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Total lymphoid irradiation for psoriatic arthritiscase report.

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Total lymphoid irradiation for psoriatic arthritis: case
To the Editor:
Total lymphoid irradiation has been used with encouraging results in the treatment of severe rheumatoid
arthritis (Kotzin BL, Strober S, Engleman EG, Calin A ,
Hoppe RT, Kansas GS, Terrell CP, Kaplan HS: Treatment
of intractable rheumatoid arthritis with total lymphoid irradiation. N Engl J Med 305:969-976, 1981). We have recently
used this treatment for a patient with psoriatic arthritis
unresponsive to conventional management, in whom the
development of hepatitis precluded the use of other cytotoxic agents.
The patient, a 31-year-old white man, first reported
to our clinic in June 1981 with a 9-year history of monarthritis of the right knee. Other than active synovitis at that joint
and a cushingoid appearance due to 9 years of continuous
steroid intake, there were no relevant findings. His steroid
dosage at the time was 1.5 mg dexamethasonelday. Rheumatoid factor, antinuclear antibodies, and HLA-B27 were all
negative. Complete blood count findings were normal, erythrocyte sedimentation rate (ESR) was 16 mm/hour, uric acid
was 4.2 mg %, and urinalysis results were normal. Radiographs of the knee showed a mildly diminished joint space
with severe periarticular osteoporosis. Synovectorny and
gradual tapering of the steroid were advised. A month later
he had the synovectomy, which revealed a nonspecific
synovitis with no lymphoid follicles.
One week after surgery, while using prednisolone 5
mg/day, he developed arthritis in the unoperated knee. This
was followed in a few days by severe arthritis of both elbows
and the neck. Meanwhile, extensive pustular psoriasis of the
nail beds emerged at the hands and feet. He became bedbound because of the severity of his arthritis. Indornethacin
150 mglday and hydroxychloroquine 400 mg/day were initiated.
Three weeks after the synovectomy he passed a
calcium phosphate stone. Intravenous pyelogram showed
normal sized, shaped, and functioning kidneys; however, he
had bilateral sacroiliitis. Six weeks after the synovectomy,
jaundice developed. Enzyme changes were consistent with
viral hepatitis. Auagand Auab were negative. All medication
was stopped except for prednisolone, which was increased
to 20 mg/day for the persistently severe arthritis. His condition worsened with this regimen, with the arthritis spreading
to his shoulders and hips.
Although he was having an uneventful recovery from
hepatitis, we felt that he should not receive nonsteroidal
antiinflammatory agents or hydroxychloroquine. It was also
Arthritis and Rheumatism, Vol. 26, No. 8 (August 1983)
our feeling that an arthritis not controlled by 20 mg of
prednisolone/day would very likely not respond to these
measures. Oral or parenteral cytotoxic agents were also not
deemed appropriate. Thus he was offered total lymphoid
irradiation for arthritis control.
Two months after the onset of his hepatitis, when
serum bilirubin, serum glutamic oxaloacetic transaminase
(SCOT), serum pyruvic oxaloacetic transaminase (SGPT),
and alkaline phosphatase levels were normal, informed
consent was obtained and irradiation was first administered
to lymphoid tissues below the diaphragm. A 10-meV linear
accelerator was used. A midline dose of 200 rads was
administered at each session for 10 sessions over 14 days for
a total of 2.000 rads. This was immediately followed by
irradiation of the “mantle field” (Kaplan HS: Hodgkin’s
Disease. Second edition. Cambridge, Massachusetts, Harvard University Press, 1980, pp 366-441). A midline dose of
150 rads for 13 sessions over 20 days, for a total of 1,950
rads, was given. His arthritis began to improve toward the
end of the “mantle” irradiation. One month after the treatment he was able to ambulate freely.
His ESR was 70 mm/hour immediately before the
treatment. Hematocrit at that time was 32% and white blood
cell count (WBC) was 6,200 with 28% lymphocytes. The
lowest lymphocyte count was 720/mm3 (WBC 4,000/mm3
with 18% lymphocytes) during the treatment. ESR began to
rise following the radiation, as previously noted by Kaplan.
Twenty-five days after the treatment, the ESR was 110
m d h o u r while his clinical condition was rapidly improving.
Sixty days after completion of the treatment his ESR was 90
m d h o u r , with hematocrit at 38% and WBC at 5,600/mm3
(22% lymphocytes). There was no elevation of SCOT,
SGPT, or alkaline phosphatase during or after the therapy.
The 20 mg of prednisolone was continued through the
treatment and was very slowly tapered thereafter. At the
fifth month after the therapy, with the patient having minimal synovitis at the unoperated knee, hydroxychloroquine
(400 mg/day) was restarted. Fourteen months after radiotherapy he is doing well, fully ambulatory with no active
synovitis, receiving hydroxychloroquine 400 mg/day and
prednisolone 8.75 mg/day. His current ESR is 30 mmlhour,
hematocrit 42%, and WBC 4,200 with 25% lymphocytes.
Psoriatic nail changes are improved, but the nails are still
Very special circumstances prompted us to utilize
total lymphoid irradiation in this patient. The favorable
results warrant consideration of this treatment modality in
severe psoriatic arthritis.
Hasan Yazici, MD
Cerrahpaja Medical Faculty
Nijad Bilge, MD
Munir Kinay, MD
Istunbid Medical Faculty
Istanbul, Turkey
HLA-DR antigen frequency (%) in seropositive and seronegative rheumatoid arthritis
Table 1.
Subjects, no.
Control, 93
arthritis, 50
factor +, 27
factor 23
* Pcorr < 0.05.
t Pcorr < 0.001.
< 0.01.
HLA antigens and rheumatoid arthritis
$ Pcorr
To the Editor:
We would Like to contribute some information about
the controversy regarding the association of HLA-DR4
antigen and 19s rheumatoid factor (RF) in rheumatoid
arthritis (RA) (1-3). Fifty-five RA patients living in Rome,
Italy were typed for HLA-A, B, and C antigens; 50 of these
were also typed for HLA-DR antigens (DRI-DRw8). Diagnosis conformed to American Rheumatism Association criteria (4). We also analyzed the following parameters: sex,
age of onset, anatomic stage (erosions), and the presence of
subcutaneous nodules.
Fourteen of the 55 patients were males and 41 were
females; 30 were seropositive and 25 were seronegative. The
patients were also classified into two groups: those without
bone lesions (1st stage) and those with bone lesions (2nd,
3rd, 4th stage) according to radiologic reports. Four hundred
eighty-three random donors were typed for the HLA-A, B,
and C antigens and 93 for HLA-DR as a control group.
Typing sera were selected from the 8th International Histocompatibility Workshop.
No association was found between HLA-A, B, C
antigens and RA. Our results (Table I ) confirm the strong
association between HLA-DR4 antigen and RA (P corr =
0.00024, relative risk = 6.51). In contrast with previous
reports (2), we found no correlation between DR4 and
rheumatoid factor, even when only patients with high titers
were considered. The difference may be due to heterogeneity of our RA patients versus those reported in the literature.
Our group of patients, originally from Rome, can be considered a representative sample of the Italian population in
relation to the distribution of the HLA antigens. No relation
was shown between DR4 and articular erosions, which is not
surprising since erosions are linked with rheumatoid factor.
No preferential genotypic combination was found among DR
antigens; our sample is on Hardy-Weinberg equilibrium.
Some antigens are under-represented-for
instance, DR2
was significantly diminished in the patient group as a whole
(Pcorr = 0.028). The meaning of this decrease is not known.
The rarity of DR2 is not unique to RA but is also rare in other
conditions, such as celiac disease (5). It has been suggested
that the DR antigen has a protective role (6), but we cannot
exclude or confirm a compensatory decrease of this allele
relative to the increased frequency of DR4 in the available
sample. On the other hand, we cannot explain why an
increase of DR4 frequency is only associated with a corresponding decrease of DR2 frequency, without a decrease
affecting any of the other DR alleles.
The family study supports our data. Two of the 10
families tested have 2 affected siblings. In Family A (Figure
I ) we find 2 HLA identical sisters who are both DR4
positive, 1 with seropositive and the other with seronegative
RA. Family B (Figure 2) presents 2 affected sisters, both
DR4 positive but with different HLA haplotypes; 1 sister
was seropositive and the other had a seronegative form of
arthritis. The failure to study the parents does not exclude a
crossing over in the family.
P. Lulli
S. Cappellacci
M. Morellini
Cattedra di Genetica Medica
Universitd degli Studi di Roma
M. Galeazzi
L. Schiavetti
T. Tuzi
Servizio di Reumatologia
Ospedale S . Camillo di Roma
Roma, Italy
Figure 1. Family A genotypes: a = Aw23,C-,Bw49,Bw4,DR5; b =
d = A-,C-,
~ ,All,C-,Bw49,Bw4,DR4;
Bw22,Bw6,DR2; e = AI,Cw3,Bw22,Bw6,DR-. Circles indicate
members with rheumatoid arthritis: + = seropositive; - =
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report, tota, arthritiscase, lymphoid, psoriatic, irradiation
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