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Misdiagnosis of a Community-Acquired Methicillin-Resistant Staphylococcus aureus Abscess as Cutaneous Loxoscelism Resulting in Dapsone-Related Methemoglobinemia

Franklin, Jeremy Alan MD, FAAP

Infectious Diseases in Clinical Practice: July 2007 - Volume 15 - Issue 4 - p 269-271
doi: 10.1097/IPC.0b013e31802b68a6
Case Reports

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are becoming much more frequent. Patients presenting with CA-MRSA infections are frequently previously healthy individuals having no identifiable traditional risk factors for infection due to MRSA. Patients presenting with skin and soft tissue infections due to CA-MRSA are frequently misdiagnosed with Loxosceles reclusa (brown recluse spider) envenomations and may be prescribed dapsone, despite a dearth of objective data to support this therapeutic intervention. Dapsone may be associated with significant adverse effects such as hemolytic anemia and methemoglobinemia. A case of CA-MRSA infection initially misdiagnosed by the primary care physician as a "brown recluse spider bite" that was treated with cephalexin and dapsone is presented. The infection dramatically worsened, and the patient developed significant dapsone-related methemoglobinemia.

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are becoming more frequent. Community-acquired MRSA isolates frequently posses the Panton-Valentine leukocidin virulence factor-an exotoxin capable of producing serious necrotizing skin and soft tissue infections. Community-acquired MRSA skin and soft tissue infections are frequently misdiagnosed as Loxosceles reclusa (brown recluse spider) envenomations even in areas where the arachnid is not endemic. Patients presenting with suspected L. reclusa envenomations may be prescribed dapsone, which has not been proven to be efficacious but has been associated with numerous, potentially serious adverse effects. A case of CA-MRSA infection initially misdiagnosed as a "brown recluse spider bite" that was treated with cephalexin and dapsone is presented. The infection dramatically worsened, and the patient developed significant dapsone-related methemoglobinemia.

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A 14-year-old previously healthy white girl presented to the emergency department (ED) with a 2-day history of progressively worsening cyanosis and intermittent headaches. Two days before presenting to the ED, the patient was seen by her primary care physician in Pampa, Tex, with an abscess and associated cellulitis on her chin. After performing an incision and drainage of the abscess, the physician placed the patient on cephalexin and dapsone for presumed cutaneous loxoscelism. Purulent material obtained from the abscess was sent for culture.

While on dapsone, the patient developed perioral cyanosis, which rapidly progressed to involve her face and hands. She also reported intermittent headaches. She had no fever, vomiting, diarrhea, respiratory distress, or other symptoms. In the ED, the patient was noted to have an oxygen saturation of 87% in room air. The patient was placed on 2 L/min of supplemental oxygen by nasal cannula, with no significant improvement in her oxygen saturation or cyanosis. A capillary blood gas revealed a methemoglobin level of 28.5%. The local poison control center was contacted for therapeutic recommendations. The patient was given a single 1-mg/kg dose of methylene blue intravenously due to the combination of her methemoglobin level and her symptoms. Subsequently, the patient's oxygen saturation improved to normal levels on room air, and her headaches and cyanosis resolved. The patient was hospitalized overnight for observation.

On the day of admission, the culture obtained by the patient's primary care physician 2 days before was reported as positive for MRSA that was sensitive to clindamycin and trimethoprim/sulfamethoxazole. The lack of traditional risk factors for MRSA infection and the characteristic antibiotic sensitivity pattern of the isolate led to the classification of this infection as a CA-MRSA infection. At the time of admission, the patient had cellulitis of the chin but no clinically apparent abscess. A computed tomography scan ordered by the ED physician confirmed that no abscess was present. While hospitalized, the patient was treated with intravenous clindamycin. The morning after admission, the erythema, edema, and calor had decreased significantly, and the patient was discharged home on oral clindamycin.

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Dapsone is a sulfone antibiotic primarily used for prophylaxis against Pneumocystis jiroveci in immunocompromised patients, treatment of leprosy, and treatment of L. reclusa envenomations. The hematologic toxicities associated with dapsone are dose-related induction of hemolytic anemia and methemoglobinemia.1-3 Most patients receiving dapsone experience at least mild, clinically insignificant, methemoglobinemia1; indeed, methemoglobinemia may occur after even a single 200-mg dose of dapsone.3

Methemoglobinemia is an uncommon hemoglobinopathy resulting from the oxidation of ferrous iron (Fe2+) to ferric iron (Fe3+) within the hemoglobin molecule.2,3 This alteration within the hemoglobin molecule decreases delivery of oxygen to tissues by shifting the oxygen dissociation curve to the left.2 The clinical presentation of methemoglobinemia is dependent upon the percentage of methemoglobin in the blood. Symptoms include cyanosis that does not improve with supplemental oxygen, weakness, lethargy, confusion, headaches, tachycardia, respiratory distress, coma, and death.3 Methemoglobinemia is most frequently the result of exposure to medications or chemicals (Table 1). Intravenous methylene blue at a dose of 1 to 2 mg/kg is the treatment of clinically symptomatic patients or asymptomatic patients with methemoglobin levels ≥20%.2



Loxosceles spiders are found worldwide in temperate and tropical climate zones.4 Over 50 species of Loxosceles spiders exist in North America.4 Loxosceles reclusa and Loxosceles deserta are endemic to the United States and are responsible for most bites in this country.4,5 Most other Loxosceles species endemic to the United States occur in areas that are uninhabited by humans. The toxicity of Loxosceles venom is species-dependent-L. deserta toxin produces a mild inflammatory reaction; therefore, serious Loxosceles envenomations in the United States are generally attributable to L. reclusa.4 Most L. reclusa envenomations occur in Arkansas, Tennessee, Missouri, Oklahoma, Kansas, and adjacent states.4,5 Loxosceles reclusa is a nocturnal arachnid with a tan to brown body, 6 eyes arranged in 3 diads, and a distinctive violin-shaped mark on the dorsal aspect of its cephalothorax.4,5 Loxosceles reclusa is endemic to only a small section of the southeastern United States.4,5 Symptoms after a L. reclusa envenomation generally consist of a mild inflammatory reaction; however, much more significant symptoms can develop. Severe symptoms are more likely to develop in children 24 to 72 h after envenomation and can include dermonecrotic lesions, diffuse morbilliform rash, nausea and vomiting, malaise, arthralgia and myalgia, fever and chills, hemolytic anemia, thrombocytopenia, and disseminated intravascular coagulation.4,5 Dapsone is sometimes prescribed in cases of suspected loxoscelism. Dapsone has a theoretical benefit in that it inhibits polymorphonuclear cell degranulation, reducing local tissue inflammation and destruction.4,5 The cutaneous necrosis seen after L. reclusa envenomation is dependent upon this inflammatory cascade.5 The benefit of dapsone is controversial, and no prospective study has demonstrated the efficacy of dapsone in treatment of loxoscelism.1,4

Methicillin-resistant S. aureus was first isolated in the United Kingdom in 1961, less than 2 years after the introduction of methicillin.6 Methicillin resistance is conferred principally by the presence of an altered penicillin-binding protein (PBP2a). PBP2a is encoded by the mecA gene, which is carried on a highly mobile genetic element known as the staphylococcal cassette chromosome mec (SCCmec).6-8 After its emergence in the United Kingdom, MRSA rapidly spread through other European countries, Australia, and Japan.6 By 1968, MRSA was reported in the United States.6 Originally, MRSA isolates were confined to patient populations with exposure to the health-care setting; however, by the 1980s, infections with MRSA were occurring in patients with no identifiable traditional risk factors. Community-acquired MRSA infections have been described with increasing frequency. Between 1999 and 2001, a 13.9-fold increase in infections CA-MRSA occurred in children in Texas.8,9 CA-MRSA isolates seem to be clonally and epidemiologically distinct from health-care-associated MRSA isolates.6 Community-acquired MRSA isolates carry a different, genetically smaller type of SCCmec known as SCCmec type IV.6,8 The presence of SCCmec type IV may explain why CA-MRSA isolates tend to have different antibiograms than health-care-associated MRSA isolates. Community-acquired MRSA isolates frequently remain sensitive to clindamycin, trimethoprim/sulfamethoxazole, and linezolid.7 Community-acquired MRSA isolates possess the Panton-Valentine leukocidin virulence factor. Panton-Valentine leukocidin is an exotoxin that is associated with necrotizing skin and soft tissue infections.6,8,10 Community-acquired MRSA infections occur in patients without identifiable traditional risk factors. Demographic factors associated with an increased risk for CA-MRSA infection include younger age, belonging to an ethnic minority group, and being a member of a lower socioeconomic level.6,8 Community-acquired MRSA lesions are frequently misdiagnosed initially as spider bites.6,7,10 A recent study of CA-MRSA infections in the Amarillo Bi-City-County Health District demonstrated that of 700 confirmed cases of CA-MRSA skin and soft tissue infections from 2003 to 2005, 41% were initially misdiagnosed as a spider bite (unpublished data from Amarillo Department of Public Health, Amarillo, Tex).

This case highlights several important issues. First, clinicians should be wary of attributing cellulitis or an abscess to L. reclusa envenomation without compelling evidence, particularly in patients living in areas to which L.reclusa is not endemic. Maps representing the geographic distribution of L. reclusa are available online.4,10 Second, the use of dapsone for presumed cutaneous loxoscelism should be considered experimental and controversial, with no proven benefit and well-characterized adverse effects. This patient presented with headaches, cyanosis, and methemoglobinemia related to dapsone prescribed for suspected cutaneous loxoscelism. Third, the incidence of CA-MRSA is increasing exponentially. This patient had no traditional risk factor for MRSA infection. Finally, CA-MRSA infections can present with serious skin and soft tissue infections and are frequently initially misdiagnosed as spider bites. Physicians must have a high index of suspicion for CA-MRSA infection in patients presenting with reported spider bites because a delay in instituting appropriate therapy due to such a misdiagnosis can lead to increased health-care costs, increased morbidity and, perhaps, mortality.

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© 2007 Lippincott Williams & Wilkins, Inc.