Granulocytotoxic antibodies in a patient with propylthiouracil-induced agranulocytosis

Guffy, M. M.

doi:10.1001/archinte.144.8.1687

Cited by 32 publications

(13 citation statements)

References 9 publications

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“…There are two possible types of AG pathogenesis: an immune-mediated process and direct or indirect drug intoxication [9]. The existence of circulating complement-dependent IgM antibodies against granulocytes and antibodies against differentiated granulocytes, monocytes, and myeloid/erythroid progenitor cells, for example, has been reported in patients receiving ATD [10,11,12]. The immune-mediated destruction of circulating granulocytes or the suppression of granulopoiesis results in rapid onset of severe neutropenia, whereas AG due to the toxic effects of a drug or its metabolites on bone marrow cells is considered to progress more slowly, taking a couple of weeks.…”

Section: Discussionmentioning

confidence: 99%

Periodic Granulocyte Count Measuring Is Useful for Detecting Asymptomatic Agranulocytosis in Antithyroid Drug-Treated Patients with Graves' Disease

et al. 2016

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Objective: Finding agranulocytosis (AG) at an early stage is important to improve outcome, but periodic granulocyte count monitoring is not generally recommended for patients with Graves' disease, because AG develops suddenly. Method: At the Kuma Hospital, Graves' patients under antithyroid drug (ATD) treatment in an outpatient clinic have a granulocyte count examination during each visit, and if it is <1,000/μl, a warning is immediately sent to the patient's physician. We evaluated the usefulness of this system. Results: We investigated 25 AG and 33 granulocytopenia (GP) cases over a recent 5-year period, excluding patients who developed AG or GP at another hospital and were referred to us for treatment. Among the 25 AG patients, 16 patients (64%; 9 asymptomatic and 7 very mild symptomatic cases) were discovered by the periodic granulocyte count examination at an outpatient clinic. The remaining 9 patients visited the Kuma Hospital or other hospitals because of infection symptoms. Most of the AG patients were given granulocyte colony-stimulating factor injections immediately and were admitted if a prompt increase in granulocytes could not be obtained. The final treatments for Graves' disease were ¹³¹I-radioisotope therapy (19 patients), thyroidectomy (2 patients), inorganic iodine (1 patient), or another ATD (1 patient). Among the 33 GP patients, 31 (94%), including 20 asymptomatic cases, were discovered during periodic granulocyte count monitoring. Most of them stopped ATD, and other treatments for Graves' disease were selected. Conclusion: Periodic monitoring of granulocyte counts is useful for identifying AG and GP patients with no or minimum infection symptoms.

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Section: Discussionmentioning

confidence: 99%

Periodic Granulocyte Count Measuring Is Useful for Detecting Asymptomatic Agranulocytosis in Antithyroid Drug-Treated Patients with Graves' Disease

et al. 2016

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“…This is inherent to the rarity of the adverse reaction. Case reports were published on all drugs listed as being frequently reported to the DSU in this article, e.g., mianserin, salazosulphapyridine, phenylbutazone, penicillamine, and dipyrone [4], the group of penicillins [5], cimetidine [6], naproxen [7], and the thiouracil derivatives [8,9], but also on drugs that were less frequently reported as a cause, such as clozapine [10][11][12], cephalosporins [13], procainamide [14], dapsone [15,16], paracetamol [17], and ticlopidine [18]. The DSU published case reports and case series on agranulocytosis attributed to aprindine [19,20], spironolactone [21], ticlopidine [22], propylthiouracil [23], pirenzepine [24], trazodone [25], and omeprazole [26], and on leukopenia attributed to mianserin [27].…”

Section: Discussionmentioning

confidence: 99%

Drug-associated agranulocytosis: 20 years of reporting in The Netherlands (1974–1994)

Klauw

Wilson²,

Stricker

1998

Am. J. Hematol.

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In this descriptive study, all 425 reports were included concerning drug-associated agranulocytosis as registered between 1974 and 1994 in the files of the Drug Safety Unit of the Dutch Inspectorate for Health Care. All reports were analysed as to the probability of agranulocytosis or neutropenia according to previously defined criteria. Subsequently , the causal relationship between exposure and outcome was assessed. It concerned 149 men and 271 women. One hundred and twelve reports were unclassifiable because age, gender, or total number of leukocytes at the time of reaction were unknown. In 100 reports agranulocytosis was probable, in 78 possible, in 8 reports neutropenia was probable, in 20 reports neutropenia was possible, and in 107 reports agranulocytosis or neutropenia were unlikely. In the 13 reports of probable agranulocytosis or neutropenia with a certain causal relationship, causative drugs were cimetidine, dipyrone, sulphasala-zine, methyldopa, spironolactone, propylthiouracil (2), thiamazole, sulphamethoxazole with trimethoprim, gentamicin, a combination preparation containing aminophenazone, benzylpenicillin and indomethacin. The individual drugs most often reported to cause agranulocytosis or neutropenia were: dipyrone (19), mianserin (15), sulphasalazine (13), sulphamethoxazole with trimethoprim (11), the group of penicillins (9), cimetidine (8), the thiouracil derivatives (8), phenylbutazone (8), and penicillamine (8). Agranulocytosis is a serious and fairly frequently reported adverse reaction. The reporting system of the Drug Safety Unit can be used very well for signal generation concerning adverse reactions to drugs. Am.

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“…In the present case, we observed agranulocytosis 3 weeks after initiation of CZ at 10 mg/d, in a patient who had previously been tolerant of MZ for 72 months. As Guffy et al suggested, immunogenic abnormalities that underlie drug sensitivities and induce direct intoxication may be genetic, and some patients may be more susceptible, as in the present case. The most important lesson from this case is that clinicians must remain vigilant for agranulocytosis from antithyroid drugs regardless of treatment duration or dose.…”

Section: Discussionmentioning

confidence: 50%

A case of antithyroid drug‐induced agranulocytosis from a second antithyroid drugs (ATD) administration in a relapsed Graves' disease patient who was tolerant to the first ATD treatment

Kim

Lee

2018

Clinical Case Reports

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Key Clinical MessageAgranulocytosis is a rare side effect of antithyroid drugs (ATD) that usually develops within the first 3‐6 months after starting treatment. We present a 64‐year‐old patient who developed agranulocytosis after starting ATD to treat relapsed Graves' disease. This patient had tolerated the first course of ATD for 72 months. This was an unusual case in which a serious side effect developed during a second ATD course. It is essential that clinicians remain vigilant to the fact that antithyroid drugs can induce agranulocytosis several years after initiated.

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Granulocytotoxic antibodies in a patient with propylthiouracil-induced agranulocytosis

Cited by 32 publications

References 9 publications

Periodic Granulocyte Count Measuring Is Useful for Detecting Asymptomatic Agranulocytosis in Antithyroid Drug-Treated Patients with Graves' Disease

Periodic Granulocyte Count Measuring Is Useful for Detecting Asymptomatic Agranulocytosis in Antithyroid Drug-Treated Patients with Graves' Disease

Drug-associated agranulocytosis: 20 years of reporting in The Netherlands (1974–1994)

A case of antithyroid drug‐induced agranulocytosis from a second antithyroid drugs (ATD) administration in a relapsed Graves' disease patient who was tolerant to the first ATD treatment

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