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To the Editor: Dr Freedman and colleagues¹ detailed the clinical course of a 7-month-old infant with cutaneous anthrax. However, I find it disturbing that the working diagnosis, which remained preeminent until hospital day 12, was cutaneous and systemic loxoscelism (ie, recluse spider envenomation). Physicians and patients often ascribe otherwise unexplained skin lesions to Loxosceles reclusa or other spider envenomations with little if any supporting evidence.^2-5 Brown recluse spider bites essentially never occur outside this species' natural geographic range in the south central United States, where they are generally not regarded as a medical calamity,³ as typical of nonendemic regions. It is exceedingly unlikely that someone in the Manhattan area could be envenomated by a brown recluse spider. Without observing either the bite or a spider, the chance that this child (or anyone in a nonendemic area) had cutaneous or systemic loxoscelism was essentially nil, even if the clinical features appeared consistent. Furthermore, assigning the diagnosis of loxoscelism served no useful purpose, because supportive care alone is the mainstay of treatment for brown recluse spider envenomation.

The incorrect assumption that spider bites are responsible for various "idiopathic" skin lesions appears to be a worldwide phenomenon. Such misdiagnoses of spider bites have been reported from Brazil, Australia, and New Zealand.^4-5 In the absence of a reliable eyewitness history or recovery of the offending animal, any diagnosis or claim of a spider bite needs to be questioned carefully. Even in Loxosceles reclusa-endemic areas, "other well-known causes for focal necrosis in the skin [exist], such as bacterial infection, infestation, trauma, artifact, emboli, thrombosis, vasculitis, and others,"³ which include several dermatologic conditions and viral and fungal infections.^{1, 4} Most claims of spider bites have on further investigation been attributable to alternative causes. Anderson goes so far as to say that "because the well-accepted rules of evidence have been ignored, a large part of the total clinical literature on loxoscelism is invalid."³

Jeffrey R. Suchard, MD
Department of Emergency Medicine
University of California Irvine Medical Center
Orange

1. Freedman A, Afonja O, Chang MW, et al. Cutaneous anthrax associated with microangiopathic hemolytic anemia and coagulopathy in a 7-month-old infant. JAMA. 2002;287:869-874. FREE FULL TEXT 2. Vetter RS. Myth: idiopathic wounds are often due to brown recluse or other spider bites throughout the United States. West J Med. 2000;173:357-358. FULL TEXT | ISI | PUBMED 3. Anderson PC. Loxoscelism and the history of the Missouri brown spider: a recollection of Dr Joseph Flynn. Mo Med. 1990;87:747-752. PUBMED 4. Isbister GK. Spider mythology across the world. West J Med. 2001;175:86-87. PUBMED 5. Nishioka Sde A. Misdiagnosis of brown recluse spider bite. West J Med. 2001;174:240. PUBMED

To the Editor: Dr Freedman and colleagues¹ report the occurrence of microangiopathic hemolytic anemia in a case of cutaneous anthrax. This represents the second recent anthrax case with this finding.² Pathological reports of inhalational anthrax cases from the Sverdlovsk epidemic³ suggest that vasculitis is the cause of the microangiopathic hemolytic anemia observed in some cases of anthrax. Although pathological findings of disseminated intravascular coagulation were not reported to be present in the Sverdlovsk cases, laboratory findings compatible with the diagnosis occurred in some patients. The vasculitis, as well as endothelial damage, were believed to be responsible for the extensive hemorrhage that is a prominent feature in disseminated anthrax infections. Thus, both microangiopathic hemolytic anemia and hemorrhage may be consequences of vasculitis.

There are limited pathological studies of cutaneous anthrax and it would be interesting to know if vasculitis was observed in the skin biopsy from the current case. Furthermore, the recent observation that anthrax lethal toxin may impair platelet function suggests an additional way in which the bacterium may promote a hemorrhagic diathesis.⁴ Antiplatelet drugs may also increase mortality due to the lethal toxin. The combination of vasculitis and possible toxin-induced platelet dysfunction suggests that the use of medications with anticoagulant effects, including aspirin, other nonsteroidal anti-inflammatory drugs, and low-dose heparin may be deleterious by exacerbating the hemorrhage occurring in cases of anthrax. Consideration should be given to discontinuing such drugs in the management of future cases. Further studies in experimental infection models may help determine whether the use of these drugs has clinical significance.

Arthur M. Friedlander, MD
US Army Medical Research Institute of Infectious Diseases
Fort Detrick
Frederick, Md

1. Freedman A, Afonja O, Chang MW, et al. Cutaneous anthrax associated with microangiopathic hemolytic anemia and coagulopathy in a 7-month-old infant. JAMA. 2002;287:869-874. FREE FULL TEXT 2. Jernigan JA, Stephens DS, Ashford DA, et al. Bioterrorism-related inhalational anthrax: the first 10 cases reported in the United States. Emerg Infect Dis. 2001;7:933-944. ISI | PUBMED 3. Grinberg LM, Abramova FA, Yampolskaya OV, Walker DH, Smith JH. Quantitative pathology of inhalational anthrax, I: quantitative microscopic findings. Mod Pathol. 2001;14:482-495. FULL TEXT | ISI | PUBMED 4. Kau J, Chang H, Huang H, et al. Platelet, the novel action target of anthrax. Presented as a poster at: 4th International Anthrax Conference; June 10-13, 2001; Annapolis, Md.

In Reply: We agree with Dr Suchard that necrotic arachnidism in an infant in Manhattan is unlikely. However, we could not rule out this possibility. Although Loxesceles spiders are most concentrated in the south central United States, Loxesceles species have been sporadically identified in virtually every state in the continental United States, probably transported in belongings.^1-2 In this case, the family's automobile had recently been driven to regions inhabited by Loxosceles species and we postulated that a spider might have hidden within the infant's stroller or the family's belongings.

In contrast, anthrax in a 7-month-old infant would seem nearly impossible in Manhattan. Between 1984 and 2000, only 5 reports of cutaneous anthrax were reported in the United States, and none of these occurred in infants or children.^3-4 During this infant's hospitalization, the first case of cutaneous anthrax in New York, NY, was reported. The correct diagnosis in this patient was then rapidly confirmed.

Our patient developed life-threatening hemolysis, thrombocytopenia, disseminated intravascular coagulopathy, hyponatremia, and acute renal failure. These complications are well described in Loxosceles envenomation but have not been reported in cutaneous anthrax in an infant even in countries where anthrax is endemic.⁵

Putative brown recluse spider bite^1-2 was the initial working diagnosis, and since there is no specific antidote, antibiotics, corticosteroids, and supportive care were given, which was appropriate therapy for this infant, even in hindsight.

We agree that skin lesions attributed to brown recluse spider bites are more often unproved than proven, and that differential diagnoses should be carefully considered for necrotic wounds. However, working diagnoses should not be discarded on the grounds that they are unlikely occurrences or difficult to prove.

In response to Dr Friedlander, we were unaware of the poster of Kau et al. We did note the report of "hemolytic anemia and thrombocytopenia" in patient 3 by Jernigan et al but, as no other data were presented in that report, it was not clear whether this individual with inhalational anthrax manifested disseminated intravascular coagulation or true microangiopathic vasculitis. Large vessel vasculitis has been reported to occur in brown recluse spider envenomation.⁶ The microangiopathic process in our patient appears to be novel. No vasculitis was noted on skin biopsy. We agree that medications with anticoagulant effects would be harmful in patients with platelet dysfunction, but are not aware of anyone suggesting that these drugs be used in anthrax. They are also not recommended for other causes of microangiopathic hemolytic anemia, such as thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. In contrast, steroidal anti-inflammatory medication has been suggested for some syndromes caused by anthrax toxin.⁷ In addition, corticosteroid therapy has been suggested as treatment for systemic effects (eg, hemolysis and renal disease) caused by brown recluse spider envenomation.⁸ This might be a better choice for any anthrax-related vasculitis.

William Borkowsky, MD; Mary Wu Chang, MD
Department of Pediatrics
New York University School of Medicine
New York, New York

1. Wilson DC, King LE Jr. Spiders and spider bites. Dermatol Clin. 1990;8:277-286. ISI | PUBMED 2. Sams HH, Dunnick CA, Smith ML, King LE Jr. Necrotic arachnidism. J Am Acad Dermatol. 2001;44:561-573. FULL TEXT | ISI | PUBMED 3. Centers for Disease Control and Prevention. Summary of Notifiable Diseases, United States 1999. MMWR Morb Mortal Wkly Rep. 1999;48:82-89. 4. Centers for Disease Control and Prevention. Summary of Notifiable Diseases, United States 1994. MMWR Morb Mortal Wkly Rep. 1994;43:69-79. PUBMED 5. Freedman A, Afonja O, Chang MW, et al. Cutaneous anthrax associated with microangiopathic hemolytic anemia and coagulopathy in a 7-month-old infant. JAMA. 2002;287:869-874. FREE FULL TEXT 6. Elston DM, Eggers JS, Schmidt WE, et al. Histological findings after brown recluse spider envenomation. Am J Dermatopathol. 2000;22:242-246. FULL TEXT | ISI | PUBMED 7. Doust JY, Sarkarzadeh A, Kavoosi K. Corticosteroid in treatment of malignant edema of chest wall and neck (anthrax). Dis Chest. 1968;53:773-774. PUBMED 8. Binder L. Acute arthropod envenomation: incidence, clinical features and management. Med Toxicol Adverse Drug Exp. 1989;4:163-173. PUBMED

Letters Section Editor: Stephen J. Lurie, MD, PhD, Senior Editor.

JAMA. 2002;288:43-44.

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Cutaneous Anthrax Associated With Microangiopathic Hemolytic Anemia and Coagulopathy in a 7-Month-Old Infant
Abigail Freedman, Olubunmi Afonja, Mary Wu Chang, Farzad Mostashari, Martin Blaser, Guillermo Perez-Perez, Herb Lazarus, Robert Schacht, Jane Guttenberg, Michael Traister, and William Borkowsky
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