Etiology
Anti-Androgenic Agents
- Bicalutamide (Casodex) (see Bicalutamide)
- Cyproterone Acetate
- Nilutamide (Nilandron) (see Nilutamide)
Antibiotics
Cephalosporins (see Cephalosporins)
- Cephalexin (Keflex) (see Cephalexin)
- Cefotiam (Pansporin) (see Cefotiam)
Fluoroquinolones (see Fluoroquinolones)
- Nalidixic Acid (see Nalidixic Acid)
- Levofloxacin (Levaquin) (see Levofloxacin)
- Tosufloxacin (Ozex) (see Tosufloxacin)
Macrolides (see Macrolides)
- Azithromycin (Zithromax) (see Azithromycin)
- Clarithromycin (Biaxin) (see Clarithromycin)
- Erythromycin (see Erythromycin)
- Roxithromycin (Biaxsig, Coroxin, Romac, Roxar, Roximycin, Roxl-150, Roxo, Roxomycin, Rulid, Rulide, Surlid, Tirabicin, Xthrocin) (see Roxithromycin)
Penicillins (see Penicillins)
- Ampicillin (see Ampicillin)
Sulfonamides (see Sulfonamides)
- Sulfasalazine (see Sulfasalazine)
- Sulfapyridine: not used in humans anymore
- Sulfamethoxazole (see Sulfamethoxazole-Trimethoprim)
- Sulfacetamide (see Sulfacetamide)
Tetracyclines (see Tetracyclines)
- Minocycline (see Minocycline)
- Tetracycline (see Tetracycline)
Other Antibiotics
- Clindamycin (see Clindamycin)
- Dapsone (see Dapsone)
- Daptomycin (see Daptomycin)
- Ethambutol (see Ethambutol)
- Furazolidone
- Inhaled Pentamidine (see Pentamidine)
- Isoniazid (see Isoniazid)
- Metronidazole (see Metronidazole)
- Niridazole
- Nitrofurantoin (Macrodantin) (see Nitrofurantoin)
- Para-Amino Salicylic Acid (PAS, 4-Amino-Salicylic Acid): previously used to treat TB
- Pyrimethamine+Dapsone/Pyrimethamine+Sulfadoxine
- Rifampin (Rifampicin, Rifadin) (see Rifampin)
- Streptomycin (see Streptomycin)
- Troleandomycin (see Troleandomycin)
Anticonvulsants
- Phenytoin (Dilantin) (see Phenytoin)
- Carbamazepine (Tegretol) (see Carbamazepine)
Anti-Hyperlipidemic Agents
- Clofibrate (see Clofibrate)
- Simvastatin (Zocor) (see Simvastatin)
Antihypertensives
- Angiotensin Converting Enzyme (ACE) Inhibitors (see Angiotensin Converting Enzyme Inhibitors)
- Captopril (Capoten) (see Captopril)
- Fosinopril (Monopril) (see Fosinopril)
- Perindopril (Coversyl, Coversum, Preterax, Aceon) (see Perindopril)
- Beta Adrenergic Receptor Blockers
- Labetalol (see Labetalol)
- Propanolol (see Propanolol)
Anti-Inflammatory Agents
- Acetaminophen (see Acetaminophen)
- Bucillamine
- Chloroquine (see Chloroquine)
- Glafenine
- Gold (see Gold)
- Infliximab (Remicade) *see Infliximab)
- Inhaled Beclomethasone (see Beclomethasone)
- Inhaled Cromolyn (see Cromolyn)
- Leflunomide (Arava) (see Leflunomide)
- Mesalamine (5-ASA) (see Mesalamine)
- Montelukast (Singulair) (see Montelukast)
- Niflumic Acid
- Penicillamine (see Penicillamine)
Chemotherapeutic Agents
- Azacitidine (Vidaza) (see Azacitidine)
- Epidemiology: case reports
- Bleomycin (Blenoxane) (see Bleomycin)
- Chlorambucil (see Chlorambucil)
- Cladribine (Leustatin, 2-Chlordeoxyadenosine, 2-CDA) (see Cladribine)
- Fludarabine (Fludara) (see Fludarabine)
- Gemcitabine (Gemzar) (see Gemcitabine)
- Interleukin-2 (IL-2) (see Interleukin-2)
- Imatinib (see Imatinib)
- Interferon-Alpha (see Interferon)
- Methotrexate (see Methotrexate)
- Oxaliplatin (see Oxaliplatin)
- Paclitaxel (see Paclitaxel)
- Procarbazine (see Procarbazine)
- Tamoxifen (see Tamoxifen)
Hypoglycemic Agents
- Tolazamide
- Chlorpropamide (Diabenese) (see Chlorpropamide)
Nonsteroidal Anti-Inflammatory Drug (NSAID) (see Nonsteroidal Anti-Inflammatory Drug)
- Acetylsalicylic Acid (Aspirin) (see Acetylsalicylic Acid)
- Diclofenac (see Diclofenac)
- Diflunisal (Dolobid)
- Fenbufen
- Fenoprofen (see Fenoprofen)
- Ibuprofen (Motrin) (see Ibuprofen)
- Indomethacin (Indocin) (see Indomethacin)
- Loxoprofen
- Meloxicam (see Meloxicam)
- Naproxen (Naprosyn) (see Naproxen)
- Nimesulide
- Phenylbutazone (see Phenylbutazone)
- Piroxicam (see Piroxicam)
- Pranoprofen
- Sulindac (see Sulindac)
- Tenidap
- Tiaprofenic Acid
- Tolfenamic Acid
Psychiatric Drugs
- Amitriptyline (see Amitriptyline)
- Chlorpromazine (Thorazine) (see Chlorpromazine)
- Desipramine (see Desipramine)
- Duloxetine (see Duloxetine)
- Fluoxetine (Prozac) (see Fluoxetine)
- Imipramine (see Imipramine)
- Maprotiline
- Methylphenidate (Ritalin) (see Methylphenidate)
- Nomifensine
- Risperidone (Risperdal) (see Risperidone)
- Sertraline (Zoloft) (see Sertraline)
- Trazodone (see Trazodone)
- Trimipramine
- Venlafaxine (Effexor) (see Venlafaxine)
Other
- Aminoglutethimide (Cytadren) (see Aminoglutethimide)
- Amiodarone (see Amiodarone): uncommonly causes PIE
- Cocaine (Snorted) (see Cocaine)
- Dexfenfluramine (see Dexfenfluramine)
- Febarbamate
- Fenfluramine (see Fenfluramine)
- GM-CSF (see GM-CSF)
- Heroin (see Heroin)
- Hydrochlorothiazide (HCTZ) (see Hydrochlorothiazide)
- Ifenprodil
- Iohexol/Iodine Radiocontrast (see Radiographic Contrast)
- Isotretinoin (see Isotretinoin)
- L-Tryptophan (see Eosinophilia-Myalgia Syndrome)
- Mefenamic Acid (see Mefenamic Acid)
- Mephenesin
- Packed Red Blood Cell Transfusion (see Packed Red Blood Cells)
- Progesterone (see Progesterone)
- Propylthiouracil (PTU) (see Propylthiouracil)
- Serrapeptase
- Tacrolimus (Prograf) (see Tacrolimus)
- Tetrahydrocannabinol (THC) (see Tetrahydrocannabinol)
- Ticlopidine (Ticlid) (see Ticlopidine)
- Tobacco (see Tobacco)
Physiology
- Possible Immune Complex Mechanism
Diagnosis
- Sputum Culture: negative
- CXR/Chest CT Patterns:
- Diffuse Alveolar Infiltrates:
- Pleural Effusion: seen only in Nitrofurantoin-associated cases
- Pulmonary Function Tests (PFT’s): decreased DLCO is seen in all cases (but reversible obstruction or restriction were not observed)
- CBC: eosinophilia
- Nitrofurantoin acute-type syndrome usually has the highest degree of eosinophilia (as compared to subacute and chronic-type syndromes)
Clinical Manifestations
General Comments
- Onset: symptoms usually occur within hours-days after starting drug
- Asymptomatic Cases: some cases may be asymptomatic
Pulmonary Manifestations
- Crackles: 66% of cases
- Dry Cough (see Cough): variable
- Dyspnea (see Dyspnea)
- Wheezing: variable
- However, reversible airway obstruction is not seen
Other Manifestations
- Low-Grade Fever (see Fever)
Drug Rash with Eosinophilia and Systemic Symptoms (DRESS Syndrome) (see Drug Rash with Eosinophilia and Systemic Symptoms)
Associated Agents
- Allopurinol (Zyloprim) (see Allopurinol)
- Carbamazepine (Tegretol) (see Carbamazepine)
- Dapsone (see Dapsone)
- Lamotrigine (Lamictal) (see Lamotrigine)
- Minocycline (see Minocycline)
- Modafinil (Alertec, Modavigil, Modiodal, Provigil, Modalert) (see Modafinil)
- Phenobarbital (see Phenobarbital)
- Phenytoin (Dilantin) (see Phenytoin)
- Sulfonamides (see Sulfonamides)
- Sulfasalazine (Azulfidine) (see Sulfasalazine)
- Ziprasidone (Geodone) (see Ziprasidone)
Clinical Manifestations
- Cardiovascular Manifestations 15% of cases)
- Myocarditis (see Myocarditis)
- Dermatologic Manifestations
- Erythroderma (see Erythroderma)
- Facial Edema (see Facial Edema)
- Morbilliform Rash (see Exanthems)
- Gastrointestinal Manifestations
- Gastrointestinal (GI) Hemorrhage (see Gastrointestinal Hemorrhage): may occur in allopurinol-associated cases
- Hepatitis (see Drug-Induced Hepatotoxicity): in 80% of cases
- Pancreatic Involvement: in 5% of cases
- Pulmonary Manifestations
- Pneumonitis (see Pneumonia): in 33% of cases
- Renal Manifestations: 40% of cases
- Acute Interstitial Nephritis (see Acute Kidney Injury and Acute Interstitial Nephritis)
- Rheumatologic/Orthopedic Manifestations
- Myositis (see Myositis)
- Other Manifestations
- Fever (see Fever)
- Lymphadenopathy (see Lymphadenopathy)
- Pseudolymphoma Syndrome: lymphadenopathy and abnormal circulating lymphocytes may especially occur in anticonvulsant-associated cases
Treatment
- Drug Withdrawal: spontaneous resolution, infiltrates and symptoms usually resolve
- Does not tend to resolve as fast as Loffler’s though
- Corticosteroids (see Corticosteroids): may or may not be useful in some cases with slow resolution
References
- Ann Pharmacother 41:696-701 (2007); J Infection 54:e211-e213 (2007)