3. case
• Male
• 12 Years
• K/C/O Sickle Cell Anaemia + Thalassaemia Major.
• Chief Complaints – 4 Episodes Of Convulsion
- Severe Pain In Lower Limbs &
- Altered Consciousness
-
3
4. Course of reaction
Patient is a k/c/o sickle cell anaemia +
thalassemia major since childhood
(family history +ve)
.
.
Requires periodic blood transfusion
.
.
Patient got admitted with
• Excruciating pain in lower limbs (L>R)
(since 2/12/16),
• 4 episodes of Convulsions (4/12/16),
• Altered Consciousness
4
5. Course of reaction
On 4/12/16
Admitted to Sion hospital
Under Dr.MVM in Ward 37
.
.
Patient has chronic bone pain but was exaggerated
since one month
On 6/11/16
For which he was started with
T. Prednisolone @ 2 mg/kg/day
Pt was continuously taking
T. Prednisolone 60 mg in two divided doses daily
( tapered to 30mg/kg on 4/12/16, 15mg/kg on
12/12/16 and 10mg/kg on 19/12/16 ) 5
8. Seriousness of reaction
• Reaction was SERIOUS as it Required
Hospitalisation of patient.
• Patient Recovered And Discharged on 20/12/16
• Diagnosis- Steroid Induced Vaso-occlusive
Crisis.
8
10. Causality assessment
• According to Naranjo Scale score is 4
POSSIBLE
BECAUSE -
1) Reasonable time-event relationship.
2) De-challenge response positive.
POSSIBLE
10
11. VASO – OCCLUSIVE CRISIS
• The Vaso-occlusive Crisis is caused by sickle-
shaped red blood cells that obstruct capillaries
and restrict blood flow to an organ.
• Resulting in Ischaemia, Pain, Necrosis, and
often Organ Damage.
11
12. SICKLE CELL DISEASE
• Inherited blood disorder.
• Inheritation of 2
abnormal copies of Hb
gene one from each
parent.
• Caused by a mutation in
the beta-globin gene that
changes the sixth amino
acid from glutamic acid
to valine.
12
13. SICKLE CELL DISEASE
• It results in an abnormal
haemoglobin found in red
blood cells.
• This leads to a rigid,
sickle-like shape under
certain circumstances.
• Problems in sickle cell
disease typically begin
around 5 to 6 months of
age.
13
14. SICKLE CELL DISEASE
• A number of health problems may develop, such
as attacks of pain ("Sickle-cell Crisis"),
Anaemia, Bacterial Infections, And Stroke.
• Long term pain may develop as people get older.
14
15. CAUSES OF VASO-OCCLUSIVE CRISIS
• Infections
• Severe dehydration
• Exposure to very high or very low temperatures,
or rapid change in temperature.
• High altitudes, where oxygen levels are low
• Drugs
15
16. PREDNISOLONE
• Prednisolone is a Steroid Medication used to
treat certain types of Allergies, Inflammatory
Conditions, Autoimmune Disorders
• Some of these conditions include Adrenocortical
Insufficiency, High Blood Calcium, Rheumatoid
Arthritis, Dermatitis, Eye Inflammation, Asthma,
And Multiple Sclerosis
• It is use by oral,intravenous injection, as a
skin cream, and as eye drops.
16
21. MECHANISMBEHINDVASO-OCCLUSIVE CRISIS
• The potential mechanism(s) involved in systemic
steroid-induced vaso-occlusion is unclear.
• Bone marrow infarction and likely associated Fat
Embolism may have contributed to the adverse
events.
• There is a well-documented association of
corticosteroid therapy and Bone Marrow Necrosis.
21
22. Mechanism BehindVaso-occlusive Crisis
• Additionally, we speculate that Steroid-induced
Leucocytosis could be another potential factor.
• High WBC counts in steady state have been linked
to worse clinical course, and Polymorphonuclear
Leukocytes appear to play an active role in vaso
-occlusive crises.
• Granulocytes or Stimulating Agents have been
associated with the apparent triggering of
sickle-related crises and multiorgan failure in
isolated case reports. 22
23. MECHANISMBEHINDVASO-OCCLUSIVE CRISIS
1. A patient with Hemoglobin-S/C Disease who
developed fatal sickle cell crisis after receiving
Granulocyte Colony Stimulating Factor was also on
daily Dexamethasone.
2. Severe complications were observed in ten of the
16 patients (62%). Eight patients experienced
severe vaso-occlusive events (VOE) within the 2
months following the initiation of steroid
treatment. Frequency of painful crises (2X),severe
pain episode, Acute Chest Syndrome, stroke,& Renal
infarction. 23
24. Management of vaso-occlusive crisis
• For Milder Crisis, manage on Nonsteroidal Anti-
inflammatory Drugs (Diclofenac or Naproxen.)
• For more Severe Crises, most patients require
inpatient management for Intravenous Opioids;
Patient-controlled Analgesia Devices are commonly
used in this setting.
• Vaso-occlusive crisis involving organs such as
the Penis or Lungs are considered an emergency
and treated with Red-blood Cell Transfusions.
24
25. MANAGEMENT OF VASO-OCCLUSIVE CRISIS
• Painful Crises are treated with Hydration,
Analgesics, & Blood Transfusion; Pain management
requires Opioid Administration at regular
intervals.
• Vigorous hydration.
• Bone pain may respond as well to Ketorolac (30–
60 mg initial dose, then 15–30 mg every 6–8 h).
• Morphine (0.1–0.15 mg/kg every 3–4 h) should be
used to control severe pain
25
26. MANAGEMENT OF VASO-OCCLUSIVE CRISIS
• Many crises can be managed at home with oral
hydration and oral analgesia.
• Most crises resolve in 1–7 days.
• Use of blood transfusion should be reserved for
extreme cases, transfusions do not shorten the
duration of the crisis.
• The most significant advance in the therapy of
sickle cell anaemia has been the introduction of
Hydroxyurea as a mainstay of therapy for
patients with severe symptoms.
26
27. MANAGEMENT OF VASO-OCCLUSIVE CRISIS
• Hydroxyurea (10–30 mg/kg per day) increases fetal
haemoglobin.
• Exert beneficial affects on RBC Hydration,
Vascular Wall Adherence, and Suppression of the
granulocyte and Reticulocyte count.
• Maintain a white cell count between 5000 and
8000/L.
• White Cells And Reticulocytes may play a major
role in the pathogenesis of sickle cell crises,
their suppression may be an important benefit of
hydroxyurea therapy. 27
28. CONCLUSION
• The present case emphasizes the poor tolerance
of steroids in SCD patients
• Review of literature suggest that systemic
corticosteroids play an important role in the
development of severe adverse events in some
patients with SCD.
• With better understanding of risk factors,
prevalence and pathophysiology of these events,
systemic corticosteroids should be used with
caution in this population.
28
29. CONCLUSION
• Prompt Red-cell Transfusion or Exchange
Transfusion along with aggressive clinical
management can improve the clinical outcome in
severe cases.
• Red blood cell transfusions given with
corticosteroid therapy in SCD patients may
attenuate the risk of such complications.
29
Keto – enzyme inhibitor
Erythro – enzyme inducer
Aceclofenac – pharmacologic synergism
Sirolimus – increase the level or effect by P-glycoprotein efflux transporter
2. The study population consisted of 16 SCD patients, less than 18 years of age, who were treated
with steroids between January 2000 and December 2005.