Zieve's syndrome is observed in suspected or known alcoholic patients and leads to the manifestation of transient jaundice due to acute hemolytic anemia and hyperlipidemia [1]. Individuals affected by the syndrome typically suffer from steatohepatitis as well.

Anemia is always present in the case of Zieve's syndrome and follows a hemolytic pathophysiological route, causing the appearance of jaundice. The symptoms such as fatigue and malaise may be seen in mild cases. A considerable number of patients, however, are affected by severe anemia, which is responsible for a profound set of symptoms, including tachycardia, tachypnea, and hypotension. Loss of consciousness and dizziness may be present due to the anemic condition of the patient in the Zieve's syndrome.

Pain in the right upper quadrant abdominal region is also a common symptom, leading to confusion between Zieve's syndrome and acute cholecystitis [2]. Patients have also reported myalgia, which occurs due to an increased serum viscosity, and retinal damage has also been observed, even though there may be no symptoms accompanying the latter [3] [4]. Some patients diagnosed with Zieve's syndrome present with intracranial hemorrhage, that has mainly been attributed to the increase in serum lipids, with this symptom being documented in only four cases [5].

• Fever

  All patients presented with acute abdominal pain and fever. Four had a history of a recent alcohol binge. Hyperlipidaemia was present in two patients; this subsided before the onset of haemolysis. [ncbi.nlm.nih.gov]

  The main symptoms of acute ascending cholangitis are jaundice, abdominal pain, chills, and fever.... Is that stomach pain appendicitis? // Consumer Reports on Health;Dec2000, Vol. 12 Issue 12, p7 Focuses on the medical symptoms of appendicitis. [connection.ebscohost.com]

  Other nonspecific symptoms include nausea, vomiting, malaise, weakness, and low-grade fever [1]. ZS can mimic alcoholic hepatitis as the two conditions share findings such as alcohol use, jaundice, and anemia [3,7]. [cureus.com]

• Fatigue

  Patient concerns: A 30-year-old Chinese woman presented with a 4-month history of fatigue, yellowish… CONTINUE READING [semanticscholar.org]

  Patient concerns: A 30-year-old Chinese woman presented with a 4-month history of fatigue, yellowish discoloration of the eyes, and tea-colored urine. [ncbi.nlm.nih.gov]

• Abdominal Pain

  It can present acutely with abdominal pain. [ncbi.nlm.nih.gov]

  The main symptoms of acute ascending cholangitis are jaundice, abdominal pain, chills, and fever.... Is that stomach pain appendicitis? // Consumer Reports on Health;Dec2000, Vol. 12 Issue 12, p7 Focuses on the medical symptoms of appendicitis. [connection.ebscohost.com]

  It is defined by hemolytic anemia (with spur cells and acanthocytes), hyperlipoproteinaemia (excessive blood lipoprotein), jaundice (elevation of unconjugated bilirubin), and abdominal pain.[1] The underlying cause is liver delipidization. [en.wikipedia.org]

  The syndrome is defined by excessive blood lipoprotein, jaundice and abdominal pain. [athena.targetwoman.com]

• Gastropathy

  At the EGDS was showed oesophageal varices (grade I) in the context of a congestive gastropathy and antral gastritis. [omicsonline.org]

  Esophagogastroduodenoscopy (EGD) showed three columns of non-bleeding grade I varices in the lower third of the esophagus and mild diffuse portal hypertensive gastropathy with no bleeding. [cureus.com]

• Hepatosplenomegaly

  a running together, tumultuous concourse; (in med.) a concurrence of symptoms, fr. syn,… … Medical dictionary Zieve syndrome — a syndrome of hypercholesterolemia, hepatosplenomegaly, fatty liver, hemolytic anemia, and hypertriglyceridemia seen in alcoholics [translate.academic.ru]

  At physical examination was revealed the presence of scleral jaundice, hepatosplenomegaly, gengiva bleeding and bronzed skin. [omicsonline.org]

• Conjunctival Pallor

  Physical examination was remarkable for scleral icterus, conjunctival pallor, and a dry oral mucosa. [ncbi.nlm.nih.gov]

• Hip Pain

  Case Presentation A 58-year-old male with a history of liver cirrhosis secondary to alcohol abuse, presented with right hip pain, abdominal pain, and severe anemia. He had been binging on alcohol and sustained a fall prior to his presentation. [cureus.com]

• Denial

  There are a small number of reported cases of Zieve syndrome, and the reason could be the lack of pathognomonic symptoms, rapid decrease of hyperlipidaemic serum levels after alcohol withdrawal, patients denial of drinking. [lmaleidykla.lt]

  There could be rapid serum level rise after alcohol withdrawal in patients with denial of drinking. Treatment Temperance for two to three weeks is essential for symptoms to disappear. [athena.targetwoman.com]

• Tremulousness

  In Zieve's 20 patients, aged 26 to 65 years, tremulousness was common and frank delirium tremens occurred at times. The condition improved once the drinking stops. Leslie Zieve in Citation Classic, September 26, 1983, 39: 18. [whonamedit.com]

The diagnosis of Zieve's syndrome may be difficult, due to the similarities with other conditions and due to the habit of alcoholism often being withheld by the patients. The primary aim is to distinguish the syndrome from other medical conditions, such as acute cholecystitis and acute alcoholic hepatitis.

The initial laboratory evaluation of any patient presenting with jaundice, signs of anemia and possibly upper right abdominal quadrant pain includes the following:

• Complete blood count: It will illustrate moderately or severely diminished hemoglobin levels, increased reticulocytes. Spherocytes and target cells may also be revealed.
• Biochemical profile: Increased serum indirect bilirubin, alkaline phosphatase, cholesterol, and triglycerides. Liver function tests render abnormal results.

Distinguishing Zieve's syndrome from acute cholecystitis requires an initial thorough physical examination. Patients affected by the syndrome do not display a positive Murphy's sign and are typically afebrile, in contradistinction to acute cholecystitis. Furthermore, indirect serum bilirubin levels are profoundly elevated in Zieve's syndrome, amounting to over 5 mg/dL, whereas values between 2 and 5 mg/dL are expected in acute cholecystitis. A right upper quadrant ultrasonographic scan (RUQ US) or cholescintigraphy are also required: a lack of gallstones or pericholecystic fluid direct the diagnostic process towards Zieve's syndrome. These procedures, however, may render inconclusive results, such as gallbladder distention, findings which do not aid in the differential diagnosis of Zieve's syndrome and acute cholecystitis [6].

Zieve's syndrome also needs to be differentiated from acute alcoholic hepatitis. These two medical entities are distinguished, due to the fact that the former leads to hyperlipidemia in combination with hemolytic anemia, whereas the latter is characterized by a remarkable increase in transaminase levels (AST< 300 IU/mL), hyperbilirubinemia and a prolonged international normalized ratio (INR) [6]. Moreover, patients suffering from acute alcoholic hepatitis exhibit a steadily declining course, despite appropriate treatment, whereas Zieve's syndrome tends to regress, once the alcoholic trigger has been removed [6].

Given that Zieve's syndrome may also induce intracranial or retinal hemorrhage, fundoscopy and a complete neurological examination may be required [7]. Neurological deficits may indicate the need for further investigation.

Also, in the cases of individuals who have not yet been diagnosed with fatty liver disease or steatohepatitis, a liver biopsy will illustrate a fatty infiltration of the liver. In general, Zieve's syndrome must be considered as a possible pathology, when a patient with a history presents with indirect hyperbilirubinemia, a medical history of alcoholism and no other probable causes for the biochemical anomaly [8].

• Bilirubin Increased

  His total bilirubin increased to a maximum of 41 (Figure 1B). Liver Doppler ultrasound showed a heterogenous liver with no focal lesions, patent hepatic and portal veins, and no biliary ductal dilatation. His lipid panel was normal. [cureus.com]

• Hypertriglyceridemia

  "Zieveʼs Syndrome Presenting With Severe Hypertriglyceridemia". ACG Case Reports Journal. 6 (7): 1–3. doi:10.14309/crj.0000000000000133. Zieve, L (March 1958). [en.wikipedia.org]

  We report a case of ZS with severe hypertriglyceridemia. [unboundmedicine.com]

  We report a case of ZS with severe hypertriglyceridemia. Among the reported cases of ZS in English literature, we believe this is the first case of the syndrome presenting with severe hypertriglyceridemia requiring plasmapheresis. [insights.ovid.com]

  a running together, tumultuous concourse; (in med.) a concurrence of symptoms, fr. syn,… … Medical dictionary Zieve syndrome — a syndrome of hypercholesterolemia, hepatosplenomegaly, fatty liver, hemolytic anemia, and hypertriglyceridemia seen in alcoholics [translate.academic.ru]

  Historical Perspective Zieve's syndrome was initially described by Leslie Zieve in patients with a combination of alcoholic liver disease, hemolytic anemia and hypertriglyceridemia. [1] Classification Pathophysiology The proposed mechanism of the characteristic [wikidoc.org]

• Anisocytosis

  A peripheral blood smear was compatible with hemolysis and revealed anisocytosis, and an occasional target cell was seen. Hemoglobin electrophoresis was normal, ruling out thalassaemia. [ncbi.nlm.nih.gov]

• Macrocytic Anemia

  The presentation of anemia is subacute and severe, differing from the chronic macrocytic anemia secondary to vitamin deficiency common in alcohol use disorder. [visualdx.com]

  A blood smear showed macrocytic anemia and thrombocytopenia with schistocytes and acanthocytes. His total bilirubin increased to a maximum of 41 (Figure 1B). [cureus.com]

• Total Bilirubin Increased

  His total bilirubin increased to a maximum of 41 (Figure 1B). Liver Doppler ultrasound showed a heterogenous liver with no focal lesions, patent hepatic and portal veins, and no biliary ductal dilatation. His lipid panel was normal. [cureus.com]

• Bone Marrow with Hyperplasia

  There could be drop in hemoglobin, reticulocytes, bone marrow erythroblastic hyperplasia, and increased erythrocyte fragility and shortened life of red blood cells. [athena.targetwoman.com]

Treatment[edit] Definitive treatment for Zieve's syndrome is alcohol cessation. [en.wikipedia.org]

Definitive treatment for Zieve's syndrome is alcohol cessation. [quizlet.com]

Medical Therapy Definitive treatment for Zieve's syndrome is alcohol cessation. [wikidoc.org]

Treatment of ZS is mainly supportive with blood transfusions and encouraging abstinence from alcohol [2]. [cureus.com]

// Reactions Weekly;4/29/2006, Issue 1099, p8 Reports on the development of a hepatic venous thrombosis in a 66-year-old woman receiving cyclosphosphamide during concomitant treatment for an autoimmune hemolytic anemia flare-up. [connection.ebscohost.com]

Natural History Complications Prognosis Diagnosis Diagnostic Criteria History and Symptoms Physical Examination Laboratory Findings Imaging Findings Other Diagnostic Studies Treatment Medical Therapy Definitive treatment for Zieve's syndrome is alcohol [wikidoc.org]

The liver damage in Zieve syndrome also warrants different management from acute alcoholic hepatitis and has better prognosis with reversibility. [visualdx.com]

[…] person's signs and symptoms, and may include: Anticonvulsant medicines for seizures Eye drops or surgery to treat glaucoma Laser therapy for port-wine stains Physical therapy for paralysis or weakness Possible brain surgery to prevent seizures Outlook (Prognosis [ufhealth.org]

The prognosis of the 2 disorders is different: 40% of patients with acute alcoholic hepatitis may progress to liver failure and even death, while in Zieve syndrome, abstaining from alcohol would result in a resolution of the symptoms.[10] Patients with [ncbi.nlm.nih.gov]

Zieve syndrome leads to subacute, severe, normocytic anemia with hemolysis, which differs from the common etiology of chronic, macrocytic anemia secondary to folic acid and B12 deficiency. [visualdx.com]

While there are many etiologies of anemia in alcoholics, Zieve's syndrome is distinct in that it is an acute hemolytic anemia.1,2 Case Report A 45-year-old man presented for voluntary admission to the alcohol detoxification unit. [ncbi.nlm.nih.gov]

[…] hemolysin such as lysolecithin. [2] Changes in membrane lipid compositions such as increased cholesterol and polyunsaturated fatty acid (PUFA) have been report during the hemolytic phase. [3] Causes Differentiating Zieve's syndrome from Other Diseases Epidemiology [wikidoc.org]

The exact pathophysiologic mechanism is unknown but, as reviewed in the article, has been postulated to be secondary to alcohol induced hyperlipidemia that in turn predisposes red cell membranes to lysis. [mayoclinic.pure.elsevier.com]

Historical Perspective Zieve's syndrome was initially described by Leslie Zieve in patients with a combination of alcoholic liver disease, hemolytic anemia and hypertriglyceridemia. [1] Classification Pathophysiology The proposed mechanism of the characteristic [wikidoc.org]

Anemia is always present in the case of Zieve's syndrome and follows a hemolytic pathophysiological route, causing the appearance of jaundice. The symptoms such as fatigue and malaise may be seen in mild cases. [symptoma.com]

The pathophysiology of hemolysis in ZS is not fully understood. Dr. Zieve suggested that hyperlipidemia and presence of abnormal lipids (possibly lysolecithin) plays a role in hemolysis by disrupting RBC membrane [1]. [cureus.com]

[…] unnecessary invasive testing or referrals and provide definitive therapy such as alcohol cessation counseling and enrollment into programs that would prevent relapse of alcoholism. [ncbi.nlm.nih.gov]

Prevention There is no known prevention. Images References Sahin M. Sturge-Weber syndrome. In: Kliegman RM, Stanton BF, St Geme JW III, Schor NF, eds. Nelson Textbook of Pediatrics. 20th ed. Philadelphia, PA: Elsevier; 2016:chap 596. [ufhealth.org]

[…] production Intravenous (through the vein) fluids Withdrawal of medicines that caused the syndrome In life-threatening cases, medicines that keep the muscles still (paralyze them), and a temporary breathing tube and breathing machine will be needed to prevent [medlineplus.gov]

This leads to instability of a critically balanced system leading to an increased bleeding tendency Prevention and treatment of bleeding in cirrhosis Our understanding of the coagulation cascade has undergone a change in recent times. [tropicalgastro.com]

1. Zieve L. Jaundice, hyperlipemia and hemolytic anemia: A heretofore unrecognized syndrome associated with alcoholic fatty liver and cirrhosis. Annals Intern Med. 1958;48(3):471–96.
2. Hashmi S, Allison MG, McCurdy MT, Reed RM. Hyperbilirubinaemia and haemolytic anaemia in acute alcoholic hepatitis: there's oil in them thar veins. BMJ Case Rep. 2014.
3. Martin JC, Ross A, Watson D, et al. A case of Zieve's syndrome presenting with myalgia: not to be confused with polymyalgia rheumatica. Br J Rheumatol. 1996;35:495–6.
4. Gross C, Bohl B, Herfurth S. A case report of unusual retinal findings in a patient with Zieve syndrome. Ophthalmology. 2002;99:876–9.
5. Hilz MJ, Bauer J, Druschky KF, et al. Zieve's syndrome and intracranial haemorrhage: coincidence or related disorders. J Neurol. 1990;237:120–1.
6. Kurzweil SM, Shapiro MJ, Andrus CH, et al. Hyperbilirubinemia without common bile duct abnormalities and hyperamylasemia without pancreatitis in patients with gallbladder disease. Arch Surg. 1994;129:829–33.
7. Lucey MR, Mathurin P, Morgan TR. Alcoholic hepatitis. N Engl J Med. 2009;360:2758–69.
8. Nath S, Peck JR. Hemolytic Anemia in Alcohol-Induced Liver Disease: A Case Report on
   Zieve’s Syndrome. Int J Blood Res Disord. 2015, 2:1.