Clinical and laboratory aspects of Jaccoud’s arthropathy

The classical clinical manifestation of JA is the presence of ‘reversible’ joint deformities, mainly in hands, but also observed in other joints, such as the feet , knees and shoulders . It may be symptomatic or painless and may even occur without any previous history of arthritis . In this regard the report by Levin is well illustrated in the following statement: “The patient had extremely mild manifestations of rheumatic fever and had had two episodes of chorea. Later rheumatic heart disease with pure mitral stenosis was diagnosed. Never were there symptoms related to any of the joints, and deformity of the hands developed so gradually that the patient was not fully aware that it had occurred until she was an adult. ”

The joint deformities most frequently seen in JA are ulnar deviation, swan neck, ‘z’-thumb, ‘boutonniere’ and hallux valgus, which, apart from their reversible character, are quite similar to those seen in RA. These deformities vary in intensity and it is not rare for them to be present without being noted by the patient or his/her physician. On the other hand, particularly in older well-established deformities, there may be limitation of function of the involved joints, probably secondary to the local residual fibrosis leading to contractures. In patients seen in this stage, the misdiagnosis of RA is common. It should be emphasised that although ‘reversible’ and sometimes painless, JA is associated with considerable loss of quality of life . Fig. 1 (A) demonstrates a classical JA case in an SLE patient, illustrating the reversibility of the deformities in hands (B). Rarely, diffuse subcutaneous swelling in the hands can be observed ( Fig. 2 ) .

Classical Jaccoud’s arthropathy in a systemic lupus erythematosus patient (A, B), illustrating the reversibility of the hand deformities (C,D).

Diffuse edema in the dorsum of the right hand in a case of Jaccoud’s arthropathy secondary to systemic lupus erythematosus.

In 1950, Bywaters observed for the first time that patients with RF and JA had more valvular heart disease (VHD) . Curiously, some cases of JA have been described in patients with hypocomplementemic urticarial vasculitis and concomitant non-rheumatic valvular disease, probably mediated by immune complexes . Recently, it was demonstrated that in SLE there is also an association between JA and VHD .

Clinically significant tenosynovitis has rarely been described in JA probably because other features of the disease overshadow the symptoms related to the tendon sheaths, but in some patients crepitus may be detected . A very intriguing point is a supposed association of JA with a predisposition for tendon rupture, at least in SLE patients. In a recent systematic review of the cases of tendon rupture in SLE patients, both were observed in a total of 55 published cases. The most frequently observed rupture sites were the patellar and Achilles’ tendons. Sixteen patients concomitantly had JA (29%) suggesting that such association has been underestimated .

In SLE, there are some reports relating the degree of deformity in JA with disease duration as well as disease activity. However, one should be aware that only the minority of SLE patients develop JA, regardless of the duration or severity of the disease . Other studies also attempted to look for an association of JA with different clinical features, as well as with several autoantibodies, but the results were not conclusive.

Esdaile et al. reported that SLE patients with JA had the disease with longer duration, and longer duration of joints being affected, but there was no difference in relation to sex, age of disease onset, Sjögren’s syndrome and presence of LE cells, antibodies or rheumatoid factor (RF) . On the other hand, Alarcon-Segóvia et al. studied 858 patients with SLE, of whom 41 had deforming arthritis of the hands, and observed that the group with joint deformities had a shorter duration of the disease, and a higher frequency of RF, anti-dsDNA antibodies and ‘ sicca symptoms’ .

Spronk et al. studied 72 patients with SLE and demonstrated that the patients with JA had the disease with longer duration, longer duration of arthritis, higher RF positivity and higher level of C-reactive protein. Whereas, there was no association with sicca syndrome, malar rash, haematologic and renal disturbances, presence of anti-SSA, anti-Sm, anti-dsDNA antibodies and perinuclear factor .

In a study of 51 SLE patients, ‘hand deformities’ were associated with the presence of anti-U1-RNP antibodies . On the other hand, Paredes et al. , in patients with superposition syndrome, did not observe any difference among the various laboratory parameters, such as anti-RNP, anti-Sm or anti-SSA antibodies in the subgroups with and without JA .

A Japanese study that enrolled 340 patients with SLE revealed that the mean age of patients with JA was significantly higher than that of the patients without JA. Furthermore, the majority of patients with JA had Sjögren’s syndrome. Anti-SSA antibodies were detected in seven out of 10 tested sera .

Others have reported an association of JA with antibodies to 52 KD SSA, phospholipid and type II collagen . A more recent study developed by Galvão et al. was specifically designed to analyse the frequency of different autoantibodies including anti-CCP, anticardiolipin, anti-mutated citrullinated vimentin (MCV), anti-SSA/Ro, anti-SSB/La, anti-Sm and anti-RNP, anti-dsDNA and RF, in a group of 24 SLE patients with JA, compared to those without JA (24 controls). The authors found a statistically significant association between the presence of anti-dsDNA antibodies and JA ( p = 0.04) as well as a marginal association with anti-MCV antibodies .

Diagnostic criteria

There are no well-established diagnostic criteria for JA. The first attempt to classify JA was made by Bywaters, referring to patients with RF. The criteria included the antecedent of RF, reversible deformities caused by soft tissue alterations, absence of erosions on X-rays and RF negativity .

Murphy and Staple, based on case reports described in the literature, suggested criteria for diagnosing JA secondary to RF. These criteria included historical data, physical and radiological exams, and laboratory findings characterised by the absence of RF and by the normal value of the erythrocyte sedimentation rate .

Later on, additional sets of criteria were proposed by Villiaumey et al. and Kahn .

Alarcon-Segovia et al. defined deforming arthropathy in SLE as any deviation of the metacarpus finger axes assessed by a goniometer .

In 1992, Spronk et al. developed a diagnostic ‘index’ which allowed for the presence of different deformities, and attributing JA a score of over five points.

An alternative system of classification of JA in SLE was recently proposed . Initially, the patients were classified as having deforming arthropathy based on the definition of Alarcon-Segovia et al. Those with deformities were sub-classified into erosive and non-erosive arthropathy based on X-rays. The subgroup with non-erosive arthropathy was later subdivided into definite JA, or mild-deforming arthropathy, which was based on a Spronk’s index score higher than 5 or ≤5, respectively.

Diagnostic criteria

There are no well-established diagnostic criteria for JA. The first attempt to classify JA was made by Bywaters, referring to patients with RF. The criteria included the antecedent of RF, reversible deformities caused by soft tissue alterations, absence of erosions on X-rays and RF negativity .

Murphy and Staple, based on case reports described in the literature, suggested criteria for diagnosing JA secondary to RF. These criteria included historical data, physical and radiological exams, and laboratory findings characterised by the absence of RF and by the normal value of the erythrocyte sedimentation rate .

Later on, additional sets of criteria were proposed by Villiaumey et al. and Kahn .

Alarcon-Segovia et al. defined deforming arthropathy in SLE as any deviation of the metacarpus finger axes assessed by a goniometer .

In 1992, Spronk et al. developed a diagnostic ‘index’ which allowed for the presence of different deformities, and attributing JA a score of over five points.

An alternative system of classification of JA in SLE was recently proposed . Initially, the patients were classified as having deforming arthropathy based on the definition of Alarcon-Segovia et al. Those with deformities were sub-classified into erosive and non-erosive arthropathy based on X-rays. The subgroup with non-erosive arthropathy was later subdivided into definite JA, or mild-deforming arthropathy, which was based on a Spronk’s index score higher than 5 or ≤5, respectively.

Mechanisms responsible for the development of JA

Generally speaking, the deformities seen in JA are secondary to soft tissue abnormalities. These include laxity of ligaments and joint capsule, with distension and secondary deviation of the tendon from its axis with the contribution of muscular imbalance. Although the presence of synovitis is well documented and may somehow contribute to the process , it is not as aggressive and does not seem to be a main feature as it is in RA . In support of this statement is the observation that, commonly, progression of the deformity in JA can be asymptomatic, meaning mild articular inflammation . Moreover, there are cases of JA in dermatomyositis , scleroderma and chronic pulmonary disease , without evidence of previous arthritis.

Tenosynovitis may also have some role in JA as it can loosen the tendon or even weaken it, predisposing to ruptures as mentioned above.

Progressive fibrosis of the capsule with contractures may explain the lack of reversibility of the deformities eventually seen in patients with longstanding JA.

Whether or not joint hypermobility participates in the development of JA is a matter of debate. Some patients with well-defined JA do indeed have hypermobile joints as illustrated in cases with involvement of multiple joints ( Fig. 3 ) . However, it is not known if hypermobility is the primary process or a consequence of the laxity of the soft tissue elements. Klemp et al. found no statistically significant difference in the number of cases with joint hypermobility among the SLE cases and among the normal control. Among those SLE patients with or without joint deformities, there was no difference with regard to the joint mobility score. On the other hand, Guma et al. , studying 81 SLE patients and 280 controls, demonstrated that 39 (48%) patients with SLE and 42 (15%) of the control group were hypermobile. Hypermobility was more profound in older patients with SLE (>49 years). Joint laxity was not associated with any clinical feature of SLE, but no detail was provided about JA in this cohort.

Evidence of articular hypermobility in elbows (A) and knees (B) in a patient with Jaccoud’s arthropathy.

Another mechanism still unproven in JA, at least in SLE, is the presence of hyperparathyroidism secondary to renal failure. Theoretically, this status could stimulate collagenases leading to laxity of ligaments and tendons . However, this does not seem to be the case in the majority of patients with SLE as there is no association between JA and renal failure.

Recently, to explain the non-erosive nature of JA, an experimental model has been proposed . It was based on the information that IFN-α may participate in the pathogenesis of SLE arthritis. In this model, the authors proposed an IFN-α biased myelopoiesis, that is, exposure to elevated systemic IFN-α increases the myeloid dendritic cells differentiation to present autoantigens at the expense of osteoclastogenesis in a mutually exclusive manner, as these cells are derived from the same myelomonocyte precursor. Thus, focal erosion becomes impossible due to the lack of mature osteoclasts.

Histopathologic findings

There are only a few reports on the histopathologic features of JA. Although the presence of synovitis has been described, in general, it is mild without marked synovial membrane proliferation . There is fibrin deposition, haematoxylin corpuscles, light inflammatory infiltrate and microvascular alteration, without the pannus , classically seen in RA .

Tissue obtained at joint surgery for JA demonstrated mild line proliferation, areas of haematoxyphilic in villi and capsule and infiltration of lymphocytes and plasma cells in synovium .

In an autopsy study on 10 SLE patients including one with JA, tissue was examined in 14 joints and from seven tendon sheaths . Inflammatory changes were slight but granulation tissue ‘ pannus ’ confined to the marginal zone of the articular cartilage was found. Fibrin-like material was present in tendon sheaths, which could explain the crepitus detected clinically in some cases. Another necropsy study on JA in a patient with RF demonstrated thickening of the joint capsule, which consisted of dense acellular fibrous tissue and no evidence of synovial pathology suggesting longstanding disease involvement. It was difficult to affirm that such capsular fibrosis was due to repeated attack of RF or secondary to the chronic trauma of the misaligned joints. It may represent an end-stage disease sometimes clinically associated to a certain degree of joint limitation as pointed out above .

Imaging issue

Characteristically plain X-ray of JA reveals deformities and subluxations, without the classical erosions seen in patients with RA ( Fig. 4 ) . However, by using more refined imaging methods such as magnetic resonance imaging (MRI) and ultra-sound imaging, erosions have been demonstrated in JA joints.

Swan neck deformity in Jaccoud’s arthropathy (A) and a plain radiograph of the left hand showing deformities but not erosions (B).

The first published study on MRI of JA was performed by Ostendorf et al. They studied both hands of 14 SLE patients with arthritis, four of them with JA as defined by ‘Spronk’s index’, using MRI. In JA joints they found tenosynovitis, capsule edema and a slight synovial hypertrophy in one case but no erosion was found. On the other hand, in a more recent publication where 20 SLE patients with JA (19 women and one man) were studied by MRI and a total of 300 joints evaluated, some degree of synovitis was observed in 67.3%, tenosynovitis in 38.5%, and in 16 out of 300 examined joints (5.3%) small areas of erosion were seen .

Seventeen SLE patients with arthritis of the hands underwent high-resolution ultra-sound (HRUS) examinations with Doppler imaging of their dominant hand. Sixteen (94%) patients had joint effusion or synovial hypertrophy in the wrist and eight (47%) patients had erosion at the second or third metacarpophalangeal (MCP) joints. In those with erosion, there was a trend towards a higher Jaccoud’s arthropathy index score. However, from the study it was not clear how many patients actually had JA .

A classical radiographic feature of JA that is rarely described at present is the hook lesion observed on the palmar-radial surface of the metacarpal heads seen in plain radiograph of the hands . These lesions are not pathognomonic for JA as they have also been described in RA, gout, pseudo-gout and osteoarthritis . Supposedly the tension placed on the metacarpal head remodels the palmar-radial aspect to produce such lesions .