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

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The bite of the brown recluse spider (Loxosceles reclusa) typically results in local, dermonecrotic skin lesions. Rarely, these bites may precipitate systemic disturbances of varying severity collectively known as systemic loxoscelism. The more severe systemic alterations attributed to the venom of this arachnid include hemolytic anemia, multiorgan failure, disseminated intravascular coagulation, or even death. Coombs-positive hemolysis associated with brown recluse spider bites has rarely been documented in the literature. We report 2 cases of systemic loxoscelism in young women associated with severe Coombs-positive hemolytic anemia and systemic symptoms requiring hospitalization. Both patients were treated with aggressive wound care, hematologic monitoring with blood transfusion, and intravenous fluid replacement. Recovery was excellent in both cases. We review the literature and discuss the controversies surrounding the treatment of more severe brown recluse bite reactions.



The bite of the brown recluse spider, also known as Loxosceles reclusa, usually causes a local hemorrhagic lesion characterized by areas of red, white, and blue discoloration.1 Rarely, the venom from this spider may cause a systemic response characterized by fever, malaise, myalgia, hemolysis, acute renal failure, disseminated intravascular coagulation, or even death. The condition is called systemic loxoscelism and can be particularly dangerous in childhood, when most deaths from loxoscelism occur. The hemolysis in patients with systemic loxoscelism is not completely understood, despite extensive research into the components of this deadly spider's venom.2-4 Why this venom results in systemic symptoms in some patients and local reactions in others also is not completely understood. This variation in symptomatology likely has to do with the location of the initial spider bite and a possible predisposition of some individuals to environmental red blood cell toxins. The treatment of necrotic arachnidism is as controversial as the pathophysiology of the hemolysis. No standard of care exists for the more severe or anatomically vital spider bites. Several systemic medications have been tried with extensive anecdotal support, but no large controlled trials have been performed in humans to prove these agents are more effective than aggressive and meticulous wound care. Previous studies have shown that patients treated with early surgery resulted in prolonged healing times and increased negative outcomes compared with patients treated with supportive wound care.5,6 Patients generally do very well with only supportive measures, which should remain the treatment of choice until larger studies elucidate the role of systemic medications. We report 2 cases of systemic loxoscelism causing a Coombs-positive intravascular hemolysis requiring blood transfusion and review the treatment options of this condition.

Case Reports

Patient 1—A 19-year-old African American woman with a medical history significant only for asthma presented to her primary care physician 2 days after a painless bite from a "brown spider" in her bed. At this initial evaluation, she had a diffuse maculopapular rash with mild systemic symptoms including malaise and arthralgia. No laboratory workups were done, and she was started on a 5-day steroid dose pack. The patient was seen in our urgent care department 2 days later with documentation of a 2X2-cm ecchymotic area on her right posterior thigh with surrounding erythema and a diffuse maculopapular rash. Her laboratory workup at this time showed a mildly elevated total bilirubin level, mild leukocytosis, anemia with a hemoglobin level of 11.7 mg/dL, elevated reticulocyte count, and normal coagulation profile. She was given intramuscular methylprednisolone 125 mg, acetaminophen for pain, and hydroxyzine for pruritus, with plans for follow-up in urgent care the next day. The patient did not follow-up until 2 days later, at which time she reported worsening systemic symptoms including nausea, peripheral edema, lymphadenopathy, fever, and dysuria, along with worsening pain and erythema at the bite site. She was febrile, and her anemia progressed when her hemoglobin level fell to 8.3 mg/dL. She was admitted for hematologic monitoring and supportive measures. At the time of admission, her skin examination results were pertinent for a diffuse, faint maculopapular rash and a 3X3-cm necrotic eschar with surrounding erythema (Figure 1).

The day after admission, the patient continued to be febrile, and her hemoglobin level dropped to 6.9 mg/dL. She was transfused with 2 units of packed red blood cells, and the hematology department was consulted to assist with the progressing anemia. The dermatology department also was consulted to assist with wound care and treatment. The hematologist recommended performing an indirect and direct Coombs test. The indirect Coombs test results were negative, but the direct Coombs test results were positive for complement 3 and negative for immunoglobulin G (IgG). The patient's anemia and systemic symptoms continued to progress (hemoglobin nadir level, 5.7 mg/dL), requiring 2 more units of blood. The hematologist recommended starting intravenous steroids to improve the patient's "immunohemolytic anemia secondary to spider bite with positive Coombs test." The patient was started on methylprednisolone 125 mg/d intravenously. Per dermatology's recommendation, wound care was initiated along with elevation and ice to the affected extremity. The patient's clinical status began to improve on hospital day 4, with absence of systemic symptoms and regression of her lesional erythema. She was discharged on a quick-taper oral steroid regimen, per the hematologist's recommendation, and was instructed to continue her wound care. At the patient's hospital follow-up visit, her bite site was healing well, and she had no further evidence of anemia. Patient 2—A 9-year-old African American girl in otherwise excellent health was transferred from an outside emergency department one week after being bitten by "a brown spider" while lying in bed. Initially, the bite was painless, but she later developed swelling and warmth in the area. Due to increased pain, swelling, and blister formation, her primary physician saw her several days later and prescribed an oral cephalosporin for presumed cellulitis. Fever, fatigue, and malaise continued throughout the week. Two days prior to presentation at our hospital, she developed scleral icterus and vomiting. During the patient's evaluation at the transferring emergency department, her laboratory workup revealed a profound anemia with a hemoglobin level of 5.2 mg/dL, elevated white blood cell count, indirect hyperbilirubinemia, and mildly prolonged international normalized ratio value. Her examination was significant for a tachycardia, holosystolic murmur, scleral icterus, and 5X2-cm necrotic eschar on her left flank with a surrounding area of erythema that was exquisitely tender to palpation (Figure 2). She was immediately admitted for close observation and treatment of her anemia. She was transfused with 2 units of packed red blood cells.


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