Clin Rheumatol (2010) 29:11811183

DOI 10.1007/s10067-010-1521-4

BRIEF REPORT

Do the radiographic features of joint destruction

in tophaceous gout imply a different pathophysiology
to 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 spectrum
of 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 evident
clinically 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 too
shorten when the gouty tophi are eliminated with medical
or surgical therapy. These clinical features suggest that the
pathophysiology of joint destruction in TG is different to
that in RA and PA. To explore this supposition, we
undertook a radiographic comparison of the articular

Authors contributions All authors read and approved the final

manuscript and all participated in this work. All are in agreement with
the views expressed.
R. Arendse : A. Gcelu : A. Kalla
Department of Medicine, Division of Rheumatology, Groote
Schuur Hospital, University of Cape Town,
Cape Town, South Africa
C. Scott
Department of Paediatrics, Red Cross Hospital,
University of Cape Town,
Cape Town, South Africa
P. Beighton
Division 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 Africa
e-mail: regan@arendse.biz

damage in persons with RA, PA and TG and interpreted

these in view of the recent reports of the pathophysiology
of bone erosions.

Methods
Radiographs of six people who had destruction of the finger
joints by RA, PA or TG were reviewed. Each had
serological, biochemical and histological evidence to
support their respective diagnoses. For the purpose of
brevity, a description of the radiograph (Fig. 1) of the digit
that is representative of the joint destruction in each person
is completed below.

Results
The distal and proximal ends of the metacarpals and
proximal phalanges, respectively, are severely eroded in the
first person with rheumatoid arthritis [RA1] illustrated in
Fig. 1. The articular surfaces of the metacarpalphalangeal
[MCP] joint are in close contact. This joint deformity is
popularly described as a pencil-in-cup. The proximal
interphalangeal [PIP] joints are similarly deformed and the
distal interphalangeal [DIP] joints are uniformly narrowed.
The MCP joint of the second person with rheumatoid
arthritis [RA2] too has the pencil-in-cup appearance
consistent with joint destruction. The articular surfaces are
closely apposed. The PIP joint is uniformly narrowed and
the DIP joint is unaffected.
A pencil-in-cup appearance of the MCP joint of the
first person with psoriatic arthritis [PA1] is evident. Here
too, there is apposition of the articular surfaces. The PIP
and DIP joints are ankylosed.

1182

Clin Rheumatol (2010) 29:11811183

Fig. 1 Radiographic features of

joint destruction in the six participants RA1 and RA2: first and
second participants with rheumatoid arthritis, respectively;
PA1 and PA2: first and second
participants with psoriatic arthritis, respectively; TG1 and
TG2: first and second participants with tophaceous gout

In the second person with psoriatic arthritis [PA2], the

destruction is limited to the DIP joint and the pencil-in-cup
appearance is evident. In contrast to the preceding illustrations
of joint destruction, there appears to be a radiolucent interval
between the articular surfaces. The PIP and MCP joints are
uninvolved.
The DIP joint of the first person with tophaceous gout
[TG1] is infiltrated by a tophus. The tophus is evident as a
cloudy opacity within the joint space, one end of which is
demarcated by a calcified crescent. This is commonly
described as an over-hanging edge and represents
apposition of bone at the border of the tophus. The eroded
articular surfaces of the DIP are sclerotic and well-defined
and may be described as punched-out. The articular
surfaces are widely spaced by the intervening tophus to
maintain the original contours of the digit. The PIP and
MCP joints are uniformly narrowed.
Multiple tophi are seen to infiltrate the PIP joint of the
second person with tophaceous gout [TG2]. These tophi are
outlined by calcified tissues which give the appearance of
over-hanging edges. The erosions on the phalanges appear
punched-out and the intervening tophi maintain the
original length of the digit. The DIP and MCP joints are
uniformly narrowed.

Discussion
These radiographic observations support our hypothesis
that there are differences in the pathophysiological
processes that lead to joint destruction in RA and PA
compared with TG. The closely apposed articular surfaces
in the destroyed joints of the former conditions suggest that
the intervening substance is pliable. Inflamed synovial

tissue closely fits this description and is probably the source

of pro-inflammatory mediators that promote the bone
destruction.
In contrast, the articular surfaces of the destroyed
joints in tophaceous gout are widely spaced to maintain
the original contour of the digits. This suggests that the
intervening substance has a solid consistency. Gouty
tophi are excellent candidates to fulfil this requirement
and intra-articular extension of gouty tophi has previously been demonstrated with computed tomography [2].
Until recently, it was hypothesized that gouty tophi
mechanically eroded the bony surfaces they were in
contact with. However, recent investigations have demonstrated that mono-sodium urate crystals [MSU] alone do
not have an erosive effect on bone and are unlikely to lead
to joint destruction. Rather, phagocytosis of the MSU by
macrophages at the peripheries of the tophi activates
macrophages to create a signal that impairs osteoprotegerin expression by osteoblasts [3]. This leads to a relative
increased expression of receptor-activator nuclear factor
kappa [RANK] ligand by synoviocytes and maturation
of osteoclast precursors by binding of the latter ligand to
RANK. The mature osteoclasts resorb bone and initiate
joint destruction in tophaceous gout. The NALP-3 inflammasome complex that promotes maturation of prointerleukin-1 [IL-1] to IL-1 is proposed as one of the
signals stimulated within the macrophages that lead to
bone erosions.
Alternatively, tophi may erode bone by the direct effect
MSU has on the phenotype of osteoblasts [4]. In this
regard, 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 the
joint destruction associated with TG.

Clin Rheumatol (2010) 29:11811183

The observation that MSU can directly activate T-cells

independent of formal presentation by an antigen-presenting
cell is relevant [5]. Not only may the activated T-cells
initiate a cascade of events that lead to bone erosions, but
they also express co-stimulatory molecules that may
promote B-cell activation. It remains to be demonstrated
whether the in vitro finding of B-cell activation has
relevance to joint destruction in TG.

Conclusion
The conclusion we draw from the observations of this study is
that the pathophysiology of joint destruction is different in TG
from that of RA and PA. Common to all three joint destructive
processes is the presence of a significant inflammatory
component that disturbs the bone resorptionformation
balance in favour of bone loss. While the emphasis in the
treatment of tophaceous gout is currently focused on
eliminating the tophi, we are of the opinion that attenuation
of the inflammatory processes that have recently been
implicated in the pathogenesis of erosions in TG may be just
as important as in rheumatoid arthritis and psoriatic arthritis.
Despite the limited success reported with the use of
interleukin-1 receptor blockers in the treatment of bone
erosions in TG, research that focuses on the attenuation of
the inflammatory processes in gout is encouraged.

1183
Acknowledgements We are grateful to the Medical Research
Council and the National Research Foundation of South Africa for
their support (PB).
Disclosures None

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27

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