December 2014 Dermatology Clinic
A previously healthy 45-year-old white woman was transferred from an external health-care facility with vomiting, abdominal pain, and painful lesions on her foot that had failed to improve despite 24 hours of broad-spectrum antibiotics; doxycycline had been started just before the transfer.
On arrival, the patient was experiencing occasional chills and was found to be febrile, mildly tachycardic, and tachypneic. Examination revealed massive edema with multiple large, hemorrhagic, and violaceous bullae on the dorsal aspect of her right foot. She reported that these lesions began approximately 1 day after cutting her foot on a rock while swimming in a river in coastal Virginia.
Submit your diagnosis to see full explanation.
Monitoring the patient in the intensive care unit was initially considered, but her hemodynamic status normalized rapidly with intravenous volume expansion. A marked neutrophilic leukocytosis with left shift, mildly elevated creatinine, mild thrombocytopenia, and metabolic acidosis were among the early laboratory abnormalities noted. Gram stain of the bullous fluid from the patient’s foot was not diagnostic.
However, the presence of fluffy bilateral infiltrates on chest radiograph supported the suspected diagnosis of vibriosis, which results from infection by a member of the Vibrio species. Doxycycline was continued and intravenous (IV) ceftazidime was initiated. Over the next 24 hours, the patient’s erythema and edema stabilized, but the hemorrhagic bullae progressed to necrosis, requiring wound debridement. Approximately 48 hours after admission, cultures from the patient’s wound were determined to be positive for Vibrio vulnificus.
Endemic to brackish waters, such as coastal and estuarine environments, Vibrio vulnificus is a free-living, opportunistic, halophilic pathogen that thrives in warm waters, preferably those at a temperature that is greater than 18° C (64° F), with a salinity between 15 and 25 parts per 1,000.1 For comparison, the average salinity of the open ocean is 35 parts per 1,000, whereas the salinity of the Dead Sea, the Great Lakes, and common city water are approximately 330 parts, 10 parts, and less than 1 part per 1,000, respectively.
Of the 3 biotypes of Vibrio vulnificus (numbered 1 to 3) that are known to exist, biotype 1 is responsible for the majority of infections.1 Infections tend to be seasonal, peaking during the summer and fall months, with 85% of cases occurring between May and October.2 The majority of cases reported in the United States are from states along the Gulf and Atlantic coasts (33% and 34%, respectively, in 2011); however, cases have also been reported to occur on the Pacific coast.3 Of the 853 cases of vibriosis reported in the United States in 2011, those due specifically to Vibrio vulnificus infection had the highest rates of hospitalization and mortality.3
The illnesses ascribed to Vibrio vulnificus infection range from mild gastroenteritis to wound infections and life-threatening septicemia,4 and conditions vary according to the site of the original infection and state of the host.5 Ingestion of raw or undercooked oysters is responsible for the majority of cases of gastroenteritis or primary sepsis.1
Cutaneous infections occur primarily when open wounds are exposed to saltwater, often following recreational activities, including swimming or boating.5 Individuals whose occupations repeatedly expose them to raw shellfish and oysters (e.g., fishermen, cooks) are also at risk for soft-tissue infections and should always wear gloves and utilize other safety precautions. Whereas most Vibrio vulnificus infections related to recreational activities typically occur on the lower extremities, those related to occupational exposure are more likely to occur on the upper extremities.5 Skin lesions, however, are not unique to primary cutaneous inoculation; patients with septicemia can also develop hemorrhagic bullae.1 In the worst-case scenario of cutaneous infection with Vibrio vulnificus, lesions can progress to necrotizing fasciitis.
The virulence of Vibrio vulnificus is attributed to its ability to produce and release numerous highly destructive cytotoxins.4 These cytotoxins have been found to facilitate destruction of the fascia, increase vascular permeability, and contribute directly to hemolysis and pulmonary injury.4,6 Associated toxins include cytolysin, hemolysin, protease, lipase, hyaluronidase, mucinase, deoxyribonuclease, and sulfatase.4,6
Healthy individuals are less likely to develop cutaneous infection following casual exposure and, if infected, are more likely to have a less virulent course. In comparison, individuals with chronic underlying diseases are at a much greater risk for infection and typically have a more aggressive course, often with a less than optimal outcome.1 In particular, chronic corticosteroid use or the presence of diabetes mellitus, immunodeficiency, hematologic and iron-storage disorders, malignancies, gouty arthritis, chronic renal failure, or chronic liver disease, especially with cirrhosis, confers a higher risk for infection and worse prognosis.5
Optimal treatment requires early intervention upon early suspicion with appropriate antimicrobial therapy and wound care.1 The preferred antibiotic regimen is a combination of 100 mg of IV doxycycline every 12 hours and 2 g of ceftazidime every 8 hours, with alternative regimens including either cefotaxime or ciprofloxacin.1 Emergent debridement, including fasciotomy in extreme cases and amputation in life-threatening cases, has been shown to significantly reduce mortality and length of hospital stay and should be included in the treatment protocol.4
Conditions to be considered in patients with bullous hemorrhagic lesions can be subdivided into 3 major groups: infections, including a variety of bacteria and viruses, especially herpes infections; autoimmune disorders, such as bullous pemphigoid, pemphigus vulgaris, and pyoderma gangrenosum; and other etiologies including purpura fulminans, contact dermatitis, and drug reaction.7
Other bacterial infections causing skin lesions in an acutely ill patient include Neisseria meningitidis, Pseudomonas aeruginosa, and species of Aeromonas, Clostridium, Staphylococcus and Streptococcus.7
However, in the setting of an exposure to brackish waters or ingestion of raw clams or oysters, especially in a patient with chronic liver disease or immunosuppression, one must always consider Vibrio vulnificus. A diagnosis of Vibrio vulnificus infection can be confirmed by isolation of the organism or by identification of the characteristic fluffy, bilateral pulmonary infiltrates on chest radiograph.
In this patient, early suspicion by the clinical team days before confirmation allowed for a positive outcome. She continued to improve during her hospital stay and was discharged with an additional 2-week course of oral doxycycline. One year later, the patient is fully functional, although the affected foot shows some minor discoloration and still swells after long periods of standing.
Padma Chitnavis, BS, is a fourth-year medical student in the Virginia Commonwealth University School of Medicine in Richmond.
Julia R. Nunley, MD, is professor and program director in the Department of Dermatology at Virginia Commonwealth University School of Medicine in Richmond.
- Horseman MA, Surani S. A comprehensive review of Vibrio vulnificus: an important cause of severe sepsis and skin and soft-tissue infection. Int J Infect Dis. 2011;15(3):e157-e166. Available at ijidonline.com/article/S1201-9712(10)02538-5/fulltext
- Jones EH, Feldman KA, Palmer A, et al. Vibrio infections and surveillance in Maryland, 2002-2008. Public Health Rep. 2013;128(6):537-545.
- Centers for Disease Control and Prevention. National Enteric Disease Surveillance: COVIS [Cholera and Other Vibrio Illness Surveillance] Annual Summary, 2011. Available at cdc.gov/ncezid/dfwed/PDFs/covis-annual-report-2011-508c.pdf
- Tsai YH, Huang TJ, Hsu RW, et al. Necrotizing soft-tissue infections and primary sepsis caused by Vibrio vulnificus and Vibrio cholerae non-O1. J Trauma. 2009;66(3):899-905.
- Bross MH, Soch K, Morales R, Mitchell RB. Vibrio vulnificus infection: diagnosis and treatment. Am Fam Physician. 2007;76(4):539-544. Available at www.aafp.org/afp/2007/0815/p539.html
- Park JW, Ma SN, Song ES, et al. Pulmonary damage by Vibrio vulnificus cytolysin. Infect Immun. 1996;64(7):2873-2876. Available at ncbi.nlm.nih.gov/pmc/articles/PMC174159
- Norton SA. Section 29: Bacterial disease. Chapter 183: Miscellaneous bacterial infections with cutaneous manifestations. In: Goldsmith LA, Katz SI, Gilchrest BA, et al., eds. Fitzpatrick’s Dermatology in General Medicine. 8th ed. New York, N.Y.: McGraw-Hill; 2012.
All electronic documents accessed on November 25, 2014.