However, only four cases of spironolactoneinduced agranulocytosis have been previously reported 36, all of which were concurrently treated with furosemide. It is a severe lack of one major class of infectionfighting white blood cells. Agranulocytosis can be treated in a number of ways. Relative lymphocytosis associated with granulocytopenia. Thompson js, herbick jm, klassen lw, severson cd, overlin vl, blaschke jw, silverman ma, vogel cl. Pdf agranulocytosis induced by nonchemotherapy drugs. Idiosyncratic druginduced agranulocytosis or acute neutropenia. Learn vocabulary, terms, and more with flashcards, games, and other study tools. Agranulocytosis induced by cinepazide springerlink. Grade 34 neutropenia or agranulocytosis and clinical manifestations related to sepsis are less common, with only a few case reports to date for. The drug etiology of agranulocytosis and aplastic anemia.
May 09, 2020 agranulocytosis is an uncommon condition 7. Agranulocytosis has been recognized as an idiosyncratic reaction to levamisole in 2. Three basic mechanisms for drug sensitivity have been found. Neutrophils are white blood cells wbcs produced in the bone marrow that ingest bacteria. Apr 27, 2020 relative lymphocytosis associated with granulocytopenia neutropenia and agranulocytosis last updated on mon, 27 apr 2020 hematology neutropenia is defined by a decrease in the number of neutrophilic granulocytes with segmented nuclei to less than 15001 1. Agranulocytosis induced by nonchemotherapy drugs article pdf available in annals of internal medicine 1484. Au andres e, zimmer j, mecili m, weitten t, alt m, maloisel f so expert rev hematol. Furosemide has been reported to be highly associated with druginduced agranulocytosis in a populationbased casecontrol study 2. Ezekiel wong, severe druginduced agranulocytosis successfully treated with recombinant human granulocyte colonystimulating factor, case reports in medicine, vol. N2 drug induced agranulocytosis is a severe complication that has been implicated with most classes of medications. State of art on idiosyncratic druginduced severe neutropenia and.
Valproic acidinduced agranulocytosis sciencedirect. Idiosyncratic drug induced agranulocytosis or acute neutropenia is an adverse event resulting in a neutrophil count of under 0. It is a medical condition or term, which is derived from a greek word that means without granulocyte, that suggest a reduction in the production of granulocytes, which is a blood disorder, under this classification includes. Genetic determinants of cocaineassociated agranulocytosis. Table 1 severe druginduced agranulocytosis successfully. Agranulocytosis management and treatment cleveland clinic. Levamisole is an antihelminthic and immunomodulator withdrawn from north american markets in 2005 after reports of agranulocytosis.
Agranulocytosis, acquired nord national organization for rare. Agranulocytosis associated with dipyrone metamizol article pdf available in european journal of clinical pharmacology 6011. We experienced a case of a 16monthold male infant with down syndrome in whom fever appeared 16 days after the start of administration of ethosuximide and then severe pneumonia developed. Stopping a medication that is believed to cause the disease. Drug induced agranulocytosis is a lifethreatening disorder that leads to a selective profound granulocytopenia. The code is valid for the year 2020 for the submission of hipaacovered transactions. Agranulocytosis induced by certain phenothiazine derivatives. This multicentre, retrospective study examined possible prognostic factors by multiple logistic regression analysis in a series of 168 clinical episodes. Agranulocytosis associated with cocaine use in four states.
Agranulocytosis and neutropenia treato found 5 discussions about neutropenia and agranulocytosis on the web. The name granulocyte refers to grainlike bodies within the cell. Management of patients with haemolytic crisis agranulocytosis is a group of pathologic disorders, characterized by severe leukopenia leukocyte count treato found 5 discussions about neutropenia and agranulocytosis on the web. Drug induced agranulocytosis is a rare, potentially fatal idiosyncratic reaction that can occur unpredictably with a wide variety of drugs when taken in a conventional dose. A first report of their relation to drug use with special reference to analgesics.
Eight deaths due to dapsone induced agranulocytosis have been reported recently. The mortality when agranulocytosis develops has been estimated to be 2. Evidence for drug induction of aplastic anemia, 10 5. One is characterised by sudden destruction of large numbers of leucocytes in peripheral blood by antibodies elicited in response to drug sensitivity. Dapsone agranulocytosis jama dermatology jama network. Jun, 2015 drug induced agranulocytosis is a recognized adverse drug event associated with serious infectious complications.
Drugs are the most common cause of agranulocytosis 1. T1 nonchemotherapy drug induced neutropenia and agranulocytosis. Idiosyncratic druginduced agranulocytosis or acute. Therefore the absolute mortality of patients on clozapine due to agranulocytosis is very low or around 0. Thiamazoleinduced agranulocytosis leading to abscessus. However, the proportion of cocaine users exposed to levamisole who might develop levamisole induced agranulocytosis, is unknown. State of art of idiosyncratic druginduced neutropenia or. Apparently promethazine and methdilazine do not cause agranulocytosis. Idiosyncratic drug induced agranulocytosis is a disorder that preferentially affects older individuals, probably reflecting higher medication use associated with older age and the incidence is higher in women than in men. Agranulocytosis was observed in a woman aged 44 years receiving treatment with 12 g intravenous nafcillin daily for staphylococcal endocarditis. Nonchemotherapy druginduced neutropenia and agranulocytosis. There has been one known case seen at the royal victoria hospital in barrie. Drug induced agranulocytosis is rare, perhaps affecting a few people per million of population per year. Objective in this article, we report and discuss the clinical presentation and management of idiosyncratic druginduced agranulocytosis neutrophil count drug induced agranulocytosis.
Agranulocytosis abnormally low levels of some white cells in the blood can occur when drugs cause injury to the bone marrow. Case fatality is around 10%,but this may depend to a large extent on the availability of prompt antibiotic treatment. Neutropenia and agranulocytosis during treatment of. Many drugs including neuroleptics lieberman et al, 1988, antithyroid medications meyer et al, 1994, analgesics, phenothiazine derivatives pisciotta, 1990 and antiinflammatory drugs are known to induce agranulocytosis. Granulocyte colonystimulating factor a number of uncontrolled case studies have reported shorter recovery times compared with historic controls while others show no change with the use of granulocyte or granulocytemacrophage colonystimulating factor gcsf or gmcsf in infected patients with druginduced agranulocytosis. Agranulocytosis induced by drugs other than chemotherapy frank andersohn, md. Drug induced thrombocytopenia is the most common drug induced hematologic disorder, with reports suggesting that between 0. Clinical presentation and management of druginduced agranulocytosis. Their exact mechanisms are unknown but most appear to be immunemediated. The major histocompatibility complex region marked by hsp701 and hsp702 variants is associated with clozapine induced agranulocytosis in two different ethnic groups. Drug induced agranulocytosis is an unexpected side effect of a drug, and delay in diagnosis of agranulocytosis can result in a fatal outcome. Ethosuximide induced agranulocytosis sciencedirect.
Acquired agranulocytosis is a rare, druginduced blood disorder that is characterized by a severe reduction in the number of. Our patient was dis covered to have severe agranulocytosis 2. This suggests that the mechanism may be autoimmune. Moreover, alternative analgesic and antipyretic agents are not devoid of serious side effects. The mechanism of neutropenia can be varied depending on the drug. Symptoms and conditions also mentioned with agranulocytosis in patients discussions. Case report of agranulocytosis induced by vinpocetine. Relation of aplastic anaemia to use of chloramphenicol eye drops in two international casecontrol studies. Neutrophils are a type of white blood cell that your. Agranulocytosis associated with cocaine use four states. On the 8th day of treatment she developed a nonpruritic maculopapular erythematous rash which resolved while nafcillin treatment continued.
In this article, we discuss its diagnosis and management and we consider the drugs most commonly involved and ways of minimising risk. The generally accepted mechanism of agranulocytosis caused by the chemically related antibiotic methicillin is. The quantification of the incidence of potentially druginduced agranulocytosis in general, and in particular its association with single drugs, requires studies on large populations and the use of strict epidemiological methodology to prevent reporting of grossly biased results. A different medication may be substituted for the original. The doctor may tell you to stop taking the drug for a while to see if you improve. Agranulocytosis is a condition which is characterized by decrease in the neutrophil count below 100ml of blood. Widespread clinical trials of leavotetramisole levamisole as an immunopotentiating agent in rheumatoid arthritis, metastatic carcinoma, and immunodeficiency states have been complicated by. It results in a severe reduction of granulocytes in the peripheral blood with an absolute neutrophil count anc of under 0. Neutropenia is sometimes called agranulocytosis or granulocytopenia because neutrophils make up about 60% of wbcs and have granules inside their cell walls. Severe druginduced agranulocytosis successfully treated with recombinant human granulocyte colonystimulating factor. It is a serious condition, and about 1 in 10 cases results in death. Original article from the new england journal of medicine agranulocytosis.
The incidence of agranulocytosis in subjects taking oral dapsone in combination with maloprim for malaria is 1 1020 000 while leprosy patients treated. An unexpected precipitous fall in peripheral leucocyte count may occur during treatment of certain sensitised individuals with drugs usually well tolerated by most people. What risk factors are associated with antithyroid drug. Thai studies of aplastic anemia and agranulocytosis. Clinical and hematologic characteristics of phenothiazineinduced agranulocytosis suggest that the mechanisms underlying the development of this condition are related to a possible suppressive effect of phenothiazines on cell division. Patients with such severe neutropenia are likely to experience lifethreatening and sometimes fatal infections. According to previous studies, the mechanism of valproic acid induced agranulocytosis may have a direct toxic effect on bone marrow. Previous studies of levamisole, suggest that the human leukocyte antigen hlab27 confers a genetic predisposition to this adverse drug event.
It is therefore necessary to establish the incidence of. It is sometimes interchanged with the medical term neutropenia. Diagnosis and management of idiopathic druginduced severe. Pdf agranulocytosis associated with dipyrone metamizol.
Druginduced neutropenia and agranulocytosis uptodate. Criteria for idiosyncratic druginduced agranulocytosis adapted from 1 3. The quantification of the incidence of potentially drug induced agranulocytosis in general, and in particular its association with single drugs, requires studies on large populations and the use of strict epidemiological methodology to prevent reporting of grossly biased results. People with this condition are at very high risk of serious infections. Acquired agranulocytosis is a rare, drug induced blood disorder that is characterized by a severe reduction in the number of white blood cells granulocytes in the circulating blood. Investigation of the mechanisms of drug induced agranulocytosis julia ring tin ip, ph. Coenzyme q10 in combination with triple therapy regimens ameliorates oxidative stress and lipid peroxidation in chronic gastritis associated with h. Neutropenia and agranulocytosis can also result from antibody or compliment mediated damage to the stem cells. Wiholm be, kelly jp, kaufman dw, issaragrisil s, levy m, anderson t, shapiro s. Many anti neoplastic drugs cause agranulocytosis and neutropenia by bone marrow suppression. Evidence for drug induction of agranulocytosis, 6 4.
These illnesses are not due to the drug but instead linked to an adulterant or cutting agent, levamisole, a known cause of agranulocytosis in susceptible individuals. Read more about symptoms, diagnosis, treatment, complications, causes and prognosis. Erratum to severe druginduced agranulocytosis successfully. Clinical and hematologic characteristics of phenothiazine induced agranulocytosis suggest that the mechanisms underlying the development of this condition are related to a possible suppressive effect of phenothiazines on cell division. Valproic acid was stopped, and the neutrophil count then returned to normal 6. Objective in this article, we report and discuss the clinical presentation and management of idiosyncratic druginduced agranulocytosis neutrophil count 60 years and those of noncaucasian descent. Management and prevention of agranulocytosis in patients. Agranulocytosis and neutropenia in crack or cocaine users.
Druginduced agranulocytosis drug and therapeutics bulletin. These blood cells play a key role in the elimination of pathogens. Agranulocytosis is defined as an absolute neutrophil count anc agranulocytosis in patients taking clozapine ranges from 12% after 1 year of therapy and can be fatal if not detected and treated early. Druginduced agranulocytosis is a rare, potentially fatal idiosyncratic reaction that can occur unpredictably with a wide variety of drugs when taken in a conventional dose. The human leukocyte antigen class ii genes containing the drb108032 allele were found to be associated with methimazole induced agranulocytosis. Idiosyncratic drug induced agranulocytosis diag is an adverse reaction to drugs due to abnormal susceptibility, peculiar to the individual. Agranulocytosis and aplastic anemia as drug induced diseases, 5 3. We do not consider the doserelated granulocytopenia that commonly complicates. Agranulocytosis is a rare condition in which your bone marrow doesnt make enough of a certain type of white cell, most often neutrophils. 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, and thus causing a neutropenia in the circulating blood. Association between the drb108032 histocompatibility antigen and methimazole induced. The international agranulocytosis and aplastic anemia study 1986 risks of agranulocytosis and aplastic anemia. If you are aware of a case report of nonchemotherapy druginduced agranulocytosis that 1 was published in a medical journal in english or german language, 2 fits our in and exclusion criteria see original paper, and that 3 is missing in this database, please submit the citation and a pdf version of the paper if possible to the e.