Inflammatory or erosive are terms used interchangeably to define a clinical subset of osteoarthritis of the hand (HOA), targeting interphalangeal joints and characterised by an abrupt onset, marked pain and functional impairment, inflammatory symptoms and signs, including stiffness, soft tissue swelling, erythema, paraesthesiae, mildly elevated C-reactive protein and a worse outcome than non-erosive HOA. This subset is defined radiographically by subchondral erosion, cortical destruction and subsequent reparative change, which may include bony ankylosis. Although the presence of both clinical and radiographic aspects are very suggestive for the diagnosis in most cases, doubts have been recently raised from some studies which, by means of sensitive imaging techniques such as magnetic resonance imaging (MRI) and sonography, had found erosive changes in most patients with HOA, including those without signs of erosions at conventional radiography. However, many findings suggest that subjects with erosive HOA exhibit more inflammatory features than those with non-erosive HOA in different ways, including clinical, laboratory and sonographic aspects. Thus, it is probably preferable to use the double term inflammatory/erosive to better define this particular subset of HOA.
Classically, osteoarthritis (OA) has been considered by rheumatologists to be a non-inflammatory joint disease, in order to distinguish it from the so-called arthritides, characterised by the presence of an inflammatory arthritis. Accordingly, in some European countries, OA is still called by terms containing the suffix ‘osis’, to underline the prevalence of degenerative features, instead of ‘itis’, the suffix indicating an inflammatory condition.
However, in past years, accumulating evidence suggests that inflammation of various types plays a key role in the pathogenesis of OA, as demonstrated by the presence of inflammatory features in the synovial membrane of at least 50% of patients with OA and by the up-regulation of inflammatory cytokines in all joint tissues involved in OA, such as synovial membrane, cartilage and subchondral bone . Chondrocytes, as well as synovial cells, of OA patients produce increased levels of interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α), which, in turn, stimulate production and activity of other cytokines and inflammatory mediators, including metalloproteinases (MMPs), prostaglandin E2, nitric oxide (NO) and reactive oxygen species (ROS) . In addition, mechanical stress, by both static and intermittent compression, increases NO production by chondrocytes as well as NO synthase (NOS) expression . ROS have been implicated in indirectly promoting chondrocyte apoptosis, catabolic processes and matrix degradation .
An important point in progress derives from the evidence that chondrocytes are programmed to respond to direct biomechanical perturbation acting as ‘mechanosensors’ by means of specific sensitive receptors, which, when activated, can stimulate the production of inflammatory cytokines, chemokines and matrix-degrading proteinases, mainly MMPs . ‘Abnormal’ mechanical loading stimulates depletion of proteoglycans, damages the collagen network and decreases the synthesis of cartilage matrix proteins .
Despite all these evidences, only in some cases clinical and laboratory features of OA appear consistent with a classical inflammatory condition. In most OA patients, the acute phase markers in blood are at normal values, the number of leucocytes in synovial fluid is usually consistent with a ‘non-inflammatory’ type, because at a number lower than 2000 per mm 3 , the swelling is moderate, and classical inflammation signs such as redness, tenderness and warmth are of a lower grade . Furthermore, pain is relieved by rest and morning stiffness lasts less than 30 min. Only in some cases, mostly associated with the presence of calcium crystals, OA of the lower limbs may reveal true inflammatory features, which, in addition, are usually episodic.
Thus, at present, the only OA variant proposed and classified as inflammatory is that of the hand. In time, since most patients with inflammatory hand OA (HOA) revealed radiographic erosions, the term ‘erosive HOA’ was considered more specific. However, although this latter term is preferred, some authors consider the two terms interchangeable. Finally, it could be that, consistent with the increasing frequency of erosive aspects in HOA revealed by the recent sensitive imaging techniques, the most appropriate term would be ‘inflammatory/erosive HOA’ (IE-HOA).
Inflammatory/erosive HOA: the difficult to search an identity
There is still no general consensus on the definition of IE-HOA. In time, its identity has been discussed and variously proposed as a subset of HOA , variant of HOA , severe form of HOA , inflammatory phase of HOA and an entity distinct from OA . These doubts have influenced many aspects of research in this particular field of HOA, therefore, leading to many difficulties in the interpretation of available data.
Since 1961, Crain underlined the existence of “a chronic inflammatory form of osteoarthritis which involves both the proximal and distal rows of finger joints and leads ultimately to marked deformity of the digits” . However, Ehrlich was the first to use the term ‘inflammatory osteoarthritis’ in 1972 to emphasise the abrupt onset and the presence of signs of inflammation in a subset of patients with interphalangeal (IP) OA . Subsequently, this term was modified in erosive OA, which was considered more appropriate to characterise those patients with inflammatory features having erosive aspects at conventional radiography (CR) .
The recent European League against Rheumatism (EULAR) recommendations for the diagnosis of HOA state that “erosive HOA is believed to be a subset of HOA targeting IP joints and characterised by an abrupt onset, marked pain and functional impairment, inflammatory symptoms and signs, including stiffness, soft tissue swelling, erythema, paraesthesiae, mildly elevated C reactive protein (CRP), and a worse outcome than non-erosive HOA.” In the same paper, a glossary specifies that erosive HOA is a “subset of HOA defined radiographically by subchondral erosion, cortical destruction and subsequent reparative change, which may include bony ankylosis.”
Therefore, we could be confident that inflammatory features and radiographic erosions are sufficient hallmarks to carefully define this HOA subset. However, various degrees of inflammatory signs are observable in a significant number of patients with non-erosive HOA. Accordingly, many years ago, Kellgren and Moore, having first proposed the concept of primary generalised OA, had drawn attention to the frequent onset at hand joints with inflammatory aspects, such as abrupt onset, pain at night and tenderness . All these features may be present in nodal OA, typically during the first year of involvement of each joint, and may regress with time, usually when the nodule is established .
Furthermore, recent studies seem to suggest that the other classic hallmarks of erosive HOA, such as the radiographic erosion, are found more frequently than expected in patients with HOA when investigated using sensitive imaging techniques, in particular, sonography and MRI . Thus, finally, to avoid some confounding aspects, the definition of IE-HOA would be the most appropriate.
Epidemiological and clinical features of inflammatory/erosive HOA
In absence of a true disease definition, no exact epidemiological data are available, especially concerning prevalence. Therefore, there are some discrepancies among old studies suggesting that IE-HOA was a rare disease and those, more recent, claiming that this variant is very frequent. Pattrick et al. found 10 cases of erosive HOA among 67 patients attending their Rheumatology Unit with polyarticular HOA . In a prospective study of 500 consecutive patients attending a rheumatology clinic with symptomatic limb joint OA, Cobby et al. identified 24 cases with erosive HOA . In a survey performed in the Venetian area of Italy, Cavasin et al. examined 640 subjects older than 40 years . Of these, 200 (31.2%) had symptomatic HOA according to the Altman criteria and were submitted to assessment by CR. EOA was found in 14 subjects (7%), all women of a mean age of 54 years (range: 40–74 years). Verbruggen and Veys found that half the numbers of patients with symptomatic menopausal HOA show erosive features at CR . Among 88 consecutive symptomatic patients with HOA, Maheu observed erosive HOA, so defined by the presence of at least two radiographic erosions, in 38 (43.1%) patients .
It seems sufficiently ascertained that this HOA subset affects almost exclusively the female sex. In our series of 141 patients considered to have erosive HOA, on the basis of at least one erosion in IP joints and excluding those with erosions at metacarpophalangeals (MCPs), 126 were females (89.3%). This peculiarity is confirmed by almost all studies.
As regards the clinical aspects, some are characteristics and may lead to an early suspicion of IE-HOA. The term ‘inflammatory OA’ seems, in this context, to be appropriate, since abrupt onset of pain, swelling, redness, warmth and limited function of IP joints of the hands are commonly found in most patients ( Table 1 ). Some features may also be observed in non-IE-HOA cases, but usually in the earliest years of disease onset. Characteristics of IE-HOA are the throbbing paraesthesias of the fingertips, which are often nocturnal It is important to underline that the IE-HOA is usually polyarticular, because it may involve multiple joints simultaneously and may persist for many years . This contrasts with nodal HOA, which exhibits its flares mainly at onset of involvement of each joint, in a ‘stuttering’ onset polyarthropathy of distal IP (DIP) and proximal IP (PIP), which resembles a ‘monoarthritis multiplex’, and is strictly related to the development of osteophytes .
| Feature | IE-HOA | Non-IE-HOA |
|---|---|---|
| Onset | Frequent abrupt | In most cases the onset is moderate |
| Pain | Marked, frequently recurrent and persistent at follow-up for many years | Present only at onset (first 1 year) sometimes may have 2–3 years duration |
| Tenderness | Frequently persistent | Present almost only at onset |
| Erythema | Frequent, recurrent during the flares | May be sometimes found at onset |
| Warmth | Frequent, chronic, recurrent | Frequent at onset |
| Swelling | Usually involving soft tissues | Postero-lateral; sometimes presenting as a cyst which, when aspirated, reveals a very viscous and clear fluid the “mucoid cyst” |
| Function | Frequent functional impairment | Less severe |
| Number of affected joints | Sometimes, more than one simultaneously | “Monoarthritis multiplex” type |
| Paresthesias of fingertips | May be seen, sometimes | Rare |
| Morning stiffness <30 min | Frequent | Frequent at onset |
| Nodose deformities of PIP, DIP joints | Common, but in some cases may be absent | Common |
| Lateral subluxation of phalanges | May be seen | May be seen, but less frequently than in IE-HOA |
| Interphalangeal instability | May be seen | Rare |
| Interphalangeal ankylosis | May be seen | Rare |
The evolution in nodose deformities of DIPs and PIPs may be seen to follow a variable course with no significant differences from non-IE-HOA, although in IE-HOA the progression is more accelerated. In some cases of IE-HOA, as in the so-called atrophic form, osteophytes are small or even absent, therefore, leading to some misinterpretation with other forms of arthritis.
Concerning distribution, the most affected joints are DIPs and, to a lesser extent, PIPs. The most involved fingers are the second and the third, frequently in a symmetrical fashion, followed by the fourth and the fifth. There is no general agreement that the first carpometacarpal localisation, found by Crain in at least one-third of patients, should be considered as a feature consistent with HOA. Large joints, such as the hip, shoulder and feet are rarely affected.
An important point is that IE-HOA frequently leads to joint deformities, some of which may be indistinguishable from those of non-IE-HOA, and include lateral subluxations and Heberden’s and Bouchard’s nodes. Other deformities are seen almost exclusively in IE-HOA, such as instability and ankylosis of DIP and PIP and, rarely, opera-glass deformity.
In terms of disease definition, the addition of erosive to inflammatory and vice versa is crucial because the only presence of inflammatory signs, especially at the disease onset, is not specific nor reliable in predicting the erosive variant of HOA because these features may be present at various degrees in almost all subsets of HOA.
Epidemiological and clinical features of inflammatory/erosive HOA
In absence of a true disease definition, no exact epidemiological data are available, especially concerning prevalence. Therefore, there are some discrepancies among old studies suggesting that IE-HOA was a rare disease and those, more recent, claiming that this variant is very frequent. Pattrick et al. found 10 cases of erosive HOA among 67 patients attending their Rheumatology Unit with polyarticular HOA . In a prospective study of 500 consecutive patients attending a rheumatology clinic with symptomatic limb joint OA, Cobby et al. identified 24 cases with erosive HOA . In a survey performed in the Venetian area of Italy, Cavasin et al. examined 640 subjects older than 40 years . Of these, 200 (31.2%) had symptomatic HOA according to the Altman criteria and were submitted to assessment by CR. EOA was found in 14 subjects (7%), all women of a mean age of 54 years (range: 40–74 years). Verbruggen and Veys found that half the numbers of patients with symptomatic menopausal HOA show erosive features at CR . Among 88 consecutive symptomatic patients with HOA, Maheu observed erosive HOA, so defined by the presence of at least two radiographic erosions, in 38 (43.1%) patients .
It seems sufficiently ascertained that this HOA subset affects almost exclusively the female sex. In our series of 141 patients considered to have erosive HOA, on the basis of at least one erosion in IP joints and excluding those with erosions at metacarpophalangeals (MCPs), 126 were females (89.3%). This peculiarity is confirmed by almost all studies.
As regards the clinical aspects, some are characteristics and may lead to an early suspicion of IE-HOA. The term ‘inflammatory OA’ seems, in this context, to be appropriate, since abrupt onset of pain, swelling, redness, warmth and limited function of IP joints of the hands are commonly found in most patients ( Table 1 ). Some features may also be observed in non-IE-HOA cases, but usually in the earliest years of disease onset. Characteristics of IE-HOA are the throbbing paraesthesias of the fingertips, which are often nocturnal It is important to underline that the IE-HOA is usually polyarticular, because it may involve multiple joints simultaneously and may persist for many years . This contrasts with nodal HOA, which exhibits its flares mainly at onset of involvement of each joint, in a ‘stuttering’ onset polyarthropathy of distal IP (DIP) and proximal IP (PIP), which resembles a ‘monoarthritis multiplex’, and is strictly related to the development of osteophytes .
| Feature | IE-HOA | Non-IE-HOA |
|---|---|---|
| Onset | Frequent abrupt | In most cases the onset is moderate |
| Pain | Marked, frequently recurrent and persistent at follow-up for many years | Present only at onset (first 1 year) sometimes may have 2–3 years duration |
| Tenderness | Frequently persistent | Present almost only at onset |
| Erythema | Frequent, recurrent during the flares | May be sometimes found at onset |
| Warmth | Frequent, chronic, recurrent | Frequent at onset |
| Swelling | Usually involving soft tissues | Postero-lateral; sometimes presenting as a cyst which, when aspirated, reveals a very viscous and clear fluid the “mucoid cyst” |
| Function | Frequent functional impairment | Less severe |
| Number of affected joints | Sometimes, more than one simultaneously | “Monoarthritis multiplex” type |
| Paresthesias of fingertips | May be seen, sometimes | Rare |
| Morning stiffness <30 min | Frequent | Frequent at onset |
| Nodose deformities of PIP, DIP joints | Common, but in some cases may be absent | Common |
| Lateral subluxation of phalanges | May be seen | May be seen, but less frequently than in IE-HOA |
| Interphalangeal instability | May be seen | Rare |
| Interphalangeal ankylosis | May be seen | Rare |
The evolution in nodose deformities of DIPs and PIPs may be seen to follow a variable course with no significant differences from non-IE-HOA, although in IE-HOA the progression is more accelerated. In some cases of IE-HOA, as in the so-called atrophic form, osteophytes are small or even absent, therefore, leading to some misinterpretation with other forms of arthritis.
Concerning distribution, the most affected joints are DIPs and, to a lesser extent, PIPs. The most involved fingers are the second and the third, frequently in a symmetrical fashion, followed by the fourth and the fifth. There is no general agreement that the first carpometacarpal localisation, found by Crain in at least one-third of patients, should be considered as a feature consistent with HOA. Large joints, such as the hip, shoulder and feet are rarely affected.
An important point is that IE-HOA frequently leads to joint deformities, some of which may be indistinguishable from those of non-IE-HOA, and include lateral subluxations and Heberden’s and Bouchard’s nodes. Other deformities are seen almost exclusively in IE-HOA, such as instability and ankylosis of DIP and PIP and, rarely, opera-glass deformity.
In terms of disease definition, the addition of erosive to inflammatory and vice versa is crucial because the only presence of inflammatory signs, especially at the disease onset, is not specific nor reliable in predicting the erosive variant of HOA because these features may be present at various degrees in almost all subsets of HOA.
Imaging features in inflammatory/erosive HOA
Radiography
Although the main hallmark of IE-HOA is the presence of erosion at CR, the precise definition of erosion in IE-HOA is still a matter for debate. Classically, as stated in the EULAR recommendations, erosive HOA is defined radiographically by subchondral erosion, cortical destruction and subsequent reparative change, which may include bony ankylosis . These apparently simple observations need to be carefully specified.
The erosions in HOA are seen in DIPs and PIPs and may occur within both the articulating surface in the subchondral bone (central), and at joint margins, between the edge of the articular cartilage and the joint capsule (marginal). The erosions considered characteristics of IE-HOA are those central, typically showing the classic ‘seagull-wing’ or ‘saw-tooth’ pattern ( Figs. 1 and 2 ). The nature of these central lesions is the subject of some controversies, and it has been suggested that they represent subchondral collapse or pressure atrophy, rather than being the result of synovial inflammation .
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