Letters to the Editor
and radiological evidence indicates improvement in the
articular topography.
The scores and time course for improvement displayed
in this study are comparable to those following i.a.
injection of corticosteroids [10]. This is in keeping with
the 3-fold elevation of synovial SAPL recorded in equine
synovial fluid following an i.a. injection of corticosteroid
commonly administered to degenerating joints [10].
Although administered ostensibly as a lubricant,
SAPL could have other physiological benefits, including
putative roles in the control of cartilage hydration [1]
and scavenging of oxygen free radicals implicated in
chondrocyte destruction [6 ]. Hence, exogenous SAPL
may act as a ‘disease-modifying’ drug in degenerative
joint disease that offers potential clinical benefits.
P. V1, R. T2, B. A. H2,3
1Rheumatology
Department,
Princess
Alexandra
Hospital, 2Department of Medicine, University of
Queensland, and 3Paediatric Respiratory Research
Centre, Mater Children’s Hospital, Brisbane, Australia
Accepted 19 April 1999
Correspondence to: B. A. Hills, Paediatric Respiratory
Research Centre, Mater Children’s Hospital, South
Brisbane, Queensland 4101, Australia.
1. Hills BA. Synovial surfactant and the hydrophobic articular
surface. J Rheumatol 1996;23:1323–5.
2. Hills BA, Monds MK. Enzymatic identification of the loadbearing boundary lubricant in the joint. Br J Rheumatol
1998;37:137–42.
3. Hills BA. Oligolamellar lubrication of joints by surface active
phospholipid. J Rheumatol 1989;16:82–91.
4. Hills BA. Oligolamellar nature of the articular surface.
J Rheumatol 1990;17:349–53.
5. Hills BA, Thomas K. Joint stiffness and ‘articular gelling’:
Inhibition of the fusion of articular surfaces by surfactant. Br
J Rheumatol 1998;37:532–8.
6. Hills BA, Monds MK. Deficiency of lubricating surfactant lining
the articular surfaces of replaced hips and knees. Br J Rheumatol
1998;37:143–7.
7. Robertson B. The European Multicentre trial of surfactant
replacement in neonatal respiratory distress syndrome. In:
Lachmann B, ed. Surfactant replacement therapy in neonatal and
adult respiratory distress syndrome. Berlin: Springer-Verlag, 1988.
8. Lequesne MG, Mery C, Samson M, Gerard P. Indexes of severity
for osteoarthritis of the hip and knee: Validation-value in comparison with other assessment tests. Scand J Rheumatol 1987;suppl.
65:85–9.
9. Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt
LW. Validation study of WOMAC: A health status instrument
for measuring clinically important patient relevant outcomes to
antirheumatic drug therapy in patients with osteoarthritis of the
hip or knee. J Rheumatol 1988;15:1833–40.
10. Hills BA, Ethell MT, Hodgson DR. Release of lubricating synovial
surfactant by intra-articular steroid. Br J Rheumatol 1998;
37:649–52.
Rheumatoid arthritis in beta-thalassaemia trait
S, The arthritis occurring in patients with betathalassaemia trait (b-thal trait) is still a controversial
issue. A mild, seronegative, HLA-B27-negative arthritis,
mainly affecting the wrists, has been reported in several
patients with b-thal trait [1, 2]. On the other hand,
1021
Gorriz et al. [3] did not find any significant difference
between b-thal trait patients and controls with regard
to the clinical features of musculoskeletal complaints,
and Arman et al. [4] did not find any exclusive form of
chronic arthritis in b-thal trait patients in spite of an
increased frequency of chronic arthralgia. So, the actual
nature of the b-thal trait-associated arthritis is still
unknown and there is no definite proof that it may be
regarded as a distinct clinical entity. A possible explanation is that arthritis in b-thal trait may represent a mild
form of seronegative rheumatoid arthritis (RA) since
RA may have a milder clinical course in people from
Mediterranean countries [5]. Furthermore, a higher
prevalence of both rheumatoid factor-positive and
rheumatoid factor-negative RA has been reported in
b-thal trait subjects from the endemic area of Ferrara,
Italy [6 ].
To ascertain whether patients with b-thal trait actually
had an increased risk of developing RA, we first undertook a retrospective analysis of 3836 clinical records of
in-patients consecutively admitted to the Department of
Internal Medicine of the University Hospital of Pavia,
Italy. Clinical records were evaluated for the presence
of b-thal trait as documented by Hb electrophoresis and
for a clinical diagnosis of RA. Among 3836 clinical
records examined, we found b-thal trait in 91 (2.37%)
patients. Among the 96 RA patients so recorded, we
found seven with b-thal trait (7.3%), i.e. a percentage
significantly higher than that found in non-RA patients
(84/3740 = 2.25%) (P <0.01). A subsequent, prospective study was carried out on Italian patients consecutively admitted to a rheumatology out-patient clinic
because of RA or other inflammatory rheumatic diseases. In this prospective study, we evaluated 374 RA
patients fulfilling the 1987 criteria of the American
College of Rheumatology. The data obtained in RA
were compared with those found in 278 consecutive
patients suffering from either connective tissue disease
(CTD) and vasculitis (198 patients) or seronegative
spondyloarthritis (SSpA) (80 patients). These patients
were chosen as a control group because they were
believed to have a geographical distribution similar to
that of patients referring to our clinic for RA and to
have at least a haemocytometric analysis performed at
the time of clinical examination. Patients with a mean
corpuscular volume of <76 fl were studied further for
iron status and Hb electrophoresis. Oral iron
supplementation was given before Hb electrophoretic
analysis in cases with iron deficiency. Patients were
considered to have b-thal trait if Hb A2 was >3.5% of
total Hb.
The percentage of b-thal trait was significantly higher
in RA patients (24/374 = 6.4%) compared to control
patients (6/278 = 2.15%) (P = 0.017). The figures
obtained for CTD and SSpA patients were similar to
those found by retrospective analysis of clinical records
in the overall in-patient population suffering from diseases other than RA.
To exclude the possibility that differences between
RA and other rheumatic diseases could be due to a
Letters to the Editor
1022
different geographical distribution of patients, we analysed RA and non-RA patients according to the place
of birth. Italy was divided into four areas with different
b-thal trait prevalence, i.e. north-west, north-east, south
and isles (Sicily and Sardinia). The geographical distribution was roughly similar for RA and other rheumatic
diseases; furthermore, an increased frequency of b-thal
trait in RA was apparent in all of the geographical
areas, while the frequency of b-thal trait in non-RA
patients was similar to that expected for the general
population ( Table 1). No differences were found
between b-thal and non-b-thal RA patients for sex, age,
disease duration and rheumatoid factor-positive cases
(67% in b-thal and 68% in non-b-thal ).
As stated, a higher prevalence of RA in b-thal trait
has already been reported [6 ], but we still do not know
the reason for this. It could be due to a genetically
determined susceptibility, even though we cannot
exclude the contribution of environmental factors which
may alter host susceptibility. Experimental and clinical
evidence support the pathogenic role of iron overload
in arthritis; although this possibility has not been fully
evaluated in b-thal trait patients, data from the literature
seem to exclude it [2]. Furthermore, none of our b-thal
trait patients had serum ferritin values over the normal
range nor had been previously transfused. As a matter
of fact, the association of b-thal trait with RA we found
in all the geographical areas of Italy seems to minimize
the relevance of environmental agents.
The association between HLA antigens and RA is
well established [7]. The relationship between HLA and
b-thal trait has been investigated only rarely. Betathalassaemia occurs worldwide, but it is most frequent
in populations of the malaria belt (Mediterranean,
Middle East, Asia and Africa). HLA-BW35 is significantly increased in the malarial environment [8] and
may offer an independent advantage in those populations in which malaria plays a pivotal selective role. A
recent survey of HLA segregation in 479 thalassaemic
Sardinian families failed to show any significant differences between the probands and the controls [9].
However, the study of more recently identified alleles
might open new perspectives in this field [10].
In conclusion, our data suggest that the subjects with
b-thal trait have a high prevalence of polyarthritis
resembling RA. The percentage of rheumatoid factorT 1. Prevalence of beta-thalassaemic trait in RA from different
Italian geographical areas as compared with patients with connective
tissue disease (CTD) and seronegative spondyloarthritis (SSpA). The
prevalence of beta-thalassaemic trait in the general population is ~1%
in the north-west, 2–5% in the north-east, 5–8% in the south and 10%
in the isles
CTD + SSpA
RA
North-west
North-east
South
Isles
Total
b-thal-trait
%
Total
b-thal trait
%
258
70
29
17
7
8
5
4
2.7
11.5
17.2
23.5
191
38
30
19
2
1
1
2
1.1
2.6
3.3
10.5
positive cases in b-thal patients was almost identical to
that found in non-b-thal RA; this supports the view
that b-thal may increase the risk of developing true RA.
The existence of a peculiar form of arthropathy associated with b-thal trait cannot be excluded by the present
study, even though it is possible that some of these cases
might be regarded as a particularly mild, seronegative
form of RA. A prospective, controlled study is in
progress to better evaluate the clinical, serological and
genetic characteristics of RA with b-thal trait as
compared with RA without b-thal trait, and to obtain
more information about whether some patients with
b-thal trait develop an arthropathy different from RA.
C. M, R. C, S. R, O. E
Servizio di Reumatologia, IRCCS Policlinico S. Matteo,
Pavia, Italy
Accepted 19 April 1999
Correspondence to: C. Montecucco, Servizio di
Reumatologia, IRCCS Policlinico S. Matteo, 27100
Pavia, Italy.
1. Schlumpf U, Gerber N, Bunzli H et al. Arthritiden bei thalassemia
minor. Schweiz Med Wochenschr 1977;107:1156–62.
2. Dorwart BB, Schumacher HR. Arthritis in beta-thalassemia trait:
clinical and pathological features. Ann Rheum Dis 1981;40:185–9.
3. Gorriz L, De Leon C, Herrero-Beaumont G. Arthritis in betathalassemia minor. Arthritis Rheum 1983;26:1292–3.
4. Arman MI, Butun B, Deseyen A, Bircan I, Guven A. Frequency
and features of rheumatic findings in thalassemia minor: a blind
controlled study. Br J Rheumatol 1992;31:197–9.
5. Drosos AA, Lanchbury JS, Panayi GS, Moutsopoulos HM.
Rheumatoid arthritis in Greek and British patients. Arthritis
Rheum 1992;35:745–8.
6. Marcolongo R, Trotta F, Scaramelli M. Beta-thalassemic trait
and rheumatoid arthritis. Lancet 1975;i:1141.
7. Wordsworth BP, Lanchbury JSS, Sakkas LI, Welsh KI, Panayi
GS, Bell JI. HLA-DR4 subtype frequencies in rheumatoid arthritis
indicate that DRB1 is the major susceptibility locus within the
HLA class II region. Proc Natl Acad Sci USA 1989;86:10049–53.
8. Piazza A, Belvedere MC, Bernoco D et al. HLA variation in four
Sardinian villages under differential selective pressure by malaria.
In: Histocompatibility testing 1972. Copenhagen: Mungsgaard,
1972:73–84.
9. Contu L, Arras M, Mulargia M et al. Study of HLA segregation
in 479 thalassemic families. Tissue Antigens 1992;39:58–67.
10. Cucca F, Frau F, Lampis R et al. HLADQB1*0305 and
DQB1*0304 alleles among Sardinians. Evolutionary and practical
implications for oligotyping. Hum Immunol 1994;40:143–9.
Th1-type cytokine mRNA in rheumatoid arthritis
mononuclear cells induced by streptococcal pyrogenic
exotoxin A
S, Subpopulations of helper T lymphocytes produce
different cytokines, such that Th1 cell products characteristically include IFN-c and IL-2, whereas Th2 cells
produce IL-4 among others (reviewed in [1, 2]). Studies
in rodent models suggest that autoimmune diseases can
be promoted by Th1 cytokines and downregulated by
Th2 cytokines. Although the validity of the Th1/Th2
paradigm is influenced by many factors, Th1 cytokines
are nevertheless linked with pathogenicity in RA [3]
and other autoimmune conditions.