A review of the diagnosis and treatment of envenomations of brown recluse spiders.
Introduction
This article will review the diagnosis and treatment of envenomations of brown recluse spiders. Whether an individual clinician will commonly treat these envenomations depends on where in the country they are practicing.
Brown Recluse Spiders
The brown recluse spider or Loxosceles reclusa, is found mainly in the Midwest and Southcentral regions of the U.S.[5] It is also called the violin or fiddleback spider because of a violin-shaped marking on its back. An adult brown recluse spider with its legs extended is about 1 to 1.5 inches long.[6] They prefer dark areas such as under tree bark and rocks. Indoors they may be found in attics, closets, drawers or under bed sheets. These spiders generally only bite as a defense mechanism when they are crushed or pressed on.[5]
Brown Recluse Venom
The spider venom is cytotoxic and hemolytic and can cause a syndrome called dermonecrotic arachnidism.[5] Sphingomyelinase D is a major component of the venom that can cause hemolysis and activate the complement system. There are other proteases in the venom that degrade collagen, fibronectin, fibrinogen, gelatin, and elastin basement membranes that have a synergistic effect with sphingomyelinase D leading to many of the skin findings detailed below. Hyaluronidase, alkaline phosphatase, esterase, and ATPase are also involved with the skin manifestations.[5]
Brown Recluse Spider Envenomation
The initial bite is usually painless until three to eight hours later when the bite may become red, swollen and tender. The majority of brown recluse spider bites remain localized, healing within three weeks without serious complication or need of medical intervention. In more severe envenomations, the victim may develop a necrotic lesion appearing as a dry sinking bluish patch with irregular edges, peripheral erythema and frequently central pallor or a blister. An elevated lesion is not typical of a brown recluse bite. As the venom continues to destroy tissue, the wound may expand up to several inches over a period of days or weeks. The necrotic ulcer can persist for several months leaving a deep scar.[6] Systemic symptoms such as chills, malaise, nausea, headache, dizziness and myalgias may also occur. In children, the elderly, or people with existing medical problems, the systemic reaction may be more severe and may include weakness, fever, joint pain, hemolytic anemia, thrombocytopenia, organ failure, disseminated intravascular coagulation, seizures, and death.[5,6] In children, systemic symptoms may occasionally occur without skin findings and should be considered in the differential of acute hemolytic anemia in regions known to have the brown recluse spiders. Hemolysis has been reported up to seven days after a bite so follow up instructions should be given to parents of children even if there are no systemic findings during the initial visit.[5]
Diagnosis of Brown Recluse Spider Bites
Misdiagnosis of brown recluse spider bites is common. Frequently methicillin resistant staphylococcus aureus(MRSA) abscesses are misidentified as a brown recluse spider bite. Unlike a brown recluse bite, MRSA abscesses may be crusted, purulent, and elevated. A mnemonic NOT RECLUSE has been created to help physicians determine if a skin lesion is or is not from a brown recluse spider. The authors suggest that if 2 or more NOT RECLUSE signs are present, a brown recluse spider bite is a less likely cause of the lesion(s).[7]
N – Numerous - A typical recluse bite is a single lesion, but occasionally can be two bites. Multiple lesions indicate some other rash or insect bite
O – Occurrence - Most commonly a recuse spider bite involves disturbance of the spider, in bed or hiding in a closet, attic or garage. If no such disturbance is noted, another diagnosis should be considered.
T – Timing - Recluse bites are most commonly seen from April to October, although occasionally they can be seen in the winter if the spider is disturbed. If the skin lesion occurs outside of this time frame, another diagnosis should be considered.
R – Red Center - A lesion with a red center is generally not a recluse spider bite. Due to tissue ischemia near the bite, the central part of the lesion will be pale, blue-white, or purple. There may be erythema around the lesion due to cytokine release.
E – Elevated - Recluse bites are generally flat or sunken. If the lesion is elevated another diagnosis should be considered.
C – Chronic - Most recluse bites, except those with a large amount of tissue destruction, heal within three months and it may be as little as three weeks for smaller lesions. Incomplete healing of the lesion suggests another diagnosis.
L – Large - The largest brown recluse bite injury generally does not exceed ten centimeters, although there may be a larger area of erythema around the wound. Very large lesions suggest another diagnosis, possible pyoderma gangrenosum.
U – Ulcerates Too Early - Recluse bites do not typically ulcerate until seven to 14 days after envenomation.
S – Swollen - Recluse bites typically do not cause massive swelling below the neck or above the feet. There may be significant swelling in recluse bites to the feet or eyelids. Swelling of lesions on the body suggests another diagnosis.
E – Exudative - With the exceptions of eyes and toes, recluse bites are not initially exudative, moist, or purulent. If pus is seen, another diagnosis hold be considered.
Treatment
Ice packs and arm elevation are initial first aid for brown recluse bites. Sphingomyelinase D has been shown to have less activity in colder temperatures.[8] Tetanus immunization should be updated if necessary.[5] Antihistamines may be used for itching. There is one article in the literature by a physician who initially in his career did many surgical excisions for brown recluse bites and then he started prescribing antihistamines for seven to ten days. He reported that by using antihistamines in a series of 100 brown recluse bites, he did not need to perform any more surgical excisions. However, there does not appear to be any other clinical studies in the medical literature supporting this claim.[9] Prophylactic antibiotics are not recommended.[10]
While most brown recluse spider bites do not require any specific therapy, suggested therapies in the literature for more severe envenomations include dapsone, corticosteroids, antivenom, and surgical excision. Unfortunately, there is a dearth of randomized studies of treatment modalities and some conflicting results. Antivenom is not currently available in the U. S., although there is one available in South America.[11]
Use of dapsone for brown recluse spider bites is controversial with conflicting animal studies, but is considered a therapeutic option. Its use is based on its ability to inhibit polymorphic leukocytes which ameliorates some of the venom’s effects.[12,13,14] There may be serious side effects associated with the use of dapsone such as dose-related hemolysis, agranulocytosis, aplastic anemias, and methemoglobinemia.[15] Because of these potential serious side effects, dapsone should be reserved for adult patients who have rapidly progressing necrotic lesions. It is not recommended for children. Adults who are selected to receive dapsone should first be screened for glucose-6-phosphate dehydrogenase deficiency, to prevent hemolysis.[15]
One study found no difference in wound healing between dapsone and brown recluse antivenom each alone or combined, although it was felt that dapsone had eliminated the need for surgical excision in some patients.[13]
Another animal study compared early surgical excision to delayed surgical excision after dapsone and found use of dapsone prior to surgery decreased scarring, complications and in one case the need for surgical excision.[14] They also found the use of corticosteroids or early surgical excision in an animal model were not effective therapies. If needed, surgical excision of a brown recluse lesion should be delayed until the wound edges are clearly demarcated. Skin grafting may be required for large lesions.[15]
Hyperbaric oxygen has been found in one animal study to reduce necrosis from brown recluse envenomation when administered within 48 hours, although other animal studies found no beneficial effect or histologic improvement without obvious clinical benefit from hyperbaric therapy. [16,17,18] Hyperbaric oxygen has also been postulated to decrease wound damage secondary to brown recluse envenomation in at least two ways. It is thought that wound damage is decreased in part because hyperbaric oxygen inactivates sphingomyelinase D by the disruption of sulfhydryl groups. Hyperbaric oxygen therapy also increases the production of collagen by fibroblasts, thereby facilitating wound healing.[15] There are someanimal studies and case reports that have demonstrated some improvement of brown recluse skin lesions with hyperbaric therapy acutely, as well as in patients with non-healing wounds.[16,17,18,19]
Conclusion
Fortunately, most of the envenomations from brown recluse spiders are not severe. However, severe systemic toxicity can occur. Disfiguring scars with deep tissue penetration are possible with brown recluse spider bites. Treatment protocols for severe brown recluse spider bites are hampered by a lack of good scientific evidence, although ice packs, dapsone in adults, hyperbaric therapy and delayed surgical excision, if needed, are most frequently recommended. Antihistamines may help with itching and there is one anecdotal case series, not confirmed by other studies, where the author suggested that antihistamines may help with wound healing.
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References
[5] Anoka IA, Robb EL, Baker MB. Brown Recluse Spider Toxicity. [Updated 2020 Aug 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; Last Update: August 10, 2020. Retrieved from: https://www.ncbi.nlm.nih.gov/books/NBK537045/
[6] Potter MF. Brown Recluse Spider. University of Kentucky College of Agriculture, Food and Environment. Last revised 7/12/18. Retrieved from: https://entomology.ca.uky.edu/ef631
[7] Stoecker WV, Vetter RS, Dyer JA. NOT RECLUSE—A Mnemonic Device to Avoid False Diagnoses of Brown Recluse Spider Bites. JAMA Dermatol. 2017;153(5):377–378. Retrieved from: https://jamanetwork.com/journals/jamadermatology/article-abstract/2603498
[8] Merchant ML, Hinton JF, Geren CR. Sphingomyelinase D activity of brown recluse spider (Loxosceles reclusa) venom as studied by 31P-NMR: effects on the time-course of sphingomyelin hydrolysis. Toxicon. 1998 Mar;36(3):537-45. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/9637373/
[9] Wilson JR et al. Brown Recluse Spider Bites: A Complex Problem Wound. A Brief Review and Case Study. Wound Care Learning Network. March 2005. Retrieved from: http://www.o-wm.com/content/brown-recluse-spider-bites-a-complex-problem-wound-a-brief-review-and-case-study
[10] Carlton Jr. PK. Brown recluse spider bite? Consider this uniquely conservative treatment -An antihistamine and observation work as well—and often better—than more intensive therapies. The Journal of Family Practice. Vol 58, No. 2. February 2009. Retrieved from: https://cdn.mdedge.com/files/s3fs-public/Document/September-2017/5802JFP_Article7.pdf
[11] Tavener B. Biting back: Taking the sting out of spider venom. BBCNews. 3 August 2013. Retrieved from: https://www.bbc.com/news/health-23408949
[12] Ree R et al. Annals of emergency Medicine. The Diagnosis and Treatment of Brown Recluse Spider Bites. 16:9 September 1987. Retrieved from: https://www.annemergmed.com/article/S0196-0644(87)80738-2/fulltext
[13] Rees, R S et al. “Brown recluse spider bites. A comparison of early surgical excision versus dapsone and delayed surgical excision.” Annals of surgery vol. 202,5 (1985): 659-63. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1250983/?page=1
[14] King LE, Rees RS. Dapsone Treatment of a Brown Recluse Bite. JAMA. 1983;250(5):648. Retrieved from: https://jamanetwork.com/journals/jama/article-abstract/387593
[15] Forks TP. Brown Recluse Spider Bites. J Am Board Fam Pract 2000;13:415-23. Retrieved from: https://www.jabfm.org/content/jabfp/13/6/415.full-text.pdf
[16] Maynor ML, Moon RE, Klitzman B, Fracica PJ, Canada A. Brown recluse spider envenomation: a prospective trial of hyperbaric oxygen therapy. Acad Emerg Med. 1997 Mar;4(3):184-92. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/9063544/
[17] Phillips S, Kohn M, Baker D, et al. Therapy of brown spider envenomation: a controlled trial of hyperbaric oxygen, dapsone, and cyproheptadine. Ann Emerg Med 1995;25:363-8. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/7864478/
[18] Strain GM, Snider TG, Tedford BL, Cohn GH. Hyperbaric oxygen effects on brown recluse spider (Loxosceles reclusa) envenomation in rabbits. Toxicon. 1991;29(8):989-96. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/1949069/
[19] Hadanny A, Fishlev G, Bechor Y, Meir O, Efrati S. Nonhealing Wounds Caused by Brown Spider Bites: Application of Hyperbaric Oxygen Therapy. Adv Skin Wound Care. 2016 Dec;29(12):560-566. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/27846029/