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AGRANULOCYTOSIS
A seminar by
- AKSHARA NAIR
- IIIrd BDS
- PMS College of Dental
Science and Research
- INTRODUCTION
- ALSO KNOWN AS
- CLASSIFICATION
- EPIDIMIOLOGY
- ETIOLOGY
- PATHOGENESIS
- CLINICAL FEATURES
- ORAL MANIFESTATIONS
- HISTOLOGICAL FEATURES
- LABORATORY FINDINGS
- TREATMENT
INDEX
2
INTRODUCTION
Agranulocytosis, also known as agranulosis or
granulopenia, is an acute condition involving a severe
and dangerous leukopenia (lowered white blood cell
count), most commonly of neutrophils causing a
neutropenia in the circulating blood.
● IT IS DEEMED A MORE SERIOUS FORM OF NEUTROPENIA.
● NORMAL NEUTROPHIL COUNT OF BLOOD= 2-8 /mcL
● AGRANULOCYTOSIS IS THE TERM WHEN NEUTROPHIL
COUNT IS <2.5 X 10^9/L AND CHILDREN AND < 1.5 X 10^9/L.
● MILD -WHEN THE COUNT IS 1000-1800/MM3.
● MODERATE- WHEN THE COUNT IS 500- 1000/MM3.
● SEVERE -WHEN THE ANC IS BELOW 500/mm3
ALSO KNOWN AS
- NEUTROPENIA
- GRANULOPENIA
- GRANULOCYTOPENIA
- A POINT TO BE NOTED IS THAT AGRANULOCYTOSIS IS
NOT TO BE CONFUSED WITH INCREASE IN
AGRANULOCYTES IN BLOOD NAMELY THE LYMPHOCYTES
AND MONOCYTES
- AGRANULOCYTOSIS HERE REFERS TO DECREASE IN
NEUTROPHILS ( GRANULOCYTE ) MUCH BELOW OPTIMUM
LEVELS.
CLASSIFICATION
IT CAN BE CLASSIFIED AS
PRIMARY
IDIOPATHIC
CAUSE IS UNKNOWN
SECONDARY
CAUSE IS KNOWN.
IT CAN ALSO BE CLASSIFIED AS
CONGENITAL
ACQUIRED
EPIDIMIOLOGY
1) Frequency : • The exact frequency of agranulocytosis is
unknown. • The estimated frequency of agranulocytosis is
1.0 -3.4 cases per million population per year.
2) Race : • Agranulocytosis has no racial predilection.
3) • Sex: • Agranulocytosis occurs slightly more frequent in
women than in men, possibly because of their increased rate
of medication usage.
• Whether this higher frequency is related to the increased
incidence of autoimmune disease in women is unknown.
4) • Age : • Agranulocytosis occurs in all age groups.
• The congenital forms are most common in childhood.
• Acquired agranulocytosis is most common in the elderly
population 6
7
ETIOLOGY
1. Drug Induced
2.Autoimmune diseases
3.Infections
4.Viral
5.Protozoal
6.Miscellaneous
* According to a Survey
8
64.4%
Average US
Population Who Visit
their GP Regularly*
$124B 40-60%
Average Profit
Margin
$175,000
Average Annual
Revenue per Doctor
3%
Market Growth Per
Year
Success
A) DRUG INDUCED
ANTIBACTERIAL
- CHLORAMPHENICOL
- CO- TRIMOXAZOLE
- PENICILLIN
- DOXYCYCLINE
ANTINFLAMMATORY
- PHENYLBUTAZONE
- AMINOPYRINE
- IBUPROFIN
ANTITHYROID
- THIOURACIL
- CARBIMAZOLE
ANTICONVULSANTS
- VALPROIC ACID
- PHENYTOIN
- TRIMETHADIONE
9
B) AUTOIMMUNE DISEASE
- SYSTEMIC LUPUS ERYTHEMATOUS
- IDIOPATHIC
- FELTY SYNDROME
C) INFECTIONS
- ETERIC FEVER
- GRAM –VE BACTERIAL SEPTICEMIA
- TUBERCULOSIS
- HIV INFECTION
D) VIRAL
- PARVOVIRUS B19 INFECTION
- HIV INFECTION
- HEPATITIS B INFECTION
- EBV INFECTION
E) PROTOZOAL
- MALARIA
- KALA AZAR
E) MISCELLANEOUS
- CHRONIC AUTOIMMUNE NEUTROPENIA
- CYCLIC NEUTROPENIA
- APLASTIC ANEMIA
- HYPERSPLENISM
- MEGALOBLASTIC ANEMIA
- XRAY IRRADIATION
PATHOGENESIS
Pathogenesis of neutropenia can be divided into following
categories
1. Inadequate or ineffective formation of granulocytes.
2. Accelerated destruction of neutrophils.
3. Decreased production.
4. Decreased survival
10
INADEQUATE OR INEFFECTIVE
FORMATION OF GRANULOCYTES
This can be due to bone marrow failure similar to the kind
that occurs in aplastic anemia, several leukemias and
chemotherapeutic agents.
There can also be isolated neutropenias where only
differentiated granulocyte precursors are affected as in the
case of neoplastic proliferation of cytotoxic T cells or NK
Cells
11
ACCELERATED DESTRUCTION OF
NEUTROPHILS
Immune mediated reactions to neutrophils which can be
caused by drugs.
An enlarged spleen can lead to splenic sequestration and
accelerated removal of neutrophils.
Utilization of neutrophils can occur in infection.
12
DECREASED PRODUCTION
• Congenital
• Dyskeratosis congenita
• Kostmanns’ syndrome
• Schawchmann Diamond syndrome
13
DECREASED PRODUCTION ACQUIRED
• Drug-induced
• Chemicals, e.g. benzene
• Infections
• Acquired aplastic anemia
• Myelodysplastic syndrome
• Acute leukaemia
• Hairy cell leukaemia
• Malignant infiltration of bone marrow, • e.g. lymphoma,
carcinomatosis 14
DECREASED SURVIVAL
• Autoimmune neutropenia
• Felty’s syndrome
• Systemic lupus erythematous
• Drugs
15
CLINICAL MANIFESTATIONS
The manifestations of neutropenia depend upon the degree of
neutropenia and of compensatory monocytosis. • The
manifestations are generally due to severe bacterial infections.
- ASYMPTOMATIC
- HIGH FEVER, CHILLS, EXHAUSTION
- SUDDEN ONSET OF MALAISE, WEAKNESS,
PHARYNGITIS, DIFFICULTY SWALLOWING
- SKIN:PALE, ANEMIC, JAUNDICE
- ORAL CAVITY, GASTROINTESTINAL TRACT,
RESPIRATORY TRACT AND SKIN AFFECTED
- FAILURE TO TREAT: LIFE THREATENING
GENERALISED SEPSIS
- DEATH IN FEW WEEKS 16
ORAL MANIFESTATIONS
- NECROTISING ULCERATIONS OF THE ORAL MUCOSA,
TONSILS AND PHARYNX
- PARTICULARLY INVOLVED PARTS ARE GINGIVA AND
PALATE
- APPEAR AS RAGGED NECROTIC ULCERS COVERED
BY GREY OR EVEN BLACK MEMBRANE
- USUALLY NO PURULENT DISCHARGE
- HEMORRHAGE OCCURS AROUND THE PERIPHERY OF
THE LESIONS ESPECIALLY IN GINGIVA BUT WITH
LITTLE TO NO INFLAMMATORY CELL INFILTRATION.
- PATIENTS ALSO MANIFEST EXCESSIVE SALIVATION
- ALL ORAL PROCEDURES ESPECIALLY TOOTH
EXTRACTION ARE CONTRAINDICATED IN
17
18
DEFIPERONE INDUCED AGRANULOCYTOSIS
19
HISTOLOGICAL FINDINGS
- MICROSCOPIC APPEARNACE IS PATHOGNOMIC AND MAY
ACCOUNT FOR CERTAIN CLINICAL FEATURES
- SINCE THE ESSENTIAL FAULT IS THE LACK OF DEVELOPMENT OF
THE NORMAL GRANULAR LEAUKOCYTES, THE ULCERATED AREAS
LACK THE TYPICAL POLYMORPHONUCLEAR REACTION TO THE
BACTERIA AND PRESENT WITH RAMPANT NECROSIS
- IT BEGINS AS NECROSIS OF SULCUS
SPREADS TO FREE GINGIVA PERIODONTAL
LIGAMENT
ALVEOLAR BONE.
20
LABORATORY FINDINGS
NEUTROPHIL COUNT IS BELOW 2000CELLS/MM3
ALMOST COMPLETE ABSENCE OF GRANULOCYTES OR
POLYMORPHONUCLEAR CELLS
RBC AND PLATELET COUNT USUALLY NORMAL BUT
ANEAMIA MIGHT BE PRESENT OCCASSIONALLY
BONE AMRROW IS NORMAL EXCEPT FOR ABSENCE OF
GRANULOCYTES, METMYLOCYTES,
POLYMORPHONUCLEAR CELLS.
21
PERIPHERAL BLOOD EXAMINATION
Complete blood examination is required to rule out various
causes of pancytopenia
- Hb : Normal
- TLC: Decreased
- DLC: Neutropenia with neutrophils being 0-20% .
- ANC: < 0.5 X 109/L
22
BONE MARROW EXAMINATION
BM is essential to rule other causes of neutropenia like…….
• sub leukemic • aleukemic leukemia • Megaloblastic anemia
• Aplastic anemia
• Cellularity : Normal
• Erythropoiesis: Normoblastic
• Myelopoiesis: Myelopoiesis in No. of cases manifests
maturation arrest at promyelocytes / myelocyte stage.
• In some cases there is depletion of the cells of myeloid
series.
• Megakaryopoiesis : Normal 23
TREATMENT
- FILAGASTRIN OR G-CSF IS STANDARD TREATMENT
FOR ACQUIRED AGRANULOCYTSOIS.
- ESSENTIAL TO IDENTIFY AND DISCONTINUE THE
CAUSATIVE DRUG , CHEMICAL OR ADMISNISTER
APPROPRIATE BROAD SPECTRUM ANTIBIOTIC.
- STEROIDS TO TREAT SHOCK.
- PATIENTS WITH LOW LEVELS OF IMMUNE FACTORS
ARE TO BE TREATED WITH INFUSIONS OF GAMMA
GLOBULIN.
24
SOURCES
- SHAFERS TEXTBOOK OF ORAL PATHOLOGY 9TH ED
- RESEARCHGATE
- GETTY IMAGES
-
https://www.google.com/url?sa=i&url=https%3A%2F%2Fww
w.researchgate.net%2Ffigure%2FPeripheral-blood-smear-
shows-
agranulocytosis_fig1_287977004&psig=AOvVaw3nTE4AauH
APlqgsuPflfeK&ust=1633258450846000&source=images&c
d=vfe&ved=0CAwQjhxqFwoTCLDm5biErPMCFQAAAAAdA
AAAABAD
25
THANK
YOU
AKSHARA NAIR
Student doctor.

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Agranulocytosis oral pathology

  • 1. AGRANULOCYTOSIS A seminar by - AKSHARA NAIR - IIIrd BDS - PMS College of Dental Science and Research
  • 2. - INTRODUCTION - ALSO KNOWN AS - CLASSIFICATION - EPIDIMIOLOGY - ETIOLOGY - PATHOGENESIS - CLINICAL FEATURES - ORAL MANIFESTATIONS - HISTOLOGICAL FEATURES - LABORATORY FINDINGS - TREATMENT INDEX 2
  • 3. INTRODUCTION Agranulocytosis, also known as agranulosis or granulopenia, is an acute condition involving a severe and dangerous leukopenia (lowered white blood cell count), most commonly of neutrophils causing a neutropenia in the circulating blood. ● IT IS DEEMED A MORE SERIOUS FORM OF NEUTROPENIA. ● NORMAL NEUTROPHIL COUNT OF BLOOD= 2-8 /mcL ● AGRANULOCYTOSIS IS THE TERM WHEN NEUTROPHIL COUNT IS <2.5 X 10^9/L AND CHILDREN AND < 1.5 X 10^9/L. ● MILD -WHEN THE COUNT IS 1000-1800/MM3. ● MODERATE- WHEN THE COUNT IS 500- 1000/MM3. ● SEVERE -WHEN THE ANC IS BELOW 500/mm3
  • 4. ALSO KNOWN AS - NEUTROPENIA - GRANULOPENIA - GRANULOCYTOPENIA - A POINT TO BE NOTED IS THAT AGRANULOCYTOSIS IS NOT TO BE CONFUSED WITH INCREASE IN AGRANULOCYTES IN BLOOD NAMELY THE LYMPHOCYTES AND MONOCYTES - AGRANULOCYTOSIS HERE REFERS TO DECREASE IN NEUTROPHILS ( GRANULOCYTE ) MUCH BELOW OPTIMUM LEVELS.
  • 5. CLASSIFICATION IT CAN BE CLASSIFIED AS PRIMARY IDIOPATHIC CAUSE IS UNKNOWN SECONDARY CAUSE IS KNOWN. IT CAN ALSO BE CLASSIFIED AS CONGENITAL ACQUIRED
  • 6. EPIDIMIOLOGY 1) Frequency : • The exact frequency of agranulocytosis is unknown. • The estimated frequency of agranulocytosis is 1.0 -3.4 cases per million population per year. 2) Race : • Agranulocytosis has no racial predilection. 3) • Sex: • Agranulocytosis occurs slightly more frequent in women than in men, possibly because of their increased rate of medication usage. • Whether this higher frequency is related to the increased incidence of autoimmune disease in women is unknown. 4) • Age : • Agranulocytosis occurs in all age groups. • The congenital forms are most common in childhood. • Acquired agranulocytosis is most common in the elderly population 6
  • 7. 7 ETIOLOGY 1. Drug Induced 2.Autoimmune diseases 3.Infections 4.Viral 5.Protozoal 6.Miscellaneous
  • 8. * According to a Survey 8 64.4% Average US Population Who Visit their GP Regularly* $124B 40-60% Average Profit Margin $175,000 Average Annual Revenue per Doctor 3% Market Growth Per Year Success A) DRUG INDUCED ANTIBACTERIAL - CHLORAMPHENICOL - CO- TRIMOXAZOLE - PENICILLIN - DOXYCYCLINE ANTINFLAMMATORY - PHENYLBUTAZONE - AMINOPYRINE - IBUPROFIN ANTITHYROID - THIOURACIL - CARBIMAZOLE ANTICONVULSANTS - VALPROIC ACID - PHENYTOIN - TRIMETHADIONE
  • 9. 9 B) AUTOIMMUNE DISEASE - SYSTEMIC LUPUS ERYTHEMATOUS - IDIOPATHIC - FELTY SYNDROME C) INFECTIONS - ETERIC FEVER - GRAM –VE BACTERIAL SEPTICEMIA - TUBERCULOSIS - HIV INFECTION D) VIRAL - PARVOVIRUS B19 INFECTION - HIV INFECTION - HEPATITIS B INFECTION - EBV INFECTION E) PROTOZOAL - MALARIA - KALA AZAR E) MISCELLANEOUS - CHRONIC AUTOIMMUNE NEUTROPENIA - CYCLIC NEUTROPENIA - APLASTIC ANEMIA - HYPERSPLENISM - MEGALOBLASTIC ANEMIA - XRAY IRRADIATION
  • 10. PATHOGENESIS Pathogenesis of neutropenia can be divided into following categories 1. Inadequate or ineffective formation of granulocytes. 2. Accelerated destruction of neutrophils. 3. Decreased production. 4. Decreased survival 10
  • 11. INADEQUATE OR INEFFECTIVE FORMATION OF GRANULOCYTES This can be due to bone marrow failure similar to the kind that occurs in aplastic anemia, several leukemias and chemotherapeutic agents. There can also be isolated neutropenias where only differentiated granulocyte precursors are affected as in the case of neoplastic proliferation of cytotoxic T cells or NK Cells 11
  • 12. ACCELERATED DESTRUCTION OF NEUTROPHILS Immune mediated reactions to neutrophils which can be caused by drugs. An enlarged spleen can lead to splenic sequestration and accelerated removal of neutrophils. Utilization of neutrophils can occur in infection. 12
  • 13. DECREASED PRODUCTION • Congenital • Dyskeratosis congenita • Kostmanns’ syndrome • Schawchmann Diamond syndrome 13
  • 14. DECREASED PRODUCTION ACQUIRED • Drug-induced • Chemicals, e.g. benzene • Infections • Acquired aplastic anemia • Myelodysplastic syndrome • Acute leukaemia • Hairy cell leukaemia • Malignant infiltration of bone marrow, • e.g. lymphoma, carcinomatosis 14
  • 15. DECREASED SURVIVAL • Autoimmune neutropenia • Felty’s syndrome • Systemic lupus erythematous • Drugs 15
  • 16. CLINICAL MANIFESTATIONS The manifestations of neutropenia depend upon the degree of neutropenia and of compensatory monocytosis. • The manifestations are generally due to severe bacterial infections. - ASYMPTOMATIC - HIGH FEVER, CHILLS, EXHAUSTION - SUDDEN ONSET OF MALAISE, WEAKNESS, PHARYNGITIS, DIFFICULTY SWALLOWING - SKIN:PALE, ANEMIC, JAUNDICE - ORAL CAVITY, GASTROINTESTINAL TRACT, RESPIRATORY TRACT AND SKIN AFFECTED - FAILURE TO TREAT: LIFE THREATENING GENERALISED SEPSIS - DEATH IN FEW WEEKS 16
  • 17. ORAL MANIFESTATIONS - NECROTISING ULCERATIONS OF THE ORAL MUCOSA, TONSILS AND PHARYNX - PARTICULARLY INVOLVED PARTS ARE GINGIVA AND PALATE - APPEAR AS RAGGED NECROTIC ULCERS COVERED BY GREY OR EVEN BLACK MEMBRANE - USUALLY NO PURULENT DISCHARGE - HEMORRHAGE OCCURS AROUND THE PERIPHERY OF THE LESIONS ESPECIALLY IN GINGIVA BUT WITH LITTLE TO NO INFLAMMATORY CELL INFILTRATION. - PATIENTS ALSO MANIFEST EXCESSIVE SALIVATION - ALL ORAL PROCEDURES ESPECIALLY TOOTH EXTRACTION ARE CONTRAINDICATED IN 17
  • 18. 18
  • 20. HISTOLOGICAL FINDINGS - MICROSCOPIC APPEARNACE IS PATHOGNOMIC AND MAY ACCOUNT FOR CERTAIN CLINICAL FEATURES - SINCE THE ESSENTIAL FAULT IS THE LACK OF DEVELOPMENT OF THE NORMAL GRANULAR LEAUKOCYTES, THE ULCERATED AREAS LACK THE TYPICAL POLYMORPHONUCLEAR REACTION TO THE BACTERIA AND PRESENT WITH RAMPANT NECROSIS - IT BEGINS AS NECROSIS OF SULCUS SPREADS TO FREE GINGIVA PERIODONTAL LIGAMENT ALVEOLAR BONE. 20
  • 21. LABORATORY FINDINGS NEUTROPHIL COUNT IS BELOW 2000CELLS/MM3 ALMOST COMPLETE ABSENCE OF GRANULOCYTES OR POLYMORPHONUCLEAR CELLS RBC AND PLATELET COUNT USUALLY NORMAL BUT ANEAMIA MIGHT BE PRESENT OCCASSIONALLY BONE AMRROW IS NORMAL EXCEPT FOR ABSENCE OF GRANULOCYTES, METMYLOCYTES, POLYMORPHONUCLEAR CELLS. 21
  • 22. PERIPHERAL BLOOD EXAMINATION Complete blood examination is required to rule out various causes of pancytopenia - Hb : Normal - TLC: Decreased - DLC: Neutropenia with neutrophils being 0-20% . - ANC: < 0.5 X 109/L 22
  • 23. BONE MARROW EXAMINATION BM is essential to rule other causes of neutropenia like……. • sub leukemic • aleukemic leukemia • Megaloblastic anemia • Aplastic anemia • Cellularity : Normal • Erythropoiesis: Normoblastic • Myelopoiesis: Myelopoiesis in No. of cases manifests maturation arrest at promyelocytes / myelocyte stage. • In some cases there is depletion of the cells of myeloid series. • Megakaryopoiesis : Normal 23
  • 24. TREATMENT - FILAGASTRIN OR G-CSF IS STANDARD TREATMENT FOR ACQUIRED AGRANULOCYTSOIS. - ESSENTIAL TO IDENTIFY AND DISCONTINUE THE CAUSATIVE DRUG , CHEMICAL OR ADMISNISTER APPROPRIATE BROAD SPECTRUM ANTIBIOTIC. - STEROIDS TO TREAT SHOCK. - PATIENTS WITH LOW LEVELS OF IMMUNE FACTORS ARE TO BE TREATED WITH INFUSIONS OF GAMMA GLOBULIN. 24
  • 25. SOURCES - SHAFERS TEXTBOOK OF ORAL PATHOLOGY 9TH ED - RESEARCHGATE - GETTY IMAGES - https://www.google.com/url?sa=i&url=https%3A%2F%2Fww w.researchgate.net%2Ffigure%2FPeripheral-blood-smear- shows- agranulocytosis_fig1_287977004&psig=AOvVaw3nTE4AauH APlqgsuPflfeK&ust=1633258450846000&source=images&c d=vfe&ved=0CAwQjhxqFwoTCLDm5biErPMCFQAAAAAdA AAAABAD 25