Download Laboratory Testing in Monitoring the Effects of Brown Recluse

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Laboratory Testing in Monitoring the Effects
of Brown Recluse Spider Bites
Amy L. Thompson, PhD, MLS(ASCP)
ABSTRACT
Most people regard brown recluse spiders as dangerous;
however, the risk associated with its bite is not widely
understood. Brown recluse spiders are among the genus
Loxosceles, a group of brown spiders. All spiders in
this genus have a violin or fiddle marking on their dorsal
cephalothorax (back surface) and are often referred to as
fiddleback spiders, but the brown recluse is considered
the most dangerous to humans (Image 1). Brown recluse
spider venom is more toxic than rattlesnake venom, but
the quantity of spider venom injected in the bite of a brown
recluse is typically smaller than the venom delivered in a
rattlesnake bite. The brown recluse (Loxosceles reclusa)
is found in the central United States, including Tennessee,
Arkansas, Missouri, Oklahoma, and Kentucky, and may be
accidentally transported to areas where it is not endemic
(Image 2). Brown recluse spider bites in areas where the
spiders are not endemic are rare.1-4
DOI: 10.1309/LMKIW3WIOO13EMMM
Abbreviations
ELISA, enzyme-linked immunosorbent assay; CBC, complete blood
count; DAT, direct antiglobulin test; ALT, alanine transaminase; AST,
aspartate aminotransferase; LDH, lactate dehydrogenase; CK, creatine
kinase; DIC, disseminated intravascular coagulation; PT, prothrombin
time; PTT, partial thromboplastin time; ESR, erythrocyte sedimentation
rate; G6PD, glucose-6 phosphate dehydrogenase
Department of Biology, Austin Peay State University, Clarksville, TN
*To whom correspondence should be addressed.
E-mail: [email protected]
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Key words: Spider bites, wounds, brown recluse spider
The brown recluse is known for its reclusive behavior and
prefers dark, secluded locations, such as in closets; under
furniture; in folded clothing or in shoes; and in basements,
garages, and crawl spaces. Human bites usually occur
when the spider is inadvertently pressed against the skin,
sometimes by getting trapped in clothing or in bed linens.1-4
Unlike most other spiders, the brown recluse prefers to
consume dead prey rather than to hunt living creatures.
The brown recluse spider does not trap its food in a web,
but rather spins haphazard webs only for the purpose of
laying its eggs.2 When the spider hunts, it bites and injects
venom, then leaves, returning later to feed on its prey.5 For
this reason humans who are bitten by the brown recluse
often do not see the spider. To confirm a brown recluse
spider bite, it is important to collect the spider and bring
it to a specialist for identification. Only 10% of bite victims
do this; some victims might not realize they have been
bitten until later, or cannot find the spider.1,6,7
If the spider is not caught and brought in for confirmation,
diagnosis is based on the patient’s report, wound
appearance, and other signs and symptoms. Although a
diagnostic test for Loxosceles reclusa bite is not available
in clinical laboratories, an enzyme-linked immunosorbent
assay (ELISA) has been developed to detect brown recluse
spider venom. This test may have potential for clinical
application, using samples collected by swabbing the bite
site.8 Without the spider, the diagnosis often is reported
as “presumptive brown recluse spider bite.” Some reports
suggest that 80% of reported brown recluse bites were
caused by another type of spider or insect or were actually
not a bite at all.1,6,7
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Brown recluse spiders are endemic to the central United States and
are highly venomous. Although most brown recluse spider bites do
not cause dangerous wounds or systemic symptoms, severe cases
can occur. Changes in laboratory values may include hemolysis,
thrombocytopenia, coagulopathy, and altered chemistry and urinalysis
results. Neutrophil involvement in wound progression and white blood
cell changes can be observed. If blood products are indicated, fresh
frozen plasma and cryoprecipitate should be avoided. There is no
single clinical lab test that can be used to diagnose a brown recluse
spider bite, but laboratory involvement in monitoring progression and
treatment may be significant.
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Image 1
Brown recluse spider. Note fiddle marking on dorsal
cephalothorax. Source: Wikipedia (Brown Recluse Spider),
http://en.wikipedia.org/wiki/File:Brown-recluse-2-edit.jpg.
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Image 2
Brown recluse spider endemic areas. Brown recluse spider
bites are unlikely outside endemic areas. Source: Wikipedia
(Brown Recluse Spider), http://upload.wikimedia.org/wikipedia/
commons/d/d9/Loxosceles_reclusa_range.png.
Initial Bite and Progression
of Wound
A brown recluse bite and envenomation has been described
as a pinprick with or without stinging and pain, although
some victims felt nothing at all.1,3,9 The envenomated area
may become swollen, red, and itchy. The bite usually
develops a purple center (local thrombosis), surrounded by
a red ring, like a bull’s eye, and a white blister will emerge.
Unlike most skin wounds, the brown recluse bite is dry
with little or no drainage. The center eventually retracts
into a lighter center with irregular dark edges surrounded
by redness. The red area may be surrounded by a white
or blanched area due to vasoconstriction and ischemia,
creating a red, white, and blue appearance. Bruising often
appears along the local lymphatic vessels (Image 3).
In rare cases, the wound can become necrotic, turning
black. Many people are familiar with this dramatic result of
brown recluse spider bites, although development into a
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necrotic lesion is not common. The severity of symptoms
depends on each individual victim’s immune response
and the amount of venom injected by the spider; 90% of
bites heal without complications. Three percent of brown
recluse bites, however, eventually require a skin graft.1,3
The bite may go unnoticed for 6 to 8 hours, with the wound
changing over a period of days to weeks; complete healing
may require weeks to months and years in some cases.
Neutrophil activation and granular secretion exacerbate the
effects seen with these bites. Treatment of brown recluse
spider bites often involves a wait-and-see approach, since
the bite typically gets worse over a period of days and then
begins to heal.1-3
Systemic Loxoscelism
Systemic symptoms (systemic loxoscelism) are observed in
fewer than 1% of brown recluse bites and are mostly seen
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Image 3
Brown recluse spider bite day 12 of patient on prednisone.
Note angry redness with white blanching and sinking in of center.
Image provided by Amy L. Thompson.
Laboratory Testing
Although no single laboratory test can be used to diagnose
a brown recluse spider bite, the laboratory is involved
in more severe bite cases involving necrosis or when
systemic symptoms exist. Important laboratory parameters
potentially involve red blood cells, white blood cells,
platelets, bilirubin, liver enzymes, and urinalysis.3,7,9
Red Blood Cell Changes
Complete blood counts (CBCs) taken over several days
are important to document changes associated with the
poisoning. Hemolysis potentially leading to hemolytic
anemia is sometimes observed with brown recluse spider
bites due to sphingomyelinase D activity as previously
described. Intravascular and/or extravascular hemolysis
may be observed and laboratory testing will be helpful
in determining whether either type is occurring. The
plasma-free hemoglobin test or serum haptoglobin can
be used to monitor hemolysis and differentiate between
intravascular and extravascular states. Increased levels of
plasma-free hemoglobin are suggestive of intravascular
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hemolysis, since normally little to no free hemoglobin
is observed in plasma. Since haptoglobin binds free
hemoglobin in the blood, decreased levels of haptoglobin
suggest intravascular hemolysis, whereas normal levels of
haptoglobin suggest extravascular hemolysis.3,7,9
The Direct Coombs’ Test (direct antiglobulin test or DAT)
result is variable among brown recluse spider bite patients
and may be positive or negative, with positive results
suggesting that complement or antibodies are present
on the red blood cell surface. One study suggested that
interleukin-8, the factor that attracts neutrophils, and
granulocyte-macrophage colony stimulating factor, the
cytokine that stimulates granulocyte production, might
be involved in this process.3,12,13 For patients requiring
blood products, packed red blood cells should be used in
place of fresh frozen plasma or cryoprecipitate, since both
contain complement and may worsen hemolysis.7
Chemistry and Urinalysis Changes
Increased total and indirect bilirubin levels often result
from hemolysis.12 Another potential finding is elevated
liver enzymes, including alanine transaminase (ALT)
and aspartate aminotransferase (AST). If liver enzymes
are elevated, supportive treatment should not include
potentially hepatotoxic medications. Elevated lactate
dehydrogenase (LDH) is consistent with hemolysis.7
Urinalysis may reveal hemoglobinuria, but not hematuria,
as a result of hemolysis.2,9 Urine may be dark and high
levels of urobilinogen may be present, suggesting
extravascular hemolysis.7 Myoglobin may be found in the
urine due to rhabdomyolysis and corresponding elevated
blood creatine kinase (CK) may be noted.12
Platelet and Coagulation Changes
Thrombocytopenia occurs due to platelet activation by
sphingomyelinase D.4 The presence of elevated fibrin
degradation products, such as the D-dimer, is suggestive of
disseminated intravascular coagulation (DIC). Prothrombin
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in children, elderly individuals, and immunocompromised
patients. Systemic symptoms include fever, chills, nausea,
vomiting, anorexia, malaise, arthralgia, myalgia, cellulitis,
and a morbilliform rash. Brown recluse spider venom
contains sphingomyelinase D, which converts erythrocytic
membrane sphingomyelin to ceramide-1-phosphate,
leading to hemolysis; platelet aggregation, and thrombosis.
Damage to myelin may cause pain and interruption of nerve
conduction. Although rare, pulmonary edema may occur as
a result of sphingomyelinase D activity in the lungs; acute
renal failure has also been reported. Even though systemic
loxoscelism is not common, it is important for those
suspecting a brown recluse bite to seek medical assistance,
as necrosis and systemic loxoscelism can be severe.3,7,9-11
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time (PT) and partial thromboplastin time (PTT) may be
elevated or normal. If not treated promptly, DIC can lead to
acute renal failure, multiple organ failure, and death.7,12
White Blood Cells and Inflammation
Mild leukocytosis is common in brown recluse spider
bites, although leukopenia may be observed.2,7 The
erythrocyte sedimentation rate (ESR) often is elevated,
supporting the presence of an inflammatory response. A
skin biopsy of the wound typically reveals eosinophils and
neutrophils, along with thrombosis and inflammation of
subcutaneous adipose (fat).2
for all healthcare professionals, especially those in
brown recluse spider endemic areas, to recognize the
signs of a brown recluse bite and the clinical symptoms
it may produce. In severe cases, particularly those
involving hemolytic changes, the laboratory is important
for monitoring the progression of disease and potential
side effects of drugs used to treat the inflammatory
response and hemolysis. Laboratory professionals
should be aware of necessary requirements to prevent
exacerbation of patient symptoms, such as G6PD with
dapsone therapy, and avoiding fresh frozen plasma and
cryoprecipitate. LM
Treatment
The treatments for a brown recluse spider bite are as
varied as the symptoms. Some healthcare providers
recommend the use of dapsone, which inhibits neutrophil
migration, attachment to the endothelium, and granular
secretion. Because of the hemolytic effects of dapsone,
glucose-6 phosphate dehydrogenase (G6PD) evaluation
prior to starting the drug is important and treatment
should be avoided in those with a G6PD deficiency.
Levels of G6PD, ALT, and AST should be followed during
dapsone treatment and the patient should additionally be
monitored for hemolysis and leukopenia. 2-4,7
The use of oral steroids, such as prednisone, to prevent
systemic inflammation has been recommended,
although there is disagreement over the benefit of steroid
treatment.2,9 Aspirin can be used to inhibit platelet
aggregation and reduce the risk of thrombosis and
possibly DIC. A tetanus shot may be given prophylactically
and antibiotics may be given to prevent secondary
wound infections.3,7,9 Additionally, antihistamines, such as
Benadryl (diphenhydramine), have been shown in some
cases to be more effective than surgical wound care in
stimulating wound healing.14
Conclusion
Most brown recluse spider bites heal without medical
input or laboratory testing. Some bites, however, result in
systemic symptoms that require prompt treatment. The
development of an ELISA for Loxosceles venom may aid
in the diagnosis of brown recluse spider bites. Until such
confirmatory testing can be established, it is important
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