|Year : 2014 | Volume
| Issue : 3 | Page : 400-402
Seizures in a patient of adult onset Still's disease
Varsha S Dabadghao, Suresh K Sharma, Sangram S Mangudkar, Subodh A Garg
Department of Medicine, Padmashree Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India
|Date of Web Publication||18-Mar-2014|
Varsha S Dabadghao
Department of Medicine, Padmashree Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pimpri, Pune - 411 018, Maharashtra
Source of Support: None, Conflict of Interest: None
Adult onset Still's disease (AOSD) is a rare systemic inflammatory disorder, characterized by high fever, salmon-colored rash, polyarthritis and multi-organ involvement. Yamaguchi's criteria and high serum ferritin levels help to diagnose this disease. It is mostly a diagnosis of exclusion. AOSD involves predominantly the joints, liver and skin, but can involve any organ. Neurological involvement is relatively rare and seizures are usually due to fulminant hepatic failure, meningoencephalitis and posterior reversible encephalopathy syndrome/thrombotic thrombocytopenic purpura. Seizures which occur without these conditions and can be exclusively ascribed to the primary disease process alone have not been reported in the literature. We report a patient of AOSD who was treated with immunosuppressants and during the course of her illness presented with generalized tonic-clonic seizures which were attributable primarily to AOSD. Hence seizures per se can be an event in such patients and need to be watched for and treated.
Keywords: Adult onset Still′s disease, cytokines, neurological complications, seizures
|How to cite this article:|
Dabadghao VS, Sharma SK, Mangudkar SS, Garg SA. Seizures in a patient of adult onset Still's disease. Med J DY Patil Univ 2014;7:400-2
| Introduction|| |
Adult onset Still's disease (AOSD) is a rare systemic inflammatory disorder characterized by high-spiking fever mostly above 39°C, an evanescent non-pruritic macular salmon-colored rash appearing on the trunk and extremities during fever, polyarthritis and multi-organ involvement.  Still's disease was first described in children by an English physician, Sir George Frederic Still who published his monograph in 1897 "On a Form of Chronic Joint Disease in Children." He described 22 children with signs and symptoms of the disease entity currently known as systemic onset juvenile idiopathic arthritis.  In 1971 Eric Bywaters described 14 adults with similar presentation.  Although AOSD is a diagnosis of exclusion, Yamaguchi criteria are useful to identify cases [Table 1].  In the presence of a compatible clinical scenario, serum ferritin higher than 3200 ng/mL is highly suggestive of AOSD.  It mainly involves joints and skin and causes liver enzyme derangements. Neurological complications are rare, occurring in 7-12% of patients, in some form or other. , Cranial nerve palsies, seizures, aseptic meningoencephalitis and Miller-Fisher syndrome have been reported. , Seizures when reported are part of other complications of AOSD such as hepatic failure, meningoencephalitis or posterior reversible encephalopathy syndrome and thrombotic thrombocytopenic purpura (PRES and TTP). , However, there are no reports of seizure in AOSD which cannot be ascribed to any other cause or organ damage. Our patient of AOSD developed generalized tonic-clonic seizures during the disease course, which could not be ascribed to any other organ damage or etiology and was due to the disease itself.
|Table 1: Yamaguchi criteria for classifi cation of adult onset Still's disease|
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| Case Report|| |
The present case report is about a 65-year-old female patient, not a known case of any illness, came with the complaints of high grade intermittent fever and chills occurring daily off and on since 2 years. She also had generalized weakness and pain in large joints. She denied any history of cough or dyspnea. A macular rash over chest, retro auricular groove and scalp during febrile episodes was noticed. Liver and spleen were just palpable. There were no inflammatory signs or deformities of involved joints. There was no pallor, edema, clubbing or lymphadenopathy. At 2 years back, she was admitted in a tertiary care hospital for similar complaints. X-ray chest at that time was suggestive of hilar lymphadenopathy but there was no parenchymal, pleural or cardiac abnormality. Transbronchial biopsy with broncho-alveolar lavage was inconclusive. A provisional diagnosis of sarcoidosis was made and she was treated with oral prednisolone which was discontinued after 6 months. At 3 months later, her symptoms reappeared after which she presented to this hospital.
At this stage, blood counts revealed persistent leucocytosis in the range of 18,000-25,000 cells/mm 3 and mild thrombocytosis. Hemoglobin was 10.5 g/dL. Erythrocyte sedimentation rate was 42 mm and C-reactive protein was positive. Blood for D dimer was 1560 ng/mL D dimer units. Serum bilirubin was normal but serum glutamic pyruvic transaminase and serum glutamic oxaloacetic transaminase were 93 and 88 IU/L respectively. Renal function tests were normal. Her tuberculin test was negative. Repeated blood and urine cultures were sterile. Tests for human immunodeficiency virus, hepatitis B surface antigen, Widal and Venereal Disease Research Laboratory were negative. Serological tests for Malaria, Brucella More Details and Rickettsia were negative. Her rheumatoid factor, antinuclear antibody, anti-double stranded deoxyribonucleic acid and U1ribonucleoprotein was negative. Angiotensin converting enzyme levels were mildly elevated. Chest X-ray and abdominal ultrasonography was consistently normal. Contrast enhanced computed tomography thorax was suggestive of very small nodular lesions seen in bilateral apical and upper lobes, subtle subpleural thickening with posterior pleural thickening but no hilar lymphadenopathy. A course of higher broad spectrum antibiotics for 2 weeks did not result in a clinical response. In view of prolonged unexplained fever, serum ferritin levels were sent, which were >16,000 mcg/L. The diagnosis of ASOD was made on the basis of Yamaguchi s criteria as she fulfilled all major and 3 min or criteria. She was started on oral prednisolone 1 mg/kg/day and azathioprine 1 mg/kg/day. After a week the patient reported relief in her constitutional symptoms and remained afebrile thereafter. She was discharged on oral prednisolone and azathioprine. At 3 days after discharge, she presented again in a post-ictal phase with history of two episodes of generalized tonic-clonic seizures 2 h apart. At that time there was no fever, headache, vomiting, loose motions, trauma or altered sensorium. She had been eating well. Detailed neurological examination was normal with no signs of meningeal irritation. Blood sugar, electrolytes, liver and renal function tests were normal. The serum and urine osmolality was normal. Magnetic resonance imaging brain was normal. Electroencephalogram (EEG) revealed epileptiform discharges (spike-waves) originating in the right frontoparietal region. Her immunosuppressives were continued at full doses and the neurologist was consulted, who suggested starting oral sodium valproate sustained release 300 mg twice a day as her EEG was abnormal. There was no recurrence of either constitutional features or seizures on follow-up visits for 1 year.
| Discussion|| |
AOSD is a rare condition usually diagnosed after excluding infective and other autoimmune etiology of prolonged fever. Yamaguchi criteria are a great help in arriving at the diagnosis.  The disease characteristically affects younger patients, mostly between 16 and 35 years of age, but can affect all ages. 
The present patient was an elderly woman, exhibiting features of AOSD. AOSD can affect any organ though commonly joints, skin, heart (pericarditis), lungs (pleuritis, effusions, fibrosis), liver (deranged enzymes, hepatic failure) and kidney (interstitial nephritis, renal amyloidosis) are affected. Neurological affection is very rare in this disease (7-12% of cases) and cranial nerve palsies, seizures, aseptic meningoencephalitis and Miller-Fisher syndrome have been reported in the literature. ,,, In most of the reported cases of AOSD with seizures, these seizures have been part of other complications such as hepatic failure, PRES/TTP or meningoencephalitis. , This patient was not part of any such syndrome complex. Other unrelated causes such as metabolic, vascular and infective were reliably ruled out. Her EEG done was abnormal, showing an epileptiform focus, although her imaging studies were normal.
Due to paucity of reports of seizures in AOSD due to the disease itself, the exact mechanism linking the two is not known. It is well-known that alterations in cytokine production have an important pathophysiological role in AOSD.  Interleukin (IL) 2, interferon γ, tumor necrosis factor-α (TNF-α) and IL-6 are the cytokines implicated in AOSD. Few of these cytokines have also been thought to play a role in seizure generation and epilepsy. TNF-α and IL-6 are the cytokines common to AOSD and seizure generation as is seen in mice models. 
It is possible that cytokines unmask epileptogenic foci in certain patients of AOSD and they may develop seizures or epilepsy as part of the disease process and not due to secondary causes. This patient's EEG showed the presence of epileptogenic foci and so maintenance anticonvulsant was started. All her other symptoms resolved on immunosuppressive medication and there was no recurrence of seizure. It is therefore imperative to monitor and follow-up patients for development of seizures and add anticonvulsants if required. Seizure disorder is a lesser known complication in AOSD and more information is required for better patient care and developing protocols about the use and duration of anticonvulsants.
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