Objective: To study the clinical characteristics of Stills disease in a tertiary care hospital of Pakistan and compare it with similar published studies.
Materials and Methods: (Retrospective descriptive study) Thirteen patients with Adult onset stills disease were identified by chart review of last ten years from 1995 to 2005 at Aga Khan University Hospital (AKU), a tertiary care private medical university in Karachi Pakistan. Demographic and other specific information was recorded on standardized data sheet and analyzed by SPSS 11.5 software.
Results: Mean age of patients was 26.54±10.34 years, of which 8 (61.5%) were males. The most common presenting features were fever (100%), arthralgias and myalgias (100%) with large joint involvement (91.7%), significant weight loss (30.8%), sore throat (53.8%). None of the patients had skin rashes with fever, chest and abdominal pains. One patient had cervical lymph node swelling and 4 (33.3%) patients had splenomegally. The common laboratory findings were: leukocytosis and anaemia (100%), elevated ESR and C reactive protein (100%). Thrombocytosis (56.2%) and elevated Liver function tests (62%). Seven patients had serum ferritin checked which was in the range of 1872 to 16652 iu/l. None of the patients had positive ANA, Anti-DNA or RA factor. Twelve patients had a chest x-ray done, among them 11 were normal, one had pleural effusion. The clinical course of the patients who were followed for three months, was monocyclic (53.8%), polycyclic (30.8%) and persistent (15.4%).
Conclusion: Clinical characteristics of Stills disease in our country are mostly similar to those seen in other regions, suggesting that same pathogenetic factors may be implicated in patients from different genetic back grounds and geographic location

Abid, Naushad

Khalid, A. B.

English

eCommons@AKU

eCommons@AKUDepartment of Medicine Department of MedicineJuly 2009Adult onset Stills disease in a tertiary care hospitalof Pakistan.Naushad AbidAga Khan UniversityA. B. KhalidAga Khan University, abdullah.khalid@aku.eduFollow this and additional works at: http://ecommons.aku.edu/pakistan_fhs_mc_med_medPart of the Gastroenterology CommonsRecommended CitationAbid, N., Khalid, A. (2009). Adult onset Stills disease in a tertiary care hospital of Pakistan.. JPMA. The Journal of the Pakistan MedicalAssociation, 59(7), 464-467.Available at: http://ecommons.aku.edu/pakistan_fhs_mc_med_med/258IntroductionA reterospective descriptive chart review wascompleted on all patients diagnosed as Adult Onset StillsDisease (ASOD) between January 1995 and January 2005,in a tertiary care hospital.To diagnose AOSD, 5 or more criteria as describedby Yamaguchi1 were used. These included 2 or more of themajor criteria (fever of 39°C or greater lasting for a week orlonger, typical rashes, and leukocytosis of 10,000/mm3 orgreater with 80% or more granulocytes), with the rest asminor ones (sore throat, lymphadenopathy, and/orsplenomegaly, liver dysfunctions, and negative RF, andnegative ANA). Other etiologies like infections,malignancies, and other Rheumatic diseases were excludedby appropriate laboratory tests.The pattern of the fever was classified as continuous(when there was persistent elevation of the temperaturewithout diurnal variation) or intermittent (when thetemperature rose above the normal and returned to baselineeach day).The clinical course of the disease was definedaccording to Cush et al.2 The clinical out come of thepatients were described in our study as monocyclic (Asingle episode of the fever and systemic disease followed bycomplete recovery), polycyclic (2 or more episode of thefever and systemic disease separated by at least two monthsinterval) and chronic articular pattern (patients who hadpredominatly articular disease with or without systemicdisease).Data was recorded on a standardized data sheet andanalysed on SPSS11.0 soft ware. Chi square and fisherexact tests were used to analyse stastical significanceamong different variables.ResultsDuring this study period, 13 patients were diagnosedwith AOSD, among them there were 8 males (61.5%) and 5(38.5%) females. Their mean age was 26.54 ± 10.34 years.All patients had fever of more than two weeks . andall of them were seen by other physicians before thediagnosis was made. Twelve patients had fever greater than39°C (92.3%). The pattern of the fever varied betweencontinous and intermittent with the intermittent patternobserved among 9 (69.2%) patients and continous among 4(30.8%). Decreased body weight was observed in 4(30.8%).Arthralgias were seen in all patients with464 J Pak Med AssocOriginal ArticleAdult onset Stills disease in a tertiary care hospital of PakistanNaushad Abid,1 Abdullah Bin Khalid2King Faisal University, College of Medicine, Hofuf Al Hasa, Saudi Arabia,1 Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan.2AbstractObjective: To study the clinical characteristics of Stills disease in a tertiary care hospital of Pakistan andcompare it with similar published studies.Materials and Methods: (Retrospective descriptive study) Thirteen patients with Adult onset stills disease wereidentified by chart review of last ten years from 1995 to 2005 at Aga Khan University Hospital (AKU), a tertiarycare private medical university in Karachi Pakistan. Demographic and other specific information was recordedon standardized data sheet and analyzed by SPSS 11.5 software.Results: Mean age of patients was 26.54±10.34 years, of which 8 (61.5%) were males. The most commonpresenting features were fever (100%), arthralgias and myalgias (100%) with large joint involvement (91.7%),significant weight loss (30.8%), sore throat (53.8%). None of the patients had skin rashes with fever, chest andabdominal pains. One patient had cervical lymph node swelling and 4 (33.3%) patients had splenomegally. Thecommon laboratory findings were: leukocytosis and anaemia (100%), elevated ESR and C reactive protein(100%). Thrombocytosis (56.2%) and elevated Liver function tests (62%). Seven patients had serum ferritinchecked which was in the range of 1872 to 16652 iu/l. None of the patients had positive ANA, Anti-DNA or RAfactor. Twelve patients had a chest x-ray done, among them 11 were normal, one had pleural effusion. Theclinical course of the patients who were followed for three months, was monocyclic (53.8%), polycyclic (30.8%)and persistent (15.4%).Conclusion: Clinical characteristics of Stills disease in our country are mostly similar to those seen in otherregions, suggesting that same pathogenetic factors may be implicated in patients from different genetic backgrounds and geographic locations (JPMA 59:464; 2009).predominant involvement of knees and ankles and lesserinvolvement of small joints. Arthritis defined as swollenwarm and tender joints was encountered in only 2 patientsand this was predominantly polyarticular arthritis.Synovial fluid analysis was not obtained in any of thepatients. Myalgias were seen in all patients but none hadelevation of muscle enzymes. Diffuse erythematousmaculopapular rashes involving trunk upper and lowerextremities were not observed in any of the patients. Seven(53.8%) patients complained of sore throat. The throat wasred but without any exudate. Throat swabs and cultureswere negative in all patients. Lymph adenopathy was seenin 1 (7.7%) with involvement of cervical lymph nodes.Hepatosplenomegaly as demonstrated by physicalexamination and confirmed by ultrasound scan waspresent in 4 (30.8%) patients.At presentation anaemia (Hgb <12gm/dl) wasobserved in 12 (92%) patients and was classified asnormochromic normocytic anaemia, with a meanHaemoglobin of 10.63±1.24 gm. Leukocytosis was presentin all patients with a mean value of 20.7±4.84/cu mm3. ESRwas elevated in all patents with mean value of 89±29.93mm/hr. C reactive protein was done in 7 patients and wasfound elevated in all with a mean value of 14.80±9.87 units.Abnormal liver function tests were seen in 12(62.2%) patients with elevated liver enzymes upto 2-3 timesof the normal .Lactic dehydrogenase ( LDH )was done in 7patients and was found elevated in all with a mean value of1314±952.91 iu/l. No patient had a positive test for hepatitisvirus serology. Serum liver enzymes returned to normalwhen disease was under control.Antinuclear antibody (ANA), and Rheumatoid factor(RF) were negative in all patients . Serum ferritin was donein 7 patients and was significantly elevated in all with amean value of 6972±5403.89 iu/l. Chest radiographsrevealed minimal effusion in one patient. Radiographs ofthe joints were performed in all patients and revealed onlyperiarticular soft tissue swelling without any erosivechanges.All patients had used NSAIDS before thehospitilisation for arthralgias and myalgias. After thediagnosis was established only one patient was treated withNSAID with good clinical response, 6 were given systemicsteroids in a dose of 0.5 -1mg/kg with a dramaticimprovement in fever , arthralgias and myalgias, 2 (15.38%)were given combination of steroids and NSAIDS, 4 (30.7%)received disease modifying drugs in addition to steroids andNSAIDS as a steroid sparing agent and to control persistentarthritis. Mean regular followup duration of our patients wasthree months with intermittent clinical follow up later on.The clinical course of these 13 patients was monocyclicsystemic disease in 7 (53.8%), polycyclic systemic diseasein 4 (30.8%), and chronic arthritis in 2 (15.4%). Among thepatient with chronic disease one is still in follow up inRheumatology clinic and her chronic arthritis is wellcontrolled with combination of steroids, and Methotrexatebut she still has episodes of fever if the dose of steroids isreduced.Discussion Adult onset Stills disease is a multisystemicinflammatory disorder. It is uncommon as observed in manypreviously published case series,2-6 but has been recognizedas an important cause of the fever of the unknown origin(FUO).7,8 In a large multicenter prospective study fromtertiary care hospitals in Turkey, Stills disease has beenidentified as the most common non infectious inflammatorydisease (NIID) causing FUO in about 13.6% of thepatients.8In our series we found 13 patients with AOSD in 10years period with an approximate a incidence of 1.3cases/year indicating that this is an uncommon disease inour population. The lower incidence in our case iscomparable to some other series. This difference could bedue to the fact that our analysis was done in a tertiary carehospital where only selected cases are admitted andmajority of our patients are seen by general practitionersand in government hospitals. Interestingly higher incidenceof AOSD was obtained from a Canadian series5 as well asseries of the FUO patients from Turkey.7,8Although AOSD is considered as a disease ofyoung adults it can also be seen in geriatric age group, andthe sexes are equally affected. The majority of our caseswere young adults and more males compared to femaleswere affected. None of our patients were in Geriatric agegroup in contrast to some series where geriatric populationwas also affected.5 Recently a few case reports have beenpublished describing Adult onset Stills disease in elderlyindividuals.9Most of our patients presented with high spikingfever, arthralgias, myalgias, anaemia leukocytosis, elevatedESR and Hyperferritinemia. The clinical features,laboratory features and out come in our series are comparedwith some other larger series (Table 1and Table-2). Highgrade spiking fever, arthralgias, sore throat, myalgias werethe predominant clinical features in our case as seen in otherseries, however in other published series2-6 in addition tothese features skin rashes lymph adenopathy, serositishepatosplenomegaly and arthritis are the important clinicalfeatures. The different clinical features in most series,including ours, were not statistically significant whichVol. 59, No. 7, July 2009 465suggests that same pathogenetic factors may be involved inthe causation of the disease.The differences in clinical manifestations aredifficult to explain except that evanescent rash may bedifficult to detect on the pigmented skin of our patients.The lower incidence of arthritis in our series is surprisingand the only explanation could be that almost all of thesepatients were treated with NSAIDS, beforehospitilisation, and that could mask findings ofinflammatory arthritis.Involvement of the Ocular, CNS, and cranialnerves has rarely been reported in AOSD series,5,6 wereport no such association.We found no significantly different changes inlaboratory findings, including complete blood counts,ESR, Liver dysfunction, serum RF, and ANA whencompared with other series (Table 2). Mild to moderateTransaminase elevation were observed in most of ourpatients however none of them progressed to severe liverfailure as reported in other series.6 It is suggested thatelevated Transaminase level is not a contraindication tothe use of NSAID in this patients and even Transaminaselevel would improve with the induction of remission withNSAIDS.7 Interestingly a case of Fulminant hepaticfailure in a patient with newly diagnosed Stills diseasehave been recently reported and it is concluded that Stillsdisease should be considered in the differential diagnosisof acute hepatic failure as early diagnosis and treatmentwith steroids will improve the outcome.10The clinical out come in our series wascomparable to other series in that the systemic diseasecourse both monocyclic and polycyclic was morecommon than Chronic articular disease.3-6 In a recentseries from Kuwait,11 self-limited, intermittent, andchronic disease course was seen in 14.3, 57.1, and 28.6%of patients, respectively. The outcome was good in about89% of patients, with no mortality. We don't have any data about the course of AOSDin our patients during pregnancy however in other series2no disease flare up was noticed during pregnancy.Traditionally NSAIDS have been recommendedas the initial mode of treatment in AOSD but they havebeen effective in only 20-25% of the cases.3,4 Only 1 of13 patients in our study responded well to NSAIDS and466 J Pak Med AssocTable-1: Comparision of the laboratory findings of AOSD PATIENTS between our study and other reports (Table 2).Lab findings Reginato(4) Cush(2) Pouchot(5) Ohta(6) Worawit (3) Presentn=23 n=21 n=62 n=34 n=16 studyHemoglobin<10mg/dl NA 16(76.2) 42(67.7) 19(64) 8(50) 12(92.)WBC/mm3>10,000 22(90.6) NA 58(93.5) 30(88.3 15(93.7) 13(100)10.000-15,000 18(78.3) 15(71.4 50(80) NA 13(81.3) NAElevated ESR 23(100) 21(100) 51(82.3) 18(89.2) 8(50) 13(100)Abnormal LFTS 10(43.5) 15(78.9) 47(75.8) 24(80) 12(75) 13(100)Positive RF 2(8.7) 1(4.8) 4(6.4) 6(17.6) 0 0Positve ANA 1(4.3) 0 7(11.3) 3(8.8) 1(6.25) 0( ) = percent. NA: Not available. * = p,.05 **= p, 0.01Table-2: Comparision of the clinical features of AOSD among different published reports (Table 1).Clinical features Reginato (4) Cush (2) Pouchot (5) Ohta (6) Worawit (3) Our StudySex (Females) 11(47.8)* 13(61.9) 28(45.2) 23(67.6) 13(81.3) 5(38.5)Age( 15-30) 18(78.3) 17(80.9) 50(80.6) 20(62.5) 14(87.5) 13(100)Arthralgia 23(100) 21(100) 62(100) 34(100) 16(100) 13(100)Arthritis 22(95.7) 21(100) 58(93,5) 27(90) 13(81.3) 2(15.58)Fever.>39 23(100) 21(100) 62(100)* 32(94.1) 14(87.5) 13(100)Weight loss NA 14(66.7) 41(75.9) 6(50) 11(84.6) 04(30.8)Skin rashes 22(95.7)* 18(85.7) 54(87.1) 28(82.4) 11(68.7) 0(0)Sore throat 21(91.3)* 18(85.7) 57(91.9)** 13(46.4) 10(62.5) 7(53.8)Lymphadenopathy 12(52.2) 19(90)* 46(74.2) 22(64.7) 8(50) 1(7.7)Hepatomegaly 6(26.1) 08(38.1) 27(43.5) 22(64. 3(18.7) 4(30.8)Splenomegaly 5(21.8) 11(52.4)* 34(54.8)* 26(76.5)** 3(18.7) 4(30.8)Pleuritis 7(30.4) 9(42.9) 34(54.8)** 4(11.8) 2(12.5) 1(7.7)Pericarditis 5(21.8) 7(33.3) 23(37.1)* 5(14.7) 1(6.3) 0(0)Myalgias 8(34.8) 16(76.2) 52(83.9) NA 16(100) 13(100)() = Percent. * = p<.05 ** = p < .0.01. Chi -square or Fischer exact test was used for categorical variables).remaining required steroids which majority of themwere able to taper at least in short out patient followup. This finding is consistent with others in thatcorticosteroids were effective in controlling systemicsymptoms.3,4 Disease modifying antirheumatic drugs(DMARDS) were used in few of our patients but theyhave been recommended in addition to steroids tocontrol systemic and chronic articular disease.12Biologic agents have been used recently for resistantcases.13The assessment of the disease activity in AOSDis difficult. Serum ferritin in AOSD is of particularinterest and it has been proposed as a marker ofdisease activity. A very high level is observed inpatients with active AOSD and the level correlateswith the disease activity.11,14 Serum ferritin waselevated in majority of our patients, however whetherlevels correlated with disease activity in our series isdifficult to detect because of the lack of follow upresults in our series. The precise mechanism leading toelevated serum ferritin in our series is unclear.ConclusionAOSD in our population has nonspecific clinicalfeatures and mimics bacterial infections such asMycobacterial infections, Pharyngitis, Endocarditisand a high clinical suspicition is required to diagnosethis relatively rare but important entity beforeprescribing unnecessary antiobiotics andantituberculous treatment. There may be interethinicdifferences in the clinical manifestations and thedisease outcomes. Large prospective studies are neededto test this hypothesis.References1. Yamaguchis M, Ohta A, Tsunematsu T, Kasukawa R, Mizushima Y,Kashiwagi H, et al. Preliminary criteria for classification of adult onsetStills Disease. J Rheumatol 1992; 19:424-30.2. Cush JJ, Medsger TA Jr., Christy WC, Herbert DC, Cooperstein LA. Adultonset Stills disease. Clinical course and out come. Arthritis Rheum 1987;30: 186-94.3. Louthrenoo W, Aramsareewong T, Sukitawut W. Adult onset Stills disease:clinical features and outcome in 16 Thai patients. J Clin Rheumatol 2001;7:301-7.4. Reginato AJ, Schumacher HR Jr, Baker DG, O'Connor CR, Ferreiros J.Adult onset stills disease: experience in 23 patients and literature reviewwith emphasis on organ failure . Semin Arthritis Rheum 1987; 17: 39-57.5. Pouchot J, Sampalis JS, Beaudet F, Carette S, Decary F, Salusinsley-Sternbach M, et al. Adult Stills disease: manifestations, disease course,and outcome in 62 patients. Medicine (Baltimore) 1991; 70: 118-36.6. Ohta A, Yamaguchi M, Kaneoka H, Nagayoshi T, Hiida M. Adult Stillsdisease. review of 228 cases from literature. J Rheumatol 1987; 14:1139-46.7. Mert A, Ozaras R, Tabak F, Bilir M, Ozturk R, Ozdogan H, et al. Fever ofunknown origin: a review of 20 patients with adult onset stills disease.Clin Rheumatol 2003; 22: 89-93.8. Kucukardali Y, Oncul O, Cavuslu S, Danaci M, Calangu S, Erdem H, et al.The spectrum of diseases causing fever of unknown origin in Turkey: amulti centre study. Int J Infect Dis 2008; 12: 71-9.9. Kurasawa M, Kotani K, Kurasawa G, Shida K, Yamada S, Tago T. Adultonset Stills disease in a patient over 80 years old successfully treated withlow-dose methotrexate therapy. Age Ageing 2007; 36: 104-6.10. Linde B, Oelzner P, Katenkamp K, Hein G, Wolf G.. Fulminate liver failurein a 39-year-old female patient with leukocytosis, unclear fever, andarthralgic pain. Med Klin (Munich) 2007; 102: 846-51.11. Upal SS, Al Mutairi M, Hayat S, Abraham M, Malaviya A. Ten years ofclinical experience with adult onset Still's disease: is the outcomeimproving? Clin Rheumatol 2007; 26:1055-60.12. Marchesoni A, Ceravolo GP, Battafarano N, Rossetti A, Tosi S, Fantini F.Cyclosporine A in the treatment of the Adult Stills disease. J Rheumatol1997; 24: 1582- 7.13. Kötter I, Wacker A, Koch S, Henes J, Richter C, Engel A, et al. Ankinra inpatients with adult adult-onset Still's Disease: four case reports with serialcytokine measurements and a review of the literature. Semin ArthritisRheum 2007; 37:189-97.14. Meijvis SC, Endeman H, Geers AB, ter Borg EJ. Extremely high serumferritin levels as diagnostic tool in adult-onset Still's disease. Neth J Med2007; 65: 212-4.Vol. 59, No. 7, July 2009 467

Adult onset Stills disease in a tertiary care hospital of Pakistan.

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Adult onset Stills disease in a tertiary care hospital of Pakistan.

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