a-38-year - old female patient consulted to our emergency outpatient clinic with complaints of fever , sore throat , coughing , shivering , chills , joint , and muscle pain , headache , chest pain continuing for nearly 2 weeks and she was hospitalized to investigate the etiology of fever .
physical examination findings were as follows : bp 130/80 mm hg , body temperature , 39.8 c ; hr 120/min ; moderately well general physical status with full cooperation , markedly hyperemic pharynx , and tonsils , herpetic rashes around her lips , bilaterally diminished respiratory sounds heard over basal segments and tachycardia .
her neck rigidity was evaluated however the kernig , and brudzinsky signs could not be elicited .
laboratory test results were as follows : hb 11 g / dl ( 12.117.2 ) , mcv 80.8 fl ( 82.299 ) , wbc 22.10 k / ul ( 410 ) , neu 90.5% ( 3773% ) , esr 92 mm / s ( 020 ) , procalcitonin 0.8776 ng / ml ( < 0.1 ) , total protein 5.66 g / dl ( 6.48.3 ) , albumin 2.9 g / dl ( 3.55 ) , inr 1.15 ( 11.5 ) , ferritin 2889 ng / ml ( 14150 ) .
glucose , creatinine , ast , alt , alp , na , k , complete urinalysis , ana , rf , and ena profile were unremarkable .
on thoracal imagings , bilateral hilar lymph nodes of which the largest being 2 cm in diameter , bilateral pleural effusion , and atelectasic areas in the parenchyma surrounding the pleural effusion were observed ( figure 1 , 2 ) . on abdominal tomograms ,
no bacterial growth was detected in urine , throat , csf , and blood cultures .
lumbar punction performed because of suspect neck rigidity did not reveal any abnormal cells in csf .
cephtriaxone at daily parenteral doses of 2 g ) . during follow - up period , rashes , and swelling on her right , and
left wrists were detected , so she was consulted to rheumatology clinic , and naproxen sodium therapy was started with the indication of suspect aosd . on physical examination dullness over traube s space
however her hyperfebrile state persisted , echocardiograms obtained for the differential diagnosis of infective endocarditis .
posteroanterior chest radiogram costodiaphragmatic sinuses are not distinctly visualized , high - lying diaphragms , and an enlarged mediastinum were observed . biochemical analysis of the fluid drained by thoracenthesis of the patient whose computed tomograms demonstrated bilateral pleural effusion revealed the presence of 2 gm / dl albumin , 3.34 g / dl protein , 483 u / l ldh ( concurrent serum albumin 2.9 gm / dl , total protein 5.99 g / dl , ldh 393 u / l ) .
antibiotherapy of the patient with pleural effusion ( exudate ) was discontinued , and methylprednisolone treatment at daily doses of 16 mg was initiated .
after initiation of steroid therapy , she maintained an afebrile state , her joint manifestations regressed , and her complaints decreased during her follow - up period .
the patient whose pleural effusion completely regressed with steroid therapy discharged to be further followed up by rheumatology outpatient clinic ( figure 3 ) .
adult onset still s disease is a disease whose diagnosis can be made by excluding infectious , malign , autoimmune , and autoinflammatory diseases , and in consideration of its characteristic clinical , and laboratory findings . for definitive diagnosis , yamaguchi criteria can be used .
its major criteria consists of higher body temperature at 39c lasting for at least one week , marked nonpruritic macular / maculopapular salmon - colored rashes on the torso or extremities persisting for at least 2 weeks , leukocytosis ( > 10.000/ml ) , and neutrophilia ( > 80% ) .
minor criteria include sore throat , lymphadenopathy , hepatomegaly or splenomegaly , abnormal hepatic function tests ( increases in especially ast , alt , and ldh levels ) , and ana , and rf negativities . for the establishment of diagnosis , 5 diagnostic criteria ( including at least 2 major criteria ) should be met . in our patient , during approximately 4 weeks up to initiation of steroid therapy , fever exceeding 39c every day , symptoms of arthralgia , marked arthritis of both wrists , leukocytosis , neutrophilia , sore throat , and lymphadenopathies fulfilled the required diagnostic criteria , and pleural exudate seen during the clinical course of the disease was assessed to be associated with the disease . in the adult onset still
s disease pleural effusion , transient pulmonary infiltration , and pericarditis can be seen in 3040% of the patients .
affected individuals may complain of mild episodes of coughing , pleuritic chest pain , and shortness of breath .
even in some patients it may progress to acute respiratory distress syndrome ( ards ) [ 6 , 7 ] . rarely , myocarditis , arrhytmias , heart failure , and cardiac tamponade can be seen .
myocarditis , and ards are more frequently seen especially in patients with mas . in the differential diagnosis , infectious diseases ( ebv , cmv , hbv , rubella , parvovirus , coxsackie , hiv , subacute bacterial endocarditis , meningococcemia , tuberculosis , syphilis ) ; vasculites ( takayasu arteritis , polyarteritis nodosa , serum disease , thrombotic thrombocytopenic purpura ) ; malign diseases ( leukemia , lymphoma ) , connective tissue diseases ( ra , sle , mixed connective tissue disease ) , granulomatous diseases ( sarcoidosis , crohn disease ) ; autoinflammatory diseases ( kikuchi disease , sweet syndrome ) , and drug hypersensitivity reactions should be considered . in our patient
serological tests , cultures , and imaging modalities were used for differential diagnosis which led to the establishment of the diagnosis of aosd .
higher ferritin levels are among the most important laboratory findings of aosd , however markedly lower glycosylated ferritin levels are detected ( < 20% ) .
increased ferritin level is an indicator of the disease activity , and also a serologic marker of treatment response . in our patient
ferritin levels may increase as a response of hepatocytes to cytokines as il-18 , and il-1b which may be thought to play a role in the pathogenesis of aosd .
as the first - line therapy nsaids ( especially endomethacin ) , and corticosteroids are recommended . in cases of severe organ involvement pulsatile high doses of steroids for few days can be used , than daily dose is dropped down to 1 mg / kg . in cases of recurrence or with the intention to decrease steroid dose , methotrexate at a weekly dose of 7.525 mg can be given .
hydroxychloroquine , sulphasalazine , azothioprine , cyclosporine can be used separately or in combination with methotrexate . in recent years ,
effectiveness of biological agents ( infliximab , etanercept , anakinra , and tocilizumab ) , and ivig therapies have been reported in the treatment patients with serious organ involvement , and mas .
still many characteristic features of aosd are not known , and a standard follow - up or a treatment protocol of the disease is not available . in patients who met diagnostic criteria , pleural effusion which may be seen in the clinical course of the disease should be presumably associated with the disease .
besides regression of pleural effusion can be expected with the treatment of underlying desease , additional locally invasive diagnostic , and/or therapeutic interventions should be avoided .
 adult onset still s disease is a rare systemic inflammatory disorder . at the onset of the disease sore throat , pharyngitis ; which does not respond to antibiotics , one or two times peaking febrile episodes , marked salmon - colored rash on the trunk and extremities , arthralgia , arthritis , myalgia , fatigue , loss of appetite with nausea and weight loss ; hepatosplenomegaly and lymphadenopathy can be seen . among laboratory examinations levels of ferritin and other acute phase reactants 
 distinctly rise , and neutrophilic leukocytosis ; ana and rf negativity are detected . 
 pleural and pericardial effusions , transient pulmonary infiltration , and rarely myocarditis can be seen during the course of the disease . here 
 we report a patient who was examined for fever of unknown origin and diagnosed with adult onset still s disease which is a rare etiology of pleural effusion . 
CASE REPORT
DISCUSSION