myasthenia gravis superimposed with proteinuria is a very rare disorder with only 39 cases reported so far . of these cases , myasthenia gravis and minimal change disease are both related to the dysfunction of t lymphocytes and hence the 2 disorders may be connected . here we report the first case on a patient diagnosed with myasthenia gravis concurrently with the minimal change disease , and it was presented in the absence of thymoma or thymic hyperplasia . minimal change disease is generally considered to occur subsequent to the onset of myasthenia gravis with causal association . after extensive literature review , we noted only 47.8% minimal change disease had occurred after the onset of myasthenia gravis . minimal change disease mostly occurs in children and if diagnosed in adults , clinicians should search for a potential cause such as myasthenia gravis and other associated thymic disorders . but mg superimposed with proteinuria is very rare and there are only 39 cases reported so far . minimal change disease ( mcd ) and mg are both related to the dysfunction of t lymphocytes and there may exist some connection between the 2 disorders . here we report an 82-year - old man diagnosed at the same time with mg and mcd . we will also discuss their relationship and report on the results of literature review regarding the temporal onset of mcd against mg . an 82-year - man who had been robust in health before was admitted to our hospital due to dizziness , blurred vision , and fluctuating weakness that lasted for 2 months . in addition to this chief complaint , nephrotic syndrome was found incidentally at the same time . neurological examinations showed limited extra - ocular movement ( eom ) to the 4 directions , especially when looking to the left side . mild improvement of left eye size and eom limitations were found 3-minute after ice pack treatment . thyroid dysfunction - related problem was not favored due to negative laboratory data of thyroid function ( 13.1  pg / ml of free t4 , 11.6  ng / ml of thyroglobulin , < 20  iu / ml of anti - tg antibody , 25.9  iu / ml of anti - tpo ) . radiographic results showed no goiter or brain lesions according to chest computed tomography ( ct ) and brain magnetic resonance angiography . laboratory data showed 9.5  g of daily urine protein , 1.1  mg / dl of serum creatinine , 221  mg / dl of low - density lipoprotein cholesterol , and 1.6  g / dl of albumin . there was no diabetic mellitus and negative results for complement 3 ( 143  mg / dl ) , complement 4 ( 35.1  mg / dl ) , syphilis test , hepatitis b , hepatitis c , immunoglobulin g ( 898  mg / dl ) , immunoglobulin a ( 288  mg / dl ) , and immunoglobulin m ( 129  mg / dl ) . he denied any prior medications before this admission , including nonsteroidal anti - inflammatory drugs . due to suspected mg , therapeutic treatment with pyridostigmine ( 60  mg ) was given 3 times . each time 30  minutes after medication we found improvements for ptosis , eom limitations , and blurred vision . one month after the diagnosis of mg and nephrotic syndrome , he was admitted again for renal biopsy . renal biopsy was done smoothly but he started to have choking , dyspnea , and muscle weakness 2 days after this procedure . the proteinuria declined from 9.5  g to 6  g even without any treatment . one month after renal biopsy , his proteinuria declined to 3.68  g per day . we obtained 30 glomeruli and the depth renal biopsy was sampled between the cortex and medulla . the renal biopsy results were unremarkable with no glomerular , tubulointerstitial , or vascular lesions under light or immunofluorescence microscopy . after discharged from the hospital , we gradually tapered the doses of pyridostigmine and steroid . unfortunately , he developed severe gastrointestinal bleeding and steroid was discontinued 1 month after the renal biopsy . then , he developed severe pneumonia ( klebsiella pneumoniae and staphylococcus aureus of sputum cultures ) and related respiratory distress syndrome before respiratory failure , followed by septic shock and death despite the treatment with piperacillin / tazobactam and erythromycin . finally , his proteinuria declined to 0.05  g per day and serum albumin was 3.7  g / dl . mcd ( also called nil [ i.e. , nothing - in - light microscopy ] ) is a major cause of nephrotic syndrome in the population from children to adults . the most frequent malignancy in mcd is lymphoma and the association suggests that mcd is a disease of lymphocyte dysfunction . the benefit of therapy using steroids and immunosuppressants suggests that mcd is related to the disordered immune system . in some cases of nephrotic syndrome , including mcd , the mechanism is presumably an imbalance between t helper cells class 1 and 2 . in brief , nephrotic syndrome , including mcd , is primarily due to immune dysregulartion , especially the dysregulated t cell functions . thymus is where t cells develop to maturity and where they get through positive and negative selection . in thymoma , thymic proliferation or mg growing evidence supported the association between mcd and thymic disease ( thymoma , thymic hyperplasia , and mg ) . from literature reviews , so far , there are merely 39 cases ( including the present one ) reported with thymoma - related nephropathy . of these cases , the most abundant type ( 22/39 , 56.4% ) is due to mcd , followed by other types like membranous nephropathy and glomerulonephropathy . it is likely that mcd does not occur as a coincident event in patients with mg . focal segmental glomerulosclerosis though could not be excluded but we believed it was less favored . that is because the 30 glomeruli we obtained were from regions of the kidney as deep as the medulla . such unusual late onset of mcd in our patient suggested some secondary causes of mcd , such as mg . second , the proteinuria of mcd dropped ( from 9.59 to 6.00  g ) after treatment with pyridostigmine ( even before plasmapheresis and steroid ) . because there is no plausible immune modulatory action of pyridostigmine in terms of antibody titer reduction however , we can not still exclude less proteinuria is due to good treatment response of mg . this closely clinical course , including diagnosis and treatment , can not exclude the probability that mcd could be associated with mg . third , t cell dysfunction could induce an imbalance between t helper and t suppressor cells . in our case , the t cell dysfunction occurring with mg could also lead to a concurrent mcd . interestingly , the onset time of mcd in patients with thymic disease is generally considered late . mcd had been reported to occur as late as 10 years after the diagnosis of thymoma and 15 years after mg . some hypotheses were put forward in the literature regarding the delayed onset of mcd following thymoma . first , thymectomy might induce altered functions in lymphocytes and that take several years to manifest as mcd . second , mcd - associated thymoma is caused by t cell dysfunction leading to the production of lymphokine , which increases the permeability of glomerular basement membrane . however , the delayed onset presentation of mcd following thymoma may not hold as a general statement as increasing number of cases are now reported . of all these 23 cases , almost half of them ( 11 cases ) the mcd had occurred months or years after thymic disease . on the contrary , only 6 cases developed thyomoa after the diagnosis of mcd , and 6 cases ( including our patient ) had the diagnosis of mcd and mg at the same time . thus , the temporal onset of mcd may or may not be delayed as previously thought . the majority of achr antibody positive mg have thymic abnormalities : 60% to 70% thymic hyperplasia and 10% to 12% thymoma . what we have reported here is the first case with mcd and mg but thymic hyperplasia or thymoma could not be demonstrated in this patient despite extensive imaging although the patient had positive achr abs . we hypothesized that the patient may have delayed diagnosis of thymic disorder after the diagnosis of mg . since 1 case report described a thymoma which was confirmed 5 years after the diagnosis of mg . as severe pneumonia - related septic shock had occurred to our patient later on , it remained unclear whether delayed diagnosis of thymic disorder may occur after mg . delayed onset of thymoma or thymic hyperplasia in mg and mcd is still rare and this is the second case reported so far . moreover , there may be some autoantibodies , such as muscle - specific receptor tyrosine kinase and low - density lipoprotein receptor - related protein , associated with mg without thymic disorder . mcd mostly occurs in children and if diagnosed in adults , clinicians should search for a potential cause such as mg and other associated thymic disorders . in spite of its rarity , clinicians should keep in mind the association between mcd and mg and that mcd may not always occur long after the diagnosis of mg .
abstractbackground : myasthenia gravis superimposed with proteinuria is a very rare disorder with only 39 cases reported so far . of these cases , the most commonly associated disorder is minimal change disease . 
 myasthenia gravis and minimal change disease are both related to the dysfunction of t lymphocytes and hence the 2 disorders may be connected.methods:here we report the first case on a patient diagnosed with myasthenia gravis concurrently with the minimal change disease , and it was presented in the absence of thymoma or thymic hyperplasia.results:treatment for myasthenia gravis also lowered proteinuria of minimal change disease . 
 he ever experienced good control for myasthenia gravis and minimal change disease . 
 however , pneumonia related septic shock occurred to him and finally he was dead . 
 minimal change disease is generally considered to occur subsequent to the onset of myasthenia gravis with causal association . 
 after extensive literature review , we noted only 47.8% minimal change disease had occurred after the onset of myasthenia gravis.conclusion:minimal change disease mostly occurs in children and if diagnosed in adults , clinicians should search for a potential cause such as myasthenia gravis and other associated thymic disorders .