Abstract
Acute kidney injury (AKI) can be seen in tropical regions following bites of various venomous animals and insects. Renal failure is seen most commonly following the bite of spiders of the Loxosceles spp. Dermonecrosis, systemic inflammatory response, hemolysis, rhabdomyolysis, and direct venom-related effects are postulated as causes of AKI. We report a documented case of AKI with pigment nephropathy following the bite of a brown spider from a tropical region which is known to have many venomous animals but has no previous reports of AKI following spider bite. Whether this is due to absence of toxic spider species or underreporting needs to be determined.
INTRODUCTION
Spiders have always infused fear in human minds and have triggered many rumors and works of fiction. Although there are more than 40,000 species of spiders reported worldwide, and only some of them cause injurious envenomation including local necrosis.1 Worldwide there are two medically important clinical syndromes resulting from spider bite: latrodectism (caused by Latrodectus spp.) and loxoscelism (caused by Loxosceles spp.). Widow spiders (Latrodectus spp.) cause local, regional, or generalized pain associated with nonspecific symptoms and autonomic effects. Loxoscelism can manifest as a cutaneous form with pain and erythema that can develop into a necrotic ulcer. Systemic loxoscelism is characterized by intravascular hemolysis and rarely by renal failure.2
Renal failure is seen predominantly following Loxosceles bites and in addition to the systemic inflammatory response, additional pathogenetic mechanisms include rhabdomyolysis, hemolysis, and direct nephrotoxic effects of the spider venom.3,4 Loxosceles (brown spiders) are spread worldwide and accidents involving members of this genus have been reported in North America, Latin America, Europe, and the Middle East and other parts of Asia, Africa, and Australia.4
According to the latest updated list of spider species found in India, Loxosceles rufescens or the Mediterranean recluse spider is the only member of the Loxosceles genus described in India.5 We could not find any reported case of renal failure following spider bites from India to the best of our knowledge.
CASE REPORT
A 50-year-old female patient was accidentally bitten over the dorsal aspect of the left forearm by a spider while she was working in the backyard of her house. The spider was not brought for examination but on matching her description with a number of representative pictures, she identified it to be similar to a brown spider (Loxosceles spp.). Even though it was not painful initially, the bite site developed a small painful blister that gradually progressed to become a necrotic lesion. After a few hours, she complained of vomiting, headache, malaise, periumbilical pain, and cola-colored urine with a decrease in the urine output. She was told to have renal failure on evaluation in a local hospital and was then referred to a higher center for further management.
She was admitted in another State hospital after 48 h of the bite, and by that time she was oliguric. She was conscious and alert with a blood pressure of 140/90 mmHg and a pulse rate of 90/min. Systemic examination was within normal limits. Initial investigations revealed a serum urea of 159 mg/dL, creatinine of 6.6 mg/dL, and hemoglobin (Hb) of 8.2 g/dL. She was then initiated on hemodialysis along with i.v. antibiotics and other supportive management including daily wound dressings. Over a period of one week in that center, the ulcer gradually spread towards the wrist and then the dorsum of the palm and the ring finger. She was then referred to our center for further management.
On admission with us, she was hemodynamically stable and hemoglobin was 4.7 g/dL with urine showing a positive dipstick test for blood without red blood cells (RBCs) on microscopy. Serum creatinine was 8.6 mg/dL, total bilirubin was 3.1 mg/dL (unconjugated fraction: 2.9 mg/dL), platelet count was 160,000/μL, total leukocyte count was 12,800/μL, creatine kinase was 280 U/L (normal range: 24–195 U/L), reticulocyte count was 3.3%, and lactate dehydrogenase (LDH) was 960 U/L (normal range: 235–470 U/L). The coagulation profile was normal. Urine and serum myoglobin levels were tested and were normal. Serum haptoglobin level was 23 mg/dL (normal range: 40–160 mg/dL). The ulcer, when examined by us, showed a “gravitational pattern” from the bite site (Figure 1). She was continued on hemodialysis and when the renal functions did not improve even after four weeks, a renal biopsy was done. The renal biopsy showed findings suggestive of acute tubular injury, pigment casts in some tubules, and interstitial edema, with normal glomeruli and vessels (Figure 2). In the meanwhile, there was a gradual increase in the hemoglobin level to 8.6 g/dL and normalization of the various laboratory parameters (bilirubin, LDH, creatine kinase, and haptoglobin).
Published online:
17 April 2013Figure 1. Dermonecrosis following bite of a brown spider over the dorsum of the forearm along with the “gravitational pattern” towards the hand and gangrene of the ring finger.
![]({"type":"image","src":"/na101/home/literatum/publisher/tandf/journals/content/irnf20/2013/irnf20.v035.i04/0886022x.2013.768936/20150616/images/medium/irnf_a_768936_f0001_b.gif"})
Figure 1. Dermonecrosis following bite of a brown spider over the dorsum of the forearm along with the “gravitational pattern” towards the hand and gangrene of the ring finger.
Published online:
17 April 2013Figure 2. Renal biopsy showing pigment casts along with acute tubular injury. H and E, ×10.
![]({"type":"image","src":"/na101/home/literatum/publisher/tandf/journals/content/irnf20/2013/irnf20.v035.i04/0886022x.2013.768936/20150616/images/medium/irnf_a_768936_f0002_b.gif"})
Figure 2. Renal biopsy showing pigment casts along with acute tubular injury. H and E, ×10.
The urine output gradually improved after five to six weeks along with a gradual decline in the serum creatinine. The left ring finger became gangrenous and had to be amputated. She was finally discharged after seven weeks of admission with a urine output of 1–1.5 L per day and a serum creatinine of 4 mg/dL. One month after discharge, the ulcer healed up leaving scars and contractures, and the serum creatinine decreased to 1.4 mg/dL.
DISCUSSION
The etiology of renal failure in our case is seemingly due to hemolysis caused by a brown spider bite. Features of intravascular hemolysis like a dramatic drop in the hemoglobin level along with a rise in unconjugated bilirubin, LDH, creatine kinase, reticulocyte count, and a fall in the serum haptoglobin were present. Renal biopsy also showed an evidence of pigment nephropathy. There could be a possibility of additional factors like rhabdomyolysis leading to a hypercatabolic acute kidney injury (AKI). But there were no suggestive clinical features and creatine kinase was also low. Incidence of AKI following rhabdomyolysis is higher at very high creatine kinase levels, typically in levels more than 15,000 U/L.6 It was impossible to exactly identify the spider species as it was not brought for identification, but all the clinical features were corroborating with loxoscelism. Acute intravascular hemolysis is a hallmark of systemic loxoscelism.2 Diagnosis of loxoscelism is based on the identification of the spider or careful evaluation of historical and clinical findings and the exclusion of other etiologies. In 90% of suspected spider bites, the actual spider is unavailable for identification, but it is improbable that other species could have caused similar lesions.7,8 In the absence of adequate epidemiological and clinical data from this part of the world, we can only assume the spider was Loxosceles rufescens also known as the Mediterranean recluse spider.5
Exact mechanisms of the toxicity of brown spider venom are still unclear. The venom was earlier believed to be Sphingomyelinase D which can trigger a powerful host inflammatory response and also has a direct hemolytic effect on RBCs. In fact, sphingomyelinase molecules are transportable between erythrocytes, serving to explain how low amounts of venom can cause severe hemolysis. It also has a direct damaging effect on the membrane of endothelial cells in the blood vessel wall.9 However, new studies suggest that the toxin has broad substrate specificity and is able to hydrolyze glycerophospholipids and sphingophospholipid to generate lysophosphatidic acid or ceramide-1-phosphate. Consequently, it has been suggested that the toxin might be more accurately described as a phospholipase-D to account for its hydroxylation activity with a broader range of lipid substrates.10
Another toxin found in brown spider venom is hyaluronidase.11,12 Hyaluronidases in venoms have been described as spreading factors due to their ability to degrade extracellular matrix components and to increase the diffusion of other toxins in tissues adjacent to the inoculation site.13 It may thus contribute to the characteristic gravitational spread of the dermonecrotic lesion in patients suffering from the effects of these venoms (Figure 1).
It is important to know about the local venomous animals and insects so that preventive strategies and anti-venoms can be manufactured. India is a vast tropical country and there are many venomous animals including spiders. But when we reviewed the literature for this case report, we could not find any reported instances of renal failure secondary to spider bites. This does not reflect the absence of such cases but the inability to report cases either due to the absence of a reporting system or misdiagnosis. Careful clinical and entomological studies should be done to look into this neglected disease entity.
Declaration of interest: The authors report no conflict of interest.
REFERENCES
- Platnick NI. Advances in Spider Taxonomy, 1988–1991: With Synonymies and Transfers, 1940–1980. New York: New York Entomological Society; 1993. [Google Scholar]
- Isbister GK, Fan HW. Spider bite. Lancet. 2011;378:2039–2047. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Hogan CJ, Barbaro KC, Winkel K. Loxoscelism: old obstacles, new directions. Ann Emerg Med. 2004;44(6):608–624. [Google Scholar]
- da Silva PH, da Silveira RB, Appel MH, Mangili OC, Gremski W, Veiga SS. Brown spider and loxoscelism. Toxicon. 2004;44:693–709. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Manju S, Molur S, Biswas BK. Indian spiders (Arachnida: Araneae): updated checklist 2005. Zoos’ Print J. 2005;20(10):1999–2049. [Google Scholar]
- Veenstra J, Smit WM, Krediet RT, Arisz L. Relationship between elevated creatine phosphokinase and the clinical spectrum of rhabdomyolysis. Nephrol Dial Transplant. 1994; 9(6):637–641. [PubMed], [Web of Science ®], [Google Scholar]
- Sezerino UM, Zannin M, Coelho LK, . A clinical and epidemiological study of Loxosceles spider envenoming in Santa Catarina, Brazil. Trans R Soc Trop Med Hyg. 1998;92:546–548. [Google Scholar]
- Krywko DM, Gomez HF. Detection of Loxosceles species venom in dermal lesions: a comparison of 4 venom recovery methods. Ann Emerg Med. 2002;39:475–480. [Google Scholar]
- de Souza AL, Malaque CM, Sztajnbok J, Romano CC, Duarte AJ, Seguro AC. Loxosceles venom-induced cytokine activation, hemolysis, and acute kidney injury. Toxicon. 2008;51(1): 151–156. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Lee S, Lynch KR. Brown recluse spider (Loxosceles reclusa) venom phospholipase D (PLD) generates lysophosphatidic acid (LPA). Biochem J. 2005;391:317–323. [Google Scholar]
- Wright RP, Elgert KD, Campbell BJ, Barrett JT. Hyaluronidase and esterase activities of the venom of the poisonous brown recluse spider. Arch Biochem Biophys. 1973;159:415–426. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Zobel-Thropp PA, Bodner MR, Binford GJ. Comparative analyses of venoms from American and African Sicarius spiders that differ in sphingomyelinase D activity. Toxicon. 2010;55:1274–1282. [Google Scholar]
- Kemparaju K, Girish KS. Snake venom hyaluronidase: A therapeutic target. Cell Biochem Funct. 2006;24:7–12. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]