BRIEF REPORT

Do the radiographic features of joint destructionin tophaceous gout imply a different pathophysiologyto that of rheumatoid and psoriatic arthritis?

Regan Arendse & Ayanda Gcelu & Christiaan Scott &Peter Beighton & Asgar Kalla

Received: 16 September 2009 /Revised: 29 April 2010 /Accepted: 2 June 2010 /Published online: 16 June 2010# Clinical Rheumatology 2010

Introduction

Joint destruction represents the extreme of the spectrumof the disease process in rheumatoid arthritis [RA],psoriatic arthritis [PA] and tophaceous gout [TG; 1].Destruction of the digital joints in RA and PA is evidentclinically as short, flail appendages with excess skin folds[1]. In contrast, despite joint destruction by gouty tophi,the digits maintain their length. However, these digits tooshorten when the gouty tophi are eliminated with medicalor surgical therapy. These clinical features suggest that thepathophysiology of joint destruction in TG is different tothat in RA and PA. To explore this supposition, weundertook a radiographic comparison of the articular

damage in persons with RA, PA and TG and interpretedthese in view of the recent reports of the pathophysiologyof bone erosions.

Methods

Radiographs of six people who had destruction of the fingerjoints by RA, PA or TG were reviewed. Each hadserological, biochemical and histological evidence tosupport their respective diagnoses. For the purpose ofbrevity, a description of the radiograph (Fig. 1) of the digitthat is representative of the joint destruction in each personis completed below.

Results

The distal and proximal ends of the metacarpals andproximal phalanges, respectively, are severely eroded in thefirst person with rheumatoid arthritis [RA1] illustrated inFig. 1. The articular surfaces of the metacarpalphalangeal[MCP] joint are in close contact. This joint deformity ispopularly described as a pencil-in-cup. The proximalinterphalangeal [PIP] joints are similarly deformed and thedistal interphalangeal [DIP] joints are uniformly narrowed.

The MCP joint of the second person with rheumatoidarthritis [RA2] too has the pencil-in-cup appearanceconsistent with joint destruction. The articular surfaces areclosely apposed. The PIP joint is uniformly narrowed andthe DIP joint is unaffected.

A pencil-in-cup appearance of the MCP joint of thefirst person with psoriatic arthritis [PA1] is evident. Heretoo, there is apposition of the articular surfaces. The PIPand DIP joints are ankylosed.

Authors contributions All authors read and approved the finalmanuscript and all participated in this work. All are in agreement withthe views expressed.

R. Arendse :A. Gcelu :A. KallaDepartment of Medicine, Division of Rheumatology, GrooteSchuur Hospital, University of Cape Town,Cape Town, South Africa

C. ScottDepartment of Paediatrics, Red Cross Hospital,University of Cape Town,Cape Town, South Africa

P. BeightonDivision of Medical Genetics, Groote Schuur Hospital,University of Cape Town,Cape Town, South Africa

R. Arendse (*)Observatory 7925, Groote Schuur Hospital,J47 Old Main Building,Cape Town, South Africae-mail: regan@arendse.biz

Clin Rheumatol (2010) 29:11811183DOI 10.1007/s10067-010-1521-4

In the second person with psoriatic arthritis [PA2], thedestruction is limited to the DIP joint and the pencil-in-cupappearance is evident. In contrast to the preceding illustrationsof joint destruction, there appears to be a radiolucent intervalbetween the articular surfaces. The PIP and MCP joints areuninvolved.

The DIP joint of the first person with tophaceous gout[TG1] is infiltrated by a tophus. The tophus is evident as acloudy opacity within the joint space, one end of which isdemarcated by a calcified crescent. This is commonlydescribed as an over-hanging edge and representsapposition of bone at the border of the tophus. The erodedarticular surfaces of the DIP are sclerotic and well-definedand may be described as punched-out. The articularsurfaces are widely spaced by the intervening tophus tomaintain the original contours of the digit. The PIP andMCP joints are uniformly narrowed.

Multiple tophi are seen to infiltrate the PIP joint of thesecond person with tophaceous gout [TG2]. These tophi areoutlined by calcified tissues which give the appearance ofover-hanging edges. The erosions on the phalanges appearpunched-out and the intervening tophi maintain theoriginal length of the digit. The DIP and MCP joints areuniformly narrowed.

Discussion

These radiographic observations support our hypothesisthat there are differences in the pathophysiologicalprocesses that lead to joint destruction in RA and PAcompared with TG. The closely apposed articular surfacesin the destroyed joints of the former conditions suggest thatthe intervening substance is pliable. Inflamed synovial

tissue closely fits this description and is probably the sourceof pro-inflammatory mediators that promote the bonedestruction.

In contrast, the articular surfaces of the destroyedjoints in tophaceous gout are widely spaced to maintainthe original contour of the digits. This suggests that theintervening substance has a solid consistency. Goutytophi are excellent candidates to fulfil this requirementand intra-articular extension of gouty tophi has previ-ously been demonstrated with computed tomography [2].Until recently, it was hypothesized that gouty tophimechanically eroded the bony surfaces they were incontact with. However, recent investigations have demon-strated that mono-sodium urate crystals [MSU] alone donot have an erosive effect on bone and are unlikely to leadto joint destruction. Rather, phagocytosis of the MSU bymacrophages at the peripheries of the tophi activatesmacrophages to create a signal that impairs osteoprote-gerin expression by osteoblasts [3]. This leads to a relativeincreased expression of receptor-activator nuclear factorkappa [RANK] ligand by synoviocytes and maturationof osteoclast precursors by binding of the latter ligand toRANK. The mature osteoclasts resorb bone and initiatejoint destruction in tophaceous gout. The NALP-3 inflam-masome complex that promotes maturation of pro-interleukin-1 [IL-1] to IL-1 is proposed as one of thesignals stimulated within the macrophages that lead tobone erosions.

Alternatively, tophi may erode bone by the direct effectMSU has on the phenotype of osteoblasts [4]. In thisregard, the osteoblast bone formation capacity is reduced,leading to an imbalance of bone formation and resorption.The unopposed activity of the osteoclasts may lead to thejoint destruction associated with TG.

Fig. 1 Radiographic features ofjoint destruction in the six par-ticipants RA1 and RA2: first andsecond participants with rheu-matoid arthritis, respectively;PA1 and PA2: first and secondparticipants with psoriatic ar-thritis, respectively; TG1 andTG2: first and second partici-pants with tophaceous gout

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The observation that MSU can directly activate T-cellsindependent of formal presentation by an antigen-presentingcell is relevant [5]. Not only may the activated T-cellsinitiate a cascade of events that lead to bone erosions, butthey also express co-stimulatory molecules that maypromote B-cell activation. It remains to be demonstratedwhether the in vitro finding of B-cell activation hasrelevance to joint destruction in TG.

Conclusion

The conclusion we draw from the observations of this study isthat the pathophysiology of joint destruction is different in TGfrom that of RA and PA. Common to all three joint destructiveprocesses is the presence of a significant inflammatorycomponent that disturbs the bone resorptionformationbalance in favour of bone loss. While the emphasis in thetreatment of tophaceous gout is currently focused oneliminating the tophi, we are of the opinion that attenuationof the inflammatory processes that have recently beenimplicated in the pathogenesis of erosions in TG may be justas important as in rheumatoid arthritis and psoriatic arthritis.Despite the limited success reported with the use ofinterleukin-1 receptor blockers in the treatment of boneerosions in TG, research that focuses on the attenuation ofthe inflammatory processes in gout is encouraged.

Acknowledgements We are grateful to the Medical ResearchCouncil and the National Research Foundation of South Africa fortheir support (PB).

Disclosures None

References

1. Belt EA, Kaarela K, Kauppi MJ, Savolainen HA, KautiainenHJ, Lehto MUK (1999) Assessment of mutilans-like handdeformities in chronic inflammatory joint diseases. A radio-graphic study of 52 patients. Ann Rheum Dis 58:250252

2. Dalbeth N, Clark B, Gregory K, Gamble G, Sheehan T, Doyle A,McQueen FM (2009) Mechanisms of bone erosion in gout: aquantitative analysis using plain radiography and computedtomography. Ann Rheum Dis 68:12901295

3. Dalbeth N, Smith T, Nicolson B, Clark B, Callon K, Naot D,Haskard DO, McQueen FM, Reid IR, Cornish J (2008)Enhanced osteoclastogenesis in patients with tophaceous gout:urate crystals promote osteoclast development throughinteractions with stromal cells. Arthritis Rheum 58(6):18541865

4. Bouchard L, de Mdicis R, Lussier A, Naccache PH, PoubellePE (2002) Inflammatory microcrystals alter the functionalphenotype of human osteoblast-like cells in vitro: synergismwith IL-1 to overexpress cyclooxygenase-2. J Immunol 168(10):53105317

5. Webb R, Jeffries M, Sawalha AH (2009) Uric acid directlypromotes human T-cell activation. Am J Med Sci 337(1):2327

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