AGRANULOCYTOSIS

Definition :
y an acute febrile condition marked by severe depression of the granulocyte-producing bone marrow and by prostration, chills,swollen neck, and sore throat sometimes with local ulceration andbelieved to be basically a response to the side effects of certaindrugs of the coaltar series (as aminopyrine) called also agranulocytic angina granulocytopeniaMerriam The overall incidence rate was 0.38 cases per 1 million inhabitant-years. Agranulocytosis occurs on both males and females. 90% of the reported patients have been females, the youngest 2 weeks and the oldest 66 years. It occurs in all classes of life and occupation but for some unknown reason. The incidence of the disease has been high among physician and nurses. The disease is not considered contagious or infectious though three cases in one family and two in another have been reported. Of 330 reported cases, 226 were females with mortality of 77% and the remainder were males with mortality of 75%. The ages varied from 20-60 years. A few cases pursue a chronic course with occasional remissions. Granulocytopenia (agranulocytosis) may result from diminished production of granulocytes in bone marrow, increased peripheral destruction of granulocytes, or greater utilization of granulocytes. Diminished production of granulocytes in bonemarrow generally stems from radiation or drug therapy; its a common adverse effectof antimetabolites and alkylating agents and may occur in the patient who ishypersensitive to phenothiazine, sulfonamides (and some sulfonamide derivatives),antibiotics, and antiarrhythmic drugs. Drug-induced granulocytopenia usuallydevelops slowly and typically correlates with the dosage and duration of therapy.Production of granulocytes also decreases in conditions such as aplastic anemia andbone marrow malignancies and in some hereditary disorders (infantile geneticagranulocytosis).The growing loss of peripheral granulocytes is due to increased splenic sequestration,diseases that destroy peripheral blood cells (viral and bacterial infections), and drugsthat act as haptens (carrying antigens that attack blood cells and causing acuteidiosyncratic or non-dose-related drug reactions). Infections suchas infectious mononucleosis may result in granulocytopenia because of increase dutilization of granulocytes.

Prevalence:
y y

Etiology :
y

Risk Factors:
y y y y y y y Undergoing chemotherapy treatment for cancer Taking certain drugs Infection Exposure to certain chemical toxins or radiation Autoimmune diseases Enlargement of the spleen- The spleen is involved in making cells that fight infection and part of that response is to enlarge. Vitamin B-12 or folate deficiency- the loss of stomach cells that make intrinsic factor. Intrinsic factor helps the body absorb vitamin B12 in the intestine. The loss of parietal cells may be due to destruction by the body's own immune system. Leukemia or Myelodysplastic Syndromes- the bone marrow makes abnormal white blood cells. The abnormal cells are leukemia cells. Unlike normal blood cells, leukemia cells don't die when they should. They may crowd out normal white blood cells, red blood cells, and platelets. This makes it hard for normal blood cells to do their work. Aplastic anemia or other diseases of the bone marrow Family history of certain genetic diseases

y y

Sign and Symptoms

Fever Sore throat Painful mouth ulcers Anal ulcers Reduced immune response Prone to bacterial infections y Characteristically, patients with granulocytopenia experience slowly progressivefatigue and weakness; however, if they develop an infection, they can exhibit suddenonset of fever and chills and mental status changes. Overt signs of infection (pusformation) are usually absent. Localized infection can quickly become systemic(bacteremic) or spread throughout an organ (pneumonia). All patients should bemeticulously evaluated for even subtle signs of infection because untreated infectionscan lead to septic shock in 8 to 24 hours. If granulocytopenia results from anidiosyncratic drug reaction, signs of infection develop abruptly, without slowlyprogressive fatigue and weakness.A severe sore throat, elevated temperature and maybe hemorrhage, can occur. Theremay be an ulceration of the throat, the glands under the jaw becoming swollen andtender. It is essential that the offending drug be discontinued if there is an obviousrelationship.

Patients with lymphocytopenia may exhibit enlarged lymph nodes, spleen, and tonsilsand signs of an associated disease.

Diagnosis:
y y y y y Blood test to determine white blood cell count Urine or other fluids may be tested for infectious agents if the person has a fever Bone marrow test ( biopsy and aspiration) Genetic tests may be needed in some people Antineutrophil antibodies may need to be tested for in people with autoimmune disease

Treatment
Broad-spectrum antibiotics Treating any underlying cause Stopping any medication cause Intensive care Granulocyte transfusions y Effective management of granulocytopenia must identify and eliminate the cause andcontrol infection until the bone marrow can generate more leukocytes. In many cases,this means drug or radiation therapy must be stopped and antibiotic treatment begunimmediately, even while awaiting test results. Treatment may also include antifungalpreparations. Administration of granulocyte colony-stimulating factor (CSF) or granulocyte-macrophage CSF is a newer treatment used to stimulate bone marrowproduction of neutrophils. Spontaneous restoration of leukocyte production in bonemarrow generally occurs within 1 to 3 weeks.Treatment of lymphocytopenia includes eliminating the cause and managing anyunderlying disorders. For infants with SCID, therapy may include bone marrowtransplantation