Systemic lupus erythematosus (SLE) and its complications: A case study

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Case Study
Clinical Case Reports and Reviews
Clin Case Rep Rev, 2015 doi: 10.15761/CCRR.1000142 Volume 1(6): 125-129
ISSN: 2059-0393ISSN: 2059-0393
Systemic lupus erythematosus (SLE) and its complications: A
case study
Salman Azeem1, Syed Wasif Gillani2*, Vinci Poh3 and Syed Azhar Syed Sulaiman4
1King Abdul Aziz Military Hospital, Tabuk, Saudi Arabia
2School of Pharmacy, Monash University, Malaysia
3School of Pharmacy, Monash University, Malaysia
4School of Pharmaceutical Sciences, Univerisiti Sains Malaysia (USM), Malaysia
Abstract
Systemic Lupus Erythematosus (SLE) is a chronic, unpredictable and relapsing disease, predominantly aecting women of childbearing age. For severe cases of SLE,
the usage of high dose toxic medications leads to a high risk of development of complications. e following case demonstrates the diculty of managing SLE and
the complications that follow.
Case presentation: KR is a 21 year old Indian female who was admitted for the chief complaint of bilateral leg swelling. She also presented with frothy urine and
haematuria and diagnosed with acute nephritis and acute myelodysplatic syndrome with pancytopenia. To these, she was treated with frusemide, haemodialysis and
prednisolone. Later on, her renal function worsened and was switched to IV methylprednisolone. She developed E.Coli pyelonephritis and bacteremia. Further
development of autoimmune haemolytic anemia and thrombocytopenia necessitated the provision of haematinics. Discovery of severe hypertension lead to a
multidrug antihypertensive regimen. A few days later, KR developed seizures likely caused by steroid toxicity, to which methylprednisolone was ceased. Phenytoin
was administered to prevent tting. However, due to her hypoalbuminemia and renal impairment she experienced phenytoin toxicity and developed nystagmus,
to which phenytoin was temporarily ceased. She was continuously warded until signicant improvement and was discharged. However her blood pressure is still
uncontrolled. She was asked to return at a later date to do a renal biopsy.
Clinical evaluation: e timeliness and choice of treatment for treating the infections were questionable. Administration of IV Immunoglobulin was untimely and
not using the usual regimen for autoimmune diseases. Miscalculation of plasma phenytoin concentration lead to phenytoin toxicity. Also, KR’s uncontrolled blood
pressure was not properly solved before discharge.
Correspondence to: Syed Wasif Gillani, School of Pharmacy, Monash University
Malaysia, PO box 46150, Bandar Sunway, Selangor, Malaysia, Tel: +6017-
4203027; E-mail: wasifgillani@gmail.com
Key words: systemic lupus erythematosus, complications, prednisolone, renal,
haemotological, neurological
Received: May 13, 2015; Accepted: June 23, 2015; Published: June 26, 2015
Introduction
Systemic Lupus Erythematosus (SLE) is a chronic autoimmune
disease that aects multiple systems, and is most predominant among
women of childbearing age. SLE is more common among Asians and
black people, and among Malaysians there have been approximately
10,000 people who have been diagnosed with SLE in the past 30 years
[1,2]. ere is great variance in clinical ndings, due to the potential
yet not compulsory involvement of any organ system, and hence there
has been much debate on the inclusion criteria for diagnosis. Currently
the worldwide accepted criteria for diagnosis is the American College
of Rheumatology criteria, where the presentation of at least 4 of 11
classication criteria would lead to a positive diagnosis. e eleven
criteria include a malar rash, discoid rash, photosensitivity, oral ulcers,
arthritis, serositis, renal manifestations, neurological manifestations,
haematological manifestations, immunological manifestations or
a positive antinuclear antibody (ANA) result. However now there is
a revised and more favoured version created by the Systemic Lupus
International Collaborating Clinics (SLICC), which includes 11
clinical criteria and 6 immunologic criteria, and a presentation of at
least 4 of these 17 criteria, with at least one coming from each group,
would lead to a positive diagnosis. e 11 clinical criteria are: acute
cutaneous lupus, chronic cutaneous lupus, non-scarring alopecia, nasal
or oral ulcers, joint disease, serositis, renal manifestations, neurologic
manifestations, haemolytic anemia, leukopenia or lymphopenia and
thrombocytopenia. e 6 immunologic criteria are: above range ANA
levels, above range anti-dsDNA levels, positive antiphospholipid
antibodies, low complement and a direct Coombs test [1,3].
SLE is a relapsing and unpredictable disease. Long term prognosis
tends to be good if the disease is controlled during the initial acute
phase, hence it is of utmost importance for the patient to not delay
in seeking treatment and for the healthcare team to identify the most
eective treatment as soon as possible. Pharmacological treatment
varies depending on the severity of the disease as well as the organ
systems involved. Mild presentation of symptoms may only require
the use of NSAIDS or antimalarials, while more severe disease may
require corticosteroids or immunosuppressants [1]. Unfortunately
with more toxic medications comes a higher mortality risk due to a
higher risk of complications, and adverse eects due to high doses can

Azeem S (2015) Systemic lupus erythematosus (SLE) and its complications: A case study
Volume 1(6): 125-129Clin Case Rep Rev, 2015 doi: 10.15761/CCRR.1000142
Liver function tests show total protein and albumin levels are too low.
Coagulation proles were taken on 14/10 and revealed that INR is too
low and activated partial prothrombin time (APPT) is too long.
e list of diagnoses, dierential diagnoses, acute and chronic
medical problems of KR are as follows:
1. Acute myelodysplatic syndrome with pancytopenia
2. Acute pyelonephritis with acute glomerulonephritis
3. Bacteremia
4. Autoimmune haemolytic anemia & thrombocytopenia
5. SLE
6. Hypertension
7. Seizure
Table 1 shows her medication regimen during her ward stay,
inclusive of medication administration times.
Table 2 shows her progress from 13-10-2003 till 20-10-2003.
Table 3 includes laboratory data taken from 24/9 till 19/10.
make interpretations of clinical presentations or clinical responses
complicated [3].
It is therefore important that the management of SLE patients
require a healthcare team of multiple disciplines and professions, with
close monitoring and control to prevent the worsening of the disease
or the development of complications. is case study presents a case of
an SLE patient who has developed complications during her course of
treatment.
Case presentation
KR was a 70 kg, 21 year old Indian femalewho was admitted on
21-09-2003, with a chief complaint of bilateral leg swelling for 2 days.
She also presented with frothy urine and haematuria, to which she was
treated with frusemide. KR was diagnosed with acute nephritis and was
hence started on haemodialysis treatment. In addition to that, she was
also diagnosed with acute myelodysplatic syndrome with pancytopenia,
to which prednisolone treatment was given.
On 25-09-2003 the patient was diagnosed with SLE. It was discovered
that her SLE has been misdiagnosed as leukemia back in 2001. Due to
worsening renal failure she has been placed on IV methylprednisolone.
She also contracted E.coli pyelonephritis which was sensitive to
ceazidime and ampicillin+sulbactam. She also has bacteremia as the
microbiology test revealed E.coli in her blood. Further development of
autoimmune haemolytic anemia and thrombocytopenia necessitated
the provision of haematinics. Diagnosis of severe hypertension lead
to treatment involving captopril, nifedipine, metoprolol, atenolol,
prazosin, diltiazem and frusemide.
On 29-09-2003 the patient’s condition took a turn for the worst
as she developed seizures secondary to either cerebral lupus or
steroid toxicity, hence she was taken o steroids. A CT scan ruled out
intracranial haemorrhage. Despite being on a total of 1250mg/day of
phenytoin, the patient continued tting and only ceased aer 2 days.
Due to phenytoin toxicity the patient developed secondary nystagmus.
It was noted that the patient was restarted on hydrocortisone on the
30th, despite there being no record of her being started on it.
KR’s past medical history included the misdiagnosis of leukemia
in 2001, and a history of myelodysplastic syndrome. She did not
have hypertension prior to admission and had never had symptoms
of anemia or bleeding. As for family history, her grandmother had
hypertension and her mother had thyrotoxicosis. e patient is
currently staying with her family and is not studying nor working.
A medical history interview revealed that other than the
complaints mentioned above, KR has also experienced headaches,
dizziness, fainting, malenic stools and sleeping problems. She does
not have any known food or drug allergies, and does not consume
alcohol nor smoke. KR is non-compliant to her medications. Her
medication history includes Ferrous Sulphate tablets 200mg once a day
(OD), Folate tablets 5 mg OD, Prednisolone tablets every other day
(EOD) and Vitamin B Complex tablets 5mg OD, all starting from 2001
onwards. Her diet is imbalanced and she does not engage in physical
exercise.
Laboratory data collected from 24/9 till 19/10 shows that her blood
urea nitrogen (BUN) and creatinine levels are too high, and hence
creatinine clearance (CrCL) is too low. Her daily uid balance steadily
decreased, which is good due to her uid retention. Haematological
wise, her haematocrit levels are too high while all other components are
too low. Only white blood cells (WBC) remain within normal levels.
Drug Name/Route Dose/Frequency Duration
Start-Stop Dates
T. BCo 1/1 od 21/9
T. folic acid 5mg od 21/9
T. CaCO3500mg tds 26/9
T. prednisolone 40mg od 1/10
T. nifedipine 20mg tds 1/10
T. Metoprolol 200mg bd 3/10 – 15/10
T. ampicillin + sulbactam 375mg bd 6/10 – 15/10
T. prazosin 3mg tds 6/10
T. frusemide 80mg tds 11/10
Mist Kcl 2g tds 12/10 – 15/10
IV vancomycin 1g stat 13/10 – 13/10
IV rocephine (ceftriaxone) 1g bd 13/10
IV Immunoglobulin 24 daily 14/10 – 15/10
IV sulperazone (cefoperazone + sulbactam) 1g bd 14/10
T. atenolol 100mg/d 14/10
T. minoxidil 2.5mg/d 16/10
Time Line: Circle actual administration times, and record appropriate medications and
meals below:
6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 12 1 2 3 4 5
am noon pm midnight
Atenolol Hemodialysis Mist Kcl Sulperazone Mist Kcl
Su lp er az on e Frusemide Rocephine Frusemide
Rocephine Prazosin Unasyn Prazosin
Mist Kcl Adalat Metoprolol Adalat
Minoxidil CaCO3 CaCO3
Frusemide
Prazosin
Unasyn
Metoprolol
Adalat
Prednisolone
Folic acid
BCo
CaCO3
Table 1. Inpatient medication record.

Azeem S (2015) Systemic lupus erythematosus (SLE) and its complications: A case study
Volume 1(6): 125-129Clin Case Rep Rev, 2015 doi: 10.15761/CCRR.1000142
Table 4 shows results of microbiology tests done from 25/9 till
13/10
Clinical evaluation
Disease presentation and progression
KR’s overall SLE disease progression from admission to discharge
involved renal, haematological and neurological manifestations.
Pancytopenia is a well described haematological manifestation in
this disease. e signicant blood cell destruction necessitated high
dose pulse prednisolone treatment. Intravenous immunoglobulin (IV
Ig) is also recommended for the removal of destructive antibodies,
however IV Ig was only administered to KR from 14/10 till 15/10, about
3 weeks aer admission, and only for 2 days, despite the laboratory
data that shows that while there was some degree of improvement,
KR’s blood component levels have yet to attain the normal ranges. IV
Ig is normally given at a dose of 0.4 g/kg/day for a duration of 5 days
[4]. KR, being 70 kg in weight, ought to receive 28 g/day. Instead she
received 24 g/day. However, this could be due to a uctuation in the
patient’s weight, as while the patient was admitted with a weight of 70
kg, control of her uid retention may render her lighter in weight by
the time they administered IV Ig.
Severely reduced renal function due to acute nephritis required
haemodialysis to aid in blood ltration. is severe renal impairment
may be the major contributor to the uid retention that was the
chief complaint during admission. Subsequent renal failure over
Date 13/10 14/10 15/10 16/10 17/10 18/10 19/10 20/10
General Pale+ Comfortable;
no cough
Afebrile °c/o, fever,
bleeding
Comfortable;
tolerating well
orally
Keeping well; no new
complaints; no new
bruise
Comfortable; tolerating
well orally; no nausea or
vomiting
Comfortable; patient
discharged and asked to
come the following week
for her renal biopsy.
BP 135/100 190/130 170/132 182/119 150/106 130/80 160/110 180/90
PR 88 75 72 74 - 80 - 74
RR - - - - - - - -
T 38.3 Afebrile 36.5 37.5 Afebrile Afebrile Afebrile Afebrile
Lungs Crepts right base Clear Clear Clear Clear Clear
EXT Pedal edema +
BP=blood pressure (mmHg); PR=pulse rate (beats/min); RR=respiratory rate (breaths/min); T=temperature (°C)
Table 2. Inpatient progress notes.
NORMAL 24/9 1/10 13/10 14/10 15/10 17/10 18/10 19/10
Blood
Chemistry
Na+ 135-145 mmol/L 137 135 131 138
K+ 3.5-5.0 mmol/L 4.3 3.5 4.2 3.3
BUN 1.7-8.3 mmol/L 20.2 24 9.5 6.5
Creatinine 57-130 mmol/L 328 390 399 287
Cr Cl 75-125 ml/min 26.7 22.47 22.0 30.5
Fluid
Input 700 620 600 500 800 850
Output 170 500 400 400 800 1000
Balance 800-1200ml 530 120 200 100 - -150
Hematology
Hct 0.36-0.46 I 17.5 26.5 29.3
HgB 12-16 g/dl 5.3 8.6 9.8
WBC 4.5-11 x109/L 5.2 5.0 5.8
RBC 4.7-6.1 x 1012/L 2.2 3.43 3.71
MCV 80 – 94 24.3 77.3 78.8
MCH 27 – 31 30.3 25.2 26.3
MCHC 330 – 370 19.6 32.6 33.3
PLT 130-400 x103/µml 91.1 91 108
Liver Ft
Total Protein 66-87g/L 60
Albumin 38-51g/L 25
Globulin 20-36 35
Tot bilirubin 0-24mol/L 7
ALT 0-42U/L 10
ALP 34-104U/L
PT 10.7-13.7 sec 13.3 10.8
INR 1.0-1.24 1.1 0.9
APPT 25-40 sec 32.2 70.6
Highlighted in red are values that do not fall within recommended range
Table 3. Laboratory data.

Azeem S (2015) Systemic lupus erythematosus (SLE) and its complications: A case study
Volume 1(6): 125-129Clin Case Rep Rev, 2015 doi: 10.15761/CCRR.1000142
the next few days necessitated the switch from oral prednisolone to
IV methylprednisolone. e use of high dose immunosuppressing
corticosteroids lead to the development of pyelonephritis by E.coli,
which also lead to bacteremia by the same organism. e use of
corticosteroids also lead to the presentation of an abnormal liver
function test. ese were mentioned in the eTG as common adverse
eects that comes with high dose immunosuppressant therapy that may
complicate clinical presentation and response interpretation [3]. Other
than these, prednisolone toxicity may also lead to hypertension and
uid retention, which may partially explain why KR’s blood pressure
throughout her stay has been uncontrolled. It may also be possible that
the water retaining adverse eect of prednisolone may have delayed the
removal of excess uids from her body [5].
e seizures that KR experienced from 29/9 were either from
cerebral lupus or steroid toxicity. e chances of the cause being steroid
toxicity is more likely as she only developed the seizures aer a course
of high dose prednisolone and later methylprednisolone; seizures are
among the more serious side eects of these corticosteroids [6]. us,
methylprednisolone was temporarily ceased and phenytoin was given
to stop the seizures. Unfortunately there has been neglect in the dosing
adjustments for the patient’s hypoalbuminemia and renal failure, and
hence the amount of free plasma fraction is higher than average and
the half-life of phenytoin in the body is extended, leading to toxicity
[7]. e pharmacist involved has detected and rectied this error by
correcting the actual plasma concentration and suggesting to withhold
phenytoin for 3 days and restarting on 3/10.
Inpatient progress notes from 13/10 to 20/10 revealed that KR was
steadily recovering and the uid balance is steadily being restored,
with the symptoms of uid retention being absent from 14/10
onwards. Laboratory data showed a steady improvement in blood cell
component and electrolyte levels as well. e only remaining area of
concern was her high, uncontrolled blood pressure. ere seems to be
no pattern of progress as the values uctuate greatly from day to day.
Despite this, the patient has been discharged. e patient’s hypertensive
treatment regimen ought to be addressed completely before discharge
as aggressive blood pressure control is crucial in improving renal
outcome [3].
Drug choice
KR’s E.coli pyelonephritis is sensitive to ceazidime and
ampicillin+sulbactam. According to the National Antibiotic
Guidelines, for acute complicated pyelonephritis, if infected by
Enterococci, the preferred treatment is ampicillin 500mg IV every 6
hours plus gentamicin 5 mg/kg (70 kg=350 mg) IV every 24 hours for 2
weeks duration. Alternative treatments may be either third generation
cephalosporins, β-lactam/β-lactamase inhibitors, piperacillin/
tazobactam or ciprooxacin [8].Oddly, despite being diagnosed
with pyelonephritis as well as bacteremia on 25/9, no antibiotic was
given until 6/10, in which she was given ampicillin+sulbactam. On
13/10, despite her microbiology tests showing negative results on
bacterial growth, KR was given a 1 g IV stat dose of vancomycin
and IV ceriaxone 1 g twice daily until discharge. IV sulperazone
(cefoperazone + sulbactam) 1g twice daily was added to the regimen
on 14/10 until discharge. e antibiotic regimen is questionable and
potentially dangerous to the patient’s health.
For the patient’s hypertension, nifedipine (calcium channel
blocker) was started on 1/10. Metoprolol (beta-blocker) was added
on 3/10 and ceased on 15/10, and on 6/10, prazosin (alpha-blocker)
was added. Frusemide (loop diuretic) was added on 11/10, and on
14/10 another beta-blocker, atenolol was added. Finally minoxidil
(peripheral vasodilator) was added into the regimen on 16/10. Despite
the continuous additions of anti-hypertensive medication, there seems
to be no continuous improvement in KR’s blood pressure control.
According to the eTG, rst line therapy for hypertensive patients with
kidney impairment are angiotensin converting enzyme inhibitors
(ACEI) or angiotensin II receptor blockers (ARB), due to their ability
to not only reduce proteinuria, but to also slow the decline of kidney
function. Calcium channel blockers are also a good choice as they also
slow the progress of kidney failure. Loop diuretics are recommended
for those with highly reduced kidney function. Care should be taken
when prescribing renally excreted beta blockers due to their deleterious
eects on potassium and lipid levels. Alpha blockers also have limited
usefulness due to initial orthostatic hypotension, though occasionally
prove to be a useful adjunct. Minoxidil is a potent vasodilator that can
be extremely eective in certain individuals that have both kidney
impairment and severe hypertension, but comes with the adverse
eects of tachycardia and sodium retention [9]. With these in mind,
the next step to control KR’s hypertension may be to try an ACEI or
ARB. Care should be taken to not give them together with a diuretic
and an NSAID to prevent the ‘triple whammy’ eect. Also, it should
be evaluated whether co-administration of other drugs have aected
the ecacy of the anti-hypertensives. Additionally, it may be suggested
that the patient practice uid restriction.
Drug-drug interactions
Below are the potential drug-drug interactions between the drugs
administered during KR’s ward stay [10]:
1. Ampicillin + Atenolol
Co-administration may lead to decreased plasma concentrations of
atenolol due to impaired gastrointestinal absorption due to ampicillin.
It is suggested to adjust the dosing intervals to avoid co-administration of
these two drugs, or to make ampicillin dosing smaller and more frequent.
Source Date Results Sensitive to Resistant to
Blood 25/9 E. coli Ampicilin; Ampi/sulbactam ;Amoxi/Clav ; Cotrimoxazole ;Genta, Ami,
Netil, Cefuroxamine; Cefoperazone ; Cefuroxime ;
Ceftazidime;Ceftriaxone;Ciprooxacin
Throat swab 25/9 Normal
Urine 1/10 Nosignicantbacteriuria
Blood (arterial) 13/10 No growth
Blood (peripheral) 13/10 No growth
Blood (venous) 13/10 No growth
Table 4. Microbiology tests results.

Azeem S (2015) Systemic lupus erythematosus (SLE) and its complications: A case study
Volume 1(6): 125-129Clin Case Rep Rev, 2015 doi: 10.15761/CCRR.1000142
2. Nifedipine + Calcium carbonate
Calcium carbonate, a calcium product, can saturate calcium
channels and hence reduce the eectiveness of nifedipine. Monitoring
is needed to determine if nifedipine is working suciently.
3. Beta-blockers + Calcium carbonate
Calcium salts can decrease oral bioavailability of beta-blockers,
though the exact mechanism is unknown. It is suggested to separate
administration times.
4. Beta-blockers + Prazosin
Other than additive hypotensive eects, the combination can
lead to an increased risk or severity of rst dose eects of prazosin,
such as syncope and postural hypotension. e reex tachycardia that
arises due to postural hypotension can be blunted by beta-blockers.
Close monitoring is advised, and to start the dosages small and titre
accordingly. Prazosin is advised to be taken at bedtime to reduce
orthostatic eect occurrences.
5. Prednisolone + antihypertensive medication
Corticosteroids can cause sodium and uid retention and hence
antagonize antihypertensive eects. For those on high dose or
prolonged corticosteroid therapy, such as KR, body weight, electrolyte
levels and blood pressure need to be regularly monitored, and the
antihypertensive medication doses may require adjustment.
6. Nifedipine + Prazosin
ere may be potential additive hypotensive eects and increase
the likelihood of postural hypotension. Close monitoring is required,
particularly during initial treatment.
7. Frusemide + beta-blockers
Some patients are at an increased risk of developing
hypertriglyceridemia and hyperglycemia with this combination,
particularly diabetics. Blood glucose, blood pressure and serum
potassium levels need to be monitored when these medications are co-
administered.
8. Nifedipine + beta-blockers
Potential for additive reductions in cardiac contractility, cardiac
conduction and heart rate. Haemodynamic response and tolerance of
the patient should be monitored.
9. Cephalosporins + Frusemide
Frusemide can possibly potentiate nephrotoxicity of cephalosporins.
Close monitoring of renal function is recommended, particularly since
KR has pre-existing renal impairment.
10. Frusemide + Prednisolone
ere is an increased risk of hypokalemia in the combination of
potassium-depleting medication and corticosteroids. Close monitoring
is required.
11. Prednisolone + Calcium Carbonate
Calcium carbonate exerts acid-neutralizing eects and can hence
impair prednisolone absorption. However, there is no particular
intervention needed for the co-administration of both drugs.
Conclusion
SLE is an exceedingly complicated disease with its involvement
of multiple organ systems, and when severe requires high dose drug
regimens that can easily complicate the presentation and clinical
response. us, it is of utmost importance for the involvement of
professionals from dierent elds, depending on the organ systems
aected, to form a multidisciplinary team. Fast and accurate
information ow is crucial among professionals working together
in order for the patient to have a good prognosis. ere needs to be
constant monitoring and evaluation of therapeutic regimens of the
patient along with their response, due to the complicated and severe
nature of the disease.
References
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2. Malaysian SLE Association. What is SLE?
3. eTGComplete. Systemic Lupus Erythematosus.
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(IVIg) in the treatment of autoimmune diseases. Clin Exp Immunol 86: 192-198.
[Crossref]
5. American College of Rheumatology (1999) Guidelines for Referral and Management
of Systemic Lupus Erythematosus in Adults. USA: Lippincott-Raven Publishers.
6. Micromedex (2015) In: Truven Health Analytics, editor. Greenwood Village, Colorado.
7. Keller F, Maiga M, Neumayer HH, Lode H, Distler A (1984) Pharmacokinetic
effects of altered plasma protein binding of drugs in renal disease. Eur J Drug Metab
Pharmacokinet 9: 275-282. [Crossref]
8. (2008) National Antibiotic Guideline 2008.
9. eTGComplete. Elevated Blood Pressure in Patients with Kidney Disease.
10. Drugs.com. Drug Interactions Checker 2015.
Copyright: ©2015 Loudjedi S. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
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