Transcript Case presentation - Thalassemia Dubai

Case presentation
Thalassemia Center
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A 14-year old Omani girl
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Known case of Beta-Thalassemia Major
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Diagnosed at the age of 6 months.
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On regular transfusion every 4 weeks since that
time.
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First visit to Thalassemia centre at the age of 9
years old.
Findings on 1st presentation:
• Mild thalassemic features.
• Severe growth retardation (below 3rd
centile).
• Liver: 8cm.
• Spleen: 14 cm.
• Hb: 6.8 g/dl.
• S. Ferritin: 8600 ug/l
• HCV RNA +ve
Chelation history:
• Not on any chelation therapy till the age of 9
years.
• Desfral started at the age of 9 years
• On Exjade since November 2006
( 500mg, 20 mg/kg daily )
Family History:
23 y
22 y
16 y
16 y
14 y
9y
6y
On Examination:
• Good general condition
• Vital signs are stable
• Growth parameters are below 3rd centile
• Pallor: ++
• No jaundice
• Abdomen: spleen 4 cm and liver 3 cm BCM.
• CVS: normal.
• Chest: clear
• CNS: grossly intact.
Investigations:
• B gene: IVS 1-5 (G C) /CD 30 (G C)
• One Alpha gene deletion.
• HCV RNA turned –ve in Nov 2007 (no
treatment).
• EF was 60% in 2006.
• Euglycemic, normal thyroid & parathyroid
functions.
Baseline investigations done before starting Exjade:
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Serum ferritin: 2992 ug/l
Serum creatinine: 0.4 mg/dl
SGPT: 168 IU/L / SGOT: 91 IU/L
IGG: 30.3/ IGA: 3.2/ IGM: 3.5 (in 2004)
Anti ds DNA: -ve (in 2004)
ANF: +ve 1/1000 speckled (in 2004)
RF: +ve (in 2004)
Anti smooth muscle Ab: +ve (in 2004)
Ferritin Investigations
ug/l
Patient’s Action taken
condition
3356
Baseline Inv:
Cr.: 0.6 mg/dl
SGPT: 247 IU/L
SGOT: 166 IU/L
stable
500 mg
4085
SGPT: 434 IU/L
SGOP: 246 IU/L
stable
March 07 500 mg
3808
SGPT: 204 IU/L
SGOT: 152 IU/L
stable
April 07
750 mg
4731
SGPT: 267 IU/L
SGOT: 196 IU/L
stable
May 07
750 mg
SGPT: 147 IU/L
SGOT: 110 IU/L
stable
June 07
750 mg
ALP
SGPT: 342 IU/L
SGOT:223 IU/L
stable
Exjade 625 mg (20.8
mg/kg)
July 07
625 mg
SGPT: 196 IU/L
SGOT: 139 IU/L
stable
Exjade to 750 mg
(25 mg/kg)
Date
Exjade
dose
Nov 06
Jan 07
3398
Start Exjade 500 mg
(20 mg/kg)
Exjade to 750 mg
(25 mg/kg)
Ferritin Investigations
Patient’s
condition
Date
Exjade
dose
Sep 07
750 mg 3477
ALP: 380
stable
SGPT: 136 IU/L
SGOT: 99 IU/L
Oct 07
875 mg 2387
SGPT: 215 IU/L stable
SGOT:145 IU/L
Nov 07
875 mg
SGPT: 11 IU/L
SGOT: 26 IU/L
HCV turned -ve
9 Dec
07
875 mg
30 Dec
07
875 mg 2422
Action taken
Exjade to 875 mg
(29 mg/kg)
stable
H/O fever for Cultures, ESR,
3/52 mainly at CRP, CXR,
night + Wt loss Start Augmentine
(5.3 kg in 7 ms)
ESR:115/CPR:11
Cultures: –ve
CXR: normal
SGPT: 24 IU/L
SGOT: 14 IU/L
Fever for 1 &
half months,
not responding
to treatment
USS abd,
Widal test, MP
,ANA, ds DNA, RF
Anti-mitoch AB,
Anti-smooth
muscle AB,
Stop Exjade
Date
Exjade
dose
Ferritin Investigations
Patient’s
condition
Action taken
22 Jan 08
Stopped
for 3/52
3488
ESR: 40
ANF was +ve
1/1000 speckled
RF +ve
Anti-smooth
muscle AB: +ve
Ig: high
Stable, fever
subsided
after
stopping
Exjade
restart
Exjade at
250 mg (8.3
mg/kg)
Feb 08
250 mg
3836
ESR: 90
SGPT: 16 IU/L
SGOT: 35 IU/L
Stable, no
fever
Exjade to
375 mg (12.5
mg/kg)
4 March 08
375 mg
3542
ESR: 65
SGPT: 20 IU/L
SGOT: 30 IU/L
Stable, no
fever
Exjade to
500 mg
27 March 08 500 mg
2971
ESR: 33
SGPT: 23 IU/L
SGOT: 28 IU/L
Stable, no
fever
5 May 08
2660
SGPT: 24 IU/L
SGOT: 22 IU/L
Stable, no
fever
500 mg
Date
Exjade
dose
Ferritin Investigations
Patient’s
condition
Action
taken
29 May 08
500 mg
1961
SGPT:140 IU/L
SGOT: 103 IU/L
Stable
Exjade to
625 mg
June 08
625 mg
2627
ESR: 24
SGPT: 59 IU/L
SGOT: 31 IU/L
July 08
625 mg
2131
ESR: 80
SGPT: 47 IU/L
SGOT: 50 IU/L
Comment: the patient
was not taking the full
dose as she was
experiencing fever and
not feeling well on
doses above 500mg
daily.
Sep 08
625 mg
ESR: 90
ANF: +ve 1/320
nucleolar
Exjade was stopped
00/07/2008
00/06/2008
00/05/2008
00/03/2008
00/12/2007
00/11/2007
00/10/2007
00/08/2007
00/07/2007
00/05/2007
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00/03/2007
00/02/2007
00/01/2007
00/12/2006
00/10/2006
500
450
400
350
300
250
200
150
100
50
0
Exjade
started
HCV RNA –ve
SGPT
SGOT
Drug fever
Definition
• A disorder characterized by fever coinciding with
the administration of the drug and disappearing
after the discontinuation of the drug, when no
other cause for the fever is evident after a careful
physical examination and laboratory investigation
Mechanisms
1.
2.
3.
4.
Hypersensitivity reactions
Altered thermoregulatory mechanisms
Directly related to administration of the drug
Direct extension of the pharmacologic action of
the drug
5. Idiosyncratic reactions
1. Hypersensitivity reactions:
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Due to: 1. Ab-Ag complexes
2. T-cell immune responce
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Fever appears several days to three weeks after
the drug has been started, but the lag time can
be as long as several years.
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Fever can arise within hours of a rechallenge, in
a previously sensitized patient.
• Fever may the sole manifestation of a
hypersensitivity reaction.
• Hepatic, renal or pulmonary involvement, rash,
mucosal ulceration, and hematologic
abnormalities are not uncommon.
• Withdrawal of the offending drug usually results
in disappearance of the fever within 72 to 96
hours which helps to confirm the diagnosis.
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1.
2.
3.
4.
5.
Five drug-classes deserve special mention:
Anticonvulsants (e.g: phenytoin)
Minocycline
Other antimicrobial agents (e.g: beta lactams)
Allopurinol
Heparin
2. Altered thermoregulatory mechanisms:
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Regulated by the anterior hypothalamus.
Fever is caused by releasing “Endogenous
Pyrogens” (e.g: IL alpha & beta, TNF and
Interferon alpha).
• Drugs that can alter these Thermoregulatory
mechanisms:
1. Exogenous thyroid hormone
2. Anticholinergics (e.g: TCA)
3. Sympathomimetics (e.g: amphetamines)
3. Directly related to administration of the
drugs:
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Contamination of the administrated drug with
endotoxin or other exogenous pyrogens.
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Phlebitis, local inflammation and/or sterile
abscesses can occur at sites of injection.
4. Fever as an extension of the
pharmacologic effect of a drug:
• Fever observed following chemotherapy for
various solid tumors, lymphomas, and leukemias
due to release of different cytokines from cell
necrosis and lysis.
• Fever starts two to three days after
chemotherapy and may last for one week or
more.
• This early febrile response usually can be
distinguished from febrile neutropenia which
rarely develops before the second week after
chemotherapy.
5. Fever due to an idiosyncratic reaction:
• These reactions include unpredictable syndromes
and genetic disorders, and there is some overlap
with hypersensitivity phenomena.
Malignant hyperthermia
Neuroleptic malignant syndrome (NMS)
Serotonin syndrome
Glucose-6-phosphate dehydrogenase deficiency:
GENERAL CLINICAL ISSUES
• Drug fever is usually a diagnosis of exclusion.
• The first assumption of most clinicians is that
fever is due to infection, which may not always
be easy to exclude.
• Connective tissue diseases or malignancy are also
often difficult to exclude.
• Absence of the rash does not exclude Drug Fever
as it is only present in 18% of cases.
Fever patterns:
• The onset is in about eight days, but varies from
less than 24 hours to many months.
• fever may vary from a low-grade fever to high
grade “hectic” fever with chills and rigors.
• Patient’s condition may vary from severely ill to
surprisingly well.
• Relative bradycardia occurs in only about 10% of
cases.
Laboratory investigations:
• WBC can be elevated with eosinophilia and
occurs in less than 20% of cases.
• ESR is usually increased but this is a nonspecific
finding.
• Unexplained disturbance of liver function and/or
renal impairment can provide clues to the
diagnosis (e.g: interstitial nephritis caused by beta
lactams).
Cessation of the drug(s):
• The only real way to know if a patient has a drug
fever in the majority of patients is by stopping the
drug(s).
• The usual clinical approach is to discontinue the
most probable offending drug first, followed by
cessation of other drugs if fever persists.
• In most cases, resolution of drug fever will occur
within 72 to 96 hours of discontinuing the
offending drug.
Rechallenge:
• Rechallenge with the offending drug can
confirm the diagnosis if fever recurs.
• Rechallenge is usually safe, particularly when
the initial febrile illness is mild, but
unexpected events can arise.
• In clinical practice, rechallenge is not often
performed.
Thank you