SPLENOMEGALY

By Dr Bashir Ahmed Dar

Associate Professor Medicine
Chinkipora Sopore Kashmir
Email drbashir123@gmail.com
Slight enlargement just palpable (less
than 5 cm)
 Infections –acute,subacute and chronic
 SLE
 Rheumatoid arthritis
 Amyloidosis
Moderate enlargement (to
umbilicus)
 Lymphomas
 Leukaemias
 Congestive splenomegaly
 Haemolytic anaemias
 Polycythaemia Vera
 ITP
 Myelodysplastic disorders
Marked enlargement (more than
8 cm or below umbilicus)
 Myelofibrosis
 Hairy cell leukaemia
 Tropical splenomegaly
 Kala azar
 Thalassaemia major
 Gaucher’s disease
 Felty’s syndrome
Infective causes of splenomegaly
 Acute causes
 Infectious mononucleosis
 Typhoid
 Brucellosis
 Infective hepatitis
 Toxoplasmosis
 Typhus
 Septicaemia
Infective causes of splenomegaly
 Subacute and chronic causes
 Bacterial endocarditis
 Tuberculosis
 Brucellosis
 Syphilis
 Histoplasmosis
 Malaria
 Kala azar
 Hydatid
 Trypanosomiasis
Massive splenomegaly
Rheumatoid arthritis (Felty’s
syndrome)

 Comprises of
 Arthritis,Splenomegaly,Leucopenia
Features of Felty’s syndrome
 Arthritis,splenomegaly,leucopenia
 Extra-Articular Manifestations
 rheumatoid nodules (76%)
 weight loss (68%)
 Sjogren's Syndrome (56%)
 lymphadenopathy (34%)
 leg ulcers (25%)
 pleuritis (19%)
 skin pigmentation (17%)
 neuropathy (peripheral) -17%
 episcleritis (8%)
 others: pericarditis
Investigations Felty's syndrome
 high Rf titre in 98%
 ANA in 67%
 elevated ESR, immunoglobulins, circulating
immune complexes
 positive LE cell test in 33%
 decreased complement levels
 elevated transaminases and alkaline
phosphatase in 25-50%
Tropical Splenomegaly
 In tropical areas massive splenomegaly
often seen
 Areas like Uganda,Nigeria,new guinea and
other parts of Africa
 The evidence suggests a relationship
between malaria and tropical splenomegaly
 Rarely occurs in malarial free areas
Tropical Splenomegaly
 Malarial parasite are not routinely seen in blood
films of pts
 The disorder usually presents in young adult life
but may occur in children
 The diagnosis is usually made by exclusion of
other causes
 There may also be 10 fold increase polyclonal igM
concentration in serum of which small portion
represents malarial antibodies liver may also show
lymphocytic infiltration
Kala azar (leishmaniasis)
 Visceral leishmaniasis
 Cutaneous leishmaniasis
 Mucocutaneous leishmaniasis (espundia)
 Diffuse Cutaneous leishmaniasis
 SYNONYMS

kala azar, black fever, sandfly

disease, Dum-Dum fever and
espundia.
Protozoan
in the family Trypanosomatidae

In the genus Leishmania

Estimates
All over world except
Not found in South-east Asia
350 million people at risk
12 million people infected / year
There are 59,000 deaths / year
Some Facts
 Incubation – 1 week to months
 Having (many reservoirs)
 No direct person to person transmission
 Spontaneous healing can happen (cutaneous
form) in months to years
 No vaccine
 LEISHMANIASIS or KALA-AZAR

It is the result of the infection with one

of the species of protozoa (leishmania).
Conveyed by:
Sandflies (Phlebotomus).
Visceral Leishmaniasis: L. donovani
Mucocutaneous : L. Braziliensis
 Leishmania
Parasites
Have specific reservoirs
 Sloths

Rodents
Vectors
Phlebotomine Sand Flies
 20 to 40 days
30

nt
ha

ys me
to
tc 70
da lop
h
1 eg
10 e to gs
5- ev
2
ld

we
pa

adults crepuscular ek
s
pu

and nocturnal

4 instars
diapauses in 4th instar
 Armadillo

Opossum
 Visceral Leishmaniasis:
 L. donovani
 Mucocutaneous
 L. Braziliensis
Cutaneous : L. tropica Old
major
L. tropica world
minor

New World : L. Braziliensis

L. Mexicana
PATHOLOGY
» L. donovani parasitizes the reticu. endoth.
cells

» Great proliferation of macrophage

»
» Cells result: Liver – spleen enlarg.

» The red bone marrow extend.

Leishmania: an obligate intracellular
protozoan parasite (2-6 µm in diameter)

r o us
p h o
a s ito s of
par acuole ages
v
r o ph
a c
m
 µ m
- 3 0
1 5 ) ,
u t µ m
bo -3
( by 2
a

Promastigotes in Sand Fly gut

and in Culture Media
Amastigote in macrophage

 The
amostigotes of
different
species are
very similar on
light
microscopy.
CLINICAL PICTURE
early stages is not easy for diagnose.
There is no constant physical signs.

☺ Changes in the blood picture

particularly Leucopenia.
☺ Outstanding physical sign is the
enlargement of the spleen 3 cm. a month.
● Liver : enlarged spleen + liver are
neither tender nor painful.

● Sometimes: Jaundice = prognost.

Significance

● Enlarged : Lymph node, could be

but its not a feature of the
disease.

● Wasting : Emaciated pat with a

protuberant
 Abdomen ( liver + spleen
enlarged)

●Fever : Without subjective symptoms

of fever – no delirium.

● Sometimes: there is no fever

● Skin : dry, rough. The natural

pigmentation of the skin over
the bone and around the
mouth is deepened. (Kala
azar??)
Clinical Forms of Leishmaniasis

• Cutaneous
•
Mucocutaneous
• Diffuse
Cutaneous
• Visceral
Cutaneous form
Wet lesion by L.
major
 L. major occurs most commonly
in rural areas, causing moist,
ulcerative lesions which may be
extensive and sometimes involve
the epithelium of lips and nose.
 These are the
commonest types of
lesion caused by L.
major.
 Prominent ‘rolled’ edge
of the lesions is the best
area to demonstrate the
parasites
Lymphatic spread of L.
major
The ink marks indicate a line
of subcutaneous nodules
along the lymphatic, passing
proximally from the lesion on
the lower part of this man’s
arm.
The nodules usually resolve
without complications when
the primary lesin heals with
or without specific therapy.
Clinical Forms
of
Leishmaniasis
Simple ‘dry’ lesion by L.
tropica
dry, usually self-
healing lesions,
Generally single
Urban area in
North Africa and
the Middle East to
the former USSR,
Afghanistan,
western states of
India
The lesions
frequently contain
very large
numbers of
parasites.
Leishmaniasis recidivans

 Infection with L. tropica may

become very chronic, with a
hyperallergic reaction leading to
lupus-like lesions such as seen in
this child.
 Amastigotes may be very difficult to
find in the lesions.
Mucocutaneous lesion by L.
aethiopica
 In addition to simple
cutaneous lesions
due to infection with
L. aethiopica, other
forms are seen in
the Ethiopian
highlands where
rock hyraxes are the
reservoirs. It has not
yet been
ascertained whether
the mucocutaneous
condition seen here
is due to this or
another species of
Leishmania.
Chiclero’s ulcer by L.
mexicana

 Forest workers
collecting gum from
wild chicle trees
commonly sleep
near the forest floor
and are bitten on
exposed parts of the
head by vectors.
 Ulcers leading to
erosion of the
auricular cartilage.
Lymphatic spread of
L. mexicana

 As noted for L. major,

lymphatic spread may
also occur with New
World species.
 This patient was
infected with L.
guyanensis the agent
of ‘Pian bois’. In such
infections the
lymphatic nodules may
ulcerate.
Early lesion of
Espundia
 The lesions of mucocutaneous
leishmaniasis due to infection
with L. braziliensis may first
become evident as ulcers
involving the mucocutaneous
junctions of the mouth and
nose
 This condition frequently
follows a primary cutaneous
lesion which may have healed
with or without specific
therapy some years earlier.
Pharyngeal involvement

 Ulceration often extends to the pharynx and soft palate,

and the first symptoms may be related to tissue destruction
in this area.
 This man had the scar of a large ulcer which had apparently
healed on his leg some 30 years before.
 PKDL
Post Kalazar Dermal Leishmaniasis
Visceral form
Clinical picture of kala-azar in Kenya

Increasing
enlargement of
the spleen and
liver is a
characteristic
feature while, in
dark-
complexioned
subjects,
deepening skin
pigmentation is
seen-hence the
 synonym kala- lymphadenopathy is common in African
A generalized
azar, the ‘black
kala-azar; the parasite in this area is considered to be in
sickness’.
the L. donovani complex.
 Diagnosis
 Demonstration of Parasite from aspirate
- lymph node
; inguinal LN, sensitivity 60%
- bone marrow
; iliac crest, sensitivity 70%
- spleen; sensitivity 95~99%
- liver
 PB smear (HIV infected patient)
 Serology
- avoid the necessity for the more invasive procedure
- direct agglutination test
 PCR
Iliac crest aspiration of bone marrow

The most direct

means of
diagnosis of kala-
azar is the
detection of
amastigotes in
bone-marrow,
spleen or blood;
the organisms are
recognized in
dried smears of
material stained
with a
Romanowsky stain
by their
characteristic
morphology.
 L. infantum in macrophage from bone marrow

 While typically found in macrophages as shown here,

isolated extracellular amastigotes from disrupted host
cells are commonly seen in such preparations.
Amastigotes in macrophage from
skin
The diagnosis is
confirmed by
demonstraing
amastigotes in
smear made
from the
cutaneous
lesions.
Punch biopsy

A piece of tissue
may be removed
under local
anesthetic with a
disposable skin
punch for
histology, culture
and the direct
demonstration of
amastigotes.
Parasitised macrophage in skin
section
 Many
parasitised
macrophages
can be seen in
this section
from an acute
lesion caused by
L. major.
 DIAGNOSIS
1. Needle aspiration
Bone – sternum – liver, spleen
Histology – culture
L. donovani body

2. a. Leucopenia: Neutropenia –
relative mononucleosis.

b. Progressive fall with the red cell

count
• Formalin gel (aldehyde)
2 drops formalin + 2 ml serum
After 20 min, white ring

5. Complement fixation and fluorescent

False positive trypanosomal infection

• The complement fixation – early positive –

negative after cure. Sometimes + or – lung. Other
diseases.
6. Fluorescent antibody

• IV + V: In trypanosomal infection

• Skin test (Montenegro)

Delayed hypersensitivity reaction
0.2 ml. suspension
 TREATMENT
• Antimonial –
i. Urea, stibamine, pentavalen + antmonyia
 I.V. daily or every 2 days
 6 – 10 dose
 First 100 mg then 200 then 250
 Total dose 2 – 5 g. adult

Side Effect: Nausea, vomiting, joint pain,

Abdominal pain, diarrhea
 Contraindication: Liver and kidney
failure
ii. Sodium stibogluconate (Pentostam)
 I.M. – 600 mg total daily for 6-10 days
 Repeated after 14 days; if needed
 Side effect: Anaphylactic shock

7. Diamidiem –
 Pentamidine isothionate
 Dose 3 -4 mg / kg / BW total 300 mg
Side effect: Hypoglycemia
Treatment
 Sodium stibogluconate
 Pentavalent antimony (Sb+5)
 demonstration of amastigotes(L. donovani bodies)

 intracellular form is usually 2-4 micron consists of

nucleus and is rod like with a homogeneous mass
of cytoplasm,while the extracelluar or culture form
is14-20 microns in length 1.5 to 3.5 breadth

 L. donovani body
Myelofibrosis or myelosclerosis
 Fibrosis and collagen formation in marrow
 Primary –developing in polycythemia vera
 Secondary – in TB,secondary
carcinoma,hodgkins disease,leukaemia,and
variety of other conditions.
 Myeloid metaplasia ,spleenomegaly
hepatomaegaly etc etc
GAUCHER’S DISEASE
History
 Discovered by Philippe Gaucher, a medical
student in Paris, in 1882.

 He was studying a woman with an enlarged

spleen
 Definition
 Gaucher's (go-SHAYZ) disease occurs
when certain harmful fatty substances
build to excessive levels in your liver,
spleen, lungs, bone marrow and, less
commonly, your brain. This
accumulation of fatty material in tissues
interferes with the normal functioning of
organs, and may cause organ
enlargement and bone pain.
 Gaucher's disease results from an
enzyme deficiency, and sometimes the
term "glucocerebrosidase deficiency" is
used to describe this condition.
 Gaucher's disease is most common in
Eastern and Central European
(Ashkenazi) Jews. It can occur at any
age in life, and affects males and
females approximately equally.
What Is It?
 Gaucher’s Disease- rare inherited metabolic
disease or disorder ; due deficiency or lack of an
enzyme called Glucocereborsidase

 Results in an accumulation of glucocerebroside

within cells in various body tissues ( spleen, liver,
bone marrow, and skeleton)
 Severity of the disease can vary and thus disease
divided into following types
TYPE 1
 Most common and can begin at any age

 1 in 10,000
 Patients are bruised very easily
 Fatigued due to anemia
 Lung and kidney injuries
 Weakening of the skeleton
TYPE 1 (continued)

 Victims have a shortened life-span

 Usually die from clots and pneumonia

TYPE 2
 Rarest of all the types

 Appears during the first few months of life

in a baby

 Great brain damage – mental retardation

TYPE 2 (continued)
 Loss of muscle control

 Enlargement of liver and spleen

 Nervous system fails to function well

 Patients usually die by age 2

TYPE 3
 Begins in childhood
 Liver and spleen enlargement
 Causes bone marrow and damages the
central nervous system
 Mental retardation is quite common
 Usually die around the ages 15-30
Symptoms
 Bone pain

 Victim bruises easily and there are many

fractures in their bones

 Difficulty walking
 Blood clotting
Symptoms (continued)
 Muscle weakness

 Poor coordination

 Seizures
How Do You Get It?
 Acquired if both parents of the disease are
carriers
 A victim receives an abnormal form of the
genes- a Gaucher Gene from both parents
 Carrier- person with one normal gene and
one Gaucher Gene ( a carrier will not show
signs of the disease)
If 2 Carriers Have Children

 There is a one in four chance of a

child inheriting the disease
Who Has It?
 10,000 to 20,000 Americans
 High rate found in the Ahkenazi Jewish
population-1 out of 500-1000 births
 Types 2 & 3 are found in 1 out of 50,000-
100,000 births
 Type 3-mainly found in people of northern
Swedish Ancestry
Prevention

 No real prevention

 Genetic Counseling is recommended for

parents with a family history of the disease
Treatments
 No CURE
 Enzyme replacement therapy-injections of
the enzyme
 Result: decrease liver and spleen size

reduce skeletal abnormalities

restores normal growth &
development
restores well being of the patient
Hairy cell leukaemia
 Hairy cell leukaemia is an uncommon
disorder of middle and late adult life.
 Characterized by the presence in bone
marrow,spleen,and peripheral blood of
abnormal mononuclear cells with hairy
cytoplasmic projections and best detected
by phase contrast microscopy.
 Males affected more than females
 Marked by splenomegaly , however
lymphadenopathy is unusual
 Splenectomy is usually regarded as
treatment of choice
 Long term use of injections of alpha
interferon cause regression of hairy cells
 Hairy cell leukemia is actually a mature B
cell neoplasm. It is usually classified as a
sub-type of chronic lymphoid leukemia for
convenience. It is uncommon, representing
about 2% of all leukemias, or less than a
total of 2000 new cases diagnosed each year
in the North America and Western Europe
combined.
 Originally known as histiocytic leukemia,
malignant reticulosis, or lymphoid
myelofibrosis in publications dating back to
the 1920s, this disease was formally named
leukemic reticuloendotheliosis
 Symptoms

 In hairy cell leukemia, the broken "hairy cells"

build up in the bone marrow, which means that the
bone marrow has difficulty producing enough
normal cells: white blood cells to fight infections,
red blood cells to carry oxygen, and platelets to
stop bleeding. Consequently, patients usually
present with infection, anemia-related fatigue,
and/or easy bleeding.
Hematologic Disorders Causing
Massive Splenomegaly
 Polycythemia Vera
 Multiple Myeloma
 POEMS Syndrome
 Waldenström's Macroglobulinemia
 chronic lymphocytic leukemia
 non-Hodgkin lymphoma
 chronic myelocytic leukemia
 malaria (hyper-reactive malarial
splenomegaly)