CONTINUING MEDICAL EDUCATION

Coombs-Positive Hemolytic Anemia Secondary to Brown Recluse Spider Bite: A Review of the Literature and Discussion of Treatment

David R. Lane, MD; Jeremy S. Youse, BS

GOAL To understand the potential reactions to a brown recluse spider bite

OBJECTIVES Upon completion of this activity, dermatologists and general practitioners should be able to: 1. Describe the cutaneous reactions encountered with brown recluse spider bites. 2. Explain the cutaneous reactions encountered with brown recluse spider bites. 3. Explore the treatment options for brown recluse spider bites.

CME Test on page 348.

This article has been peer reviewed and is accredited by the ACCME to provide continuing approved by Michael Fisher, MD, Professor of medical education for physicians. Medicine, Albert Einstein College of Medicine. Albert Einstein College of Medicine designates Review date: November 2004. this educational activity for a maximum of 1 This activity has been planned and implemented category 1 credit toward the AMA Physician’s in accordance with the Essential Areas and Policies Recognition Award. Each physician should of the Accreditation Council for Continuing Medical claim only that credit that he/she actually spent Education through the joint sponsorship of Albert in the activity. Einstein College of Medicine and Quadrant This activity has been planned and produced in HealthCom, Inc. Albert Einstein College of Medicine accordance with ACCME Essentials.

Dr. Lane and Mr. Youse report no conflict of interest. The authors report no discussion of off-label use. Dr. Fisher reports no conflict of interest.

The bite of the brown recluse spider (Loxosceles systemic disturbances of varying severity collec- reclusa) typically results in local, dermonecrotic tively known as systemic loxoscelism. The more skin lesions. Rarely, these bites may precipitate severe systemic alterations attributed to the venom of this arachnid include hemolytic ane- Accepted for publication June 3, 2004. mia, multiorgan failure, disseminated intravascu- From the University of Missouri-Columbia, University Health lar coagulation, or even death. Coombs-positive Care. Dr. Lane is Chief Resident in the Department of hemolysis associated with brown recluse spider Dermatology. Mr. Youse is a medical student. Reprints: David R. Lane, MD, 1 Hospital Dr, MA111, Columbia, bites has rarely been documented in the litera- MO 65212 (e-mail: [email protected]). ture. We report 2 cases of systemic loxoscelism

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in young women associated with severe Coombs- presented to her primary care physician 2 days after a positive hemolytic anemia and systemic symp- painless bite from a “brown spider” in her bed. At this toms requiring hospitalization. Both patients were initial evaluation, she had a diffuse maculopapular treated with aggressive wound care, hematologic rash with mild systemic symptoms including malaise monitoring with blood transfusion, and intra- and arthralgia. No laboratory workups were done, and venous fluid replacement. Recovery was excellent she was started on a 5-day steroid dose pack. in both cases. We review the literature and dis- The patient was seen in our urgent care depart- cuss the controversies surrounding the treatment ment 2 days later with documentation of a 22-cm of more severe brown recluse bite reactions. ecchymotic area on her right posterior thigh with Cutis. 2004;74:341-347. surrounding erythema and a diffuse maculopapular rash. Her laboratory workup at this time showed a mildly elevated total bilirubin level, mild leukocy- he bite of the brown recluse spider, also known tosis, anemia with a hemoglobin level of as Loxosceles reclusa, usually causes a local 11.7 mg/dL, elevated reticulocyte count, and nor- T hemorrhagic lesion characterized by areas of mal coagulation profile. She was given intramuscu- red, white, and blue discoloration.1 Rarely, the lar methylprednisolone 125 mg, acetaminophen for venom from this spider may cause a systemic pain, and hydroxyzine for pruritus, with plans response characterized by fever, malaise, myalgia, for follow-up in urgent care the next day. hemolysis, acute renal failure, disseminated The patient did not follow-up until 2 days later, intravascular coagulation, or even death. The con- at which time she reported worsening systemic dition is called systemic loxoscelism and can be par- symptoms including nausea, peripheral edema, ticularly dangerous in childhood, when most deaths lymphadenopathy, fever, and dysuria, along with from loxoscelism occur. The hemolysis in patients worsening pain and erythema at the bite site. She with systemic loxoscelism is not completely under- was febrile, and her anemia progressed when her stood, despite extensive research into the compo- hemoglobin level fell to 8.3 mg/dL. She was admit- nents of this deadly spider’s venom.2-4 Why this ted for hematologic monitoring and supportive venom results in systemic symptoms in some measures. At the time of admission, her skin exam- patients and local reactions in others also is not ination results were pertinent for a diffuse, faint completely understood. This variation in symptom- maculopapular rash and a 33-cm necrotic eschar atology likely has to do with the location of the ini- with surrounding erythema (Figure 1). tial spider bite and a possible predisposition of some The day after admission, the patient continued individuals to environmental red blood cell toxins. to be febrile, and her hemoglobin level dropped to The treatment of necrotic arachnidism is as con- 6.9 mg/dL. She was transfused with 2 units of troversial as the pathophysiology of the hemolysis. packed red blood cells, and the hematology depart- No standard of care exists for the more severe or ment was consulted to assist with the progressing anatomically vital spider bites. Several systemic anemia. The dermatology department also was con- medications have been tried with extensive anecdo- sulted to assist with wound care and treatment. The tal support, but no large controlled trials have been hematologist recommended performing an indirect performed in humans to prove these agents are more and direct Coombs test. The indirect Coombs test effective than aggressive and meticulous wound results were negative, but the direct Coombs test care. Previous studies have shown that patients results were positive for complement 3 and negative treated with early surgery resulted in prolonged for immunoglobulin G (IgG). The patient’s anemia healing times and increased negative outcomes com- and systemic symptoms continued to progress pared with patients treated with supportive wound (hemoglobin nadir level, 5.7 mg/dL), requiring care.5,6 Patients generally do very well with only sup- 2 more units of blood. The hematologist recom- portive measures, which should remain the treat- mended starting intravenous steroids to improve ment of choice until larger studies elucidate the role the patient’s “immunohemolytic anemia secondary of systemic medications. We report 2 cases of sys- to spider bite with positive Coombs test.” The temic loxoscelism causing a Coombs-positive patient was started on methylprednisolone 125 mg/d intravascular hemolysis requiring blood transfusion intravenously. Per dermatology’s recommendation, and review the treatment options of this condition. wound care was initiated along with elevation and ice to the affected extremity. Case Reports The patient’s clinical status began to improve on Patient 1—A 19-year-old African American woman hospital day 4, with absence of systemic symptoms with a medical history significant only for asthma and regression of her lesional erythema. She was

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Figure 1. A diffuse, faint maculopapular rash and a Figure 2. A 52-cm necrotic eschar on the left flank 33-cm necrotic eschar with surrounding erythema of patient 2 with a surrounding area of erythema. in patient 1. discharged on a quick-taper oral steroid regimen, The patient’s hemoglobin level rebounded to per the hematologist’s recommendation, and was 8.2 mg/dL on hospital day 2, at which time the der- instructed to continue her wound care. At the matology department was consulted for assistance patient’s hospital follow-up visit, her bite site was with wound care management. Elevation of the healing well, and she had no further evidence extremity and continuing wound care was recom- of anemia. mended, and debridement or systemic therapy was Patient 2—A 9-year-old African American girl in advised against. Results of the patient’s direct otherwise excellent health was transferred from an Coombs test were positive for IgG and negative for outside emergency department one week after being complement 3. No specific treatment changes were bitten by “a brown spider” while lying in bed. Ini- made based on the Coombs test result. tially, the bite was painless, but she later developed The patient continued to improve with wound swelling and warmth in the area. Due to increased care and hemodynamic support and displayed pain, swelling, and blister formation, her primary improved erythema with less tenderness at the bite physician saw her several days later and prescribed an site after several days of hospitalization. She was oral cephalosporin for presumed cellulitis. Fever, sent home on hospital day 4 in improved condition. fatigue, and malaise continued throughout the week. She was seen by a dermatologist at her follow-up Two days prior to presentation at our hospital, she visit, and her eschar was treated with hydrocolloid developed scleral icterus and vomiting. dressing changes and eventual debridement of the During the patient’s evaluation at the transfer- eschar with follow-up occlusive dressings until ring emergency department, her laboratory workup the lesion was completely healed. revealed a profound anemia with a hemoglobin level of 5.2 mg/dL, elevated white blood cell count, Comment indirect hyperbilirubinemia, and mildly prolonged Brown Recluse-Induced Hemolysis—Brown recluse international normalized ratio value. Her examina- spider bites are common in the Midwest, Southeast, tion was significant for a tachycardia, holosystolic and south central United States.7 Although there murmur, scleral icterus, and 52-cm necrotic are more than 70 species of Loxosceles found eschar on her left flank with a surrounding area of throughout the world, only approximately 15 species erythema that was exquisitely tender to palpation inhabit North America, with L reclusa being the (Figure 2). She was immediately admitted for close most common encountered by humans.8 Patients observation and treatment of her anemia. She was affected by this malady are often seen by physicians transfused with 2 units of packed red blood cells. in various specialties, including primary care

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providers, emergency physicians, dermatologists, the case at our institution until recently.11 We report general surgeons, and surgical subspecialists. It is 2 cases of life-threatening hemolytic anemia with important that physicians in these specialties rec- positive direct Coombs testing in a span of ognize and treat this condition appropriately. 9 months. These results are a rarity but may help us Although these bites usually cause a local understand the pathophysiology of systemic lox- necrotic lesion, sometimes a more serious systemic oscelism. To our knowledge, these are the fifth and syndrome, known as systemic loxoscelism, occurs. sixth reported cases of a Coombs-positive hemolytic This can result in high fever, significant intravas- anemia from a brown recluse spider bite. The first cular hemolysis, renal failure, disseminated intra- case was documented by Nance18 in 1961, but there vascular coagulation, and even death. Although was no mention of whether complement or most fatalities have been reported in children, immunoglobulin was involved. Eichner17 reported 2 cases of adult deaths have been reported.9,10 the second and third cases of Coombs-positive The hemolytic anemia that accompanies systemic anemia in loxoscelism, with both cases involving loxoscelism has been only partially described, and complement-mediated hemolysis. The fourth case of the full mechanism by which the venom of the Coombs-positive anemia was reported by William et brown recluse causes this syndrome is still a al9 in 1995, and the Coombs test was positive for mystery. The prevailing theory for the cause of both IgG and complement. Our cases affirm that hemolysis has incriminated the phospholipase both IgG and complement can be involved in sphingomyelin D, an enzyme isolated from brown Coombs-positive hemolytic anemia. It is likely that recluse venom, because of its effect on cell walls in the venom of the brown recluse is able to activate vivo to cause lysis.11 It was thought that sphin- both IgG and complement in predisposed individu- gomyelinase disrupted cell membranes either als by activation of an unknown endogenous media- directly or indirectly and resulted in the release of tor (eg, metalloproteinase) to cause massive phospholipid-derived substances that bound com- intravascular hemolysis. Investigations into which plement and resulted in tissue hypoxia and necro- patients may be predisposed to develop this compli- sis.12-14 Because such a small amount of venom and cation are warranted. toxin actually enter the body after a bite, another Treatment—The treatment of local and systemic mechanism is likely taking place to produce the brown recluse spider bites also has been a source of symptoms involved in systemic loxoscelism. Acti- controversy over the years. Several treatment regi- vation and propagation of the immune system by a mens, including early and late surgical excision and toxin in the venom could explain such a reaction. debridement, systemic steroids, hyperbaric oxygen A study on another member of the Loxosceles therapy, cryproheptadine, electric shock therapy, family, Loxosceles intermedia, may help elucidate and dapsone, have been anecdotally described in the the factors involved in the overwhelming reaction literature; however, none of these treatments have to the Loxosceles venom in some people.15 In this prospective human trials to back up this anecdotal study, it was found that the sphingomyelinase in evidence. With conservative wound management, the spider toxin did not directly affect glycophorins ice, elevation, and analgesics, almost all patients on red blood cell membranes but instead activated exhibit a full recovery with minimal scarring that an endogenous metalloproteinase that then rarely needs surgical revision.19 cleaved these glycophorins. The authors proposed Dapsone has been the most controversial of the that the altered glycophorins destabilized the red treatments for brown recluse bites. Dapsone makes blood cell membrane, rendering the glycophorins theoretical sense in the treatment of these lesions vulnerable for complement-mediated lysis. The because of its ability to inhibit polymorphonuclear authors also observed that the hemolysis-inducing leukocytes from entering the wound area and and glycophorin-cleaving activity of this activated causing local destruction. There are many anecdo- metalloproteinase could be transferred from one tal reports supporting the use of dapsone for more erythrocyte to another, thereby propagating the severe bites, the most famous being the King and hemolyzing response.15 This type of transfer of Rees20 case report of a patient with a brown recluse sphingomyelinase and metalloproteinase activity bite of the leg that was seen 24 hours after the bite between cells has been described before and could had occurred. They reported that 2 days after pre- explain the overwhelming systemic response of the scribing dapsone 100 mg twice daily along with ice Loxosceles toxin in some individuals.16 and local wound care, the bite site was pain free Historically, most cases of massive hemolysis due with marked reduction in induration and ery- to brown recluse bites documented in the literature thema. Their argument was based on an assump- have been Coombs negative.17 This also has been tion that the lesion “probably would have

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developed an indolent ulcer.” They supported their Conservative debridement may be performed to use of dapsone with an animal model of guinea pigs prevent secondary infection, but surgery should gen- that were pretreated with dapsone before being erally be withheld for 4 to 6 weeks. Early local injected with Loxosceles venom. The authors wound care during this time followed by late surgi- reported that pretreated guinea pigs showed a cal excision and grafting are more successful than reduction in lesion size at 24 hours compared with early surgical excision. However, most wounds, if those without treatment.20 The methods of this treated with supportive therapy alone, will ulti- study have come into question primarily due to the mately heal with minimal scarring.28 A retrospective rarity of patients with brown recluse bites pre- study of 149 patients with brown recluse bites treated with dapsone. Also, follow-up animal stud- showed that nearly half of all bites healed within ies have conflicted with the benefit of dapsone for 2 weeks and only 13% of bites left a visible scar. this indication.21,22 None of these patients were treated with surgery.29 Although the benefit of dapsone is controversial, Corticosteroids also have been used extensively the side effects of this medicine are protean and well for more serious reactions after envenomation from known. The development of hemolytic anemia has a brown recluse spider, but documentation in the long been attributed to this medication and will occur literature is sparse. In a white rabbit model, Jansen to some degree in all patients.23 This predictable et al30 did not find any treatment value for either hemolysis can sometimes become confused with the intramuscular or intralesional methylprednisolone direct effects of the brown recluse venom, which can in the prevention of dermonecrosis after a brown delay definitive diagnosis of the etiology of the recluse spider bite. Berger et al31 also concluded hemolysis and expose patients to an unproven drug that large doses of steroids had no effect on the with multiple toxicities. Severe hemolysis can be progression or development of necrotic arach- expected in patients with glucose-6-phosphate nidism. Despite this evidence, there are many who dehydrogenase deficiency; therefore, dapsone is still advocate the use of steroids for more serious absolutely contraindicated in this patient population. bites and for those associated with systemic symp- Methemoglobinemia is another feared side toms.32 Given the extensive use of corticosteroids effect of dapsone. Although mostly asymptomatic in patients with autoimmune hemolytic anemia, and usually undetectable, sometimes elevated lev- this treatment may be of use in patients with els of methemoglobin can cause severe systemic Coombs-positive hemolytic anemia secondary to symptoms requiring hospitalization.24 Unfortu- brown recluse envenomation.33,34 For this reason, nately, it is impossible to predict who will experi- direct Coombs testing in patients with hemolytic ence this complication because of a lack of simple anemia due to brown recluse bites could provide blood testing such as that available for patients useful information in the inpatient management of with subclinical glucose-6-phosphate dehydro- these patients. genase deficiency. Because of these serious and Other treatments also have been reported, sometimes common adverse events attributed to including colchicine, hyperbaric oxygen, cyprohep- dapsone, and the lack of solid evidence to support tadine, electrical shock treatment, and brown its effectiveness, there is no place for dapsone in recluse specific antivenin.7,21,35 Despite early the treatment of loxoscelism at this time. promise, all of these treatments have been met with The role of early surgical excision has changed mixed results in subsequent studies. In one study, over the past few decades. Reports prior to 1975 the early use of intradermal injection of polyclonal often suggested early surgical excision of bites with antiloxosceles Fab fragments was shown to attenu- grafting as the treatment of choice.25,26 Since then, ate necrosis in an animal model up to 4 hours after multiple reports have shown that early surgical exci- envenomation.36 Unfortunately, it is difficult to sion often does more harm than good in the treat- predict which patients would benefit from the ment of brown recluse bites.5,6 Early surgical antivenin. Additionally, the antivenin has to be excision is contraindicated because of the rapid administered in the first 24 hours after a bite, before spread of the toxin through the wound in the first most patients are seen by a physician. weeks following a bite. The toxin may continue to In our cases, both patients were young and pre- spread for at least 4 weeks, which makes demarca- sented with a recent history of a bite by a brown spi- tion between envenomed and healthy tissue diffi- der consistent with a brown recluse. They were cult.27 DeLozier et al6 suggested that the added both systemically ill with a profound hemolytic surgical trauma from early excision may potentiate anemia. They were both treated with aggressive the inflammatory response to the brown recluse wound management, hematologic monitoring with venom, prolonging healing time. blood transfusion, and expectant care. Patient 1 was

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given intravenous corticosteroids, and patient 2 was brown recluse spider (Loxosceles reclusa). Toxicon. treated with aggressive wound management only. It 1979;17:355-362. is not known whether the corticosteroids given in 4. Rekow MA, Civello DJ, Geren CR. Enzymatic and our first patient affected her clinical course because hemolytic properties of brown recluse spider (Loxosceles both patients experienced a complete recovery. reclusa) toxin and extracts of venom apparatus, cephalo- Like other case reports of treatment in brown thorax and abdomen. Toxicon. 1983;21:443-446. recluse spider bites, it is difficult to tell what effect, 5. Rees RS, Altenbern DP, Lynch JB, et al. Brown recluse if any, the treatment has on clinical outcome spider bites: a comparison of early surgical excision because most patients, even those with serious sys- versus dapsone and delayed surgical excision. Ann Surg. temic symptoms, make a complete recovery. This 1985;202:659-663. routine excellent outcome with supportive care 6. DeLozier JB, Reaves L, King LE, et al. Brown recluse bites only suggests that the use of systemic treatment or of the upper extremity. South Med J. 1988;81:181-184. surgery is unnecessary and exposes the patient to 7. Forks TP. Brown recluse spider bites. J Am Board Fam Pract. risks of treatments with unproven efficacies. 2000;13:415-423. 8. Futrell JM. Loxoscelism. Am J Med Sci. 1993;304:261-267. Conclusion 9. Williams ST, Khare VK, Johnston GA, et al. Severe Brown recluse spider bites usually cause a local der- intravascular hemolysis associated with brown recluse monecrotic reaction but can cause a serious sys- spider envenomation. a report of two cases and review of temic illness and rarely death. We report the fifth the literature. Am J Clin Pathol. 1995;104:463-467. and sixth cases of Coombs-positive hemolytic ane- 10. Taylor EH, Denny WF. Hemolysis, renal failure and death, mia associated with presumed L reclusa envenoma- presumed secondary to bite of brown recluse spider. South tion. The first 4 reported cases of Coombs-positive Med J. 1966;59:1209-1211. hemolysis were positive for IgG and/or comple- 11. Anderson PC. Spider bites in the United States. Dermatol ment. This was confirmed in our cases. Clin. 1997;15:307-311. The treatment of loxoscelism is controversial in 12. Ginsburg CM, Weinbert AG. Hemolytic anemia and mul- the literature and in practice. We must keep in mind tiorgan failure associated with localized cutaneous lesion. J to “first, do no harm” when choosing treatments for Pediatr. 1988;112:496-499. patients with brown recluse bites. Many of the treat- 13. Kurpiewski G, Forrester LJ, Barret JT, et al. Platelet ments previously described, including dapsone, have aggregation and sphingomyelinase D activity of a puri- only anecdotal support for their use. Others, such as fied toxin from the venom of Loxosceles reclusa. Biochim early surgery, have been shown to actually delay Biophys Acta. 1981;678:467-476. healing and worsen outcomes. Patients with brown 14. Rees RS, Nanney LB, Yates RA, et al. Interaction of brown recluse bites typically do well with conservative recluse spider venom on cell membranes: the inciting management alone and agents such as dapsone and mechanism. J Invest Dermatol. 1984;83:270-275. systemic corticosteroids can have serious adverse 15. Tambourgi DV, Morgan BP, de Andrade RM, et al. Lox- reactions. It is our view that patients with local der- osceles intermedia spider envenomation induces activation monecrotic skin lesions should be treated with of an endogenous metalloproteinase, resulting in cleavage aggressive wound care only. For patients who of glycophorins from the erythrocyte surface and facilitating develop systemic loxoscelism, hemodynamic support complement-mediated lysis. Blood. 2000;95:683-691. and blood transfusion should remain the mainstay of 16. Rowe E, Welch RA. Assays of hemolytic toxins. Methods therapy. Further study is needed to determine the Enzymol. 1994;235:657-667. benefits of systemic corticosteroid use in patients 17. Eichner ER. Spider bite hemolytic anemia: positive with Coombs-positive hemolytic anemia secondary Coombs’ test, erythrophagocytosis, and leukoerythroblastic to systemic loxoscelism. smear. Am J Clin Pathol. 1984;81:683-687. 18. Nance W. Hemolytic anemia of necrotic arachnidism. Am J Med. 1961;31:801-807. REFERENCES 19. Wright SW, Wrenn KD, Murray L, et al. Clinical presenta- 1. Leung LK, David R. Life-threatening hemolysis follow- tion and outcome of brown recluse spider bite. Ann Emerg ing a brown recluse spider bite. J Tenn Med Assoc. Med. 1997;30:28-32. 1995;88:396-397. 20. King LE Jr, Rees RS. Dapsone treatment of a brown recluse 2. Murray LM, Seger DL. Hemolytic anemia following a bite. JAMA. 1983;250:648. presumptive brown recluse spider bite. Clin Toxicol. 21. Phillips S, Kohn M, Baker D, et al. Therapy of brown 1994;32:451-456. spider envenomation: a controlled trial of hyperbaric 3. Futrell JM, Morgan BB, Morgan PN. An in vitro model oxygen, dapsone, and cyproheptadine. Ann Emerg Med. for studying hemolysis associated with venom from the 1995;25:363-368.

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22. Beilman GJ, Winslow DL, Teslow TW. Experimental brown 30. Jansen GT, Morgan PN, McQueen JN, et al. The brown spider bite in the guinea pig: results of treatment with dapsone recluse spider bite: controlled evaluation of treatment using or hyperbaric oxygen. J Wilderness Med. 1994;5:287-294. the white rabbit as an animal model. South Med J. 23. Hall RP III. Dapsone. In: Wolverton SE, ed. Comprehensive 1971;64:1194-1202. Dermatologic Drug Therapy. 1st ed. Philadelphia, Pa: WB 31. Berger RS, Adelstein EH, Anderson PC. Intravascular Saunders Co; 2001:230-250. coagulation—the cause of necrotic arachnidism. J Invest 24. Bryant SM, Pittman LM. Dapsone use in Loxosceles reclusa Dermatol. 1973;61:142-150. envenomation: is there an indication? Am J Emerg Med. 32. Sauer GC. Transverse myelitis and paralysis from a brown 2003;21:89-90. recluse spider bite. Mo Med. 1975;72:603-604. 25. Auer A, Hershey F. Proceedings: surgery for necrotic bites 33. Schrier SL. Extrinsic nonautoimmune hemolytic anemia due of the brown spider. Arch Surg. 1974;108:612-618. to drugs and toxins. Available at: http://www.uptodate.com. 26. Fardon DW, Wingo CW, Robinson DW, et al. The treat- Accessed October 10, 2003. ment of brown spider bite. Plast Reconstr Surg. 34. Ware RE. Autoimmune hemolytic anemia in children. 1967;40:482-488. Available at: http://www.uptodate.com. Accessed October 27. Clowers TD. Wound assessment of the Loxosceles reclusa 10, 2003. spider bite. J Emerg Nurs. 1996;22:283-287. 35. Rees RS, Altenbern DP, Lynch JB, et al. Brown recluse 28. Majeski J. Necrotizing fasciitis developing from a brown spider bites: a comparison of early surgical excision versus recluse spider bite. Am Surg. 2001;67:188-190. dapsone and delayed surgical excision. Ann Surg. 29. Cacy J. Mold JW. The clinical characteristics of brown 1985;202:659-663. recluse spider bites treated by family physicians: an 36. Gomez HF, Miller MJ, Trachy JW, et al. Intradermal anti- OKPRN Study Oklahoma Physicians Research Network. J loxosceles Fab fragments attenuate dermonecrotic arach- Fam Pract. 1999;48:536-542. nidism. Acad Emerg Med. 1999;6:1195-1202.

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FACULTY DISCLOSURE The Faculty Disclosure Policy of the Albert Einstein College of Medicine requires that faculty participating in a CME activity disclose to the audience any relationship with a pharmaceutical or equipment company that might pose a potential, apparent, or real conflict of interest with regard to their contribution to the activity. Any discussions of unlabeled or investigational use of any commercial product or device not yet approved by the US Food and Drug Administration must be disclosed.

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