Emergency Management of Brown Recluse Spider Bites: A Review Submitted to GEMA on 10/29/96 Gary W. Tamkin, MD Attending Physician Highland General Hospital - Alameda County Medical Center Oakland , California Clinical Instructor University of California San Francisco Abstract Brown Recluse spider bite is a common occurrence. Diagnosis is difficult due to multiple clinical presentations. Though most bites follow an uncomplicated course with simple wound care, the necrotic lesion of the bite must be promptly recognized if severe tissue necrosis is to be avoided. Systemic loxocelism is a rare, but is a fatal complication seen in children. Ice, local wound care, NSAIDs, tetanus prophylaxis, and empiric antibiotics are appropriate conservative management. Treatment with Dapsone, antivenin, corticosteroids, and hyperbaric oxygen are under investigation. Keywords brown recluse spider; spider bites; systemic loxocelism; necrotic arachnidism Introduction The Prompt diagnosis and proper treatment of the brown recluse (BR) spider bite can mean the difference between a simple well healed wound, and a necrotic wound requiring extensive surgical care, or a systemic illness that can lead to death. This paper will review the the pathophysiology, clinical presentation, diagnosis, and treatment of the BR spider bite as it relates to the emergency physician. The Spider The anatomy of most spiders includes a cephalothorax and abdomen joined by a thin pedicle, eight legs, and a chelicerae(jaw) with a distal opening through which venom is ejected. Most spiders do not have a jaw which is capable of breaking human skin. The BR spider has a cephalothorax bearing a violin-shaped marking, leading to the common names "fiddleback spider", or "violin spider". The BR spider ranges in length from 10-15mm, has a leg span that is usually greater than 25mm, and is nonhairy. Most are yellow to brown in color, and have six eyes, rather than the customary eight. The female may be twice as long as the male and each leg has two claws. The BR spider has been identified in every state, but the greatest concentrations are found in the southern regions of the United States , particularly Missouri, Kansas, Tennessee, and Arkansas. The BR spider is not inherently aggressive, and tends to bite only when trapped or crushed.(1) The BR spider prefers warm, dry locations such as animal burrows and the undersides of rocks. Their quest for warmth and protection leads them into homes, firewood, boxes and clothing. Many patients are bitten during summer outdoor activities, or by spiders that have taken refuge in stored clothing(1). Because of the BR spider's nocturnal hunting habits, many bites occur while the victim is asleep, and thus go unnoticed. The Venom The BR spider bite is significant primarily in its ability to cause major tissue necrosis. The primary dermonecrotic factor of the venom is phospholipase sphingomyelinase D that acts by disrupting cell membranes(2). A variety of other enzymes are present in the venom of the BR spider(3,4,5). The patient's immune response to the foreign antigens found in the venom may be responsible for the resultant tissue necrosis(6,7,8). The fact that the quantity of cytotoxic proteins in venom are inadequate to account for the degree of necrosis observed., and that reduced PMN leukocyte migration results in decreased necrosis supports the role of immunity in the necrotic process(9,10). Altering the body's immune response to the BR spider's venom is the focus of many investigational treatment modalities. Clinical Presentation The factors associated with the severity of any type of envenomation include: 1.) host susceptibility (ie.children, elderly, immunocompromised), 2.) the amount of venom injected, and 3.) the site where the bite occurs (ie.extremities). The majority of BR spider bites may go unnoticed or result only in mild local stinging. A minority of patients will suffer more significant symptoms including: local pruritis, pain, swelling, induration, erythema, blister formation, and pustule formation. If the patient does not experience the above within 48-96 hours, significant necrosis is unlikely. Severe BR spider bites are characterized by a deep blue to purple central area caused by thrombosis of local vasculature. A surrounding area of vasoconstriction, surrounded by a larger area of erythema may lead to the characteristic "red, white, and blue sign". Wound healing in the case of minimal site reactions may require only hours to days for the symptoms to abate. More severe bites involve two to three months for eschar development and subsequent skin healing. Complications resulting from severe BR spider bite are related to the location of the bite. Areas of little subcutaneous fat appear to result in greater complication rates, whereas areas of greater fat density have minimal reactions(11). The Eyelids and extremities, specifically the dorsum of the hands and feet are at risk for complication(12, 13, 14). BR spider bites have been associated with deep venous thrombosis, pyoderma gangrenosum and Pseudoepitheliomatous hyperplasia(15,16). Systemic reactions to the severe BR spider bite are rare and have a wide range of presentations. Fever and malaise are the most common symptoms, but headache, anorexia, arthralgias, generalized maculopapular rash, nausea, vomiting, abdominal pain, and chest pain may be systemic manifestations of BR spider bite(17). Systemic loxoscelism(SL) refers to severe systemic illness following BR spider bite. The majority of fatalities from Loxoscelism occur in children less than seven years of age, and results from massive hemolysis, usually two to three days following the bite(18). Other findings include: acute renal failure secondary to hemoglobinuria, leukocytosis, leukopenia, thrombocytopenia, disseminated intravascular coagulation, convulsions, and coma.(19,20,21) The diagnosis of SL is often complicated by the fact that it usually accompanies bites that are characterized by little skin involvement. It is hypothesized that this is due to increased absorption of venom, as opposed to intradermal deposition(22). Diagnosis Wilson and King classify bites into four categories based upon historical and clinical data(appendix I), while Auer's classification is used to assess a patient's condition following a BR spider bites(appendix II). At present no test is available to identify the presence of Loxosceles venom, nor is it possible to identify which lesions will spontaneously regress(3). The lymphocyte transformation test at four weeks following the bite is experimental, but is not generally available, or clinically useful(23). CBC, platelet count, and urinalysis are useful in the early diagnosis of systemic loxoscelism. Leukocytosis and an elevated ESR are the most common laboratory anomalies(17). In general, all causes of focal blistering, skin necrosis, and pyodermas must be considered in the differential diagnosis. When systemic manifestations present, the differential diagnosis for DIC and hemolysis must be entertained. Clinical examination of the wound, and lack of severe clinical symptoms at the time of the bite exclude the diagnosis of Scorpion and snake bite. The misdiagnosis of Lyme disease for BR spider bite has been reported. The awareness of areas endemic for Lyme disease, and the recognition of the development of the secondary lesions and prolonged clinical course characteristic for Lyme disease, can prevent this misdiagnosis(24). Treatment Conservative treatment with rest, ice and elevation of the affected wound site will result in good outcome for the vast majority BR spider bites . While ice alone clearly does not prevent necrosis in all patients, it consistently lessens tissue damage from the bite(15). It is hypothesized that cooling the wound limits the activity of sphingomyelinase D(25). BR spider bites treated with heat result in greater tissue damage. Heat appears to increase the activity of phospholipases. NSAIDS inflammation and pain relief , empiric antibiotics for cellulitis, and tetanus prophylaxis are appropriate. Early surgical excision of the BR spider wound is controversial . Several studies have associated increased wound breakdown and graft rejection with early surgical excision(26,27,28). Even with the aid of flouresein dye, it appears that venom is often left behind despite the surgical procedure(26,29,30). Delayed wide excision and skin grafting once eschar formation has occurred is a more conservative approach(26,31). Dapsone treatment for BR spider bites has been found to alleviate the need for surgical intervention in some cases. A Sulfone drug used historically for the treatment of Leprosy, Dapsone is an inhibitor of neutrophill function, a major mechanism of skin necrosis brought on by envenomation. King and Rees demonstrated that pigs pretreated with Dapsone had smaller skin lesions following envenomation when compared with a control group(32). Clinical studies have also demonstrated the need for fewer surgical intervention in patients treated with Dapsone(33). Clinical studies dosed Dapsone at 50-100mg b.i.d. until the necrosis subsided, and sometimes treated up to 25 days in cases of severe necrosis. Most required only several days of treatment. G6pd deficiency, and methemoglobinuria are contraindications to Dapsone therapy due to potential massive hemolysis in individuals with these disorders. Complications arising from Dapsone therapy include agranulocytosis and a hypersensitivity reaction to the drug. Dapsone hypersensitivity syndrome occurs in probably less than 0.5% of those who take the drug, and it is not dose dependent. Onset usually occurs two to six weeks following initiation of the drug and can present with any combination of the following: fever, headache, dermatitis, hepatitis, hemolytic anemia, leukopenia, and mononucleosis. This rae hypersensitivity syndrome usually resolves in one to two weeks following cessation of the drug, however, fatal reactions have been reported(34). The use of corticosteroids in an effort to prevent chemotaxis associated with envenomation from the BR spider bite is controversial. Ingber, et al in a retrospective study of thirity-five cases of BR spider bite found that lesions with a necrotic area of 2- 3cm benefited from the use of corticosteroids added to conservative wound management. Prednisone 30-60mg/day was the dosage used in this study(17). However, more recent studies in animals and humans using intralesional, intradermal, and systemic steroids in various forms have failed to show improved outcome(27,28,35,36). The role of steroid therapy in the treatment of systemic loxoscelism is equally controversial. Wilson and King suggest methylprednisone 1-2mg/kg/day in cases of suspected loxoscelism. While there are case reports of usefulness in children, and decreased hemolysis with steroid treatment, Rees and colleagues have been unable to prevent systemic loxoselism in guinea pigs pretreated with Methylprednisone(19). The use of corticosteroids in the local reaction of BR spider bite, as well as in systemic loxoscelism warrants further investigation. Treatment with heparin, phentolamine, and Dextran have not been shown to mitigate tissue damage from thrombosis caused by BR spider bite envenomation(27,35). The use of hyperbaric oxygen has been shown useful in small clinical studies, but further experience is needed to determine its clinical efficacy.(7,37) Antibody raised in rabbits against sphingomyelinase D has been shown to decrease morbidity and mortality in both local BR spider envenomation and systemic loxocelism(38). However, antivenin is not yet available for clinical use. Summary Brown Recluse Spider bite is most common in the southern portion of the United States and often occurs during the summer. Diagnosis is difficult due to multiple clinical presentations , and the fact there is no definitive laboratory test to confirm significant envenomation. Though most bites follow an uncomplicated course with simple wound care, the necrotic lesion of BR spider bite can produce severe tissue necrosis. Systemic loxocelism is an even rarer, yet potentially fatal complication, and is most often seen in young children. Ice, local wound care, NSAIDs, tetanus prophylaxis, and empiric antibiotics are appropriate conservative management of BR spider bite. Dapsone treatment appears to lessen the need for surgical intervention. Surgical debridement, steroid therapy, antithrombosis drugs and hyperbaric oxygen therapy are controversial. Antivenin, while promising, is not yet clinically available. Appendix One Wilson and King Classification of Brown Recluse Spider Bite15 Classification Characteristics 1.Putative Referred Patient, Subjective diagnosis Brown recluse spiders not in area Atypical skin lesion 2.Presumptive Brown recluse spiders in area Compatible lesions, often early Typical clinical course Responds to specific therapy .3Clinically Typical Brown recluse spiders in area Felt bite, saw spider Appendix Two Auer Classification of Patient Condition following Brown Recluse Spider Bite11 Grade Characteristics 1Mild local erythema at puncture site 2aNecrotic area less than 1cm in diameter 2bLesion as in 2a accomp. by mild systemic reaction (Nausea, fever) 3Necrosis measuring 1-4cm accompanied by moderate systemic reaction (chills, fever, arthralgia, petechiae, generalized rash) 4aNecrosis measuring more than 4cm, accompanied by coagulopathy, severe hemolysis, and hemoglobinuria 4bFindings as in 4a, plus renal failure, secondary infection and shock References 1. 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