| Abstract|| |
Piperazine as an antihelminth has many adverse effects, especially on patients with renal insufficiency. We report the use of piperazine in a girl with a moderately severe kidney disease due to Biedl Bardet syndrome. She developed coma and acute kidney injury due to acute interstitial nephritis (AIN), anemia and thrombocytopenia. The presence of fever, proteinuria, acidosis, anemia, sterile pyuria and non-oliguric renal failure strongly suggested AIN. Her problems abated mostly by discontinuing of piperazine and supportive therapy, except anemia and thrombocytopenia.
|How to cite this article:|
Malaki M. Piperazine side-effects in a patient with pre-existing renal insufficiency. Saudi J Kidney Dis Transpl 2014;25:390-3
|How to cite this URL:|
Malaki M. Piperazine side-effects in a patient with pre-existing renal insufficiency. Saudi J Kidney Dis Transpl [serial online] 2014 [cited 2020 Jun 5];25:390-3. Available from: http://www.sjkdt.org/text.asp?2014/25/2/390/128573
| Introduction|| |
Piperazine has been used to treat pinworm and roundworm infections for over 40 years. However, it may induce cerebellar ataxia, dropping of objects, clumsiness and gait abnormalities in the setting of overdose or renal insufficiency.  In pediatric patients, the usual oral dose ranges from 65 to 75 mg/kg/day (max: 3.5 g/day as a single dose). Piperazin in less than 1% of patients may be associated with adverse reactions, including cause bronchospasm, diarrhea, dizziness, EEG changes, headache, hemolytic anemia, hypersensitivity reactions, nausea, seizure, vertigo, visual impairment, vomiting and generalized weakness. 
Biedl Bardet syndrome (BBS) is an autosomal recessive disorder that presents as obesity, polydactyli, mental retardation, retinal dystrophy, hypogonadism and renal abnormalities due to cystic dysplasia. 
In this report, we describe a BBS patient who used piperazine for two days. The patient developed, afterwards, neurological, renal and hematological side-effects.
| Case Report|| |
An 8-year-old girl diagnosed as BBS because of polydactyli (six toes in her feet), obesity (body mass index: 30, which is above the 97% percentile for her age), mental retardation and renal insufficiency [Figure 1] and [Figure 2]. She presented to the emergency room in coma that developed in the morning after waking up and progressed during day. She received piperazin hydrate for two days in a total dose of 150 mg/ kg (75 mg/kg/d × 2).
|Figure 1: A girl affected by BBS - obesity and polydactyli in both feet.|
Click here to view
|Figure 2: A girl affected by BBS - obesity and polydactyli in both feet.|
Click here to view
Initially, her laboratory findings revealed blood urea nitrogen (BUN) of 90 mmol/L and creatinine 3.9 mg/dL. She was mildly anemic and acidotic [Table 1]. Her clinical condition worsened on the third day and her temperature fluctuated between 37.9 and 40°C, but without oliguria or dehydration. She suffered from respiratory distress. Her blood pressure was normal. On physical examination, her Glasgow coma scale (GCS) was 7 and she had involuntary jerking movements in her legs, arms and trunks accentuated by sensory triggers.
|Table 1: Physical and laboratory findings on the first, third and tenth days after admission.|
Click here to view
The patient's chest radiograph was normal, but her blood BUN and creatinine increased and urinalysis revealed sterile pyuria besides negative blood/urine culture, and all suggested acute interstitial nephritis (AIN).
In renal ultrasound, the patient had severely atrophic bilateral kidneys (long axis: 55 mm) and increased echogenicity with undifferentiated corticomedullay boundaries, but without evidence for ascites or volume overload.
We started Methylprednisolone pulse 10 mg/kg for two days, followed by prednisone 1 mg/kg/ daily for two weeks. Her clinical and laboratory conditions resolved dramatically [Table 1]. She had a significant proteinuria at first (urine protein/urine creatinine: 3 mg/g normal <0.5); after one month of therapy for AIN, it decreased to normal.
During the first three days she was febrile and, in spite of her body fluids being sterile, there was no leukocytosis or serum-reactive proteins like C-reactive protein in her serum. After three days of supportive therapy, she opened her eyes for a moment and then her alertness recovered, but she could not sit or stand as she had intentional tremor and slurred speech. After one week, she could sit and then walked with help, while after two weeks she left the hospital in a good condition.
| Discussion|| |
BBS is characterized by obesity, polydactyli, mental retardation, retinal dystrophy, hypogonadism and some grades of renal abnormalities, typically cystic renal dysplasia.  Our case had similar signs and symptoms including obesity, polydactyli, mental retardation, retinal degeneration, nystagmus and chronic kidney disease presenting Piperazine, an antihelminthic drug, used widely for the treatment of ascaris and thread-worm infestations. Brown et al  described neurotoxic symptoms following piperazin as transient neurological disturbance, characterized by vertigo, tremor, incoordination, visual and memory disturbances, sense of detachment and muscular weakness due to overdosage and retention of piperazine in the patients with poor renal function.  Other adverse effects were reported for piperazine in normal people such as hypersensitivity and urticaria in a child who developed hemolytic anemia after two days of use of piperazine,  severe thrombocytopenia that developed in a 61-year-old man due to sensitization,  a reaction resembling viral hepatitis that occurred in a 25-year-old woman  and serum sickness in another patient.  Our patient was categorized as stage 4 of chronic kidney disease (CKD) with a measured GFR of 25 mL/min/1.73 m 2 . She received piperazine of 75 mg/kg/d for two days, her signs and symptoms appeared on the third day and were compatible with AIN. She also revealed hypochromic microcytic anemia, mild thrombocytopenia, moderate acidosis, respiratory distress, deep coma, mycolonic jerks, hypersensitivity to sensory stimulation, tremor, incoordination, scanned speech, delusion and muscle weakness. Her acidosis appeared and resolved sooner and her fever abated in one week and proteinuria after one month, but her anemia and thrombocytopenia persisted and mild eosinophilia appeared (600 cells/mm 3 ) in the second week.
Piperazine in a total dose 150 mg/kg after two days caused encephalopathy, respiratory distress, metabolic acidosis and acute kidney injury (AKI) imposed on CKD. All the side-effects were transient, but the hematological adverse effects (anemia, non-hemolytic thrombocytopenia and eosinophilia) persisted.
Conflict of interest: None
| References|| |
|1.||Conners GP. Piperazine neurotoxicity: Worm wobble revisited. J Emerg Med 1995;13:341-3. |
|2.||Drugs for Parasitic Infections," Med Lett Drugs Ther 1993;35:111-22. |
|3.||Green JS, Parfrey PS, Harnett JD, et al. The cardinal manifestations of Bardet-Biedl syndrome, a form of Laurence-Moon-Biedl syndrome. N Engl J Med 1989;321:1002-9. |
|4.||Brown HW, Chan KF, Hussey KL. Treatment of enterobiosis and ascariasis with piperazine. JAMA 1956;161:515-20. |
|5.||Miller CG, Carpenter R. Neurotoxic side-effects of piperazine. Lancet 1967;1:895-6. |
|6.||Buchanan N, Cassel R, Jenkins T. G-6-PD deficiency and pipeazine. Br Med J 1971;2:110. |
|7.||Cork MJ, Cooke NJ, Mellor E. Pruritus ani, piperazine, and thrombocytopenia. BMJ 1990; 301:1398. |
|8.||Hamlyn AN, Morris JS, Sarkany I, Sherlock S. Piperazine hepatitis. Gasteroenterology 1976; 70:1144-7. |
|9.||Balzan M, Cocciottolo JM. Hypersensitivity vasculitis associated with piperazine therapy. Br JDeramatol 1994;131:133-4. |
Department of Pediatric Nephrology, Pediatric Health Research Center, Post Code 5136735886, Tabriz
[Figure 1], [Figure 2]