Pediatric TB , two doubts

One problem discussed by friend today .

Four year old kid ,Father diagnosed Sputum positive pulmonary tuberculosis.Child was symptomatic ,ill nourished. He was put on Cat I ATT . Next week he developed extensive skin rash .

Not sick, No jaundice.

LFT normal .

How to proceed.

Answer for the question was based on following thought. Here i share it to hear your views. Mine is not final comment

" Commonest situation we encounter following ATT in kids are alteration of liver function ,leading to varying levels of derangement and clinical features. Most of them reverse on stopping ATT .

When we take decision we consider two opposing arguments

On one side 1. How important is ATT in this case .
If i stop for short period will this cause major problems due to progression of TB. Most of the cases we see milder cases and few days or weeks of not giving ATT does not matter , So we stop it and there is a method to re introduce . But a situation of TB meningitis or miliary TB withholding ATT even for days is may tilt the balance.

In short how severe is the problem caused by TB

On the other side 2. If we continue any of the drug or all of the drug will it lead to problems.

That is how dangerous is the problem caused by the drug

Eg . Liver dysfunction ,can not be taken lightly . We should view any significant Liver dysfunction very seriously , eg Transaminase level rise more than Twice with or without other parameters or clinical ,We have to stop

But what about other drug related problems .

We occasionally encounter. INH related. psychosis or neurological problems ( peripheral neuropathy is least we encounter.)

Arthritis due to Pyrazinamide. Rashes due to pyrazinamide

Ethambutol causing rash . ( i have nt seen an optic neuritis so far in kids on ETB

We had rifampicin related thrombocytopenia

We had rifampicin related interstitial nephritis

So in these situations what ?

Eg we take a situation of Primary complex ( mild TB in the first argument ) and a Drug problem serious one like deranged LFT , No doubt . Stop all drugs. Put on SM , ETB , moniter Transaminase when it comes down below twice the normal value ,introduce INH and and RFP one by one weekly

But is there any guidelines when we encounter a situation of

Serious TB and a milder of the drug problem Eg drug rash . '

Here are we justified in Stopping all ATT , wait and re introduce ?

What should be the basis of re introduction of drug . ie when re introduce one of them , what should be the sequence?

If the rash disappearance take long and the TB is serious one ?

So considering the above points we discussed the following

" what is the seriousness of TB? how sick the kid is ?

" Ill nourished. Vitals stable, frequent respiratory symptoms , Now chest is clear .Xray , para hilar infiltrates.

So it is not a serious situation of TB. a few days of ATT stopping may not cause problem

"What is the type of reaction and what is the Liver function ?

"Skin lesion maculopapular rashes through t body , Itching. No jaundice. No lymph nodes. No fever . Other reasons for Skin rash thought of , and excluded.Possibility of drug related rash high

Liver function tests came as normal

Already all drugs is stopped since yesterday "

So final decision taken and advised

"So , let us not re introduce the drugs for few days . Normal LFT ,

Chances of skin lesion are more likely to be due to ETB ro PZN .

So let us wait for few days for rash to disappear.

Introduce INH and RFP first

Then introduce PZN , wait for one week. if tolerating it must be ETB .

Then introduce PZN , wait for one week. if tolerating it must be ETB the culprit .

in that case again one problem?

Should we re introduce ETB and see

Should we substitute SM ?

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One more Doubt

Sibling of this kid is two and half years.

Not symptomatic .

Mantauxe 25 mms positive .

What should be the advise

Guidelines say INH 10 mg for six months .

Below 6 years with contact. or mantauxe positivity guidelines say INH only

But strong positivity . of 25 mms , is there a need for doubt " whether to put him on Cat I ATT ?

Case of status epilepticus

Case presentation Patient reported on 24 /10 at 7pm .Seen by me on 26 at 8 am 
8 year old girl child previously normal had low grade fever three days back , controlled with paracetamol. Yesterday developed generalized tonic clonic seizures . .Had mild head ache , vomited once before this. Parents were not sure about the onset progression. As the seizures not controlled with anti convulsants she was referred to us yesterday night . Managed as status epilepticus in PICU ( dilantin loading , and valproate infusion )
She was born at term ,no significant perinatal events , development normal going to school average in scholastic performance.
No fever, weight loss .
 No contact with Chronic cough case. no travel outside .
No family history of seizure mental retardation
No history of trauma, no significant bleeding diathesis
Chance of drug consumption unlikely
Immunized update .

I saw her today morning .
She was conscious ,behavior abnormal ,crying and laughing .In between seems normal , Mood swings frequent .
BP 96-60 . Pulse 80 /mt ,normal in rhythm,volume Temp 98 F ,Breathing normal in depth 20 /mt
She is ill nourished ( both weight and height , not recorded
No significant pallor .
No Injury on scalp,No ear discharge.
No significant lymph nodes No rash or bleeds on skin .
No neurocutaneous markers
No abnormal movement ,Moving all limbs .
(She took one dosha and tea , but vomited. She slapped the staff nurse when she tried to give IV inj)

CNS
Heigher functions , emotional and behvioural alteration as mentioned. He told her name ,but no more answers to other questions.
Craneal nerves , which could be tested. Eye no ptosis , no nystagmus , movements normal. Pupils normal size and reaction Fundus normal , no bleeds
Other craneal nerves normal
Motor system,tone ,power reflexes normal , Yesterday her planter was upgoing , today down going both sides.
No signs of meningeal irriation
Skull , spine normal No bruit ,Crack pot sign neg
Cerebellar signs obviously not there ( she had dilantin bolus .)

Other systems 
P/A. Liver , spleen not palpable No other mass , no distention NO free fluid
Chest clear
CVS normal

Thoughts at this stage? teaching points 
Previously normal child developing fever followed by Generalised tonic clonic seizures ,where most of the other reasons negative 
1. Infection . 
2. Metabolic error triggered by infection 
3 Central demyelination/immune encephalitis 
4.Connective tissue disorders/malignancies 
Out of this chance of infection is highest . 
Among the infection, bacterial and viral highest . Tuberculous ,malaria or rarer organisms like ricketsiels 
Here fever is  not high grade, patient not toxic .No signs of meningeal irritation

In the absence of pallor , No spleen malaria less likely . 

So out of the infections viral infection was top in the list , then bacterial infections .If the patient had antibiotics from outside partially treated pyogenic meningitis would have been a closer DD. Here patient was not put on any antibiotics. No features of immunocompromised state. So by the time this much of features of parenchymal involvment (seizure ,behaviour problem without Raised ICT ) we expect signs of meningeal irritation in case of Bacterial meningitis. So order of possibilities among infection Viral first. 

Out of the viral infections , Herpes and Jap B are the commonest in our areas and Herpes major treatable entity . Features which will help to differentiate between these two are 1. Focal seizures more likely in Herpes. 2. History of smell abnormalities if elicited suggest herpes. 3.Extrapyramical signs in Jap B .( but need not be early ) 

Investigations 
Blood . Total count 16000,DC neutrophil 74, Lymphocytes 24 ,Eosinophil 2.

ESR 10

Serum Calcium 9 , Sodium 135 , Potasium 4. Blood sugar 116 mg /dl

LP done. CSF pressure normal , Clear ,Cells total 60 , Neutrophil 20 per Lymphocytes 80 ,No RBC

Sugar 84, Protein 50 .
CSF collected and sent for virological studies and CBNAT

So where are we now ? after the  basic  investigation results 

Metabolic , electrolyte abnormalities ruled out

CSF contains Cells . Lymphocyte predominant

So ?

Infection

ADEM
Questions here .

Out of the infections which will be first possibility ?
ADEM can it present this way .
Very important to decide clinically as Final confirmation with investigations will take time. We wont get MRI today . We wont get Viral studies result today . Putting the kid covering all these possibilities is possible but does nt seems good , Can you rule out or narrow down further and decide what should be the drug of choice.
 If you are asked to choose just one drug out of Antibiotics, Methyl pred. Acyclovir or Antituberculous

Pyogenic meningitis ?and putting on Antibiotic . Points arguing for jpyogenic meningitis
Total count High. Neutrophil predemonance ?  Good , but what about ESR ..it is 10 .So which way to go , Leucocytosis with neutrophilia argues for PM. but this low ESR very unusual , which of this is to be given weight ? I ll give more weight for normal or Low ESR . The negative predictive value of this is more useful point against PM than the leucocytosis with neutrophila. ( Viral infections occasionally cause this blood picture But high ESR less likely in viral infection ,So viral infection is a better explanation for this Count and ESR

CSF picture

Cells are there. count less than 100 ,predominantly lymphocytes , but some neutrophils. This LP done on the third day of illness.
 , Yes you may get this picture  in pyogenic meningitis , but usually if patient is exposed to antibiotics. Usually the count is higher than this by the time patient presents with this clinical state. One more point , CSF sugar is normal and the ratio with blood sugar is above 75 percent .Above all patient is not having high grade fever , toxicity . Even though it is treatable entity pyogenic meningitis possibility in this case is less likely
Will you avoid antibiotics altogether in this case ?
No , because in medicine unless we are sure about diagnosis , You cant take a decision not to give treatment for a treatable common entity . So i ll put the patient on Antibiotics at this stage. May be i ll stop when i get a stronger evidence against this or more points for other possibilities

Is it virl meningitis or Viral encephalitis ?
Viral meningitis Pathology is mainly meninges with or without minimal brain parenchyma involvment . So features usually are signs of meningeal irritation , raised ICT , but less of focal neurological deficit or seizures. ( Of course these are not hard and fast rules. )
Viral meningitis , usually no meningeal inflamation, more of parenchymal involvment So less chance of meningeal signs, more chance of focal deficit seizures and altered sensorium in the abscence of raised ICT .
In our case more chance of viral encephalitis. than viral meningitis
What is the chance of TB meningitis . Yes CSF cytology argues for it . There can be initial neutrophils even though after 72 hours it ll be replaced fully by lymphocytes. Count of cells used to be little higher , but wont be that high as pyogenic. But biochemistry is not supporting. No rise in proteins
Clinical presention of TBM is usually bit slow ( it can present acutely also ,but rare ), No contact with TB , no lymph node, no Chest signs. Not many points supporting this .
Malaria ? NO , no pallor , no spleen

What is the chance of demyelination and other immune encephalopathies.?
Possible , and to be considered in this case . Points in favor are low grade fever , which disappeared now. . It can present with seizures. behavioural abnormalities. CSF picture supports.
So at this stage Till we get an Imaging ADEM is high in the list
Other immune encephalopathies like NMDA receptar encephalitis , a bit unusual , the seizures charecteristic peri oral movements not present here. Still one of the DDs at this stage

So what drug  put on at this stage

At this stage patient was put on Ceftriaxone only ,
Ideally at this stage Ceftriaxone and Acyclovir are to be started imperically , But as the seizures were under control , and the general condition stable , I decided to get an MRI at the earliest .

MRI .We got after 12 hours of this 

So main DDs were between Encephalitis and ADEM . 

Findings ..There is a hyperintense lesion on the right tempero parietal ares , with local dilatation of lteral ventricles. It is not related to this event. Probably an old lesion
There is diffuse hyper intensity frontal base and temporal area on left side .I am not able to comment on the diffusion and perfusion restriction images. 
These lesions are more suggestive of encephalitis , most probably herpes because of location and the diffuse nature. Less points for ADEM . Basal ganglion not affected argues against possibility of Jap B 

So ..
Now patient is put on Acyclovir and Ceftriaxone stopped. 
There may be difference of opinion , is it fair to cut Ceftriaxone . All of us agree with starting of Acyclovir. Most of us may not consider putting on methyl pred. 
But stopping ceftriaxone? .. 
My decision is based on taking whole picture. Considering many points starting from clinical picture , CSF , MRI. chances of Pyogenic meningitis are very unlikely . 
So let us see ..


26/10/2016 
8 AM

She had generalised seizure at night ,controlled with lorazepam. Now febrile. neck stiffness + 
One finding which we missed yesterday became more prominent today

Small grouped vesicles ,of herpes . 
As the kid looked sick , even though diagnosis is 99 percent herpes encephalitis , we restarted ceftriaxone. ( yesterday she got morning dose ceftriaxone, and skipped night dose )

We could do EEG today

3/11/2016 
12th day 
Fully conscious , afebrile .no focal deficit

Follow up 

case of pale stool

Eight month old boy second child born to a 24 year old mother and 28 year old father both out of non consanguinous marriage .
Bought now with pale stools since newborn period, edema and abdominal distention for the last month .
No antenatal problems in the form of exposure to terratogens or infections,no meternal illness,delivered at term normally with a birth weight of 2.7  kg .Baby not asphyxiated breast fed normally . Mother complained of jaundice from third day ,urine was normal .She says the baby had pale stools at that time. No blood group incompactibility .Baby was active was under phototherappy for three days .From the fifth day onwards vomiting started which was nonbilious . Bowel was normal , no abdominal distention . No history of seizures no altered sensorium. Did nt notice any unusual smell or color of urine or body .He did nt gain weight in spite of feeding normally . ( Mother successfully breast fed the first baby and her feeding technique was normal ) . As this combination was suggestive of inborn error of metabolism he was investigated but no conclusion . As the jaundice subsided by end of first week, vomiting by the end of second week. Baby was discharged on breast feeds. 
Next visit was at three months with pale stools and discoloration of urine noted two days prior .Baby weight was 4.3 kg .Since then stool remained pale ,urine yellow baby did nt gain weight and for the last one month further loss of weight ,abdominal distention and odema both legs . 
No alteration of sensorium ,no seizures any time. 
No bleeding manifestations. 

Teaching point for PGs 
Very important point here is to answer the question when is the onset of this problem .In the newborn period there was vomiting ,jaundice and now again the jaundice reappeared with definite pale stools abdominal distention and odema. One thing is clear there is a cholestatic liver disorder with decompensation of liver function which is fast progressing in an early infant .We are tempted to say the onset is from new born period 
But few points argue against this idea. Jaundice disappeared on the seventh day and it was not there till three months. Vomiting disappeared by end of second week. Above all baby gained weight from 2.7 to 4.3 by the end of third month.Mother says stool color was white. Here you have to take a decision , which of these points to be relied on . If a cholestatic disorder had an onset on third day and the yellowish discoloration of urine did nt persist the stool color she says must be wrong. This is one point to be remembered. a mother is likely to attribute the present problem had a relation to the newborn period .In this case most likely the problems in the newborn period both the vomiting and the jaundice are unrelated to this problem which has an onset and gradual progression from three months. That may be sepsis , or physiological jaundice with another problem responsible for vomiting .

O/E
Breathing normal (not acidotic) ,circulation stable,Irritable .Pedal odema .tinge of jaundice in eyes ,marked wasting around groin axilla,abdomen spine Abdomen distended shiny .

Teaching points

Assessment points in GE

Vital signs .Not only for stabilisation ,but may give diagnostic clues
Findings which gives diagnostic clues
Complications and sequel of the problem ,to assess the extent . 

Vitals...Altered sensorium in this context ,argue for hepatic encephalopathy, IC bleed, electrolyte imbalance 
Breathing Acidotic argues for the type of metabolic abnormalities which may be responsible for the hepatic involvement .
Cirulatory status . If baby sick argues for sepsis 

Clues towards diagnosis in Cholestatic liver disorder .In this case no dysmorphic features. ( If there is abnormal look malformation type possibility of trisomies, watson alagille ,zelweger synrome and few other  intrahepatic cholestasis )
In the eyes , apart from abnormal dismorphic features cataract ,relevent for galactosemia ,Intrauterine infections , trisomies .
Look for other features of intra uterine infections. 
Head size may be abnormal in IU infections and genetic disorders

Hypothyroidism .

Findings which helps to assess the extent of problem and compli
Features of nutrient/micro nutrient deficiency due to malabsorption, eg wasting,bleed , rickets.vitamin E ,Vitamin A deficiency . So look at the eyes for bleed, vitamin A def . apart from the findings which already discussed 
Skin for bleeds , rash ,lipid deposits ,scratch mark in an older child, findings in relation with nutritional deficiency . Few of metabolic disorders also may leave some clue on the skin .
Head.. Wide AF and features of rickets. Palpate fontanels not only for rickets but for bulging due to Intra cranial bleed. Rickets a bit unusual if associated malnutrition is severe 
Tone of baby is important . Hypotonia may occur in many of genetic syndromes with cholestasis,nutrient deficiency .

In this baby skin was normal . No bleeds , rash 
Now very important findings which are relevent for diagnosis in this case. The limbs were spastic and bit rotated position , suspicios of dystonia , cortical fisting. 
Development assessment also interesting. Here there is significant motor delay. ( head control not achieved , not only that other field also delayed. If it is a isolated liver disorder development delay usually in gross motor field. 
When we get delay in other fields it suggest it affect Nervous system also , many entities which cause this considered here eg hypothyroidism , intra uterine infection , Inborn error of metabolism which affects brain and liver cells simultaneously . 
Here one point to be discussed is .. kwoshorkor , in a baby who is not gaining weight , odema, one of the treatable entities is malnutrition either protein calory or other micro nutrients like zinc, iron ,thiamin all of which may cause odema 

Here this baby is not apathetic , but irritable, No skin lesions both of which are imp to consider kwashorkor . One very imp point is abdominal distention. ( System exam showed free fluid ) very uncommon in Kwashorkor unless other complications like Tuberculosis . So malnutrition may be contributing, but not per se responsible for this odema 
About possibility of anemia as cause. No , baby not that pale and he is not dyspneic. By the time anemia causes odema patient ll have all features of congestive failure 

Gastro intestinal system 

Abdomen grossly distended , shiny abdomen  dilated veins mainly sides of abdomen and chest , flow of veins can not be made out easily. All tests of free fluid positive, Liver , spleen not palpable , scrotal odema 

So where are we now. ( We are yet to examine CNS which i ll consider after bit of discussion of the features we got so far . I ll try to link the CNS findings at the end )

A case of liver problem may present 

1. No symptoms , just palpable liver , with or without spleen. 
2. Features of liver dysfunction eg jaundice, bleeds. odema , encephalopathy 

In the first category Just consider the structure of liver and how it can be enlarged. eg ,hyperplasia of cells, reticulo end system, congestion of vein , or bile tree. infliteration of inflamatory cells, infilteration with fat or glycogen ( all of the above cause soft enlargement , Infilteration with malignancies or storage meterials other than glycogen lead to firm liver . None of the above interfere with hepatic cells. They just invade without interfering with cellular organells , So just hepatomegaly . If somehow above pathology block the portal system spleen also enlarges. Spleen may be enlarged in some pathologies which affect liver and spleen both eg viral infectionsn leukemia , malaria etc 
Second category . Features of liver cell function derangement . What that mean , liver cells are damaged. This again depends on to what extent it is due to bilary tract pathology , to what extent cell damage. Pure duct pathology jaundice and fat soluble vitamin deficiency , but no features of cell damage. Cell damage later. 
If cell damage early we ll get featurs of failure. 
The above pattern reflects the biochemistry also . Cell injury leads to release of transaminase . No injury , but canal block more of other enzymes like alkaline po4 ,GGT etc 
Here features of decompensation , and liver not palpable. means liver cells are damaged .
So the type of liver problem is progressively damaging the cells . 
We need not consider entities which lead to storage only .
What are the examples of these groups.
Classical is galactosemia, 
Next tyrosinemia
Fructose intolerence
Hemochromatosis 

Commonest one is galactosemia. In this case is it galactosemia 
No . the onset is early , progress fast. Here no hypoglycemia, no cateract. 
Tyrosinemia , hemochromatosis ..possible 
alfa one antitrypsin deficiency .. Possible but usually a bit late onset and slower progress
PFIC .. possible but slow progression and more of cholestasis 

Now  We ll try to assess the CNS

Development assessment shows delay in other fields also. In the limbs there are features of spasticity and dystonia .

So at the end 
Metabolic liver disorder with early onset and fast progression to decompensation , with CNS involvement , diffuse . interstingly extrapyramidal also 

Investigations 

Now after investigation ?