Brown Recluse Spider Toxicity

Etiology

In the USA, the venom of the Loxosceles reclusa is the most potent among arachnids and most likely to cause dermonecrotic arachnidism.[2]

Epidemiology

Systemic involvement, while rare, is more likely to occur in children than in adults. There has recently been an increase in reports of brown recluse spider bites even in nonendemic areas. Most of these reports are likely because of other causes of similar appearing skin lesions like methicillin-resistant staph aureus skin infections.[3]

Pathophysiology

Brown recluse spider venom is cytotoxic and hemolytic. It has many enzymes that contribute to the clinical manifestations. Sphingomyelinase D, one of the more well-studied components, has been shown to direct toxin-mediated hemolysis and complement-mediated erythrocyte destruction. It does this by activating the complement system.  Within the venom, there are additional proteases that degrade collagen, fibronectin, fibrinogen, gelatin, elastin basement membranes that on their own may not be able to cause the local reaction seen with brown recluse bites but seem to have a synergistic effect with sphingomyelinase D leading to many of the cutaneous findings. Hyaluronidase, alkaline phosphatase, esterase, and ATPase also seem to have effects leading to the cutaneous manifestations of bites.[4]

Histopathology

To further study the necrotic effects of the brown recluse spider bite, there was a study done with rabbits injected with the venom. Although a small sample size, findings showed inflammatory infiltrates, coagulative necrosis and vasculitis. With all samples, there was a zone of eosinophils referred to as "mummified" coagulative necrosis seen between the epidermal and dermal layers.[5]

History and Physical

Brown recluse spider bites usually occur while indoors and as a defense mechanism as they are crushed or rolled over in bed. Some bites will present with only an urticarial rash. If the bite is more severe, the course usually is as follows.  The initial bite will be painless, but over the subsequent two to eight hours it will become increasingly painful. Systemic symptoms of brown recluse venom can present as malaise, nausea, headache, and myalgias. In children, the systemic reaction is more severe and may also include weakness, fever, joint pain, hemolytic anemia, thrombocytopenia, organ failure, disseminated intravascular coagulation, seizures, and death.

The bite site may initially have two small puncture wounds with surrounding erythema. From there, the center of the bite will become paler as the outer edge becomes red and edematous; this relates to vasospasm which will cause the pain to become more severe. Over the next few days, a blister will form, and the center of the ulcer will turn a blue/violet color with a hard, stellate, sunken center. After this step, skin sloughing can occur, and the wound will eventually heal by secondary intention, but this can take several weeks.

Evaluation

The bite of a brown recluse spider bite is a clinical diagnosis. A diagnosis of a spider bite can be made definitively only if the patient has a lesion that is consistent with a spider bite, or the spider was seen biting the patient, and the spider is caught and identified by an entomologist. 

If the clinician makes a working diagnosis of a brown recluse spider bite, lab testing is unnecessary except if there are systemic complaints, especially in children.[6] In these patients the following laboratory studies are performed;

• CBC
• BMP 
• Serum calcium and phosphate 
• LFT 
• CK/myoglobin 
• Reticulocyte count 
• Haptoglobin 
• LDH 
• PT/ INR 
• D Dimer 
• Fibrinogen 

Often a bite from a presumed arachnid can be mistaken as a bite from the brown recluse spider. Most patients aren't able to find the spider. A helpful mnemonic to use is NOT RECLUSE,[7] to help exclude the cause of bite from a brown recluse spider. 

• N (numerous) - only one lesion is usually present in a brown recluse spider bite. 
• O (occurrence) - A bite usually occurs when disturbing the spider. As the name suggests, they tend to avoid people, hiding in dark spaces like in a box or the attic. 
• T (timing) - Most bites occur between April and October. 
• R (red center) - characteristic bites will have a pale central area secondary to the capillary bed destruction causing ischemia.
• E (elevated) - Usually the bites are flat. If the area is elevated >1 cm, then this is most likely not a brown recluse spider bite.
• C (chronic)- bites from a brown recluse spider most commonly heal within 3 months. 
• L (large) - Rarely are these bites >10 cm.  
• U (Ulcerates too early) - If the bite is from a brown recluse spider, they do not ulcerate until 7-14 days. 
• S (swollen) - often brown recluse spider bites do not exhibit significant swelling unless they occur on the face or the feet
• E (exudative) - brown recluse spider bites do not cause exudative lesions

Treatment / Management

Initial treatment should begin with simple first aid. Elevate the extremity above the heart or at least in a neutral position. The activity of sphingomyelinase D is temperature dependent so an ice pack to the area should help halt the necrosis process.[8] Clean the wound with soap and water and ensure the patient’s tetanus immunization is up to date. NSAIDs can provide pain management, but some people may need opioids. Antibiotics are only necessary if there is associated cellulitis.(B3)

There is scant evidence for the use of dapsone or antivenom.[9] Also, note that dapsone is harmful in patients with G6PD deficiency,[10] and can also cause deadly hypersensitivity reactions.[11]  Steroids may be beneficial as they have been shown to decrease hemolysis and help prevent renal failure. If the infection is severe, consider hyperbaric oxygen therapy and surgical excision after the wound is well demarcated may be a consideration.[2] Early surgical debridement is not advisable.(A1)

Management for systemic symptoms is different than for local effects; hospital admission is the recommendation for patients with hemolytic anemia, rhabdomyolysis, disseminated intravascular coagulation or end-stage organ failure.  Treatment of these conditions is not different in this scenario than it would be for any other cause. 

In children, systemic loxoscelism may preclude skin findings and should be considered as a differential in pediatric patients with undifferentiated acute hemolytic anemia especially in regions known to have the brown recluse spider. Hemolysis has been reported up to 7 days after spider bite so adequate follow up instructions should be given to parents of children even if there are no systemic findings during the ED visit.[12] At a minimum, one should obtain a urinalysis at the initial visit if the working diagnosis is a brown recluse spider bite and the patient is being discharged.(B3)

Differential Diagnosis

• MRSA skin infections 
• Deep fungal infections 
• Cutaneous anthrax 
• Pyoderma gangrenosum 
• Other insect bites
• Stevens-Johnson syndrome 
• Toxic epidermal necrolysis 

Prognosis

Most cases of Brown recluse Spider envenomation manifest only as local soft tissue destruction. Death is rare but has been reported especially in children.[13][14]

Complications

After 4 to 6 weeks of therapy, it may be necessary to proceed with delayed skin grafting.