Core components:

History (Patient’s data, chief complaint, HOPI)

Physical Exam

Investigation

Provisional Diagnosis/Differential Diagnosis

Discussion: Identify problems, management and progress of patient

References

Department of Paediatrics

Cyberjaya University College of Medical Sciences

Case Write-UP

Student Name: Farhawa Bt Zamri Matrix No: 0908-1231

Supervisor: Dr AzlinaYear/Group: 3/05

The case write up should contain the following components:

Topic of the case:

Steroid Resistance Nephrotic Syndrome

Complicated by Infections

(Relapsed of Nephrotic syndrome secondary to URTI)

A. HISTORY

a. Identification DataName: Hemalata Sex: FemaleAddress: ManjongAge: 11 years oldRace: IndianDate of admission: 26th February 2012Parental occupation: Tractor driver (father); coconut collector (mother)Position in family: The youngest in the family

b. Chief ComplainHemalata is a 11 year old girl with a known case of nephrotic syndrome came to hospital with generalized edema and severe back pain that is associated with severe headache for the past 3 days. This history is obtained from her parents and herself.

c. History of Presenting IllnessMy patient was apparently well until 3 days prior to admission, she developed generalized swelling. Her parents noticed the swelling after she came back from her school. They described that the swelling started from her face and progressing worsen to the abdomen, arms and legs. This episode has had happened 2 weeks ago where she was diagnosed with nephrotic syndrome. She took prednisolone that was prescribed by the medical practitioner since then and it was resolved. However, 3 days prior to admission, the symptoms reappeared.

Day 2 of illness, patient started to develop severe back pain that was described as throbbing and not able to lean forward the body. She was not able to bear the pain as she was crying when the pain came and she was not able to go to school. The pain was localized at the central of the back of body and it is precipitated by leaning forward the body but relieved by restricting body movement and bending the body to the back. It was occurred as sudden and intermittent throughout whole day. However, the pain did not worsen in severity and it did not radiate to elsewhere. There is no specific aggravating factor.

On the same day which she developed back pain, she suddenly felt stiffed on her neck and throbbing sensation on occipital region of her head. The pain occurred intermittent and was localized at the same area. It did not radiate to elsewhere. The pain started at night and patient was able to tolerate the pain and able to sleep. However, the sensation was worsening on the next day in the morning and she was not able to tolerate the pain. There are no specific aggravating, precipitating and relieving factors. The pain persists until the day she admitted into the ward.

Throughout the period of illness, her mother realized she became lethargic and less active. Her illnesses were associated with symptom of productive cough with white sputum 3 days prior to admission. However, she did not have symptom of fever, sore throat, vomiting or myalgia. She also passed out normal amount of urine yet frequent concentrated urine, but patient did not complain of frothy urine, hematuria or any urinary tract infections which were dysuria, incomplete voiding and dribbling. She also experienced loss of appetite and she only drank small amount of water. Bowel output was normal where there was no diarrhea or constipation.

d. Systemic Review

Other than that, she did not experience seizure, loss of consciousness and loss of memory. There is also no blurring vision or weaknesses of limbs. She did not have history of malar rashes on her face or shortness of breath.

e. Medical / Surgical HistoryShe was diagnosed with nephrotic syndrome 2 weeks ago and was given with high dose prednisolone. She claimed that she was compliant to the medication. She practiced urine dipstick everyday and she recorded her medication intake. (how she was diagnosed, any 24 Hr urine protein or protein/creatinine ratio)

She is also an asthmatic patient that was diagnosed at the age of 4 years old. Her parents claimed that her asthma is well controlled and she also had one attack in a month. She used inhaler to relieve the symptom. She is allergic extreme weather changes and dust that can aggravate her illness.

However, this is her first admission into the ward and she did not allergic to any medications.

f. Family HistoryHer mother was a resolved asthmatic patient. There was no other family history of kidney disease or genetic disease. Her parents have first level of family relation that is her parents are cousins to each other.

g. Antenatal and Postnatal History

She was delivered via caesarean with not known of birth weight but her parents claimed that her size was small. She was crying after she was delivered. Antenatal and postnatal was uneventful.

h. Breastfeeding and Dietary HistoryHer parents were not able to recall her breastfeeding and weaning. However, parents claimed that their daughter do not eat much every day. She only eats 2 times per day with not a balance diet such as rice and proteins only. She did not favour to vegetable. She likes to have sweet drinks where she drinks can drinks every day at school and adds extra of 2-3 table spoon of sugar into any of her drinks. She did not allergy to any foods.

i. Immunization and Development HistoryHer immunization was up to date. The latest immunization was given at the age of 7 which he received second dose for Hepatitis B, Measles, Mumps and Rubella (MMR) as well as vaccination for Diphteria, Tetanus, and Pertussis (DtaP) and inactivated poliovirus vaccine (IPV). As for development, his development was corresponding to his age and his development was not delayed. She studies at Tamil school. She is barely able to speak Malay but able to speak Tamil very well. She loves go to school very much. (tell more what could she do-speaking, writing, help mom??)Patient’s weight: 29 kg; height: 138 cm; BMI: 15.22 kg/m2

Hemalata, 11yr/old

Based in the growth chart, the current patient’s weight is at 5th percentile and her height is in normal distribution i.e. between 25th and 50th percentile. As for her BMI, it is 15.22 kg/m2 that is plotted as below 15th percentile. Therefore, this indicates that patient is in normal distribution growth. However, her growth must continue to monitor to avoid failure to thrive.

j. Social History She is the youngest out of 2 siblings and the eldest is 14 years old. She lives with her parents with affordable life. Her father works as tractor driver while her mother works as coconut collector. There was nobody smokes in the house.

Hemalata, 11yr/old

B. PHYSICAL EXAMINATION

i. Vital SignsTemperature: 37 ºCPulse rate: 142/minRespiratory rate: 30/minBlood pressure: 130/90 mmHgSpO2: 100% under room air

ii. General inspectionOn general inspection, patient was lying comfortably, conscious, alert and not in respiratory distress. However, she appeared to be tired and weak. A branula inserted into her left dorsum of her hand. Her face looks puffiness, there were slightly periorbital swelling and abdomen was slightly distended. She was thin for her age and there was no appropriate fat distribution on her body. There was a measurement cup on her desk.

On inspection, her hands were warm, capillary refill rate < 2 seconds. No koilonychias, no peripheral cyanosis. Her pulse rate was 142/min, with good volume and regular character. Her respiratory rate was 30/min Conjunctivae were pink, sclera was not jaundiced. She was slightly dehydrated as her lips were dry but her tongue has no white coated on it, no beefy tongue, no angular stomatitis. There was no ulceration in her mouth, tonsils are not swelling and the throat appeared normal reddish in colour. No signs of central or peripheral cyanosis. Moderate pitting edema was noted upon face and leg inspection. No lymph adenopathy noted. Blood pressure on her examination was 130/90 mmHg.

iii. Abdominal examinationOn abdominal inspection, the abdomen was slightly distended and it moves symmetrically with respiration. There were no visible mass or pulsatile mass noted. There was no scar appeared on the patient’s abdomen. There were no stigmata of liver disease appeared upon abdominal inspection.

Upon examination, patient’s abdomen was soft but no tenderness. There was no palpable mass noted upon superficial and deep palpation. The liver span was normal in size. However, there was no splenomegaly and no ballotable kidney. There is presence of fluid thrill but shifting dullness was not able to appreciate.

On auscultation, the bowel sound was heard, it was not hyperactive and there was no renal bruit noted.

iv. Respiratory examinationOn respiratory inspection, the chest was bilaterally normal in shape as it was not pigeon or barrel in shaped and no scars noted. Her chest move with respiration and patient was not in respiratory distress with respiratory rate was 30 breaths per minute. There was no harrison sulci or recessation noted.

Upon examination, patient’s trachea was not deviated and her chest expansion was equal bilaterally and there was no tactile vocal fremitus. On percussion, there was stony dullness on bibasal (lower) lobe of the lungs. On auscultation, the breath sound was vesicular but there was crepitation on bibasal lobe of lungs. Thus, it is indicated that this patient has sign of pleural effusion.

v. Cardiovascular examination On cardiovascular examination, the apex beat was at the midclavicular line and forth intercostals space. Upon palpation, thrills and parasternal heave was negative. On auscultation, first and second heart sounds was heard and there was no murmurs noted.

vi. Central Nervous system examination Upon motor examination, both upper and lower limb bilaterally the power was good 5/5, the tone was good and the reflex was intact. Sensation examination showed patient has all and normal sensory and propioception.

C. SUMMARYMs Hemalata is a 11 year old girl who is a known case of nephrotic syndrome presented to the ward due to generalized swelling, severe back pain and headache for the past 3 days. The swelling worsening as it progressed from her face to the lower limbs and abdomen. As for back pain and headache, it occurred intermittent and progressing worsen on the day of admission. Patient has been taking prednisolone and urine dipstick to monitor her illness.

On examination, vital signs are normal except patient is tachycardia and hypertensive. Her face looked puffy, ascites and pedal edema were present. Hepatomegaly was noted with 3 finger breath enlarged upon palpation. There were also bibasal stony dullness and crepitation. Other systemic review was normal.

D. PROBLEMS IN THIS PATIENT

i. Generalized edema i.e.: periorbital swelling, facial puffiness, ascites, pedal edemaii. Severe occipital headacheiii. Severe back painiv. Productive cough (whitish sputum)v. Hypertension: 130/90mmHgvi. Tarchycardia: 142 beat/minvii. Bibasal lungs stony dullness and crepitation (pleural effusion symptoms)

E. PROVISIONAL DIAGNOSISRespiratory tract infection secondary to steroid resistant nephrotic syndrome (not yet coz she might miss her medication)

Patient with failure to achieve response to an initial 4 weeks treatment of prednisolone indicates patient is having steroid resistant nephrotic syndrome. My patient has been taking prednisolone for 2 weeks after she was diagnosed with nephrotic syndrome and currently, the symptoms such as generalized edema and pleural effusion reappeared back. Besides that, 50-60% cases of patient with steroid resistant presented with hypertension. Hemalata presented with all the symptoms and signs that were mentioned above. Therefore, she is very likely suffered from steroid resistant nephrotic syndrome.

She was also having productive cough that produced white sputum in colour. Although she did not have symptoms of fever, sore throat, shortness of breath or other respiratory tract illnesses symptoms, she might still suffer from respiratory tract infection. This is because most of the patients with nephrotic syndrome have complication to predispose with infection such as respiratory tract infection. To confirm this, full blood count must be assessed to exclude this diagnosis.

Other associated symptoms such as back pain might due to severe edema of her body. The generalized edema had stretched her posterior abdominal muscles and wall and thus, causing intermittent back pain. Hemalata described that her back pain causing her not able to lean forward her body but relieved by bending her body backward. Bending of body to the back may

reduce tension to the posterior abdominal muscle. Therefore, this symptom is very likely due to tension from generalized edema.As for severe occipital headache, it may due to stress-induced headache that was aggravated by severe back pain or discomfort of her body. She claimed that she was not able to tolerate her backache and the headache started after she had backache. Thus, this symptom may be due to stress-induced headache.

F. DIFFERENTIAL DIAGNOSIS

Supporting points Points against1. Nephritic syndrome

Periorbital swelling, ascites, pedal edema and facial puffinessPresence of pleural effusion symptomsHypertension

Patient did not complaint of haematuriaNo history of sore throat or purpura

2. Allergic reaction

Periorbital swelling and facial puffinessSevere occipital headachetarchycardia

No rashesNo shortness of breathNo palpitationNo fever

3. Acute renal failure

Generalized edemaKnown case of nephrotic syndromeFrequent concentrated urine

Hypertension and tarchycardiaNo hematuriaNo oliguria

4. Urinary tract infection

Severe back painIncrease frequency of urination

No dysuriaNo feverBack pain precipitated by bending the bodyPresence of generalized edema

G. INVESTIGATIONS1. Blood Glucose level

Fasting: 16.8 mmol/L [chronic high] (N: 4.5 – 7.8 mmol/L) [IDDM: insulin dependent DM – must be excluded as this is fasting]

Fasting blood glucose level was taken as patient is very favours to consume sweet foods and drinks. Her result shows that it is chronic high that may due to excessive sweet nutritional intake.

2. Full blood countReadings

Haemoglobin 10.4 g/dL ReducedHematocrit 34.8% ReducedMCV 71.5 fl Reduced MCH 21.8pg Reduced Platelet 227 x103/uL NormalTotal white count 20.1 x103/uL RaisedNeutrophils 88.3% RaisedLymphocytes 11.0 Normal

Full blood count was done to review the level of total white cell counts that is indicated for occurrence of infection in my patient’s body. The result shows that total white cell count increased with neutrophils predominance that is suggestive for bacterial infections.

The result also reveals that she is having hypochromic microcytic anemia as her haemoglobin, MCV and MCH level are below the normal range. This may indicate that she is having iron deficiency anaemia as her nutritional history reveals her poor diet intake of foods.

3. Blood Urea Serum Electrolytes (BUSE)Readings (mmol/L)

Urea 5.9 NormalSodium 140 Normal Potassium 2.9 Chronic reducedChloride 102 Normal

Blood urea serum electrolyte (BUSE) was done to assess the hydration status and electrolyte imbalance of the patient. BUSE is to assess renal function and hydration status Result demonstrates patient is having chronic lost of potassium from her body. The reduction of potassium is most likely due elevated of glucose level in her body. Concentrated glucose level may worsen hypokalaemia by stimulating insulin release, which increases cellular uptake of potassium (Reference:clinical handbook paeads, pg 373).

4. Serum creatinine Result: 79 umol/L NormalSerum creatinine was done to assess function of kidneys. Patient has normal function of kidney.

5. UrinalysisReadings (mmol/L)

Colour Straw-yellow Normal Appearance clear Normal Specific gravity >1.030 Slightly elevatedpH 6 NormalProtein +++ PresenceUrine glucose ++++ Presence ketone -ve Normal Nitrates -ve NormalRed blood celld -ve NormalUrine WBC Few Abnormal

Patient with nephrotic syndrome must always monitor their protein level in urine. Thus, urinalysis is an indicator to monitor this parameter. For this patient, her proteinuria is positive that indicates that patient has been losing proteins from her body through urine. Besides that, there are a few concerned based on the result i.e. there are presence of glucose in urine and white cell count in her urine. Excessive level of glucose in the blood may lead to glucosuria (d/t: due to renal impairment) and presence of few WBC in her urine indicates that she is having mild urinary tract infection.

6. Liver function testReadings

AST 31 NormalALT 14 NormalALP 97 NormalDirect Bilirubin 0.9 NormalIndirect Bilirubin 3.0 Normal Total protein 55 ReducedAlbumin 22 Reduced

Globulin 33 Normal

Liver function test was done to measure the albumin level. In this patient, she is hypoalbuminemia and low serum protein level. (kena cerita albumin low sebab protein leakage through glomeruli) The reduction of albumin and protein may lead to edema as it is related to the disturbance of oncotic pressure between intracellular space and extracellular space. Hypoalbuminemia may reduce oncotic pressure in intracellular space that eventually leads to fluid accumulation in extracellular space. The albumin/protein have been lost through urination based on urinalysis result.

7. Autoimmnune serology test

DS DNA: negativeAnti nuclear antibody: negativeIt can be concluded that patient is having idiopathic nephrotic syndrome.(tulis, to ruled out SLE since patient is female)

H. FINAL DIAGNOSIS:Respiratory tract infection secondary to steroid resistant nephrotic syndrome

I. MANAGEMENT:Management can be divided into two which are non-pharmacology treatment and pharmacological treatment.

For supportive treatment, strict monitoring need to be done which include monitoring of fluid intake, urine output, daily weight and blood pressure. Catheter bladder drainage was inserted and monitored strictly input and output using chart. Since patient in dehydration state, fluid therapy was given to maintain the fluid level in body.

As for pharmacological treatment, respiratory tract infection should be treated with antibiotic such as cefuroxime. Cefuroxime is used to treat certain infections caused by bacteria, such as bronchitis and infections of the ears, throat, sinuses, urinary tract, and skin. Cefuroxime is in a class of medications called cephalosporin antibiotics. It works by stopping the growth of bacteria. As for his hypertension (vital signs), bed rest was suggested and his blood pressure needs to be monitored 4 hourly. Nifedipine can give orally to control the blood pressure if the blood pressure still high after bed rest. This patient might have resistant to steroid due to occurrence of infection on her body. Therefore, infection must be treated in order to treat her major disease i.e. nephrotic syndrome.

J. DISCUSSION:

1. Difference between nephrotic and nephritic

Nephrotic syndrome Nephritic syndrome

Massive Proteinuria > 4 gm/24hours Proteinuria < 4 gm/24hours

Loss of protein from intravascular space which will reduce the oncotic pressure in the intravascular space. This can cause fluid leaks out to extravascular and form generalised edema

Due to the increase in hydrostatic pressure

Increase permeability to albuminIn nephrotic syndrome, the underlying pathological condition is the increases of permeability of the glomeruli towards albumin which gives rise to the hypoalbuminemia. Other than that, lost of the negative charges from the protein can also contributes to leakage of albumin into the urine.

Inflammation of GFR can give rise to hematuria. In nephritic syndrome, the underlying pathological condition is the inflammation of the glomeruli.

Not symptoms of Hematuria Hematuria presented in nephritic syndrome can be due to immunologic injury (poststreptococcal acute glomerulonephritis), inherited disease or vascular injury (acute tubular necrosis)

Hemalata who is a known case of nephrotic syndrome patient presented with recurrent generalized edema during admission to the ward. Upon investigation, she is hypoalbuminemia and there is presence of proteinuria. This indicates that the albumin/protein in her body has been lost through urination that eventually leads to alteration of oncotic pressure in her body. The decreased of oncotic pressure in the intravascular space is then contributing to the lost of fluid into extracellular space and thus, causing formation of generalized edema. Therefore, presentations such as hypoalbuminemia, proteinuria and edema are highly suggestive to nephrotic syndrome.

Patient was just only started on taking prednisolone for the past 2 weeks and suddenly developed recurrent generalized edema. She also presented with minor respiratory tract infection. Thus, it can be concluded that patient is having steroid resistant nephrotic syndrome due to concurrent of infections.

2. Causes of nephrotic syndrome

The glomerular diseases that cause nephrotic syndrome generally can be divided into primary and secondary etiologies. Primary nephrotic syndrome (PNS), also known as idiopathic nephrotic syndrome (INS), is associated with glomerular diseases intrinsic to the kidney and not related to systemic causes. The subcategories of INS are based on histological descriptions, but clinical-pathological correlations have been made. There are a few histological patterns in INS which includes mininal change glomerular lesion (MCNS), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), membranoproliferative glomerulonephritis (MPGN), diffuse mesangial proliferation and others.

MCNS Steroid sensitive nephrotic syndromeFSGS Steroid resistant nephrotic syndromeMNMPGN

As for secondary nephrotic syndrome, it refers to an etiology extrinsic to the kidney. Secondary causes of nephrotic syndrome include Henoch-Schönlein purpura (HSP), systemic lupus erythematosus, diabetes mellitus, syphilis, human immunodeficiency virus (HIV) infection, hepatitis B and C, malignancy, vasculitis, and drug exposure (eg, heroin, mercury), among many other causes.

For this patient, her clinical presentation strongly suggestive that she is having idiopathic nephrotic syndrome (INS) as her past medical history revealed that her illness presented without any specific etiology or origin and her serology test was negative. Since currently she is having steroid resistant NS that might induce by infection, she has chances of getting any 3 types of INS. This histological presentation can only be clarified through renal biopsy. However, for Hemalata, renal biopsy has not yet been done as she had just recently developed NS for past 2 weeks. Therefore, she is only being monitor on her urine FEME and ingestion of high dose steroid to treat her illness.

3. Patient’s education on nephrotic syndrome

It is important to educate the families and patient on how to deal with nephrotic syndrome. Therefore, soon after nephrotic syndrome is diagnosed, the patient and family should be educated about the disease, its management, and its expected course. The family should participate in therapeutic decisions and should be encouraged to adhere to the medical regimen.

Similar to other chronic illnesses, there would be psychosocial issues that may need to be addressed that including her behavior, adherence to medication, adequate parental/caretaker supervision and missed school due to hospitalizations and outpatient visits. Therefore, Hemalata’s parents have to understand that Hemalata must always compliant to medication that was prescribed by the doctor and her urine FEME must be taken daily to monitor her health status. Hemalata is from a poor family with income of not more than RM 1000. Therefore, they might facing problem in getting the urine dipstick apparatus and medication as they are not well supported by the financial and thus, some suggestive parameters should be given to the family to encounter this issue in order to ease burden on the family especially the parents.

As for Hemalata, she must understand her illness and she must be educated on taking care of her diet consumption. She is very favours to sweet foods and as her glucose level has been very high throughout her hospitalization. Therefore, this issue must address to her and her parents so that she did not develop into diabetes mellitus at younger age by giving education and awareness to them.

K. PROGRESSION OF PATIENT

Hemalata is still being hospitalized until today (7th March 2012) as her hypertension and fasting glucose level did not resolve normally. However, her infection had been subsided after taking cefuroxime. Since her infection has resolved, she would be continuing on her medication i.e. prednisolone. Her vital signs such as blood pressure and blood glucose level will be monitored throughout hospitalization period.

L. PROGNOSISApproximately 10% of patients overall with INS do not respond to an initial trial of steroids. Additionally, about 1-3% of patients who initially do respond to steroids later become resistant to treatment ("late non-responders"). Thus, patients with steroid-resistant INS have a good prognosis if remission of proteinuria can be achieved by other medications. Failure to respond to treatment (i.e., failure to achieve remission) and kidney insufficiency at presentation are predictors of poor outcome and progression to end stage kidney disease (ESKD).

Hemalata might only have temporary resistant to the medication as she develop infection in her body system. Thus, prednisolone should continue to take after the infection resolved in order to monitor the reaction of her body system towards the medication. If she failed to respond to the medication and other steroid medication, the prognosis would be poor for her.