Adults Still’s Disease in Qatar

ADULTS STILL’S DISEASE IN QATAR
CLINICAL AND LABORATORY FEATURES AND TREATMENT

Al Ani A.M., Hammoudeh M. and Khanjar I.
Department of Medicine, Hamad Medical Corporation, Doha, Qatar

Abstract:

Adult-onset Still’s disease remains a clinical diagnosis and a diagnosis of exclusion: its prompt recognition will avoid unnecessary diagnostic procedures and delay in initiating therapy.

The clinical and laboratory features and treatment of 16 patients with Adult-onset Still’s Disease (AOSD) at Hamad General Hospital (HGH) were studied and compared with 62 patients of G. Pouchot(1).

Eight patients were female (50%), ten (62.5%) had poly-arthritis and rash, fourteen (87%) had fever > 39ºC. Leukocytosis, thrombocytosis and hyperferritinemia were present in most of the patients.

Key Words: AOSD = Adult-onset Still’s Disease

Introduction:

AOSD is a febrile disorder of unknown etiology characterized by typical spiking fever with evanescent rash and involvement of various organs(2,3), with acute phase reaction including elevated erythrocytic sedimentation rate, C-reative protein and leucocytosis resembling acute bacterial infection. Physicians often have difficulty in making a definite diagnosis especially in the early stages of a case.

AOSD occurs after 15 years of age(2). In addition to the high spiking fever, evanescent rash and arthritis, the patient may have pleuritis, pericarditis and leukocytosis(2,4). Hyperferritinemia (serum ferritin > 1000ng/l) was found to be of diagnostic value in acute AOSD(5).

We have studied the clinical and laboratory features and the treatment of 16 cases with this disease.

Materials & Methods:

Files were reviewed of all patients with the diagnosis of AOSD admitted to the medical wards of HGH between 1991- 2000. Only patients who fulfilled the criteria of AOSD by Yamagushi(6) were included i.e five or more criteria including at least two major criteria.

Major Criteria:

1. Fever of 39ºC or higher, lasting one week or longer.
2. Arthralgia lasting two weeks or longer.
3. Typical rash.
4. Leucocytosis (10,000/mm3 or greater) including 80% or more of granulocytes.

Minor Criteria:
1. Sore throat.
2. Lymphadenopathy and/or splenomegaly.
3. Liver dysfunction.
4. Negative rheumatoid factor and negative anti-nuclear antibody.

The clinical features at presentation, laboratory data and the medication used for the treatment of the patients were recorded. Pericarditis was diagnosed when left-sided chest pain with pericardial rub or an effusion on echo-cardiogram was found. Pleuritis was diagnosed by the presence of pleuritic chest pain, pleural rub or pleural effusion. The typical rash of AOSD is a non-pruritic evanescent macular or maculopapular rash that occurs mostly during the febrile episodes and fades once the fever subsides.

Results:

Sixteen patients fulfilled the criteria for AOSD. All patients were followed in the Rheumatology clinic except four patients who left for their home countries and one patient who died with pancarditis and heart failure while in the hospital. There were equal numbers of male and female patients. Table I shows the clinical findings in our patients. Fever > 39ºC was present in 14/16 (87%). Rash was seen in 11/16 (69%) and sore throat was present in 11/16 (69%). Myalgia was present in 10/16 (62.5%) and hepatomegaly in a similar number. The spleen was enlarged in 6/16 (38%). Serositis (pericarditis or pleurisy) was present in 7/16 (44%) and abdominal pain in 7/16 (44%). Arthralgia was a very common presentation 14/16 (87%) while frank arthritis occurred only in 10/16 (62.5%).

Laboratory findings are shown in Table II. Elevated ESR was present in 14/16 (87%) patients, the two cases with normal ESR were case 6 and case 13 (who expired with heart failure). Leucocytosis (WBCs > 10,000) was present in 87%, and was over 20,000 in 75% of patients. Four patients (25%) had WBCs count over 30,000. The range was 9300 to 41,600. Thrombocytosis (platelets count over 400,000 /mm3) was present in 9/16 (56%). The highest platelets count was 739,000/mm3. Abnormal liver function tests were seen in eight patients (50%). Hypoalbuminemia of less than 35gm/l was seen in twelve patients (75%).

Ultrasound of the abdomen was done in 15 patients and it revealed hepatomegaly in 9/15 (60%), splenomegaly in 7/15 (46%).

Five patients responded well to non-steroidal anti-inflammatory drugs (NSAIDs) and did not need steroids. The other eleven patients were treated with steroids either immediately after diagnosis or if the patient failed to respond to NSAIDs. Of those eleven patients, one required azathioprine and four required methotrexate to control the symptoms.

Discussion:

In 1887, while a medical registrar at the Hospital for Sick Children in London, Dr. Stlll described both acute and chronic forms of juvenile onset arthritis. He singled out twelve children who presented with lymphadenopathy, splenomegaly and fever. In some patients pleurisy and pericarditis developed and an evanescent rash was noted(7). He emphasized that joint pain was infrequent although there was a tendency to early contracture, muscle atrophy and involvement of the cervical spine(7). This acute onset systemic rheumatic disease is now recognized in adults(2).

The adult-onset Still’s disease was first reported by Bywaters in 1971 who described 14 adults with arthritis and systemic features identical to those in the systemic form of juvenile rheumatoid arthritis. Bywaters originally stated that long term articular prognosis was good with the exception of ankylosing of the cervical spine(2). This optimism was shared by some but not by others(8-10).

Six sets of criteria for the adult disease in a well defined patient population have been proposed in published papers(11). Yamagushi’s criteria are the most sensitive (93.5%) while Medsegr’s is 80.6%, Khan’s is 69.5%, Reginato’s is 55.2% and Goldman is 43.7%.

Three major series have been reported in the literature; one from Canada (65 cases from five university centers)(1), one from France (65 cases)(11) and one from Japan (90 cases from 29 institutions)(12).

In the Canadian study, ASOD diagnosis was based on the criteria by Medsger and Christy(13,14) which include the presence of high spiking fever > 39ºC, arthralgia, or arthritis, rheumatoid titer < 1:80, anti-nuclear antibody (ANA) titer < 1:100 or any two of the followings: leucocytosis > 15000/mm3, evanescent macular or maculopapular rash, serositis (pleuritis or pericarditis), reticuloendothelial involvement (hepatomegaly, splenomegaly or generalized lymphadenopathy).

We applied the classification criteria of AOSD designed by the Adult Still’s Disease Research Committee in Japan(6).

Frequently the first episode occurs between the age of 16 to 35 years (81% of Pouchot et al study)(1). In our series 68% of the episodes occurred in this age group. Onset as late as the seventh decade has been described(15). The onset in case 10 was at the age 62 while in case 16 it started when the patient was thirteen. The female to male ratio was 1:1 which was slightly different from the Canadian study which was 1:1.2.

Differences between our series and the Canadian study was noticed in the occurrence of arthritis (62.5 vs 100%) and the presence of lymphadenopathy (6% vs 46%). Lymphadenopathy could have been overlooked or not documented in our patients’ files. Furthermore it was noticed that most patients who had splenomegaly also had hepatomegaly. In only one patient with splenomegaly the liver was not enlarged. The rash, splenomegaly, pleuritis and pericarditis were observed more frequently in the Canadian study compared to our series.

Bujak et al was first to draw the attention to pharyngitis as a common presenting feature(4). This was observed more frequently in the Canadian study (92%) compared to our study (69%). Leucocytosis is a useful diagnostic clue. The majority of our patients (87%) had leucytosis. The count was over 20,000mm3 in 75% of the patients which makes it a very important finding in ASOD.

At the onset of the disease five patients responded to NSAIDs only, while the other 11 patients required steroids and in four of them methotrexate(16) was added and in one patient immuran was added. Case No. 13 had a very aggressive course and expired with pancarditis and heart failure despite the use of pulse high dose steroids, immunoglobulin and cyclosporine.

The most striking features in our patients were the presence of severe joint pain, sore throat, myalgia and spiking fever in the majority of the cases together with hyperferritinemia. All patients appeared severely ill and were subjected to extensive investigations into possible infectious, inflammatory or neoplastic causes.

Although ASOD is not a common disease, our findings of 16 cases admitted to the medical ward at HGH over a ten-year period (1991-2000) suggest that it is an important entity of which physicians should be aware.

This paper reports the clinical spectrum and treatment of 16 patients with ASOD from our institute. No pathognomonic laboratory or histological abnormalities have been found so far in ASOD. The diagnosis is clinical, based upon persistent high spiking fever, evanescent rash and arthritis as the most important symptoms(2,3). The presence of high serum ferritin level is a very helpful clue to the diagnosis(5) although it is not included in the diagnostic criteria of ASOD.

References:

1. G. Pouchot, Sampalis JM, Biaadet F, Et al – Adult Still’s Disease Manifestation, Disease, Course and Out Come In 62 Patients-Medicine 991 Vol. 70, No. 2, 118-135.

2. Bywater, EGL Still’s Disease In The Adult – Ann Rheum. Dis. 1971: 30: 121-23.

3. Ohta A, Yamaguche M, Kaneoka H, Nagayoshi T, Hilda M., Adult Still’s Disease Review of 228 Cases from the Literature J. Rheumatol 1987: 14 : 1139-46.

4. Bujak JS, Apteker RG, Decker JL, Wolf SM: J. Rheumatoid Arthritis: Presenting In The Acute Adult As Fever of Unknown Origin. Medicine 1973. 52:431-44.

5. Ota T, Higashi S, Suzuki H, Eto S: Increased Serum Ferritin Levels In Adult Still’s Disease (Letter). Lancet 1987; 1: 562-3.

6. M. Yamaguchi, A Ohta, T Tsunematsu, et al: Preliminary Criteria For Classification of Adult Still’s Disease, J. Rheumatol 1992. 19: 3: 424-435.

7. Still GF On A Form of Chronic Joint Disease In Children Med Chin. Trans. 1897.80.47 (Reprinted in Arch Int. Med. 1941; 16: 156).

8. Esdaile JM, Tennenbaum H, Hawkini D, Adult Still’s Disease. Am J Med. 1980: 825-30.

9. Elkon KB, Hughes GRV, Bywater EGL et al: Adult Onset Still’s Disease Twenty Year Follow Up and Further Studies of Patients with Active Disease. Arthritis Rheum. 1982: 25; 647: 54.

10. Regninatet AJ, Schumacher MR, Baker DG, et al: Adult Onset Still’s Disease Experience In 23 Patients and Literature Review with Emphasis on Organ Failure, Semin Arthritis Rheum 1987: 17; 39-57.

11. Masson C, Le Loet X, Dubost JJ, et al Comparative Study of 6 Types of Criteria In Adult Still’s Disease. J. rheumatol 1996 Mar 23 (3) 495-7.

12. Ohta A, M. Yamaguchi, T Tsunematsu, et al: Adult Still’s Disease: A Multicenter Survey of Japanese Patients. J. Rheumatol 1990, 17: 1058-63.

13. Cush JJ., Medsger TA, Christy WC et al: Adult Onset of Still’s Disease, Clinical Course and Out Come, Arthritis Rheum 1987, 30: 186-94.

14. Medsgar TA: Carpal Arthritis with Ankylosis In Late Onset Still’s Disease, Arthritis Rheum 1976, 19: 232-42.

15. Wouters JM, Martin H, Van Rijswijk and L. Van de Putte: Adult Onset Still’s Disease In Elderly A report of 2 Cases, J Rheumatol 1985: 12: 791-3. 16. A Olcay AY Dintug Cruz, Ricard Cervara, Munther A, Khamashta, Graham RV Hughes: Low Dose Methotrexate Treatment In Adult Still’s Disease. J. Rhematol 1992: 19: 431-5.