Initial signs and symptoms of agranulocytosis include onset of sudden fever accompanied by chills with development of weakness in hands and legs. In addition to these, there is development of sores in the mouth, throat. In severe cases ulcers are also known to develop and which can lead to bleeding. Affected individuals can also experience rapid breathing, development of skin abscesses, rapid heart rate and a sudden drop in blood pressure [8].

• Fever

  Signs and symptoms[edit] Agranulocytosis may be asymptomatic, or may clinically present with sudden fever, rigors and sore throat. Infection of any organ may be rapidly progressive (e.g., pneumonia, urinary tract infection). [en.wikipedia.org]

  […] infection Alternative Title: agranulocytic angina Agranulocytosis, also called agranulocytic angina, acute infection characterized by severe sore throat, fever, and fatigue and associated with an extreme reduction of white blood cells, or leukocytes [britannica.com]

  Prevailing low grade fever may progress into a high fever or hypothermia along with rapid breathing, confusion, and body swelling. Urine output may decrease as well. [medicaljoyworks.com]

  Abstract A granulocytosis in dengue hemorrhagic fever has not been mentioned, it mayprobably be included under the term of leucopenia. Here is the case of a 14-year Thai boy presenting with fever and diarrhea for 3 days. [ncbi.nlm.nih.gov]

  Clinical findings Fever, malaise, mucocutaneous ulcers (throat, GI tract, skin). agranulocytosis Granulocytopenia, granulopenia Hematology A marked ↓ in PMNs < 500/mm3 Clinical Fever, malaise, mucocutaneous ulcers–throat, GI tract, skin Etiology Acquired [medical-dictionary.thefreedictionary.com]

• Chills

  Initially patients may be asymptomatic or may present with malaise, fever with or without chills, marked weakness and fatigue. All these symptoms are acute in onset. [medicaljoyworks.com]

  For other uses, see Chill (disambiguation). Chills Specialty Infectious disease Chills is a feeling of coldness occurring during a high fever, but sometimes is also a common symptom which occurs alone in specific people. [en.wikipedia.org]

  The first manifestations are usually produced by a severe infection and include high fever, chills, prostration, and ulcerations of mucous membranes such as in the mouth, rectum, or vagina. [medical-dictionary.thefreedictionary.com]

  Initial signs and symptoms of agranulocytosis include onset of sudden fever accompanied by chills with development of weakness in hands and legs. In addition to these, there is development of sores in the mouth, throat. [symptoma.com]

• High Fever

  Within 4 days of the initiation of AZA therapy, the patient developed a high fever, leucopenia, and cranial alopecia. [ncbi.nlm.nih.gov]

  Prevailing low grade fever may progress into a high fever or hypothermia along with rapid breathing, confusion, and body swelling. Urine output may decrease as well. [medicaljoyworks.com]

• Rigor

  Signs and symptoms[edit] Agranulocytosis may be asymptomatic, or may clinically present with sudden fever, rigors and sore throat. Infection of any organ may be rapidly progressive (e.g., pneumonia, urinary tract infection). [en.wikipedia.org]

  To decipher the genetic architecture of CIA, it is necessary to apply more rigorous standards of phenotyping and study much larger sample sizes. [ncbi.nlm.nih.gov]

  Staphylococcus aureus was identified in cultures and he was treated with oxacillin and rifampin, however, on the 22nd day of treatment, he developed fever with rigors and tachycardia. [pulmonologyadvisor.com]

• Shivering

  Shivering also occurs along with chills because the patient's body produces heat during muscle contraction in a physiological attempt to increase body temperature to the new set point. [en.wikipedia.org]

  You may also need specific treatment: to boost your white blood cells if you've got an infection Signs of an infection may include: high temperature of 38C or above chills and shivering sore throat mouth sores that keep returning toothache skin rashes [nhs.uk]

  Symptoms associated with an infection can include: a high temperature (fever) chills and shivering headaches sweating facial flushing a sore throat or mouth mouth ulcers swollen glands a lack of energy flu -like symptoms In some people, infections can [your.md]

  Symptoms associated with an infection can include: a high temperature (fever) chills and shivering headaches sweating facial flushing a sore throat or mouth mouth ulcers swollen glands a lack of energy flu-like symptoms In some people, infections can [nhsdirect.wales.nhs.uk]

• Bleeding Gums

  The early symptoms of agranulocytosis may include: sudden fever chills sore throat weakness in your limbs sore mouth and gums mouth ulcers bleeding gums Other signs and symptoms of agranulocytosis can include: fast heart rate rapid breathing low blood [healthline.com]

  SIGNS & SYMPTOMS The early symptoms of agranulocytosis may include: • sudden fever • chills • sore throat • weakness in your limbs • HIGH FEVER • mouth ulcers • bleeding gums Other signs and symptoms of agranulocytosis can include: • fast heart rate • [slideshare.net]

• Sore Mouth

  The early symptoms of agranulocytosis may include: sudden fever chills sore throat weakness in your limbs sore mouth and gums mouth ulcers bleeding gums Other signs and symptoms of agranulocytosis can include: fast heart rate rapid breathing low blood [healthline.com]

• Urticaria

  Ten percent of patients report skin eruptions (such as macules and papules), urticaria, dermatitis, fever, and arthralgia; 0.03% of all patients develop agranulocytosis. [fr.bab.la]

  Physical stress Thymoma Decreased circulating basophils may be associated with the following: Anaphylaxis Acute infection Drug-induced hypersensitivity Congenital absence of basophils Hemorrhage Hyperthyroidism Ionizing radiation Neoplasia Ovulation Urticaria [emedicine.medscape.com]

  Side-effects of these drugs are few, and include skin rashes, urticaria, arthralgia and fever. [academic.oup.com]

  These have been characterized by systemic symptoms which involve at least 2 body systems, most often skin (rash, urticaria, facial edema), respiratory (shortness of breath, dyspnea) and cardiovascular (hypotension, tachycardia). [pheniciagroup.com]

A routine blood test to determine complete blood count is performed at the preliminary level. Complete blood count would reveal neutrophil count below 500 or can even reach 0 cells/mm3. Urine samples would also be checked for signs of infections and count of white blood cells. If bone marrow diseases are the underlying cause, then a sample from bone marrow will be analyzed. In addition to these, various tests would be employed for determining autoimmune diseases. If the agranulocytosis is inherited, then genetic testing would also follow [9].

Long bone radiographs are suggested if congenital agranulocytosis is suspected. If the patient appears febrile, then chest radiographs would also be required when signs of pneumonia are evident. Along with these, ultrasonography and CT scan would be done to evaluate splenomegaly [10].

• Neutropenia

  A case of profound neutropenia and agranulocytosis associated with the off-label use of ceftaroline is reported. [ncbi.nlm.nih.gov]

  Neutropenia indicates a deficiency of neutrophils (the most common granulocyte cell) only. [en.wikipedia.org]

  Drug-induced neutropenia or agranulocytosis occurs as an idiosyncratic reaction, most often secondary to accelerated immune-mediated destruction of neutrophils and their progenitors (not including Neutropenia that follows cytotoxic chemotherapy, which [flipper.diff.org]

  She received intravenous propranolol, hydrocortisone, broad-spectrum antibiotics, digoxin and Lugols iodine via a nasogastric tube along with G-CSF for neutropenia. TFT's normalised over 8 days and WBC over 6 days. [endocrine-abstracts.org]

• Leukopenia

  Leukopenia, abnormally low number of white blood cells (leukocytes) in the blood circulation, defined as less than 5,000 leukocytes per cubic millimetre of blood. [britannica.com]

  Called also malignant or pernicious leukopenia and idiopathic or malignant neutropenia. Symptoms. [medical-dictionary.thefreedictionary.com]

  Abstract The risks of severe leukopenia and agranulocytosis have varied over time and among geographical regions and cultures, with little information available on South American populations. [ncbi.nlm.nih.gov]

  […] blood count, bone marrow examination Differential diagnosis Aplastic anemia, paroxysmal nocturnal hemoglobinuria, myelodysplasia, leukemia Agranulocytosis, also known as agranulosis or granulopenia, is an acute condition involving a severe and dangerous leukopenia [en.wikipedia.org]

• Neutrophilia

  Reduction in polymorphonuclear neutrophils is neutrophilia, whereby the body is severely depleted in its ability to defend itself from bacterial infection. [medical-dictionary.thefreedictionary.com]

  Critical care clinics, 16(2): 179-92 [ PM ] [ EČ ][ GS ] Buck, B.H., Liebeskind, D.S., Saver, J.L., Bang, O.Y., Yun, S.W., Starkman, S., Ali, L.K., Kim, D., Villablanca, J., Salamon, N., Razinia, T., Ovbiagele, B. (2008) Early neutrophilia is associated [scindeks.ceon.rs]

  Likewise, the definitions of neutrophilia and leucocytosis were a neutrophil count of less than 7.5 × 10 9 /L and a white blood cell count less than 11.5 × 10 9 /L respectively. [elsevier.es]

  This side effect of lithium can occur when the serum concentration is between 0.4 mEq/L and 1.1 mEq/L.18 The neutrophilia caused by lithium does not appear to be dose related; however, a minimum serum concentration (i.e., 0.4 mEq/L) may be required to [mhc.cpnp.org]

• Neutrophil Count Decreased

  Following discontinuation of Neutromax therapy, circulating neutrophil count decreases by 50% after 1 to 2 days, and returns to baseline levels within 1 to 7 days. [pheniciagroup.com]

Treatment of the underlying disease conditions would be the primary requirement. Following this, the symptoms of agranulocytosis would be managed with medications and other therapies. If the patient is suffering from drug-induced agranulocytosis, then the drug which is cause of the problem will be withdrawn and a substitute drug would then be suggested. Antibiotics or antifungal medications would be given for correcting infections.

Colony stimulating factor therapy is suggested for those individuals who have developed agranulocytosis due to chemotherapy treatment in the past. Granulocyte transfusion is the treatment of choice in cases when the individual has suffered gram negative sepsis and no considerable improvement has been noticed within 24 to 48 hours of initiation of other treatment methods [11].

Prognosis largely depends on the etiology and the severity of the disease. Mortality is high in patients who suffer from severe agranulocytosis. Death occurs due to uncontrolled sepsis, which is a secondary accompaniment of the condition. With prompt initiation of treatment, prognosis is good with a significant reduction in mortality rate. When agranulocytosis occurs as a secondary complication to viral infections, then such patients have a good prognosis [7].

Congenital agranulocytosis is a result of genetic abnormalities present at birth. In such cases, a family history of the disease is evident and therefore, children are likely to develop genetic anomalies which in turn favor decreased neutrophils content in blood.

The acquired form occurs due to the following factors [2]:

• Cancer treatment such as radiation and chemotherapy
• Nutritional deficiencies
• Cancer affecting the bone marrow
• Various drugs such as clozapine [3]
• Infections
• Autoimmune diseases like systemic lupus erythematosus
• Exposure to chemicals such as DDT

A recent outbreak of agranulocytosis was reported amongst cocaine users in the period of 2008 – 2009 in the US and Canada by the Center for Disease Control and Prevention [4]. Such a type of trend suggests a strong link between use of cocaine and development of agranulocytosis.

The exact incidence of agranulocytosis is unknown. From the available data, it can be estimated that the condition occurs in 1 – 3.4 cases per million every year. For the drug induced variety, 1 case is reported to occur per million individuals each year.

Women are more prone to develop the condition compared to males; the reason being that females consume more medications. Agranulocytosis has predilection for the Black race and is a common phenomenon amongst those population [5].

Under normal conditions there are approximately 1500 granulocytes/ml of blood. Granulocytes are originally comprised of 3 types of cells; namely neutrophils, lymphocytes and monocytes. Amongst these, neutrophils make up for the larger share and play a major role in preventing the body against infections and helps in building immunity.

The mature forms of neutrophils are made by precursors in the bone marrow. Once the neutrophils mature and leave the bone marrow, they enter the blood without re-entering the bone marrow. Factors or conditions that interfere with production of mature neutrophils in the bone marrow give rise to the condition of agranulocytosis [6].

Agranulocytosis cannot always be prevented. However, if drugs are the cause, then withdrawing the drugs can also help prevent its onset. Use of prophylactic antibiotics can go a long way in preventing the condition [12].

Agranulocytosis can either be acquired or may be present from birth – congenital. In the acquired type, the bone marrow is unable to produce stem cells that eventually mature into granulocytes. Or it may so happen that the granulocytes are destroyed faster than normal. In the congenital agranulocytosis, there is some kind of genetic defect that is present from birth. Affected individuals are highly susceptible to infections due to severely suppressed immune system [1].

Definition: Agranulocytosis is a condition, characterized by very low levels of neutrophil count in blood. Such individuals are frequently prone to contract infections due to compromised immunity.

Cause: Underlying disease conditions such as bone marrow diseases, autoimmune disorders and cancer, pave way for development of agranulocytosis. Other factors that causes the neutrophils count to fall too low include genetic defects, poor nutrition, drugs and therapies employed for cancer treatment.

Symptoms: Symptoms include fever, chills, infections and sore throat. Affected individuals can also develop mouth ulcers which in severe cases can even bleed. Infections of organ can develop and progress at a rapid rate.

Diagnosis: A preliminary complete blood profile to determine the neutrophil count is carried out. In addition, urine analysis would also be done to determine infections. Imaging studies such as radiographs and CT scan are indicated in cases, when there is infection of lungs and congenital agranulocytosis is suspected. Long bone radiographs are required in cases when the patient appears febrile.

Treatment: Treatment is geared towards correcting the underlying condition that is causing the problem. In addition, antibiotics or antiviral agents are administered if infections have set in. If drugs are the offending agents, then these are withdrawn and replaced with a substitute.

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