2. Chief Complaint
9 years old boy
◦ yellowish discoloration of skin and pallor
for 2 wks
◦ fever for 2 days
◦ RT leg swelling For 2 days
3. History of Present Illness
9 yrs old boy K/C congenital
lymphedema and frequent soft tissue
infection.
usual health of status till 2 wks ago when
he started to have
◦ yellowish discoloration of the skin and sclera.
◦ decrease activity
◦ Runny nose , sore thraot , mild fever but no
cough or SOB . not seen by doctor, treated
with antibiotics (Over-the-counter) for 5 days
.
4. History of Present Illness
His condition getting worse : continuous
yellowish discoloration and pallor ,more
lethargic and sleepy . no SOB , palpitation
or bleeding.
Stat to have dark urine but normal
frequency and amount , no foul smell or
pain in micturition, no changes in color of
stool
decrease appetite, no weight loss .
2 days prior the admission he started to
have:
◦ high grade fever documented at home tympanic
(40)
◦ increase the size of RT leg with redness , pain
,limping , unable to stand. no joint swelling ,
5. Past History
Neonatal : uneventful pregnancy , FT ,
NSVD . no NICU admission.
congenital lymphedema, novel gene
mutation THSD1, diagnosed at KFSH at
age 3 years .
◦ it has been proposed that THSD1 has a
potential role in angiogenesis and
maintenance of vascular integrity.
compromise vascular integrity resulting in a
range of phenotypes from embryonic lethality
to persistent or self-limiting edema .
Frequent soft tissue infection , mostly in
lower limbs, bilateral. 4 times in last year
, need IV antibiotics.
6. Past History
patient on follow up with immunology ,
still under work up ( mild T cell
depression by blastogensis )
he was on bactrim prophylaxis but
stopped for more than 3 months (poor
compliance).
No surgical Hx
Allergies not known to have allergy
Diet : home diet.
Immunizations : up to date ,no
complications .
Development : normal for his age
7. History
Family History
Parents are third degree relative .
Healthy
His brother is 13 years old , has
congenital lymphedema, same gene
mutation but less frequent soft tissue
infection.
No history of congenital anemia or
hemoglobinopathy, liver disease ,
malignancy, gallstone or splenectomy.
Social History : mother is teacher ,
father works in military . good social
economic status. Live in Riyadh , no
animal contact
8. Physical examination
alert ,looks jaundiced , pale , not in distress
, edema on whole body mainly on face and
LL.
No dysmorphic features .
T: 39.4 °C HR: 160 RR: 24 BP: 91 / 53
SpO2: 99% WT: 25 kg (25-50th) Hight : 130 cm
(50th)
ENT: runny nose ,throat congestion, normal
ear .
No palpable LN .
9. Physical examination
CVS: good peripheral pulses , CRT < 2 sec ,
normal apex beat position , no thrill , normal first
and second hart sound with no added sounds or
murmur.
chest : no chest deformity , good chest
expansion , normal vesicular breathing with no
added sound.
abdomen: soft and lax ,no tenderness , palpable
liver 1 cm BCM , liver span 6 cm and spleen is
not palpable.
MSK: non pitting edema on both legs but more
on the right leg and tender , warm , redness ,
mild ulceration and petechiae on RT leg . No
bone deformity.
CNS: normal tone , power and reflexes
10. Summary
◦ 9 yrs old boy K/C congenital lymphedema
and frequent soft tissue infection , came
with fever and leg swelling and pain For 2
days and yellowish discoloration for 2 wks
.
◦ O/E : looks pale and jaundiced , febrile .
edema on both legs ,more on the right ,
tender , warm , redness . No
organomegaly .
13. work up
• Commbs test
• direct positive , IgG +4. C3 -ve
• indirect : positive
• Blood group O+ve
14. work up
• C3 1.340 gm/L
• C4 0.421 gm/l
• DNA DS 16.64 IU/ml
• ANA 1:80
• CMV -ve
• EBV –ve
• Blood C/S –ve
• Abdominal US :
• Tiny lymph node measuring 0.9x0.5cm in the porta hepatis.
Unremarkable GB , kidney, CBD , pancreas .
Spleen and liver within normal size, no focal lesion
16. Hospital course
Initially patient started on
methylprednisolone and after 2 days
,received 2 doses of IVIG then shifted
on prednisolone reaching now 25 mg
q12h.
Did not receive blood be cause there
was no compatible blood .
Hg drops to 3.9 , and discharged on 7.6
Clindamycin for 7 days.
Discharged on : prednisolone ,
fluconazole , Bactrim and folic acid with
follow up .
17. Autoimmune Hemolytic
Anemia
collection of disorders characterized by the
presence of autoantibodies that bind to the
patient's own erythrocytes, leading to
premature red cell destruction.
Specific characteristics of the autoantibodies
: especially the type of antibody, its optimal
binding temperature and whether
complement is fixed , effect the clinical
picture.
estimated annual incidence of 1 in 80,000
persons in the general population , it is more
common than acquired aplastic anemia but
less common than immune thrombocytopenia
.
19. Warm-reactive AIHA
Most common, usually IgG, that bind to the red
cells at 37ºC, fix complement in some cases, and
lead to extravascular hemolysis regardless of the
presence of complement.
These red cells pass through the spleen and other
parts of the reticuloendothelial system, where they
interact with complement and Fc receptors on the
macrophages. Erythrocytes may be fully ingested
by macrophages, however, if only a portion of the
surface membrane is removed, the erythrocyte
reforms into a spherocyte, which is identifiable on
the peripheral blood smear .
In IgG-coated erythrocytes, the majority of immune
clearance occurs within the spleen ( extravascular
hemolysis) , which does not lead to
hemoglobinemia and/or hemoglobinuria.
20. Paroxysmal cold hemoglobinuria
common in children after a viral-like illness.
IgG autoantibodies that bind at colder temperatures 4ºC and
fixes complement efficiently,
At normal body temperature, no antibody is identifiable on the
cell surface, but complement components, particularly C3b,
can be identified using the antiglobulin reagent.
If complement is activated to completion on the cell surface,
erythrocytes will hemolyze intravascularly, resulting in
hemoglobinemia and hemoglobinuria .
When complement is deposited on the red cell but not fully
activated to the point of cell lysis, macrophages within the
reticuloendothelial system bind the erythrocytes using
complement receptors and engulf them in a manner similar to
warm-reactive AIHA .
21. Cold agglutinin disease
Relatively rare in children, but can
occur after Mycoplasma infection.
IgM autoantibodies bind erythrocyte at
colder temperatures and fix
complement, which leads to either
complement-mediated intravascular
hemolysis (like PCH) or immune-
mediated extravascular clearance,
mainly by hepatic macrophages
22. Autoimmune disease
◦ Most common form of secondary AIHA in
older children occurs in association with a
broad autoimmune disease such as systemic
lupus erythematosus .
◦ Other systemic autoimmune or inflammatory
disorders (scleroderma, rheumatoid arthritis,
dermatomyositis, ulcerative colitis,
autoimmune thyroiditis) also have been
associated with AIHA
◦ Often there is a family history of autoimmune
disorders (not necessarily immune-mediated
hematologic conditions) such as lupus,
thyroid disease, or rheumatoid arthritis.
23. Immune deficiency
Children with congenital
immunodeficiency also can develop
secondary AIHA, almost caused by
altered immune regulation .
AIHA can present as the initial
manifestation of an unsuspected
congenital immunodeficiency disorder,
particularly common variable immune
deficiency (CVID).
Children with acquired
immunodeficiency, including those
infected with the HIV , can develop
24. Malignancy
AIHA also can occur in children with
Hodgkin lymphoma, acute leukemia,
myelodysplasia, or following allogeneic
hematopoietic cell transplantation .
The pathogenesis of the erythrocyte
autoantibodies in association with cancer
is unknown, but an underlying immune
deficiency may lead to both autoimmune
phenomena and malignancy.
Malignancy can present during or even
after the hemolytic anemia.
25. Infections
Most children who present with PCH
have had a recent viral-like illness.
Occasionally a specific infectious
agent, including Mycoplasma
pneumoniae , Epstein-Barr virus ,
measles, varicella, mumps, and
rubella, triggers AIHA.
Most of these infections are
associated with IgM autoantibodies.
26. Medication exposure
Medications that are particularly
important in causing AIHA in children
include :
penicillins,cephalosporins, tetracycline,
erythromycin,probenecid, acetaminophen,
and ibuprofen.
In a 2014 review of this
subject, piperacillin was identified as the
most frequent etiologic agent
27. Treatment
Optimal treatment depends initially
upon the severity of the anemia, the
signs and symptoms, and the
characteristics of the autoantibodies.
In the setting of severe intravascular
hemolysis, maintaining a good renal
blood flow and urine output is
essential.
28. Glucocorticoids
Best primary therapy for warm-reactive AIHA,
particularly for children with IgG antibodies,
as they interfere with the basic
pathophysiology and immune destruction of
erythrocytes.
Rapid effect within 24 to 48 hours. They may
also diminish the production of
autoantibodies, but this effect may require
several weeks.
For the very anemic child with warm-reactive
AIHA, intravenous methylprednisolone should
be administered every six hours at a dose of
1 to 2 mg/kg for the first 24 to 72 hours.
29. Glucocorticoids
Oral prednisone at a total dose of 1 to
2 mg/kg per day is then used after the child is
more clinically stable. Typically, high doses are
used for two to four weeks, followed by a slow
taper over two to six months, based upon the
hemoglobin concentration, reticulocyte count,
and direct antiglobulin test results.
Overall response rate of approximately 80
percent .
In contrast, children with PCH usually have a
self-limited hemolytic process, but may need a
short course of glucocorticoids to reduce
hemolysis and improve anemia.
Less commonly, glucocorticoids may be
beneficial in cold-agglutinin disease
30. Warming
For patients with cold-reactive
antibodies, keeping the patient warm
at all times is important:
◦ Avoiding exposure to cold environments
◦ Warming the patient's room with
additional space heaters, if needed
◦ Use of socks and warm clothing
◦ Using a blood warming apparatus during
any intravenous
31. Intravenous immunoglobulin
occasionally effective in the treatment
of autoimmune hemolytic anemia
refractory to conventional therapy
with prednisone and splenectomy.
used as part of the initial regimen to
establish control in patients with very
severe disease.
32. Transfusion
if the anemia is causing
cardiovascular compromise (usually
when the hemoglobin concentration is
below 5g/dL), strong consideration
must be given to transfusing the
patient with erythrocytes to provide the
needed oxygen-carrying capacity.
despite the risks, transfusion therapy
should not be withheld from a patient
with AIHA and life-threatening anemia
33. Exchange transfusion
Patients with IgM autoantibodies respond
better to plasmapheresis than do those with
IgG autoantibodies because the larger IgM
molecules are found mostly within the
intravascular space . In addition, at warm
temperatures IgM autoantibodies are bound
less tightly to red cells than are IgG
autoantibodies, allowing them to be removed
more easily by plasmapheresis.
In contrast, IgG autoantibodies diffuse into
the extravascular space, so that
plasmapheresis removes only a portion of the
total IgG autoantibodies.
34. Rituximab
Well-tolerated and lead to remission in 50 to
60 percent of patients.
Four weekly intravenous infusions
(375mg/m2/dose) lead to good therapeutic
responses.
hypogammaglobulinemia and prolonged
absence of circulating B cells will occur after
rituximab therapy . Therefore (IVIG) may be
useful as replacement therapy after rituximab
use .
rituximab is another option for children who
do not respond to treatment with
glucocorticoids, and is generally suggested
before splenectomy.