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SCOMBROID POISONING: MINI-REVIEW WITH CASE HISTORIES FiNDLAY E . RUSSELL I Snd ZVONIMIR MARETICZ 'College of Pharmacy, University of Arizona, Tucson, Arizona 85721, U .S .A., and fi9edical Center, Pule 52000, Yugoslavia (Accepted jor publication 17 June 1986) F. E . RusseLL and Z . MAteenC. Scombroid poisoning : mini-review with case histories . Toxicon 24, %7 - 973, 1986 - Scombroid poisoning has become an almost world-wide medical problem . It is probably the most common cause of fish poisoning, ahhough frequently misdisgaoaed as 'Salmonella infection' . while there remains some question as to the definitive etiology, there is little doubt that the poisoning is caused by the Ingestion of certain mackerel-like fishes whose tissues have undergone a number of chaaga provoked by bacteria, and involving the conversion of hiatidine to histamine, potmtiated by diaminea . Improper storage of the fishes, usually at temperatures above 20°C, appear to be the moat important predisposing factor . The organisms moat commonly involved are Proteus sp., Clostrldlum ap., Fsrluxlchla sp., Salmonella sp . and Shlgella sp . Twenty-five canes of scombroid poisoning are pnsentod. The clinical maaifestatlons wen very similar in moat cases, oonaistia8 of : alterations is taste ; anxiety: hyperemia, particularly of the face and neck; nausea ; pruritis ; headache; certain other symptoms and sigrla . Most patients responded to antihi ARIltica~ and all cases wen self-limiting .
poisoning is a form of ichthyotoxism or ichthyosarcotoxism (HALSTEAD, 1%~, caused by spoiled fish that have undergone a number of tissue changes provoked, for the greater part, by bacteria. Most cases of poisoning are attributed to the eating of the mackerel-like fishes : the hulas, albacores, bonitos and mackerel (RUSSELL, 1965; HALSTEAD, 1%7) . The species most often implicated in scombroid poisoning are shown in Table 1 . The improper storing of these fish, usually at temperatures above 20°C, appears to be the most important predisposing factor . In the presence of certain bacteria, particularly Proteus morganü and P. vulgaris, but also with Clostridium, Escherichia, Salmonella and Shigella, the affected tissues undergo changes, perhaps the conversion of histidine to histamine, potentiated by diamines. The tissues of scombroid fishes usually contain a high level of histamine and many workers have implicated histamine as the sole agent in scombroid poisoning. In addition, the similarity between the clinical picture of histamine poisoning and scombroid poisoning, and the value of antibi s, minCg III the treatment of both, further implicate histamine as a causative agent. However, the studies by GEIGER (1955) and ICAWABATA (1962) and the data supplied in the review by ARNOLD and BROWN (1978) indicate that histamine, acting alone, cannot be the sole responsible agent. Among other things, large amounts of histamine phosphate or histamine dihydrochloride, much larger than those found in soombroid fishes, do not elicit the scombroid syndrome . Neither does the eating of fresh tuna `spiked' with histamine (ARNOLD and BROWN, 1978). There is a relationship, however, between fish spoilage, histamine levels and scombroid poisoning. Histamine levels in excess of 100 mg SCOMBROID
F . E . RUSSELL and Z MARETIC TABLE I . SOIS FISHFS RESPONSIBLE tbR SCOMHROID POISONING
Arripidae Arripis trotta
Coryphaenidae Coryphanla hippurus (Lt^saM ,s)
Cupeidae Amblygaster sire (Walbaum)
Scombereaocidae Cololabis Boira (Brevoort)
Scombridae Auxis thazard (Lacepede) Euthynrrus alJttteratur (Rafineaque) E. pelamis (I-innaeus) Sarda sivda (Bloch) Scomba japonicas (Houttuyn) S . srombrus Linneaua Scomberomorvs cavalla (Couler) S. maculates (Mitchill) S. rrgalis (Bloch) 771wmus olaherega (Bonnalerte) T. abbacarrs (BonDaterre) T. obesas (Lowe) T. thynrtes (I,lnnnrc)
frigau mackerel black akipjack skipjack bonito Pacific mackerel Atlantic mackerel king mackerel Spanish mackerel Cero albacore yellowfin tuna bigeye tuna bluefm tuna
Xiphüdae Makair audax (Poey) Xiphias gladles (Linneaua)
striped marlin awordfuh
free base per 100 g of fish are frequently seen in clinical cases of scombroid poisoning, and this level is often considered the critical concentration for histamine poisoning ($IMIDU and HIBIxI, 1955) . Yet scombroid poisoning has occurred when histamine levels were only in excess of 20 mg/100 g (CiILBERT et al., 1980) and doses above 400 mg have been consumod without producing a scombroid-like poisoning (WEIS.S, et al ., 1932) . The unofficial maximum allowable commercial levels for histamine in fish tissues in the United States is 10 mg/100 g. Nevertheless, histamine level is considered a good index of fish deterioration and scombroid poisoning. In answering the question whether scombroid toxicity is due to histamine, ARNOLD and BROWN (1978) state "In our considered judgement, the answer to this question is no. . .This is not to say . . .that histamine is not involved . . . histamine may be caused to be released by a variety of factors . . .histamine itself is not toxic when taken orally . . .it is evident that there must be synergistic or potentiating substances or conditions involved ." This statement sums up current thinking on the etiology of scombroid poisoning. With respect to the `holding' of potential scombroid fishes by fishermen and the relationship of such holding to scombroid poisoning, several thoughts should be noted. Fishermen generally set aside the choicest of their fishes for the `fresh fish' market . In most cases these tend to be the larger fishes and rarely are they stored for more than two or three days, never for more than four . Often they are the first fish to go into the hatch or hold and thus they are cooled more rapidly, sometimes in brine to 0°C; in the case of tuna or albacore the chilling usually requires approximately 12 hr. No salt is added to the fresh
fish catch, but fish intended for canning are salted and then frown and kept frozen until processed. in most of the scombroid cases in which reliable histories have been obtained by the authors, one or two factors seem to have been involved . Firstly, the period between catch and cooling to 0°C, or thereabouts, was prolonged, i.e. 12 or more hours; secondly, a temperature of less than 20°C was never reached. In reviewing the data in more than SO of the author's cases it became apparent that, some of the fishes in a particular catch were associated with one or both of these factors yet were not affected by these circumstances, or at least they did not cause poisoning. Some authors use the terms `red meat' and `white meat' when describing fish muscle, and perhaps a word of caution is indicated. These terms are generally directed at the predominant muscle color: cod and halibut are white meat fishes, while mackerel, tuna and albacore are red meat fishes . All scombroid fishes, however, contain both muscle color types. Some white fish have been involved in scombroid poisoning. In the commercial processing of tuna white muscle is usually used, the red being set aside primarily for pet food (ARNOLD and BROWN, 1978). SIMIDU and HIBIIQ (1954) found that by far the largest amounts of histamine in a specific toxic fish would be found in the red meat. The randomness of histamine levels in the flesh of a single spoiled fish probably accounts for the fact that a number of people may eat of the same toxic fish and not all of them will be poisoned (LERN et al., 1978). Storing, freezing, cooking, autoclaving, canning and smoking do not apprxiably lessen the likelihood of poisoning. CHEMISTRY AND PHARMACOLOGY
There are no specific assays for scombroid toxin, although there are a number of tests for histamine. In the past the most commonly employed assay has been the guinea pig ileum preparation (BARSOUM and GADDUM, 1935). This was first applied to histamine studies in fish tissues by ßEIGER (1944) . On the basis of a guinea pig ileum study and twodimensional chromatography, a compound was found that was suspected of acting synergistically with, or in addition to, histamine in foods causing histamine poisoning (KAWAIiATA et al., 1955a) . It was subsequently called `saurine', in reference to the fish Cololabis saira (saury), which had frequently been implicated in histamine poisoning in Japan (KAWABATA et al., 19SSb) . OLCOTT and LUKTON (1%1) demonstrated that saurine and histamine were probably the same . In spite of this finding, which unfortunately was not read by many investigators (being in a journal not readily available), saurine has continued to be discussed separately in the literature . The various bioassays and chemical techniques up until 1956 have been summarized by CODE and MCINTIRE (1956) . DE WAHRT et al. (1972) studied 32 bioassays and found that the freshwater crustacean Daphnia was particularly sensitive to histamine. This discovery led to the work of Blonz (BLONZ and OLCOTT, 1978), who found that extracts of toxic tuna tissues added to fresh water caused 90-100% deaths in Daphnia, as compared to 0-4% with extracts of fresh tuna. This appears to be an easy, rapid and reliable laboratory bioassay test. Unfortunately, however, bioassays do not make good field tests and even in the laboratory there are a number of inherent difficulties . Thug more recent studies have turned to various chemical techniques for the identification and quantitation of histamine. One of these has been the simple fluorometric method proposed by SHORE et al. (1959), who also reviewed the tissue histamine problem (SHORE, 1971). Chemical aSSays have been prOpOSed by UDENFRIEND et al. (1972), SCHWARTZMAN (1973),
F . E . RUSSELL and Z MARETIC` TABLE
SYMPTOMS AND SIGNS IN A SERIES OF SCOMBAOID POISONINGS
Symptom or aigu Unusual taste (sharp, hot, peppery, metallic or irritating) Anxitty or apprehension Hyperemia of face snd neck with burning sensation or discomfort Hyperemia of other parts of body Nausea Pruritia, particularly scalp Headache, bitempolar or frontal Diarrhea Tachycardia Thirst Weakness Abdominal cramps Swelling of the lips and/or tongue Vomiting Dimness Urticaria Flatus Burning of the throat Vomiting (induced)
Number of cases
17/17 17/17 16/ 17 11/17 14/17 13/17 10/16 10/17 9/15 9/15 7/16 7/17 4/17 9/17 4/ 17 4/17 3/17 3/17 2/17
5-20 10-40 7 -10 10-60 20-120 15-90 10-120 40-240 10-40 15-120 60-120 30-120 45-120 20-120 43 - 60 60-300 120-420 10-60 45 - 60
HAKANSON and BONNBERG (1974), YAMADA and WAKABAYASHI (1974), NAVERT (1975), HERDWITZ (1975), STARUSZKIEWICZ et ßl. (1975), LERKE and BELL (1976), SCHUTZ et al. (197, LIN et al. (1977) and ARNOLD et al. (1980) . CASE REPORTS
In the fall of 1980, 35 of 1100 people attending a fish fry on Catalina Island, California, were poisoned when they ate portions of 11 marlin, Markair audax. The fishes had been caught 1- 3 days previously, gutted and cleaned the same day and then either kept in the cold or at 0-10°C in brine until the time of the fry. It is not known which of the fishes were responsible for the poisoning or how many were involved, for the 11 marlin had been cut and divided into 27 buckets the morning of the fish fry. Only one person, a dock-hand working on the pier at weigh-in, later thought he remembered one swordfish that was not quite right; it was a little "unusual" and had a slightly pungent smell, but "not like spoiled fish." Other than this single observation, no one noted any problems with the fish . The symptoms and signs of poisoning in 17 victims interviewed by the senior author are summarized in Table 2. It was not possible to obtain histories from the remaining 18 victims. No muscle pain or cramps, other than abdominal, were reported by these patients, nor was there any hypotension, disorientation or changes in body temperature. Unfortunately, no samples of the offending fish were obtained for laboratory study. On 11 August 1981 tourists from three families purchased several fresh mackerel, Scomberjaponicas, in the fish market at Pula, Istria, Yugoslavia, at approximately 0700 hr. The fish had not been gutted . Having no facilities for refrigeration, the fish were placed in a net and submerged in the sea at a temperature of 23-24°C, where they remained unti12000 hr . They were then gutted, grilled and eaten, each person consuming approximately 250 g of fish. Eight of the victims reported that the fish tasted good, but two complained that they noted a "strange peppery taste" to the fish . Within 10 min of eating the fish six, of the
victims complained of numbness about the mouth and over the tongue, described by some as a burning sensation. These individuals also complained of dryness in the mouth. However, two of the patients did not develop significant symptoms until 1- 2 hr later. Four of the victims complained of headache, weakness, dizziness and epigastric cramps, while three victims complained of nausea . On admission, swelling of the lips and tongue were observed in most patients and were most marked in a boy aged 8, whose lower lip was markedly edematous and his cheeks flushed and swollen. He also had hemorrhages on the palatal arches . This child had a previous history of bronchial asthma . He was somnolent, voided frequently and without control and had reportedly suffered respiratory collapse on the way to the hospital, requiring mouth-to-mouth resuscitation . Vomiting occurred in four patients and watery stools in two. The epigastrium was sensitive to pressure in four patients. In one patient there was gastric distension, hyperemia was observed and the patient complained of a burning sensation . Conjunctivitis was observed in all patients . In four patients mydriasis was present and the pupillary reaction was decreased . Mild hypertension was found in four patients. One patient complained of palpitations . Four patients showed mild diffuse dysrhythmias in their electroencephalograms, while in the other four there were no changes. All eight patients received gastric lavage and the stomach washings and the remainders of the fish were subjected to bacteriological and biochemical studies. Analysis by thinlayer chromatography revealed excessive amounts of histamine (500 mg/100 g meat). Bacterial examination revealed Enterobacter aeogenes, Escherichia coli, Klebsiella sp. and others . DISCUSSION
The first group of cases was the third series in Southern California known to the author and not previously reported . An incident of four cases occurred at Balboa, California, in 1952, following the eating of some improperly refrigerated albacore, Thunnus germs. The patients were seen by Dr George MacGinitie and the senior author and were treated with antihistamines at the Kerckhoff Marine Laboratory at Corona del Mar, California. A further incident involving two males was reported to the author in 1965 by Dr Mark Steele, who gave the patients intramuscular diphenhydramine hydrocholoride . All of these patients were seen two days after the poisoning and were completely asymptomatic . The onset of symptoms and signs of scombroid poisoning often occurs within S min of the eating of the offending fish. They include a sharp or peppery taste, hyperemia, particularly of the head and neck, burning of the throat, headache, tachycardia, weakness, pruritis, abdominal pain, nausea, vomiting, diarrhea, dizziness and, in some cases, severe respiratory distress and shock. We have observed, principally in the Catalina Island cases, a relationship between the severity of the clinical manifestations and the consumption of alcohol. This has been documented by LEItt~ et al. (1978) . Most cases of scombroid poisoning respond to antihistamines, the author employing relatively large doses of the H2 antagonist cryproheptadine hydrochloride parenterally in acute poisonings . Successful treatment with cimetidine has also . been reported (BLAICFSLEY, 1983). Fortunately, scombroid poisoning is a self-limiting disease. Although it has been known since 1799 (HALSTEAD, 1 %7), not until the fme review by Halstead did its medical significance become apparent . Since that compendium, numerous reports on scombroid poisoning have been published in the medical literature . Although some
F. E. RUSSELL and Z MARETIC
reports appear to imply that this is a new and increasingly frequent entity, Halstead (personal correspondence, 1985) and we both believe that these reports reflect a more general awareness of the disease by physicians . Nevertheless, it has bocome apparent that scombroid poisoning occurs on an almost world-wide basis and is perhaps thé most common cause of fish poisoning . In most patients, probably because the poisoning is rarely incapacitating, it is seldom considered for what it is, or is generally thought to be nothing more than `food poisoning' due to Salmonella. REFERENCES ARNOLD, S. H. and BROWN, W. D. (1978) Histamine(?) toxicity from fish products. In : AdvancYS in Food Research, Vol . 24, p . 113 . London : Academic Press. ARNOLD, S. H., PRtcE, R. J. and BROWN, W. D. (1980) Histamine formation by bacteria isolated from skipjack tuna, Katsuwonus pelamis. Bull, Jpn. Soc. crient. Fishh. 46, 991,995 . BARSOUM, G. S. and GADLKIM, J. H. (1935) The pharmacological estimation of adenosine and histamine in blood. J. PhysioL, Lond. 8S, 1 . Bt.wt~sLex, M. L. (1983) Scombroid poisoning: prompt resolution of symptoms with cimetidine. Ann . Emerg.
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