antiphospholipid syndrome ( aps ) may predispose the patient to deep vein thrombosis ( dvt ) , pulmonary thromboembolism ( pte ) , pulmonary hypertension and pulmonary infarction , and occasionally progress to pulmonary cavitations .
corticosteroid and immunosuppressive therapy directed at reducing antibody are not advised routinely . in a special situation ,
recognized as catastrophic apl syndrome with recurrent pte along with anticoagulant therapy , the recommendations is to start therapy with immunosuppressive agents .
however , treatment with corticosteroid and other immunosuppressive agents predispose the patients to diabetes mellitus and opportunistic infections such as fungal infection .
opportunistic fungal infection such as mucormycosis and invasive aspergilosis are almost always reported in patients with major risk factors such as diabetic ketoacidosis , long term neutropenia , post transplantation , and high dose long term corticosteroid treatment .
these infections are aggressive , rapidly progressive , angioinvasive , and life  threatening diseases .
pulmonary mucormycosis has a rapid progressive course and result in lung cavitations with high a mortality rate . 
 
some less common condition resulting in catastrophic condition are surgical procedures , anticoagulation withdrawal , medications , obstetric complications , neoplasia and systemic lopus erythmatosus ( sle ) flares .
the present case is one of the unique presentations of apl syndrome complicated with catastrophic flare up in a young woman , who died after a possible of fungal infection and immunosuppressive withdrawal .
a 35-year - old woman presented to respiratory clinic because of acute onset of fever , dyspnea exacerbation , hemoptesis , and aggravated bilateral lower limbs edema .
she had two significant episodes of dvt 12 and 10 years earlier after each childbearing .
her first infant suffered from congenital heart disease , and died at the age of 5 months .
afterwards , her condition progressed to pulmonary hypertension and right sided heart failure gradually in the last years . in spite of conventional treatment for dvt and pulmonary thromboembolism
, her condition had developed to severe pulmonary hypertension , severe dyspnea and severe lower limb edema .
she had high serum concentration of antiphospholipid antibodies ( igg : 22 gpl , igm : 17 mpl ) and anticardiolipine antibody ( igg : 25gpl , igm : 21mpl ) , but normal rheumatologic tests including antinuclear antibody ( ana ) , rheumatoid factor ( rf ) , and anti - neutrophil cytoplasmic antibodies ( anca ) .
perfusion lung scanning demonstrated perfusion defects , which was interpreted as high probability of pulmonary thromboembolism ( figure 1 ) .
perfusion lung scan : multiple segmental perfusion defects compatible with the presence of pulmonary thromboembolism .
she started receiving warfarin aiming at an international normalized ratio ( inr ) of 3 to 4 .
the measurement of serum levels of antiphospholipid antibodies was repeated on the occasion of deciding about immunosuppressive therapy . assuming the presence of multiple deep vein thrombosis , pulmonary thromboembolism , progressive pulmonary hypertension and positive antiphospholipid antibodies , prednisolone ( 60 mg / day ) and azathioprine ( 50 mg twice a day ) started hoping to prevent more catastrophic events .
she was on treatment with warfarine , azathioprine and prednisolon for 12 months , after which corticosteroid was tapered and discontinued because of hyperglycemia .
the patient then continued to receive azathioprine , warfarine and oral glucose lowering agents , and felt well until recently .
last year , she suffered from several attacks of paroxsismal atrial tachycardia ; therefore , she was admitted to the hospital . because of poor compliance , glycemic control was poor .
there was no history of any serious infection during the last four years , and serial assays for complete blood count was normal . at the last presentation ,
the laboratory findings were as follows : urea ; 55 mg / dl , creatinine ; 1.1 mg / dl , glucose ; 350 mg / dl , prothromobine time ; 25 seconds , inr ; 4.4 , wbc ; 10000/l / with 75% segment and 20% lymphocyte .
microscopic examination of urine showed : wbc ; 4 - 5/high power field , rbc ; 4 - 5/high power field and negative for bacteria .
chest computer tomography ( ct ) scan showed cavity in the medial segment of left lower lobe and a cavity in the apical segment of right lower lobe ( figure 3 ) .
blood culture for bacterial infections , and sputum smear for acid fast bacillus ( afb ) were negative .
the patient was in poor condition , and semi invasive or invasive procedures were not performed .
liposomal amphotricine was not available ; therefore , amphotricin b started empirically for possible invasive fungal infection of lung , and azathioprine was discontinued .
blood glucose remained in an acceptable range by regular insulin therapy . at the end of the first week
, the patient continued to be much better , and blood sugar , urea and creatinine were remained in acceptable range .
after two weeks of treatment , the patient was discharged and amphotricine was replaced by oral itraconasol . because of recurrent paroxysmal atrial tachycardia , the patient was readmitted on day 7 after discharge . at this admission ,
the patient succumbed to severe dyspnea , increased urea ( 192 mg / dl ) and creatinine ( 4.4 mg / dl ) , state of confusion , and was transferred to icu on the day 5 of the admission .
the portable chest radiography was not remarkable for complications such as pneumothorax or new infection .
the patient failed to improve , and died on the second day of icu care with multi organ failure and homodynamic instability .
chest computed tomography showing a cavity in the medial segment of left lower lobe and a cavity in the apical segment of right lower lobe ( arrows ) .
the patients did have the criteria for apl syndrome such as recurrent venous thrombosis , pte , pulmonary hypertension , and pregnancy morbidity as well as the presence of high serum levels of antiphospholipid antibody and anticardiolipine .   as it occurred in the present case , pulmonary thromboembolism accompanied by dvt
anticoagulant therapies with heparin followed by life - long warfarine is the optimal prophylactic treatment .
since apl syndrome was not suspected in the present patient , anticoagulant was discontinued at the end of 6 month ; therefore , subsequent multiple thromboembolic events resulted in pulmonary hypertension .  
as this case illustrates , apl syndrome can be associated with chronic thromboembolic pulmonary hypertension .
the prevalence of pulmonary hypertension in patient with apl syndrome is estimated to be 2 to 4% .
on the other hand , the prevalence of apl in patients with chronic thromboembolic pulmonary hypertension is around 10 to 20% .
primary non - thromboembolic pulmonary hypertension was also reported in patients with primary apl syndrome .
however , the prevalence of apl has been reported more frequently in thrombembolic type than in primary non - thromboembolic type of pulmonary hypertension .
there is also evidence that apl may contribute to the pathogenesis of pulmonary hypertension in patients with connective tissue diseases . 
 
some cases of apl syndrome fall into a catastrophic situation , which is characterized by overwhelming small vessel occlusive disease simultaneously affecting many organs in a short period of time .
the catastrophic situation represents less than 1% of all patients with apl syndrome , and is usually life - threatening with a 50% mortality rate .
cerebral and cardiac involvements are the main causes of death in catastrophic variant of the syndrome , followed by bacterial and fungal infections . because of highly - suspected fungal infection in the present case , azathioprine was discontinued .
this might have predisposed the patient to flare up of catastrophic syndrome , which was presented as stupor , hemodynamic instability and renal failure after an initial improvement in the condition of patient due to amphotricine therapy .
infections ( 22% ) and surgical procedures ( 10% ) are the most common precipitating factors of catastrophic syndrome reported in catastrophic antiphospholipid syndrome registry followed by anticoagulation withdrawal or low inr ( 8% ) , medications ( 7% ) , obstetric complications ( 7% ) , neoplasia ( 5% ) and sle flare up ( 3% ) . in the present case ,
pulmonary cavitations in patients with apl syndrome are rare , and there are only few case reports of the condition caused by pulmonary embolism and infarction followed by cavitations
. it might be important to mention that the lung cavitations in the present case could not be due to microthrombosis , which is one of the major features of catastrophic syndrome .
however constellation of long term uncontrolled hyperglycemia state , immunosuppressive therapy , and severely decompensated pulmonary circulation , could be predisposing the patient into opportunistic angioinvasive fungal infection such as mucurmycosis .
pulmonary mucormycosis is most often encountered in patients with diabetic ketoacidosis , uncontrolled diabetes , hematological malignancy , severe burn , and after solid organ transplantation .
the definite diagnosis of pulmonary mucormycosis is usually difficult and ante - mortem diagnosis has been made infrequently . because of ill and decompensated condition in the present case , invasive diagnostic procedures such as bronchoscopy either percutaneous or open lung biopsy , were not possible .
the signs and symptoms of the present case might suggest that physicians should be aware of flare up of a catastrophic situation in patients with apl syndrome , if they decide to taper or discontinue the immunosuppressive or corticosteroid regimens .
besides , as the infection may be a possible cause of flare up or relapse , close observation of any infectious condition must be considered .
 antiphospholipid syndrome ( aps ) is a systemic disease that causes venous and arterial thrombosis in virtually any organ . 
 sometimes it is complicated into pulmonary infarction and cavitation , pulmonary hypertension , and catastrophic course with high morbidity and mortality . 
 the present case is a 35-year - old woman with one episode of postpartum deep veins thrombosis ( dvt ) 12 years earlier and the second one after the second labor two years later . in spite of usual therapy for each episode of dvt 
 , the condition had progressed into severe pulmonary hypertension . the diagnosis of primary apl syndrome was confirmed four years ago . 
 she had been on warfarin , low dose of steroid , and azathioprine since the diagnosis of apl syndrome . 
 after one year treatment with steroid and azathiprine the patient showed progressive well being ; however , because of hyperglycemia the steroid tapered and discontinued . 
 she had several attacks of paroxismal atrial tachycardia in the last year . 
 on the last time , she presented with severe dyspnea , hemoptesis , and lower limbs edema . 
 chest radiography and lung ct scan demonsterated the presence of lung cavitations . 
 because of high suspicious for fungal pulmonary infection , azathioprine was also discontinued . however , constellation renal failure , hemodynamic instability , and confusion caused the patient to succumb to death . 
 the definite diagnosis of lung cavitations was not obtained . 