Brown Recluse Spider Envenomation 

Brown Recluse Spider Envenomation – 13 Interesting Facts

1. Brown recluse envenomation and similar types of loxoscelism are caused by species of Loxosceles spiders
2. Bite has the potential to cause dermonecrosis (cutaneous loxoscelism) and acute hemolysis (systemic loxoscelism); brown recluse spider is the most common Loxosceles species encountered in the United States
3. Hallmark of cutaneous loxoscelism is progressive dermatologic spread in a gravitational direction from site of envenomation, resulting in a dermonecrotic lesion
4. Hallmark of systemic loxoscelism is acute hemolytic anemia. Systemic form is uncommon; increased risk occurs with envenomations by South American Loxosceles species and in children
5. Diagnosis is based on epidemiologic and clinical features; no universally accepted test is available to confirm disease
6. Common cutaneous lesions that mimic brown recluse envenomation include disease caused by MRSA, Lyme disease, burns, pyoderma gangrenosum, diabetic ulcers, focal vasculitis, contact dermatitis, herpetic lesions, and other spider envenomation
7. Mainstay of therapy in the United States is supportive care with expectant observation for both dermatologic and systemic loxoscelism
8. Treat severe hemolytic anemia with RBC transfusions, and prevent acute kidney injury and renal failure with fluid replacement and urinary alkalinization
9. Individuals with significant systemic signs (eg, high fever, jaundice, dark urine) require evaluation for systemic loxoscelism and admission for expectant care and monitoring
10. Main complication of dermonecrosis is cutaneous scarring; wounds requiring skin grafting are unusual, and secondary infection of cutaneous disease is uncommon
11. Acute renal failure owing to acute hemolytic anemia with mild rhabdomyolysis can complicate systemic loxoscelism
12. Overall prognosis is good for brown recluse spider envenomation; typical brown recluse spider bite is self-limited without severe necrosis or systemic symptoms; dermonecrotic lesions heal over 1 to 2 months ¹ by secondary intention; full recovery is expected from systemic loxoscelism with appropriate supportive care
13. Preventive measures include avoiding and managing household infestations and avoiding bites when dressing and when working outdoors

Urgent Action

• Initiate renal protective measures in patients presenting with systemic loxoscelism: use fluid replacement, urinary alkalinization, and hemodynamic support to maintain renal perfusion and adequate urine output

Pitfalls

• Avoid frequent misdiagnosis of necrotic skin lesions by carefully excluding other treatable causes of dermonecrosis; historically, brown recluse spider envenomations are rare outside known spider habitat and are rare in the months of November through March in the United States
• Children are at increased risk for systemic loxoscelism; maintain a high degree of suspicion for systemic disease manifestations in this population so that supportive care and monitoring can be initiated

Introduction

• Brown recluse envenomation and similar types of loxoscelism are caused by species of Loxosceles spiders ²
  • Bite has the potential to cause dermonecrosis (cutaneous loxoscelism) and acute hemolysis (systemic loxoscelism)
• Brown recluse spider (Loxosceles reclusa) is the most common Loxosceles species encountered in the United States

Classification

• Classification based on extent of venom effects
  • Cutaneous loxoscelism ²
    • Variable dermatologic manifestations ranging from minimal localized dermatologic reactions to extensive dermonecrosis (dermonecrotic arachnidism)
    • Common manifestation of envenomation
  • Systemic loxoscelism (viscerocutaneous loxoscelism) ²
    • Hallmark is intravascular hemolysis
    • Uncommon manifestation of envenomation
• Classification based on severity of cutaneous reaction ³
  • Grade 1: mild
    • Mild erythema, puncta, and no necrosis
  • Grade 2: moderate
    • Erythema, mild edema, vesicle, and skin necrosis 1 cm² or less
  • Grade 3: severe
    • Extensive erythema, edema, bulla, ulcer, and skin necrosis greater than 1 cm²

Diagnosis

Clinical Presentation

• Brown recluse spider. – Loxosceles reclusa (mature male). Note the fiddle-shaped marking on the dorsal surface.From Sams HH et al: Nineteen documented cases of Loxosceles reclusa envenomation. J Am Acad Dermatol. 44(4):603-8, 2001, Figure 1.
• Brown recluse spider anatomy. – Loxosceles reclusa displays classic violin markings on the cephalothorax (1), 3 pairs of eyes (2), and hairy legs (3). Note that several legs are missing.From Furbee RB et al: Brown recluse spider envenomation. Clin Lab Med. 26(1):211-26, 2006, Figure 3.

History

• Background
  • Most bites occur during sleep or when patient is dressing; bites occur when spider is trapped against a person’s skin ²
  • Bites often occur in the morning ⁴
  • Initial bite is often painless and goes unnoticed; up to 60% recall a bite sensation ²
  • Sometimes a spider is seen in the area; occasionally, irregular spider webs resembling cotton thread are reported in the home ⁵
  • Spider is captured or killed and brought in for identification in only 10% of cases ⁶
  • Most patients present for care between 12 and 24 hours after envenomation ²
• Symptoms of cutaneous envenomation
  • Dermatologic manifestations range from no effect to minor (mild edema with erythema) to severe (extensive dermonecrosis) ⁵
    • Cutaneous manifestations are often worse with envenomation over fatty areas of body
  • Hallmark feature of cutaneous loxoscelism is progressive dermatologic spread in a gravitational direction from the site of envenomation, resulting in a dermonecrotic lesion ^2 6
  • Distribution of cutaneous loxoscelism ⁷
    • Most envenomation involves thigh, trunk, or proximal arm in areas covered by clothing
    • Envenomation is uncommon on neck
    • Envenomation is uncommon on hands, feet, and face
  • Classic evolution and progression of skin lesion
    • Progressive pruritus, pain, and erythema develop in area of venom inoculation in first 2 to 8 hours ⁵
    • Pain may be progressive and become severe over first 24 hours as erythema expands and ecchymosis develops ⁸
    • Classically, a halo of pale skin surrounds the lesion
    • Early signs of necrosis are hyperesthesia and vesicle formation, which can develop by 72 hours ⁹
    • Expanding central necrosis develops at site of envenomation
    • Dark necrotic eschar forms by 1 week ^10 11
    • After 2 to 3 weeks, eschar detaches and leaves a painful necrotic ulcer
    • Ulcer takes several weeks to heal; scarring may result
• Constitutional symptoms often accompany cutaneous envenomation ²
  • Nonspecific mild symptoms develop in up to 50% of patients in first 12 to 24 hours ²
    • Low-grade fever, headache, nausea, mild arthralgia, and mild myalgia ¹²
  • Generalized macular rash occurs in up to one-third of patients ⁷
• Systemic loxoscelism
  • Severity of cutaneous lesion does not correlate with risk of developing systemic loxoscelism ⁹
  • Early stages of systemic loxoscelism resemble constitutional symptoms that accompany cutaneous loxoscelism but rapidly progress in severity ¹²
  • Systemic symptoms include:
    • Severe malaise and diffuse rash
    • Fever (up to 40.5 °C) and chills ⁹
    • Severe myalgias and arthralgias
  • Symptoms associated with significant hemolysis can occur as early as 24 hours after envenomation but are most common between 48 and 72 hours after envenomation ¹²
    • Hematuria ¹³
    • Jaundice
    • Pallor
  • Oliguria is associated with diminished renal function

Physical examination

• Common timeline of evolution of dermatologic manifestations
  • First 6 hours ⁹
    • 2 small central puncta occur at venom inoculation site; surrounding halo of erythema and mild edema develops
    • Initial cutaneous reaction resembles an insect bite
  • By 12 to 24 hours ⁹
    • Erythematous margin around inoculation site enlarges peripherally ^10 11
    • Edema increases; a perimeter of blanched skin from vasoconstriction develops
    • Areas of ecchymosis with scattered, blanched areas evolve
    • Eventually a marble plaque appearance results (eg, irregular erythema and ecchymosis mixed with blanched areas superimposed on intralesional edema) ⁶
    • Vesicles or bullae develop centrally and may become hemorrhagic
    • Vesicles, bullae, and local cyanosis are early signs of necrosis ⁹
  • After 72 hours ²
    • Well-defined deep central necrosis around area of venom inoculation develops in up to half of patients ²
    • Necrotic tissue appears as dull violaceous color ⁵
    • Dark necrotic lesion advances and is surrounded by an inner ring of pallor from vasoconstriction and an outer ring of expanding erythema and ecchymosis
    • Red, white, and blue sign or bulls-eye pattern describes typical dermonecrotic appearance of expanding lesion at this stage ¹⁴
    • Gravitational spread of venom results in irregular lesion margins
  • By 5 to 7 days ²
    • Borders of lesion stop advancing
    • Dry necrotic eschar with well-defined borders develops
    • Eschar sinks below surface of surrounding skin ¹²
  • After 2 to 3 weeks ²
    • Necrotic eschar detaches, leaving a sharply demarcated ulcer with granulating tissue base surrounded by healthy border of skin
    • Ulcers assume varying depths but spare musculature ¹⁵
  • After several weeks ⁶
    • Healing occurs at variable rates
• Systemic loxoscelism
  • Fever
  • Abnormal vital signs (eg, tachycardia, hypotension)
  • Diffuse macular rash (possible herald sign)
  • Jaundice and pallor (associated with significant hemolysis)
• Facial envenomation edema variant ²
  • Significant edema with little or no dermonecrosis development

Causes

• Transcutaneous envenomation from spiders of Loxosceles genus can result in dermatologic and systemic clinical manifestations
  • Loxosceles venom
    • Venom contains a number of cytotoxic enzymes and proteins; key components are a family of sphingomyelinase D and hyaluronidase ²
      • Sphingomyelinase D is responsible for dermonecrosis and hemolysis ¹⁵
      • Hyaluronidase is responsible for progressive enlargement and gravitational spread of lesion ^7 12
      • Injected venom components act in synergy to cause a complex inflammatory response that includes release of proinflammatory cytokines and lipid mediators; result is complement activation, neutrophil chemotaxis, platelet aggregation, thrombosis, and endothelial damage ^2 7
  • Development of systemic loxoscelism depends on size of person, amount of venom injected, and specific characteristics of spider (eg, sex, species, developmental stage) ⁶
    • Severity of cutaneous lesion does not correlate with risk of developing systemic loxoscelism ⁹
    • Smaller patients (eg, children, infants) are at increased risk of systemic loxoscelism
    • Acute kidney injury occurs exclusively in patients with extensive hemolysis ⁶
• Loxosceles biology
  • Characteristic morphology of Loxosceles
    • Most distinguishing feature is number of eyes ⁶
      • Loxosceles species have 6 eyes arranged in a distinctive pattern of 3 dyads ⁹
        • Most arachnids have 8 eyes ⁷
      • 1 pair is located in anterior portion of cephalothorax directly above fangs, and the other pairs are located posteriorly on side of cephalothorax ⁹
    • Dark brown violin-shaped marking is often noted on dorsal cephalothorax; neck of violin points toward rear of body ⁶
      • This fiddleback marking is not unique to spiders of this species ⁷
      • Some immature spiders and recently molted spiders do not display this marking ⁷
    • Spiders are yellow-brown to gray-brown in color with spiked hairs on legs ⁷
    • Loxosceles has a largely flat body with large leg to body ratio; ² adult leg length is about 5 cm and body length is 6 to 11 mm ⁷
  • Characteristic behavior of Loxosceles
    • Spider is nocturnal and nonaggressive ⁵
    • Spider prefers dark, quiet, dry, and secluded spaces indoors (eg, attics, basements, boxes, sheds) and outdoors (eg, in wood piles, under porches, under rocks, in leaf piles) ²
    • Spider is well adapted to life indoors; it prefers to hide in furniture, in cupboards, in drawers, behind wall hangings, and in clothes, towels, bed sheets, and shoes ⁹
    • Loxosceles does not typically migrate from natural home range habitat unless transported by humans to nonnative areas ⁹
  • Species vary by geographic region; 5 species are responsible for most envenomation cases that result in significant disease
    • Spiders of Loxosceles genus are also referred to as recluse spiders, fiddlebacks, violin spiders, and brown fiddlers ²
    • Loxosceles reclusa
      • Commonly known as the brown recluse ¹⁵
      • Most widely distributed species of the genus in the United States; species most often implicated in necrotic arachnidism in the United States
      • Home range includes the Midwest from Nebraska to southern Ohio, and the South from Georgia to Texas ⁹
      • Rarely causes systemic loxoscelism (less than 1% of cases) ⁵
    • Loxosceles laeta²
      • Native to South America; ² home range includes California ¹⁶
      • Responsible for most cases of severe systemic loxoscelism
      • Systemic loxoscelism develops in up to 27% of bites ⁶
    • Loxosceles rufescens¹⁷
      • Indigenous to the Mediterranean region and Africa; found widespread throughout the world, including Central America, Africa, Australia, Gulf of Mexico area of Texas, and Hawaii ¹⁶
      • Rarely a cause of systemic loxoscelism ¹⁸
    • Loxosceles intermedia
      • Found in Brazil and Argentina ²
      • Does not cause systemic loxoscelism ²
    • Loxosceles gaucho
      • Found in Brazil ²
      • Mild hemolysis is frequent ⁶
    • Other species less commonly encountered in the United States
      • Loxosceles deserta is found in the deserts of the western states ¹⁷
      • Loxosceles arizonica is found in Arizona, New Mexico, Nevada, Texas, Utah, and southern California ¹⁹

Risk factors and/or associations

Age

• Envenomation is most common in young adults ¹
• Systemic loxoscelism is more common in children younger than 7 years but can occur in any age group ¹²

Sex

• Slightly more women are bitten than men ²

Other risk factors/associations

• Brown recluse envenomations often occur in warm seasons (ie, April through October) in the United States; envenomations are rare in November through March ^10 20
• Bites over fatty tissue or areas of end circulation are at increased risk of extensive dermonecrosis ⁶

Diagnostic Procedures

Primary diagnostic tools

• Diagnosis is based on epidemiologic and clinical features; ⁶ no universally accepted test is available ¹⁵ to confirm disease
  • Diagnosis is often probable or presumptive
    • Assign probable diagnosis in the presence of a cutaneous lesion and epidemiologic history consistent with Loxosceles envenomation, when alternative diagnoses are excluded ²
    • Assign presumptive diagnosis in the presence of a cutaneous lesion that might be consistent with envenomation in a region where the brown recluse is known to live ¹²
  • Documented brown recluse spider bite
    • Confirmed envenomation is diagnosed only with direct spider identification by a qualified professional (eg, toxicologist, arachnologist, clinician); ⁷ however, not many patients present with spider for identification (about 10%)
• Loxosceles cutaneous reactions are a diagnosis of exclusion
  • Suspicious necrotic lesions are often misdiagnosed as brown recluse spider envenomation; it is important to consider alternative diagnoses ¹⁰
  • Very unlikely for brown recluse envenomation to occur outside of known habitat ¹⁷ or outside the months of April through October in the United States ¹⁰
• Evaluate for suspected systemic loxoscelism only in patients presenting with severe disease manifestations ²¹
  • Screening laboratory tests are indicated for patients presenting with rapidly expanding dermonecrosis, extensive dermonecrosis, and significant systemic symptoms, especially children
  • Obtain the following:
    • CBC with peripheral smear to assess for signs of intravascular hemolysis and to quantify hemoglobin level ¹²
    • Urinalysis to assess for hemoglobinuria ¹²
    • Consider screening tests for intravascular hemolysis (eg, serum haptoglobin level, plasma-free hemoglobin level) ¹²
  • Absence of hemolysis excludes systemic involvement ¹²
  • If evidence of hemolysis exists, assess baseline renal function and evaluate for rhabdomyolysis
  • Assess for disseminated intravascular coagulation if patient appears severely ill
• Testing for venom is not in widespread clinical use in the United States; available tests in some areas of South America and some research laboratories include: ⁷
  • Indirect (passive) hemagglutination test to detect antibodies to venom in wound exudate ⁶
  • ELISA to detect venom from skin biopsy of lesion^4 7 22

Laboratory

• CBC and peripheral smear
  • Hemolytic anemia with spherocytes on peripheral smear, leukocytosis, and thrombocytopenia are characteristic hematologic abnormalities ³
  • Significant hemolytic anemia develops in up to half of patients with systemic effects ¹³²³
    • Acute hemolytic anemia may develop within hours or insidiously over first 2 to 3 days after envenomation; can recur 7 to 10 days after envenomation ²²
    • Significant acute hemolytic anemia rarely develops more than 96 hours after envenomation ²²
    • Acute hemolysis usually persists for 4 to 7 days ²²
    • Maximum decrease in hemoglobin level is observed between days 2 and 3 in 40% of patients and between days 4 and 9 in 60% of patients ¹³
    • Hemoglobin level often declines to between 5 and 8 g/dL ²
    • Hemolysis is usually intravascular; less common presentation is combined intravascular and extravascular ²²
  • Hemoglobin level is the most direct indicator of hemolytic disease severity ²⁴
    • More than 10 g/dL indicates mild disease ²⁴
    • 8 to 10 g/dL indicates moderate disease ²⁴
    • 6 to 8 g/dL indicates severe disease ²⁴
    • Less than 6 g/dL indicates very severe disease ²⁴
• Urinalysis
  • Hemoglobinuria without RBCs on urine microscopy indicates intravascular hemolysis
  • Myoglobinuria indicates rhabdomyolysis
• Serum haptoglobin level
  • Sensitive screening test for hemolysis
  • Significantly decreased haptoglobin level is consistent with hemolysis ²⁵
  • Normal serum haptoglobin level excludes intravascular hemolysis ¹²
• Plasma-free hemoglobin (free hemoglobin) level ²²
  • Screening test for hemolysis
  • Quantitative measure of intravascular free hemoglobin
  • Sensitive for detecting intravascular hemolysis on nontraumatic blood draw
  • False-positive results occur when blood draw is traumatic and hemolysis in specimen occurs from blood draw technique
• BUN and creatinine levels
  • Acute renal failure develops in 12% of patients with systemic effects owing to combined effects of hemolysis and rhabdomyolysis ¹³
• Other common laboratory findings in patients with acute intravascular hemolysis
  • Unconjugated hyperbilirubinemia with high serum lactate dehydrogenase level
  • Direct Coombs test (direct antiglobulin test) result may be positive ^2 22
  • Reticulocytosis occurs by 3 to 4 days after onset of hemolysis ²²
• Other common findings in patients with rhabdomyolysis
  • Mild rhabdomyolysis develops in up to 27% of patients with systemic effects ¹³
  • Small rise in serum creatine kinase level to the low thousands (units/L) ²
• Findings consistent with mild diffuse intravascular coagulation are rare; clotting times can double ²
• Indirect (passive) hemagglutination test
  • Sensitivity is approximately 90% and specificity is approximately 100% in laboratory animals as long as 3 days after envenomation ^4 7
• ELISA for detecting Loxosceles antigens ²²²⁶
  • Can detect venom antigens up to 2 weeks after envenomation ²⁷
  • Sensitivity is estimated between 60% and 70% in humans ²⁷

Other diagnostic tools

• Modified Statin-Associated Muscle Symptom clinical criteria ¹⁰
  • Classification system used to determine the likelihood that a lesion is compatible with a brown recluse spider bite
  • Based on presence of positive examination features, negative examination features, and geographic likelihood of envenomation
    • Positive examination features ¹⁰
      • Small central blister without pus
      • Pale area in center of lesion
      • Purpura/bruising
      • Purpura with gravitational spread
      • Outer part of lesion is red and either pale area or purpura present in center
      • Outer part of lesion is red (red, white, and blue sign)
    • Negative examination features ¹⁰
      • Pus observed in lesion
      • Center raised and red
      • Drainage within 1 week
      • Tender, enlarged lymph node
      • Ulcer forms within 1 week
      • Ulcer is more than 10 cm in diameter or more than 0.5 cm deep
      • More than 2 separate lesions
      • Lesion is present for more than 3 months
  • 4 levels to diagnose probability of brown recluse spider envenomation include:
    • Putative
      • Patient has subjective diagnosis, geographic location is outside known brown recluse habitat, and clinical features typical of brown recluse bites are absent (ie, no positive examination features) ¹⁰
    • Presumptive
      • Geographic location is within known brown recluse habitat, and lesion has 1 or more positive examination features ¹⁰
    • Probable
      • Geographic location is within known brown recluse habitat, and lesion has 1 or more positive examination features and no features indicative of an alternative diagnosis (ie, no negative examination features) ¹⁰
    • Documented
      • Lesion fulfills at least 1 positive examination feature and brown recluse spider has been captured in vicinity and identified by arachnologist ¹⁰

Differential Diagnosis

• Skin abscesses associated with MRSA.From Monina Klevens R et al: Methicillin-resistant Staphylococcus aureus. J Am Dent Assoc. 139(10):1328-37, 2008, Figure.
• Plantar diabetic foot ulcer.From Charles CA et al: Leg ulcer management. In: Surgery of the Skin. Mosby; 2005:743-66, Figure 46.1C.
• Erythema migrans in Lyme disease. – Erythema migrans skin lesion on posterior aspect of right thigh.From Wormser GP: Lyme disease. In: Goldman L et al, eds: Goldman-Cecil Medicine. 25th ed. Elsevier; 2021-7, 2016, Figure 321-2.
• Herpes zoster (shingles). – Herpes zoster lesions that show typical grouped vesicular lesions with erythematous base in a dermatomal distribution.From Dhanireddy S et al: Human immunodeficiency virus infection and the acquired immunodeficiency syndrome: diagnosis and management. In: Mores SA et al, eds: Atlas of Sexually Transmitted Diseases and AIDS. 4th ed. Saunders; 2010:256-86, Figure 15.13A.
• Poison ivy dermatitis with linear distribution of papules and vesicles.From Sasseville D: Clinical patterns of phytodermatitis. Dermatologic Clin. 27(3):299-308, 2009, Figure 2.
• Right posterior shoulder burns.From Landman A et al: Magnetic resonance-induced thermal burn. Ann Emerg Med. 52(3):308-9, 2008, Figure 1.
• Classic pyoderma gangrenosum manifested by large, tender ulceration on leg.From Callen JP et al: Pyoderma gangrenosum: an update. Rheum Dis Clin North Am. 33(4):787-802, 2007, Figure 1.
• Typical palpable purpura on legs of patient with cutaneous small vessel vasculitis after exposure to an antibiotic.From Micheletti RG et al: Small vessel vasculitis of the skin. Rheum Dis Clin North Am. 41(1):21-32, 2015, Figure 1.

Most common

• MRSA infection²⁸
  • Lesions present similarly to early cutaneous loxoscelism with erythema and pain; superficial cutaneous abscess formation appears as a central purpuric area of dermonecrosis surrounded by an area of cellulitis
  • As opposed to brown recluse envenomation, the central necrosis of a superficial cutaneous MRSA abscess is raised above the surrounding skin and purulent material can be expressed or obtained by local incision and drainage
  • Differentiate by clinical presentation and clinical course; purulent drainage and classic findings associated with cutaneous loxoscelism (marble plaque formation followed by red, white, and blue sign) are inconsistent with MRSA
  • Culture of purulent material obtained from a wound confirms MRSA
• Lyme disease²⁹
  • Erythema migrans is the rash of Lyme disease and resembles early cutaneous loxoscelism with a progressive local erythematous macule or bulls-eye lesion (ie, erythema with central clearing) that develops at site of tick bite; often, constitutional symptoms accompany erythema migrans ³⁰
  • Erythematous macule of erythema migrans progresses over several days, reaching 5 or more cm in diameter; a central bluish color or vesicles can develop at center of macule
  • Differentiate by presentation and clinical course; erythema migrans resolves without progressing to dermonecrosis, and classic findings associated with cutaneous loxoscelism (ie, marble plaque formation followed by red, white, and blue sign) are inconsistent with erythema migrans
  • Classic erythema migrans rash acquired in a geographic region known to have relevant ticks is sufficient for a definitive diagnosis of Lyme disease
  • Confirm Lyme disease diagnosis with 2-tiered testing for Borrelia burgdorferi with ELISA followed by confirmatory Western blot if diagnosis remains in question
• Herpes zoster (shingles)³¹
  • Reactivation of varicella-zoster virus from its latent state in a posterior dorsal root ganglion results in herpes zoster; resembles early cutaneous loxoscelism with painful erythema followed by formation of vesicular clusters
  • Progression of herpes zoster rash involves crops of new vesicles that form over several days; rash is often confined to a dermatomal pattern; lesions progressively dry and crust over then heal over several weeks
  • Burning pain and pruritus usually precede rash by a few days; nonspecific constitutional symptoms often accompany rash
  • Differentiate by clinical presentation and clinical course; cutaneous loxoscelism is not confined to a dermatomal distribution, and classic findings associated with cutaneous loxoscelism (ie, marble plaque formation followed by red, white, and blue sign) are inconsistent with herpes zoster
  • Herpes zoster is diagnosed by typical clinical presentation; direct fluorescent antibody testing or polymerase chain reaction assay of vesicular fluid can yield the varicella-zoster virus antigen if the diagnosis remains in question; gold standard method of viral isolation remains culture, despite low sensitivity
• Other spider envenomations ¹⁵
  • Tegenaria agrestis (hobo spider or northwestern brown spider) envenomation
    • Spider is found in the Pacific Northwest region of the United States
    • Envenomation mimics cutaneous loxoscelism with a progressive erythematous lesion that becomes vesicular and results in dermonecrosis
    • Systemic symptoms can occur with envenomation and include headache, visual disturbances, hallucinations, weakness, and lethargy; symptoms develop between 30 minutes and 10 hours after envenomation ³²
    • May differentiate from brown recluse envenomation by geographic location where bite occurs and by distinct systemic symptoms; otherwise, without direct spider identification, it is difficult to differentiate envenomation
  • Other spiders found in the United States whose envenomation can result in dermonecrosis include Chiracanthium species (running spiders and sac spiders), Phidippus (jumping spider), and Argiope (golden orb weaver or black and yellow garden spider) ¹⁶
• Diabetic ulcer ³³
  • Foot ulcers are a common development in individuals with diabetes (lifetime risk approaches 15%)³⁴
  • Ulceration in foot of person with diabetes can occur after minor trauma; once the skin is compromised, many processes (eg, peripheral microvascular disease, peripheral neuropathy, superimposed infection) contribute to defective healing
  • Punched-out necrotic ulcers often develop under callus formation and worsen over time; ulcerative diabetic foot lesions are similar to ulcers that form late in cutaneous loxoscelism
  • Differentiate by clinical presentation and clinical course; brown recluse envenomation is uncommon on the foot unless the bite occurs when spider is trapped inside a shoe; treat any necrotic ulcerative lesion on the foot of a person with diabetes as a diabetic foot ulcer regardless of underlying cause
• Poison ivy allergic contact dermatitis ³⁵
  • Erythematous, intensely pruritic lesions often develop between 24 and 48 hours after exposure to plant. In a linear array, erythematous papules develop and evolve to vesicles and bullae; rash is self-resolving by 3 weeks without development of dermonecrosis
  • Erythema and blistering of lesions are similar in appearance to early cutaneous loxoscelism
  • Differentiate by clinical presentation and clinical course; contact pattern with linear streaks, often involving extremities in nonclothed areas, intense pruritus, and absence of dermonecrosis development distinguishes these diseases clinically
• Pyoderma gangrenosum ³⁶
  • Uncommon neutrophilic dermatosis; results in ulcerative lesions that can resemble the dermonecrotic ulceration that occurs in patients with cutaneous loxoscelism
  • Associated with various conditions, including chronic inflammatory bowel disease, hematologic disorders, and malignancies; up to 50% of patients have a triggering event, such as trauma, surgery, stings, or bites ³⁶
  • Characterized by an enlarging sterile pustule that can evolve into an ulcer with undermined livid borders
  • Differentiate disease based on clinical presentation and clinical course; underlying systemic disorder, chronic nonhealing wound, and triggering event suggest pyoderma gangrenosum
  • Definitive diagnosis is clinical with biopsy findings that exclude alternative diagnoses (eg, vasculitis, pyodermatitis, vasculopathy)
• Burns
  • Ulcerating lesions caused by chemical or thermal burns resemble vesicular phase with ulceration that occurs in patients with cutaneous loxoscelism; individuals with burns usually present with a clear history of trauma
  • Victims of child abuse can present with burns without substantiating history of trauma; localized inflicted contact burns can present with a distinct pattern (eg, metal end plate of cigarette lighter, circular pattern caused by cigarette or cigar)
    • Some historical features concerning for child abuse are previous involvement with children’s services, domestic violence in the home, previous unexplained injuries, and injuries that do not match developmental level of child ³⁷
  • Differentiate conditions based on clinical presentation; distinct regular wound margins or symmetrical wound pattern without evidence of gravitational direction of spread are concerning for abuse rather than cutaneous loxoscelism
  • If an inflicted burn is suspected, child abuse investigation is warranted to determine likelihood of abuse (eg, social services evaluation, careful evaluation for previous unexplained injuries, hepatic transaminase testing, other imaging to exclude occult injury) ^37 38
• Vasculitis ³⁹
  • Inflammatory processes involving blood vessels can result in cutaneous ulceration mimicking the dermonecrotic ulceration that occurs in patients with cutaneous loxoscelism
  • Many underlying causes exist for vasculitis associated with ulcer formation, including connective tissue diseases, malignancy, and drug reactions; lower extremities are often involved
  • Usually, presentation includes development of palpable purpura or vesiculobullous lesions that result in superficial ulceration with regular borders; occasionally, punched-out, irregularly shaped ulcers can result
  • Differentiate conditions based on clinical presentation and disease progression; classic findings associated with cutaneous loxoscelism (ie, marble plaque formation followed by red, white, and blue sign) are inconsistent with underlying vasculitis as cause of lesion
  • Extensive evaluation (eg, biopsy, laboratory tests) is often needed to determine exact underlying cause of vasculitis

Treatment

Goals

• Provide supportive wound care treatment
• For patients who develop systemic loxoscelism
  • Treat hemolytic anemia with packed RBC transfusions
  • Prevent acute kidney injury and renal failure with fluid replacement and urinary alkalinization
  • Monitor for disseminated intravascular coagulation

Disposition

Admission criteria

• Hospitalize patients with severe or significant wounds ⁴⁰ or evidence of systemic loxoscelism ² for observation and further management ²¹

Recommendations for specialist referral

• Consult medical toxicologist for patients with significant necrotic wounds or evidence of systemic loxoscelism for diagnostic and treatment recommendations
• Consult wound care specialist for patients with necrotic wounds for further wound management recommendations (eg, debridement, hyperbaric oxygen therapy)
• Consult hematologist for patients with significant hemolysis or hemolytic anemia for treatment recommendations
• Consult nephrologist for patients requiring dialysis for treatment recommendations
• Late surgical consultation for skin grafting is required for large unacceptable scars in cosmetically sensitive areas

Treatment Options

Mainstay of therapy in the United States is supportive care with expectant observation for both dermatologic and systemic loxoscelism ⁷

• First line supportive care for dermatologic manifestations ⁹
  • Most cutaneous lesions heal with local wound care without aggressive medical treatment
  • Local wound care
    • Antihistamine for itching ⁹
    • Aspirin ⁹ or acetaminophen for pain
    • Rest, cool compress, ⁴¹ compression, and elevation ⁸⁹
      • Avoid aggressive cooling of the skin to avoid exacerbation of tissue damage
    • Loose immobilization of affected extremity ¹⁵
    • Wound cleaning ⁹
      • Recommend general wound care several times daily until wound heals ⁴²
    • Tetanus prophylaxis when indicated ¹⁵
    • Debridement of necrotic wounds in consultation with wound care specialist or surgeon ¹⁵
      • Timing of wound care is debated; most specialists perform it once the wound margins are well defined without advancing margins after 1 to 2 weeks ^1 15
    • Vacuum-assisted wound closure (negative pressure wound therapy)
      • Animal studies indicate accelerated wound healing rates with this novel, largely experimental therapy ⁴³
    • Hyperbaric oxygen therapy
      • Consider for any rapidly deteriorating wounds in consultation with medical toxicologist and wound care/hyperbaric medicine specialist; evidence for efficacy is conflicting ⁴¹
• Care for systemic loxoscelism
  • Serial monitoring for renal impairment and progressive anemia is indicated in patients with significant hemolysis
  • Begin renal protective measures in patients with signs of hemolysis or rhabdomyolysis ⁶¹²
    • Fluid replacement to maintain adequate urine output
    • Urinary alkalinization to maintain urinary pH above 6 or 6.5 (Related: Rhabdomyolysis)⁴⁴
      • Can often be achieved by fluid repletion alone ⁴⁴
      • Add sodium bicarbonate if target pH is not achieved with fluid repletion ⁴⁴
      • Consider mannitol to maintain urine output if it is not established by fluid repletion ⁴⁴
    • Pressor support to maintain renal perfusion
  • Packed RBC transfusions for significant anemia ¹²
  • Dialysis is very rarely required for patients with progressive deterioration in renal function resulting from intravascular hemolysis and rhabdomyolysis ¹⁵

No consensus treatment specific to loxoscelism exists ⁶

• Treatment is largely regional depending on area of world where envenomation occurs
• Loxosceles-specific antivenom is limited to use in South America
  • Available in Brazil, Argentina, Peru, and Mexico; not available in the United States ²
  • Limited and conflicting data about benefit in humans ^2 22
  • Theoretic use is aimed at reducing extent of cutaneous lesion and preventing systemic venom effects ²
  • Delayed presentation often limits use
    • Animal studies have yielded inconsistent findings; ² however, treatment appears most beneficial when administered within 1 hour of envenomation ⁷
      • Some reports suggest benefit if antivenom is administered within 4 hours ¹⁴ and others if it is administered within 48 hours ²
    • Generally, antivenom is not recommended more than 72 hours after envenomation ²
    • Indications vary but are usually based on severity of envenomation ²
• Treatment for hemolysis
  • Use of corticosteroids for severe hemolysis is controversial ¹⁵²²
    • Individualized use of corticosteroids is advocated by some hematologists to treat severe hemolysis ^12 22
    • Theory is that corticosteroids protect reticulocytes from venom effects ¹²
    • Paucity of data to support this approach ^12 45
  • Consider plasma exchange for patients with profound refractory hemolysis ⁴⁶
    • Treatment with plasma exchange in consultation with a hematologist is considered experimental, with success documented in case reports ⁴⁵
• Other unproven treatments for hemolysis are not routinely recommended in the United States owing to lack of efficacy and risk of harm associated with treatment (especially in light of frequent lack of diagnostic certainty in most patients presenting with possible brown recluse envenomation); these modalities include dapsone, colchicine, hyperbaric oxygen, steroids, nitroglycerin, prophylactic antibiotics, electric shock therapy, anticoagulants, and early surgical excision ²⁷⁹
  • Common treatments that may be recommended in consultation with medical toxicologist or surgical subspecialist despite limited evidence of efficacy in humans include the following:
    • Dapsone
      • Dapsone is a sulfone antibiotic with polymorphonuclear leukocyte inhibitory properties and can theoretically antagonize the local inflammatory response triggered by venom ⁴⁷
      • Anecdotal evidence exists for benefit in some animal models when dapsone is begun within 12 hours of envenomation; ⁴⁸ evidence in humans for efficacy is limited and conflicting ⁹
      • Few experts advocate use for adults with proven brown recluse envenomation for potentially necrotic wounds when oral administration is started within 48 to 72 hours ¹⁵
      • Baseline assessment for glucose-6-phosphate dehydrogenase deficiency is indicated before administration; dapsone is contraindicated in patients with glucose-6-phosphate dehydrogenase deficiency and in children⁹⁴¹
      • Adverse effects are a major concern with dapsone administration; some degree of hemolysis occurs in most patients; methemoglobinemia, aplastic anemia, peripheral neuropathy, and cholestatic jaundice are other serious adverse effects ^9 41
    • Hyperbaric oxygen therapy
      • Theory is that this therapy can inactivate some contents of venom by oxidation and improve wound healing by increasing oxygen tension in tissue ⁴¹
      • Evidence for specific use with brown recluse envenomations is limited in humans; there are reports of good outcomes in some uncontrolled human trials ^9 15
      • Some experts advocate use for rapidly deteriorating wounds, whether or not known cause is Loxosceles envenomation ⁴¹
      • Barotrauma and oxygen toxicity are potential adverse effects of treatment ⁹

Nondrug and supportive care

Avoid application of heat or heated compresses to wound; avoid excessive cooling of wound ¹⁵

Avoid fresh frozen plasma or cryoprecipitate administration in patients with significant hemolysis; complement contained in these preparations can trigger further hemolysis ²²

Monitoring

• Monitor cutaneous lesions for wound healing and secondary infection
  • Larger necrotic wounds heal by secondary intention over a period of months
  • Secondary infection is rare; use of antibiotics is discouraged unless definitive evidence of secondary infection is present on examination
  • Referral to a surgical specialist (eg, plastic surgeon) for delayed skin grafting is indicated for any unusually large amount of scarring in a cosmetically sensitive area
• Monitoring in patients with systemic loxoscelism
  • Monitor renal function and electrolytes with serial BUN, creatinine, urinalysis, ⁹ and electrolyte panels ⁴
  • Monitor hemolysis with serial hemoglobin measurements ⁹
  • Monitor for rhabdomyolysis with serial creatine kinase measurements
  • Monitor patients with severe systemic illness for development of disseminated intravascular coagulation with platelet count, D-dimer assay, coagulation tests (prothrombin time/partial thromboplastin time), and fibrin split product testing ⁴

Complications

• Morbidity and mortality are more often associated with envenomation from species native to South America ⁶
• Major morbidity is uncommon ¹³
  • Overall, 10% to 15% of bites lead to major complications (eg, hospitalization, unacceptable scarring, chronic lesions) ⁹
  • Wound-related complications
    • Major scarring can occur
      • Wounds requiring skin grafting are unusual ¹³
    • Chronic lesions and delayed wound healing happen occasionally
    • Pyoderma gangrenosum–like ulcers ^3 9
    • Secondary infection is uncommon ^2 6
  • Systemic loxoscelism
    • Acute hemolysis and hemolytic anemia ^9 49
    • Rhabdomyolysis
    • Acute renal failure⁶
    • Pulmonary edema ⁹
    • Thrombocytopenia ⁶
    • Disseminated intravascular coagulation ⁶
• Mortality is exceedingly rare
  • Most fatalities occur in children ⁶
  • Acute renal failure is primary cause of death ⁶
  • There are case reports of cardiovascular collapse with massive hemolysis and disseminated intravascular coagulation ⁷
  • Reported deaths involving brown recluse species are circumstantial ⁷

Prognosis

• More than 90% of brown recluse spider bites are self-limited without severe necrosis or systemic symptoms ^1 50
• Cutaneous lesions often heal slowly; ulcerative necrotic lesions may persist for 1 to 2 months, leaving a deep scar ¹
• Full recovery is expected from systemic loxoscelism with appropriate supportive care

Screening and Prevention

Prevention

• Advise patient as follows:
  • Protect bed and sleeping area
    • Keep bed away from wall ⁸
    • Inspect sheets and bedding before sleep
  • Avoid and manage household infestations
    • Use screens on basement and ground-floor windows to block spider entry ³²
    • Use insulation strips under doors (may decrease spider infestation) ³²
    • Carefully clean areas of house where spiders commonly hide ¹²
    • Employ glue traps
    • Consult professional to eliminate household infestations
    • Minimize presence of insects on which spiders prey ¹²
  • Avoid bites when dressing
    • Shake out clothing that has not been worn recently to ensure spiders are removed ¹²
    • Carefully inspect clothes that have not been worn recently ⁸
    • Store clothes, shoes, and gloves in sealed plastic bags
  • Avoid bites while working outdoors
    • Remove and reduce debris and rubble; trim or eliminate tall grasses from around outdoor work areas ⁵¹
    • Inspect wood piles before gathering firewood or clearing brush
    • Wear gloves when retrieving firewood or other items stored in potentially infested areas
  • Avoid bites in potentially infested areas (eg, crawl spaces, attics, closets, storage areas, basements)
    • Wear gloves and cover skin while working in potentially infested areas ³²
    • Warn spiders by making noise or vibrations (eg, stomping your feet) before entering potentially infested areas
  • Avoid bites if a spider is found on body by brushing it off and avoiding crushing it ¹²

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