Newborn With Cyanosis

Case details

55 day old baby admitted with excessive cry and low grade fever for 2 days. First born baby to 29 year old father and 22 year old mother conceived within four months of marriage. Antenatal period     uneventful. No history of fever, rash, drug intake. No pregnancy related or other medical  disorders in second and last trimesters. She had usual antenatal care with injection tetanus toxoid, iron and folic acid tablets. Weight gain normal. Antenatal ultra-sonogram was normal. Delivery normal at full term with 2.8 kg birthweight. She cried immediately after birth, started feeds normally. During routine check up doctor detected heart murmur and was investigated by a cardiologist and later referred to Sree Chithra Thirunal Institute. After work up, the baby  was on put on drugs in syrup form to be taken daily. Mother did not notice any problem in the first four weeks. Feeding was normal, no bluish discoloration. Gaining weight in the first 4 weeks was adequate. Since last  three weeks mother noticed feeding difficulty  in the form of suck rest cycle and slowing of weight gain. She also noticed head sweating. His development is proceeding normally .

No family history of any congenital heart disease .

Immunization is upto date

Now baby is admitted for low grade fever and excessive crying. After getting admitted, provisional diagnosis of acute otitis media was made and is now put on oral antibiotics. Fever subsided next day and no  irritability now . 

Before we proceed further, few points for Undergraduates:

Obviously why this baby landed up here now is unrelated to the problem which the parents are worried.

                         " Sir, is it related to his heart condition ?

Can you say -    " NO "   without a second thought ?

Before you reassure the parents, consider few entities related to heart which can be one of the manifestation of heart problem. Here, baby is brought with inconsolable cry. Parents complained of excessive head sweating already. In that setting especially when the baby was all right up to four weeks, one entity to be kept in mind is an 'ALCAPA' ie Anomalous Left Coronary Artery Arising from the Aorta. This is the usual time of presentation of this entity. It usually presents with features of congestive failure. Baby with features of myocardial ischaemia and excessive cry can be one of the manifestations. Most of these cases there wont be any abnormal clinical findings in the newborn examination.

( Please read about this entity. Why late presentation, embryological basis of this entity etc)

 Any way common things always common . 

A patient coming with fever at this age, some infections or inflammations are more important entities eg: Acute otitis media, meningitis .

In our case it turned out to be acute otitis media.

One more condition when a baby  with fever, irritability. excessive cry where we should consider cardiac cause  for excessive cry is Kawasaki disease. Of course not  common at this age,  Kawasaki disease may present in an atypical form occasionally. Always check for other signs like redness of lips and eyes and if other diagnostic possibilities are excluded better to include ECG as an investigation? Irritability is part of the illness. Excessive cry and irritability may be due to cardiac ischemia

A patient diagnosed as heart problem in neonatal period coming with unexplained cry is to be observed for the possibility of cyanotic spell if there is any finding supporting for that. One point to be kept in mind is cyanotic spell does not depend on the severity of cyanosis in an individual case. Spell may be more prominent in a case with mild cyanosis and the other way cyanotic spell need not occur at all in a case with  severe cyanosis.

Babies already worked by the experts is brought to you with some complaint, it is natural only for you to check the the papers and then proceed with your evaluations .Better try to analyse on your own without going through the papers. If you are in a busy OP or if patients general condition is unstable this is not practicable.

Now come to our case . Here what are the diagnostically  useful points?

Stable new born baby was detected to have some abnormal clinical findings in the CVS exam, worked by experts and he was put on some oral medications and baby is surviving at 54 days   

The possibilities are:

1. Congenital heart disease which does not need any emergency intervention, but need medications. May be their plan is to put the patient on medications and decide based on the response.

Just because he is on medications, we cannot say that it must be a structural lesion.

Most common scenario which we are familiar with are structural heart disease going in for failure, most common being left to right shunts and increased flow cyanotic heart diseases where we put the patient on decongestants vasodilators, digoxin etc

But other situations like arrhythmias and cyanotic heart diseases with decreased flow also may be put on long term medications like beta blockers and iron.

So don't be biased, it need not be diuretics and digoxin always.

2. As no interventions  done, we can rule out few of the possibilities like critical stenotic situations on left or right side, TGA without communication, obstructed TAPVC and other situation where baby wont survive without immediate intervention of some sort.

3. Baby did not have much of problems during the first four weeks and was gaining weight. So what drug he was put on in the first week ?
 a. May be drugs for congestive failure which was adequate initially but dose not modified as he gained weight.
 b.May be it is an entity where congestive failure starts later eg.VSD, Endocardial cushion defect etc where the onset of failure may be after initial normal period .

4.May be the diagnosed entity did not have anything to do with the dyspnea or failure to gain weight. Dyspnea and failure to gain weight may be respiratory or metabolic and just because he was worked up in a higher institution for cardiac condition we attribute everything to cardiac condition. May be it may be a benign murmur or few of other benign situations as in small ASD, valve prolapse, bicuspid aortic valve etc.

Asymptomatic period of initial four weeks helps to rule out few other reasons of dyspnea also . Most of the respiratory causes of dyspnea baby can not be totally asymptomatic during this period .Commonest reason for this late onset dyspnoea is pneumonia , in this case unlikely . ( persisting from 30 days to 54 days with mild dyspnoea and no fever. Ocasionally lung malformations like congenital lobar emphysema , Cystic adenomatoid malformation , sequestration lung etc may present in this manner .

What about a metabolic cause responsible for dyspnea? Inborn errors of metabolism with metabolic acidosis usually they start to manifest earlier than . Alos there are  not much points to suggest this possibility here.
So what remains as cause for dyspnea here ?

Suck rest cycle starting from one month of age must be due to congestive failure situation itself. underlying condition of heart is one which becomes symptomatic gradually after first few weeks .

What are the entities to be considered which ll fit with the above situation?

1. Common things always common , left to right shunt VSD , moderate or large is the classical example . They usually presents after a gap . ( please read why they present after a gap even when the size is large.One important point to remind you is just because a baby presented with failure in the early newborn period we cant say it is unlikely to be VSD . VSD can present at that age also in special situations

2.Most of the cyanotic heart diseases with increased flow presenting with failure do so earlier then this .
Other rarer causes of congestive failure like Pompes , carnithin and other causes of Dilated cardiomyopathy , severe anemia , thyroid dysfuntion , hypertension  arrhythmia's are to be considered and ruled out by clinical clues .

Now come to the examination findings 

Baby  active  playful. There is  tinge of  bluish discoloration of lips which increased on crying. Weight was 3.5 kg ie,700 grams over 50 days. About 15 gram per day on an average . According to history this sluggishness in the weight gain is over last four weeks .

Pulse rate was 120 per minute Respiratory rate 40 per minute , no in drawing of chest or noisy

breathing.

Respiratory system exam. RR 40 per minute , no in drawing of chest wall  Chest movement normal ,apex of heart not visible. Air entry equal on both side ,no abnormal or added sounds

Cardiovascular system examination findings

Pulse normal volume ,all peripheral pulses palpable BP not checked

JVP , not seen 

Pre cordial exam .. No pulsations over precordium /jugular or epigastrium . Apex palpated fifth space in the mid clavicular line on the left side not forceful . That means there is left ventricle dilatation .No thrill ,no pulsations felt in suprasternal and epi gastrium

On auscultation First heart sound normal ( pan systolic murmur is there starting from first sound still it is clearly made out  ,second heart sound normal intensity single in the pulmonary area .Third heart sound in the Lower left sternal border and apex .There is a pan systolic murmur grade III maximum internsity in the lower left sternal border .There is a mid diastolic murmur in the lower left sternal border and apex  ( almost equal intensity in the two areas

SO

Step wise analysis .

1.There is tinge of cyanosis , no doubt .

2. Cyanosis is not due to peripheral causes , it is central cyanosis

3. Respiratory causes of cyanosis ruled out as there is no dyspnea at rest to account for it and findings does nt support

4. Cardiac causes  Left right shunt with reversal ? Less likely at this age 

So we are dealing with a case of cyanotic heart disease .

Basically there are two types, decreased flow and increased flow state.

Important ones in the decreased flow state are Fallots, DORV with PS , Single ventricle with PS , Ebsteins anomaly TGA ,VSD with PS.

Important ones among increased flow states are TGV with or without VSD ,DORV without PS and Single ventricle without PS , TAPVC ,Persistent Truncus .

How to differentiate between them and which of the above category our case belong to ?

Any features of failure and mild cyanosis argue for the increased flow state  . In this group TGV even with VSD will have noticable cyanosis . All the others cyanosis ll be mild and we may miss cyanosis

Any spell , severe cyanosis and absence of features of failure argue for the decreased flow states . In this group ebsteins anomaly cyanosis may be mild .

Our case there is no history of spell so far .Baby is not dyspnoic but from mothers history there is suck rest cycle and failure to gain weight both of them should be taken as evidence of failure. So it is an increased flow state CCHD

So from the above list of entities which is fitting here ?

Out of the increased flow group TGV without communcations  is ruled out for sure . they wont survive beyond hours without any intervention. No intervention so far

TGV with VSD ? Yes possible . But more points against this possibility  . They ll be more symptomatic with features of failure dominant and the cyanosis with whatever mixing happening through the vsd , will be much more than this 

Out of the other situations with increased flow state , TAPVC without obstruction is the more likely situation .

DORV without PS , Single ventricle without PS , Persistent truncus are possible but rarer situations . One point difficult to explain in all the above situations is the comparatively asymptomatic state in the first month .

One entity possible here is Endocardial cushion defect which ll present some where in the third or fourth week .

So what does the clinical findings suggest 

Pulse and BP reflects the left side of heart and JVP reflects the right side . In the evaluation of cyanotic heart diseases JVP analysis is more useful than analysis of pulse and BP.
Few clinical useful points  of pulse examination  in a case of CCHD
High volume collapsing nature of pulse in persistant trunkus
High rate and irregularity in ebstein as a rare complication of SVT in associated Pre excitation pathway
Absence of radial pulse in case where BT shunt is done ,or due to embolic phenomenon .
Out of this in our case only useful point is pulse volume . We are considering persistant trunkus as one possibility . In this case pulse volume is normal . 

Precordial examination showed LV enlargement , No RV impulse , percussion not done to elicit RA enlargement or pulmonary area .
Among heart sounds analysis of second sound is the most important in case of cyanotic heart disease. Out of the possibilities considered TAPVC , Endocardial cushin defect was high in the list , but one strong point against these two possibilities Second sound is not wide split , In our case it was single or narrow split .
One useful asuculatory finding is diastolic murmer in the lower left sternal border and apex. What all conditions in this situation we ll get diastolic events .
1. Regurgitation from Persistant trunkus or Pulmoary regurgitation in rare variants of fallots ( absent pulmonary valve . Remember in Persistant trunkus there is one common valve which ll be in competent in 90 percent of cases . So a single closing sound and a regurgitant murmur with high volume collapsing pulse are the rules in a case this high flow cyanotic heart disease state . Both these situations diastolic murmer will be early diastolic one with a high pitch

2 in this case the murmer is low pitch middiastolic murmer , If we get it in the lower left sternal border in a case with tinge of cyanosis possibilities are 1. TAPVC where the high flow across the tricuspid valve causes MDM as we get in ASD .
B Any situation with Tricuspid regurgitation , PAPVC also we ll get this , In TR we ll get Pan systolic murmer and MDM
C Ebateins anomaly multiple sounds in diastole at this area may mimic this entity , Also the systolic muremur of Tricuspid regurgitation can occur
So out of these what is the likely reason in this case ? What is common for the first two situations is the prominent right ventricle . In TAPVC there is volume overloaded right ventricle , in TR most of the cases are due to high outlet pressure the RV ishypertrophic . In our case we did nt get RV impulse
Is it ebstein ?  Can Ebstein be considered in a case where we consider high flow cyanotic heart disease ? Yes . In few cases pulmonary vascularity may be high .
Few very valuable points which we could nt make sure are JVP , RA enlargement we tried to elicit but could nt make out .In ebstein usually we get a comparatively silent precordium . Even though the diastolic clicking sound is described we rarely get this prominent murnur .
Above all one question remains. What is the reason for the MDM which is prominent at the Apex ?

So at this stage , where are we
At the end of clinical examination we had TAPVC and ECD as first possibilities , After clinial examination few strong points arguing against both possibilities. In ECD we get all chambers enlarged. Second sound ll be split . In TAPVC , Right atria and right ventricle ll be enlarged. Here right ventricle not enlarged and LV is enalarged. Second sound is not split . There is one point favoring TAPVC ie MDM at the Lower left sternal border.So most of the points argue out these possibiities
We considered persistant trukus , but here no high volume pulse , no regurgitant murmer. It is out
Can it be single ventricle or DORV there is systolic murmer which is common in both . But very difficult to explain the mid diastolic murmer which is prominent finding.
Many of the findings are favoring Ebsteins anomaly , but history wise our case is one of high pulmonary flow state
So
At the end of our clinical analysis we are nowhere

Investigations 

Not a good film .But cardiomegaly with LV enlargement and increased vascularity . So it is one of the increased flow states.
Thymus not prominent .

ECG  

Rate 120 , rhythm regular . Prominent P waves duration almost 3 divisions ,duration almost 3 divisions ie right atrial enlargement , left atria also .PR interval normal , QRS morphology does nt show any evidence of pre excitation.

Axis left .

Prominent LV , No RV forces

So out of the possibilites we considered all the entities with RV enlargement and RV forces is out. ie TAPVC

Entities with this negative axis
1. Ebsteins anomaly
2.Tricuspid atresia
3.Endocardial cusion defect

Out of this entities Endocardial cushion defect many points are against in clinical examination In the ECG we expect RV forces

Out of the first two both can cause Left axis. Prominent Right atria Promiennt LV forces and atretic RV. so ECG is consistant with Either of the two .
But clinically Out of the two both are decreased flow states . If at all ebsteins can occasionally lead to Increased flow and cause congestive failure.
So at the end
We considered possbility of Ebsteins 

Now what was the ECHO finding?

First ECHO from periphery . this is the reference letter to Chithra 


with the ECHO result which of our finding can be explained.
1. Onset after a gap can be explained
2. Failure with a tinge of cyanosis can be explained
3. Cardiomegaly , but we expect RV forces which is not here
4. Split second sound , not here , which is almost always the case. Is it because of early PH. ? No . RV forces are not there
5. Left axis argues of osteum primum ASD or ECD . it need not always be right upper quadrant axis


This case was worked up in Sreechithithra 





So where are we now

We never heard of a Tricuspid atresia case causing flooding of lung , causing pulmonary hypertension
One doubt here , when the RV is atretic and pulmonary hypertension develops

So not at all conviced with the arguements
Our arguements were
When the Tricuspid valve is atretic the source of blood to pulmonary circulation is through VSD or PDA . from the blood which reaches the left ventricle from two sources. Can this flood the lung when it takes a devious route through VSD or PDA ?
We did an ECHO from our institution also
Findings were agreing to the above
So we learned from mistake
ie .
In tricuspid atresia also rarely there is a possibility of pulmonary flooding if the communication is large and it can behave like an increased flow state.
Anatomy described in the above ECHO ie almost single atrium , allows the blood flow freely to LA . , then to Dilated LV . Here the VSD is so large that it behaves like a single mixing chamber. In that context a low resitance pulmonary vascular system blood takes the less resistant pathway .

One question remains un answered
What is the reason for MDM which we heard very well and that was the main point discussed and we approached the case based on this finding .
For MDM in the Lower left sternal border there should be either smaller than normal patency of the tricuspid  or higher than normal flow across the tricuspid valve. Here in Tricuspid atresia whole aperture here is closed . So both of above can serve as an explanation.. In Tricuspid atresia here ASD is so large that it looks like single atrium. So the volume of LA is twice the normal , So the flow across the Mitral is much higher. May be this higher flow across the mitral caused a flow murmer MDM at the apex and the same murmur heard in the lower  left sternal border.
Fine , that is a good explanation .
But if some body ask back.............Sir , what is the situation in Ebsteins and Tricuspid atresia . the same is the case in all case of tricuspid atresia and ebstein always. In your case if it is taken as an explanation this finding should be there in all cases of TA and Ebstein. But it is not there .
What may be the reason ?
My postulate .........In TA and Ebstein in most of the cases LA is so large and Mitral valve annular dilatation just like what is happeing in Dilated cardiiomyopathy and mitral valve is no more small , so not much of MDM . If the LV is not large due to any reason as in this case annular dialatation may not be significant and this can lead to MDM
This is just a postulate.
We ll wait for experts comments and criticism for our findings , our explanations and wild postulations

Difficult case of Bleeding Disorder

First born girl child of healthy young couple. She was normal and healthy till four and half years of age when she developed spontaneous skin and mucosal bleeds . She was diagnosed from another hospital as a case of ITP after clinical examination and bone marrow studies and was put on oral prednisolone 2 mg /kg for three weeks. She had good response. While dose of steroids was tapered, platelet count decreased and bleeding manifestations restarted.
Tab mycophenolate mofetil was started daily 250mg for two months and later tacrolimus (dose and duration ?) both with low dose steroids. As the condition remained same, she was referred to us.
There is no past history of medications, or significant medical illness . She is immunized up to date. No family history of excessive bleeding tendency in family for three generations.

Analysis of such a case. Few learning  points 

Common complaints of a case with excessive bleeding are superficial bleed in skin or mucosal bleed and occasionally deeper bleeds like GI, hematuria, IC bleed or hematoma or hemarthrosis. In the step wise clinical evaluation of these cases, we need to asses the bleeding with the following questions :
1.Is it a bleed at all?
Why this question ?Occasionally drug rash like fixed drug eruption, a pigmented scar may look like a fading ecchymotic patch.
If the answer is 'yes', it is bleed.
Is this bleeding explainable by a local cause?
Just because bleeding occurs repeatedly, many cases are investigated as bleeding tendency. If it is local cause, you have to tackle the local problem responsible for the bleeding rather than doing work up of bleeding tendency.
For example, recurrent epistaxis form same side of nose may be due to epistaxis digitorum(Little's area bleeding). Patient presenting with hematemesis consider upper GI pathology as reasons eg: peptic ulcer, portal hypertension. Rule out them by clinical or appropriate investigations before asking for coagulation study or platelet workup.
If bleeding is from two or more anatomically unrelated sites, we are dealing with a case with excessive bleeding tendency. Some common mistakes which can happen when we analyse a case is epistaxis, spitting blood, hemetemasis and later malena. Just because bleeding is from multiple sites, we may decide on investigating. Here, anatomical continuity bleeding at one site may mislead you. A problem in the nose may lead on to all the above and our detailed work up will be a waste . Occasionally child abuse patient may come with skin bleeds, hematuria, hemarthrosis and mislead you .
If you ask back, "If the bleeding is from one site only, can I decide the bleeding is unlikely to be having a bleeding tendency ?" - Not always .
Bleeding on one site, we usually consider as a local problem. But, if the bleeding is out of proportion to the injury we should consider underlying bleeding tendency even if it is occurring from single site.
So, what about this case? She had bleeding from skin in the form of ecchymosis, petechiae, purpura, mucosal bleed from lips, gums and epistaxis. It cannot be explained by a local problem, she is having a bleeding tendency .
What is the pattern of bleeding ?
Is it suggestive of primary or seconday hemostasis ?
All of us know how bleeding stops following injury. First step is vasospasm and platelet plug formation. Vascular factors, platelets and Von Willebrand factor are needed for this stage (primary hemostasis ). Once this stage is over, true coagulation process sets in (secondary hemostasis). Pattern of bleeding in primary and secondary hemostasis is different which helps us in clinical evaluation to categorize these two major groups.
A bleeding in to the joint, deep hematoma occur only in coagulation disorder. It wont occur in primary hemostatic disorder.
Bleeding pattern of primary hemostatic disorder is skin, mucosal bleed, petechie, pupura and echymosis. Hematuria, GI bleeds, inracranial bleed etc can occur in severe cases of primary and secondary hemostatic disorder.
One useful point about skin bleed is to look for petechiae. Pin point bleeds will not occur in coagulation disorders. Ecchymosis can occur in both. So most useful points are bleed into a joint which definitely suggest coagulation problem and petechie which argue for primary hemostatic problem .
Occasionally we get a combination pattern of joint bleed and petechie eg in Von Willebrands's disease.
In our case, she did not have joint bleeds. She has mainly skin and mucosal bleeds, she has petechie . So we are dealing with a case of primary hemostatic problem ie vascular, platelet number, platelet function or remote possibility of Von Willebrands .
So we are half way through the analysis. It is most likely a primary hemostatic problem

Is this problem inherited one or an acquired one ?

Late onset of problem argues for an acquired condition, But that is not always the case. Occasionally milder degrees of problem may not manifest. They may manifest during a severe injury or or abnormal investigation result before preparation for surgery.
One more helpful point to answer this question is positive family history. Family history is helpful in two ways.

1. It argues for a hereditary disorder


2. Constructing pedigree chart helps to indicate the pattern of inheritance and hence the type of disorder .


Classical example

So at the end of these four steps, we can narrow down in to six major group of possibilities.

Disorder of primary hemostasis - Inherited or Acquired.

Disorder of Secondary hemostasis - Inherited or Acquired.

Combination - Inherited or Acquired .

Examples of inherited primary hemostasis - hereditary thrombocytopenias, platelet function disorders, Von Willebrand's disease
Examples of acquired primary hemostasis - ITP, hematologic malignancies, SLE, disorders with small vessel vasculitis, drugs interfering with platelet function

Examples of inherited secondary/coagulation disorder - various inherited factor deficiencies

Examples of acquired coagulation disorders. liver disorders, drugs

Examples of inherited disorders of combination -Von Willebrand's

Examples of acquired disorders with combination - DIC

Most likely, our case belongs to the acquired primary hemostatic disorder. Inherited disorders of primary hemostatic disorders like inherited thrombocytopenias and platelet function disorders may present this way. But, late onset and severe manifestations from that point of time onwards. If the late manifestation is explained by mild nature it should behave as mild disorder always. In this case it is not so. So, inherited disorders less likely.
Once we have narrowed down to one of these group, try to further analyse to pin point the problem .

What are the possibilities in this group ?

1. Acquired thrombocytopenias


2. Aquired vascular lesions


3. Acquired platelet function disorder


(in adults rarely acquired problems with Von Willebrand's factor occur in certain malignancies )

• We can rule out the last two easily. Acquired platelet function disorders usually occur due to drugs , toxins systems,dysfunctions like uremia etc
• Nothing supporting these possibilities are present in this case. Vascular disorders of acquired nature, vasculitis ? 
• Here it is not palpable purpura. no other features of a vasculitic disorder. 
• So what remains is a number problem, decrease number of platelets. 

Decreased number of platelets

1. Is it due to decreased production from marrow ?

2. Is it due to increased destruction ?

Decreased number from bone marrow, we know of malignancies leukemia , lymphoma and rarely other ones invading bone marrow like neuroblastoma OR bone marrow aplasia .
Is it one of them? - "No "

Why ?

Total duration is more than for 2 years till now. Without definitive treatment which malignancy will survive that duration ?

OK agreed. That question is easily answered here because the duration is long. Suppose you see the case at the onset of the problem? This point of duration will not help you there.

But, one point is helpful here. Look at the other blood elements- RBC and WBC. There is no evidence of involvement of RBC or WBC. Most of the time, her hemoglobin was well maintained and peripheral smear repeatedly reported their morphology as normal .

OK . If so why can't this be a selective platelet formation problem ?


Decreased production of platelet alone from bone marrow ?

Yes, it is possible. But it is rare.


So what remains is increased destruction of platelets .

What are the reasons for increased destruction? One major possibility which comes to our mind is ITP. Other rarer reasons like mechanical destruction eg microangiopathy, heart valves and other immune mediated destruction like SLE, EVANS syndrome .
Commonest among these is ITP. Thought of the above possibilities, but features supporting them were not there.
ITP .most likely. But why she has persistent bleeding and thrombocytopenia in spite of all the treatment even after two years.
How common is chronic ITP in this young kids? Chronicity is more and more common as age advances)

Coming back to our Case:

O/E

Vitals stable, No pallor, No jaundice , No significant lymph nodes.
(A patient with bleeding tendency may get admitted in our ICU with unstable state .Circulatory status and sensorium are the most important vitals in such cases, severe bleed or an internal bleed can cause shock.
A bleed not significant enough to cause volume loss but causing problems due to the location eg bleed in to the CNS or eyes can cause major problems. Now answer me, if his BP is high and pulse shows bradycardia, what possibility do you consider? Which physical sign will you check?).
*Features of raised intra cranial tension, level of sensorium and pupils.
(All these situations are emergencies, to be addressed without delay.)
Skin and mucosal bleeds present. Caries teeth with bleeding gums.
No skeletal malformations or abnormal appearance ( This point is important in case. In view of non response always better to have a rethinking, inherited thrombocytopenias may be missed. Absent thumb, lobster thumb, triphalngeal thumb, absent radius. Spine and foot anomalies if present argue for these possibilities )
http://www.indianpediatrics.net/dec2005/dec-1246-1247.HTM

Clinical features supporting SLE and other vasculitis were not present ( HIV and SLE are to be considered in all cases like this. Girl child, especially if adolescent consider underlying SLE even when diagnostic criteria is not met )
Abdomen examination- No liver or spleen enlargement. No other palpable mass.

Other system examination were normal

Bone marrow was revised and was suggestive of ITP. She was put on full course of steroid again. She responded for a short period but became symptomatic again.
She was referred to CMC for work up and they did bone marrow as suggestive of ITP .
ANA, HIV, HbsAg negative .
She was put on Dapsone 1mg /kg which she continued for one year.
Since then she was admitted many times with symptomatic bleeds. Throughout platelets remained around 20000/mm3. Hemoglobin and RBC parameters were depending on the severity of bleed. WBC count and morphology remained normal.

Other managements tried in sequence.

• IV gamma globulin,
• 
  
• Azathioprine 1.5 mg /kg, 
• 
  
• Anti D 75 mg/kg
• 
  
• and Pulse Dexona 20 mg/m2 monthly.

All the other measures for mucosal bleeds like tranexamic acid, other supportive measures were being given during episodes.
Now she is six and half years more than two years since the onset
In January 2016, she was admitted with intracranial bleeds in the ICU . Multiple platelet transfusion done did not raise the platelet count . here one point could nt be answered. He was not given platelet transfusion for these episodes. Usually patients transfused frequenly with platelets develop antibodies so that we wont get anticipated rise of platelets with platelet transfusion .
Only option left was to do a splenectomy. But surgical risk was very high .But we had no other choice.
Paediatric surgeons did surgery with full support from paediatric team, platelet concentrate infused immediately before surgery and during surgery. Almost 10 platelet rich plasma transfused.
Surgery completed without problem, her count raised and the bleeding manifestations controlled and there was rise in platelet count following surgery.

She was discharged . Azathioprine, dapsone were continued .

But that response did not last long. She started to have skin and mucosal bleeds again. Platelet counts dropped again.
Why did this happen? She showed initial response but gradual worsening again, is it accessory spleen?
Peripheral smear was checked for the evidence of splenectomy. Peripheral smear did not show changes which we expect in splenectomy. So possibility of accessory spleen was high .

An ultra sonogram abdomen to look for accessory spleen did not show any. Accessory spleen may not be picked up in USG. May be CT or nucleotide scan will give better results.But was not done.

She showed better  response following pulse Dexamethazone.
She is now admitted for pulse Dexamethazone , Azathioprine dose increased to 2 mg/kg .

What next ?

We are planning a trial with with Rituximab. Of course cost is an issue.

Follow up

She was given a course of Rituximab . Doing well after six months now . Azathiprim and Dapsone is continued .
Now she is admitted with pneumonia

Two cases of precocious puberty- Case 2

Second case of precocity was a ten and half year old boy, second child born to an elderly couple (36 year old mother and 44 year old father). Older girl child 17 years is normal and healthy. This boy born preterm at eight month with normal delivery with birth weight of 2 kg. Not asphyxiated, no neonatal problems in the form of hypoglycemia, jaundice, infections. All his milestones were normal (correction for prematurity at earlier ages), catch up growth in all parameters normal . He was normal in studies. 

There was no family history relevant for such a case (please refer to the previous case)

When he was seven years old, one day he came back from school telling that his classmates laughed at him as he had moustache. Parents also noticed hair growth on upper lips. He was taken to an endocrinologist . His growth parameters were normal, he had some hair growth at the pubic area.

They did not have a documentation( it is better to take a photograph for later comparison in such cases ). His bone age was normal for his age. Ultrasonogram abdomen was normal.

FSH and LH showed upper limit of normal. But the ratio was normal . 

He was under regular follow up then, without any intervention.

Now, for the last three months, parents noticed that the pace of the pubic hair growth is increasing. 

Other than this observation he did not have any problems, goes to school and is good in his studies. No head ache, visual problems or any other system problems 

O/E 

Vitals stable .

Height normal for age (no advancement in height )

Weight a bit lower for age 

No neurocutaneus markers . 

He is fair .

Genital examination showed G3. No axillary hair, no facial hair 

Testes size is normal

(upto 3 ml  pre -pubertal )

Stretched penile length normal 

So, what are the points to be remembered here ?

Boy with some features of precocity ( At the age of seven, parents noticed hair growth on face and to some extent genitals, but it was not progressing significantly for the last 3 years. Now he is ten and half years. Onset of sexual hair at this age is normal, but not G3.

Here, testicular volume estimation is crucial. In central precocity, first sign will be enlargement of testes. Here interestingly Testicular volume is normal. But genital hair is advanced.

Peripheral reasons for precocity ie, adrenal, ovarian, testicular or exogenous androgenic source cause advance in sexual maturity in boys mainly in the form of sexual hair, penile length and other features like muscularity,nchange in voice, advancement of height etc.

So here, height is not advanced, sexual hair is advanced, but testes and  stretched penile length normal . USG abdomen done and is normal . 

Questions: 

1. Is there any organic cause underlying or is it just a normal variant? If we consider the onset at seven and half, we should consider pathological causes. But, it did not progress till recently till ten and half year , So ?

2. If we consider pathological causes, is it central or peripheral? The absence of tesicular volume increase argue again it being of central type. But, the commonest reason for peripheral isosexual precocity is virilising adrenal hyperplasia milder variants. But, there is no pigmentation, stretched penile length normal ,  no advancement in height .

The following investigations were planned( in view of the above confusion )

• Bone age
• X-ray hands and elbow
• Cortisol ( one random sample when we take the other test .knowing the limitations)
• Electrolytes sodium and potassium 
• FSH and LH 

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Our thoughts, analysis and decisions may be wrong. Hope, experts in this area may have different views . Let us hear .

Two cases of precocious puberty- Case 1

Two year old girl child brought with left breast enlargement for the last three months .
First born baby to an young couple delivered without any treatment of infertility after one year of marriage. All trimesters of pregnancy was uneventful , no medical illness , no pregnancy related problems . Except for iron tablets  and inj tetanus toxoid , no drugs taken by mother  .

 No family history of precocious puberty, disorders of sexual differentiation, bony problems ,early child death or prolonged medications ( suggestive of a familial endocrinology or syndrome association with precocity. Little bit of explanation about the relevance of above points. Few conditions of precocity have a high chance of inheritance. eg Congenital adrenal hyperplasia virilising types .Other entities like Mecune Albright syndrome basic problem is G protein mutation and hyper function of many endocrine organs out of which precocity is one. Skull and other bony problems are part of this entity .Hormonal medication of mothers are relevant for  evaluation of disorders of sexual differentiation in newborn baby , not much relevant in a case like this with onset of problems after such a normal gap ).

Baby was born at term by vaginal delivery , no resuscitation needed . No neonatal problems suggestive of hypoxia, meningitis, intracranial bleed. Her growth was normal and milestones in all fields of development proceeded normally . Precocity obesity  other hypothalamic /pituitary disorders may occur as a    sequelae of neonatal brain injury .
No history of head trauma, ear discharge, irritability, vomiting suggestive of raised intracranial tension .No recent behavioural changes, seizures, frequent falls or any other history suggestive of an associated neurological problem. Tuberculous meningitis ,  tuberculoma ,craneopharyngeoma are important organic entities behind precocity . One important entity to be kept in mind is hypothalamic hamartoma  , which presents in an interesting way ,gelastic seizures bout of laughter ,
When we take history one point to assess is the onset and course and evolution . Males are more likely to have organic reason underlying. Overall course progressing faster is likely to  have organic basis . Of course other neurological signs like visual field defect ,raised ICT etc always argue for underlying organic pathology . Many cases especially in females idiopathic. ( Experts in endocrinology may not agree with this point as what was considered idiopathic , actual pathogenesis is known now. Only point is i dont know these new advances

She is not on medications from any system . There was no features suggestive of hypothalamic disturbance like polyuria,somnolence , temperature regulation problems .
Immunization up to date.

The breast nodule is remaining almost same during these last three months. Apart from this swelling she did not have any other problem , active alert and playful.
She was worked up in a case by endocrinologist and was suggested to take leuprolide injection they thought of taking a second opinon before that , Hence she was with us

O/E
Her weight is 11 kg . expected for a 2 year old is 12 kg , as above 90 percent of expected.
Her length is  84 cm , expected length is 87 cm, ie a bit lower than normal. This point is very important in the analysis . Unlike when we take measurements  in a child with other medical problems  where we are interested on the lower side or normalcy (which is the situation in our country ) here in a case of suspected advanced sexual maturation we are interested in her height /length ,are they on the heigher side ? as  an advance in the length /height indicates  true precocity .
There are very few situations where we get precocity with normal or lower height . One of the main reason is hypothyroidism .(Peripheral hypothyroidism in a baby can rarely present with sexual precocity . You know why ?  When thyroid hormones goes down if the hypothalamo-pituitary system is normal it will try to compensate by producing more TSH (there can be elevation of gonadotrophic hormones also ). In this baby  her height was a bit on the  lower side. But she did not have any features of hypothyroidism . She was intelligent girl , no constipation , skin normal ,fontanels closed
No  dysmorphic features .
There was no neurocutaneous markers. Cafe au lait spot is relevent in two ways in precocity .
1. Part of neurofibromatosis
2. Maccune albright syndrome. Here she did not have any of the features of these Her head circumstance normal.
 No pallor, lymph node, rash, bony swelling, deformities .
There was breast enlargement on left side with palpable nodule 3 x 3 cm non tender .

Her system examination CNS and GIT normal ,

 Higher function, cranial nerve especially the field of vision and fundus normal . 

Abdomen examination did not show organomegaly or palpable mass. No bruit over abdomen or skull .Her SMR genital was prepubertal .One point relevant here is when we mention SMR always tell the status of genital hair , penile/testes and breast staging separte. There can be discordance in these which are very helpful to pin point the underlying pathology .Here in this girl genital examination showed no hair ,we did nt check the vaginal mucosa. clitoris was normal 

So at the end of clinical exam. what is our provisional diagnosis ? 

Isolated thelarche , YES most probably .which is very common and benign condition . 

Should we investigate at all ?  Yes. 

In fact we can adopt a policy to keep the patient under regular frequent follow up. May be one of the cheapest and simple investigation we can do is bone age assessment 

Investigations : already done from outside 

Counts, hemoglobin, peripheral smear was normal, urine routine normal, Mantoux negative 

Her growth card. 

Plotting leghth/ height over time is very important in the evaluation of precocity . Here we plotted today just one measurement . Changes in height  over time is not available. A growth card which shows a recent advance in the height /length , crossing percentile ( without corresponding change in weight ) is a point arguing for it. One time measurement also may help if it is interpreted with the mid parental height. Here height is not advanced. Weight also is below 50th centile . ( When we record the measurements always measure parents height and record mid parental height . 

Next very important investigation is X Ray hand 

In the evaluation always choose cheaper , non invasive simple ones. Plotting growth chart is the simplest and assessing the bone age the next. For assessing the bone age part to be chosen appropriately. One point is do not ask for wrist X-ray. Instead, always ask for X-ray hand ( This xray does nt show the tip of terminal phalanx ) Bone age is not assessed by looking at wrists only. This should be done more accurately by comparing with standard charts and taking in to consideration epiphysis of metacarpals phalanx also  

Here we compared it with charts and assessed bone age is 2.5. ie a bit advanced bone age . Her age is two 

So now ?

Till now we did nt have any reason for concern . Apart from a breast nodule which is a bit larger , no other indicators to suggest an organic problem to worry . 

But now, her bone age is a bit on the higher side. 

One question here. If she is having an advanced bone age, if it is due to influence of sex hormones why her height is not advanced? Which one is more dependable ? To depend on the normal height and not to go for higher investigations which are costly . 

Or ignore the normal height and give more weight to the advance bone age and go for costly investigations. 

What about the parents height? If they are short, whether the advance in the height masked by her inherent chance of familial trait of stunting ? This is just an argument. In this case both parents are tall above average . 

So what we should do?  

In a parent who can afford, in this scenario better to go ahead with hormonal assay. First FSH and LH . Depending on the level we will decide if the problem is central or peripheral and further investigations depending on their level.

In fact we need not worry about this point . This investigation was already done.

Here comes another confusion.

From the above chart there is no normal value for younger child 

If FSH, LH or both suppressed we need to investigate peripheral reasons ie exogenous introduction of estrogen hormones , ectopic ovarian or adrenal source.

If FSH/LH shows a high value that helps to exclude peripheral disorders as a reason  and we need to consider central causes only . 

In that case what is the cut off value of FSH /LH in this age group ?

 Is FSH high ? A value above 1 in a young child is to be considered doubtful . 

Is LH high? A value above 1 also to be considered significant. More important is LH /FSH ratio. A central hyperactivity.

Here again we are in confusion ; The FSH /LH ratio is not changed. FSH only is raised  , 

So what to do next?

We checked the values for children from standard charts. For that age FSH value can go up to 3.9 m iu/ml

So,

In summary,

Clinically it looks like isolated thelarche  and till few years back we ll take a decision just to  leave alone and follow up.

But few points we cant take it so lightly 

Bone age, advanced , even though minimally which can not be ignored 

Hormonal assay,  FSH is upper limit of normal and LH normal and Ratio is normal . That again creates bit of a confusion , but not strong enough to argue for a organic cause 

What to do?

Endocrinologist have advised Leuprolide . Can we take a stand not to give the drug without further investigation?

We have decided to Take MRI brain. If MRI is normal, keep the patient on regular follow up without any medication .

They will come for follow up with MRI next week. I shall update then.

19/05/2016

MRI was done today 

was normal . Decided to follow up

Atrial Septal Defect

14 year old girl, who had ASD closure five years back, was asymptomatic since then. Normal girl going to school, she was bit depressed as she had deformity of spine which was noticed in early childhood but later progressing. She now complaints of chest pain not related to exertion, mostly at night .Pain is vague she points to left side .She does not have dyspnea on routine activities. As she is having the deformity she does not participate in competitive play activities. No palpitation.

O/E

She is short 146 cms, no shortening of neck or webbing. Apart from deformity of spine, and shoulders no features suggestive of any syndrome.

CVS

Pulse 40 per minute, regular .high volume .

Blood pressure 100/70 in upper limb.

Did not record in the other limbs .

All peripheral pulses palpable.

(At this stage , two important points in the history …1.She is not on drugs .2. Bowel habits ,recent school performance ,3 Head ache vomiting .No need to explain the relevance of these questions in this context )

JVP not raised in her case 

(Again , JVP analysis is important in this context .This low pulse rate , after ruling out other reasons we consider cardiac origin . One of the reasons for this low rate is complete heart block. JVP will show giant “a “waves  episodically .Giant a waves seen with all atrial contractios when there is a mechanical obstruction to the RA eg Tricuspid atresia .

This video in you tube is another case ,  not this girls . Just to stress the usefulness of this examination in bradycardia

Precordial exam. Median sternotomy scar .Apex normal ,Heart sounds normal intensity ,Second sound wide split and fixed.Here again one interesting point. Second sound after surgical correction split remains as such . We all learned about the reasons for wide fixed split in ASD .Major reason we learned is the RA to RV contribution of volume is more than normal leading to wide split , and same volume irrespective of the phase of respiration . If that was the only reason , it should have disappeared once we close the ASD .But that does nt happen . So wide ,fixed split of second heart sound is not due to this alone.

There was an ejection systolic murmur ,grade II .at the pulmonary area . There was no third heart sound ,no clicks.

Why i said about all the above. You expect the systolic murmur also to disappear once the extra amount of RV outflow ceases with closure of ASD . That again does not happen. Why i said about third heart sound.? RV Third heart sound in an ASD indicates and helps to quantify the shunt , You dont expect that in a corrected situation , If it is there there must be another reason .The other reason for mentioning , We may get a residual lesion after closure. or an associated defect like small VSD or PS.The importance of mentioning Ejection click are two 1. Associated PS is so common in ASD ,If it is valvular there can be thrill , higher grades of murmur at second space and a click .One of the commonest association of Secundum ASD is mitral valve prolapse

Her other systems were within normal limits .

   .

Chest Xray PA view . (some artifacts )

v5 v6

AVF &V1

Narrow QRS complexes. <40 /mt . regular , P waves , same rate , P wave and QRS relation maintained .

So it is not a AV dissociation .So something wrong with the atrial generation of impulse at the SA node , and the lower centers are not generating on its own . What about P wave morphology . There are more than one morphology . Few of them positive, most of them negative very close to the QRS , So it is going in the direction below up .Obviously Impulse from SA node is not reaching Atrium , either SA arrest or type III SA block and the electrical activity from atria is originating from another site. most of the cases from much lower near to the AV node .Usually in such situation lower centers will take over  but that did nt happen here. This is an important point for decision making . Whether to intervene or not in this case is decided by 1. Is she symptomatic 2 Whether there is taking over by lower centers and she can maintain the hemo dynamics. 

Here hemo dynamics is maintained , but if it fails and if no lower center taking over, sudden de compensation likely .

Discussed with my friends in cardiology, suggested Holter monitoring , Fixed a date ,

Arrhythmia most common in ASD is atrial fibrillation , but not common in pediatric age groups . I dont know the chance of atrial fibrillation in surgically corrected patients.What is the explanation of SA node problem in this case ? , We diagnosed ASD from this institution and referred her for surgery . At that time her  pulse rate was normal and her ECG did nt show this.So it happended after surgery . They dont have the details of surgery now. This can happen if the ASD was near the SA node.eg Sinus venosus type ASD 

We did an ECHO yesterday .

Holter monitoring is yet to be done.