23. Adult-onset Still’s disease presenting as SLE

Abstract

Introduction: A case of adult-onset Still's disease initially diagnosed as lupus. A patient presented with clinical and immunological features consistent with SLE, however did not respond to conventional treatment. Over time she had recurrent flares associated with high inflammatory markers. Following extensive investigation she was diagnosed with adult-onset Still's disease. She remains well controlled on tocilizumab and methotrexate. Thiswassignificant, as the history and results of initial investigation were consistent with SLE. Adult-onset Still's disease was a diagnosis of exclusion following years of investigation. Diagnosis and an appropriate treatment regimen has resulted in prevention of further flares. Casedescription: A49-year-old lady presented in 2011 with a history of joint pain, rashandfevers.Herinflammatory markerswereraised,CRPof 267.7 mg/L, white cell count 14.8109/L and neutrophil count 13.6109/L. ANA positive, with positive anti-RNP and anti-SM, dsDNA 73.3 IU/mL, pANCA positive, MPO 64. She was initially diagnosed with lupus. She was treated with multiple steroid sparing agents including mycophenolate mofetil, azathioprine and cyclophosphamide between 2011 and 2013. During this period she developed presumed cyclophosphamide-induced cardiomyopathy, and the cyclophosphamide was subsequentlystopped. She has had recurrent flares presenting with rash and joint pain associated with raised inflammatory markers, neutrophilia andelevatedferritin, responding well to treatment with highdosesteroids. During this timeshe has been extensively investigated for pyrexia of unknown origin. These investigations include two prior CT-PET scans in 2013 and 2015, which identified no source of sepsis or malignancy.Bone marrow aspirate performed 2015 demonstrated non-specific appearances with no malignancy. Symptomatic control was achieved for some timewithmethotrexate and low-dosesteroids;howevershehadasignificant flareandbecameacutely unwellwitharash,feverandraisedinflammatorymarkers,requiringadmission to intensive care in 2017. During this flare, her white cell count was 28.1109/L, neutrophil count 26.4109/L, ferritin was 11741 ug/L. She respondedwell topulsedmethylprednisolone andmadeagoodrecovery. Shewassubsequentlycommencedontocilizumab. Following this episode, she was seen at the Periodic Fever Clinic at the Royal Free, where they confirmed a diagnosis of phenotypical adultonset Still's disease, however her genetic testing was negative. In the interim she has remained stable with well controlled symptoms on methotrexate and tocilizumab. Hermost recentANAandENAhave been negative, with normal inflammatorymarkersandferritin sincecommencingcurrenttreatment. Discussion: Initiallyduetoatypicalhistory ofjoint pain,rashesandfevers with an associated positive ANA, anti-RNP, anti-SM, raised dsDNA and positive pANCA, a diagnosis of SLE seemed highly likely. As time progressed, several different therapeutic agents were trialled, with varying success.Sherespondedwelltosteroids,howeversteroidsparingagents did not seem to control her symptoms and she developed presumed cyclophosphamide induced cardiomyopathy, which led to this being withdrawn. She continued to have recurrent flares during this period. Alternativedifferentialdiagnoseswereexplored, includingmalignancyor unusualinfections. Thiswasan interesting case, as this patient initially presented witha clinical andimmunological phenotype typical of SLE.Dueto the non-specific nature of adult-onset Still's disease and its rarity, this was a diagnosis of exclusion. The persistent pyrexia with neutrophilia and raised ferritin during flares, and poor response to azathioprine, mycophenolate and cyclophosphamide were features more consistent with adult-onset Still's disease, however she was ANA, RNP and SM positive until 2017, andremainspANCApositive. Despite a phenotypical diagnosis of adult-onset Still's disease and good response to treatment with methotrexate and tocilizumab, this patient's geneticscreeningwasnegative.HerpersistentpositivepANCAandinitial positive anti-nuclear antibodies are unusual forapatient with adult-onset Still's disease, however the resolution of positive ANA, neutrophilia and raised ferritin with tocilizumab and methotrexate suggest an IL-6 mediatedprocess. Key learning points: This case was highly unusual and interesting, and highlighted several important points. Firstly, with many rheumatological conditionsdiagnosis isnotalwaysclearcut,andwhile this patientmetthe diagnostic criteria for SLE, she continued to have atypical flaresand poor response to conventional steroid sparing agents. Differential diagnoses such as malignancy or infection have to be thoroughly investigated prior to diagnosis and commencing treatment for autoinflammatory conditions such as adult-onset Still's disease. On a practical level, it can be challenging in today's NHS to organise specialist investigations rapidly, especiallyasanoutpatient. This case hasemphasises the importance of consideration ofa wider differential for patients presenting with unexplained symptoms, especially whenthereisapoorresponsetoconventionaltreatment. Conflicts of interest: The authors have declared no conflicts of interest.