolvement. This growing body of knowledge suggeststhat nail changes deserve increased attention in theevaluation of patients with psoriasis and PsA.

In recent years, evidence from magnetic resonanceimaging (MRI) and pathology studies have suggestedthat inflammation of the DIP joint in PsA extends alongentheseal structures to involve the nail matrix as well asthe entire nail bed (8, 9). This is consistent with thetheory that nail pitting arises from the dorsal nail matrix,while onycholysis is the result of involvement of the nailbed and hyponychium (2). Because of the observedextension of inflammation along entheses from the DIPjoint to the nail matrix, it has been suggested that pitting

Table 1. Clinical characteristics of 154 patients with psoriaticarthritis (PsA).

SexMen, n (%) 58 (38)Women, n (%) 96 (62)

Age, yearsMean ± SD 54.2 ± 13.6Median (minimum, maximum) 55 (18, 83)

Duration of PsA, yearsMean ± SD 19.6 ± 11.6Median (minimum, maximum) 17 (2, 61)

Number of swollen jointsMean ± SD 3.54 ± 4.08Median (minimum, maximum) 2.5 (0, 20.0)

PASI scoreMean ± SD 3.47 ± 4.01Median (minimum, maximum) 2.1 (0, 24.2)

Small joint and nail involvement, n (%)Small joint involvement 60 (39)Any nail dystrophy 122 (79)Oil spots 9 (6)Pitting 91 (59)Onycholysis 100 (65)Subungual hyperkeratosis 74 (48)

Table 2. Predictors of small joint involvement among 154patients with psoriatic arthritis (PsA). Results are presented asodds ratios with 95% confidence intervals.

Univariate analysis

Multivariate analysis

Age 0.98 (0.96–1.00) 0.98 (0.95–1.02)Male sex 1.66 (0.85–3.23) 1.36 (0.58–3.16)Duration of PsA 0.97 (0.93–0.99) 0.95 (0.91–0.99)*BMI 1.03 (0.98–1.10)Current smoker 0.92 (0.44–1.93)Number of swollen joints 1.30 (1.17–1.46) 1.32 (1.19–1.51)*PASI score 1.01 (0.93–1.10)Any nail involvement 0.45 (0.19–1.08)

Nail pitting 1.33 (0.69–2.60)Nail oil spots 0.43 (0.09–2.14)Nail subungual hyperkeratosis

1.58 (0.82–3.03)

Nail onycholysis 2.80 (1.34–5.85) 3.42 (1.41–8.92)*

BMI, body mass index.*p ≤ 0.05 on multivariate analysis.

Scan

d J

Rhe

umat

ol D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y SU

NY

Sta

te U

nive

rsity

of

New

Yor

k at

Sto

ny B

rook

on

10/3

0/14

For

pers

onal

use

onl

y.

302 TJ Love et al

www.scandjrheumatol.dk

is the result of entheseal inflammation in PsA, and anassociation between DIP arthritis and nail pitting hasbeen described (16). This is probably a true association,but because nail pitting is commonly observed in otherrheumatic patients as well as in general medical patients,it may not be a specific enough finding to emerge asclearly associated with PsA (5). This is further sup-ported by a study showing that in healthy subjects pit-ting is found in 58% while onycholysis is found in lessthan 2% (17). However, high numbers of nail pits, atleast 20 or more, and perhaps 60 or more, seem to bemore specific for PsA and rare in other groups (5).Therefore, it would seem appropriate to record carefullythe extent of pitting as well as the presence of onycholy-sis in future studies examining the link between nailchanges and PsA.

Unfortunately, the present study does not have dataon the spatial relationship between the involved nailsand the involved joints, precluding us from determiningwhether the nail changes are more often close to aninvolved joint than would be expected by chance alone.Being a cross-sectional study, the observations pre-sented here can only suggest an association but nocausal link can be identified. Further studies are neededwhere the location and type of nail change as well asjoint changes are carefully documented and followedover time. Recording the nail changes through digitalphotography could allow standardized, objective evalua-tion of nail involvement in patients with psoriasis and/orPsA, resulting in a clearer picture of the relationshipbetween the different types of nail changes, skin disease,and arthritis in these patients.

Recognizing PsA in a patient who presents with aseronegative small joint arthritis without skin changes ischallenging. With new treatments such as ustekinumab,which appears to have efficacy in psoriasis and PsA (18)but is not being studied for use in rheumatoid arthritis(RA), recognizing PsA early in patients without skinfindings becomes more important. Furthermore, the datasuggesting that nail changes predict the onset of jointdisease (7), combined with the observations regardingdifferential frequencies of subtypes of nail changesreferred to above, suggest that it would be worthwhile toexplore the value of individual subtypes of nail changesin predicting PsA among patients with psoriasis.

The findings presented here support the idea that ony-cholysis is part of the pathology that leads to arthritisrather than skin disease. Prospective studies are neededto determine whether this finding can help to predictPsA in patients who present with seronegative smalljoint arthritis without skin findings.

References1. Scarpa R, Cosentini E, Manguso F, Oriente A, Peluso R, Atteno

M, et al. Clinical and genetic aspects of psoriatic arthritis ‘sinepsoriasis’. J Rheumatol 2003;30:2638–40.

2. Jiaravuthisan MM, Sasseville D, Vender RB, Murphy F, MuhnCY. Psoriasis of the nail: anatomy, pathology, clinical presentation,and a review of the literature on therapy. J Am Acad Dermatol2007;57:1–27.

3. de Jong EM, Seegers BA, Gulinck MK, Boezeman JB, van deKerkhof PC. Psoriasis of the nails associated with disability in alarge number of patients: results of a recent interview with 1,728patients. Dermatology 1996;193:300–3.

4. Gladman DD, Shuckett R, Russell ML, Thorne JC, Schachter RK.Psoriatic arthritis (PSA) – an analysis of 220 patients. Q J Med1987;62:127–41.

5. Lavaroni G, Kokelj F, Pauluzzi P, Trevisan G. The nails in psoriaticarthritis. Acta Derm Venereol Suppl (Stockh) 1994;186:113.

6. Love TJ, Gudbjornsson B, Gudjonsson JE, Valdimarsson H.Psoriatic arthritis in Reykjavik, Iceland: prevalence, demographics,and disease course. J Rheumatol 2007;34:2082–8.

7. Wilson FC, Icen M, Crowson CS, McEvoy MT, Gabriel SE, Kre-mers HM. Incidence and clinical predictors of psoriatic arthritis inpatients with psoriasis: a population-based study. Arthritis Rheum2009;61:233–9.

8. Scarpa R, Soscia E, Peluso R, Atteno M, Manguso F, Del PuenteA, et al. Nail and distal interphalangeal joint in psoriatic arthritis. JRheumatol 2006;33:1315–19.

9. Tan AL, Benjamin M, Toumi H, Grainger AJ, Tanner SF,Emery P, et al. The relationship between the extensor tendonenthesis and the nail in distal interphalangeal joint disease inpsoriatic arthritis – a high-resolution MRI and histological study.Rheumatology (Oxford) 2007;46:253–6.

10. Svensson B, Holmstrom G, Lindqvist U. Development and earlyexperiences of a Swedish psoriatic arthritis register. Scand JRheumatol 2002;31:221–5.

11. Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P,Mielants H. Classification criteria for psoriatic arthritis: develop-ment of new criteria from a large international study. ArthritisRheum 2006;54:2665–73.

12. Fredriksson T, Pettersson U. Severe psoriasis – oral therapy with anew retinoid. Dermatologica 1978;157:238–44.

13. Gladman DD, Helliwell P, Mease PJ, Nash P, Ritchlin C, TaylorW. Assessment of patients with psoriatic arthritis: a review ofcurrently available measures. Arthritis Rheum 2004;50:24–35.

14. Eastmond CJ, Wright V. The nail dystrophy of psoriatic arthritis.Ann Rheum Dis 1979;38:226–8.

15. Torre Alonso JC, Rodriguez Perez A, Arribas Castrillo JM, BallinaGarcia J, Riestra Noriega JL, Lopez Larrea C. Psoriatic arthritis(PA): a clinical, immunological and radiological study of 180patients. Br J Rheumatol 1991;30:245–50.

16. McGonagle D, Tan AL, Benjamin M. The nail as a musculoskele-tal appendage –implications for an improved understanding ofthe link between psoriasis and arthritis. Dermatology (Basel,Switzerland) 2009;218:97–102.

17. Robertson JC, Braune ML. Splinter haemorrhages, pitting, and otherfindings in fingernails of healthy adults. Br Med J 1974;4:279–81.

18. Gottlieb A, Menter A, Mendelsohn A, Shen YK, Li S, Guzzo C,et al. Ustekinumab, a human interleukin 12/23 monoclonal anti-body, for psoriatic arthritis: randomised, double-blind, placebo-controlled, crossover trial. Lancet 2009;373:633–40.

Scan

d J

Rhe

umat

ol D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y SU

NY

Sta

te U

nive

rsity

of

New

Yor

k at

Sto

ny B

rook

on

10/3

0/14

For

pers

onal

use

onl

y.