STAR FRUIT INTOXICATION IN URAEMIC PATIENTS

Discussion = Board=20

Paneles de Discussi=F3n=20

Paneais de Discussio

Free=20 Papers=20

Comunicaciones libres=20

Comunica=E7oes livres=20

Home=20 cin2003=20

Volver = al Inicio=20 cin2003=20

Voltar = ao inicio=20 cin2003=20

STAR FRUIT INTOXICATION IN URAEMIC PATIENTS

Miguel Moyses Neto, MD

Division of Nephrology, Faculty of Medicine of Ribeir=E3o = Preto, S=E3o=20 Paulo University (USP), Brazil

mmoyses@convex.com.br

Star fruit, an exotic seasonal fruit is = believed to have=20 originated in Ceylon and the Moluccas, but it has been cultivated = in=20 southeast Asia and Malaysia for many centuries. It belongs to the=20 Oxalidaceae family, species averrhoa carambola

Fig 1: averrhoa = carambola=20

It is commonly found in southern China, Taiwan = , India,=20 Philippines, Australia, Central America, Africa and Brazil in the = tropical=20 and subtropical areas. It is served as as a fresh beverage, in=20 natura or as an industrialized juice, and used in restaurants = for=20 decorative purposes throughout the world^1,2

Martin et al³ described an outbreak = of=20 intractable hiccups in patients on a regular program of = hemodialysis after=20 ingestion of star fruit that improved only after the hemodialysis=20 sessions. The authors did not describe any signs of neurological=20 involvement as behavioral disturbances or mental confusion.

The hiccups had been seen as a curiosity and = not as a=20 threat till 1997. In that year, we described 2 patients under = dialysis=20 that presented with neurological disturbances after eating star = fruit :=20 one patient died with convulsions and another patient improved = after a few=20 hemodialysis sessions⁴. Both patients had intractable = hiccups=20 as their first symptoms.

In 1998⁵ we published the = description of 6=20 cases of patients under dialysis that developed a variety of = neurological=20 symptoms after eating star fruit: insomnia, hiccups, vomiting, = mental=20 confusion, convulsions. The extract of star fruit was injected in=20 different quantities into the cisterna magna of mice or the=20 intracerebroventricular cavity of rats and provoked convulsions. = These=20 first observations^{3, 4, 5} also suggested that = hemodialysis=20 removed the toxic substance.

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

After these observations other reports of star = fruit=20 intoxication were published^{7,8,9,10,11,12,13}. In table = 1 we=20 summarize all these reports excluding our 2 first reports^{4, =
5}=20 because these patients were included in our last = report¹⁴

Table 1: Reports of star = fruit=20 intoxication

Reports	Number of cases	Type of treatment Before intoxication	Symptoms	Treatment	Outcome
Martin et al, 1993=20 ³	08	HDI	Hiccups	HDI	All recovered
Chang JM et al, 2000=20 ^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^{=20 ⁷}	02	Conservative	Hiccups, consciousness=20 changes,seizures	HDI	Both died
Lo KY et al, 2001=20 ^⁸	01	CAPD	Hiccups, insomnia	Maintained on CAPD	Recovered
Wu CC et al, 2002=20 ^⁹	02	Conservative	Hiccups, consciousness = changes	HDI	Recovered
Yap HJ et al, 2002^{=20 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=20 ¹¹	01	Conservative	Hiccup, vomiting, consciousness=20 change	HDI	Recovered
Chan YL et al, 2002=20 ¹²	01	Conservative	Hiccups, consciosuness changes,=20 seizure	HDI	Died
Tse KC et al, 2003=20 ¹³	07	CAPD: 4 HDI: 1 Conservative: 2	Hiccup, consciousness changes,=20 vomiting	Intensive HDI: 4 IPD: 1 Conservative: 2	All recovered
Neto MM et al, 2003=20 ¹⁴	32	HDI: 20 CAPD: 8 Conservative: 4	Hiccup, vomiting, consciousness changes,=20 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=20 died

HDI: routine hemodialysis, CAPD: continuous = ambulatory=20 peritoneal dialysis

Our clinical findings and reports from others, = have=20 allowed us to classify the neurotoxic effects of star fruit into 3 = levels=20 of intoxication that may provide a useful guideline for = institution of=20 proper treatment (Table 2).

Table 2: = Symptoms of star=20 fruit intoxication

Level of=20 intoxication	Symptoms and signs
Mild	Hiccups, vomiting and insomnia
Moderate	Psychomotor agitation, numbness and paresthesias of the = limbs,=20 decreased muscle power, mild mental = confusion
Severe	Severe mental confusion progressing to coma, seizures = progressing=20 to status epilepticus, hemodynamic instability = progressing to=20 hypotension and = shock

These symptoms can initiate from 30 minutes of = ingestion=20 (half fruit to 500 ml of juice) to a couple of hours. Although the = initial=20 symptoms may start with hiccups, some patients, with severe = intoxication,=20 come to the hospital with a clinical syndrome that resembles = strokes or=20 "metabolic" and uremic disturbances. Certain cases of mild = intoxication=20 may progress to severe symptoms and this progression is extremely=20 variable, depending on the characteristics of each patient. = Therefore, any=20 patient with a suspected star fruit intoxication should not be = discharged=20 and should be observed very closely.

Nevertheless, mild symptoms such as hiccups may = persist=20 for several days and upon stopping treatment the hiccups may = continue,=20 with the symptoms disappearing slowly. The variations of symptoms = and=20 severity of intoxication differ among individuals and might be = explained=20 by individual biological responses, amount of toxin content in = each fruit,=20 various star fruit subspecies, age and the detoxification, = excretion or=20 both, of this toxin from the bloodstream. Rebound effects after = treatment=20 are frequently seen¹⁴

In most of our cases, attempts to treat = intractable=20 hiccups with chlorpromazine and metoclopramide, were unsuccessful. = In=20 contrast, we observed that only hemodialysis improves this = symptom. In the=20 last 2 reports^13,14 it is clear that intensive = hemodialysis=20 (daily dialysis up to 8 hours each session, depending of the = severity of=20 symptoms), removed the neurotoxicity activity in most patients = with severe=20 intoxication allowing them to recover without sequelae within 1-12 = days.=20

In addition to causing neurotoxic symptoms as = described=20 before, star fruit has a high oxalic acid content that may cause = acute=20 reversible nephrotoxic effects^{15, 16}.

The putative excitatory neurotoxin that induces = clonic=20 tonic convulsions when injected in the intracerebroventricular = space in=20 rats or mice, may act specifically by displacing GABA specific = binding in=20 rat brain synaptic membrane (unpublished data). Although the exact = nature=20 of star fruit neurotoxicity acitivy remains obscure, oxalate had = been=20 proposed as a possible candidate¹⁷, but our data = (unpublished)=20 do not confirm this hypothesis.

Although star fruit, like other fruits, = probably has a=20 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=20 neurological sequelae although is might be possible as = demonstrated by=20 Chan YL et al.¹²

These observations, serve to warn physicians = that star=20 fruit intoxication may be harmful end even life threatening in = uremic=20 patients either on supportive or dialytic treatment. Neurological = symptoms=20 are common presentations and hiccups and vomits are the most = frequent=20 symptoms. Hemodialysis, instituted as early as possible, = especially daily=20 and intensive dialysis, is the ideal treatment, and in severe = cases=20 continuous treatment methods may provide a superior initial = procedure,=20 since rebound effects are a common event. Peritoneal dialysis is = of no use=20 when disturbance of consciousness ensues.

References

1- Morton JF. Fruits of warm climates. = Flair=20 Books, Miami, FL, 1987:125-128.

2- Margen S. The Wellness Encyclopedia of = Food and=20 Nutrition. Health Letter Assoc. New York, NY; = 1992:271-272.

3- Martin LC, Caramori JST, Barretti P, Soares = VA. (In=20 portuguese) Solu=E7o intrat=E1vel desencadeado por ingest=E3o de = carambola=20 (averrhoa carambola) em portadores de insufici=EAncia renal = cr=F4nica.=20 J Bras Nefrol 1993; 15:92-94

4- Moyses Neto M, Coutinho Netto J, Vannucchi = MTI,=20 Batista MEP, Raspanti EO, Vieira Neto OM. Psychomotor agitation = and death=20 after ingestion of Averrhoa carambola (star fruit) among = patients=20 with end stage renal disease submitted to dialysis.Abstracts of = the XIV=20 International Congress of Nephrology, Sidney, 1997; = 3:S426.

5- Neto MM, Robl F, Netto JC. Intoxication by = star fruit=20 (averrhoa carambola) in six dialysis patients? ( = Preliminary=20 report). Nephrol Dial Transpl 1998: 13:570-572

6- Chang JM, Hwang SJ, Kuo HT, Tsai JC, Guh JY, = Chen HC,=20 Tsai JH, Lai YH. Fatal outcome after ingestion of star fruit = (averrhoa=20 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=20 Chinese) Status epilepticus in two patients with chronic = renal=20 failure after ingestion of star fruit. Kidney Dialysis 2000,=20 8:166-169.

8- Lo KL, Tong GMW, Wong PN, Mak SK, Wong AKM. = Persistent=20 hiccup in a continuous ambulatory peritoneal dialysis patient = following=20 ingestion of star fruit. Hong Kong Journal of Nephrology. 2001;=20 3(1):45-46

9- Wu CW, Denq JC, Tsai WS, Lin SH. Star = fruit-induced=20 neurotoxicity in two patients with chronic renal failure. J Med = Sci 2002;=20 22(2): 75-78

10 =96 Yap HJ, Chen YC, Fang JT, Huang CC. Star = fruit: a=20 neglected bu serious fruit intoxicant in chronic renal failure. = Dialysis=20 & Transplantation. 2002, 31:564

11- Chang CT, Chen YC, Fang JT, Huang CC. Star = fruit=20 (averrhoa carambola) intoxication: an important cause of=20 consciousness disturbance in patients with renal failure. Renal = failure,=20 2002 24:379-382

12- Chan YL, Leung CB, Yeung DKW. Phosporus and = single=20 voxel proton MR spectroscopy and diffusion-weighted imaging in a = case of=20 star fruit poisoning. Am J Neuroradiol, 2002. 23: 1557-1560

13- Tse KC, Yip PS, Lam MF, Choy BY, Li FK, Lui = SL, Lo=20 WK, Chan TM. Star fruit intoxication in uraemic patients: case = series and=20 review of the literature. Internal Medicine Journal, 2003, = 33:314-316

14- Neto MM, Costa JAC, Garcia =96Cairasco N, = Netto JC,=20 Nakagawa B, Dantas M. Intoxication by star fruit (averrhoa=20 carambola) in 32 uraemic patients: treatment and outcome. = Nephrol Dial=20 Transpl , 2003, 18: 120-125

15- Chen CL, Fang HC, Chou KJ, Wang JS, Chung = HM. Acute=20 nephropathy after ingestion of star fruit. Am J Kidney Dis. 2001,=20 37:418-422

16- Fang HC, Chen CL, Wang JS, Chou KJ, Chiou = YS, Lee PT,=20 Yeh MY, Chung HM. Acute oxalate nephropathy induced by star fruit = in rats.=20 Am J Kidney Dis 2001: 38:876-880

17- Chen CL, Chou KJ, Wang JS, Yeh JS, Fang HC, = Chung HM.=20 Neurotoxic effects of carambola in rats: the role of oxalate. J = Formos Med=20 Assoc 2002, 101: 337-341.