Toxic Fungi of Western North America
The clinical course of amanitin poisoning
The clinical picture of amanitin poisoning is characterized by delayed onset of gastrointestinal symptoms, often a transient remission of these symptoms, during which time the liver and kidney damage increases, and finally either spontaneous recovery or death. The course is best described by the latency period: the number of hours or days since ingestion, rather than the onset of symptoms. Thus day 2 would start 24 hours from ingestion. Between days 2 and 4, there are frequently some hours during which most or all symptoms subside. This “honeymoon” period (rarely more than 24 hours) may not occur at all. (47,48E,49A,50),(51,52,53) Experience with numerous cases in the San Francisco area from 1970 on would not support statements in the literature that the remission period frequently lasts longer than 36-48 hours. Statements to the contrary are baffling; some reports may include the latency period.
One report notes occasional absence of abdominal pain. (54) Diarrhea is often continuous in severe poisonings for 3-6 days, after which jaundice and progressive liver failure usually dominate the clinical picture. Blood liver enzymes such as ALT and AST (alanine transaminase and aspartate aminotransferase) are with rare exception elevated by the time of admission to the emergency room. Levels may go up into thousands of units. Prothrombin, a protein manufactured by the liver and essential to blood clotting, may be low.
Vomiting and diarrhea usually begin between 10 and 16 hours, but may be present as early as 6 hours in severe poisoning and as late as 36 hours. The diarrhea is usually profuse and may be bloody and painful. Occasionally diarrhea is mild or the clinical picture may present as severe ileus, a condition in which normal propulsive bowel waves are markedly reduced. This unusual complication is accompanied by bloating, reduced bowel sounds and decreased or absent fecal output. Mild ileus is fairly common and presents only with slightly decreased, but high-pitched, bowel sounds and minor bloating. Earlier speculations that phalloidin produced the GI symptoms have been proven incorrect. (55)
The liver is often tender on admission or becomes so in the first 24-48 hours. The liver may enlarge in the first few days to as much as 5-15 cm below the right rib margin. (56c) The spleen also sometimes enlarges during the course of acute poisoning. (47) Such enlargement presumably occurs only during the acute phase of the illness.
Kidney failure is almost never an early finding and most often occurs, if at all, along with severe acidosis and liver failure as a late event. When renal failure does occur early, a study of 106 patients has shown oliguria (decreased urine output). (57) Renal failure most commonly occurs between the fifth and tenth days, preceded by increasing protein, protein casts and blood cells in the urine. Such kidney failure may occur in mild to moderate poisoning, most commonly when dehydration goes untreated 36 hours or more.
Liver failure manifests itself by jaundice, fluctuations of blood sugar, sometimes bleeding and changes in mentation (encephalopathy). The stages of encephalopathy are grade I (confusion), II (somnolence), III (coma, but responses to painful stimuli present) and IV (coma with no response to painful stimuli). Abnormal cardiac rhythms, shock and lactic acidosis may appear. Systemic acidosis is a regular feature of severe poisonings. However, lactic acidosis caused by poorly oxygenated cells is usually a fatal event.
Both high and low blood sugar levels have been reported in the course of poisoning. The liver stores glucose as a more complex carbohydrate called glycogen and a sudden toxic insult may release sugar causing a high blood sugar. As it turns out, either hyperglycemia (high glucose) or hypoglycemia (low glucose) may be present early. When hypoglycemia is present, insulin levels have been elevated, providing at least one mechanism for an early low blood glucose. (58) Late hypoglycemia also occurs and presumably reflects depletion of glycogen stores in a badly damaged liver.
Both low calcium and low phosphate levels have been noted along with varying levels of the two hormones--parathyroid hormone and calcitonin--that control calcium and phosphate metabolism. A Polish study of 21 poisoned children found low phosphate levels predominant in cases of moderate severity. Low calcium levels were more commonly seen in severe poisonings. (59)
Intestinal perforation, mesenteric venous thrombosis (clotting in the bowel veins), rhabdomyolysis (death of muscle tissue), septicemia (toxic blood infection), seizures due to cerebral edema and respiratory distress syndrome are rare complications. (60),(61) Occasional patients require a transvenous pacemaker for temporary heart block presenting as marked slowing of the heart rate. A number of fatal cases have had septicemia, an event due to the patient's poor resistance and/or the venous/arterial lines inserted.
Disseminated intravascular coagulopathy (DIC) is a rare complication of amatoxin poisoning. This is a dreaded catastrophe in which systemic clotting is inappropriately set off with small clots forming in tiny vessels, followed by depletion of clotting agents with often fatal bleeding. Although reported in amanitin poisoning, the incidence is probably very small. (62) Most of the severe cases of coagulation factor depletion can be explained not by DIC, but by liver failure with decreased liver production of these coagulating proteins. (48C),(63)
Other than death, outcomes in severe poisonings include possible brain damage and chronic active hepatitis, the latter up to 20% of survivors in one series. (56a) Most reports show a lower incidence. Persistent poor kidney function is extremely rare. (57)