Treatment (!{ psoriatic arthritis with cyclosporin A Short therapeutical report 
1reatment oj psoriatic arthritis 
with cycwsporinA 
I. Prelog, I. Krajnc and K. Lukanovič 
ABSTRACT 
The purpose of this study was to determine the efficacy and toxicity of cyclosporin A (CsA) in treatment 
of patients affected with psoriatic arthritis (PsA). 
Methods: This study includes 11 patients with PsA. Clinical and functional parameters are assessed: 
Ritchie lndex, duration of the morning stiffness of joints in minutes, and pain. Laboratory values in serum 
were checked: SR, CRP, urea, creatinin, cholesterol, trigliceride, electrolyte, and liver enzymes. 
Measurements of blood pressure were taken monthly. 
Results: With a therapeutic dose of CsA 3 mg/kg/daily we noticed an improvement of clinical parameters, 
but not of laboratory values. 
Conclusion: The investigation showed that CsA in the dosis of 3 mg/kg/daily was efficient and sate in 
the treatment of PsA. 
Introduction 
Psoriatic arthritis (PsA, psoriasis arthropathica) is 
characterizecl by a negative rheumatoicl factor in bloocl 
serum and arthritic manifestations. For a long time it 
was considered amile! form of arthritis. During the last 
years, however, this opinion has changed. In 1978, 
Gladman and coworkers (1) reported 40% out of 220 
patients with PsA to be suffering from deforming and 
erosive arthritis, 17% of those with 5 or more affected 
joints. Arthritic manifestations can be subclivided into 
110 
five subgroups: l. Predominantly peripheral mono or 
asymmetrical oligoarthritis (sausage-like finger), often 
overlooked; 2. Predominantly clistal interphalangeal 
arthritis; 3. Preclominantly symmetrical rheumatoid like 
polyarthritis: 4. Arthritis mutilans involving fingers ancl 
toes. 5. Predominantly spondylitis ancl/or sacroileitis (2). 
In mile! cases PsA can successfully be treatecl with 
nonsteroid anti-inflammato1y dmgs (NSAR) ancl local 
corticosteroid injections, whereas the so-callecl second 
line of medicines are intended for NSAR refract01y and 
progressively destructive forms of PsA (3). As a rule, 
Acta Dermatoven APA Vol 9, 2000, No 3 
Short therapeutical report 
patients with minimal skin lesions and an active invol-
vement of joints react positively to treatment using anti-
malarials, gole! salts, D penicillinamin and sulfosalazine 
( 4, 5). In a generalizecl form of psoriasis, which is accom-
panied by severe affection of joints, it is logical to use 
drugs efficacious in both manifestations of this disease. 
These are methotrexate, retinoids, azathioprine, sulfa-
salazin and cyclosporin A. 
Patients and methods 
This st:udy included 11 patient, with active peripheral 
PsA who were unsuccessfully treated with nonsteroid 
antirheumatics and/or corticosteroicls. 
We have registered the principal clata of each patient. 
Over a period of 6 months they were treatecl with CsA 
in closes of 3mg/kg/ claily. At the same tirne, 4 patients 
were also receiving lower doses of corticosteroids. 
At the beginning and at the ene.! of this study clinical 
and functional parameters were assessed: Ritchie Index, 
duration of morning stiffness of joints in minutes, and 
pain. 
Measurements of bloocl pressure were taken mont-
hly ancl laboratory values in sera were checked: ESR, 
CRP, urea, creatinine, cholesterol, triglyceride , electro-
lyte, and !iver enzymes. At the beginning and at the 
ene! of this study we have also measured concentration 
of cyclosporin in serum with fluorescence polarization 
immuno assay (ABBOTT) methoc.l. 
Results 
Out of 11 patients with PsA includecl in this study 
there were 6 females and 5 males of an average age of 
51 (34-74). 
The results ofthis study, assessed on the basis ofT-
student test, revealed a statistically significant lowering 
ofRithchie Index (p < 0.05), of morning stiffness ancl of 
pain (p < 0.05), but there was no significant lowering 
of e1ythrocyte sedimentation rate (p > 0.05) and CRP (p 
> 0.05). 
One of our patients was subsequently dropped from 
the test list because of increasecl bloocl pressure. 
Discussion 
PsA is a disease, which includes inflammation of 
joints, involving about 5% of patients affected by 
psoriasis. The disease is characterizecl by a negative 
rheumatoicl factor. In approximately 50% of patients 
who are HLA B27 positive there also clevelops sponclylo-
arthropathy, so that PsA is includecl in the group of 
seronegative spondyloarthropathies ( 6). 
Treatment of'psoriatic arthritis with cyclosporin A 
In the etiopathogenesis of the disease the influence 
of the immune system has been praven. Immuno-
histochemical changes of synovial membranes in PsA 
were describecl. The infiltration of activatecl CD4+ T 
lymphocytes ancl macrophages is clominating in syno-
vial membranes as well as in the skin. The mononuclear 
inflammato1y infiltration in PsA is smaller than in rheu-
matoicl arthritis (RA), whereas the pathogenetic mecha-
nism causing the inflammation of synovial membranes 
is probably equal (7). 
Moreover, there are also clescriptions of numerous 
irregularities in the subpopulations of circulating lym-
phocytes during the active pl1ase of the joint disease. 
In the first place, the percentages of CD8+ T and activa-
ted CD 3+ T lymphocytes, as well as of B lymphocytes 
and killer cells (8) are lowered, while the leve! of the 
serum soluble interleukin 2 receptor (S IL-2R) ancl of 
IL-6 is increasecl (9). 
Certain stuclies clealt with the levels of cytokines ancl 
their receptors in the synovial fluid of patients with PsA. 
They establishecl an increasecl leve! of IL-1, IL-6, IL-8, 
ancl of the tumor necrosis factor receptor (TNFr) (3). 
The most important immunosuppressive effect CsA 
is the blockage of the early stage ofT lymphocyte activa-
tion, i.e. of the procluction of cytokines, inclucling IL-2, 
IL-4, ancl interferon gamma (3). In adclition, CsA acts as 
a clirect anti-inflammato1y agent by inhibiting the release 
of inflammatory mecliators from tissue mastocytes, 
basophil substances and polymorphonuclear cells (3). 
There are only few stuclies assessing effects in vivo 
on seroimmunological parameters in patients with PsA. 
After a 6-month treatn1ent they describecl a significant 
lowering of the IL-6 leve! accompanied by significant 
clecrease of joint ailments and of the CRP leve!. (2) There 
occurred also a recluction of s IL-2R parallel with a 
reclucecl number of swollen and painful joints (3). 
Olivieri ancl coworkers (3) have reviewecl 16 stuclies 
clealing with the treatment of 170 PsA patients using 
CsA. Analyses confirmecl the safety of such treatment. 
Only 16 patients (9.4%) stoppecl taking this medicine 
clue to sicle effects: nephrotoxicity 10, uncontrollecl 
hypertension 4, gastrointestinal disturbances 2. The 
authors concluclecl that CsA was successful in treatment 
of psoriasis, of both skin lesions ancl joint symptoms 
(3). 
Sporaclo ancl coworkers (10) reportecl similar 
positive effects of CsA. The main reason for breaking 
offthe treatmentwas hypertension (10). In 1989, Gupta 
and coworkers (11) notecl a short period of successful 
activity of CsA in 6 patients who hacl been treatecl for 8 
weeks with closes of 6 mg/kg/claily. A few clays after 
the ene! of the therapy skin efflorescences reappearecl, 
ancl after two weeks joint symptoms emerged again. 
Mazzanti ancl coworkers (12) treatecl 8 patients with 
a combination of CsA (5 mg/kg/ claily) ancl methotrexate 
(10-15 mg/weekly). After a 6-month treatment they 
Acta Dermatoven APA Vol 9, 2000, No 3 -------------------111 
Treatment ri(psoriatic arthritis with cyclosporin A Short therapeutical report 
noted a regression of skin and joint symptoms (12), 
except in one case. 
The results of our study have also revealec\ the effi-
cacy anc\ tolerance of CsA in the treatment of PsA. We 
establishec\ an improvement of the clinical parameters 
of arthritis, measured by Ritchie Index, morning stiff-
ness, anc\ pain in the joints. However, we c\ic\ not notice 
any c\ecrease in CRP and in the sec\imentation rate of 
erythrocytes. 
In ali studies published so far only the effect of CsA 
on the peripheral arthritis has been observed. Likewise, 
there are few studies evaluating longer lasting effects 
of CsA on the radiologically verified evolution of the 
disease (2) . One of such studies is a 2-year study by 
Macchioni and coworkers (13) who have established 
that CsA controlled the progression of damages intlicted 
on peripheral joints in 60% of patients with PsA. This 
presupposes that the normal leve! of the s IL-2R after a 
six-month therapy is a reason for assuming a good prog-
nosis of the disease, while SR and CRP Jack any progno-
stic value (1). 
During treatment attention must be paid to possible 
toxic sicle effects of the drng, inclucling a regular control 
of the blood count, liver and renal tests , cholesterol, 
triglycericle, ancl electrolyte. Of utmost importance are 
regular measurements of bloocl pressure. Medica! 
personnel must also be on lookout for other possible 
sicle effects. 
REFERENCE§ 
AUTHORS' 
ADDRESSES 
112 
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Ida Prelog MD, dermatologist, Dermatological Department, University 
Hospital Maribor, Ljubljanska 5, 2000 Maribor, Slovenia 
Ivan !{rajne MD, PhD, projessor, Clinical Department oj Interna Z Medicine, 
RheumatologicalDepartment, University HospitalMaribor, Ljubljanska 5, 
2000 Maribor, Slovenia 
!{amila Lukanovič MD, Novartis, Subsidiary Slovenia, 1000 Ljubljana, 
Slovenia 
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