Download Rheumatologists: inflammation doctors of the future!

RHEUMATOLOGY
Letters to the Editor
Rheumatology 2010;49:607–608
doi:10.1093/rheumatology/kep337
Advance Access publication 16 November 2009
Rheumatologists: inflammation doctors of the
future!
SIR, The eye has often been spoken of as the window to
medicine. The expertise of rheumatologists in the use of
immunosuppressant drugs, including biologic agents, in
inflammatory diseases, is invaluable to many specialties,
including ophthalmology. In an audit performed within the
Rheumatology Department at Norfolk and Norwich
University Hospital, we identified 19 patients with various
ophthalmological conditions who have been treated with
immunosuppressant drugs and monitored in specialist
rheumatology clinics (Table 1).
In the majority of cases (n ¼ 12, 63%), patients showed
an excellent response to treatment, with either improvement or stabilization of their eye disease. Nine (75%) of
these were patients with primary eye disease (Group I).
Response was measured with visual acuity tests
(objective measurement) and with documenting patients’
symptoms (subjective measurement). Less pain and redness in the eyes was suggestive of improved inflammation
levels. Sixty per cent of the patients (n ¼ 3) established on
biologic drugs responded well to treatment. Six (32%)
patients failed to respond to immunosuppressive therapy
(two with primary eye disease and four with secondary
eye disease) and one patient was lost to follow-up.
Below we describe two patients of special interest.
A patient with autoimmune retinopathy, an uncommon
ophthalmic disorder where autoantibodies are directed
at various retinal components causing progressive visual
loss, had been treated successfully with cyclophosphamide and rituximab. Eye monitoring in his case,
which included visual acuity tests, showed that the
cyclophosphamide–rituximab regimen, recommended by
the rheumatologists, was the only treatment that proved
to be effective in halting disease progression.
A second patient with orbital pseudotumour and ocular
surface inflammatory eye disease was treated successfully with a combination of steroids and MTX and was
able to discontinue treatment after 20 months.
Our audit has shown the importance of rheumatological
expertise in treating complex inflammatory eye disease
successfully. In Norwich, rheumatologists, with their
expertise in the use of biologic agents and other immunosuppressant drugs, play an important role in the management and treatment of patients with eye diseases,
and other inflammatory disease within other specialties.
As biological therapies evolve, the status of rheumatologists as experts in the management of ‘inflammation’
will become more established, requiring a broader cooperation with many specialties including ophthalmology.
TABLE 1 Ophthalmic diagnoses and immunosuppressant treatments
Group I—Patients with primary eye disease, n ¼ 12 (63%)
Diseases treated
DMARDs, n ¼ 11 (92%)
Retinal vasculitis, n ¼ 3
Scleritis, n ¼ 2
Uveitis, n ¼ 2
Mooren’s ulcers, n ¼ 2
Orbital pseudotumour
Autoimmune retinopathy
Ocular cicatricial pemphigoid
Chorioretinitis
Biologics, n ¼ 1 (8%)
MTX
AZA
Cyclosporin
Mycophenolate mofetil
Tacrolimus
Rituximab
Five patients (42%) also
received cyclophosphamide
Diseases treated
DMARDs, n ¼ 3 (43%)
Uveitis þ PsA (n ¼ 2)
Uveitis þ AS (n ¼ 2)
Uveitis þ RA
Scleritis þ RA
Vitreitis þ Behcet’s disease
Five patients (71%) diagnosed
with uveitis linked to either
Psoriatic Arthritis, RA or AS.
DMARDs þ Biologics, n ¼ 4 (57%)
MTX
Cyclosporin
AZA
Mycophenolate mofetil
LEF
MTX, SSZ þ infliximab
MTX þ infliximab
MTX þ etanercept, then
switched to infliximab
Mycophenolate mofetil,
cyclophosphamideþ
adalimumab
Total number of patients on biologic drugs, n ¼ 5 (26%)
Primary eye disease, n ¼ 1(20%) (rituximab)
Secondary eye disease, n ¼ 4 (80%) (anti-TNF)
! The Author 2009. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: [email protected]
LETTERS
Group II—Patients with secondary eye disease, n ¼ 7 (37%)
Letters to the Editor
Our experience has shown that establishment of joint
rheumatology–ophthalmology or other ‘. . . ology’ clinics
is an efficient way of providing early treatment of uncommon multisystem inflammatory conditions. In addition,
they utilize the expertise of rheumatologists in the treatment of inflammation and ophthalmologists in the diagnosis and monitoring of the response to treatment. Not only
is the eye the window to medicine, but it may also be a
window to the future evolution of rheumatology as a
specialty.
Rheumatology key message
.
As ‘inflammation’ therapies evolve, rheumatologists
are in pole position to expand their therapeutic
expertise into many other specialties.
transfers from other rheumatologists were excluded.
Recorded family history (FH) was noted, specifically
whether there was a first- or second-degree relative with
(i) RA or (ii) ‘arthritis’ (patient offering no precise diagnosis). Patient’s ‘final’ diagnosis (FH) was also recorded. The
study was approved by the local ethics committee (South
Glasgow and Clyde REC).
Fisher’s exact test was performed for relationships
between FH and diagnosis of RA, whereas sensitivity,
specificity and positive predictive value (PPV) estimates
were calculated as if using FH as a ‘test’ for the presence
of RA using the standard formulae:
. sensitivity (in %) ¼ true positives per total affected
patients tested.
. specificity (in %) ¼ true negatives per total unaffected
patients tested.
Disclosure statement: The authors have declared no
conflicts of interest.
Elena Nikiphorou1, Nicola Kerrigan1, Karen Mills1
and Peter Merry1
1
Department of Rheumatology, Norfolk and Norwich
University Hospital, Norwich, UK
Accepted 21 September 2009
Correspondence to: Elena Nikiphorou, Department of
Rheumatology, Norfolk and Norwich University Hospital,
Colney Lane, Norwich NR4 7UY, UK.
E-mail: [email protected]
Rheumatology 2009;49:608–609
doi:10.1093/rheumatology/kep386
Advance Access publication 4 December 2009
Family history of rheumatoid arthritis—a
non-predictor of inflammatory disease?
SIR, An inherited component of RA has been assumed by
everyone—doctors and patients alike—for many years.
Early family studies gave uncertain results [1, 2], and
hard evidence was sparse until 1986 when Aho et al. [3]
showed increased concordance in monozygotic twins vs
dizygotic (12.3 vs 3.5%, respectively)—a result echoed
by Silman et al. [4] in 1993 (15.4 vs 3.6%, respectively).
These figures translate as a ‘heritability’ of 60% [5] and
a quadrupled risk in siblings [6].
Studies of mechanisms focused on HLA-DR4 as early
as 1978 [7], and specific haplotypes have since been
singled out, many including the ‘shared epitope’ [8].
These findings may implicate antigen presentation to
CD4þ cells in the pathogenesis of RA. But what does all
this mean in the clinical setting? If my next patient says
her mother had RA, does that make it more likely my
patient has?
In an attempt to find out, a retrospective case sheet
study was performed on 1 year of General Practitioner
(GP) and hospital practitioners’ referrals to a single rheumatologist. Ward referrals, urgent side-room cases and
608
. PPV (in %) ¼ true positives per all positive tests.
(Epimax Table calculator; http://www.healthstrategy
.com)
One hundred and ninety-four patients’ case notes were
admissible. One hundred and eighty-eight patients had a
‘diagnosis’ recorded (non-specific complaints 38, RA 29,
PsA 5, AS 3, gout 7, CTD 6, PMR 2, vitamin D deficiency
9, hypermobility 17, OA 43 and others/not sure 35).
One hundred and twelve patients (60%) had FH recorded.
Further analysis focused on the 108 patients with both
FH (RA 18, ‘arthritis’ 12 and neither 78) and diagnosis
(RA 18 and ‘not RA’ 90) (Table 1).
Fisher’s exact test was not significant, showing only a
trend towards an inverse association between FH of RA
and the actual diagnosis of RA (P ¼ 0.194).
If we consider FH of RA as a ‘test’ for the presence of
RA, then its parameters are: sensitivity (1:18) 6% (95% CI
0.3%, 26%); specificity (73:90) 81% (95% CI 80%, 85%);
and PPV (1:18) 6% (95% CI 0.3%, 26%). If we use FH of
RA or ‘arthritis’, the parameters are: sensitivity (3:18) 17%
(95% CI 4.5%, 40%); specificity (63:90) 70% (95% CI
68%, 75%); and PPV (3:30) 10% (95% CI 2.7%, 24%).
If FH of RA is used as a predictor of not having RA
(‘not RA’), its parameters are: sensitivity (17:90) 19%
(95% CI 15%, 20%); specificity (17:18) 94% (95% CI
74%, 99.7%); and PPV (17:18) 94% (95% CI 74%,
99.7%). If we use FH of RA or ‘arthritis’: sensitivity
(27:90) 30% (95% CI 25%, 32%); specificity (15:18) 83%
TABLE 1 Family history vs true diagnosis
True diagnosis ?RA
Yes
Family history RA
Yes
1
No
17
Family history ‘arthritis’
Yes
3
No
15
No
17
73
27
63
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