STAR FRUIT INTOXICATION IN URAEMIC PATIENTS

Miguel Moyses Neto, MD

Division of Nephrology, Faculty of Medicine of Ribeirão Preto, São Paulo University (USP), Brazil

mmoyses@convex.com.br

Star fruit, an exotic seasonal fruit is believed to have originated in Ceylon and the Moluccas, but it has been cultivated in southeast Asia and Malaysia for many centuries. It belongs to the Oxalidaceae family, species averrhoa carambola

Fig 1: averrhoa carambola

It is commonly found in southern China, Taiwan , India, Philippines, Australia, Central America, Africa and Brazil in the tropical and subtropical areas. It is served as as a fresh beverage, in natura or as an industrialized juice, and used in restaurants for decorative purposes throughout the world^1,2

Martin et al³ described an outbreak of intractable hiccups in patients on a regular program of hemodialysis after ingestion of star fruit that improved only after the hemodialysis sessions. The authors did not describe any signs of neurological involvement as behavioral disturbances or mental confusion.

The hiccups had been seen as a curiosity and not as a threat till 1997. In that year, we described 2 patients under dialysis that presented with neurological disturbances after eating star fruit : one patient died with convulsions and another patient improved after a few hemodialysis sessions⁴. Both patients had intractable hiccups as their first symptoms.

In 1998⁵ we published the description of 6 cases of patients under dialysis that developed a variety of neurological symptoms after eating star fruit: insomnia, hiccups, vomiting, mental confusion, convulsions. The extract of star fruit was injected in different quantities into the cisterna magna of mice or the intracerebroventricular cavity of rats and provoked convulsions. These first observations^{3, 4, 5} also suggested that hemodialysis removed the toxic substance.

After these reports, Chang JM et al 2000⁶ described 20 patients with renal failure that presented neurological symptoms after eating star fruit. Eight patients died. The time between ingestion and onset of symptoms varied from 2,5 hours to 14 hours. The symptoms varied from hiccups, consciousness disturbances, numbness of limbs, decreased muscle power and seizures. Ten patients with abnormal levels of consciousness underwent computerized tomographic brain scans, but no organic lesion could be identified. Their report says that emergent hemodialysis was performed to those 10 cases with consciousness disturbance, but 8 patients died.

After these observations other reports of star fruit intoxication were published^{7,8,9,10,11,12,13}. In table 1 we summarize all these reports excluding our 2 first reports^{4, 5} because these patients were included in our last report¹⁴

Table 1: Reports of star fruit intoxication

Reports	Number of cases	Type of treatment Before intoxication	Symptoms	Treatment	Outcome
Martin et al, 1993 ³	08	HDI	Hiccups	HDI	All recovered
Chang JM et al, 2000 ^⁶	20	HDI: 15 Peritoneal: 4 Conservative: 1	Hiccups, Consciousness Changes, Seizure	a)No treatment: 1 b)Emergent HDI + routine HDI: 19	a) died b) 9 died
Wang JL et al, 2000^⁷	02	Conservative	Hiccups, consciousness changes,seizures	HDI	Both died
Lo KY et al, 2001 ^⁸	01	CAPD	Hiccups, insomnia	Maintained on CAPD	Recovered
Wu CC et al, 2002 ^⁹	02	Conservative	Hiccups, consciousness changes	HDI	Recovered
Yap HJ et al, 2002^¹⁰	03	HDI: 1 Conservative:1 Conservative:1	Hiccups, insomnia, consciounouss changes, seizure	a)Conservative b)HDI c)Plasma exchange	a)Recovered b)Recovered c)Died
Chang CT et al, 2002 ¹¹	01	Conservative	Hiccup, vomiting, consciousness change	HDI	Recovered
Chan YL et al, 2002 ¹²	01	Conservative	Hiccups, consciosuness changes, seizure	HDI	Died
Tse KC et al, 2003 ¹³	07	CAPD: 4 HDI: 1 Conservative: 2	Hiccup, consciousness changes, vomiting	Intensive HDI: 4 IPD: 1 Conservative: 2	All recovered
Neto MM et al, 2003 ¹⁴	32	HDI: 20 CAPD: 8 Conservative: 4	Hiccup, vomiting, consciousness changes, seizures	a)Routine + intensive HDI: 19 b)Peritoneal dialysis: 7 c)-Conservative: 6	a) recovered b) 4 died c) 3 died
Total	77				21 patients died

HDI: routine hemodialysis, CAPD: continuous ambulatory peritoneal dialysis

Our clinical findings and reports from others, have allowed us to classify the neurotoxic effects of star fruit into 3 levels of intoxication that may provide a useful guideline for institution of proper treatment (Table 2).

Table 2: Symptoms of star fruit intoxication

Level of intoxication	Symptoms and signs
Mild	Hiccups, vomiting and insomnia
Moderate	Psychomotor agitation, numbness and paresthesias of the limbs, decreased muscle power, mild mental confusion
Severe	Severe mental confusion progressing to coma, seizures progressing to status epilepticus, hemodynamic instability progressing to hypotension and shock

These symptoms can initiate from 30 minutes of ingestion (half fruit to 500 ml of juice) to a couple of hours. Although the initial symptoms may start with hiccups, some patients, with severe intoxication, come to the hospital with a clinical syndrome that resembles strokes or "metabolic" and uremic disturbances. Certain cases of mild intoxication may progress to severe symptoms and this progression is extremely variable, depending on the characteristics of each patient. Therefore, any patient with a suspected star fruit intoxication should not be discharged and should be observed very closely.

Nevertheless, mild symptoms such as hiccups may persist for several days and upon stopping treatment the hiccups may continue, with the symptoms disappearing slowly. The variations of symptoms and severity of intoxication differ among individuals and might be explained by individual biological responses, amount of toxin content in each fruit, various star fruit subspecies, age and the detoxification, excretion or both, of this toxin from the bloodstream. Rebound effects after treatment are frequently seen¹⁴

In most of our cases, attempts to treat intractable hiccups with chlorpromazine and metoclopramide, were unsuccessful. In contrast, we observed that only hemodialysis improves this symptom. In the last 2 reports^13,14 it is clear that intensive hemodialysis (daily dialysis up to 8 hours each session, depending of the severity of symptoms), removed the neurotoxicity activity in most patients with severe intoxication allowing them to recover without sequelae within 1-12 days.

In addition to causing neurotoxic symptoms as described before, star fruit has a high oxalic acid content that may cause acute reversible nephrotoxic effects^{15, 16}.

The putative excitatory neurotoxin that induces clonic tonic convulsions when injected in the intracerebroventricular space in rats or mice, may act specifically by displacing GABA specific binding in rat brain synaptic membrane (unpublished data). Although the exact nature of star fruit neurotoxicity acitivy remains obscure, oxalate had been proposed as a possible candidate¹⁷, but our data (unpublished) do not confirm this hypothesis.

Although star fruit, like other fruits, probably has a high potassium content, we did not detect any alterations in serum potassium in the patients that were measured as described by other previous reports.

Most of the patients that recovered did not show further neurological sequelae although is might be possible as demonstrated by Chan YL et al.¹²

These observations, serve to warn physicians that star fruit intoxication may be harmful end even life threatening in uremic patients either on supportive or dialytic treatment. Neurological symptoms are common presentations and hiccups and vomits are the most frequent symptoms. Hemodialysis, instituted as early as possible, especially daily and intensive dialysis, is the ideal treatment, and in severe cases continuous treatment methods may provide a superior initial procedure, since rebound effects are a common event. Peritoneal dialysis is of no use when disturbance of consciousness ensues.

References

1- Morton JF. Fruits of warm climates. Flair Books, Miami, FL, 1987:125-128.

2- Margen S. The Wellness Encyclopedia of Food and Nutrition. Health Letter Assoc. New York, NY; 1992:271-272.

3- Martin LC, Caramori JST, Barretti P, Soares VA. (In portuguese) Soluço intratável desencadeado por ingestão de carambola (averrhoa carambola) em portadores de insuficiência renal crônica. J Bras Nefrol 1993; 15:92-94

4- Moyses Neto M, Coutinho Netto J, Vannucchi MTI, Batista MEP, Raspanti EO, Vieira Neto OM. Psychomotor agitation and death after ingestion of Averrhoa carambola (star fruit) among patients with end stage renal disease submitted to dialysis.Abstracts of the XIV International Congress of Nephrology, Sidney, 1997; 3:S426.

5- Neto MM, Robl F, Netto JC. Intoxication by star fruit (averrhoa carambola) in six dialysis patients? ( Preliminary report). Nephrol Dial Transpl 1998: 13:570-572

6- Chang JM, Hwang SJ, Kuo HT, Tsai JC, Guh JY, Chen HC, Tsai JH, Lai YH. Fatal outcome after ingestion of star fruit (averrhoa carambola) in uremic patients.Am J Kidney Dis 35:189-193, 2000.

7- Wang JL, Cheng CH, Wu MJ, Chen CH, D, Shu KH. (In Chinese) Status epilepticus in two patients with chronic renal failure after ingestion of star fruit. Kidney Dialysis 2000, 8:166-169.

8- Lo KL, Tong GMW, Wong PN, Mak SK, Wong AKM. Persistent hiccup in a continuous ambulatory peritoneal dialysis patient following ingestion of star fruit. Hong Kong Journal of Nephrology. 2001; 3(1):45-46

9- Wu CW, Denq JC, Tsai WS, Lin SH. Star fruit-induced neurotoxicity in two patients with chronic renal failure. J Med Sci 2002; 22(2): 75-78

10 – Yap HJ, Chen YC, Fang JT, Huang CC. Star fruit: a neglected bu serious fruit intoxicant in chronic renal failure. Dialysis & Transplantation. 2002, 31:564

11- Chang CT, Chen YC, Fang JT, Huang CC. Star fruit (averrhoa carambola) intoxication: an important cause of consciousness disturbance in patients with renal failure. Renal failure, 2002 24:379-382

12- Chan YL, Leung CB, Yeung DKW. Phosporus and single voxel proton MR spectroscopy and diffusion-weighted imaging in a case of star fruit poisoning. Am J Neuroradiol, 2002. 23: 1557-1560

13- Tse KC, Yip PS, Lam MF, Choy BY, Li FK, Lui SL, Lo WK, Chan TM. Star fruit intoxication in uraemic patients: case series and review of the literature. Internal Medicine Journal, 2003, 33:314-316

14- Neto MM, Costa JAC, Garcia –Cairasco N, Netto JC, Nakagawa B, Dantas M. Intoxication by star fruit (averrhoa carambola) in 32 uraemic patients: treatment and outcome. Nephrol Dial Transpl , 2003, 18: 120-125

15- Chen CL, Fang HC, Chou KJ, Wang JS, Chung HM. Acute nephropathy after ingestion of star fruit. Am J Kidney Dis. 2001, 37:418-422

16- Fang HC, Chen CL, Wang JS, Chou KJ, Chiou YS, Lee PT, Yeh MY, Chung HM. Acute oxalate nephropathy induced by star fruit in rats. Am J Kidney Dis 2001: 38:876-880

17- Chen CL, Chou KJ, Wang JS, Yeh JS, Fang HC, Chung HM. Neurotoxic effects of carambola in rats: the role of oxalate. J Formos Med Assoc 2002, 101: 337-341.