Drug fever: Difference between revisions

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==Background==
* A drug reaction of unclear mechanism that causes isolated fever


*A drug reaction of unclear mechanism that causes isolated fever
== Pathophysiology ==
* Stipulated to involve any of five mechanisms:
** Altered thermoregulation, including anticholinergics
** Drug administration-related fever, including [[amphotericin B]], cephalosporins, and [[vancomycin]]
** Expected drug effect, including chemotherapy (tumour lysis) and penicillins ([[Jarisch-Herxheimer reaction]])
** Idiosyncratic reactions, including [[primaquine]], [[quinidine]], [[quinine]], and sulfonamides
** Hypersensitivity reaction, including allopurinol, [[quinidine]], [[quinine]], and sulfonamides


===Pathophysiology===
== Etiology ==
* Antimicrobials are the most common overall class[[CiteRef::mackowiak1987dr]][[patel2010dr]]
** Penicillins are most common, including [[penicillin]], [[piperacillin]], [[ticarcillin]] [[ampicillin]], [[methicillin]], [[carbenicillin]], [[mezlocillin]], [[staphcillin]], [[nafcillin], [[oxacillin]], and [[cloxacillin]]
** Cephalosporins, including [[cefazolin]], [[cefotaxime]], [[ceftazidime]], [[cephalexin]], and [[cephalothin]]
** [[Tetracycline]] and [[minocyline]]
** [[Trimethoprim-sulfamethoxazole]]
** [[Isoniazid]]
** [[Nitrofurantoin]]
** Case reports of [[acyclovir]], [[amphotericin B]], [[aureomycin]], [[colistin]], [[declomycin]], [[erythromycin]], [[furadantin]], [[mebendazole]], [[novobiocin]], [[para-aminosalicylic acid]], [[rifampin]], [[streptomycin]], [[terramycin]], and [[vancomycin]]
* Cardiovascular
** Methyldopa
** Quinidine and quinine
** Procainamide
** Dobutamine
** Case reports with clofibrate, diltiazem, furosemide, heparin, hydralazine, hydrochlorothiazide, nifedipine, oxprenelol, and triameterene
* Neurologic medications
** Phenytoin is the most common within this class
** Lysergic acid
** Carbamazepine
** Nomifensine
** Thioradazine
** Case reports of amphetamine, doxepin, haloperidol, nomifensine, sulfasalazine, triamterene, benztropine, and trifluoperazine
* Chemotherapy and immunomodulators
** Bleomycin
** Streptomycin
** Case reports of 6-mercaptopurine, chlorambucil, cisplatin, cytarabine, cytosine arabinoside, daunorubicin, hydroxyurea, L-asparaginase, procarbazine, streptozocin, and vincristine
* Antiinflammatory or immunomodulatory medications
** Azathioprine
** NSAIDs, including ibuprofen, tolmetin, and aspirin
** Case reports of everolimus, mycophenolate mofetil, and sirolimus
* Other medications, including allopurinol, cimetidine, clofibrate, folate, interferon, iodide, levamisole, metoclopramide, piperazine, propylthiouracil, prostaglandin E2, ritodrine, theeophylline, and thyroxine


*Stipulated to involve any of five mechanisms:
== Clinical Presentation ==
**Altered thermoregulation, including anticholinergics
* Fever without focus and no other likely causes
**Drug administration-related fever, including [[amphotericin B]], cephalosporins, and [[vancomycin]]
* Can occur at any point in administration of the medication, but most often 7 to 10 days after starting
**Expected drug effect, including chemotherapy (tumour lysis) and penicillins ([[Jarisch-Herxheimer reaction]])
* Fever pattern was mostly unpredictable, but could be intermittent or remittent (high but fluctuating); rarely continuous
**Idiosyncratic reactions, including [[primaquine]], [[quinidine]], [[quinine]], and sulfonamides
* Fever most commonly high, but could be low-grade
**Hypersensitivity reaction, including allopurinol, [[quinidine]], [[quinine]], and sulfonamides
* Usually appear well, even when febrile, including a relative bradycardia
* Many have rigors, and may occasionally have other systemic signs or symptoms
* Occasional leukocytosis or eosinophilia


===Etiology===
== Further Reading ==

* Drug fever. ''Pharmacotherapy''. 2010;30(1):57-69. doi: [https://doi.org/10.1592/phco.30.1.57 10.1592/phco.30.1.57]
*Long list of offending medication, mostly based on collections of case reports[[CiteRef::mackowiak1987dr]][[CiteRef::patel2010dr]]
*Antimicrobials are the most common overall class
**Penicillins are most common, including [[penicillin]], [[piperacillin]], [[ticarcillin]] [[ampicillin]], [[methicillin]], [[carbenicillin]], [[mezlocillin]], [[staphcillin]], [[nafcillin]], [[oxacillin]], and [[cloxacillin]]
**Cephalosporins, including [[cefazolin]], [[cefotaxime]], [[ceftazidime]], [[cephalexin]], and [[cephalothin]]
**[[Tetracycline]] and [[minocyline]]
**[[Trimethoprim-sulfamethoxazole]]
**[[Isoniazid]]
**[[Nitrofurantoin]]
**Case reports of [[acyclovir]], [[amphotericin B]], [[aureomycin]], [[colistin]], [[declomycin]], [[erythromycin]], [[furadantin]], [[mebendazole]], [[novobiocin]], [[para-aminosalicylic acid]], [[rifampin]], [[streptomycin]], [[terramycin]], and [[vancomycin]]
*Cardiovascular
**[[Methyldopa]]
**[[Quinidine]] and [[quinine]]
**[[Procainamide]]
**[[Dobutamine]]
**Case reports with [[clofibrate]], [[diltiazem]], [[furosemide]], [[heparin]], [[hydralazine]], [[hydrochlorothiazide]], [[nifedipine]], [[oxprenelol]], and [[triameterene]]
*Neurologic medications
**[[Phenytoin]] is the most common within this class
**[[Dexmedetomidine]]
**[[Lysergic acid]]
**[[Carbamazepine]]
**[[Nomifensine]]
**[[Thioradazine]]
**Case reports of [[amphetamine]], [[doxepin]], [[haloperidol]], [[nomifensine]], [[sulfasalazine]], [[triamterene]], [[benztropine]], and [[trifluoperazine]]
*Chemotherapy and immunomodulators
**[[Bleomycin]]
**[[Streptomycin]]
**Case reports of [[6-mercaptopurine]], [[chlorambucil]], [[cisplatin]], [[cytarabine]], [[cytosine arabinoside]], [[daunorubicin]], [[hydroxyurea]], [[L-asparaginase]], [[procarbazine]], [[streptozocin]], and [[vincristine]]
*Antiinflammatory or immunomodulatory medications
**[[Azathioprine]]
**[[NSAIDs]], including [[ibuprofen]], [[tolmetin]], and [[aspirin]]
**Case reports of [[everolimus]], [[mycophenolate mofetil]], and [[sirolimus]]
*Other medications, including [[allopurinol]], [[cimetidine]], [[clofibrate]], [[folate]], [[interferon]], [[iodide]], [[levamisole]], [[metoclopramide]], [[piperazine]], [[propylthiouracil]], [[prostaglandin E2]], [[ritodrine]], [[theophylline]], and [[thyroxine]]

==Clinical Manifestations==

*Fever without focus and no other likely causes
*Can occur at any point in administration of the medication, but most often 7 to 10 days after starting
*Fever pattern was mostly unpredictable, but could be intermittent or remittent (high but fluctuating); rarely continuous
*Fever most commonly high, but could be low-grade
*Usually appear well, even when febrile, including a relative bradycardia
*Many have rigors, and may occasionally have other systemic signs or symptoms
*Occasional leukocytosis or eosinophilia

==Management==

*Stop offending medication

==Further Reading==

*Drug fever. ''Pharmacotherapy''. 2010;30(1):57-69. doi: [https://doi.org/10.1592/phco.30.1.57 10.1592/phco.30.1.57]


[[Category:Fever syndromes]]
[[Category:Fever syndromes]]

Latest revision as of 19:48, 14 December 2022

Background

  • A drug reaction of unclear mechanism that causes isolated fever

Pathophysiology

  • Stipulated to involve any of five mechanisms:

Etiology

Clinical Manifestations

  • Fever without focus and no other likely causes
  • Can occur at any point in administration of the medication, but most often 7 to 10 days after starting
  • Fever pattern was mostly unpredictable, but could be intermittent or remittent (high but fluctuating); rarely continuous
  • Fever most commonly high, but could be low-grade
  • Usually appear well, even when febrile, including a relative bradycardia
  • Many have rigors, and may occasionally have other systemic signs or symptoms
  • Occasional leukocytosis or eosinophilia

Management

  • Stop offending medication

Further Reading

References

  1. ^  Philip A. Mackowiak. Drug Fever: A Critical Appraisal of Conventional Concepts. Annals of Internal Medicine. 1987;106(5):728. doi:10.7326/0003-4819-106-5-728.
  2. ^  Ruchi A Patel, Jason C Gallagher. Drug Fever. Pharmacotherapy. 2010;30(1):57-69. doi:10.1592/phco.30.1.57.