Jaundice causes

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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Overview

Common causes of jaundice are classified under conjugated and unconjugated hyperbilirubinemia. Unconjugated hyperbilirubinemia is caused by eiether increased bilirubin production in the body, impaired hepatic bilirubin uptake in the liver or impaired bilirubin uptake in the liver, all of which causes pooling of unconjugated bilirubin in the body leading to unconjugated hyperbilirubinemia. On the other hand, intra or extra hepatic cholestasis lead to accumulation of conjugated bilirubin causing conjugated hyperbilirubinemia.

Causes

Jaundice may be caused by:

Unconjugated hyperbilirubinemia

Causes of unconjugated hyperbilirubenemia includes:

Common Causes

• Increased bilirubin production:
  • Extravascular hemolysis
  • Extravasation of blood into tissues
  • Intravascular hemolysis
  • Wilson's disease
• Impaired hepatic bilirubin uptake:
  • Heart failure
  • Portosystemic shunts
  • Drugs - Rifampin, Probenecid
• Impaired bilirubin conjugation:
  • Crigler-Najjar syndrome types I and II
  • Gilbert syndrome
  • Ethinyl estradiol
  • Liver diseases - chronic hepatitis, advanced cirrhosis

Less Common Causes

• Increased bilirubin production:
  • Dyserythropoiesis
• Impaired hepatic bilirubin uptake:
  • Some patients with Gilbert syndrome
  • Drugs - Flavaspadic acid, Bunamiodyl
• Impaired bilirubin conjugation:
  • Neonates
  • Hyperthyroidism

Conjugated hyperbilirubinemia

Causes of conjugated hyperbilirubinemia include:

Common Causes

• Intrahepatic cholestasis:
  • Viral hepatitis
  • Alcoholic hepatitis
  • Non-alcoholic fatty liver disease
  • Chronic hepatitis
  • Primary biliary cirrhosis
  • Drugs and toxins (eg, alkylated steroids, chlorpromazine, herbal medications [eg, Jamaican bush tea], arsenic)
  • Sepsis and hypoperfusion states
  • Infiltrative diseases (eg, amyloidosis, lymphoma, sarcoidosis, tuberculosis)
  • Pregnancy
  • Cirrhosis
• Extrahepatic cholestasis (biliary obstruction):
  • Choledocholithiasis
  • Intrinsic and extrinsic tumors (eg, cholangiocarcinoma)
  • Primary sclerosing cholangitis
  • Acute and chronic pancreatitis

Less Common Causes

• Intrahepatic cholestasis:
  • Total parenteral nutrition
  • Postoperative cholestasis
  • Following organ transplantation
  • Hepatic crisis in sickle-cell disease
• Extrahepatic cholestasis (biliary obstruction):
  • AIDS cholangiopathy
  • Certain parasitic infections (eg, Ascaris lumbricoides, liver flukes)
  • Strictures after invasive procedures
• Defect of canalicular organic anion transport:
  • Dubin-Johnson syndrome
• Defect of sinusoidal re uptake of conjugated bilirubin:
  • Rotor syndrome

Causes by Organ System

Cardiovascular	Eclampsia, Alagille syndrome, Infective endocarditis, Lupus, Trisomy 18, Heart failure
Chemical / poisoning	1,2-Dibromoethane, 2-acetylamino-fluorene, 2-Nitropropane, 3,3-Dichlorobenzidine, 4-Dimethylaminoazobenzene, 8-Hydroxyquinolone, Acer rubrum, Acetates, Acetonitrile, Acetylene Tetrabromide, Acrylonitrile, Aflatoxin, Albitocin, Alicyclic Hydrocarbons, Aliphatic Amines, Aliphatic Hydrocarbons, Aliphatic hydrogenated hydrocarbons, Allyl alcohol, Amanita phalloides, Aromatic amines, Aromatic halogenated hydrocarbons, Aromatic Hydrocarbons, Arsenic, Arsine, Benzene, Benzyl chloride, Beryllium, Bipyridyl pesticides, Black nightshade poisoning, Boron, Cadmium, Capecitabine, Carbarsone, Carbolic Acids and Anhydrides, Carbon Disulfide, Carbon Tetrachloride, caspofungin acetate, Chloramphenicol, Chlorate salts, Chlordane, Chlorinated benzenes, Chlorinated naphthalene, Chlorodiphenyls and derivatives, Chloroform, Chloromethane, Chloroprene, Chromium, Comfrey, Copper, Cresol, Cycasin, Cyclochlorotine,Dapsone, Dibromochloropropane, Diethylene Glycol, Dimethyl sulfate, Dimethylnitrosamine, Dinitrobenzene, Dinitrocresol, Dinitrophenol, Dinitrotoluene, Eltrombopag, Ethanolamines, Ethyl Acetate, Ethyl alcohol, Ethyl benzene, Ethyl Ether, Ethyl Salicylate, Ethylene chlorohydrin, Ethylene Dibromide, Ethylene dichloride, Ethylene oxide, Ethylenediamine, Fluoxymesterone, Germander, Germanium, Gold, Hafnium, Horse nettle , Hydrochlorothiazide ,Icterogenin, Hydrogen bromides, Hydrogen Cyanide, Indospicine, Isopropyl acetate, Kepone pesticides, Lanthanides, Lead, Mercaptans, Mercury, Meropenem, Methoxyflurane, Methyl acetate, Methyl Bromide, Methyl Chloride, Methylene chloride, Methylene Dianiline, Metolachlor, miltefosine, Monomethylhydrazine,Nabumetone, N,N-Dimethylformamide, N-butyl acetate, N-N-Dimethylacetamide, N-Nitrosodimethylamine, N-propyl acetate, Naphthalene, Naphthol, Ngaione, Nickel, Niobium, Nitriles, Nitrobenzene, Nitromethane, Nitroparaffins, Ochratoxin, Para-Dichlorobenzene, Phosphine, Phosphorus, Phthalic Anhydride, Picric Acid, Polybrominated biphenyls, Polychlorinated biphenyls, Polygonum multiflorum, Probenecid, Propylene dichloride, Psoralea Corylifolia, Pyrogallol, Pyrrolidizine, Ragwort, Rubratoxin, Safrole, Solanine, Solder, Sterigmatocystin, Stibine,, Tellurium, Tetrachloroethane, Tetrachloroethylene, Tetramethylthiuram disulfide, Thallium, Thioxanthene, Thorium dioxide, Thorotrast , Toluene, Trichloroethylene, Trinitrotoluene, Uranium, Vicia faba, Vinyl Chloride, White Phosphorus, Xylene, alkylated steroids, chlorpromazine, Jamaican bush tea
Dermatologic	Griscelli disease, NISCH syndrome, Hashimoto-Pritzker syndrome, Kawasaki disease, Deal-Barratt-Dillon syndrome, Lupus, Hemochromatosis
Drug Side Effect	5-Fluorocytosine, Acetaminophen and Oxycodone, Aldesleukin, Allopurinol, Alprazolam, Amineptine, Amiodarone, Amlodipine, Amodiaquine, Amphotericin, Anabolic C-17, Aztreonam, Bicalutamide, Bromazepam, Buprenorphine, Butyrophenones, Bunamiodyl, Cabozantinib, Cefaclor, Cefotaxime sodium, Ceftazidime, Ceftibuten, Cephalosporins, Chlordiazepoxide, Chlorpromazine, Cidofovir, Cimetidine, Clarithromycin, Clavulanic acid, Clindamycin, Co-amoxiclav, Cobicistat, Colchicine,crofelemer, Cyclopropane, Cycloserine, Cytarabine, Dantrolene, Dapsone, Daptomycin, Deracoxib, Diazepam, Diflunisal, Diphenoxylate and Atropine, Disulfiram, Docetaxel, Doxepine, Duloxetine, Dydrogesterone, Erythromycin estolate, Erythromycin Ethyl succinate, Estrogen and Progestin, Ethionamide, Fenoprofen, Flavaspadic acid, Flucloxacillin, Flurbiprofen, Framycetin, Fusidic acid, Griseofulvin, Halothane, Hycanthone, Hydroxyzine, Ibuprofen, ibuprofen lysine, Idoxuridine, Imipramine, Indinavir, Indomethacin, Isoniazid, Itraconazole, Ixabepilone, Ketoconazole, Loprazolam, Loratadine, Lorazepam, Lormetazepam, Meloxicam, Mepacrine, Mephenytoin, Mercaptopurinr, Metaxalone, Methocarbamol, Methimazole, Methyldopa, Metronidazole, Minocycline, Mirtazapine, Monoamine oxidase inhibitors, Naproxen, Niacin, Nitrofurantoin, Nitrous Oxide, Nizatidine, Novobiocin, Olanzapine, Oxandrolone, Oxaprozin, Oxycodone, p-aminosalicylic acid, Papaverine, Paroxetine, Pegaspargase, Penicillin, Pergolide, Phenol, Phenothiazine, Phenylbutazone, Phenytoin, Piperacillin/tazobactam, pomalidomide, Promethazine, Pyridine, Rifampin, Quinupristin dalfopristin, Quinidine-induced Immune Hemolytic Anemia, Quinolone, Ranitidine, Repaglinide, Rifampicin, Salicylate, sodium sulfate, potassium sulfate and magnesium sulfate Sibutramine, Sorafenib, Spectinomycin, Sulindac, Sulfasalazine, Sulphonamides, Tamoxifen, Tegaserod, Telithromycin, Tetracycline, Thalidomide, Thiabendazole, Trazodone, Triazolam, Trovafloxacin mesylate, Valproic acid, Vidarabine, Zoxazolamine, zileuton
Ear Nose Throat	Arthrogryposis -- renal dysfunction -- cholestasis syndrome
Endocrine	Gestational diabetes, Growth hormone deficiency, Hyperthyroidism, Hypopituitarism, Hypothyroidism, Thyroid agenesis
Environmental	No underlying causes
Gastroenterologic	Accessory pancreas, Acinic cell carcinoma, Acral dysostosis -- dyserythropoiesis , Acute Cholecystitis, Acute fatty liver of pregnancy, Acute hepatitis, Acute liver failure, Addison-Gull syndrome, Alagille syndrome, Alcoholic Hepatitis, Alcoholic liver disease, Angiosarcoma of the liver, Arthrogryposis -- renal dysfunction -- cholestasis syndrome, Ascending cholangitis, Autoimmune Hepatitis, Baber's syndrome, Banti's syndrome, Bile duct cancer, Bile duct paucity, non syndromic form, Bile plug syndrome, Biliary atresia, Biliary cirrhosis, Biliary colic, Budd-Chiari syndrome, Byler Disease, Caroli's Disease, Chlorpropamide, Cholangiocarcinoma, Cholangitis, Choledochal cyst, hand malformation, Choledochal cysts, Choledocholithiasis, Cholestasis, Cholestasis -- pigmentary retinopathy -- cleft palate, Chronic cholecystitis, Chronic Hepatitis, Cirrhosis of liver, Colorectal cancer, Crigler-Najjar syndrome, Eosinophilic gastroenteritis, Esophageal cancer, Gallbladder cancer, Gallstones, Gilbert's syndrome, Hemosuccus pancreaticus, Hepatic amyloidosis with intrahepatic cholestasis, Hepatic encephalopathy syndrome, Hepatoma, Hyperemesis gravidarum, Idiopathic liver cirrhosis, Intrahepatic cholangiocarcinoma, Intrahepatic cholestasis of pregnancy, Islet Cell adenoma, Liver cancer, Mirizzi's syndrome, Mosse syndrome, Neonatal hepatitis, Neuroma biliary tract, Non-alcoholic fatty liver disease, Obliterative portal venopathy, Pancreatic adenoma, Pancreatic cancer, Pancreatitis, Pancreatoblastoma, Papillary stenosis, Peliosis hepatis, Portal hypertension, Portosystemic shunts, Primary biliary cirrhosis, Primary sclerosing cholangitis, Sarcoma botryoides of common bile duct, Secondary Biliary Cirrhosis, Xanthogranulomatous cholecystitis, Xanthomatous biliary cirrhosis, Zieve's syndrome, NISCH syndrome, Benign intrahepatic cholestasis , Dubin-Johnson syndrome, Familial Selective Vitamin B12 Malabsorption, Hemochromatosis, Imerslund-Najman-Grasbeck Syndrome, Progressive familial intrahepatic cholestasis (PFIC) , Summerskill-Walshe-Tygstrup syndrome, HELLP syndrome, Heptaosplenic T-cell Lymphoma, Pernicious anemia, Alpha 1-Antitrypsin Deficiency , Viral Hepatitis A, Viral Hepatitis B, Viral Hepatitis C, Viral Hepatitis D, Viral Hepatitis E, Viral hepatitis X (non-A,-B,-C,-D,-E), Reynolds syndrome, Deal-Barratt-Dillon syndrome, Aagenaes syndrome , Infectious mononucleosis, Fanconi-ichthyosis-dysmorphism, Wilson's Disease, Cholesteryl ester storage disease, Chediak-Higashi syndrome, Weil's disease, Exocrine Pancreatic Insufficiency, Dyserythropoietic Anemia, And Calvarial Hyperostosis, Zellweger syndrome, Trisomy 18
Genetic	Aagenaes syndrome , Aldolase A deficiency , Arthrogryposis -- renal dysfunction -- cholestasis syndrome, Benign intrahepatic cholestasis , Chediak-Higashi syndrome, Cholesteryl ester storage disease, Dubin-Johnson syndrome, Exocrine Pancreatic Insufficiency, Dyserythropoietic Anemia, And Calvarial Hyperostosis, Familial Selective Vitamin B12 Malabsorption, Galactosemia, Glucose-6-phosphate dehydrogenase deficiency, Glutaric aciduria , Hemochromatosis, Hereditary elliptocytosis, Hereditary fructose intolerance, Hereditary xerocytosis, Imerslund-Najman-Grasbeck Syndrome, Lucey-Driscoll syndrome, Lymphoproliferative syndrome, EBV-Associated, Autosomal, Niemann-Pick disease, Porphyria, Progressive familial intrahepatic cholestasis (PFIC) , Pseudo-torch syndrome, Rotor syndrome, Sotos syndrome, Summerskill-Walshe-Tygstrup syndrome, Tyrosinemia, Wilson's Disease, Wolman disease, X-linked alpha thalassemia mental retardation syndrome (ATR-X), X-linked lymphoproliferative syndrome, X-linked sideroblastic anaemia, Zellweger syndrome, Griscelli disease, Hemoglobin C homozygous (CC), Hereditary spherocytosis, Thalassemia, Fructose intolerance, Alpha 1-Antitrypsin Deficiency , Acral dysostosis -- dyserythropoiesis , Pyruvate kinase deficiency, Arthrogryposis -- renal dysfunction -- cholestasis syndrome, Alagille syndrome, Trisomy 18
Hematologic	Achrestic anemia, Autoimmune hemolytic anemia, Evans syndrome, Fanconi-ichthyosis-dysmorphism, Favism, Hashimoto-Pritzker syndrome, HELLP syndrome, Hemoglobin C homozygous (CC), Hemolytic anemia, Hemolytic disease of the newborn, Hemophagocytic lymphohistiocytosis familial ,Hepatic veno-occlusive disease with immunodeficiency , Heptaosplenic T-cell Lymphoma, Hereditary spherocytosis, HLH (Hemophagocytic lymphohistiocytosis), Hodgkin's Disease, Kawasaki disease, Langerhans Cell Histiocytosis, Lymphoma, Myelofibrosis-osteosclerosis ,Pernicious anemia, Rh deficiency syndrome, Thalassemia, Thrombotic thrombocytopenic purpura, Acral dysostosis -- dyserythropoiesis , Mosse syndrome, Zieve's syndrome, Aagenaes syndrome , Exocrine Pancreatic Insufficiency, Dyserythropoietic Anemia, And Calvarial Hyperostosis, Glucose-6-phosphate dehydrogenase deficiency, Sickle-cell disease, Hereditary elliptocytosis, Hereditary xerocytosis, Porphyria, X-linked lymphoproliferative syndrome, X-linked sideroblastic anaemia, Pyruvate kinase deficiency, Kaposiform hemangio-endothelioma, Goldstein-Hutt syndrome, Infectious mononucleosis, Rh disease, Kawasaki disease, Sickle-cell disease, Griscelli disease, Lymphoproliferative syndrome, EBV-Associated, Autosomal, Aldolase A deficiency , X-linked alpha thalassemia mental retardation syndrome (ATR-X), Lupus
Iatrogenic	Post operative jaundice, Strictures after invasive procedures
Infectious Disease	Alveolar Hydatid Disease ., Aspergillosis, Congenital TORCH infections, Fascioliasis, Infective endocarditis, Malignant boutonneuse fever, Nanukayami, Neonatal sepsis, Omphalitis, Pneumonia, Sepsis, Tuberculosis, Q fever, Relapsing fever, Syphilis, Weil's disease, Histoplasmosis, Malaria, Cytomegalovirus, Hepadnaviruses, Herpes, Infectious mononucleosis, Lábrea fever, Marburg virus, Viral Hepatitis A, Viral Hepatitis B, Viral Hepatitis C, Viral Hepatitis D, Viral Hepatitis E, Viral hepatitis X (non-A,-B,-C,-D,-E), Ascending cholangitis, Lymphoproliferative syndrome, EBV-Associated, Autosomal, Acute meningitis, AIDS,  Ascaris lumbricoides, liver flukes
Musculoskeletal / Ortho	Deal-Barratt-Dillon syndrome, Choledochal cyst, hand malformation, X-linked alpha thalassemia mental retardation syndrome (ATR-X), Fanconi-ichthyosis-dysmorphism, Myelofibrosis-osteosclerosis, Lupus, Exocrine Pancreatic Insufficiency, Dyserythropoietic Anemia, And Calvarial Hyperostosis, Sotos syndrome, Cholestasis -- pigmentary retinopathy -- cleft palate, Alagille syndrome, Hemochromatosis, Aldolase A deficiency , Lupus, Trisomy 18, Arthrogryposis -- renal dysfunction -- cholestasis syndrome
Neurologic	Absence of septum pellucidum and septo-optic dysplasia , Acute meningitis, Eclampsia, Hepatic encephalopathy syndrome, Pseudo-torch syndrome, Sotos syndrome, Wilson's Disease, Zellweger syndrome, Lissencephalic syndromes, Chediak-Higashi syndrome, Alagille syndrome, Arthrogryposis -- renal dysfunction -- cholestasis syndrome, Trisomy 18
Nutritional / Metabolic	Breast feeding jaundice, Breast milk jaundice, Congenital disorders of glycosylation, Fructose intolerance, Manganese deficiency, Molybdenum deficiency, Organic acidemia, Pyruvate kinase deficiency, Selenium deficiency, Vitamin A overdose, Vitamin B12 Deficiency, Crigler-Najjar syndrome, Gilbert's syndrome, Cholesteryl ester storage disease, Galactosemia, Glutaric aciduria , Hereditary fructose intolerance, Lucey-Driscoll syndrome, Niemann-Pick disease, Tyrosinemia, Wolman disease, Acute fatty liver of pregnancy, Aldolase A deficiency, Total parenteral nutrition
Obstetric/Gynecologic	HELLP syndrome, Acute fatty liver of pregnancy, Eclampsia
Oncologic	Breast cancer, Embryonal rhabdomyosarcoma, Kaposiform hemangio-endothelioma, Acinic cell carcinoma, Angiosarcoma of the liver, Bile duct cancer, Cholangiocarcinoma, Colorectal cancer, Esophageal cancer, Gallbladder cancer, Hepatoma, Intrahepatic cholangiocarcinoma, Islet Cell adenoma, Liver cancer, Neuroma biliary tract, Pancreatic adenoma, Pancreatic cancer, Pancreatoblastoma, Lymphoma, Zellweger syndrome, Mesothelioma
Opthalmologic	Goldstein-Hutt syndrome, Cholestasis -- pigmentary retinopathy -- cleft palate, Chediak-Higashi syndrome, Absence of septum pellucidum and septo-optic dysplasia , Wilson's Disease, Alagille syndrome
Overdose / Toxicity	Acetaminophen, Iron, Vitamin C , Vitamin A
Psychiatric	No underlying causes
Pulmonary	Alpha 1-Antitrypsin Deficiency , Mesothelioma, Sarcoidosis, Pneumonia, Tuberculosis
Renal / Electrolyte	Arthrogryposis -- renal dysfunction -- cholestasis syndrome, Weil's disease, Alagille syndrome, Deal-Barratt-Dillon syndrome, Lupus
Rheum / Immune / Allergy	Autoimmune Hepatitis, Primary biliary cirrhosis, Primary sclerosing cholangitis, Autoimmune hemolytic anemia, Evans syndrome, Hemolytic disease of the newborn, Hepatic veno-occlusive disease with immunodeficiency , Sarcoidosis, Lupus, Transfusion reaction
Sexual	X-linked alpha thalassemia mental retardation syndrome (ATR-X), Lupus, Hemochromatosis
Trauma	Cephalhematoma, Hepatic trauma
Urologic	No underlying causes
Dental	No underlying causes
Miscellaneous	Brown Recluse spider bite , Neonatal adrenal hemorrhage, Neonatal physiological jaundice, Premature birth, Reye's syndrome,  organ transplantation

Causes in Alphabetical Order

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