CASE MANAGEMENT ON

HYPOKALEMIA AND
STEVEN – JOHNSON’S
SYNDROME
Christian Gallardo, MD
1st Year Resident
Department of Internal
Medicine
University of Perpetual Help
DALTA Medical Center
Objectives

 To discuss the diagnosis,

management and treatment of
Hypokalemia
 To discuss the pathophysiology and
clinical features of Hypokalemic
Periodic Paralysis and Renal Tubular
Acidosis
 To discuss Allopurinol as one of the
causes of Steven Johnson’s
Syndrome

General Data

 S.A
 31 year old
 Female
 Cavite City
 Roman Catholic
 Admitted for the first time
on July 30, 2009
Chief Complaint:

 RASHES on FACE
History of Present Illness
 Known Dyslipidemic and
with Hyperuricemia
recently diagnosed a
month ago maintained on
Simvastatin 20mg OD and
Allopurinol 100mg OD.




History of Present Illness

(-) Nausea, vomiting, LBM

History of Present Illness

(-) Nausea, vomiting, LBM

Past Medical History

 Hypokalemia – Cavite City

Medical Center (2002)
 Unrecalled potassium levels
 Consultation at SJDH –
Thyroid Function Test -
normal levels
 No Maintenance given
 Bronchial Asthma – Last
attack - 7 years old, no
exacerbations afterwards
 No Allergies
 No Operations
 No Hypertension, No Diabetes
Family History

 Hypokalemia –
 Father – with weakness episodes
 Had also cousins with hypokalemia on
father side
 Sister has also history of hypokalemia
maintained on potassium supplements
 Hypertension – Maternal side
 Diabetes Mellitus – Maternal side
 Asthma – Maternal side
 Cervical Cancer and Breast Cancer –
Mother
 Leukemia – Maternal side
 Polycethemia Vera – Paternal side
Personal and Social History

 Non smoker
 Non Alcoholic Beverage
drinker
 Works as a nurse
Review of Systems

 General: (-) Weight Loss

 HEENT: (-) blurring of vision, (-) sorethroat
 Cardiology: (-) chest pains, (-) PNDs, (-)
Orthopnea
 Gastroenterology: (-) abdominal pain, (-)
diarrhea, (-) constipation, (-) melena, (-)
hematochazia
 GUT: (-) dysuria, (-) oliguria (-)anuria
 Endocrinology: (-) polyuria, polydipsia,
polyphagia,
 Musculoskeletal: (-) myalgia
 Hematology: (-)easy brusability
 Neurology: (-) neuropathy, (-)seizures, (-)
headache
Physical Examination
 General: Conscious, coherent, Not
in cardiorespiratory distress
 VS: BP: 110/80 CR: 92 bpm
 RR: 20 cpm T: 36.7°C
 Skin: (+)maculopapular rashes,
non-scaling, non – blanching on
malar region, cheeks, frontal
area, neck, abdomen, trunks,
back, upper and lower
extremities
 HEENT: Anicteric Sclerae, pale PC,
(+) conjunctival erythema, (+)
oral mucocutaneous lesion, (-)
TPC, (-) NAD, (-) CLAD
Physical Examination

 Chest and Lungs: Symmetrical

Chest Expansion, No
retractions, (+) expiratory
wheezes at both lung fields
 Heart: Adynamic Precordium,
PMI 5th ICS MCL, Normal
Rate, Regular Rhythm,
Normal S1 and S2, No S3
and S4, No Murmur.
 Abdomen: Flat, Soft, NABS,
Non-tender, No
organomegaly
 Extremities: No cyanosis, Full
Pulses, No Edema
Neurologic Examination

 Oriented to time, person and place

 Cranial Nerves:
 I: can smell
 II: 2-3mm PERTL, Fundoscopy: (+)
ROR, Clear Media, Distinct Cup
borders, CDR: 1:3, AVR: 2:3, No
exudates, No Hemorrhage
 III, IV, VI: Full EOM
 V: (+) bilateral corneal reflex, good
masseter tone
 VII: (-) facial asymmetry
 VIII: can hear
 IX, X: (+) gag Reflex
 XI: can equally shrug shoulder
 XII: no tongue deviation

Neurological Examination

1 /5 1 /5 100% 100% ++ ++

100% 1 0 0 %+ + ++
1 /5 1 /5

3 /5 3 /5 100% 100%

++ ++

3 /5 3 /5 100%
100%
++ ++

 (-) dysdiadochokinesia, (-) dysmetria,

 (-) Babinski (-) Brudzinski
 (-) Nuchal Rigidity
Salient Features

 35 year Old
 Female
 1 month History of Allopurinol use
 Cough
 DOB
 History of hypokalemia and asthma
 Stong family history of hypokalemia on
father and siblings
 Conjunctival erythema
 Maculopapular Rashes on the face,
abdomen, trunks and extremities
 Wheezes at both lung field
 Generalized weakness of Upper and
Lower Extremities

Working Impression:

 Hypokalemia Probably
Secondary to Renal
Losses
 Hypokalemic Periodic
Paralysis vs Renal
Tubular Acidosis
 Hypersensitivity Vasculitis
vs Steven-Johnson’s
Syndrome Secondary to
 Allopurinol
Problem #1: Weakness of
extremities
 S> Body Weakness:
 Weakness of upper and lower
extremities
 (-) vomiting, headache and fever
 O> conscious, coherent, not in
respiratory distress



 Laboratories
1st HD 2nd HD 3rd HD 1st HD 1st HD 2nd HD
mmol/L
9pm
CBC
Na 142 145
WBC 13.5 16.6 14.1 Cl 107
Hematocrit 0.46 0.43 0.43 Mg 0.8
Hemoglobin 146 128 139
Segmenters 0.77 0.74 0.58 ABG
Lymphocyte 0.17 0.15 0.28 pH 7.32
s
Monocytes 0.04 0.09 0.09 pCO2 27.4
Eosinophils 0.02 0.02 .05 pO2 96.5
Platelets Adequa 256 281 HCO3 14.0
te S02 97.0
S im p le M e ta b o lic A cid o sis
W ith a d e q u a te oxyg e n a tio n
 Potassium Trend
1/5 upper extremity
4/5 lower extremity

4 kalium Durule Q6hrs

drip : PNSS 8O cc + 40 meqs KCL x 6 hrs
Spirinolactone 50mg / tab then 25mg / tab BID

5/5 upper extremity

Hypokalemia 2 ndto 5/5 lower extremity
3 / 5 u p p e r extre m ity
Hypokalemic Periodic Paralysis
2 / 5 lo w e r extre m ity
2 ) RTA Type2 1kalium Durule TID
KCL drip : PNSS 8O cc + 40 meqs KCL x 6 hrs
Oral K durule 2 durule TID
NaHCO3 1 Tab TID Spirinolactone 25mg/tab BID
Mg Oxide Repeat Electrolytes OPD basis
Other Laboratories
Chemistry
Creatinine 94 mg/dL
Urine Potassium 34.4 mmol/L
Urine Osmolality 211mOsm/kg H2O
Urine Cl 68 mmol/L
Plasma Osmolality 212 mOsm/kg H20 Na 142
Cl mmol/mL
107mmol/m
Computation
Transtubular K+ Concentration17.23 HCO3 L
14
Gradient
Anion Gap(TTKG) 21 mmol/mL
Anion gap = Na- (Cl +
HCO3)
Urine K (Uk) x Plasma
Osmolality (Posm)
TTKG= --------------------------------------------------------------
Plasma Potassium (Pk) x Urine
Osmolality (Uosm)
Weiner D and Dingo C. Hypokalemia – Consequences, Causes and Correction. American Journal of Nephrology 1999.
 Hypokalemic Periodic Paralysis

 Primary (Familial)
 Autosomal
The precipitating dominant
factors : disorder
- carbohydrate - or sodium
 Characterized rich meals
by -episodic ,
attacks of
- emotional
lly sparing stressweakness
facial
muscle ,
and respiratory muscles
with concomitant , and
- and resthypokalemia
after exercise (<3.5 mEq/L), which
gradual
- exposureusually
to cold resolution .
involves the four limbs.
- events associated with increase
 Age
epinephrine at onset of paralytic crises - within
or insulin
the are
Serum potassium first normal
or second decade.
during asymptomatic peri
 The frequency of attacks is maximal
between 15 and 35 yr of age and
then decreases with age .
Nand B, Vohra S. Hypokalemic Periodic Paralysis: An Unusual Cause. Hospital Physician
January 2003
Hypokalemic Periodic Paralysis

 Mutations in a calcium channel gene

(CACNA1S) or a sodium channel
gene (SCN4A)
 Majority of mutations in the CACNA1S
gene located on chromosome 1q31-
32.

Nand B, Vohra S. Hypokalemic Periodic Paralysis: An Unusual Cause. Hospital Physician

January 2003
 Hypokalemic Periodic Paralysis

 The mechanism for depolarization-

induced attacks of weakness in HPP
is not understood.
mutations
readily Missense
occur
 explain in
themutations
highly inof
the
conserved
episodes a1arginine
subunit r
depolarization
sitive K current , which is more easily tied to
loss -of-function
m patientsofwith manifest
the HypoPP as reduced
L-type depolarize
calcium in current
low Korsod
channel
less commonly in the voltage-gated
sodium channel cause HPP.

Venance S et al. The primary periodic paralyses: diagnosis, pathogenesis and treatment. Brain
(2006), 129, 8–17
 Renal Tubular Acidosis

 Characterized by
 Metabolic acidosis, secondary to
d. defects in renal tubular reabsorption
temic acidosis
mmune diseases. ,ofsuch as Sjogren
bicarbonate ’s syndrome.
(HCO3)
ublesome
ood than in theexcretion
 Urinary
bicarbonate acquired
concentration ofautoimmune form of dist
hydrogen (H+)
is normal
tomatic , especially
demonstrated by a if
failure a
to thiazide
lower diuretic
urine pH below is
 Glomerular function is little or not followi
5 . 5 prescr
affected
 All forms of RTA present
hyperchloremic metabolic acidosis,
with normal anion gap
Pereira P, Miranda D, Oliveira E. Molecular Pathophysiology of
Renal Tubular Acidosis . Current Genomics , 2009 , 10 , 51 - 59
Nand B, Vohra S. Hypokalemic Periodic Paralysis: An Unusual Cause. Hospital Physician
 Mechanism of Hypokalemia in
Mg Deficiency
 Magnesium deficiency exacerbates
potassium wasting by increasing
distal potassium secretion.
 A
necessarily decrease
cause hypokalemiain
. intracellular
magnesium,
vated aldosterone levels caused by magnesium
may be required for exacerb
deficiency, releases the
magnesium-mediated inhibition of
ROMK channels and increases
potassium secretion.

Huang C and Kuo E. Mechanism of Hypokalemia in Magnesium Deficiency. J Am Soc

Nephrol 18: 2649–2652, 2007
 Problem #2: Rashes

Hemorrhagic and erythematous and vesicular lesion of

Presence of erythema of the

Hemorrhagic and crusted lesions affecting the lip, palate

 Problem #2: Rashes

1st HD
CBC
rashes, Increase Conjunctival Redness WBC 13.5
Urine Culture
Hematocrit 0.46 12,000 col/mL
CXR CRP 146
Hemoglobin Diptheroids
Normal
Negative
Segmenters
Hbs AGESR 0.77 Non- reactive
1 mm/hr
Lymphocyte
Hbs ABANA 0.17 Non-reactive
Negative
Monocytes
s 0.04(1:40
SGOT
Eosinophils 0.0241
Hydrocortisone IV SGPT
Platelets dilution)
88
Adequa
Hydroxyzine
Mometasone Furoate te
 Allopurinol-Induced DRESS
Syndrome


Drug Rash with Eosinophilia and Systemic S
 Describes the association of drug
lymph node enlargement and
(allopurinol) single or multipl
together with
lar eruption and facial edema
eosinophilia and systemic
after commencement
symptoms of medication
(hepatitis and
progressive renal failure)


Markel, A. Allopurinol - Induced Dress Syndrome . Internal Medicine American

Journal 2005. Vol 7: 656-660.
 Allopurinol Dress Syndrome
 Prevelence: 2% of taking drug
A documented
Criteria
Lack of exposure
Presence intake
to2a major
of at least of
different
Allopurinol
drugand
criteria causing a similar
1 minor picture
criteria
- Worsening renal function
Major Criteria
- Acute hepatocellular injury
- Rash, manifesting by toxic epidermal necrolysis, erythema multiforme,
diffuse maculopapular rash or exfoliative dermatitis
Minor Criteria include fever, leukocytosis and eosinophila


Markel, A. Allopurinol - Induced Dress Syndrome . Internal Medicine American

Journal 2005. Vol 7: 656-660.
 Problem #2: Rashes

2nd HD
CBC
rashes,WBC MildConjunctival
Increase clearing of rashes
Redness
16.6
Hematocrit 0.43
Hemoglobin 128
Segmenters 0.74
Lymphocyte 0.15 Skin Biopsy - contemplated
s
Monocytes 0.09
Eosinophils 0.02
Platelets Desloratadine
256 Butamirate Citrate
Laboratories

CRP Negative
ESR 1 mm/hr
ANA Negative (1:40
dilution)

Urine Culture 12,000 col/mL

CXR Diptheroids
Normal
Hbs AG Non- reactive
Hbs AB Non-reactive
SGOT 41
SGPT 88
 Hypersensitivity Vasculitis
 American College of Rheumatology
1990
 Criteria for the Classification of
Hypersensitivity Vasculitis
 3+ present, sesitivity 71%, specificity
84%

eutrophils, eosinophils or both) in a privascular or

Ruddy et al. Kelly ’ s Textbook of Rheumatology 6th Edition 2001. Volume 2:1197
Hypersensitivity Vasculitis

 Clinical Manifestation
 Palpable purpura, fever, urticaria,
arthralgia, lymphadenopathy
 Begin 7-10 days after antigen exposure
 Includes glomerulonephritis, instertitial
nephritis, hepatocelluar injury and GI,
CNS or pulmonary vasculitis
Diagnosis:
Biopsy

Ruddy et al. Kelly ’ s Textbook of Rheumatology 6th Edition 2001. Volume 2:1197
 Problem #2: Rashes

3rd HD
CBC
rashes, Increase Conjunctival RednessClearing of rashes
WBC 14.1
Hematocrit 0.43
Hemoglobin 139
Segmenters 0.58
Lymphocyte 0.28
sMonocytes 0.09 Betamethasone
Eosinophils .05 Prednisone 15mg TID
Petroleum Jelly TID
Platelets 281
Steven Johnson’s Syndrome(SJS)

 Life treatening, bullous,

mucocutaneous disease, generally
considerd to be immune-medicated
reactions to drugs.
 Epidermal necrosis, extensive
detachment to the epidermis,
erosions of mucous membranes and
SJS severe
(< 10% constitutional
BSA) syndrome
Toxic epidermal necrolysis (TEN) (>30%

Halevy S, Ghislain PD, MockenhauptM et al. Allopurinol is the most common

cause of SJS and TEN in Europe and Israel. Journal of American Academy of
 Steven Johnsons Syndrome(SJS)

 European Case-Control Surveillance

of severe cutaneous adverse drug
reactions (EuroSCAR)
 A daily dose of 200mg or more of
allopurinolwas associated with
increased risk for SJS and TEN
ore and Taiwan studies
compared : 28
with % ofdaily
lower SJSdoses.
due to al
 Risk: Recent users ≤ 8 weeks

Halevy S, Ghislain PD, MockenhauptM et al. Allopurinol is the most common

cause of SJS and TEN in Europe and Israel. Journal of American Academy of
Final Diagnosis:

 Hypokalemia Secondary to
Hypokalemic Periodic Paralysis
 Steven Johnson’s Syndrome Drug
Induced (Allopurinol)
Hypokalemia

 The average daily potassium intake:

70 mEq.
 90% of potassium excreted in the
urine and the vast majority of the
remainder in the stool.
 Most potassium is present in the
intracellular space.

Weiner D and Dingo C. Hypokalemia – Caonsequences, Causes and Correction. American Journal of
Nephology 1999. Vol 2:1179-1188
 Hypokalemia

 Potassium is freely filtered at the

glomerulus, followed by
reabsorption of approximately 85%
by the proximal tubule and the loop
↓ Serum of Henle.
K from 3.5 to 3.0 mEq/L
Total
 body potassium deficit = 100 to 300 mEq,
↓ 2.0 mEq/L
Total body deficit = 600 to 800 mEq.

Weiner D and Dingo C. Hypokalemia – Caonsequences, Causes and Correction. American Journal of
Nephology 1999. Vol 2:1179-1188
 Reabsorbtion and Secretion

numerous cell, comprising 60 to 70% of the CCD, and i

d cells (A cell and B cell), which comprise the remain

Weiner D and Dingo C. Hypokalemia – Consequences, Causes and Correction. American Journal of
Nephrology 1999. Vol 2:1179-1188
Other Causes
of
Hypokalemia
 Manifestation of Hypokalemia

 Symptoms generally do not become

manifest until the serum is below
3.0 meq/L
 Severe muscle weakness or paralysis
– occur usually < 2.5 meq/L
 Lower extremities progresses to the
tations: trunk and upper extremities
eakness, ileus, distention, anorexia, nausea, vo

Rose B, Sterns R, Post T. Clinical Manifestation and Treatment of Hypokalemia.

UpToDate 2009.
 Cardiac Arrythmias and ECG
Abnormalities
 Premature atrial beat and ventricular
beat, sinus beat, paroxysmal atrial
tachycardia, atrioventricular block
mplitude of the T wave and increase in the amplitude
6 and ventricular tachycardia.

Rose B, Sterns R, Post T. Clinical Manifestation and Treatment of Hypokalemia.

UpToDate 2009.
Manifestation of Hypokalemia

 Rhabdomyolysis
 K<2.5meq/L can lead to
rhabdomyolysis, muscle cramps and
myoglobinuria
 Renal Abnormalities (reversible)
 Urinary concentrating abilities,
increased renal ammonia production
due to intracellular acidosis,
increased renal bicarbonate
reabsorbtion and hypokalemic
nephropathy
Rose B, Sterns R, Post T. Clinical Manifestation and Treatment of Hypokalemia.
UpToDate 2009.
 Correction of Hypokalemia

 There is no strict correlation between

the serum K concentration and total
body K stores – can only be
istributionapproximated in chronic
hypokalemia
does not apply
 K deficit
- may have of 200-400
normal plasma meqlevels despite los
potassium
 Lower the serum K by 1 meq/L

Rose B, Sterns R, Post T. Clinical Manifestation and Treatment of Hypokalemia.

UpToDate 2009.
 Correction of Hypokalemia
(Oral)
 K preparations:
 Intravenous or oral potassium is
generally preferred over K citrate or
s usually K bicarbonate
preferred over parenteral replacemen
 Metabolic alkalosis due to diuretic
therapy, vomiting, hyperaldosterism
 K citrate or K bicarbonate
 Hypokalemia and metabolic acidosis


Rose B, Sterns R, Post T. Clinical Manifestation and Treatment of Hypokalemia.

UpToDate 2009.
Correction of Hypokalemia (IV)

 Intravenous administration
 Who cannot eat
 Had severe symptomatic hypokalemia
 20-40 meq/L – peripheral vein
 More concentrated solutions can be
infused into large veins in severe
symptomatic hypokalemia


Rose B, Sterns R, Post T. Clinical Manifestation and Treatment of Hypokalemia.

UpToDate 2009.
Correction of Hypokalemia (IV)

 Maximum recommended rate (IV):

 10-20meq/hr
 However, 40-100meq/hr – patients
with paralysis of life threatening
arrhythmias
 Should be prepared as 10-20 meqs of K
in 100ml of fluid to avoid accidental
administration of IV K.
 Careful monitoring of physiologic
effects of severe hypokalemia is
essential
Rose B, Sterns R, Post T. Clinical Manifestation and Treatment of Hypokalemia.
UpToDate 2009.
Correction of Hypokalemia (IV)

 Saline rather than dextrose is

recommended
 Dextrose can lead to transient 0.2-1.4
meq/L reduction in the serum K,
particularly if only 20 meq/L of KCl
 Can induce arrhythmias in susceptible
patients
 Mediated by dextrose-stimulated
release of insulin and enhancing the
activity of cellular NA-K-ATPase pump

Rose B, Sterns R, Post T. Clinical Manifestation and Treatment of Hypokalemia.

UpToDate 2009.
Correction of Hypokalemia

 Mild to moderate hypokalemia (3.0-

3.5 meq/L)
 Directed toward replacing the lost
potassium and treating the
underlying disorder (vomiting or
diarrhea).
 10-20 KCL 2-4x/day (20-80meqs/day)
 Sequential monitoring of the serum K

Rose B, Sterns R, Post T. Clinical Manifestation and Treatment of Hypokalemia.

UpToDate 2009.
 Correction of Hypokalemia

 Severe Hypokalemia (<2.5 to 3.0

meq/L or symptomatic)
 Potassium must be given more rapidly
s much as 1 – 1to.5 patients with oral
meq/L after severe hypokalemia
dose of 40-60meq an
ion but is transient
Caution must be exercise
it  When treated, will tend to drive K into
serum K above 3.0cells
to and
3.5 worsen
or symptoms resolve and the
hypokalemia

Rose B, Sterns R, Post T. Clinical Manifestation and Treatment of Hypokalemia.

UpToDate 2009.
Correction of Hypokalemia

 For chronic replacement – serum K

should be measured 3-4x a month
 Oral KCl preparation salt substitutes
sprinkled on food (50-65meqs KCl
per level teaspoon)

Rose B, Sterns R, Post T. Clinical Manifestation and Treatment of Hypokalemia.

UpToDate 2009.
Summary

 HPP is a rare disorder of uncertain

cause characterized by potentially
fatal episodes of muscle weakness
or paralysis.
 RTA present hyperchloremic
metabolic acidosis, with normal
anion gap.
 SJS is a life treatening, bullous,
mucocutaneous disease, generally
considerd to be immune-medicated
reactions to drugs.
Summary

 Oral therapy is usually preferred over

parenteral replacement of potassium
 Mild to moderate hypokalemia (3.0-3.5
meq/L)
 10-20 KCL 2-4x/day (20-80meqs/day)
 Severe Hypokalemia (<2.5 to 3.0 meq/L
or symptomatic)
 Potassium must be given more rapidly to
patients with severe hypokalemia



THANK YOU.