S H O RT C O M M U N I C AT I O N

JIACM 2004; 5(4): 327-30

A Rare Cause of Pyrexia of Unknown Origin:

Adult Onset Stills Disease
Atul Kakar*, Lalit Duggal*

Introduction
Adult onset Stills disease is a rare cause of pyrexia of
unknown origin in India. In various series adult onset Stills
disease is responsible for 5-9% patients of pyrexia of
unknown origin. Bywater first described this condition in
1971 with descriptions of 14 patients1 and since then small
series have been reported from India2-4. We report a series
of this multi-systemic inflammatory disorder which is
characterised by spiking fever, skin rash, arthralgia/
arthritis, and myalgia.

Material and methods

This study was done at Sir Ganga Ram Hospital, Delhi. All
patients who were admitted in medical wards with a
differential diagnosis of pyrexia of unknown origin were
considered for possible diagnosis of adult onset Stills
disease. The study period was July 2002 to Dec 2002.
All patients who satisfied Yamaguchi et al6 criteria were
diagnosed as adult onset Stills disease. The criteria are
tabulated in table I.

Table I : Criteria for diagnosis of adult onset Stills

disease (Yamaguchi et al6).
Major criteria
1. Fever of 39 C or higher, lasting one week or longer.
2. Arthralgias lasting two weeks or longer.
3. Typical rash.
4. Leukocytosis (10,000/mm3 or greater) including >
80% granulocytes.
Minor criteria
1. Sore throat.
2. Lymphadenopathy and /or splenomegaly.
3. Liver dysfunction.
4. Negative rheumatoid Factor and ANA.
Total of more than 5 criteria (including 2 major) were
required for diagnosis.
* The above criteria are applicable if other causes are excluded, since
this disease is relatively uncommon.
* Sensitivity 96.2%; Specificity 92.1%.

Observations

Complete blood counts, liver, and renal function test,

radiology of chest and hands was done in all patients.
Rheumatoid factor was tested by latex agglutination and
ANA by immunofluroscopy in all patients. Serum ferritin
was done in all patients. Bone marrow aspiration/biopsy
and lymph node biopsy was done if a case required so.

The onset of symptoms were acute or abrupt in all

patients. Eight patients were diagnosed as patients with
adult onset Stills disease out of 67 patients being referred
to department of Medicine for management of pyrexia
of unknown origin. The mean delay in diagnosis was 9
months (4-16 months).

The following were exclusion criteria for adult onset Stills

disease:

2. Patients less than 16 years of age.

The male to female ratio was 5:3. The age varied from 18
to 65 years with mean age of 26.2 years. All patients
presented with high grade fever. All patients had taken
course of antibiotics (> 2). Four patients were on antitubercular therapy. Two patients were being treated as
cases of rheumatic fever.

Clinical remission was defined as absence of articular or

laboratory evidence of disease activity for at least 2
consecutive months.

Three patients gave history of sore throat at onset of

illness. Rash was seen in 1 patient and was maculopapular
type seen over the neck and trunk. Lymph node

1. History of intake of steroids, hydroxychloroquine prior

to diagnosis.

* ImmnoRheumatology Clinic, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi-100 060.

enlargement was seen in 5/8 patients. Liver and spleen

enlargement was seen in 5 and 3 patients respectively.
Two patients had evidence of serositis.
Joint pains were seen in all patients. The details of joint
involvement were distal interphalangeal joint- 4/8,
proximal interphalangeal joint- 8/8, metacarpophalangeal
joint- 6/8, wrists- 4/8, elbow- 3/8, shoulder joint- 2/8, hip2/8, knee- 7/8, ankle- 5/8, feet- 4/8.
Common laboratory observations were leucocytosis,
normocytic normochromic anaemia, high ESR and ASO
and high serum ferritin levels. The findings are
enumerated in Table II. Rheumatoid factor and ANA were
negative in all patients. The X-rays of hand and feet
showed evidence of carpal/tarsal ankylosis in 1/8, no
erosions was seen in all the patients. Bone marrow
aspiration was reactive marrow in 5/8.
Table II : Shows selected laboratory test in adult onset
Stills disease.
Leucocytosis
Anaemia
High ESR
High ASO
High serum ferritin
Liver abnormalities
Lymph node biopsy
Pleural biopsy
Rheumatoid factor/ANA
Carpal/tarsal ankylosis

87.5%
87.5%
100%
50%
100%
37.5%
25%
12.5%
0%
12.5%

Seven patients required steroids due to persistent

synovitis. The break-up of the treatment was NSAIDs only
- 1/8, oral steroids with NSAIDS - 7/8, intra-muscular pulse
steroids - 2/8, DMARDS (methorexate, hydrochloroquine)
- 2/8, intra-articular steroids - 2/8, and combination of
NSAIDs, methotrexate, and steroids - 1/8.
All patients were followed-up for atleast 6 months, 3
patients required disease modifying anti-rheumatic agents.
Three patients were followed-up for a period of 11 months.
One patient shifted to alternative medication system. At 1
year he was seen again with relapse of symptoms. Serum
ferritin levels normalised in all patients by 4 weeks duration.

Discussion
Adult onset Stills disease remains a difficult clinical
diagnosis, largely because of its rarity, protean

328

manifestations, and lack of pathognomic features or

diagnostic tests. It resembles the systemic form of juvenile
rheumatoid arthritis. The adult onset syndrome is
common in age 16-35 years.
The aetiology of this disorder is not known. An increase in
frequency of HLA-35 has been found both in children and
adults with this disorder. Circadian cytokine may be
responsible for paroxysms of fever and other systemic
features. Majority of patients with systemic disease will
have self-limiting episodes of less than 1 year and fare
well once the disease is abated. Few patients have
recurrence with life threatening complications. Chronic
disease is most disabling and can lead to chronic arthritis.
Adult onset Stills disease is a mimic of tuberculosis as
patients continue to run temperature and have high ESR,
hepatosplenomegaly, lymphadenopathy in many patients.
In our series, 4 patients were on anti-tubercular treatment.
It was differentiated on the basis of leucocytosis, multiple
joint involvement, no response to anti-tubercular
treatment, and no evidence of tuberculosis on biopsy of
lymph node/pleura.
Rash was seen only in 1 patient; however, in Western
literature it is described very commonly. This could be due
to difficulty in detecting rash in Indian pigmented skin.
The involvement of DIP was seen in 4 patients and is a
notable feature of adult onset Stills disease. The
involvement of DIP is also a feature of psoriatic arthritis,
but this joint is commonly spared in inflammatory joint
diseases of young (rheumatoid arthritis, SLE, and acute
rheumatic fever).
The joint involvement was polyarticular and symmetrical
in majority of patients. The commonest joint involved in
our patient was proximal interphalangeal joints followed
by knee joint; however, knee and wrist have been reported
by others.
Hyperferritinaemia was seen in all patients of adult
onset Stills disease. Ferrtin is an acute phase reactant.
It has a diagnostic value of assessing adult onset Stills
disease and high ferritin levels are associated with high
spikes of fever. Ferritin levels show rapid response to
anti-inflammatory therapy as also seen in our series.
The cause of hyperferritinemia is thought to be

Journal, Indian Academy of Clinical Medicine

Vol. 5, No. 4

October-December, 2004

unrelated to iron metabolism and is likely to be a

consequence of cytokine-induced augmented
synthesis by reticulo-endothelial system or hepatocyte
damage resulting in increased release. Table III
compares clinical parameters in various series from
India.

Conclusions
Early diagnosis of adult onset Stills disease is possible if
treating physician is aware of the rare condition. Delay in
diagnosis is due to expensive investigations to exclude
occult infection or neoplasm. Value of hyperferritinaemia

Table III : Compares the important clinical parameters of adult onset Stills disease.
Features
Male : Female
Fever T > 39F
Rash
Arthralgia / Arthritis
Sore thorat
Lymphadenopathy
Splenomegaly
Hepatomegaly
Pleuritis / effusion

Present series (2004)

N=8
5:3
100%
12.5%
100%
37.5%
62.5%
32.5%
62.5%
12.5%

Uppal et al (1995)
N = 31

Bambery et al (1992)
N = 18

17:14
100%
36%
100%
39%
45%
58%
58%
7%

10:8
100%
50%
100%

67%
56%
56%
28%

Fig. 1 : Bilateral ankle arthritis.

Journal, Indian Academy of Clinical Medicine

Vol. 5, No. 4

October-December, 2004

329

in northern India. Ann Rheum Dis 1992; 51: 529-32.

as important diagnostic tool cannot be over emphasised.

4.

Uppal SS, Pande LRA, Kumar A et al. Adult onset Still s in

northern India: comparison with juvenile onset Stills. Br J
Rheumatol 1995: 34: 429-34.

5.

Ohta A, Yamoguchti M, Kanooke H et al. Stills disease: review

of 228 cases from the literature. J Rheumatol 1987; 14: 113946.

6.

Yamaguchi M, Ohta A, Tsuenmatsu et al. Preliminary criteria

for classification of adult onset Stills disease. J Rheumatol
1992; 23: 712-9.

References
1.

Bywaters EGL. Still s disease in the adult. Ann Rheum Dis

1971; 30: 121-32.

2.

Singh VN, Adya CM, Kumar A, Malaviya AN. Adult onset

Still s in India. Br J Rheumatol 1992; 31: 417-9.

3.

Bamberry P, Thomas RS, Malhotre HS et al. Adult onset Still

s disease: clinical experience with 18 patients over 15 years

Flavedon AD

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Journal, Indian Academy of Clinical Medicine

Vol. 5, No. 4

October-December, 2004