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CLINICAL Long Cases in Pediatrics

Edited by Dr. KALIM MARWAT


HMC PESHAWAR
SOURCES:
• Dr. Huma Notes
• Nelson 20th edition
• Web sources
• NC Joshi Clinical Pediatrics

1. FORMAT AND CPSP MARKING OF LONG CASE


2. ASTHMA
3. CAH
4. CEREBRAL PALSY
5. NEPHROTIC SYNDROME BY SUIT

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LONG CASE FORMAT
PRESENTING COMPLAINT (P.C):
❖ Always ask in in the beginning (after P.C that was the child absolutely physically n mentally well
before these complaints to know abt chronicity of disease)
❖ There should be maximum of 3 presenting complaints
❖ Write in chronological order

HISTORY OF PRESENT ILLNESS: divide in 4 para

a) Elaboration of presenting complaints


b) R/O differential diagnosis, Associations/complications of disease
c) Treatment history of this episode
d) Systemic inquiry

PAST HISTORY: PAST MEDICAL HISTORY….


• Initial diagnosis when, where, how
• Investigations done so far
• T/M so far at home, S/E of drugs
• # of hospitalizations, reason, T/M at hosp, outcome
• Follow up… how frequently done, what labs done at follow up
• Monitoring of disease

PAST SURGICAL HISTORY:

BIRTH/FEEDING/VACCINATION/DEVELOPMENTAL/FAMILY/SOCIOECONOMIC

ALWAYS ASK PARENTS UNDERSTANDING OF DISEASE plus whether future T/M strategies
discussed like transplant

NOTE: sequence may be tailored according to case, format is made so no aspect of history is left

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GENERAL PATTERN OF HISTORY TAKING IN LONG CASE Marks 10
(CPSP WEBSITE)

Intro 1

o Name
o Age
o Sex
o Relation of attendant with pt.
o Resident of
o Admission date
o through Medical emergency

P/Complaint.... 3

o Chronologic order
o Detail of each symptom
o D/D(questions related to D/D)
o Systemic review(Head to toe)
o Impact on life
o Current Labs and interpretation
o Rx received & their interpretation
o Current status of symptoms...
o Satisfied with Rx or not…
Past history : 3
o K/c...yrs./c...D/D...Cause
o Labs.Rx interpretation
o Counseling abt disease
o Course illness, Follow up and Rx compliance
o Knowledge abt disease
o Complications of the disease
o Complications of Rx
o Associations...(autoimmune diseases)
o Surgery ,transfusion
Birth,feeding,vaccination 0.5
Development, schooling history...impact 0.5
Nutrition history with calorie 0.5
Family history...cousin marriage 0.5
Socioeconomic history... 0.5
Occupation, education, supported by any group, impact 0.5
on life, parents concerns

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Marks obtained
Distribution of marks

History, examination and


methods...20 marks

presentation...5

correct finding....10

Logical interpretation...15

D/D.....10

investigation...10

management plan....15

prognosis and counselling....10

Recent advances....5 mark......

Total marks obtained

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SROUTINE QUESTIONS ABOUT CARDINAL SYMPTOMS
PAIN:
Site, intensity, radiation, character, duration, frequency & periodicity, special time of occurrence,
aggravating & relieving factor, associated phenomenon.

FEVER:
Onset, rigors & chills, grade, diurnal variation, night sweats, pattern, associated symptoms like
cough, ear discharge, sore throat, diarrhea, flank pain, dysuria, fits etc.

WEIGHT LOSS:
• Is weight loss subjective or documented?
• How is the appetite, wt loss with loss of appetite is associated with chronic infections like TB or
malignancy, wt loss with good appetite occurs in hyperthyroidism & DM

MASS:
Duration, site, how it was noted, initial size, any recent change in size, pain, change in overlying skin,
any draining sinus, pressure symptoms like dyspnea& dysphagia.

EDEMA:
• Sudden or gradual onset?
• Localized or generalized? Extent of edema like up to ankles or knees
• How it started? Initial start as early morning periorbital puffiness denotes underlying renal disorder,
starting from feet (CCF)
• Ask associated symptoms like SOB (CCF), anorexia, vomiting, oliguria (renal failure), jaundice (CLD),
diarrhea (malabsorption).

DYSPNEA:
• Is it at rest or on exertion?
• If on exertion, mild, mod or on severe exertion? Ask SOB occurs after walking how many steps or on
climbing stairs etc.
• Is it episodic or continuous? Is dyspnea progressively worsening?
• Duration
• H/O orthopnea, PND
• Is quality of life impaired due to SOB? How many pillows used at night.
• H/O chronic cough, wheezing, allergy, wt loss, edema, cyanosis.

PALPATATIONS:
• At rest or on exertion?
• Duration of attack?
• Does it start or terminate gradually or suddenly?
• H/O chest pain, SOB, heat intolerance, wt los

COUGH:
• Duration? Frequency & severity? Diurnal variation? Is sleep disturbed due to cough?
• Dry or productive? Is sputum scanty or copious, thick or thin, color, hemoptysis, amount of sputum
• H/O wheeze (asthma), wt loss. Anorexia (TB), post tussive vomiting, whoop, change in color of face
during cough i.e. bluish discoloration of face (pertussis)
VOMITING:
Duration, frequency, amount, specific timing, color, hematemesis, relation with food, pain
abdomen, jaundice, anorexia, headache.

DIARRHEA:
duration, amount, frequency, consistency, grading of stools, bloating, flatulence, blood in stools,
mucus, foul smelling, oily, bulky, greasy, difficult to flush, perianal rash, rectal prolapse, abdominal distension,
fever, wt loss.

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JAUNDICE:
Onset, duration, anorexia, vomiting, color of urine, colour of stool, pain abdomen, pruritus, pain
abdomen, edema, bleeding diathesis, altered behavior due to encephalopathy.

HEADACHE:
Duration, onset, severity, character, continuous or intermittent, site, aura, unilateral or diffuse
headache, family history, vomiting, fits, personality changes, specific time of occurrence, early morning
headache in SOL brain, aggravating or relieving factor.

FITS:
• Age of occurrence of 1st seizure? Aura? Generalized or focal? Associated with fever?
• Sphincter incontinence? LOC? Post ictal state? Duration of fit? Frequency? Tongue bite? Frothing?
• Any episode of status epilepticus, H/O head trauma, developmental history, family h/o fits.
• Any specific time of occurrence of seizure.

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ASTHMA

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ASTHMA
P.C
• Known asthmatic
• Recurrent chest symptoms

HOPI:
• Cough… dry, nocturnal, continuous, episodic
• SOB, at rest, on exertion, orthopnea, number of pillows used at night, degree of limitation,
difficulty in talking coz of dyspnea, h/o post tussive vomiting, cyanosis, syncope
• Chest tightness, wheezing
• Night awakenings due to these symptoms
• Seasonal variation of cough plus diurnal variation
• Are symptoms triggered by URTI or viral infections
• Fever…. Absent
• Some degree of FTT
• Eye redness and watering n swelling of eyes…. Allergic conjunctivitis
• Eczema rash
• Other … hx of atopy
• Sneezing and rhinorrhea (allergic rhinitis)

PATTERN OF DISEASE:
✓ Acute & infrequent exacerbation
✓ Episodic, frequent attacks with complete resolution bw attacks
✓ Chronic with persistence of symptoms b/w attacks

CLASSIFY AND CONTROL OF DISEASE Clinically


✓ Day symptoms in 1 mth or week
✓ Night symptoms in 1mth/week

R/O DD:
1) CF: ch diarrhea, marked FTT, fever, green sputum
2) PCD: ear discharge
3) GERD: stomach pain, bad taste in mouth at night while sleeping, vomiting, heart burn

▪ Ask about wheezing as an infant


▪ Age when symptoms begun

LABS: CXR, PFTs, sweat chloride, CT scan, Blood tests, PPD, Sputum

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MANAGMENT:
▪ inhaler… colour, dose, # of puff used, technique, spacer used, how spacer is cleaned, from which
age inhaler is used
▪ How frequently rescue medicines are needed?
▪ Are symptoms reversible with inhaler?
▪ Change in dose and y?
▪ Prophylaxis, LUCAST at night
▪ Compliance to TM
▪ Number of hospitalizations, reason, outcome
▪ How frequently oral steroids used/year? S/E of steroids
▪ How many times in a year ER visits?
▪ Any ICU admissions, intubation for pneumothorax, ventilator needed?
▪ of episodes of status asthmaticus (severe dyspnea, difficulty lying down, drowsiness, cyanosis,
difficulty talking), TM then, length of stay at hospital, outcome
▪ Previous TM , current T/M
▪ Any recent change in symptoms… ABPA

ALLERGENS identified:
▪ Seasonal variation, perfume, cooking, pollen allergy, harvesting season, food allergy, perfume, dust
allergy, smoke, cold, exercise, stress
▪ Are there pets and plants at home?
▪ Any smoker at home? Carpets at home?

LIFESTYLE MODIFICATION:
Damp dusting, removal of carpets, nylon carpets, hypoallergen cover for pillows and mattresses

MONITORING: PEFR, how frequently, technique, record kept, how frequent OPD visits
FAMILY HISTORY of TB asthma, allergies
SCHOOLING:
▪ How many days missed at school?
▪ Does he walks to school? Is inhaler taken with him to school?
▪ Does teachers know abt disease & management?

PARENTS UNDERSTANDING OF DISEASE:

✓ Do they know inhaler should always be with him?


✓ Do they know when to seek medical help?
✓ Do they know sports is not CI?
✓ Use of inhaler before exercise
✓ When 2 hrly inhaler doesn’t relief symptoms and wheezing persists for 24 hrs or more, it’s
an indication to seek medical help

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ASTHMA
Asthma is the chronic inflammation of the lung airways resulting in episodic airflow obstruction due to
increased hypersensitivity to provocative stimuli which is recurrent & reversible.
ETIOLOGY AND PATHOPHYSIOLOGY:

❖ ENVIRONMENTAL RISK FACTORS: allergens, infections, pollutants, microbes, stress leads to chronic
inflammation & aberrant repair of injured airways. Lung dysfunction i.e AHR airway hyper
responsiveness develops, these factors during early life adversely affects airway growth.
❖ GENETIC predisposition…> 100 genetic loci identified, loci containing proallergen, proinflammatory
genes (IL-4) gene cluster on ch 5, ADAM33 gene

CLINICAL FEATURES OF ASTHMA:


Dry cough which is worse at night
Seasonal variation
Recurrent wheezing
Chest tightness
Family history
Improvement with use of bronchodilators

80% of asthmatic patients have disease onset prior to 6 yrs. of age

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EARLY CHILDHOOD RISK FACTORS FOR PERSISTENT ASTHMA:
Parental asthma
Allergy i.e eczema, rhinitis, food allergy
Severe LRTI
Wheezing apart from colds
Males
LBW
Tobacco exposure
Possible use of paracetamol
Reduced lung function at birth

TYPES OF ASTHMA IN CHILDREN:


1) Recurrent wheezing in early childhood
2) Chronic asthma
3) Late onset asthma in obese females at puberty
4) Occupational type asthma in children

ASTHMA TRIGGERS:
Viral infections
Animal dancers/dust mites/cockroach/molds
Pollens
Tobacco
Pollution
Ozone/Sulphur dioxide/dust
Perfumes/hair spray
Cold air/dry air
Occupational pollutants
Exercise/crying/laughter/hyperventilation
Co morbids… rhinitis, sinusitis, GERD

D/D of childhood asthma:


Upper resp tract conditions • Allergic/Ch. rhinitis
• Sinusitis
• Adenoid/tonsillar hypertrophy… (snoring)
• Nasal foreign body
Middle resp tract conditions • Laryngeotracheo bronchomalacia
• Laryngeal web
• Vocal cord paralysis
• TEF, pertussis, vascular ring
• Foreign body aspiration
• Chronic bronchitis
Lower resp tract conditions • Broncho pulmonary dysplasia
• GERD, viral bronchiolitis
• CF, immune def., BO
• PCD, TB, Churg Strauss vasculitis

INVESTIGATIONS:
ASTHMA generally is a clinical diagnosis, certain labs that can help in diagnosis are
1) CXR: hyperinflation, flat diaphragm
INDICATIONS OF CXR IN ASTHMA:
1st episode
Any complication like pneumothorax is suspected
If consolidation/pneumonia is suspected
When conventional therapy has failed

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2) LUNG FUNCTION ABNORMALITIES IN ASTHMA
SPIROMETRY:
1) Low FEV1, FEV1/FVC ratio<0.80
2) Bronchodilator response to inhaled beta2 agonist Improvement in FEV1>12% or > 200ml
3) Exercise challenge... worsening in FEV1>15%
4) PEFR……diurnal variation > 20%

3) PERIPHERAL EOSINOPHILIA...

MANAGEMENT:

1) PARENTAL EDUCATION
2) AVOIDANCE OF TRIGGERS
3) PHARMACOTHERAPY
4) WHEN TO REFER TO HOSPITAL
5) HOME MANAGEMENT
6) FOLLOW UP

➢ GREEN ZONE: 80-100% of personal best… good control


➢ YELLOW ZONE: 50-80% less than optimal control
➢ RED ZONE: <50% of personal best…….. Poor control
• Green zone……….step down
• Yellow zone…. Check technique & advice trigger avoidance
• Red zone … step up

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NATIONAL ASTHMA EDUCATION & PREVENTION PROGRAM
CLASSIFICATION
1ST EPISODE OF ASTHMA/NOT ON LONG TERM TM

persistent
Component Intermittent
mild Moderate severe

< 2 days/week
Day times symptoms < 2 days/week but not daily Daily Throughout day

> 1/week but not


Night awakenings < 2/mth 3-4 times/mth nightly Often every night

Use of rescue > 2 days/week Several times a


medicines < 2 days/week but not daily Daily day

Extreme
Activity limitation None Minor Some limitation limitation

FEV1 % > 80% > 80% 60-80% <60%

Need for systemic


steroids 5 yrs & > 0-1 /yr >2/yr >2 /yr >2 /yr
Recommended step for
initiating therapy STEP 1 STEP 2 STEP 3 STEP 3

Note: In 2-6 week, evaluate level of asthma control that is achieved & adjust therapy, if no clear benefit
within 4-6 week, consider adjusting therapy or think of alternate diagnosis

STEP 1 STEP 2 STEP 3 STEP 4 STEP 5 STEP 6

Medium dose ICS or Medium dose Hi dose


SABA Low dose low dose ICS+LABA/LTR Hi dose ICS+LABA/LTRA+
PREFERRED Pm ICS ICS+LTRA/LABA A ICS+LABA/LTRA oral steroids

ALTERNATIVE Lucast

• LTRA…. Leukotriene receptor antagonist LABA… long acting beta 2 agonist

• At each step patient education, environmental control & treatment of co morbidities.


• Use of SABA > 2 /week for symptom control indicates poor control & need to step up

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Nelson Tables (page # 1095-1115)

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ASSESSING ASTHMA CONTROL & ADJUSTING THERAPY

Components Well controlled


Not well controlled Very poorly controlled

Day time symptoms < 2 days/week < 2 days/week Throughout day

Night awakenings < 1/mth >2 times/months >2/week

Several time/day
Use of rescue medicines < 2 days/week >2 days/week

Activity limitation None Some Severe limitation

FEV1 % >80 % 60-80% <60%

Need for systemic


steroids 5 yrs. & > 0-1 /yr >2/yr >2/yr
Consider short course of
oral steroids. Step up 1-2
STEP up & reassess in 2- steps , reassess in 2-6
Maintain current step, 6 weeks, if no benefits in wks , if no improvement
follow-up 1-6 monthly. If 4-6 wks. Consider in 4-6 wks , consider
Recommended step for well controlled for 3 alternate diagnosis or alternate diagnosis or
initiating therapy months , step down adjust therapy. adjust therapy

DRUG DOSAGE:

Drug Dose
Low dose ICS 200-400 micgm
Medium dose ICS 800 micgm
Hi dose ICS >1000 micgm
0-4 yrs… 4 mg HS 5-11 yrs… 5mg HS
Lucast LTRA >12 yrs … 10 mg
Theophylline 10 mg/kg/day
Salmeterol 50 mg BD
Formoterol 12mg BD
150-375 mg SC 2-4 weekly in severe Persistent
OMALIZUMAB anti IgE asthma in >12 yrs old.

RECENT ADVANCES: omalizumab & allergen immune therapy

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RISK FACTORS FOR ASTHMA MORBIDITY & MORTALITY

BIOLOGIC Previous severe exacerbation requiring ICU admission or intubation


Sudden arrest or resp failure
2 or > hospital admission in previous year
3 or > ER visits due to asthma in previous year
2 or > canisters of SABA used/mth
Increasing & large diurnal variation in peak flows
Male gender/LBW
Poor response to systemic cortical steroids

ENVIROMENT Allergen, tobacco exposure, air pollution, urban area

PSYCOSOCIAL AND ECONOMICAL Poverty, crowding, mother <20 yrs old, uneducated mother
Substance abuse, lack of medical facility
Poor perception of asthma symptoms
Psychopathology in parents

What is PEEK flow Meter / its use?

➢ An instrument to measure peak expiratory flow rate


➢ PEFR is the maximum flow achieved on full, forceful expiration from total lung capacity (after
full inspiration)
➢ Used to monitor effect of day-to-day treatment on airway obstruction in asthma
➢ Daily morning Dips in PEFR suggests worsening of asthma

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STATUS ASTHMATICUS:
A sever exacerbation of asthma that does not improve with standard
therapy is termed as status asthmaticus
1) Oxygen via mask or nasal cannula to maintain sats>92%
2) SABA, salbutamol(0.1-0.3mg/kg) inhaled every 20 min for 1 hr or continuous 5-15
mg/hr / albuterol 0.15 mg/kg every 1-4 hr as needed
3) Systemic steroids pred 0.5-1 mg/kg every 6-12 hrs for 48 hrs
4) Ipratropium bromide 0.5 mg 6-8 hrly
5) Adrenaline SC/IM 0.01mg/kg
6) Terbutaline 1-10 micgm/kg
7) MgSO4... 20-75 mg/kg over 20 min IV

DISCHARGE HOME
IF sats>92% in air, PEFR >70% of best, sustained, Imp in symptoms &
bronchodilator therapy at least three Hrs apart taken at hospital, normal physical
findings... follow up after 2 weeks

IF ALL FAILS……. INTUBATE & VENTILLATE with following settings


• Mild –mod hypercapnia… PC02... 50-70mmHg, short insp, long exp time, 10 15ml/kg VT,
• RR... 8-15 breaths/min, (Low rate) peak pressures <60cmH20

INSTRUCTION NEEDED AT DISCHARGE


I. Avoidance of precipating factors
• Resp. infection
• Vigorous exercise
• Atmospheric pollution
• Inhaled and ingested allergens
II. Advise and adjust child
• prophylactic medications
• Check inhaler and spacer technique and just
III. Provide written plan of action (if asthma worsen) and give instruction on how to recognize
asthma
• Fever, rising RR and Pulse rate
• Restlessness means hypoxia, drowsiness suggests hypercapnia
• To differentiate between tachypnea and wheezing
IV. Teach PEFR measurements for diurnal variation and explain what is adequate or inadequate
control and give diary/card to document PEFR, symptomatology and nomogram of PEFR
Adequate control Inadequate control
• Minimum symptoms • Daily symptoms
• Minimal nocturnal asthma • Daily nocturnal asthma
• No limitation of activity • Reduced activity
• PEFR > 80% of predicted value • < 80% of predicted value
V. Advice regular follow up visits

Advantages of inhaled route


Medications are directly delivered to its site of action, giving a faster onset with
• smaller doses of drug and
• reduced side effects

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What are the types of delivery Devices?
3 main types of inhaled delivery devices according to drug dispersion method
1. pressurized metered dose inhaler(MDI)
• containing a mixture of propellant (Chlorofluorocarbon, Hydrofluroalkanes) and the
drug
• problem with MDI is coordination between actuation and inhalation
2. Dry powder inhaler (DPI)
Utilizing patient’s inspiratory efforts to disperse medications-
Accuhaler/turbohaler/rotahaler
3. Nebulizers
Using the vibration of a piezoelectric crystal to aerosolized liquid

What are the spacer Devices?

Spacer devices are developed to overcome of MDI and are of 2 types


• Valved holding chambers (Volumetric, nebulhaler, baby haler) - the patient can breathe
tidally from a reservoir. Face masks allow spacer to be used by infants.
• Extension devices provide a space between the inhaler and the patient
Choice of inhaler in children
Depends upon
• Type of device
• Patient’s age
• Drug
In 1st two yrs bronchodilators alone may not work due to deficient muscle in bronchial wall.

Age (yrs) Drug 1st choice 2nd choice


0-2 Steroids MDI + Spacer + Face Mask Nebulizer
3-6 Steroids + MDI + Spacer Nebulizer
Bronchodilators
6-12 Bronchodilators MDI + Spacer or Dry Powder Spacer
Steroids MDI + Spacer Breath Actuated MDI
>12 Bronchodilators Dry Powder inhaler or Breath actuated
MDI
Steroids MDI + Spacer Breath Actuated MDI
All ages Acute Asthma MDI + Inhaler Nebulizer

Pattern of asthma in children

1) Episodic virus associated wheezing

• Episodes are more frequent in winter


• Always associated with URTI
• Always asymptomatic between URTI episodes
2) Classic Atopic Asthma
• Most have an atopic background of allergies and eczema
• Day to day triggering of symptoms with exercise or occurrence at night as cough
without URTI
• Responds fast with anti-inflammatory treatment

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3) Cough variant asthma
• Cough without wheezing
• Symptoms relapse when therapy is withdrawn

What is Exercise induced Asthma with pathogenesis?


Vigorous exercise causes hyperventilation with airway cooling.
Pathogenesis:
• Mouth breathing during hyperventilation bypasses nose leading to heat loss that causes
airway cooling
• The mediators, stored in mast cells in temp. Depended airways are released causing airway
narrowing. It is a transient increase in airway resistance and a manageable disorder.

Rx:
The release can be prevented by stabilizing mast cells with
• pre-exercise oral chromoglycate alone or
• with Beta agonists

D/Ds of wheezing

A) Respiratory … intrathoracic anatomic obstruction


• tracheal web or stenosis
• tracheobronchomalacia
• vascular ring
B) Respiratory … functional obstruction
• Cystic fibrosis
• Recurrent aspiration
• Bronchopulmonary dysplasia
• Acute viral bronchitis
C) Cardiovascular
• LVF with pul. Edema and
• cardiomegaly
D) GIT:
• GER

E) Lympholenticular
• Mediastinal mass

D/Ds of Asthma

• Bronchiectasis
• Bronchiolitis in infants
• Bronchopulmonary dysplasia
• CHD/Myocarditis
• TEF
• GER
• Vascular Ring

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What are the classical signs of chronic asthma?

✓ Hyper expansion of chest


✓ Pectus carinatum
✓ Harrison sulcus
✓ Absence of clubbing
✓ Increased RR but decrease breath sounds

What Signs exclude asthma?

✓ Clubbing
✓ Focal resp. signs
✓ Presence of nasal polyp along with sinusitis (immotile cilia syndrome)
✓ Abd. Scar (meconium ileus in neonatal period)
✓ Firm hepatomegaly with signs of CLD (CF)
✓ Association of wheezing with oral feeds-palatopharyngeal incoordination (H-shaped
TEF and GER)

What are issues to be reviewed when child not responding to antiasthamatics Rx?

1) Noncompliance
✓ Not following regularity in using inhaled corticosteroids
✓ Fear of depennce or side effects of steroids

2) Poor inhaler technique


✓ Choose a suitable age appropriate inhaler device
✓ Not to use inhaler when child is crying

3) Ongoing trigger factors


✓ Aeroallergens
✓ Environmental allergens-tobacco smoke

4) Concomitant disease
✓ Sinusitis
✓ GER
✓ Cleft palate

5) All wheezing is not asthma


✓ Review Diagnosis of asthma

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Nelson Tables (page #1095-1115)

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CONGENITAL ADRENAL HYPERPLASIA

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Cholesterol

Cholesterol
desmolase

17α-Hydroxylase (A) 17α-Hydroxylase


Pregnenolone 17-OH Pregnenolone Dehydroepiandrosterone

3β-Hydroxysteriod
Dehydrogenase
(D)
Progesterone 17-OH Progesterone Androstenedione

21β-Hydroxylase
(B) 11-Deoxycorticosterone 11-Deoxycortisol
Testosterone

11β-Hydroxylase
(C) ZONA RETICULARIS
ANDROGENS
Corticosterone Cortisol

Aldosterone
synthetase

Aldosterone cortisone

ZONA FASCICULATA
ZONA GRANUMERULOSA GLUCOCORTICOIDS
MINERALOCORTICOIDS

Salt-wasting CAH
• 3β-Hydroxysteriod Dehydrogenase (3β-HSD)
• 21β-Hydroxylase
Hypertension with CAH
• 11β-Hydroxylase
• 17α-Hydroxylase

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Summary of CAH
17α-Hydroxylase 21β-Hydroxylase 11β-Hydroxylase 3β-Hydroxysteriod
Enzyme (A) (B) (C) Dehydrogenase (3β-
↓ ↑ HSD) ... (D)

Aldesterone ↑ ↓ ↓se Aldosterone ↓


↑ 11-
Deoxycorticosterone
Cortisol ↓ ↓ ↓ ↓
Androgens ↓ ↑ ↑ ↑
BP ↑ ↓ ↑ ↓
K+ ↓ ↑ ↓ ↑
Labs ↓se ↑se Renin & ↓se Renin ↑se sex hormones
Androstenedione 17-OH Progesterone

Presentation • 1% of CAH • Most common • 5% of CAH • 2%


• HTNsive (90%) • HTNsive type • Salt-losing
• Boys(XY): • Salt-losing • Female: • Both male
incomplete form-70% (in virilization (incomplete
virilization, infancy) (ambiguous virilization) &
ambiguous • Simple virilising genatalia) female(virilization)
genatalia, form-30% have ambiguous
undescended (childhood genatalia
testis precocious
• Female(XX): puberty)
normal, lack • Female :
2ndary sexual ambiguous
characteristics genatalia
(delayed (virilization)
puberty)

Treatment • Hydrocortisone • Hydrocortisone • Hydrocortisone – • Hydrocortisone


• Male: Estrogen • Fludrocortisone also resolve HTN • Fludrocortisone
or Androgens • NaCl • May need • Testosterone
• Female: antiHTNsive Like 25mg every 4
Gonadectomy Ca- channel week
blockers

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CAH
P/C………. recurrent vomiting, fever, failure to thrive,

HOPI…….

R/O causes of vomiting, GERD, pyloric stenosis, IEM

Ask # of vomiting per day, relation of vomiting with feed, is the child hungry after vomiting, mass
abdomen, age of onset of vomiting (pyloric stenosis) technique of feeding, burping, is vomiting more
with liquid or semisolid(GERD) wt loss, fever, irritabity, excessive crying, jaundice, FTT(IEM)

❖ Polyuria, FTT(RTA)

✓ Neonatal…. hypoglycemia, fits, dehydration, collapse, skin pigmentation, ambiguous


genital

✓ Older child….
1. male...precocious puberty… (21-α, 11-β hydroxylase)
2. Female…clitoromegaly, pubic hair, acne, deep voice, facial hair (11-β hydroxylase, 17-α
hydroxylase)
3. Hypertension… (11-β, 17-α)
4. Lethargy, disorientation (cortisol lack)
5. Salt craving (aldosterone lack)
6. Anorexia, wt loss
7. Ambiguous genitalia
8. Skin pigmentation generalized
9. Increased pigmentation in axilla & genitalia
10. H/O jaundice, urinary problems abnormal odor…. R/O IEM
11. Recurrent sinus or pul. Infections (poor response from stress of infection)
12. Drug/infection/ autoimmune diseases hx which cause Addison’s disease
13. R/O causes of 2nday Addison’s disease (pituitary tumors, Pituitary radiation, isolated cong.
ACTH def, Head trauma)

Past medical history

• When, where, how… diagnosis made, length of hospital stay, education given and Rx at
hospital and for home.

• If older child with CAH ask about deterioting school performance, ataxia… ALD

BIRTH HISTORY: mode of delivery, vigorous resuscitation at birth…NICU admission… adrenal


hemorrhage

INVESTIGATIONS…. electrolytes, USG, karyotyping, hormonal studies, cystourethroscopy, urinary


Testing (for reducing substances)

TREATMENT...iv rehydration, hydrocortisone, fludrocortisone, compliance, change in dose during


stress and infection

✓ # of admissions? duration? Reason? Outcome?


✓ Past surgical history… Surgery for genitalia

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✓ F. up and monitoring… frequency, wt, ht, bone age, electrolytes at each visit and drug compliance.

COMPLICATIONS

• Adrenal crisis…vomiting, diarrhea, dehydration, fits, drowsiness, skin pigmentation

• Psychosocial behavior, Treatment complication (steroid side effects)

FAMILY HISTORY… consanguinity, similar illness, sib’s death, antenatal screening, sib screening and
Genetic counselling.

PARENTS UNDERSTANDING OF DISEASE


• inheritance pattern?
• prenatal diagnosis?
• steroid use during pregnancy
• Gender of rearing? Any surgery advised & at what age?
• Stress dose knowledge Impact of disease on the child and family

SOCIAL HISTORY:

✓ Psychosocial growth of children Impact of disease on child’s psychological state… Male


or female type play activities
✓ Impact of disease on family

DIAGNOSIS
1. PRENATAL:
Hormonal level in amniotic fluid AF
HLA typing of AF or CVS cells
Molecular genetic testing of AF or CVS cells
CYP21 gene mutation

2. NEONATAL:
✓ Neonatal screening method.
✓ ↑ 17-OH progesterone
✓ Affected females have ↑↑ testosterone levels
✓ Both genders have ↑ androstenedione levels

CAUSES OF ADRENAL INSUFFICIENCY:

AUTOIMMUNE ADRENALITIS APS I, APS II, APS IV

INFECTIOUS SDRENALITIS TB, AIDs, fungal infections

GENETIC CAUSES CAH, ALD, TRIPPLE A syndrome, Kearns sayre syndrome


OTHERS ✓ B/L adrenal haemorrhage
✓ B/L adrenalectomy
✓ Adrenal infiltrates due to mets/lymphoma
✓ Drugs…. Ketoconazole, mitotane (anticancer), etomidate (I/V
GA)

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Management of CAH
✓ Function of adrenal

✓ Multidisciplinary approach
• Neonatologist
• Pediatrician
• Endocrinologist
• Urologist
• Plastic surgeon
• Radiologist
• Geneticist
❖ 21-β hydroxylase Deficiency
>90 % cases, 2 types

a. Classical b. Nonclassical

2 types… ✓ EZ activity 50-80%


✓ Salt wasting (70%) having EZ activity < 1%
✓ Simple virilizing (30%) … EZ activity < 1-50 %

1. SALT WATING 21-β HYDROXYLASE DEFICINCY


✓ In 21 OH def, aldosterone and cortisol are not formed and step before the deficient EZ
shunts the 17-OH progesterone towards formation of excessive androgens resulting in
ambiguous genatalia in females and precocious puberty in males.
✓ Aldosterone /cortisol def. leads to salt wasting
Rx:
• Aldosterone def. loss of salt and H2O Rx with Fludrocortisone.
• Excessive Androgens suppression then by Glucocorticoids (hydrocortisone).
• Ambiguous genatalia Plastic surgery.

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o GLUCOCORTICOIDS THERAPY
• HYDROCORTSINE SODIUM SUCCINATE 15-20 mg/m2/day in 3 equally divided
doses with
✓ Single morning dose
✓ 2/3rd dose in afternoon and
✓ Rest in evening
• Double or triple doses are required in times of stress, surgery or infections.
• Natural steroids like Hydrocortisone and corticosterone are the only steroids that
have necessary mineralocorticoids activity.
• Synthetic steroids like dexamethasone, prednisolone don’t have sufficient
mineralocorticoid effect.
• Monitoring therapy:
✓ Pubertal development by period examination
✓ Skeletal maturation by serial radiograph of wrists and hands
✓ 17-OH progesterone level and androstenedione level early in morning
before taking the morning medications.
✓ Desirable 17-OH progesterone is in high normal or several times normal
level … low level indicate high excess glucocorticoids therapy.
✓ linear growth… maintain along percentile. Higher height percentile under
treatment while loss of percentile and weight gain overtreatment.

o ADRENAL CRISES
• Triggered by stress, infection, surgery.
• Presents as vomiting, dehydration, collapse and shock.
• Decrease (Na, glucose), increase K+ + Hormones (Renin, ACTH, 17-OH
progesterone)
• Mx: Of
✓ of dehydration and shock
✓ correction of electrolytes imbalance
✓ Hydrocortisone IV --mg/m2 stat & then --mg/m2 in 4 divided doses for 1st 24
hrs (infant- 10mg, toddler-25 mg, child-50mg, adolescent-100mg)
✓ Fluid of choice is 5-10% dextrose water with normal saline.

o MINERALOCORTICOIDS THERAPY
FLUDROCORTISONE (FRLURINEF)
• Infant--- (0.1-0.3 mg in 2 divided doses, up to 0.4 mg can be given) often require
sodium supplementation (sodium chloride, 8 mmol/kg) in addition to the
mineralocorticoid.
• Children: --- 0.05 – 0.1 mg daily which is a maintenance dose
• Monitoring therapy:
✓ Vital signs; tachycardia and hypertension are signs of overtreatment with
mineralocorticoids.
✓ Serum electrolytes should be measured frequently in early infancy as
therapy is adjusted.
✓ Plasma renin activity is a useful way to determine adequacy of therapy; it
should be maintained in or near the normal range but not suppressed.
o ANTIANDROGEN
• such as FLUTAMIDE to block the effects of excessive androgen levels, and/or

38
• an aromatase inhibitor such as ANASTROZOLE, which blocks conversion of androgens to
estrogen and thus retards skeletal maturation, a process that is sensitive to estrogens in
both boys and girls. Aromatase inhibitors generally should not be used in pubertal girls
because they will obviously retard normal puberty and may expose the ovaries to
excessive levels of gonadotropins.
o GROWTH HORMONE,
with or without LUTEINIZING HORMONE–RELEASING HORMONE AGONISTS to retard
skeletal maturation, has been suggested to improve adult height.
o SURGICAL MANAGEMENT OF AMBIGUOUS GENITALS
• 2-6 months of age should be the age of intervention
• Each reconstructive surgery should be preceded by cystourethroscopy.
• Steps of surgery
✓ Clitoral resection
✓ Vaginal extravasation
✓ Labioscrotal resection
✓ Reconstruction of labia minora
• Revised surgery at adolescence.
2. SIMPLE VIRILIZING 21-β HYDROXYLASE DEFICINCY
• Hydrocortisone to suppress adrenal androgen synthesis
• This may stimulate pituitary gonadotrophins release leading to true precocious puberty.
• Such patient should be treated with GnRH analogue like Leuprolide
• PRENATAL RX
✓ Dexamethasone that crosses placenta 20 µg/kg pre-pregnancy maternal weight
in 2 or 3 divided doses.
✓ This suppresses secretion of steroids by the fetal adrenal, including secretion of
adrenal androgens. If started by 6 wk of gestation, it ameliorates virilization of
the external genitals in affected females.
✓ CVS is then performed and Rx continued only if fetus is female.
✓ Effects of therapy:
➢ Fetus: Low birth weight, increased shyness
➢ Maternal side effects of prenatal treatment have included edema,
excessive weight gain, hypertension, glucose intolerance, cushingoid
facial features, and severe striae.
3. 11- β HYDROXYLASE DEFICINCY
• In 11-Oh def, aldosterone and cortisol are not formed but Deoxycortisone (DOC),
precursor of aldosterone is formed in excess causing HTN & Hypokalemia, alkalosis,
• Salt wasting doesn’t occur
• 17-OH progesterone towards formation of excessive androgens resulting ambiguous
genatalia in females and precocious puberty in male.
RX:
• ↑ DOC HTN Rx with Antihypertensive
• Excessive Androgens suppression then by Glucocorticoids
(hydrocortisone).
• Ambiguous genatalia in female Plastic surgery

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4. 3-Β HYDROXYSTEROID DEHYDROGENASE (3Β-HSD) DEF,
• In 3β-HSD def neither cortisol nor aldosterone is formed
• Testosterone is also not formed while DHEA is formed which causes mild virilization in
female and males so both with ambiguous genatalia due to lack of DHT.
• They are salt loser as both aldosterone and cortisol are absent.
Rx:
• Fludrocortisone
• Hydrocortisone
• Male will require Testosterone depots for phallic enlargement in infancy and
replacement therapy at puberty.
5. 17-Α HYDROXYLASE Def
• ↑ DOC HTN
• ↑ progesterone & Pregnenolone
• Hypokalemia
• Suppression of renin
• Male will have ambiguous genatalia
• Female with delayed puberty
Rx:
• Antihypertensive
• Genetic males will require Estrogen/Testosterone replacement at puberty depending
upon gender of rearing.
• If Severe def… even if genetic male … do Gonadectomy & Estrogen replacement at
puberty.
6. LIPOID ADRENAL HYPERPLASIA
• Rare disorder of lipid accumulation in adrenals
• Majority die in infancy
• Severe salt wasting
• Male … pseudo hermaphrodite
• Female … normal at birth, delayed puberty
Rx:
• Glucocorticoid, Flurinef & Estrogen replacement at puberty
7. P450 OXIDOREDUCTASE DEF
• POR is required for activity of CYP17 & CYP21
• Partial def of 17-α & 21-β hydroxylase
• an alternative (“backdoor”) biosynthetic pathway is utilized in which 17 -
hydroxyprogesterone is converted to intermediate metabolite that is a much better
substrate for the 17,20-lyase activity of CYP17 than the usual substrate, 17-
hydroxypregnenolone. The metabolite is then converted in several enzymatic steps to
dihydrotestosterone, a potent androgen.
• Glucocorticoid def
• Male & Female…pseudo hermaphrodite
• Maternal virilization
• Antley Bixler syndrome with features of craniosynostosis; brachycephaly; frontal
bossing; severe midface hypoplasia with proptosis and choanal stenosis or atresia;
humeroradial synostosis; medial bowing of ulnas; long, slender fingers with
camptodactyly; narrow iliac wings; anterior bowing of femurs; and malformations of
the heart and kidneys.

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COUNSELING
Family including parents and patients
✓ AR pattern of inheritance
✓ Prenatal diagnosis
✓ Gender of rearing
✓ Fertility issues

GENDRE OF REARING
In case of 17 hydroxylase & 3Β-HSD) DEF
✓ Controversial issue
✓ Discuss with parents?
✓ Genetic sex & sex of rearing should be the same.
▪ Drugs
✓ Antiandrogen (flutemide)
✓ Aromatase inhibitors
✓ GH with or without LHRH agonists
1st approach
• Regime include Low dose glucocorticoid plus an antiandrogen or aromatase inhibitor
2 approach
nd

• GnRH + GH + standard therapy


➢ GH therapy… start at 7-9 yrs. of age & continue for 3-4 yrs
➢ GnRH therapy… start at 7-9 yrs & continued for 3-5 yrs.
• This approach addresses short height & central precocious puberty.

RECENT ADVANCES IN CAH

1. Timed release preparation of Hydrocortisone


2. Clinical trial of Gene therapy

Manifestation Type of CAH


Hypertension 11-β hydroxylase , 17-α hydroxylase
Salt wasting 21-β hydroxylase, 3-βHSD, Lipoid adrenal hyperplasia
Ambiguous genatalia Male... 3-βHSD & 17-α hydroxylase
Female … 21-β hydroxylase, 11-β hydroxylase, 3-βHSD
Precocious puberty 21 & 11-β hydroxylase

Delayed puberty 17-α hydroxylase, lipoid adrenal hyperplasia in female

Hypokalemia 11-β hydroxylase, 17-α hydroxylase

PCOs Late onset CAH

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Adrenocortical insufficiency
Clinical presentation: suspected in any moderately or severally ill child who has
1. Unexplained hypoglycemia, hyponatremia and hyperkalemia
2. Antecedent weight loss
3. Hyperpigmentation due to increase in MSH
4. Vomiting
5. Vitiligo
6. Normochromic anemia or unexplained eosinophilia

Symptoms of cortisol def. Symptoms of aldosterone def.


• Weakness and Wt. loss • Hyponatremia
• Nausea, vomiting, Hypotension, shock • Hyperkalemia
• Hyperpigmentation • Acidosis
• Hypoglycemia and Mild hyponatremia • Dehydration
• Anemia and eosinophilia • Small heart on CXR

Diagnosis
Step I: confirm diagnosis & define cause for Adrenocortical insufficiency
Quantity of: cortisol, ACTH, Aldosterone, Renin, 17-OH Progesterone (in newborn)
Diagnosis Cortisol ACTH Aldosterone Renin
Addison’s disease ↓ ↑ ↓ ↑
Aldosterone Def N N ↓ ↓
Pseudohypoaldesteronism N N ↓ N
Adrenal hypoplasia ↓ ↓ or ↑ ↓ ↑
ACTH unresponsiveness ↓ ↑ N N

Step II: tests needed for therapy


• S. electrolytes
• Blood glucose
• Urea

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Management
❖ Emergency:
1. Fluid to restore intravascular vol. & Renal perfusion
a) 0.9 % NaCl 500 ml/m2 over 1 hr for vol. expansion
b) If hypoglycemia 25 % glucose 2ml/kg (10% in newborn)
2. Glucocorticoids Replacement- Hydrocortisone succinate 75mg/m2/day divided
into 4 doses (this amount has mineralocorticoids activity & can make up for
mineralocorticoids due to infused Na). Normally BP improves in an hr.
Drug Dose
Hydrocortisone 1-2 mg/kg
Prednisone 2 mg/kg divided 3 doses
Methylprednisolone 0.25 mg/kg/day
Triamcinolone 0.03-0.2 mg/kg
Dexamethasone 0.2 mg/kg

3. Treatment for hyperkalemia

❖ Maintenance:
• Oral Fludrocortisone if salt losing variety with physiologic 0.1-0.3 mg/day
• Hydrocortisone 15-20 mg/m2/3 doses

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Addison’s Disease
D/Dx
• ALD… gait issues, regression of milestones
• CAH… dehydration, vomiting, genatalia, FTT
• APG… celiac, thyroid, alopecia, DM, etc
• Fanconi … blood Ix, bleeding, skeletal abnormalities
Cause:
• TB… fever, wt loss, TB contact
• Meningococcemia… rash, child abuse, difficult to sort
• HIV… AIDS
• Drugs … ketoconazole
Labs:
• ACTH, stimulation test, cortisol, aldosterone
• Glucose, S. electrolytes and RFTs
Complication:
• Growth
• Puberty
• Infections
• Fits
• Drug S/E
Course:
• # of admissions
• Complications & management
• Maintaining Rx

END

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CEREBRAL PALSY

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CEREBRAL PALSY
BIODATA: Name, Age, Sex, Address, who is Historian
PRESENTING COMPLAINT:
• Chest infection with fever & cough
• seizures,
• GER
• delayed milestones

HOPI: After elaboration of presenting complaint directly go to birth history


• Fever:
✓ ↓ or ↑, On/Off, Chills/Rigors, Diurnal variations Rx Response
✓ Ass. Cough + sputum, blood
✓ Ear discharge, L/motions, Pus in urine, Rash
• Cough:
✓ Dry/wet
✓ With / absent during /after … feeding
✓ With Resp. distress
✓ Seasonal cough
✓ TB contact, vaccination Hx for Pneumococcal/H.infleunza
• Fits:
✓ GTC, Focal, Ass. With fever, Rx response
✓ Last episode when occur
✓ Rx taken (calculate dose)/ Rx change (by doctor or other advice)
✓ Rx skipped …reason
✓ S/E of AEDs like hepatitis, bleeding etc
✓ Where taken … Hospital name & stay
✓ Ix: CXR, Blood Tests
✓ Rx given … iv fluids at AER
✓ Condition: ↓ or ↑, injuries, state/prognosis explained

BIRTH/PAST HISTORY: establish diagnosis


ANTENATAL:
• H/0 drug intake, HTN, Anemia
• Fever, rash (TORCH inf),
• UTI,
• APH,
• PROM/difficult or prolong labour
• antenatal scan… structural brain malformation,
• Quality of fetal movement/abortion/vaccination

NATAL:
Mode of Delivery, Gestational Age, Birth Wt, Instrumental Delivery, Delayed Cry,
Resuscitation, Oxygen Given at Birth, Admission in NICU, Duration of Stay, Reason,

POST NATAL:
NNS, Resp Distress, Seizures, Jaundice(NNJ), Phototherapy, Exchange Transfusion, Meningitis in
Early Infancy, Head Trauma

✓ When taken to hospital at that time


✓ What labs was done (CSF, USG, CT Scan/ MRI Brain)
✓ What Rx given (IV Abx, AEDs) … dose/fits controlled
✓ Disease progressed.

50
DEVELOPMENTAL HISTORY: (establish Isolated or globally)

• Social smile… comes at 4 weeks, does plays with sibs


• Neck holding… 3 mths,
• Sitting with support. 6 mths without…8 mths walking, talking
• Fine motor. does holds spoon, pencil, toys
• Vision, hearing…. Ask about milestones at present
• Does recognizes mothers face, sibs, responds to her voice
• Spoon, cup drinking water
• Ask about hand preference (hemiplegic CP), bunny hopping, bottom shufflers, commando
crawl (paraplegic)

ASK IS DISEASE STATIC, PROGRESSIVE OR IMPROVING

R/O DD: ask Qs for


• exaggerated startle response… Tay-sachs
• Colicky baby, excessive crying… Krabbe
• DBD/SSPE
• Post-meningetic Squale
• Tumor
• Muscular dystrophy/SMA

DETAILED HISTORY/Complications:
❖ FITS (frequency, duration, age of onset, type, last fit, TM compliance, S/E, drug level,
change of TM, episodes of status epilepticus)
❖ Vision (Focus/Clonus, Squint, Nystagmus)
❖ HEARING… Response/ Aids
❖ SPEECH (dysarthria, expressive or receptive aphasia)
❖ MR
❖ Spasticity… contractures(motor) & ascertain type of CP… quadriplegic spastic, diplegic,
dyskinetic, hemi, floppy
✓ Establish type of CP
• Spastic … Hemiplegic/diplegic/quadriplegic
• Ataxia
• Dyskinetic … 1st ataxia then spastic
❖ Abnormal movements/ fine Motor… Toy play
❖ Behavior (hyperactivity, depression)
❖ Activity of daily living (sitting/standing/walking, teething, bathing, washing, combing hair,
toilet, feeding … calculate calories/current calories)
❖ Ask abt recurrent LRTI, UTI, otitis media, constipation
❖ Bed sores…. Dental caries... incontinence, neurogenic bladder, sphincter control

PAST HISTORY: # of admissions, reasons, duration, outcome

PAST SURGICAL HISTORY: any contracture, tendon release operation

FEEDING HISTORY:

• Feeding & nutrition (sucking, swallowing difficulty, NG feed, GERD, gastrostomy, aspiration,
FTT)
• # of calories taken per day

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INVESTIGATIONS: CT/MRI brain, EEG, karyotyping, metabolic, TORCH screening

T/M: physiotherapy, speech therapy by whom, # of times/day, multivitamins, anti-epileptics

FAMILY HISTORY: if +ve consider DBD

PERSONAL HISTORY: does child goes to special school

FOLLOW UP: # of visits, local GP, pediatrician, physio or speech therapist, ortho, neuro

SOCIAL HISTORY:
• impact on family, financial burden, social burden, how much time mother spends with
child?
• Are other children affected/neglected?
• Is family relation affected by child’s illness?

PARENTS UNDERSTANDING OF DISEASE


• Parents education, is disease curable?
• Mobility (walking aid, gait disturbance, wheel chair, skeletal problem)

DRUGS:
• Epival: fast, bleeding & jaundice
• Revotril: increase secretion of resp. tract and drowsiness
• Debritone:
• Carbamazepine:
• Lerace:

EXAMINATION:
• Introduction, consent, Rt side of patient
• Inspection: posture, accessary, dysmorphism
• GPE:
✓ Pallor, clubbing, vitals, jaundice, Ht & Wt(plot), OFC
✓ Signs of micronutrient … hairs, eye, oral hygiene & thrush, ears
✓ Pedal edema, hypo/hyperpigmentation
✓ Bed sores
• Developmental assessment: hand preference
• Primitive reflexes:
✓ Moro
✓ Grasp
✓ Landau
✓ Tonic neck reflex
• Motor:
✓ UL + LL
✓ Contracture & range of movement
✓ If patient can walk … look for gait
• Cereberal signs:
• SOMI:
• Fundoscopy: optic atrophy
• Sensory system + spine:
• Relative:
✓ Heart: murmur
✓ Chest: detail for infections
✓ Abdomen: fecal impaction, urinary bladder, kidneys

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D/Dx of CP

a) Post-meningetic sequale:
sudden regression, ↑ ICP, large head.

b) DBD/SSPE:
regression of mile stones, Hx of measle, ↑CSF protein

c) Tumor:
regression and ↑ ICP,

d) Muscular dystrophy:
No spasticity, ↓↓ /absent reflexes, normal /↑ CPK,

e) SMA:
• Mimic atonic cp
• Early hpotonia
• Normal mentally
• Absent reflexes

3 types of presentation … commonly

1. A child with static, nonprogressive perinatal encephalopathy … CP


2. A child with gross global dev. Delay since birth … Global Delay
3. A child with regression of already achieved milestones … Neuroregression

53
CEREBRAL PALSY
It is a static encephalopathy/ disorder of posture & movement due to any insult to growing brain in
1st 2 years of life often accompanied by disorder of speech, vision & hearing.

CAUSES: 80% structural brain malformation, 10% HIE…. MRI is more useful

❖ Commando crawl: the child uses arms in normal reciprocal fashion but tends to drag the legs
behind the arm as rudder. Most common muscles involved are paraspinal, hip flexors,
adductors, hamstrings, gastrocnemius

❖ SPASTICITY: increased resistance in 1st few degrees of passive movt & then suddenly
decreases. UMNL… lead pipe rigidity

❖ RIGIDITY: increased resistance thruout passive movt… basal ganglia lesion… clasp knife

❖ Periventricular leukomalacia (PVL) is a form of white-matter brain injury, characterized by the


necrosis (more often coagulation) of white matter near the lateral ventricles
❖ Lesions either of gray matter & white matter of Motor area, Basal Ganglia and Cerebellum are
associated with CP
❖ Clinical Classifications is based on
1) Extremities involved
2) Type of tone abnormalities
3) Characteristic of involuntary movements

TYPE MRI CAUSES S/S


Spastic diplegia (35%) most PVL 70% cases, PV cysts, or Prematurity, Lower limbs
common scars in white matter, ischemia, infections, affected>
enlargement of ventricles, endocrine, upper limbs,
squared of posterior metabolic, thyroid Commando
Ventricles crawl, tip toe
walking,
scissoring,
Difficult to
apply diaper
due to
excessive
adduction of
hip, normal
intellect &
seizures are
rare
Spastic quadriplegia PVL, Ischemia, infection, All limbs
20% Corticospinal/pyramidal Multicystic encephalomalacia metabolic, involved,
tract defect , cortical malformations endocrine, genetic, contractures,
Gross brain malformations developmental bulbar palsy,
aspiration,
severe MR,
fits, visual &
hearing

54
problems,
athetosis is
often present

Hemiplegic 25% Stroke in utero or in Thromboembolic Hand


neonatal life Disorder preference at
Focal infarct/cortical or Infection, early age
subcortical damage developmental Walking
Cortical malformation CMV inf, calcification delayed at 18-
lissen. schizencephaly 24 mths,
circumductive
gait
1/3rd…
seizures
25%...MR

DYSKINETIC 15% Asphyxia: symmetric infarcts Kernicterus Upper limbs


in putamen & thalamus. Asphyxia more affected.
Kernicterus… scar in Mitochondrial Pts are hypotonic
globyspallidus, hippocampus Genetic Speech, feeding,
Mitochondrial. scars in
brainstem, gp, putamen,
caudate, No lesion…DRD . swallowing,
Drooling affected
UMNL signs
absent. Fits rare,
intellect
preserved.

MANAGEMENT IS MULTIDISCIPLINARY APPROACH

❖ Pediatrician, physiotherapist, speech therapist, social worker, nurse, occupational therapist,


ortho surgeon, neurologist

❖ SPASTICITY:
➢ oral diazepam… 0.5-7.5mg/dose BD/QID
➢ BACLOFEN…. 0.2-2mg/kg/day BD/TDS or dantrolene… 0.5-10/kg/day BD
➢ L DOPA … 0.5-2mg/kg/day for dystonia,
➢ Trihexyphenidyl 0.25mg/day BD/TDS
➢ Resperine ….0.01micgm/kg/day
➢ IT baclofen, implantable pump continuous delivery S/E… apnea, dec HR, RR, BP, local inf,
meningitis
➢ BTX A I/M: prevents release of Ach…. Onset of action in 1-3 days, duration for 3-6 mths
indication…
• dynamic contracture in absence of fixed deformity, given to gastrocnemius,
tibilalis posterior, hamstring, neck flexor, iliopsoas.

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• S/E: local weakness, falls, local pain, incontinence, gait disturbance

❖ SDR: selective dorsal rhizotomy… intraoperative stimulation of lumbar nerves,


monitored by EMG, that have increased tone are cut.

❖ ORTHOPEDIC SURGERY:

✓ SEML: single event multilevel surgery,


▪ soft tissue surgery,
▪ tendon release, tenotomy,
▪ iliopsoas lengthening,
▪ osteotomy, open reduction,
▪ salvage arthroplasty,
▪ hip replacement

❖ PHYSIOTHERAPY: selection of orthosis/splints by 3D gait analysis act as ankle arthrosis,


exoskeleton, Soft & hard orthosis, in shoe orthosis, serial casting

❖ OCCUPATIONAL THERAPY: talking type writer, electronic speech generating devices,


special computer

❖ OPTHALMOLOGICAL: for strabismus etc

▪ Squint:50-60%... patching of good eye… surgery


▪ Dec VA… common in spastic quadriplegia… spectacles
▪ Visual field defect, common in hemiplegic

❖ HEARING:
▪ Mild (25- 45 db) … No T/M
▪ Moderate. (45-65 db) … hearing aid
▪ Severe (65-85 db) … Aid
▪ Profound (> 85db) … special education of deaf

HEARING ASSESSMENT AT DIFFERENT AGES of Delayed Child

NEONATE BERA/ABR…. Brainstem evoked response audiometry

INFANT Behavioural audiometry


6-12 months Distraction test… needs 2 trained members
Toddler Play audiometry
VRA…. Visual reinforcement audiometry
Speech Discrimination Test
Older child Pure tone audiometry/ tympanometry

❖ EXCESSIVE SALIVATION….
▪ Reimplant duct into pharynx,
▪ Gland removal,
▪ Section of chorda tympani,
▪ BTX inj in salivary gland,

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▪ Anti-cholinergic
❖ GERD, FEEDING, VISION, HEARING, DIET, SCHOOLING, SPEECH THERAPY

Manifestation Percentage
Fits 60
Hearing defect 10-15
MR 25-50
Visual defect 30 %
Microcephaly 25%
Speech defects 40%

❖ IQ: (mental age/ch age ×100)


✓ MR
▪ MILD = IQ 50-70 … Educatable
▪ Mod = IQ 35-50 … Trainable
▪ Severe = 20-35
▪ Profound = <20.
o CP is a static disorder but manifestation can change from one type to other.
o Earliest diagnosis of CP can be made at 3mths due to persistence of primitive reflexes but full
blown picture is not shown till 2yrs till when the brain growth ceases.

❖ What is developmental delay?


Child getting skills at later age than normal in either one area (Dissociation of growth) or
>2 areas (Global dev. Delay).
What is developmental disorder?
Unusual pattern or sequence of development to underlying disorder & child is unlikely to
catch-up.
Pattern of development delay:
• Speech & language delay
• Delay in gross motor development
• Global dev. Delay

Pattern of dev. Delay Causes


Speech & language delay • Hearing impairment
• Mental sub normality, elective mutism
• Familial environmental bilinguation
• Autism spectrum disorder
• CP
• Mechanical problems
• Dysarthria weakness of muscle of speech
• Dysphonia ab. Of phonation of sound
Delay in gross motor • Environmental … emotional deprivation
development • Familial … lack of opportunity
• Hpotonia … Benign cong. Hpotonia
• Hypertonia … CP
• Neuromuscular disorder … Muscular Dystrophy
• Diminished visual perception … Blindness
Global Delay • Cong. Syndromes … Down syndrome
• Central Neurologic deficit … CP
• MR … chromosomal Defect

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• Familial Delay … IEMs
• Environmental … Neglected Child

Red Flags of Dev. Delay:

Age Dev. Mile Stones


10 weeks No smile, persistent primitive reflexes
Tendency to maintain a fisted one or both hands after 2months
Early head holding due to spasm of neck muscles
6 months Persistent Squint & hand Preference, less interest in people, noises, toys
An obligatory asymmetric tonic neck reflex (in 1st 6 month)
A nonobligatory asymmetric tonic neck reflex after 6 month
10-12 months Not sitting yet, absence of pincer grasp, absence of double syllable babbles
Commando crawl using only upper extremities
18 months Not walking independently, not > 6 words, persisting mouthing & drooling

2 ½ yrs Abcence of 2-3 word sentence

4 yrs Unintelliliglbe speech

❖ WALKING PROGNOSIS IN CP:

Sit unsupported
< 2yrs 97% will walk
Bw 2-4 yrs 50%will walk
After 4 yrs 3% will walk
ATNR at 4 yrs 0%
Hemi.100%
di.90
Walking prognosis Ataxic… 88% Quadriplegic..18%

❖ GMFC: gross motor functional classification

LEVEL- I Ambulatory in all settings


LEVEL-II Walks without aids
Walks with aids, limitation in community
LEVEL-III ambulation
LEVEL-IV Wheel chair or adult assistance required
LEVEL-V Dependent Mobility

❖ PRIMITIVE REFLEXES:

▪ ATNR: is present from birth till 3 mths, if present till 6 mths, suspect cerebral palsy
▪ Dolls eye reflex: neonates eye moves in direction of head till 3 week.

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NEPHROTIC SYNDROME

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Approach to a child with Generalized Body Swelling

Generalised
Body Swelling

CCF Low Albumin Fluid Overload

Renal Loss GI Loss Eematous


CLD
NS Malabsorption Malnutrition

History Taking
Greet and take consent
Name? Age? Resident of?
• Swelling:
✓ For how long? is it increasing, decreasing or static?
✓ More marked in morning and gradually subsides as the day passes?
✓ Ask for associated hematuria, oliguria, dysuria, cola colored urine, headache, upper
respiratory tract infection (1-2 weeks back) or skin infection (2-3weeks back)→nephritic
symptoms
• Chronic diarrhea (PLE)
History of jaundice? Duration? Vaccination? Blood Tx? Surgical interventions (CLD)
• Dyspnea, palpitation, recurrent chest infection, chest pain (CCF)
• Detail dietary history with caloric intake (Malnutrition)
• Fever, joint pain, rash, seizure, oral ulcer, abdominal pain, hematochezia (SLE/HSP)
Rule out complications of NS:
▪ Cough and respiratory distress (Pleural effusion)
▪ Abdominal pain, vomiting and fever (SBP)
▪ Seizure and Hemiplegia (Emboli)
▪ Unilateral limb swelling (DVT)

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Previous history of swelling, age at onset, hospitalization, reason of admission, labs conducted,
duration of treatment, drugs, steroid exposure pattern (Try to establish SDNS, FRNS and SRNS),
and complications related to disease or drugs, biopsy done or not
Past history of prolonged cough, TB or DM
Family history of NS, anyone on dialysis or renal transplant
Drug history:
• -Steroids: striae, skin infections, cushingoid, oral thrush, cataract, hypertension
• -Cyclophosphamide (Endoxan): Leucopenia, hemorrhagic cystitis, alopecia and gonadal
toxicity
• -Levamisole: leucopenia, pruritis, alopecia
• -Cyclosporine: nephrotoxicity, hypercholesterolemia, gout, HTN
• -Tacrolimus: nephrotoxicity, hyperglycemia, GI upset
Vaccination status/Development/ Birth history
Examination:
Refer to Wayne Harris short case of edema
✓ Greet and consent
✓ Height, weight and blood pressure
✓ Edema- extent and grade
✓ Look for pleural, pericardial, ascetic and scrotal fluid collection
✓ Look for signs of drug toxicity
✓ Eye exam cataract
✓ Neurological exam→weakness of any limb
❖ Definition / criteria:
o Edema: Progressively increasing edema (1)Decreased intravascular oncotic pressure
→Dec renal perfusion→ RAAS, 2)ADH release secondary to increased Osmolality
3)Inhibition of ANP
o Proteinuria: > 3 gm/day or Spot ratio urinary protein and creatinine > 2 (Filtration
barrier defect)
o Low serum albumin: < 2.5mg/dl
o High cholesterol: > 200 (increased hepatic anabolic activity production of proteins and
lipids)

Management:

1)Edema:
-Daily weight
-Fluid and salt restriction
-Diuresis in NS is indicated only if child develops respiratory distress, tense ascites or
anasarca compromising daily activity.
-Furosemide – bolus or infusion

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2)Proteinuria

Nephrotic Syndrome 1st episode:


▪ Steroids 2mg/kg/day for 4 weeks then
▪ 1.5 mg/kg EOD for 8 weeks then stop

Nephrotic Syndrome Relapse:


▪ Steroids 2mg/kg for 2 weeks then
▪ 1.5 mg /kg/day EOD for 6 weeks then stop

❖ Steroid dependent nephrotic syndrome (Two consecutive relapses on tapering steroids


or within 2 weeks of stopping steroids)

➢ Per oral Cyclophosphamide


▪ 168 mg/kg over 8 to 12 weeks
▪ Example calculation: Weight 10 kg
▪ Cumulative dose: 168mg /kg = 1680 mg
▪ Daily Dose (2-3mg / kg): 25mg
▪ Number of days = cumulative dose/daily dose = 1680/25 = 67 days or 9 weeks
and 4 days
➢ Steroids
▪ 1.5mg/kg EOD 2 weeks
▪ Then, 1mg/kg EOD 2 weeks
▪ 0.5mg/kg EOD 2 weeks
▪ 0.25mg/kg EOD till completion of therapy
✓ Follow-up with complete blood count every 2 weeks to look for leucopenia
✓ Withhold cyclophosphamide if leukocyte count is < 4000

❖ Relapse post cyclophosphamide:


▪ Consider renal biopsy and
▪ calcineurin inhibitors

❖ Treatment of FRNS (Two relapses in 6 months or 4 relapses in 12months)


▪ Achieve remission with 2mg/kg steroids for 2 weeks
▪ Start Levamisole 2-2.5mg/kg daily (Tablet Ketress 40mg and syrup 40mg/5ml)
for 2 years
▪ Steroids: 1.5mg/kg EOD 6 weeks
✓ 1mg/kg EOD 2 weeks
✓ 0.5mg/kg EOD 2 weeks
✓ 0.25mg/kg to be continued till 1 year of Levamisole
❖ Relapse on steroids:
▪ Switch to full dose steroids 2mg/kg daily for weeks 2 weeks then
▪ 1.5mg/kg EOD for 6 weeks then
▪ keep on original dose of steroids on which child relapsed

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❖ Relapse off steroids:
▪ Treat as per relapse protocol. Steroids 2mg /kg daily for 2 weeks then
▪ 1.5mg/kg EOD 6 weeks and then stop

❖ Levamisole failure:
▪ Two relapses during any 6 months of Levamisole therapy

Follow-up and monitoring:


✓ Initial follow-up at 6, 10 and 14 weeks and then every 3months
✓ Monitor weight, height, compliance and complete blood count at each visit

❖ Steroid resistant Nephrotic syndrome: (No urinary remission despite 4-6 weeks of full
dose steroids)
➢ Nelson text book and Wyne Harris → 8 weeks
▪ Cyclosporine 5mg/kg/day divided twice a day OR Tacrolimus 0.1mg/kg/day divided
twice a day
▪ Steroid 1mg/kg every alternate day

➢ Other Treatment options:


▪ -Mendoza protocol for SRNS: almost obsolete now due to steroid toxicity

Week Methylprednisolone 30mg/kg Oral Prednisolone

1-2 Every other day 6 doses None

3-10 Every week 8 doses 2mg/kg/EOD

11-18 Fortnightly 4 doses Taper

19-50 Every month 8 doses Taper

51-82 Alternate month 4 doses Taper

▪ -MMF
▪ -Rituximab

3) Hypoproteinemia
▪ Albumin infusion in case of significant edema
▪ Dose: 1gm/kg over 45-60min with Furosemide 2mg/kg

4) High Cholesterol: role of statins is controversial

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Special Considerations
➢ Nutrition:
✓ Restrict fluids and added salt till edema is present. Otherwise advise normal healthy
diet.
✓ Increase proteins in diet by 130-140% of RDA
✓ Avoid saturated fats

➢ Vaccination: All live vaccines are contraindicated in children on immunosuppressive drugs


(Varicella, measles, mumps, rubella, rotavirus, oral polio)
✓ Live vaccines should be deferred until:
• Prednisolone < 1mg/kg/day or < 20mg /day
• At least 3 months’ post cyclophosphamide
• More than 4 weeks after CNI and MMF

➢ NPO children: If child is NPO for any reason then administer intravenous hydrocortisone
1/4th dose of prednisolone or equivalent dose of methylprednisolone

Recent Advances:
• Genetic workup and avoidance of immunosuppression in hereditary and Syndromic NS
• Diagnosis of steroid resistance on the basis of biomarkers

Renal Biopsy indication:

1. -Steroid resistant NS
2. -Nephrotic syndrome with persistent renal failure
3. -Adolescent NS (age > 12 years)
4. -NS with low compliment levels
5. -Prior to starting CNIs in SDNS or FRNS

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Nephrotic Syndrome
Nephrotic Syndrome is characterized by
a) edema,
b) Hypoalbuminemia (< 2.5 mg /dl),
c) proteinuria (> 40mg/m2/hr or Pr: Cr > 2) and
d) hypercholesterolemia (> 20mmg /dl)

A. Classification on the basis of onset of symptoms (age)


✓ - Congenital NS (< 3months)
✓ - Infantile NS (3months to 1 year)
✓ - Childhood NS (1 to 12 years)
✓ - Adolescent NS (> 12 years)

B. Classification on the basis of relapse pattern


▪ Steroid dependent NS: Two consecutive relapses on tapering steroids or within 2
weeks of stopping steroids
▪ Frequently relapsing NS: 2 relapses in 6 months or 4 relapses in 12 months

SDNS

Steroid sensative FRNS


NS(80-85%)
Nephrotic
Syndrome
iFRNS
Steroid resistant
NS (15-20%)

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Treatment of first Episode

Deltacortil 2mg/kg/day

F/U 2 weeks with urine dipstick

Deltacortil 2mg/kg/day
F/U 2 weeks with urine dipstick

Deltacortil 1.5mg/kg EOD

F/U 8 weeks with urine dipstick

Stop deltacortil if in remission

▪ Prednisolone 2m/kg/day daily 4 weeks then 1.5mg/kg/day EOD 8 weeks


▪ Follow-up at 2 weeks to check whether remission is achieved or not (Median time
to become protein free is 11 days {10 to 15 days})

▪ After completion of therapy advise follow-up at 3 months, if continues to maintain


remission then at 6 and 12 months
▪ Single daily dose is associated with lesser side effects as compared to divided
dosing
▪ Weight and surface area based dose calculations have no significant difference in
outcome

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Treatment of Relapse

Deltacortil 2mg/kg/day

F/U 2 weeks with urine dipstick

Deltacortil 1.5mg/kg EOD

F/U 6 weeks with urine dipstick

Stop deltacortil if in remission

▪ Prednisolone 2m/kg/day daily for 2 weeks then 1.5mg/kg/day EOD 6 weeks if in


remission stop steroids

❖ Relapse with Upper respiratory infection


▪ Prednisolone 0.5m/kg/day daily 1week
▪ If already on alternate day steroids, then switch to daily for 1 week
▪ Follow-up at 1 week: Urinary Protein negative →Stop steroids
▪ Proteinuria persistent→ Treat as relapse

❖ Treatment of Adolescent NS
▪ Protocol for the treatment of Adolescent NS remains same as that of childhood.
Few additional steps are followed like:
✓ Renal biopsy to establish histopathological diagnosis at the initial visit
✓ -Labs: Hepatitis B and C Serology Compliments C3, C4, ANA and dsDNA

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Treatment of SDNS

Cyclophosphamide 168mg/kg(Daily dose 2-3mg/kg) and


Deltacortil 1.5mg/kg EOD

F/U 2 weeks with UDR and CP

Continue CyP
Deltacortil 1mg/kg EOD

F/U 2 weeks with UDR and CP

Continue CyP
Deltacortil 0.5mg/kg EOD

F/U 2 weeks with UDR and CP


Continue CyP till calculated duration
Deltacortil 0.25mg/kg EOD till completion of CyP

▪ Example calculation: Weight 10 kg


▪ Cumulative dose: 168mg /kg = 1680 mg
▪ Daily Dose (2-3mg / kg): 25mg
▪ Number of days = cumulative dose/daily dose = 1680/25 = 67 days or 9 weeks and
4 days
▪ Follow-up with complete blood count every 2 weeks to look for leucopenia
▪ Withhold cyclophosphamide if leukocyte count is < 4000

❖ Relapse post cyclophosphamide:


▪ Consider renal biopsy and
▪ calcineurin inhibitors

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Treatment of FRNS

Levamisole 2-2.5mg/kg daily


Deltacortil 1.5mg/kg EOD 4 weeks
F/U 4 weeks with UDR and CP

Continue Levamisole
Deltacortil 1.5mg/kg EOD 2 weeks
Deltacortil 1 mg/kg EOD 2 weeks

F/U 4 weeks with UDR and CP


Continue Levamisole
Deltacortil 0.5 mg/kg EOD 2 weeks
Deltacortil 0.25mg/kg 2 weeks
F/U 4 weeks with UDR and CP

Continue Levamisole for 2 years


Deltacortil 0.25 mg/kg EOD till 1 year of
Levamisole
Follow every 3 months with
UDR and CP

▪ Achieve remission with 2mg/kg steroids for2 weeks


▪ Start Levamisole 2-2.5mg/kg daily (Tablet Ketress 40mg and syrup 40mg/5ml) for
2 years

❖ Relapse on steroids:
▪ Switch to full dose steroids 2mg/kg daily for weeks 2 weeks then
▪ 1.5mg/kg EOD for 6 weeks
▪ Then keep on original dose of steroids on which child relapsed

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❖ Relapse off steroids:
▪ Treat as per relapse protocol. Steroids 2mg /kg daily for 2 weeks then
▪ 1.5mg/kg EOD 6 weeks and then stop

❖ Levamisole failure:
▪ Two relapses during any 6 months of Levamisole therapy

❖ Follow-up and monitoring:


▪ Initial follow-up at 4, 8 and 12 weeks and then every 2 months
▪ Monitor weight, height, compliance and complete blood count at
each visit

Treatment of steroid resistant nephrotic syndrome


▪ Definition: Failure to achieve urinary remission despite full dose 2mg/kg steroids
for 4 – 6 weeks

▪ Renal biopsy to establish histopathological diagnosis

▪ Rx: In case of Minimal change disease (MCD), Focal Segmental glomerulosclerosis


(FSGS), Mesangioproliferative glomerulonephritis (MesPGN) and IgM
nephropathy (IgMN) start cyclosporine or Tacrolimus.

£…. End …. £

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