Evidence Based Strategies for Common Clinical Questions

The Itsy-Bitsy Spider … Put Me in the Hospital? An Overview of Loxoscelism 

Author: Jessica Boerner, MD | Pediatric Resident

Column Editor: Kathleen Berg, MD | Co-Director, Department of Evidence Based Practice | Pediatric Hospitalist, Division of Pediatric Hospital Medicine | Associate Professor of Pediatrics, UMKC School of Medicine 

Complications of insect bites are commonly seen in pediatric offices. However, bites from the brown recluse spider, Loxosceles reclusa, can lead to severe complications and can even be life-threatening. The constellation of systemic symptoms, known as loxoscelism, can be tricky to identify and may mimic many other conditions. A high index of suspicion and detailed anticipatory guidance are critical in providing appropriate, timely care for these patients.¹ 

Brown recluse spider bites are most common between May and September in the south-central region of the United States.² Most envenomations occur in Missouri, Kansas, Arkansas and Tennessee. Often, victims do not feel the bite when it occurs. They typically only notice pain and swelling several hours later. A classic “red, white and blue sign” consists of a dark blue/purple center surrounded by a ring of pallor with a larger outer area of erythema. These bites typically cause localized skin reactions that lead to ulceration with eschar formation and potentially necrosis that may require surgical intervention.³ 

Although most bites occur in the adult population, children are more likely to develop systemic toxicity and severe disease.^1,3 Patients with systemic toxicity can present with nausea, vomiting, fever, rash (maculopapular or erythrodermic), dark urine, myalgias or sometimes jaundice. These may be the first indicators of severe complications including massive hemolysis, rhabdomyolysis, renal failure and disseminated intravascular coagulation. Hemolysis may be acute within the first 24-48 hours, but can occur much later, up to nine days after the bite.¹ Although a patient may have minimal systemic signs and symptoms initially, thorough anticipatory guidance and return precautions are critical to ensure that potentially life-threatening disease is identified early. 

The toxicity from these bites is likely related to sphingomyelinase D, a component of brown recluse venom, which produces both toxin-mediated and complement-mediated hemolysis³ in addition to a severe cytokine-mediated inflammatory response.² There is also an unclear immune-mediated component to the disease process, as some – but not all – patients with loxoscelism will have a positive direct antibody test (DAT) to IgG and/or complement.⁴ 

When evaluating a case of potential loxoscelism, several screening tests should be obtained as summarized in Table 1. Hemoglobin is the best indicator of clinical severity, as it shows the degree of hemolysis most directly. However, identifying patients at risk before hemoglobin begins to drop is ideal. Haptoglobin has been recommended by some guidelines; however, a haptoglobin level can be difficult to interpret because it may be elevated in the setting of other diseases with acute inflammation.³ Earlier this year, a retrospective, cross-sectional study evaluated early laboratory predictors of hemolysis in patients with known brown recluse bites. Out of 275 patients, 64 had hemolytic anemia. Of the laboratory tests studied, the combination of elevated total bilirubin and elevated lactate dehydrogenase (LDH) was the most sensitive and specific indicator for detecting hemolysis before a fall in hemoglobin. The presence of blood on urinalysis was less reliable.⁵ 

 
Unfortunately, most proposed treatments for loxoscelism have inconclusive evidence, since study is limited by low disease incidence. Instead, treatment centers around supportive care, including blood transfusions and fluid resuscitation, and avoidance of nephrotoxins. Treatment should be provided in conjunction with a toxicologist or poison control center if possible. Systemic corticosteroids, dapsone, hyperbaric oxygen and surgical excision have been used, although their efficacy is unclear.⁶ In other countries (most often in South America), Loxosceles species cause more severe bites, and antivenom can be used for treatment. However, this antivenom is not available in the United States. As with any bite, tetanus immunization status should be reviewed and updated as indicated. Antimicrobials are not indicated, though many patients receive antibiotics during their treatment course because the presentation can mimic sepsis.¹ 

While most brown recluse bites do not result in severe systemic disease, early identification of loxoscelism is key to mitigating severe complications. However, early identification can be challenging due to the nonspecific signs and symptoms. When in doubt, obtain a complete blood count, total bilirubin and LDH to assess for hemolysis, and consider contacting a toxicologist for additional recommendations. If patients are discharged, provide careful instructions to return with signs or symptoms suspicious of developing hemolysis, including worsening fatigue, pallor, dark urine and/or decreased urine output.

Table 1: Laboratory evaluation for loxoscelism

References:

1. Hubbard JJ, James LP. Complications and outcomes of brown recluse spider bites in children. Clin Pediatr (Phila). 2011;50(3):252-258. doi:10.1177/0009922810388510 
2. Loden JK, Seger DL, Spiller HA, Wang L, Byrne DW. Cutaneous-hemolytic loxoscelism following brown recluse spider envenomation: new understandings. Clin Toxicol. 2020;58(12):1297-1305. doi:10.1080/15563650.2020.1739701 
3. Robinson JR, Kennedy VE, Doss Y, Bastarache L, Denny J, Warner JL. Defining the complex phenotype of severe systemic loxoscelism using a large electronic health record cohort. PLoS One. 2017;12(4):e0174941. doi:10.1371/journal.pone.0174941 
4. Calhoun B, Moore A, Dickey A, Shoemaker DM. Systemic loxoscelism induced warm autoimmune hemolytic anemia: clinical series and review. Hematology. 2022;27(1):543-554. doi:10.1080/16078454.2022.2065086 
5. Jacobs JW, Bastarache L, Thompson MA. Laboratory predictors of hemolytic anemia in patients with systemic loxoscelism. Am J Clin Pathol. 2022;157(4):566-572. doi:10.1093/ajcp/aqab169 
6. Warpinski GP, Ruha AM. North American envenomation syndromes. Emerg Med Clin North Am. 2022;40(2):313-326. doi:10.1016/j.emc.2022.01.006