Myoglobin cast nephropathy following multiple bee stings

Bee stings usually result in mild allergic reactions; however, mass envenomation can cause severe complications such as rhabdomyolysis, hemolysis, shock, or multi-organ damage. Rhabdomyolysis can result in acute renal failure either by tubular obstruction by myoglobin casts or by direct cytotoxic injury. We present a case of a 12-year-old female child who presented with sudden onset anuria and hypertension following mass envenomation by bees. A renal biopsy was performed, the microscopic evaluation of which revealed tubular injury, with associated intratubular pigmented casts. The casts stained positive for myoglobin immunohistochemical stain, thus confirming a diagnosis of myoglobin cast nephropathy. The patient was given IV steroids and underwent seven sessions of hemodialysis, following which there was complete recovery of renal function.

Keywords: Acute renal failure, bee-sting, pigmented casts, rhabdomyolysis

How to cite this article:
Madireddy N, Swain M, Yalamarty R. Myoglobin cast nephropathy following multiple bee stings. Indian J Pathol Microbiol 2023;66:177-9

Introduction

Rhabdomyolysis is a potentially lethal, multi-factorial, clinical syndrome, which occurs as a consequence of necrosis of the skeletal muscle fibers and subsequent efflux of toxic intra-cellular contents such as myoglobin into the circulation.[1] It accounts for 7–10% of all cases of acute kidney injury (AKI).[2] The clinical manifestations of rhabdomyolysis range from an asymptomatic rise in creatine kinase to fatal complications including acute renal failure, cardiac arrest, and disseminated intra-vascular coagulation.[1],[2]

Although drug abuse, medication, alcoholism, trauma, and seizures have been identified as the most common causes of rhabdomyolysis in the western countries, in India, snake envenomation, strenuous physical activities, and wasp envenomation seem to be the most common causes.[3],[4],[5] In general, bee envenomation is well tolerated and causes only a mild IgE-mediated allergic reaction. However, in the event of multiple bee stings, AKI can ensue as a result of hypotension, rhabdomyolysis, hemolysis, or direct nephrotoxicity.[6] We present the case of a 12-year-old child who was stung by numerous honey bees and presented with sudden onset anuria.

Case review

A 12-year-old girl presented with a history of numerous bee stings, which was followed by sudden onset anuria and hypertension [Figure 1]. Physical examination revealed multiple sting marks all over the body. There was a rapid rise in serum creatinine from 5 mg/dl to 8 mg/dl over 24 hours. Urine analysis revealed an active urine sediment. The hematological parameters were within normal limits. The patient was given three doses of 500 mg IV methylprednisolone and underwent one session of hemodialysis following which a renal biopsy was performed.

Microscopic examination revealed a core of renal cortical tissue with up to 22 glomeruli and two arteries. The glomeruli were fairly unremarkable; however, there was significant tubular injury with flattening and denudation of the lining epithelium. Numerous intra-tubular pigmented granular, ropy casts were identified, which were brownish-red on hematoxylin and eosin (H&E) and stained bright red on Masson's trichrome. Immunofluorescence showed no immune deposits, and the casts showed no monoclonal restriction. These casts showed strong positivity for myoglobin immunohistochemical stain. Based on the above H and E, immunofluorescence, and immunohistochemical findings we arrived at a diagnosis of myoglobin cast nephropathy [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d.

Figure 2: Representative histopathology images: (a) Renal core biopsy showing intra-tubular brownish casts (H&E, x40); (b) Intra-tubular casts appearing brightly fuschinophilic (MT, x20); (c) Intra-tubular casts showing strong positivity with myoglobin immunohistochemical stain (x40)

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The creatinine phosphokinase (CPK) levels evaluated after the diagnosis of myoglobin cast nephropathy were not elevated. The patient underwent seven sessions of hemodialysis, following which the child showed a rapid recovery. Two months after the diagnosis, the child is currently off hemodialysis with a serum creatinine of 0.6 mg/dl.

Discussion

Numerous causes of rhabdomyolysis have been identified, which can be categorized as inherited and acquired.[2],[4],[5],[7] Among children, viral myositis, metabolic disorders, dermatomyositis, and trauma are the main triggers for rhabdomyolysis.[8] An acquired cause must be suspected in the scenario of a recurrence.[2] Jansi Prema et al.[4] studied the etiological and histomorphological spectra of rhabdomyolysis among Indians and found that the triggers for rhabdomyolysis varied from that of the western population. Snake bites, unaccustomed physical activity, seizures, and wasp stings were the most common causes in their study.

In India, honeycombs are commonly encountered in both rural and urban areas. Bees belong to the hymenoptera order of stinging insects and trigger IgE-mediated allergic reactions such as urticaria, angioedema, flushing, and hypotension. However, mass envenomation can lead to serious complications such as hemolysis, rhabdomyolysis, cardiovascular collapse, acute respiratory distress syndrome, AKI, or multi-organ failure.[6],[7] Mortality rates following bee stings lie between 15 and 23%.[7] Melitinin, apamin, phospholipase A2, and hyaluronidase are the principal components of the bee venom causing kidney injury by toxic damage of renal tubules and hypotensive effects, intra-vascular hemolysis, and rhabdomyolysis.[6]

Under normal circumstances, myoglobin is bound to globulins in the plasma and only a negligible amount reaches the urine.[1],[2] It reaches the tubules when it exceeds the renal threshold value of 1.5 mg/dl, wherein it forms myoglobin casts by precipitating with Tamm-Horsfall protein resulting in obstruction and AKI.[1],[2],[5],[7] Dehydration, renal vasoconstriction, and low urine pH further promote the formation of tubular casts.[1],[2],[3] Besides obstruction, vasoconstriction and direct toxicity also contribute to renal injury in rhabdomyolysis.[5],[7] Tubular obstruction is usually seen in the distal tubules, whereas direct cytotoxicity is seen in the proximal tubules.[2],[5]

Depending on the extent of injury, the clinical features can range from elevated serum creatinine to non-specific symptoms such as myalgia, weakness, headache, edema, or nausea. Cardiovascular collapse and acute kidney injury are the most perilous complications.[1],[3],[4],[7] The classic clinical features of rhabdomyolysis such as muscle pain, edema, and dark-colored urine may not always be present.[4] Elevated CPK levels point toward rhabdomyolysis; however, it is not uncommon to have normal CPK levels at the time of biopsy. This can be attributed to the short half-life of CPK, which is approximately 36 hours. CPK rises 12 hours post injury and declines to normal levels with 3–5 days following cessation of injury.[9]

Morphologically, the myoglobin casts appear beaded, granular, globular, or ropy or as rods and chains and vary in color from pink to brownish to dark red on H and E.[3],[4],[5] They are brightly fuschinophilic on Masson's trichrome and can range from weakly argyrophilic to intensely black with methenamine silver stain and stain positive with myoglobin immunohistochemical stain.[3],[4],[5],[9] These casts must be differentiated from other pigmented casts including hemoglobin, bile, or red blood cell casts. Hemoglobin casts are morphologically similar to myoglobin casts; however, negative staining with myoglobin immunohistochemical stain differentiates them from myoglobin cats.[5],[9] Bile casts are typically seen in association with hyperbilirubinemia and have a greenish tinge and stain emerald green with Fouchet's stain. Although light chain casts hardly ever appear granular, it is important to keep this among the differentials.[9]

Rhabdomyolysis has a relatively good prognosis with long-term survival of close to 80% if the underlying cause is reversible.[2],[4],[7] Hence, recognizing the morphology and instituting appropriate immunohistochemical stains to confirm the diagnosis with early and aggressive therapy are the key to recovery in these patients.

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Conflicts of interest

There are no conflicts of interest.

References

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2.El-Abdellati E, Eyselbergs M, Sirimsi H, Hoof VV, Wouters K, Verbrugghe W, et al. An observational study on rhabdomyolysis in the intensive care unit. Exploring its risk factors and main complication: Acute kidney injury. Ann Intensive Care 2013;3:8.

3.Melli G, Chaudhry V, Cornblath DR. Rhabdomyolysis: An evaluation of 475 hospitalized patients. Medicine (Baltimore) 2005;84:377-85.

4.Jansi Prema KS, Kurien AA. Etiological spectrum and histopathological diagnosis of rhabdomyolysis associated myoglobin cast nephropathy in South India. Indian J Nephrol 2021;31:22-6.

5.Sakthirajan R, Dhanapriya J, Varghese A, Saravanakumar K, Dineshkumar T, Balasubramaniyan T, et al. Clinical profile and outcome of pigment-induced nephropathy. Clin Kidney J 2018;11:348-52.

6.Silva GBD Junior, Vasconcelos AG Junior, Rocha AMT, Vasconcelos VR, Barros J Neto, Fujishima JS, et al. Acute kidney injury complicating bee stings-A review. Rev Inst Med Trop Sao Paulo 2017;59:e25. doi: 10.1590/S1678-9946201759025.