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he hand is a frequently involved site in osteoarthritis(OA). Hand OA is classically characterized by nodes,

adiologic changes, pain, and functional impairment. Therototype subject is a woman of perimenopausal age with aositive familial history, overweight, and OA in other sites.adiology reveals swollen periarticular tissues and some de-ree of joint-space reduction in the initial stage, followed byhe development of osteophytes, subchondral sclerosis, andysts. In the late stage, subluxation and fibrotic ankylosis areommon, but in some patients, the dominant aspect is bonerosion.

In clinical practice, differences among patients have beensed to define disease subsets: nodal OA, generalized OA,rosive OA, and thumb-base OA. Atypical localizations arehe metacarpophalangeal joints and wrist, the presence ofhich should lead to the suspicion of secondary OA.Common questions include: 1) Are these subsets real, or

o they simply reflect different disease stages? 2) What is therevalence of hand OA? What are the diagnostic criteria used

n clinical and epidemiologic studies? 3) What are the influ-nces of genetic or environmental factors? 4) What is theatural course of the disease? 5) What is the most appropriateherapeutic approach?

A review of the literature may help to answer these ques-ions.

isk Factors and Epidemiologyenetics and Ethnicityarious studies have shown that genetic factors play an im-ortant role in hand OA, especially in the nodal subset. Kell-ren and Lawrence found Heberden’s and Bouchard’s nod-les in the relatives of 36% of men and 49% of women withand OA, as compared with 17% and 26%, respectively, in

Chief of the Rehabilitative Medicine Unit, Istituti Clinici di Perfeziona-mento, Milan, Italy.

Rheumatology Unit, L Sacco University Hospital, Milan, Italy.Resident, Rheumatology Unit, L. Sacco University Hospital, Milan, Italy.rom the Medicina Riabilitativa II, Istituti Clinici di Perfezionamento, Milan,

Italy; and Unità Operativa di Reumatologia, Azienda Ospedaliera PoloUniversitario L Sacco, Milan, Italy.

ddress reprint request to: Mario Fumagalli, MD, Medicina Riabilitativa II,Istituti Clinici di Perfezionamento, Via Bignami 1, 20144 Milan, Italy.

hE-mail: mario.fumagalli@icp.mi.it

049-0172/05/$-see front matter © 2005 Elsevier Inc. All rights reserved.oi:10.1016/j.semarthrit.2004.03.014

he general population (1). A classical twin study demon-trated the clear influence of genetic factors using a calculatedcore indicating that the influence of heredity ranged from9% to 65% (2). Possible linkage to a region on the short armf chromosome 2 in sib pairs with nodal OA has been re-orted (3). The Baltimore Longitudinal Study on Aging (4)valuated the familial aggregation of hand OA. A correlationas found for the distal interphalangeal joints (DIP), proxi-al interphalangeal joints (PIP), and first carpometacarpal

oints (CMC) at 2 or 3 hand sites, thus demonstrating familialggregation and indicating that OA can be inherited. Wrighteported evidence for genetic participation in 30 pairs ofarents/offspring in nodal OA (5).In the Framingham familial study (6), the best-fitting in-

eritance model was the Mendelian recessive model, thusupporting a significant genetic contribution to hand OA,ith evidence for a major recessive gene and a multifactorial

omponent representing polygenic or environmental factors.Convincing epidemiologic evidence supporting a heredi-

ary component in hand OA consists of: 1) greater concor-ance in monozygotic than in dizygotic twins; and 2) theubstantially increased risk of hand OA in the first-degreeelatives of subjects with hand OA. Possible associations ofand OA on chromosome 2q are emerging (7).A comparison of the frequency of Heberden’s nodes in a

akistani population and white subjects revealed a lower ab-olute frequency in the former and a less frequent associationith knee OA (8). Ethnicity affects the severity of hand OA,ith Ashkenazi Jews having significantly higher severity

cores than Sephardic Jews (9).In conclusion, many well-designed studies have indicated

he importance of genetic factors in hand OA, although theature of the inheritance has not been elucidated.

revalencehe published prevalence data vary depending on the diag-ostic criteria (clinical, radiologic, or both) and the age of theopulation. Radiologic hand OA was detected in 57% of a

arge sample of 1,422 elderly women and was significantlyssociated with bilateral and unilateral hip OA (odds ratioOR], 3.2) (10). A study of an elderly population in Icelandased on the American College of Rheumatology (ACR) clas-ification criteria (11) found that the prevalence of clinical

and OA was 3% in men and 7% in women. However, the

47

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48 M. Fumagalli, P. Sarzi-Puttini, and F. Atzeni

act that 19% of the men and 32% of the women fulfilled theCR examination criteria but lacked the required clinicalymptoms indicates that the ACR criteria are too insensitivend unstable over time to be used in epidemiologic studies oropulation surveys.Jonsson studied the distribution and prevalence of handA using bone scans (12). The prevalence of positive scansas low before the age of 40 years, but rapidly increaseduring the fifth and sixth decades. Women had a higherrevalence than men in first CMC OA. There was a strongoncordance by joint row.

In the 3-year longitudinal Michigan Bone Health study, therevalence of radiologic hand OA in women aged 28 to 48ears was 7%, and the period incidence was 3% (13). Aross-sectional study evaluated the prevalence of radio-raphic (dominant) hand OA in a young population of white19%) and black women (25%), thus providing strong evi-ence that primary prevention must be implemented inoung adulthood (14).The Italian ICARe Dicomano Studypplied the ACR clinical diagnostic criteria for hand OA andound a prevalence of 15% among 693 subjects (15). ThePISER study (16) evaluated the prevalence of hand OA in andult Spanish population, and found a clinical prevalence of% with a significant number of medical examinations, workisability, and medication use. The US Health Examinationurvey for OA of the hands and feet found that radiographicand OA was present in �5% of the subjects age youngerhan 35 years, but in �70% of those older than 65 years (17).

In a Tasmanian study of 522 subjects (18), the prevalencef hand OA was 44% to 71%; pain and dysfunction increasedith age, whereas grip strength decreased. In 253 consecu-

ive Jewish elderly patients, OA was frequent (about 80%)nd most severely involved the second and third DIP, rightrst interphalangeal, and both CMC joints. The prevalenceas similar in men and women, but women had a higher

adiologic score and men showed greater metacarpophalan-eal joint involvement (9).

It can be concluded that the prevalence of the radiologiceatures of OA ranges from 6% to 20% in young adults to0% in the elderly, although clinical criteria reduce it to 6%o 7%. The ACR criteria requiring the presence of symptomsre, therefore, perhaps unsuitable for epidemiologic studies.

nvironmental (Risk) Factorshe prevalence and severity of hand OA are greater in women19). A longitudinal study evaluating body weight found thatncreased weight precedes the presentation of hand OA (20),hich also correlated with body weight and body mass index

BMI) in a prospective case-control study that found ORsanging from 3 to 10.5 for women in the upper tertiles (21).owever, no significant difference in body weight was ob-

erved in twin pairs discordant for hand OA (22).The role of physical activity was investigated in an animalodel (23), which showed that the prevalence of clinical OA

n the hands of elderly rhesus macaques was 72% (DIP) and6% (PIP), with nodes being present in 31%. The prevalencef radiographic OA was 55% (DIP), 9% (PIP), and 0%

thumb base). The prevalence in the interphalangeal joints w

as similar to that found in hand OA in humans except forhe thumb base, which may be the result of the relativelyudimental manipulative role of the macaque thumb.

In the Framingham OA study, 453 subjects without radio-ogic hand OA were followed for 24 years; the occurrence ofand OA correlated with baseline grip strength (24): in men,reater grip strength was associated with an increased risk ofA in the PIP (OR, 2.8), metacarpophalangeal (OR, 2.9), and

humb base (OR, 2.8); in women, there was an increased riskf OA in the metacarpophalangeal joints (OR, 2.7). No asso-iation emerged for the DIP joints. In elderly patients, hemi-aresis reduces the ipsilateral hand expression of OA, thusuggesting that biomechanical factors play a role in the de-elopment of OA (25). The effect of heavy manual work onand OA still is debated. In a population of farmers, a dis-repancy emerged between clinical PIP hypertrophy and ra-iologic involvement (26).Hand OA mostly occurs in women at the time of meno-

ause (27), but its relationship with sexual hormones is con-roversial. A prospective study evaluated this relationship in aarge group of patients with clinical or silent OA and controls,nd found no difference in the characteristics of hand OAetween the patients treated or untreated with hormone re-lacement therapy (HRT), regardless of symptoms.In relation to osteoporosis, the 3-year longitudinal Michi-

an Bone Health study (13) found no relationship betweenand OA and bone mineral density (BMD) values, althoughhe average serum osteocalcin levels were lower in subjectsith hand OA. Among other diseases, diabetes has been par-

icularly investigated in terms of the prevalence of clinicalA. One population study (28) found no positive associationetween clinical hand OA and non–insulin-resistant diabetesellitus (NIDDM) as defined by oral glucose test tolerance,

onfirming other population studies that radiographically as-essed OA and diabetes.

In conclusion, the existence of clear risk factors for handA has not been definitely established, particularly in rela-

ion to DIP localization. In the case of the PIP and thumb-ase joints, there is a possible relationship with manual ac-ivity, hypermobility, and OA.

linical Aspectsymptoms and Clinical Forms of Hand OAawrence found that only 9% of men and 25% of womenith radiographic evidence of moderate-to-severe OA in theIP joints reported symptoms (29). Of 500 patients witheripheral OA (30), 30% showed radiologic hand involve-ent; a close, positive correlation was found between hand

nd knee disease in women, and the hand-knee group alsoas more likely to have excess weight, hypertension, and a

amily history of OA. It was suggested that a proportion of theopulation with generalized OA has a systemic predisposi-ion, and that biomechanical factors then dictate the site andeverity of the disease.

In the prospective Tecumseh study of 1,411 subjects (31),he prevalence of hand pain among those with radiologic OA

as 46%, and nearly 40% of the subjects with severe OA did

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Hand osteoarthritis 49

ot report any hand pain. The prevalence of pain was highern women than in men, with a relative risk of 1.94. The meanMI values were higher in subjects with OA and pain than inhose without pain, and hand pain correlated with a poorducation and low-income levels.

Of 261 mostly female OA patients (32), 88% were right-anded and 48% had a family history of hand OA. Further-ore, they had 4.4 flares per year, 3.7 painful joints, 3.1odal joints in the right hand, 4.4 radiographically affected

oints, a mean hand OA functional index of 10.4, a meanorning stiffness duration of 20 minutes, and a mean grip

trength of 59 mm Hg. The most frequently affected sitesere the first CMC (62%), PIP (48%), and DIP joints (68%).

n a population of 1,000 disabled women, symptomatic handA was recorded in 23% older than 65 years, and the fre-uency increased with age (33). The most affected sites werehe DIP and first CMC joints. Thus, pain and other symptomso not correlate with radiologic findings, and pain may be

imited to some phases of OA.

odulesodules are typical hallmarks of hand OA and account for

he definition of nodal OA; however, nodules may resultrom other conditions. The prevalence of palpable fingeroint nodules was almost double in patients with diffuse id-opathic skeletal hyperostosis (DISH) (OR, 1.84), mainly inhe PIP joints, in men, and in subjects older than 65 years34). DISH should be considered an independent risk factoror finger joint nodules, although a second independent riskn this study was a history of heavy physical work (OR, 2.10).

Fibroblastic rheumatism is a rare disorder whose early in-ammatory stage is characterized by cutaneous nodules and

s followed by a chronic stage with sclerodactyly, joint anky-osis, deformities, and dense dermal fibrosis. Patients withubcutaneous sarcoidosis and dactylitis also may have fingerodules (35).According to Cicuttini (36), Heberden’s nodules are not

ynonymous with DIP osteophytes, because poor agreementas observed in the same finger of the same hand. Osteo-hytes are a better marker of generalized OA. In the case ofeberden’s nodules, a biopsy study showed that OA startsith subchondral ossification (37).Depending on the anatomy of the interphalangeal joints,

he osteophyte marker for OA is a lateral node (a local area ofow resistance), whereas a central node is a traction spur andmarker of contracture. The familial incidence of nodal OAay reflect the inheritance of anatomic characteristics thatetermine the level of resistance to osteophyte growth (38).Mucous cysts are solitary, clear, or flesh-colored nodules

hat develop on the dorsal digits between the DIP and theroximal nail fold. There are 2 types: 1 is associated withegenerative changes in the DIP, whereas the other is joint-

ndependent and arises as a result of fibroblast metabolicerangement that leads to the production of large amounts ofyaluronic acid (39). OA also may predispose to the deposi-ion of urate crystals (40).

Heberden’s finger nodules are reported to be extremely

are in rheumatoid arthritis (RA) (41). s

magingadiography is still the simplest means of diagnosing OA,lthough articular scintigraphy has been proposed for early-hase studies. In a 2-year follow-up study (42), a correlationas found between scintigraphic and radiologic scores; the

oints with a positive baseline scintigram were significantlyore likely to show radiographic progression.

unctionhe degree of functional impairment varies and is generallyot very severe. A controlled study (43) assessing daily livingctivities in patients with nodal and erosive OA and matchedontrols found only minor global impairment in the OA pa-ients, with the worst function in those with erosive OA. Inlderly subjects (�80 years), hand function was essentiallyhe same as controls. Carrabba found a correlation betweenlinical and functional scores in Italian patients, but no cor-elation between functional and radiologic scores (44). Innother study (45), hand OA explained only 5% to 7% of theariation in function, grip strength, and pain; the associationith function and grip strength seems to be mediated byain. Similarly, the Framingham study found that symptom-tic hand OA was associated with significantly impaired griptrength and frequently limited hand function (46).

ubsets of Hand OAodal OA, Generalized OA, and Thumb-base OAublished data show the existence of a polyarticular subset ofand OA in women. There are 3 major determinants of theattern of polyarticular involvement: symmetry, clusteringy row, and clustering ray (in descending order of impor-ance) (47).

The Baltimore study (4) found an association betweenand and knee OA, with a closer association between bilat-ral PIP involvement and knee OA. In thumb-base OA, aausal relationship was found with articular hypermobility,hich may define a clinical and radiologic subset of hand OA

48). On the contrary, hypermobility seems to protect PIPoints (49). Polyarticular involvement of hand joints is com-

on, but may include various subtypes of different signifi-ance (50). There is no widely accepted definition of gener-lized OA, and the topography and number of affected jointsemain unidentified. The Dicomano study (15) evaluatedubsets of hand OA and found isolated right or left thumb-ase OA in 9% of the cases, isolated bilateral thumb-base OA

n 16%, unilateral thumb-base OA � nodal OA in 5%, nodalA in 21%, and bilateral thumb-base OA � nodal OA in8%.

rosive Hand OAuch attention has been dedicated to this subset of OA,hich often is striking because of its acute inflammatorynset and high degree of clinical impairment. Opinions differs to whether erosive OA is a distinct entity or only a differenttage of common hand OA. Erosive OA is associated withore severe hand disease, but apparently is not a marker of a

eparate disease. It seems to be an aggressive acute form of

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50 M. Fumagalli, P. Sarzi-Puttini, and F. Atzeni

and OA and may represent the equivalent of similar forms ofhoulder, hip, and knee OA (51).

Scintigraphy predicted radiographic changes in 1 longitu-inal study (31). There are a number of reports of cases ofapid progression and spontaneous healing, thus confirminghat erosive OA may reflect a stage of severe disease activityather than a different disorder. The prevalence of erosive OAn patients with chronic renal failure was 3 times greater inatients younger than 65 years than in a control population52). Smith compared the radiologic appearance of patientsith erosive and classical nodal OA: only joint-space narrow-

ng was more severe in patients with erosive OA (53).According to Belhorn (54), erosive hand OA is more com-on in postmenopausal women (F:M � 12:1). The DIP

oints are most frequently involved, followed by the PIPoints. A slight increase in the erythrocyte sedimentation rate

ay occur. The disorder is characterized by central erosionsnd the “gull-wing” deformity. Synovial pathology consistentith RA or OA may be related to the time of biopsy. Theverall prognosis is good, although deformity and impairedand function may occur.Erosive OA (55) can be suspected clinically because of its

hlogistic presentation, especially in the DIP and PIP joints.scintiscan may be useful in early diagnosis, but the final

iagnosis always is radiologic and depends on the presence ofentral erosions. In a follow-up study lasting 3 to 5 years,erbruggen (56) found a significant increase in the numberf affected joints and anatomic disease progression. OA wasomplicated by erosive changes in approximately 40% of theatients. Erosive azotemic OA was detected in 13% of a sam-le of subjects undergoing chronic dialysis, with the DIP

oint being the most frequently affected. It was not related toarathyroid hormone levels (57). The absence of a strong

emale predominance and osteophytosis, and the presence ofxtensive subchondral lesions, may distinguish erosivezotemic OA from erosive OA. Dhilmann (58) described aubtype of arthritis deformans as osteoclastic finger arthritis,haracterized by subchondral osteolysis.

The use of different scores for the progression of erosivend nonerosive OA has been proposed by Verbruggen (59) inhe form of an anatomic lesion progression score and annatomic phase progression score.

A capillaroscopic study (60) found abnormalities in ero-ive OA resembling psoriatic arthritis, which may be a relatedondition.

In conclusion, erosive hand OA has particular characteris-ics, but is not considered a distinct entity. It can be identifiedy clinical signs, because its radiologic appearance is notxclusive.

reatmentraditional ACR strategies recommend only a symptomaticharmacologic approach.Given the availability of safer nonsteroidal anti-inflamma-

ory drugs (NSAIDs), the new recommendations (61) sup-ort their use as initial treatment, particularly in patients with

oderate-to-severe pain and inflammation. The importance 1

f nonpharmacologic approaches, including appropriate ex-rcises and orthotics, was re-emphasized. The effectivenessf symptom-relieving, slow-acting drugs in hand OA re-uires long-term, controlled studies. A 2-year study (62) ofhe treatment of erosive hand OA with glucosamine sulphatehowed that it influenced joint pain, but doubtfully affectedone scintiscan results. Consensus on diagnosis criteriawhich must be valid, reliable, and sensitive to changes inlinical assessments and validated methods of radiologic as-essment) is needed for the conduction of clinical trials (63).here still is a lack of studies of disease-modifying OA drugs.The use of hydroxychloroquine in patients with erosiveA unresponsive to NSAID appears promising (64).lodronate in erosive hand OA has been anecdotally pro-osed (65).The Chingford Study (66) evaluated the effect ofRT on hand OA and found a weak effect. Joint protection

nd home exercises, which are easily administered andeadily acceptable interventions, increased grip strength andlobal hand function (67).

The surgical options for thumb-base OA range from liga-ent reconstruction or osteotomy for early stage disease

painful laxity), to trapeziectomy, arthrodesis, and arthro-lasty for more severe OA, but satisfactory results can bechieved by various surgical treatments (68). Nevertheless,ccupational therapy, splint support, and articular economyave eliminated the need for surgery for isolated first CMC

oint OA in 70% of patients (69).

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Hand osteoarthritis 51

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