other concomitant symptoms should be considered for diagnostic approach in a child with pleuritic chest pain . in this report
we discuss chest pain in a 6-year - old child with regard to other signs and symptoms .
this six - year old boy was presented to the emergency department of children 's medical center , tehran , with dyspnea and pleuritic chest pain .
the symptoms had begun two months ago and gradually aggravated for the past two weeks .
some of the differential diagnoses of chest pain in the pediatric patient are pneumonia , pleurisy , pneumothorax , pericarditis , endocarditis , costochondritis ( tietze syndrome ) , herpes zoster ( cutaneous ) , angina ( familial hypercholesterolemia , anomalous coronary artery ) , epidemic pleurodynia , trauma and rib fracture , lesions of the dorsal root ganglia , tumors of the spinal cord , and gallbladder disease .
gastro - intestinal diseases like peptic ulcer , esophagitis ( gastroesophageal reflux , infectious , pill ) , cholecystitis , perihepatitis ( fitz - hugh - curtis syndrome ) , esophageal foreign body and spasm are less common causes of chest pain in children .
the chronicity of the symptom indicates that a systemic chronic problem could be the main cause .
cardiac diseases like pericarditis , endocarditis , mitral valve prolapse , and arrhythmias are among the''must not miss '' diagnoses and should be ruled out .
heart beat was 110/min , respiratory rate 38/min , blood pressure 110/70 , temperature 39c , body weight 15 kg and height 107 cm .
the medical history was notable for 25 days of hospitalization at 4 years of age , because of a history of 3 months fever and bad appetite .
the medical files were not available , but his mother had been told that her son was treated for typhoid .
six months after getting discharged from the hospital , the patient again developed fever and general asthenia , and his mother noted that since then he continuously felt weak , had low growth rate , and developed fever occasionally .
he also had an intermittent fever which according to his mother lasts for a few years . as his mother told , he has not received vaccination since four years of age .
however , we had to check for typhoid , but it should be considered that another underlying chronic febrile disease involvement was probable .
now in physical examination we searched for signs and symptoms of a chronic disease and specific organ involvement . at admission ,
the patient was in apparent respiratory distress , which worsened on supine position and he preferred to remain in semi - sitting position .
conjunctivae were pale and auscultation of heart and lung was normal . on abdominal examination , a generalized tenderness interfered with the examination process .
the mother reported of a generalized bone pain , weight loss , nocturnal sweating and fever during the last three months .
his father also had a three years history of night - fever and cough without any medical evaluation .
the symptoms of pale conjunctivae , weight loss , night sweating and fever , indicate the chronic pattern of the illness .
iran is an endemic area for tuberculosis , so it also had to be considered , especially with the positive suspicious family history .
cardiopulmonary causes had to be ruled out , because of pleuritic chest pain and orthopnea .
infectious , rheumatologic and maybe malignant causes of serositis are among the possible diagnoses , which could be the reason for other signs and symptoms of the patient .
the first blood - work tests showed the following results ( normal values in parentheses ) : complete blood count : wbc 8130/l ( neutr 59% , lymph 34% , mono 6% , eosin 0% ) , rbc 3.600,000/l , hb 8.1 g / dl , mcv 75.7 fl , mch 22.5 pg , plt 377000 /l , blood glucose 102 mg / dl , creatinine 0.6 mg / dl ( 0.3 - 0.7 ) , blood urea nitrogen 10 mg / dl ( 5 - 20 ) , c - reactive protein 24 mg / l ( < 6 ) .
the most important findings were the very high level of esr , and low hemoglobin level .
however , malignancies were less probable as the ill condition of the patient started four years ago and malignancies would have caused much more problems during this period of time . because of fever and elevated esr , the patient was admitted to the infectious disease ward .
negative ppd test , bone marrow aspiration with normal cellularity and negative for ziehl - neelson staining , and negative culture results for typhoid .
wright , coombs wright , and widal tests , as well as blood and urine cultures were also negative .
these results indicate a low probability of infectious and malignant diseases , so rheumatologic diseases had to be taken into account and evaluated .
more laboratory tests were performed with suspicion to malignancies , rheumatologic , autoimmunity and immunodeficiency .
anti nucleotide antibody ( ana ) was positive [ 16 ( neg < 0.8 , pos > 1.2 ) ] .
amylase , lipase , uric acid , cholesterol , triglycerides , calcium , phosphorous , liver function tests , lactate dehydrogenase , total protein and albumin were normal .
the presence of serositic arthritis and a positive ana made the rheumatologic diseases , especially sle to be the first in the list of the differential diagnosis .
systemic - onset juvenile rheumatoid arthritis could also be a possible cause . some more tests , especially anti - dsdna , and rf were needed .
antinuclear antibodies ( anas ) can be positive in systemic lupus erythematosus , drug - induced lupus , juvenile arthritis , juvenile dermatomyositis , vasculitis syndromes , scleraderma , infectious mononucleosis , chronic active hepatitis and hyperextensibility .
the latest cbc : wbc 3180 ( neut 58% , lymph 36% , mono 14.6% , eos 0 , baso 0.3% ) , rbc 3.18 , hb 7 g / dl , mcv 69.2 , mch 21.6 , platelets 293000 .
results of the new tests are as follow : anticcp 1.7/ml ( within normal range , neg < 6.25 ) , c3 132 mg / ml ( 88 - 155 ) , c4 57 mg / dl ( 12 - 32 ) , anti - dsdna 585 iu / ml ( neg < 100 , pos > 100 ) , rf + + + + , aso 100 todd units ( up to 200 todd units ) . on the criteria for lupus , diagnosis of sle was made ( table 1 ) and treatment with prednisolone tablets ( 2mg / kg / day ) and hydroxychloroquine ( 5mg / kg / day ) initiated .
a few days later , the patient 's condition improved gradually and the fever subsided . 
  criteria for systemic lupus erythematosus the diagnosis of lupus is established by combination of clinical and laboratory manifestations . the company of 4 ( serositis , arthritis , abnormal titer of anti - dna antibody , antinuclear antibody ) of 11 criteria serially or simultaneously strongly suggests the diagnosis .
patients who are suspect to have lupus , but show fewer than 4 criteria should receive proper medical treatment .
a positive ana test is not necessary for diagnosis ; absence of ana in lupus is very rare .
hypocomplementemia is not diagnostic , and very low levels or absence of total hemolytic complement suggests the likelihood of complement component insufficiency .
having different pictures , lupus must be among the differential diagnoses of many problems , from fevers of unknown origin to arthralgias , anemia , and nephritis .
the differential diagnosis depends on the presenting manifestation and affected organ and includes systemic - onset juvenile rheumatoid arthritis , acute poststreptococcal glomerulonephritis , acute rheumatic fever , infective endocarditis , leukemia , immune thrombocytopenic purpura , and idiopathic hemolytic anemia .
sometimes the early presentation is atypical such as parotitis , abdominal pain , transverse myelitis , ordizziness .
lupus should also be considered in patients with multiorgan involvement , especially in the presence of hematologic or urinalysis problems .
clinical manifestations of sle include constitutional symptoms ( fatigue , prolonged fever , anorexia , lymphadenopathy , weight loss ) , musculoskeletal ( arthralgias , arthritis ) cardiovas - cular , pulmonary ( pulmonary hemorrhage , pleuritic pain ) , skin , renal , hematologic , neurologic ( seizures , psychosis , stroke , cerebral venous thrombosis , pseudotumor cerebri , aseptic meningitis , chorea , global cognitive deficits , mood disorders , transverse myelitis , and peripheral neuritis ( mononeuritis multiplex ) . on the sixth day of treatment our patient 's condition suddenly deteriorated .
he was found in apparent respiratory distress , high fever , dyspnea and having an enlarged liver span .
he was then transferred to picu , and cotrimoxazole , ceftazidim , and stress dose of hydrocortisone was initiated .
other blood work test results in picu were as follow : 
  trend of cbc tests in the patient in picu ferritin 8654 ng / ml ( 7 - 140 ) , fibrinogen 1300 mg / dl ( 172 - 539 ) , cholesterol 199 mg / dl ( 120 - 200 ) , triglycerides 398 mg / dl ( 60 - 165 ) , adenosine deaminase 18 u / l ( 0 - 15 ) , calcium 8 mg / dl , na 127 meq / l ( 135 - 145 ) , ast 57
u / l ( up to 40 ) , alt 24 u / l ( up to 40 ) , c - reactive protein 48 mg / dl ( neg < 6 ) , esr 148 mm / h , reticulocytes 0.8% , c3 89 mg / dl ( 88 - 155 ) , c4 56 mg / dl ( 12 - 32 ) , ch50 0 u ( 70 - 150 ) , igg 1256 mg / dl ( 633 - 1280 ) , lactate dehydrogenase 705 iu / l ( 120 - 300 ) .
other tests such as creatine phosphokinase , serum iga and igm , bun , creatinine , blood glucose and serum potassium were in normal range .
after respiratory distress as the first presenting manifestation , we evaluated our patient for pulmonary and cardio - vascular involvement , which may occur in the course of sle .
he developed fever again while receiving immunosuppressive medications and empirical antibiotics for opportunistic infections started .
the acute deterioration of the patient 's condition during treatment of sle , is suggestive of macrophage activation syndrome ( mas ) .
the diagnosis is supported by acute leucopenia , high liver function tests , hepatomegaly , and high ferritin level .
this diagnosis was suggested by clinical presentation and confirmed by bone marrow biopsy . in the most cases of mas ,
urgent treatment with intravenous pulse of methyl - prednisolone , cyclosporine , and sometimes , etanercept , are generally effective .
administration of ivig , is useful in infections and mas syndrome and was highly recommended in our immunodefficient patient . performing a cxr ,
having mas in mind , which is an occasionally fatal condition , may save the patient .
mas may not have its typical manifestation at the beginning , but if it progresses , it would be more difficult to manage .
a chest x - ray showed the possibility of atypical bronchopneumonia and patchy bilateral paracardiac opacities .
echocardiography revealed no pericardial effusions , no vegetation , no limbman - sacks lesion , good systolic and diastolic function , and an ejection fraction of 50% .
cardiac enzyme test results : ck - mb - mass 1.14 ng / ml ( 0 - 4.94 ) , cpk 43
u / l ( 24 - 229 ) , troponin t 0.011 ng / ml ( < 0.05 neg ) , troponin i 0.147 ng / ml ( < 0.16 neg ) , nt - pro bnp
a new bone marrow aspiration showed : hypo - cellular marrow without any specific diagnosis .
as no significant improvement was observed , a three - day pulse - therapy with methylprednisolone ( 30mg / kg / day ) was prescribed and cyclosporine a added to the regimen . because of severe neutropenia , granulocyte colony stimulating factor ( gcsf ) was initiated on the fifth day of admission to icu .
the level of serum b - type natriuretic peptide ( bnp ) , raised in response to abnormal ventricular wall tension , heart failure , systolic dysfunction , volume overload and cardiomyopathy .
measurement of bnp ( elevated in heart disease ) , can help distinguish cardiac from pulmonary causes of pulmonary edema .
a bnp > 500pg / ml suggests heart problems , < 100pg / ml suggests lung disease . the level of esr , creatine phosphokinase , lactate dehydrogenase , and bnp may be elevated in acute or chronic myocarditis . 
 
we expect that treatment with immunosuppressives along with antibiotics and supportive care , may cause the presenting critical condition to subside and also improve heart condition involved in the process of background disease . receiving medication for opportunistic infections , mas and supportive care , the patient 's respiratory distress and general condition improved gradually and he was transferred to rheumatology ward and after 2 weeks he was discharged with an appropriate regimen for sle . in long time follow up the disease went into reemission and treatment was reduced gradually . a flare up of the disease after 1.5 years forced to increase the drugs which could be decreased again after remission . after 3 years follow up , the disease is in remission and he is on low dose prednisolone ( 5 mg / daily ) and hydroxychlroquine ( 100 mg / daily ) .
the patient initially came to the emergency room with mild respiratory distress , pleuritic chest pain and other signs and symptoms that indicate a chronic disease .
the initial evaluation revealed diminished growth pattern , bone pain , night sweating and fever , pleuritic dyspnea , high esr and serositis , which have a long list of differential diagnosis ( cardiopulmonary , infectious , rheumato - logic and malignancies ) , but the chronic pattern of the illness made the malignancies less probable .
the infectious causes were ruled out by laboratory tests , and soon after , the rheumatologic causes were taken into consideration .
mas is a potentially fatal complication of childhood systemic inflammatory diseases [ 2 , 3 ] .
it can be one of the causes of secondary hemophagocytic lymphohistiocytosis ( hlh ) [ 3 , 6 ] .
this syndrome is characterized by excessive activation of t lymphocytes and macrophages and massive production of cytokines .
the clinical presentation of mas includes persistent high fever , pancytopenia , hepatosplenomegaly , hepatic dysfunction , ence - phalopathy and coagulation abnormalities[2 , 5 ] .
mas can occur as a complication of rheumatic diseases or triggered by an infection or by a change in treatment regimen [ 2 , 7 , 8 ] .
there are few case reports , that describe mas as the first manifestation of rheumatic and also kawasaki disease .
abnormal immune system reaction and regulation that leads to the lack of control of an exaggerated immune response is one of the mechanisms suggested for mas . the diagnostic criteria for mas that complicates systemic juvenile idiopathic arthritis ( s - jia ) , include decreased platelet count , elevated aspartate aminotransferase , decreased white blood cells , hypofibrinogenemia , central nervous system impairment , hemorrhages , hepatomegaly and histologic evidence of macrophage hemophagocytosis in bone marrow aspirates .
it is also diagnosed in systemic lupus erythematous [ 11 , 13 ] . in our patient
, mas happened during the treatment of sle , and it should always be kept in mind , if the condition of a rheumatologic patient deteriorates acutely without any obvious reason rapid initiation of the treatment is very important and critical .
 pleuritic pain is not an unusual problem in children . 
 other concomitant symptoms should be considered for diagnostic approach in a child with pleuritic chest pain . in this report 
 we discuss chest pain in a 6-year - old child with regard to other signs and symptoms . 
 finally , we found a rare life - threatening complication of juvenile systemic lupus erythematosus ( jsle ) in our patient . 
Introduction
Case presentation
Commentary