Severe Hemolysis in Systemic Loxoscelism
Authors: Kodali Murali , Shortridge James , Doll Donald 
Published: October 2019

Abstract
Introduction: Brown recluse spider bites are encountered commonly in endemic areas of North and South America. Loxosceles reclusa is the species of Loxosceles most commonly seen in the states of MO, KS, OK, TX, AK, LA, KY, TN, MS, AL and parts of IL, IA, IN and GA. The incidence of hemolytic anemia with systemic loxoscelism in the USA seems to be significantly higher and more severe than the incidence and severity reported in studies from South America (13%-15% incidence). In our 6 cases of loxoscelism associated with severe hemolysis, we noticed that there are signs and symptoms that could be helpful to guide the follow up and facilitate early diagnosis.
Method: We reviewed 6 cases of hemolytic anemia from Loxoscelism treated at the University of Missouri Hospitals. Of these 6 cases 4 were treated within 1 year. All of the cases presented with systemic and cutaneous manifestations. Each patient was initially treated symptomatically and discharged without a close follow up. This resulted in delayed presentations with symptoms of severe hemolytic anemia associated with significant morbidity [Syncope (1), Syncope with fracture (1), Hypotension needing ICU care (1), Necrotizing fasciitis (1), and severe hepatosplenomegaly with hyperbilirubinemia (1)]. We have summarized the systemic symptoms, peripheral blood smear and laboratory findings that correlate with hemolytic anemia.
Results:Patients presented with Nausea (6/6), Vomiting (5/6), Fever (5/6), and Target lesion (6/6) within 48 hours after spider bite [Table 1]. Severe hemolysis developed at a median of 6.5 days after the spider bite. DAT was positive for IgG and C3 in all of the cases. Peripheral smear findings included leukocytosis with toxic granulations, Dohle bodies and left shift, Nucleated RBC, anisopoikilocytosis with some schistocytes, hemophagocytosis and normal to decreased platelets [Figure 1] [Figure 3]. When not recognized patients presented with sudden and severe hemolysis (median drop in Hb =7.5 g/dL) [Table2] resulting in hospitalization with severe morbidity (Figure 2).
Table 1 Initial Presentation Significant Morbidity Patient 1 Nausea and vomiting. Fever. Diffuse rash, RUQ pain Target lesion on back Severe Jaundice Hepatomegaly Splenomegaly Patient 2 Nausea, vomiting and diarrhea. Fever Target lesion on left arm Syncope Ankle fracture Patient 3 Nausea, fatigue and malaise. Target lesion on right back Recurrent syncope Patient 4 Nausea, Vomiting Fever Target lesion right arm. Severe Hypotension ICU care Patient 5 Nausea, dry heaves Fever. Thigh pain Target lesion right thigh. Necrotizing fasciitis Fasciotomy Patient 6 Nausea, vomiting and fatigue. Fever. Target lesion right shoulder.
Figure 1: Peripheral Smear Findings of Systemic Loxoscelism Figure 1:. Peripheral Smear Findings of Systemic Loxoscelism
Figure 2: Significant Morbidity from Systemic Loxoscelism Figure 2:. Significant Morbidity from Systemic Loxoscelism
Figure 3: Peripheral smear findings Figure 3:. Peripheral smear findings
Table 2 Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Median Age 34 31 21 25 21 22 23.5 Days after bite to lowest Hemoglobin 8 5 6 6 7 9 6.5 Baseline Hb (g/dL) 11 12 15 13 13.8 15.7 13.4 Lowest Hb (g/dL) 5.7 4 5 6 6.6 8.4 5.85 MCV with lowest Hb (fL) 70 107 100 90 96.6 101 98.3 WBC (103/µL) 12.6 42 32.3 14.5 33.4 26.6 29.45 Platelets (103/µL) 160 141 234 64 261 576 197 LDH (unit/L) hemolysed 2080 951 1348 744 346 951 T. Bili (mg/dL) 35.4 13.2 5 1.8 3.7 7.4 D. Bili (mg/dL) >10 9.2 .3 .5 0.3 1.4 Ind. Bili (mg/dL) 3.9 4.7 AST (unit/L) 100 52 25 201 120 156 ALT (unit/L) 86 95 19 91 104 294 Alk phos (unit/L) 94 88 67 36 160 159 Blood group A Pos A Pos O Pos B Pos O Pos
Discussion: Systemic loxoscelism from Loxosceles reclusa in USA is associated with a high incidence of severe hemolytic anemia. Increased awareness of the delayed presentation with hemolysis after initial signs of systemic loxoscelism could avoid life threatening events. Initial symptoms developed within 48 hours of the spider bite and led to medical attention in all of the reported cases.
With appropriate follow up, peripheral smear review and labs at 5-7 days after the spider bite most of the cases would have been recognized early and could have potentially avoided life threatening complications.
The different species of Loxosceles prevalent in South America could explain the difference in the incidence of hemolytic anemia. Studies from Brazil have reported the use of antivenom in about 50% of loxoscelism cases. Effectiveness of antivenom is not established and is seldom used in the USA but, could account for some differences in the incidence of hemolysis.

Disclosures
No relevant conflicts of interest to declare.