Article

Coombs-Positive Hemolytic Anemia Secondary to Brown Recluse Spider Bite: A Review of the Literature and Discussion of Treatment

Author and Disclosure Information

 

References


The patient's hemoglobin level rebounded to 8.2 mg/dL on hospital day 2, at which time the dermatology department was consulted for assistance with wound care management. Elevation of the extremity and continuing wound care was recommended, and debridement or systemic therapy was advised against. Results of the patient's direct Coombs test were positive for IgG and negative for complement 3. No specific treatment changes were made based on the Coombs test result. The patient continued to improve with wound care and hemodynamic support and displayed improved erythema with less tenderness at the bite site after several days of hospitalization. She was sent home on hospital day 4 in improved condition. She was seen by a dermatologist at her follow-up visit, and her eschar was treated with hydrocolloid dressing changes and eventual debridement of the eschar with follow-up occlusive dressings until the lesion was completely healed.


Comment

Brown Recluse-Induced Hemolysis—Brown recluse spider bites are common in the Midwest, Southeast, and south central United States.7 Although there are more than 70 species of Loxosceles found throughout the world, only approximately 15 species inhabit North America, with L reclusa being the most common encountered by humans.8 Patients affected by this malady are often seen by physicians in various specialties, including primary care providers, emergency physicians, dermatologists, general surgeons, and surgical subspecialists. It is important that physicians in these specialties recognize and treat this condition appropriately.

Although these bites usually cause a local necrotic lesion, sometimes a more serious systemic syndrome, known as systemic loxoscelism, occurs. This can result in high fever, significant intravascular hemolysis, renal failure, disseminated intravascular coagulation, and even death. Although most fatalities have been reported in children, 2 cases of adult deaths have been reported.9,10 The hemolytic anemia that accompanies systemic loxoscelism has been only partially described, and the full mechanism by which the venom of the brown recluse causes this syndrome is still a mystery. The prevailing theory for the cause of hemolysis has incriminated the phospholipase sphingomyelin D, an enzyme isolated from brown recluse venom, because of its effect on cell walls in vivo to cause lysis.11 It was thought that sphingomyelinase disrupted cell membranes either directly or indirectly and resulted in the release of phospholipid-derived substances that bound complement and resulted in tissue hypoxia and necrosis.12-14 Because such a small amount of venom and toxin actually enter the body after a bite, another mechanism is likely taking place to produce the symptoms involved in systemic loxoscelism. Activation and propagation of the immune system by a toxin in the venom could explain such a reaction.

A study on another member of the Loxosceles family, Loxosceles intermedia, may help elucidate the factors involved in the overwhelming reaction to the Loxosceles venom in some people.15 In this study, it was found that the sphingomyelinase in the spider toxin did not directly affect glycophorins on red blood cell membranes but instead activated an endogenous metalloproteinase that then cleaved these glycophorins. The authors proposed that the altered glycophorins destabilized the red blood cell membrane, rendering the glycophorins vulnerable for complement-mediated lysis. The authors also observed that the hemolysis-inducing and glycophorin-cleaving activity of this activated metalloproteinase could be transferred from one erythrocyte to another, thereby propagating the hemolyzing response.15 This type of transfer of sphingomyelinase and metalloproteinase activity between cells has been described before and could explain the overwhelming systemic response of the Loxosceles toxin in some individuals.16

Historically, most cases of massive hemolysis due to brown recluse bites documented in the literature have been Coombs negative.17 This also has been the case at our institution until recently.11 We report 2 cases of life-threatening hemolytic anemia with positive direct Coombs testing in a span of 9 months. These results are a rarity but may help us understand the pathophysiology of systemic loxoscelism. To our knowledge, these are the fifth and sixth reported cases of a Coombs-positive hemolytic anemia from a brown recluse spider bite. The first case was documented by Nance18 in 1961, but there was no mention of whether complement or immunoglobulin was involved. Eichner17 reported the second and third cases of Coombs-positive anemia in loxoscelism, with both cases involving complement-mediated hemolysis. The fourth case of Coombs-positive anemia was reported by William et al9 in 1995, and the Coombs test was positive for both IgG and complement. Our cases affirm that both IgG and complement can be involved in Coombs-positive hemolytic anemia. It is likely that the venom of the brown recluse is able to activate both IgG and complement in predisposed individuals by activation of an unknown endogenous mediator (eg, metalloproteinase) to cause massive intravascular hemolysis. Investigations into which patients may be predisposed to develop this complication are warranted.

Pages

Next Article: