Nephrotic syndrome

Three year old girl only child born to a  young couple was diagnosed as Nephrotic syndrome at one and half years of age. No consanguinity , no family history of kidney disorders . Antenatal natal ,postnatal developmental history all normal .

Was treated by an "adult nephrologist" with daily treatment .A different schedule was used (Not ISKDC ) Daily treatment 2 mg/kg once a day till remission and lower dose continuation .Total duration was two months . She came to remission in the first episode . She had relapses many times during this one and half years . She was on daily steroid through out . Increasing doses while on proteinuria ,but continuing daily treatment almost always the dose was almost one mg per kg .

She was put on cyclophosphamide orally 2.5 mg /kg for three months last year 

She was on Tab levamizol 2.5 mg per kg thrice a day for six months 

She is now on 20 mg daily steroid 

They noticed some difference in the way she looked at things and noticed some white shadow inside  her left eye . 

On examination, She is stunted. weight normal , Blood pressure above 95 centile both systolic and diastolic .

Obviously she is a case of Steroid dependent nephrotic syndrome. Poorly managed and followed up.

Critically analyzing,

1.Duration of steroid in the ISKDC regime or other where at least three  months of adequate dose steroid would have been better to reduce the number of relapses 

2.What about renal biopsy? Renal biopsy was not done .Is it justified to put her on Cyclophosphamide ?

 Yes , she responded to steroid , only thing she relapsed early and frequent relapses Every time she responds to steroid . Total cumulative dose of steroid caused toxicity . Renal biopsy is not indicated in cases of steroid dependent or frequent relapsing. 

We may choose one of the policies for treatment of these cases. 
Most favored one  is taper slowly ,titrate and continue low dose steroid .If the needed dose is 0.5 or .0.7 mg per kg ,continue for one and half years. Of course monitor for toxicity . 
If the minimum dose needed to prevent relapse is above this dose ,toxicity is high. ( or toxicity already occurred go for higher options . Here cyclophosphamide is the best . Either oral for three months as in the above case or monthly pulse for six months. 

3.Here proper monitoring of toxicity was lacking .There is stunting , Hypertension and cataract well established. 

Evaluation from Our institution 

 Her blood sugar, Electrolytes, calcium magnesium are normal 
Her system functions are normal , Hemoglobin is 11 grams 


Our Plans .

She is posted for cataract surgery next week 

After surgery What about her management after cataract surgery? 

Can we continue steroid ? 
if not What other drugs ? 

My first impression was 
" we cant continue steroids as she had all the major three complications. Now any way we have to continue the steroid till her surgery is over as her HPA axis is likely to be suppressed and surgery to be done under stress dose"
 After that ? 
She had already had a three month course of cyclophosphamide. So among the other choices Mycophenolate mofetil is the best. Tacrolymus and cyclosporin. Out of this we have few patients on MMF very good choice as they tolerate it very well , only thing is the cost .
Should we go for it ? "

We discussed with our ophthalmology team 

" Sir , we are going to take away the lens and she needs glass with full correction. Good progressive lenses  which can be worn for distant and reading she needs. Right side is normal now. Even if she develops cataract on the right , no problem we ll tackle it the same way. So if you need steroid , no problem , continue steroid "

That is better  logic . 

Now our task is to bring down the BP ,to make her fit for Aneasthesia . She is put on antihypertensive , Not on Nifedepine only 

Here  one question remian 

OK steroid low dose with good monitoring , dose just enough to prevent relapse is good option for long term.Here BP may come down with lower dose of steroid. and anti hypertensive also we may be able to taper and stop. 
What about stunting ? How much of this grade II stunting due to steroid. How much is it due to other reasons . . Will this steroid affect her final height
Both parents average height, we have plotted in graph, mid parental height . 
We ll follow up her closely , plot her height and weight for next six months 
That is the plan 


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Another ocular problem on steroid therapy which is likely to be missed is steroid induced glaucoma 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4544383/

Patient on long term steroid therapy we monitor most of the complications on daily basis or on follow ups. Eg Hypertension, Secondary diabetes ,infections like tuberculosis and fungal ,steroid induced myopathy ,avascular necrosis of hip osteoporosis etc .
In this context if patient complains of Persisting   head ache we ll search for common causes like Hypertension ,sinusitis .We may exclude benign intracranial hypertension ,TBM ,but very often wont think possibility of glaucoma . We ll check the fundus . 

But testing for Vision and ocular pressure rarely measured 

dengue

Each day we learn some thing new from ICU . Even when features are typical for an entity there ll be something unique in each case . 
Few experiences about cases referred to us as dengue from Periphery 
Common clinical features shared by all of them were fever more than one week , rash circulatory insufficiency and bit of ascitis and pleural effusion .
No doubt most of them turned out to be dengue ,few of them referred withNS1 positive or second week Dengue IgM positive. 
Managed as usual . 
Mortality in dengue is very unusual now with early detection and proper management according to guidelines. Cases missed if at all are due to major complications . 
Out of this case one turned out to be NSI and IgM degue negative , weil felix positive . He responded to Doxicycline. 

Here is another one Now under Treatment in PICU 
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Five year old boy developed fever 10 days back . No running nose cough bowel ,urinary disturbances. Fever subsided with paracetamol . Fever recurred after a gap of two days . High grade fever associated with abdominal pain and vomiting. Vomiting non -bile stained. No bowel disturbances. He was hospitalized and was put on Inj Cefotaxime and IV fluids . As the complaints worsened he was referred to us .
There was no history of rashes. bleeds joint pains . Urine and stools normally colored . 
Routine Investigations done from that hospital showed leucopenia thrombocytopenia . NS1 was done negative ( on the fourth day of fever )

No past history of significant illness. Immunized update. No visits outside . There is contact with a prolonged fever case in neighborhood.

On admission he was fully conscious ,dyspneic RR 80 per minute , no cyanosis. BP 70/40 Capillary refill time <3 second .No edema. No jaundice , No rash or bleeds, No  significant lymph node enlargement .
No pallor , no congestion eyes. irritable child .


System Examination

Upper GI , tongue, lips , throat normal 

Abdomen distended. Liver soft 4 cm non tender ,Spleen 3 cms soft 
Free fluid present 

Respiratory system . Trachea not shifted. Both side percussion dull infrascapular and axillary area . Scattered creps bilaterally . 

CVS. JVP not raised. Heart sounds normal intensity , no third heart sound 
CNS. no focal neurological deficit No signs of meningeal irriation
Provisional diagnosis of Dengue fever with warning signs was made and management accordingly done

Dengue igM negative 

Case was managed as dengue with meticulous fluid management and other supportive measures. 

He is recovering now

Message 

Dont rely too much on the Lab tests when clinical features are typical . NS1 and Ig M sensitivity is not hundred percent even when both taken together .

ENCEPHALITIS

11 year old girl who was healthy  till one week back had low grade fever followed by focal seizures on right  side. Seizure lasted five minutes.She regained consciousness but recurred after few hours. Fever subsided with one dose of paracetamol and lasted one day only .
No past history of significant illness, 
No contact wit PT, no ear discharge, head trauma
Born our of non consanguinous marriage,Antenatal ,natal postnatal period uneventful 
Development all normal , 
Immunised update
No family history of any neurological disorders 

On admission altered sensorium  ,
breathing normal ,
 BP 110/70 ,pulse 80/min,afebrile. 
No bleeds ,rash jaundice .
Eye movements normal ,pupils normal size and reaction fundus normal . 
other Cranial nerves normal 
Motor system ,power normal ,tone lower all limbs reflexes sluggish ,plantar up going 
No signs of meningeal irritation

Provisional diagnosis of ADEM /Herpes encephalitis was made 

First level investigations done 

LP done , CSF clear ,normal pressure 

With this Possibility of Encephaltis was high in the list and considering treatable encephalitis patient was put on Acyclovir and supportive measures 

Teaching points 

Patient had mild fever at onset only and dominant fever of encephalitis possibility of bacterial /tuberculosu meningitis not considered high in the list. 
With the blood and CSF result also was not favoring. we did nt put the patient on antibiotics. 
( This is a major decision , in an ICU setting with altered sensorium focal seizures and CSF showing cells it is dictum to put patient on treatable drugs , life is more important and time too short. So usually we take a policy to start management of pyogenic meningitis , acyclovir . At the same time send for virological studies , cultures. A policy to start this and stop later once the possibility is disproved. That ll be a better decision in an ICU . Here many points arguing against pyogenic or tuberculous and we took a decision not to start imperical antibiotics or ATT , but acyclovir only .

With evidence of diffuse brain involvement ,no fever possibility  of biochemical /metabolic , toxic /system function derangement to be ruled out .
Here  biochemical report did not support any of them . ie blood sugar ,electrolytes ,RFT ,LFT .Possibility of poisoning ,no circumstancial or clinical supporting evidences .
With the CSF finding of Lymphocytes possibility again increased for possibility of infection . But this may be misleading , the cell number is low , only lymphocytes. This can happen following any seizure. 
Argument for Herpes encephalitis usually are , cells , lymphocytes but more important is RBC in atraumatic LP . Here RBC were not there. Protein minimal elevation and sugar normal 

We sent the CSF for Virological studies . 

Next day patient developed this movements 

(consent taken from parents in writing )

These were abnormal movements ,(not seizures ) repetitive involving left hands picking hair and dress. Abnormal movement around mouth was prominent. 
Encephalitis with extrapyramidal movements were suggestive of Jap B encephaltis . But this movement is more suggestive of another entity - NMDA receptar encephaltis . In fact many cases earlier were diagnosed as Jap  B encephalitis  before this entity was not known . 
With this possibility in mind we send the CSF for NMDA receptar antibody and 
She was Put on Methylprednisolone and IVIG ( better to give both in this condition ) 

MRI was taken next day

This was the report from radiologist  , but i think there is some basal ganglion hyper intensity in flair images 

NMDA receptar antibody result came as high titre positive 
CSF virological study results from ICMR lab Manipal reported herpes , Jap B Dengue , westnile  viruses negative .

Sensorium improved , but she had seizure on the third day . She was put on Levetirazetam 
Since the last two days the abnormal movement worsened and sensorium deteriorating. Possibility of levetirazetam worsening the situation it was stopped and she was put on dilantin sodium . Short period she was on midazolam drip 

Movements are less today , but the sensorium same. 

Today She is put on Rituximab. 375 mg per meter square . 500 mg per day IV. 
For the abnormal movement she is put on Tetrabenazine 25 mg half tab BD.
Supportive measures continuing. Nutrition fluid ,electrolyte balance maintained mainly be IG tube feeding .


In this context just sharing experience with few cases of NMDA encephalitis came to us during  last two years. 
First case of NMDA was not diagnosed as we did nt give importance to the movement of his face , he was managed as jap B encephalitis . Only after two weeks this possibility was known , We send for NMDA receptar antibody , we managed with IVIG , no response. Later he responded to IVIG plus methylprednislone. Later he was investigated for underlying conditions like gonadal tumors , All negative. He was put on Azathioprim , Now asymptomatic
Another boy diagnosed early because of this experience. but did nt respond to IVIG plus methylprednisolone, We could mobilise Rituximab in govt set up Weely once was given four doses. 
He recovered , He also is under followup now on Azathioprim 

Shall update 

Please read 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2607118/

girl with rash

Six year old girl,previously healthy had low grade fever yesterday. As the fever subsided with paracetamol she was send to school today morning. Teacher noticed to have some odd skin lesions ,brought home. Local pediatrician was consulted ,he referred here 
At the time of admission , her vitals were stable, afebrile .These were the lesions noticed by the parents

No history of mucosal bleeds . She complains of body ache .No lymph nodes ,Joints normal 
Abdomen examination no organomegaly .
CVS and RS normal
CNS fully conscious, oriented, No focal neurological deficit 
No signs of meningeal irritation

Blood results done from outside showed , Total count of 17200 with 70 percent polymorphs . Platelet count 2.3 laksh .ESR was not done 

Possibilities considered 
Previously normal child cutaneous bluish lesions and conjuctival bleed following one day fever first possibility of some infections considered. 
Another possibility was ITP , but the platelet counts done from outside was not supporting. May be they can go wrong. Clinical features very well supporting ITP . 
As there were no pallor ,lymph node or organomegaly , possibility of malignancy was least 
Vasculitis as manifestation of connective tissue disorders at this age bit unusual . CVS examination and other features were not supporting infective endocarditis 
Out of the infections , Dengue was considered top in the list .
Conjuctival congestion , body ache was supporting.Circulatory status was normal . Main point here also was the investigation. Blood count done from outside were against .
Leptospirosis  was possible , but no jaundice , liver was just palpable soft . 
Another possibility considered was Ricketsiel infections which are increasingly reported . 

How to proceed 
Blood culture ,NS 1 antigen , PCV , LFT , Weil felix , Peripheral smear were send . Lepto not send  

Possibility of dengue was high in the list but few odd points clinically and investigations.No rash other than bleed, no cutaneous fleshing , This high count and neutrophil predomiance a bacterial infection was thought of. 
Ceftriaxone will cover possibility of menigococcemia and lepto also we decided to put here on Inj Ceftriaxone. 
Another thought was to put on Doxycycline.  

After four hours she had a generalised seizure. Neck stiffness positive. LP done showed neutrophils .gram stains showed meningococci.

Now question of chemoprophylaxis of contacts, contact tracing . 
We are getting meningococcal meningitis more often . 
Till late nintees we used to see many cases of meningococcemia then. Pyogenic meningitis as such was coming down.
Last year we had few cases of meningococal meningitis . Is it increasing ?


UPDATES 

24/03/2017
She responded very well to Inj .Ceftriaxone. Was afebrile from 48 hours of antibiotics. Antibiotics was continued for ten days 
On 9th day there was an interesting development
She developed painful swelling of right knee and right ankle joint on the same day . There was no fever, no rash , vitals were stable. System examination normal
All other joints were normal. Knee painful restriction of movement and patella tap positive 
USG knee and ankle was done , showed effusion

There was suggestion to aspirate , to put on NSAIDS , steroids. 

Antibiotics was stopped on next day , ie tenth day . No new drugs added, patient was kept on follow up. 
Logic ?
No evidence of active infection by organism . No fever no toxicity . Two joints simultaneously involved due to bacteria in a scenario where every other features support control of infection. Most likely this is immune mediated, reactive arthritis.
Ok , 
Now comes next question.
Should nt we give drugs for that. Steroids. NSAIDS. 
No need 
Swelling gradually reduced and patient discharged