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Age and Ageing 2007; 36: 104–106
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Published electronically 6 December 2006
Adult-onset Still’s disease in a patient
over 80 years old successfully treated with
low-dose methotrexate therapy
MIWA KURASAWA1 , KAZUHIKO KOTANI2 , GOTARO KURASAWA1 , KOUSUKE SHIDA3 , SHIGEKI YAMADA4,
TOSHIHIKO TAGO5
1 Department
of Internal Medicine, Nishiagatsuma Welfare Hospital, Naganohara, Japan
of Health Administration and Promotion, Faculty of Medicine, Tottori University, Yonago, Japan
3
Department of Orthopaedics, Nishiagatsuma Welfare Hospital, Naganohara, Japan
4 Department of Pathology, Omiya Medical Centre, Jichi Medical University, Omiya, Japan
5 Department of Surgery, Nishiagatsuma Welfare Hospital, Naganohara, Japan
2 Division
Address correspondence to: M. Kurasawa. Tel: (+81)-279-83-7111 Fax: (+81)-279-83-8032. Email: [email protected]
Abstract
We report on an 83-year-old Japanese woman with adult-onset Still’s disease (AOSD), with marked hypercytokinemia
(serum levels of ferritin (Fer) and interleukin (IL)-18 were markedly high). On seeing older patients with fever of unknown
origin (FUO), particularly Asians, AOSD should be considered. Reduced doses of oral prednisolone following intravenous
methylprednisolone (mPSL) therapy caused a flare-up of AOSD and led to Pneumocystis carinii ( jeroveci) pneumonia. Low-dose
methotrexate (MTX) therapy was administered as a steroid-sparing agent with good response. Our case suggests that in very
elderly people, as in younger patients, MTX is useful for controlling AOSD with marked hypercytokinemia, and avoiding
corticosteroid-induced adverse effects.
Keywords: adult-onset Still’s disease, super-old patients, Japanese, hypercytokinaemia, pulse methylprednisolone, low-dose methotrexate,
elderly
Introduction
Adult-onset Still’s disease (AOSD) is rare and has a bimodal
age distribution in all ethnic groups with peaks at 15–25 and
36–46 years of age [1]. Onset in older people is very rare,
and it has been described only occasionally in Japan, Europe
and the USA [2–9]. Patients of Asian origin tend to be older
for reasons that are not clear, and more than half of the
reported cases older than 70 are Japanese [2, 3, 6–8]. Even in
Japan, however, very few cases of initial onset of AOSD in
104
old patients have been reported [6]. We describe an AOSD
patient aged over 80 years with marked hypercytokinaemia
(HCK) and was administered methylprednisolone (mPSL)
pulse therapy with methotrexate (MTX), who we believe is
the oldest reported case treated with MTX.
Case presentation
An 83-year-old Japanese female complaining of appetite
loss, sore throat, quotidian fever (max 39◦ C, peak in the
AOSD and low-dose MTX therapy
late afternoon), and polyarthralgia for several days, was
admitted. She had an evanescent maculopapular rash on her
right lower leg, which disappeared as the fever abated. The
white blood cell (WBC) count was elevated to 14,300/ µl
(max 43,800). The erythrocyte sedimentation rate (ESR)
and C-reactive protein (CRP) were 22 mm/h (max 48) and
10.5 mg/dl (max 18.7), respectively. The liver function test
scores were elevated: AST = 672 IU/l, ALT = 368 IU/l, and
LDH = 911 mg/dl. The serum ferritin (Fer) and interleukin
(IL)-18 were 10,340 ng/ml and 125,000 pg/ml, respectively.
Serum was negative for anti-nuclear antibodies/rheumatoid
factor, and no lymphadenopathy or hepatosplenomegaly
was seen. Images of the Joints were normal. Blood,
sputum and urine cultures grew no bacteria. There was no
serological evidence of infection with either cytomegalovirus
or Epstein–Barr virus. Therefore, we diagnosed AOSD
according to the Yamaguchi criteria [10]. Following therapy
with acetaminophen and loxoprofen, prednisolone (PSL)
therapy (20 mg/day) was started, with a poor response.
High-dose oral PSL (60 mg/day) plus intravenous mPSL
(500 mg/day) pulse therapy improved her clinical symptoms
and laboratory findings slightly, particularly, the values
of the liver function tests. Nine weeks after admission,
when the PSL was tapered to 30 mg/day, Pneumocystis carinii
(jeroveci) pneumonia developed, for which trimethoprimsulfamethoxazole therapy was effective. Her AOSD flaredup with an increased ferritin level (1,397 ng/ml) during the
slow tapering of PSL. We used oral MTX in a single weekly
dose of 6 mg. (In Japan, MTX is available as a 2-mg tablet,
and 6 mg weekly can be given as an initial dosage.) During
the MTX therapy, no other additional drugs were used. After
2 months, all signs and symptoms had improved and the
blood inflammation indexes, such as the WBC, ESR, CRP,
Fer and IL-18 had normalised.
Discussion
AOSD in very old people is difficult to diagnose unless
suspected, because it is generally considered a disorder
of youth. However, when older patients with a fever of
unknown origin (FUO) have a rash, AOSD should be
suspected, because a rash, as seen in our case, is a valuable
diagnostic sign [10]. Because the rash in AOSD often appears
over the trunk or extremities, the area where the rash
appeared in our case was somewhat atypical, but we still
suspected AOSD on the basis of the features of the rash,
such as its disappearance with the reduction in fever [10].
This is the first case of a patient aged over 80 years
with AOSD receiving MTX therapy. Five additional cases in
patients over 80 have been reported: two were treated with
oral PSL plus mPSL therapy [6, 7] and one each with oral PSL
only [3], non-steroidal anti-inflammatory drugs (NSAIDs)
[8] and intravenous immunoglobulin plus NSAIDs [9].
Although MTX is not usually used for the super-old, we
chose it for three reasons. First, MTX is more popular
with Japanese physicians than other immunomodulating
drugs (e.g. cyclophosphamide, azathioprine, cyclosporine,
intravenous immunoglobulin, anakinra, or infliximab). In
particular, MTX therapy is established in rheumatoid
disorders, which have a pathophysiology similar to that
of AOSD. Second, although low-dose MTX can lead
to opportunistic infections, as can PSL, we wanted the
corticosteroid-sparing effects of MTX [11], because our case
recurred at a reduced PSL and had the adverse effects of
long-term PSL, such as immunosuppression (i.e. P. carinii
pneumonia). Third, although Fer is an evident marker of the
disease activity [12], as in our case, it was the marked HCK
evident as high IL-18 levels that attracted our attention rather
than hyperferritinaemia. It has been reported that the mean
serum IL-18 in AOSD is 1243.4 pg/dl [13], but our patient
had very high levels. We postulate that the remarkable HCK
reflected the disease activity better than routine inflammatory
markers, such as ESR and CRP. The good outcome with
MTX in our case suggests that marked HCK is a sign of PSL
resistance, which should lead physicians to switch to MTX.
In the future, the role of HCK in AOSD disease activity and
therapy should be studied.
In summary, we report a super-old AOSD patient with
HCK treated with MTX. AOSD should not be overlooked
in older patients with FUO, particularly Asians. In older
people, MTX might be useful for controlling HCK and for
avoiding relapse and corticosteroid-induced adverse effects.
Key points
•
•
•
AOSD could appear even in patients over 80 years with
FUO.
Our AOSD patient (83 years) was successfully treated not
with corticosteroid but with methotrexate (MTX). This
case is perhaps the oldest patient treated with MTX, and
the resistence of corticosteroid may be due to marked
hypercytokinaemia (HCK).
In patients over 80 years with AOSD and HCK, MTX
might be useful for controlling the disease status and
avoiding relapse of the disease and corticosteroid-induced
adverse effects.
Conflicts of interest
None
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Received 30 April 2006; accepted in revised form 1 September
2006