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The black widow spider bite: differential diagnosis, clinical manifestations, and treatment options.

INTRODUCTION

Although taxonomic analyses have revealed some 45,019 spider species worldwide, few are a threat to humans as few have venom that carries components active against vertebrates. (1-3) In the US, five black widow (Latrodectus) species are found in all states except Alaska, account for over 2,500 medically significant bites (envenomations) each year, although the actual number of envenomations is likely underreported. (4,5) Only female spiders are dangerous and are usually identified as dark grey to black, 30-40 mm in size, displaying red to orange markings such as an hourglass, geometric patterns, spots, or stripes on the ventral abdomen. (4-6) (Figure 1). Two widow species do not have this "classic Latrodectus look." L. geometricus, an introduced widow species increasingly common in the South, is smaller and usually lighter than most widow species, and ranges from tan to dark brown. It often has a black and white geometric pattern on its dorsal abdomen and a ventral abdominal orange to yellowish hourglass pattern. Its envenomations can be severe. (4-9) (Figure 2) L. bishopi found in Florida has a reddish-orange head, thorax, legs, a black abdomen with red spots with yellow borders, and lacks a complete ventral hourglass pattern. (4-6) (Figure 3). Envenomations by this species are rare. (4-7,10) Male widow spiders are smaller, lighter, and rarely inflict medically significant bites. (4-6) Black widow spiders are most active in the warmer months, tend to avoid occupied buildings, and are usually not aggressive, biting only when disturbed in their habitats of outbuildings, garages, and wood piles. (4-7) They are common in the Southern US. (4-7,10) When disturbed and torn, Latrodectus webs make an unmistakable crinkling sound that is usually different from other spider webs and may serve as a warning to individuals familiar with widow spider webs. (11)

[alpha]-LATROTOXIN AND LATRODECTISM

In the early 1900's black widow bites gained recognition as a medically significant event. (4-6) Several neurotoxins that selectively affect insect and crustacean neurons are present in widow toxin, and one a-latrotoxin is 130 kDa vertebrate-specific neurotoxin, roughly 15-fold more potent than prairie rattlesnake venom. (12) a-latrotoxin manifests a significant role when capturing mice, small snakes, and lizards. It binds to mammalian pre-synaptic neurons forming a transmembrane channel, causing a calcium influx followed by exhaustive vesicular release of acetylcholine, norepinephrine, glutamate, and enkephalins from the nerve terminals. (5,12-15,17) Initially, pain, edema, and erythema occur at the bite area, forming an annular lesion followed by latrodectism: a syndrome of generalized diaphoresis, extreme muscle pain, tachypnea, tachycardia, hypertension, flushing, headache, nausea, anxiety, and vomiting, and rarely myocarditis and priapism. (5,12,13,17-20) (Figure 4). Despite the extreme pain and severe symptoms of latrodectism, permanent disability or death is rare. (5,13,17-20) Bites are most common on the lower extremities, followed by the upper extremities, and less commonly on the trunk. No correlation between the bite location and the clinical course of latrodectism has been identified. (20)

LATRODECTUS ENVENOMATION TREATMENT

Most black widow bites resolve in three days, and are usually treated with opioid analgesics, antihypertensive agents, calcium gluconate, and muscle relaxants, such as benzodiazepines, to provide symptomatic relief. (5,13,17-20) In many cases calcium gluconate and muscle relaxants do not provide sufficient relief, and the more effective benzodiazepines and opioid treatments require repeated administration in individuals with severe reactions to [alpha]-latrotoxin. (21,22) When unsuccessful, an equine partially purified IgG antivenin may be used that is specifically directed against the common southern widow spider's venom (L. mactans, Merck & Co. Inc. Whitehouse Station, NJ. (17,18,20,23) A single pre-diluted 2.5 ml antivenin vile, infused over a 15 to 30 minute period provides symptom relief within an average of 31 minutes of infusion. (23) Interestingly, the antivenin has been used successfully 90 hours post-envenomation. (23,24) Additionally, individuals treated with the antivenin usually require shorter hospitalization time than those given opioid analgesics and benzodiazepines. (23)

Adverse reactions to the antivenin include anaphylactic or hypersensitivity reactions due to infusing equine-derived whole IgG. However, these reactions are rare and withholding antivenin based on these issues alone is unfounded. (18,19,23-25) The indications for antivenin use include: (1) continuing severe pain unresponsive to opioids; (2) extremes of age, e.g., children under the ages of 3-10 and the elderly, especially those with cardiovascular disease and the inability to tolerate autonomic stresses of latrodectism; and (3) evenomations in pregnant patients. Contra-indications to antivenin use include severe atopy and prior antivenin reactions. (17,18,22-25)

Although anaphylactic reactions to the L. mactans equine antivenin are rare, its use does carry risks, and examples of anaphylactic reactions and two deaths have followed antivenin use. (23,25,26) Recently a highly purified equine F(ab)2 fragment black widow antivenin (Analatrol) has undergone a randomized, placebo-controlled Phase II clinical trial. A purified F(ab)2 fragment should be less antigenic than whole IgG and be a safer treatment. (27) In the Phase II study, 24 envenomated individuals were divided into two groups, one treated with three vials of F(ab)2 fragment antivenin 50ml normal saline and a placebo group given 50ml normal saline only.

Antivenin administration reduced pain more quickly than in the placebo group in individuals with moderate to severe latrodectism. Anti-venin treatment had an adverse event profile similar to that of the placebo. (27) A Phase III clinical will be required to further evaluate this antivenin.

Antivenin use requires definitive identification of a Latrodectus bite, and often patients often do not know they have been bitten. (18,19,23-26) Managing such cases requires: 1) a high level of clinical suspicion, 2) a thorough patient history, especially concerning places where a bite could have occurred, and 3) knowledge of how a spider bite presents. (18,19,23-26) Failure to recognize a bite and give appropriate treatment can result in significant patient morbidity.

EXAMPLE: A CASE REPORT OF A PEDIATRIC ENVENOMATION

Gonzalez described an envenomation in a two year old girl. The girl had put on a costume and became agitated. (28) The costume was removed and a widow spider was found. In the emergency room (ER) bite marks were identified on her right thigh which had surrounding erythema. The girl was anxious and restless, and treated with a narcotic. She improved and was discharged. Later that night she developed intractable periodic emesis, was given an antiemetic in the ER, and her symptoms temporally resolved. Later her emesis returned accompanied by a urticarial rash. She was re-admitted, the antiemetic was continued, and diphenhydramine, codeine and intravenous diazepam were initiated. She became tachycardic and hypertensive with a systolic blood pressure of 140-166 mm Hg and a diastolic of 110 mm Hg. Oral nifedipine was administered to treat her hypertension. Antivenin use was considered, but since 48 hours had passed, it was not used as her symptoms were expected to lessen soon. Her hypertension and tachycardia soon resolved and remained normal for 24 hours. Forty-eight hours later her symptoms improved considerably, she was discharged with no long-term sequelae.

DIFFERENTIAL DIAGNOSIS

The differential diagnosis of a black widow bite is broad and includes other arthropod bites and stings, allergic and chemical contact dermatitides, and different infection diseases, especially Staphylococcal and problems due to Methicillin-resistant Staphylococcus aureus (MRSA). A short list of differential diagnoses for black widow bites is outlined below. (29) (Table 1) The differential diagnosis for the systemic/neuromuscular manifestations is also quite broad and can include such diverse events as alcohol/opiate withdrawal, tetanus, or an acute surgical abdomen. (30-33) A short list of these differential diagnoses is given in Table 2.

CONCLUSION

Black widow spider bites cause significant patient morbidity. (5,13,17-20,25) Recognition that a bite has occurred can be difficult, as frequently patients do not know they have been bitten, and physicians fail to recognize the signs and symptoms of latrodectism. (5,13,17-20,25) Effective treatment of black widow bites requires physician recognition of the signs and symptoms of latrodectism, combined with a thorough patient history. A recent patient history of contact in areas of black widow habitat is especially useful. (5, 13, 17-20,25)

Rodney Shackelford, DO, PhD; Diana Veillon, MD; Nicole Maxwell, BS; Lisa LaChance, BA; Tamara Jusino, MS; James Cotelingam, MD; Patrick Carrington, MD

REFERENCES

(1.) World Spider Catalog (2014). Natural History Museum Bern; http:// wsc.nmbe.ch. version 15.5; Accessed on September 18, 2014.

(2.) Holve S. Venomous spiders, snakes, and scorpions in the United States. Pediatr Ann. 2009;38:210-217.

(3.) Saucier JR. Arachnid envenomation. Emerg Med Clin North Am. 2004;22:405'422.

(4.) Bronstein AC, Spyker DA, Cantilena LR, Jr, Green JL, Rumack BH, Giffin SL. 2008 Annual report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 26th annual report. Clin Toxicol (Phila). 2009;47:911-1084.

(5.) Daly FFS, White J. Widow and related Latrodectus spiders. In: Brent J, Wallace K, Burkhart K, Phillips S, Donovan J, editors. Critical care toxicology: diagnosis and management of the critically poisoned patient. Philadelphia, PA: Elsevier Mosby; 2005. pp. 1187-1193.

(6.) Maretic Z. Latrodectism: variations in clinical manifestations provoked by Latrodectus species of spiders. Toxicon. 1983;21:457-466.

(7.) Goddard J, Upshaw S, Held D, Johnnson K. Severe reaction from envenomation by the brown widow spider, Latrodectus geometricus (Araneae: Theridiidae). South Med J. 2008;101:12691270.

(8.) Carbonaro PA, Janniger CK, Schwartz RA. Spider bite reactions. Cutis 1995;56:256-259.

(9.) http://www.cirrusimage.com/spider brown widow.htm

(10.) http://bugguide.net/node/view/708167

(11.) Matthews ET. Black widow spider [letter]. N Engl J Med 1997;337:1248.

(12.) Garb JE, Hayashi CY. Molecular evolution of [alpha]-latrotoxin, the exceptionally potent vertebrate neurotoxin in black widow spider venom. Mol Biol Evol. 2013;30:999-1014.

(13.) Vetter RS, Isbister GK. Medical aspects of spider bites. Ann Rev Entomol. 2008;53:409-429.

(14.) McCormick S, Polis GA. Arthropods that prey on vertebrates. Biol Rev. 1982;57:29-58.

(15.) Hodar JA, Sanchez-Pinero F. Feeding habits of the black widow spider Latrodectus lilianae (Araneae: Theridiidae) in an arid zone of south-east Spain. J Zool. 2002;257:101-109.

(16.) Rosenthal L, Zacchetti D, Madeddu L, Meldolesi J. Mode of action of alpha-latrotoxin: role of divalent cations in Ca2(+)-dependent and Ca2(+)-independent effects mediated by the toxin. Mol Pharmacol. 1990;38:917-923.

(17.) Gaisford K, Kautz DD. Black widow spider bite: a case study. Dimens Crit Care Nurs. 2011;30:79-86.

(18.) Offerman SR, Daubert GP, Clark RF. The treatment of black widow spider envenomation with antivenin latrodectus mactans: a case series. Perm J. 2011;15:76-81.

(19.) Shlamovitz GZ. Man with back pain. Black widow spider bite. Ann Emerg Med. 2011;58:496-500.

(20.) Moss HS, Binder LS. A retrospective review of black widow spider envenomation. Ann Emerg Med. 1987;16:188-192.

(21.) Bloom JW, Chernick DA, Davidson AB, et al. Reversal of central benzodiazepine effects by flumazenil after intravenous conscious sedation with diazepam and opioids: report of a double-blind multicenter study. The Flumazenil in intravenous conscious sedation with diazepam multicenter study group II; Clin Ther. 1992;14:910-923.

(22.) Key GF. A comparison of calcium gluconate and methocarbamol (Robaxin) in the treatment of Latrodectism (black widow spider envenomation). Am J Trop Med Hyg. 1981;30:273-277.

(23.) Clark RF, Wethern-Kestner S, Vance MV, Gerkin R. Clinical presentation and treatment of black widow spider envenomation: a review of 163 cases. Ann Emerg Med. 1992;21:782-787.

(24.) O'Malley GF, Dart RC, Kuffner EF. Successful treatment of latrodectism with antivenin after 90 hours. N Engl J Med. 1999;340:657.

(25.) Hoyte CO, Cushing TA, Heard KJ. Anaphylaxis to black widow spider antivenom. Am J Emerg Med. 2012;30:836.

(26.) Murphy CM, Hong JJ, Beuhler MC. Anaphylaxis with Latrodectus antivenin resulting in cardiac arrest. J Med Toxicol. 2011;7:317-321.

(27.) Dart RC1, Bogdan G, Heard K, et al. A randomized, double-blind, placebo-controlled trial of a highly purified equine F(ab)2 antibody black widow spider antivenom. Ann Emerg Med. 2013;61:458-467.

(28.) Gonzalez F. Black widow bites in children. J Am Osteopath Assoc. 2001;101:229-231.

(29.) Diaz JH, Leblanc KE. Common spider bites. Am Fam Physician. 2007;75:869-873.

(30.) Muller GJ. Black and brown widow spider bites in South Africa. A series of 45 cases. S Afr Med J. 1993;83:399-405.

(31.) Kara H, Ak A, Bayir A, Avci A. Reversible myocarditis after spider bite. BMJ Case Rep. 2013:8;2013.

(32.) Mofenson HC, Caraccio TR. Spider bites aren't an itsy-bitsy problem in kids. Contemp Pediatr. 1993;10:18-24.

(33.) Binder LS. Acute arthropod envenomation. Incidence, clinical features and management. Med Toxicol Adverse Drug Exp. 1989;4:163-173.

Dr's. Shackelford, Veillon, Cotelingam and Ms. LaChance are associated with the Department of Pathology, LSU Health Sciences Center-Shreveport, LA.; Ms. Maxwell is an independent researcher, Lee's Summit, MO; Dr. Carrington is associated with the Section of Dermatology, Department of Medicine, LSU Health Sciences Center, Shreveport, LA; and Dr. Jusino is affiliated with Clinical Molecular Pathology Consultative Services, LSU Health Sciences Center, Shreveport, LA.

Table 1: A short differential diagnosis
of black widow bites (modified from 29).

Arthropod
Bites/Stings       Infectious Diseases     Other Conditions

Bee/Hornet/Wasp/   Dermatomycosis          Allergic/Chemical
  Yellow Jacket                              Contact dermatitides
Scorpion           Chagas Disease          Autoimmune Vasculitides
Centipede          Boils/Furuncles         Chemical Burns
Tick               Herpes Simples/Zoster   Poison Ivy/Oak/Sumac
Mosquito           Impetigo                Erythema Multiforme
Reduviid bug       Lyme Disease            Lymphomatoid Papulosis

Table 2: A short differential diagnosis of the neuromuscular
manifestations of black widow envenomations.

Disease               Comments                               References

Myocardial ischemia   Latrodectism should be considered       24,30,31
or infarction         when treatments aimed at cardiac
                      problems fail and/or ECG and cardiac
                      biomarkers fail to show a myocardial
                      ischemia. Widow bites rarely cause
                      myocarditis with ECG changes and
                      increases in cardiac biomarkers,
                      thus latrodectism can closely mimic
                      myocardial ischemia

Alcohol/opiate        Alcohol and opiate withdrawal can       24,30,31
withdrawal            resemble an envenomation. A history
                      of alcoholism/opiate abuse and with
                      recent drug cessation is helpful.

Organophosphate       This poisoning can closely mimic           26
poisoning (OP)        latrodectism. A history of OP
                      exposure and blood/urine OP
                      metabolites is useful.

Acute surgical        Abdominal muscle spasms can mimic a     24,30,32
abdomen               surgical abdomen, with widow bites
                      the muscle spasms are more likely
                      intermittent and hypertension is
                      more common with widow bites.
                      Individuals with a surgical abdomen
                      often avoid movement, while those
                      with latrodectism tend to move and
                      seek a comfortable position.

Other                 Scorpion stings present with severe     24,29,30
envenomations         immediate pain. Profuse sweating and
                      abdominal rigidity are not typical
                      of scorpion stings. Snake bites are
                      almost always identified and often
                      cause visual disturbances. Cytotoxic
                      spider envenomations (Brown Recluse)
                      cause local tissue necrosis.

Rabies                Rabies usually has a history of            30
                      contact/bite with an animal. Rabies
                      shows excessive motor activity,
                      hydrophobia, and
                      excitation/agitation.

Tetanus               Tetanus can closely resemble             32,33
                      latrodectism. A history of a
                      puncture would and lack of a recent
                      tetanus vaccination is useful.

Renal colic           Renal colic causes severe abdominal      24,32
                      pain, much like latrodectism. Thus a
                      widow envenomation should be in the
                      differential, especially with a
                      history of spider habitat exposure.

Sepsis                Latrodectism can mimic sepsis,           24,29
                      especially Staphylococcal and
                      problems due to MRSA. A poor
                      response to antimicrobial therapies,
                      combined with a history of spider
                      habitat exposure should place
                      latrodectism in the differential.

Food poisoning        Latrodectism and food poisoning can        24
                      both cause severe abdominal pain and
                      severe cramping, with nausea and
                      vomiting. A good clinical history on
                      recent food intake and possible
                      spider exposure is useful. Food
                      poisoning rarely causes hypertension
                      and the muscle cramping in
                      latrodectism typically migrates
                      proximally from the site of the
                      bite.
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Author:Shackelford, Rodney; Veillon, Diana; Maxwell, Nicole; LaChance, Lisa; Jusino, Tamara; Cotelingam, Ja
Publication:The Journal of the Louisiana State Medical Society
Article Type:Report
Date:Mar 1, 2015
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