Causes of Spleenomegaly By Dr Bashir Ahm...

SPLENOMEGALY : 

SPLENOMEGALY By Dr Bashir Ahmed Dar Associate Professor Medicine Chinkipora Sopore Kashmir Email drbashir123@gmail.com

Slight enlargement just palpable (less than 5 cm) : 

Slight enlargement just palpable (less than 5 cm) Infections –acute,subacute and chronic SLE Rheumatoid arthritis Amyloidosis

Moderate enlargement (to umbilicus) : 

Moderate enlargement (to umbilicus) Lymphomas Leukaemias Congestive splenomegaly Haemolytic anaemias Polycythaemia Vera ITP Myelodysplastic disorders

Marked enlargement (more than 8 cm or below umbilicus) : 

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 : 

Infective causes of splenomegaly Acute causes Infectious mononucleosis Typhoid Brucellosis Infective hepatitis Toxoplasmosis Typhus Septicaemia

Infective causes of splenomegaly : 

Infective causes of splenomegaly Subacute and chronic causes Bacterial endocarditis Tuberculosis Brucellosis Syphilis Histoplasmosis Malaria Kala azar Hydatid Trypanosomiasis

Massive splenomegaly : 

Massive splenomegaly

Rheumatoid arthritis (Felty’s syndrome) : 

Rheumatoid arthritis (Felty’s syndrome) Comprises of Arthritis,Splenomegaly,Leucopenia

Features of Felty’s syndrome : 

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 : 

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 : 

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 : 

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) : 

Kala azar (leishmaniasis) Visceral leishmaniasis Cutaneous leishmaniasis Mucocutaneous leishmaniasis (espundia) Diffuse Cutaneous leishmaniasis

Slide 14: 

kala azar, black fever, sandfly disease, Dum-Dum fever and espundia. SYNONYMS

Protozoanin the family Trypanosomatidae In the genus Leishmania : 

Protozoanin the family Trypanosomatidae In the genus Leishmania

Slide 16: 

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

Slide 17: 

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 Some Facts

LEISHMANIASIS or KALA-AZAR : 

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

Slide 20: 

Have specific reservoirs Leishmania Parasites

Slide 21: 

Rodents Sloths

Vectors : 

Vectors Phlebotomine Sand Flies

Slide 23: 

30 to 70 eggs hatch 1 to 2 weeks 4 instars diapauses in 4th instar pupal development 5-10 days adults crepuscular and nocturnal

Slide 24: 

Opossum Armadillo

Slide 26: 

Visceral Leishmaniasis: L. donovani Mucocutaneous L. Braziliensis

Cutaneous : L. tropica major L. tropica minor New World : L. Braziliensis L. Mexicana : 

Cutaneous : L. tropica major L. tropica minor New World : L. Braziliensis L. Mexicana Old world

PATHOLOGY : 

PATHOLOGY » L. donovani parasitizes the reticu. endoth. cells » Great proliferation of macrophage » Cells result: Liver – spleen enlarg. » The red bone marrow extend. »

Slide 29: 

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

Slide 30: 

Promastigotes in Sand Fly gut and in Culture Media (about 15-30 µm by 2-3 µm),

Slide 31: 

Amastigote in macrophage The amostigotes of different species are very similar on light microscopy.

CLINICAL PICTURE : 

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.

Slide 33: 

? 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

Slide 34: 

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??)

Slide 35: 

Clinical Forms of Leishmaniasis Cutaneous Mucocutaneous Diffuse Cutaneous Visceral

Cutaneous form : 

Cutaneous form

Slide 37: 

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

Slide 38: 

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.

Slide 39: 

Clinical Forms of Leishmaniasis

Slide 40: 

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.

Slide 41: 

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.

Slide 42: 

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.

Slide 43: 

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.

Slide 44: 

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.

Slide 45: 

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.

Slide 46: 

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.

Slide 48: 

PKDL Post Kalazar Dermal Leishmaniasis

Visceral form : 

Visceral form

Slide 58: 

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-azar, the ‘black sickness’. A generalized lymphadenopathy is common in African kala-azar; the parasite in this area is considered to be in the L. donovani complex.

Diagnosis : 

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

Slide 61: 

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 : 

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.

Slide 63: 

Amastigotes in macrophage from skin The diagnosis is confirmed by demonstraing amastigotes in smear made from the cutaneous lesions.

Slide 64: 

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.

Slide 65: 

Parasitised macrophage in skin section Many parasitised macrophages can be seen in this section from an acute lesion caused by L. major.

DIAGNOSIS : 

DIAGNOSIS 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

Slide 67: 

Formalin gel (aldehyde) 2 drops formalin + 2 ml serum After 20 min, white ring Complement fixation and fluorescent False positive trypanosomal infection The complement fixation – early positive – negative after cure. Sometimes + or – lung. Other diseases.

Slide 68: 

6. Fluorescent antibody IV + V: In trypanosomal infection Skin test (Montenegro) Delayed hypersensitivity reaction 0.2 ml. suspension

TREATMENT : 

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

Slide 70: 

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 Diamidiem – Pentamidine isothionate Dose 3 -4 mg / kg / BW total 300 mg Side effect: Hypoglycemia

Treatment : 

Treatment Sodium stibogluconate Pentavalent antimony (Sb+5)

Slide 72: 

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 : 

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 : 

GAUCHER’S DISEASE

History : 

History Discovered by Philippe Gaucher, a medical student in Paris, in 1882. He was studying a woman with an enlarged spleen

Slide 76: 

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.

Slide 77: 

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? : 

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 : 

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) : 

TYPE 1 (continued) Victims have a shortened life-span Usually die from clots and pneumonia

TYPE 2 : 

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) : 

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 : 

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 : 

Symptoms Bone pain Victim bruises easily and there are many fractures in their bones Difficulty walking Blood clotting

Symptoms (continued) : 

Symptoms (continued) Muscle weakness Poor coordination Seizures

How Do You Get It? : 

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 : 

If 2 Carriers Have Children There is a one in four chance of a child inheriting the disease

Who Has It? : 

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 : 

Prevention No real prevention Genetic Counseling is recommended for parents with a family history of the disease

Treatments : 

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 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.

Slide 92: 

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

Slide 93: 

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.

Slide 94: 

Originally known as histiocytic leukemia, malignant reticulosis, or lymphoid myelofibrosis in publications dating back to the 1920s, this disease was formally named leukemic reticuloendotheliosis

Slide 95: 

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 : 

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)