Case Report: Adult-onset Still’s Disease

Andi Raga Ginting

, R. M. Suryo Anggoro

, Anna Ariane

, Bambang Setyohadi

Rheumatology Division, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Rumah Sakit Umum

Pusat Nasional Cipto Mangunkusumo, Jakarta, Indonesia

Keyword: Adult-Onset Still’s Disease, Polyarthritis, Fever, Hyperferritinemia, Methotrexate.

Abstract: Adult-onset Still’s disease (AOSD) is an uncommon systemic inflammatory disease of unknown etiology

and pathogenesis, characterized by high spiking fever, arthralgia or arthritis, skin rash and other systemic

presentation. AOSD, one of the most important causes of fever of unknown origin, is diagnosed after ruling

out infection, malignancy, and rheumatologic diseases. This report described a 19-year-old male who

presented with, arthritis, fever, sore throat, evanescent rash, raised liver enzyme and hyperferritinemia. He

was diagnosed to have AOSD based on Yamaguchi criteria after the exclusion of other potential diagnoses.

The patient responded to combined methylprednisolone and methotrexate.

1 INTRODUCTION

Adult-onset Still’s disease (AOSD) is a chronic

systemic inflammatory disorder of unknown

etiology, typically characterized by a clinical triad

(daily spiking high fevers, evanescent rash, and

arthritis) and a biological triad (hyperferitinemia,

hyperleukocytosis with neutrophilia and abnormal

liver function test (Bywaters, 1971; Magadur-joly et

al., 1995).

AOSD is a rare disorder and has a bimodal age

distribution in all ethnic groups with peaks at 15-25

and 36-46 years of age and equal distribution

between sexes (Efthimiou, Paik and Bielory, 2006;

Chakr et al., 2007).

There are no specific diagnostic test for AOSD.

The diagnosis of AOSD remains one of exclusion;

with typical clinical features, laboratory

abnormalities and absence of other explanations.

Several sets of different classification criteria have

been proposed for AOSD. Among them Yamaguchi

criteria are the most widely used (Bywaters, 1971).

There is no cure for AOSD; however,

treatment may offer symptom relief and help to

prevent complication. Treatment options include

non-steroid anti-inflammatory drugs (NSAIDs) and

aspirin, glucocorticoids, and immunomodulating

drugs. Most patients require steroids at some point in

the course of their AOSD. As it progresses without

proper treatment, AOSD may lead to chronic

arthritis and other complications. We describe the

typical presentations of a patient with AOSD.

2 CASE REPORT

We present a case of 19-year-old male

patient, admitted in our hospital with multiple joint

pains associated with unresolved fever for two

weeks. The patient had also having fever from

afternoon until early evening associated with sore

throat for the past two weeks. This was preceded by

an evanescent, non-pruritic malar rash distributed on

upper chest. Patient had been suffering from joint

pains involving the shoulder, knee, hip wrist and

small joint of the hands , pain was worsening with

movement until he could hardly ambulate on his

own three days before admission. There were no

early morning stiffness, ocular symptoms, orogenital

ulcers, gastrointestinal symptoms, urinary

symptoms, contact to infected person or major

systemic symptoms.

Examination revealed well built, oriented

young male with fever of 39

C. There was no

lymphadenopathy or splenomegaly. He had

synovitis of wrists, elbows, shoulders, ankles, knees

and small joints of the hands, the range of movement

was limited due to pain. He had reddish evanescent

rash on upper chest (figure 1). Other systems were

216

Ginting, A., Anggoro, R., Ar iane, A. and Setyohadi, B.

Case Report: Adult-onset Still’s Disease.

DOI: 10.5220/0008792002160218

In Proceedings of the 2nd Syiah Kuala International Conference on Medicine and Health Sciences (SKIC-MHS 2018), pages 216-218

ISBN: 978-989-758-438-1

unremarkable. Hematological investigations showed

leukocytosis of 36,000/uL (93% neutrophils),

thrombocytosis of 573,000/uL, elevated liver

enzymes (alanine transaminase 303.9 U/L; aspartate

transaminase: 67.7 U/L). C reactive protein (CRP)

was 6 mg/L and erythrocyte sedimentation rate

(ESR) was 110 mm/h. Rheumatoid factor (RF),

antinuclear antibody (ANA) and anti-double

stranded DNA antibodies were all negative. HbsAg,

Anti-HCV, anti-HIV were non-reactive. Renal,

coagulation profiles and procalcitonin were normal.

Blood and urine cultures revealed no evidence of

bacterial or fungal infection. Thorax, thoraco-

lumbosacral, pelvic radiograph were normal.

Ultrasonography of the whole abdomen was normal.

But there was very high ferritin 23,745 ng/mL

(normal 15-120 ng/mL).

Figure 1. Evanescent rash on upper chest.

Based on his clinical features and review of

laboratory evaluations, he was diagnosed to have

AOSD using the Yamaguchi criteria (Yamaguchi et

al., 1992). He was started on methylprednisolone

125mg intravenously for 3 days and was followed

by 0.5mg/kg prednisone, methotrexate 10

mg/weekly and folic acid 5 mg/weekly. Over the

next few days, the patient became afebrile.

Polyarthritis improved and he was able to ambulate

himself. The patient was discharged after one week

on methylprednisolone 24 mg daily with tapering

doses of 4 mg weekly. Besides, he was also given

lansoprazole 30 mg/od, methotrexate 10mg/weekly,

folic acid 5mg/weekly. During follow up; the

steroids were tapered off , the symptoms improved

and decreased of ferritin to 1,254 ng/mL, leucocyte

to 12,804/uL (72.1% neutrophils), ESR to 18 mm/h

and CRP to 2.4 mg/L.

3 DISCUSSION

Still’s disease is named after an English doctor name

George Still, who described the condition in children

in 1897. Still’s disease is now knows as systemic

onset juvenile rheumatoid arthritis (JRA). Adult-

onset Still’s disease was used to describe adults who

had a condition similar to systemic onset JRA. It

was firs described by Eric Bywaters in

1971(Bywaters, 1971). Although cause and

pathogenesis of AOSD remains unclear, the

condition may be triggered by infection, and also

there are role of genetic and environmental factors

(Daibata and Taguchi, 2002; Youm et al., 2007).

Most common clinical features of AOSD are

arthritis or arthralgia, fever, myalgia, rash, sore

throat (Pouchot et al., 1991). Fever is an early

feature, usually quotidian (a daily recurring fever) or

double-quotidian (two fever spikes per day) in

pattern with rise of temperature in early morning/late

afternoon and normally exceeds 39

C, as presented

in this patient. The typical rash in AOSD is

asymptomatic and is described as salmon-pink,

maculopapular eruptions mainly affecting the trunk

and extremities (Phillips et al., 1994).

Serum ferritin is considered to be specific

diagnostic criteria for AOSD (Cagatay et al., 2009).

Elevated serum ferritin levels 5-fold greater than the

upper limit of normal has been reported to have a

sensitivity of 80% and specificity of 46% for the

diagnosis of ASD (Van Reeth et al., 1994).

Hyperferritinemia was thought to be due to cytokine

secretion induced by the reticuloendothelial system

or hepatic damage. Elevated ferritin levels may be

observed as an acute phase reactant in

rheumatological disease, although levels in these

disease are not elevated high as in AOSD. Our

patient had a serum ferritin level higher than 190

times the upper limit of normal. Liver enzymes are

elevated in almost three quarters of patients (Motoo

et al., 1991). Rheumatoid factor and antinuclear

antibody are generally negative (Pouchot et al.,

1991), as seen in our patient.

According to the Yamaguchi criteria, its

diagnosis first requires ruling out infectious,

malignant (especially lymphoma), and

rheumatological diseases, followed by the presence

of at least five features, with at least two of these

being major diagnostic criteria (Yamaguchi et al.,

1992). Yamaguchi criteria are shown in Table 1.

Investigations were done to rule out the possible

cause before this patient’s diagnosis was reached.

Our patient was considered to have AOSD, since his

symptoms and signs met three major and three

Case Report: Adult-onset Still’s Disease

217

minor criteria of the Yamaguchi criteria are given

below: Our patient had fever, arthritis, and

neutrophilic leukocytosis from major criteria, and

sore throat, liver dysfunction and RF and ANA

negativity from minor criteria.

Table 1: Yamaguchi Criteria.

Major criteria Minor criteria

Fever > 39

C Sore throat

Arthralgia/arthritis>2

weeks

Lymphadenopathy

Typical rash Hepatomegaly or

lenome

Neutrophilic

leukoc

tosis

Hepatic dysfunction

RF/ANA ne

ative

Treatment for AOSD may include NSAIDS,

aspirin, corticosteroids, and immune-modulating

drugs, depending on disease severity and organ

involvement. Presence of high fever attacks, severe

articular symptoms, or internal organ involvement

may justify corticosteroid. In patient with severe

disease, such as life-threatening organ involvement

and/or conditions such as severe hepatic

involvement, cardiac tamponade, and/or

disseminated intravascular coagulation, treatment

with high-dose intravenous (IV) pulse

glucocorticoid, followed by high-dose oral

glucocorticoid. Methotrexate has been used

successfully in a small series of people to treat

AOSD. It may also be used as “steroid-sparing

agent,” meaning that if one gives methotrexate,

smaller dose of corticosteroid may be sufficient to

control disease (Ebrahim et al., 2006). As seen in

our patient had hepatic involvement and very high

serum ferritin level we treated with intravenous high

dose methylprednisolone for 3 days followed by 0.5

mg/kg prednisone. This was combined with

methotrexate tablets, 10 mg weekly and folic acid

5mg weekly.

It is difficult to predict the course of AOSD,

even with treatment. Three different patterns have

been described in AOSD (Fautrel, 2008), and the

prognosis is variable. The first category of patients

tend to have monocyclic or self-limited pattern with

complete remission within a year. Two other groups

are have intermittent or polycyclic pattern and

chronic joint problems. About one-third of people

with the disorder may fall into each of the above

patterns. Even if the patient symptoms free

sometime they need to continue medications to

control inflammation and prevent complications, at

least 6 months of treatment (Ebrahim et al., 2006).

4 CONCLUSION

AOSD is a rare disease with unclear etiology and

pathogenesis. It should be considered in patients

presenting with fever, arthritis and rash after

excluding other possible diagnoses. We present this

case is a typical presentation AOSD which was

consistent with Yamaguchi criteria and responded

well to methylprednisolone and methotrexate.

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