Case Report

Nephritic syndrome following multiple bee stings: a late hypersensitivity reaction Shankha Subhra Nag1, Nilanjan Ghosh1, Arvind Kumar Singh1, Kaustav Nayek1, Piyali Mitra2 Departments of 1Paediatrics and 2Pathology, Burdwan Medical College and Hospital, West Bengal, India Most hypersensitivity reactions to insect stings are immediate, ranging from transient local reactions of little medical consequence to fatal anaphylaxis. Rarely, some patients have delayed reactions after a period of apparent normality which manifest as systemic features which can be life-threatening. A 3-year-old boy was attacked by a swarm of bees, estimated to be about 200 in number. There was an immediate cutaneous reaction which was treated at a local hospital. After 9 days, he presented with oliguria, dark-coloured urine, pedal oedema, hypertension and acute kidney injury (AKI). He was managed conservatively with fluid restriction, control of blood pressure and peritoneal dialysis, and renal function returned to normal gradually over the following 9 days. The delayed-onset AKI and other laboratory abnormalities suggested a immunemediated type III hypersensitivity reaction leading to renal insufficiency. After improvement of initial hypersensitivity reactions, patients with bee stings should be followed up in order to detect any late-onset complications which might be life-threatening. Keywords: Bee sting, Nephritic syndrome, Acute kidney injury, Late hypersensitivity

Introduction

Case Report

Honey bees are medically important insects belonging to the genus Hymenoptera. When stinging, they deposit the barbed sting with venom sac attached, which is what distinguishes honey bees from other bees. The muscles in the sting apparatus continue to pulsate even after the honey bee has flown away, driving the sting deeper into the skin and injecting more venom. The usual manifestation of bee sting in a non-allergic individual is mild local reaction. Systemic manifestations are rare and range from constitutional symptoms to dysfunction of various organs. Renal involvement has been documented mostly as a nephritic presentation while a few developed a nephrotic syndrome. Anaphylaxis, acute pigmentary tubulopathy secondary to haemolysis or rhabdomyolysis and direct toxin-related acute kidney injury (AKI) developing almost immediately are the most common renal manifestations.1–3 Sometimes, AKI may occur as part of a late (type III) hypersensitivity reaction to bee venom. A 3-year-old boy is reported who developed late-onset AKI following multiple bee stings but recovered completely with conservative management.

A 3-year-old boy was stung by a swarm of approximately 200 bees. Immediately he developed severe local reaction with swelling, redness, itching and pain, mostly over the chest and back. He was treated at a primary health-care facility with local cold compresses, oral promethazine and intravenous hydrocortisone. His symptoms subsided the next day and he was discharged, but 8 days later he presented to Burdwan Medical College and Hospital with a 3day history of dark, scanty urine and swollen legs. On presentation, he had multiple faint sting marks over the chest and back along with a few on the face and scalp. His temperature was 37.4uC, pulse 88/min (sinus rhythm), respiratory rate 32/min, blood pressure 138/84 mmHg (systolic BP 19 mmHg, above the 99th percentile for age, sex and height), capillary refill time within 3 seconds and with SpO2 97%. There was bilateral slightly pitting pedal oedema. Neck veins were not engorged. There was no pallor, jaundice, cyanosis or significant lymphadenopathy. Investigations. Haemoglobin was 11.5 g/dl, total leucocyte count 8.56109/L (differential count: neutrophils 52%, lymphocytes 47%, eosinophils 1%) and platelets 1906109/L. ESR was 78 mm in the 1st hour. Peripheral blood smear showed no evidence of haemolysis. Reticulocyte count was 1.5%. Urine analysis demonstrated numerous (uncountable) red cells, crenated red cells, red cell casts, albumin zzz

Correspondence to: S S Nag, Department of Paediatrics, Burdwan Medical College and Hospital, Burdwan, West Bengal, India. Email: [email protected]

ß W. S. Maney & Son Ltd 2014 DOI 10.1179/2046905514Y.0000000131

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(approximates to 5 g/L). BUN was 25.5 mmol/L (1.8–6.4), creatinine 627.64 mmol/L (27–62), sodium 130 mmol/L and potassium 5.9 mmol/L. Liver function tests including serum albumin 40 g/L (39–50), serum cholesterol, serum creatinine phosphokinase, lactate dehydrogenase, anti-nuclear antibody, antineutrophil cytoplasmic antibody, serum and urine haptoglobin, urine haemoglobin and myoglobin were all within normal limits. Antistreptolysin-O titre was 109 Todd units (upper limit of normal 120–160) and anti-deoxyribonucleasese B titre was 194 U (upper limit of normal 240–480). Throat swab cultured only commensal organisms. C3 complement level was 0.58 g/L (0.90–1.80). Electrocardiogram, ultrasonography of kidney-ureter-bladder region and chest radiograph were unremarkable. The patient was managed conservatively with fluid restriction, control of blood pressure and peritoneal dialysis. Nifedipine and frusemide were used to control blood pressure. Initially, the blood pressure was reduced slowly to 128/78 mmHg over the first 24 hours and then further reduced to 116/64 mmHg over the following 2 days. BUN and serum creatinine were 18.7 mmol/L and 468.5 mmol/L, respectively, at that time. Over the next 6 days, the clinical findings and laboratory parameters, including peripheral oedema and blood pressure, gradually normalised. On the 13th day of admission, he was discharged at which time BUN and serum creatinine were 3.8 mmol/L and 53.0 mmol/L, respectively. Two weeks later BUN was 3.7 mmol/L and serum creatinine 35.4 mmol/L. C3 level returned to normal (1.13 g/L) 4 weeks after discharge.

Bee venom is a complex cocktail containing biogenic amines, basic peptides, toxins and glycoproteins, most of which are enzymes.4 Active components include melittin, apamin, precipitin, histamine, phospholipidase A2 and hyaluronidase which are cytotoxic, neurotoxic, haemolytic, vaso-active and hypersensitising. Clinical reactions to stings by venomous insects are categorised as local, large local, generalised cutaneous, systemic, toxic and delayed/late. Most of the reactions are caused by IgE-mediated type I hypersensitivity. Large doses of venom may result in toxic reactions manifesting as fever, malaise, nausea and vomiting caused by the pharmacological properties of its components. Delayed/late reactions include serum sickness, nephritic syndrome, nephrotic syndrome, vasculitis, neuritis or encephalopathy. The pathogenesis of late reactions is not clear, but it is perceived to be a non-IgE-mediated immunological response (type III hypersensitivity) to hymenoptera venom involving deposition of immune complexes and complement activation.5 Acute kidney injury is an uncommon complication of bee stings. The proposed mechanisms of kidney injury are acute tubular necrosis secondary to intravascular haemolysis, rhabdomyolysis, shock from the anaphylactic reaction and toxin-induced nephropathy.1–3 In a clinically relevant experimental model, the mechanisms for bee venom-induced AKI were found to be severe vasoconstriction, intense direct tubular toxicity and rhabdomyolysis.6 Allergens in insect venom can mediate various types of renal injury – immune complex-mediated glomerulonephritis, interstitial nephritis, renal micro-angitis and vasculitis.7 Acute interstitial nephritis has been documented following multiple stings by other insects of the same order – hornet and wasp.5,7,8 The clinical presentations of various renal injuries are essentially the same and are differentiated from one another by laboratory studies. While eosinophilia and eosinophiluria suggest acute interstitial nephritis, acute glomerulonephritis is suspected if dysmorphic red cells are detected in the urine. Renal biopsy may be performed subsequently to confirm the exact site of involvement. Biphasic renal failure following bee sting has also been described with early renal failure owing to haemolysis and a second episode of azotaemia about 10 days later along with depressed serum C3 complement level and nephritic changes on renal biopsy, probably representing serum sickness reaction caused by a large volume of foreign proteins.9 Bee sting has been reported to also cause the nephrotic syndrome.10,11 Initial management should be removal of the barbed stings within 10–20 seconds by flicking or scraping off, which may prevent injection of additional venom.12 Local reaction to bee sting is generally transient and does not require medical

Discussion The patient developed late-onset AKI following multiple bee stings and recovered subsequently with management of hypertension, fluid restriction and peritoneal dialysis. He had no known history of previous renal insufficiency nor of using any drugs with nephrotoxic properties. He was well for several days after being stung, except for the healing local reactions. There was nothing to suggest haemolysis, rhabdomyolysis, hypotension or other causes of AKI, apart from a reaction to having been stung. Lateonset kidney injury suggests immune mechanisms in the pathogenesis of AKI. With low serum C3, it is likely that the renal injury was due to a serum sickness reaction, although a component of direct toxin-mediated renal damage can not be ruled out. The possibility of acute interstitial nephritis is remote in the absence of peripheral blood eosinophilia and eosinophiluria. The nephritic presentation, crenated red cells and high protein in the urine point towards glomerular injury. Therefore, the child most probably had immune-mediated acute glomerulonephritis.

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treatment. More severe and persistent local reactions are helped by cold compresses, oral anti-histaminics and analgesics. In patients with a history of large local reactions, use of oral corticosteroids may limit the swelling. Management of hypertension, fluid and electrolyte imbalance and renal function with dialysis play a pivotal role in both immediate and late-onset AKI. Early treatment of myoglobinrelated pigment tubulopathy with alkaline diuresis has been shown to avert dialysis and reduce mortality.13 Management of delayed reactions including AKI is mostly supportive. Insect stinginduced acute interstitial nephritis and nephrotic syndrome have shown improvement following use of corticosteroids.7,8,10,11 Although an immunological mechanism is thought to have played a significant role in the pathogenesis of renal involvement in this patient, corticosteroids were not used because of the clinical improvement. In view of the possibility of late-onset ‘postscript’-like complications which can be life-threatening, the need to follow-up such cases after initial improvement of hypersensitivity reactions is important. The importance of tracking the patient along with proper and timely management cannot be over-emphasised.

Nephritic syndrome after bee stings

References 1 Bresolin NL, Carvalho FLC, Goes JEC, Fernandes VR, Barotto AM. Acute renal failure following massive attack by Africanized bee stings. Pediatr Nephrol. 2002;17:625–7. 2 Betten DP, Richardson WH, Tong TC, Clark RF. Massive honey bee envenomation-induced rhabdomyolysis in an adolescent. Pediatrics. 2006;117:231–5. 3 Daher E de F, da Silva GB Jr, Bezerra GP, Pontes LB, Martins AM, Guimara˜es JA. Acute renal failure after massive honeybee stings. Rev Inst Med Trop Sao Paulo. 2003;45:45–50. 4 Kettner A, Henry H, Hughes G, Corradin G, Spertini F. IgE and T-cell responses to high-molecular weight allergens from bee venom. Clin Exp Allergy. 1999;29:394–401. 5 Ghosh JB, Roy M, Bala AK. Delayed-onset interstitial nephritis following multiple wasp stings. Indian J Nephrol. 2009;19:71–3. 6 Grisotto LS, Menels GE, Castro I, Baptista MA, Alves VA, Yu L, et al. Mechanism of bee venom-induced acute renal failure. Toxicon. 2006;48:44–54. 7 Zhang R, Meleg-Smith S, Batuman V. Acute tubulointerstitial nephritis after wasp stings. Am J Kidney Dis. 2001;38:E33. 8 Sharma A, Wanchu A, Mahesha V, Sakhuja V, Bambery P, Singh S. Acute tubulo-interstitial nephritis leading to acute renal failure following multiple hornet stings. BMC Nephrol. 2006;7:18. 9 Deshmukh LS, Borse BT. Acute renal failure following multiple stings by honeybees. Indian Pediatr. 1996;33:781–3. 10 Kaarthigeyan K, Sivanandam S, Jothilakshmi K, Matthai J. Nephrotic syndrome following a single bee sting in a child. Indian J Nephrol. 2012;22:57–8. 11 Tasik V. Nephrotic syndrome in a child after a bee sting. Pediatr Nephrol. 2000;15:245–7. 12 Schumacher MJ, Tveten MS, Egen NB. Rate and quantity of delivery of venom from honeybee stings. J Allergy Clin Immunol. 1994;93:831–5. 13 Thiruventhiran T, Goh BL, Leong CL, Cheah PL, Looi LM, Tan SY. Acute renal failure following multiple wasp stings. Nephrol Dial Transplant. 1999;14:214–17.

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Nephritic syndrome following multiple bee stings: a late hypersensitivity reaction.

Most hypersensitivity reactions to insect stings are immediate, ranging from transient local reactions of little medical consequence to fatal anaphyla...
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