In the latest Case Record of the Massachusetts General Hospital, a 60-year-old man from coastal New England was admitted to this hospital because of fever, weakness, rash, and renal failure. An initial measurement of creatine kinase was 20,437 U per liter. A diagnostic test was performed.
The differential diagnosis of a maculopapular rash with an acral purpuric component and systemic symptoms including fever is broad, but the most common causes include enterovirus, meningococcemia, human monocytic ehrlichiosis, and Rocky Mountain spotted fever. Causes that are less likely but important to consider include atypical measles, the syndrome of drug reaction with eosinophilia and systemic symptoms, and leukocytoclastic vasculitis.
• What is the differential diagnosis of nontraumatic rhabdomyolysis?
Nontraumatic causes of rhabdomyolysis include electrolyte abnormalities, endocrinopathies, inflammatory myopathies, alcoholism, drugs and toxins, and infections. Statins are well known to cause elevated creatine kinase levels. Metabolic and mitochondrial myopathies, malignant hyperthermia, and neuroleptic malignant syndrome (associated with rigidity and high fever) all can cause severe rhabdomyolysis. Additional exertional causes of rhabdomyolysis include heavy exercise, heat exposure, seizures, and a hyperkinetic state. Numerous infectious agents have been reported to be associated with rhabdomyolysis, including mycoplasma, legionella, influenza A and B, Epstein-Barr virus, coxsackievirus, acute human immunodeficiency virus, and adenovirus. Tickborne infections appear to be commonly associated with rhabdomyolysis. These include ehrlichia and anaplasma, babesiosis, Lyme disease, and Rocky Mountain spotted fever.
• How do ehrlichia and anaplasma infections present?
Ehrlichia and anaplasma are tickborne infections that can cause systemic symptoms and rhabdomyolysis. Most patients are febrile; nonspecific symptoms such as malaise, headache, mayalgias, and chills often occur. A lower percentage of patients present with nausea, vomiting, cough, and arthralgias. Up to 36% of patients with human monocytic ehrlichiosis, an infection caused by E. chaffeensis, present with a rash. Cutaneous involvement is most common in children and includes macules, papules, petechiae, diffuse erythema, and edema of the hands and feet. Cases without a rash can be clinically indistinguishable from “spotless” Rocky Mountain spotted fever. Cases of human monocytic ehrlichiosis have been reported in coastal towns of New England, although this ehrlichiosis is more common in other regions of the United States. Although human anaplasmosis (caused by A. phagocytophilum) is more common in coastal New England than elsewhere, presentation with a rash is rare. In both infections, leukopenia, thrombocytopenia, and elevated liver function tests are common.
Morning Report Questions
Q: What are the manifestations of Rocky Mountain spotted fever?
A: Rocky Mountain spotted fever (RMSF) is caused by Rickettsia rickettsii and is transmitted by various ticks in the eastern United States; patients frequently will not recall a tick bite. Cutaneous findings develop between day 3 and day 5 of the illness. Lesions typically start on the ankles and wrists and spread centrally and to the palms and soles; they range from maculopapular to petechial. Up to 10% of cases of Rocky Mountain spotted fever occur without a rash. Despite its name, Rocky Mountain spotted fever has been reported throughout the Americas. Well-documented cases have been seen in coastal areas of Massachusetts, including Cape Cod and Martha’s Vineyard. Most cases of tickborne illnesses, including Rocky Mountain spotted fever, occur in late spring and early summer. Although Rocky Mountain spotted fever can present in a number of nonspecific ways, patients often present with initial muscle weakness followed by a systemic illness that may include severe rhabdomyolysis.
Q: How is RMSF diagnosed and treated?
A: The diagnosis of RMSF can be made via serology as well as direct detection of the organism in a skin biopsy specimen. In most cases, antigen can be detected in endothelial cells of affected vessels with immunostaining. However, the sensitivity of immunohistochemical techniques ranges from 73 to 92%, and therefore, serologic studies still remain the standard in the diagnosis of Rocky Mountain spotted fever. Even before diagnostic tests return, empirical treatment with doxycycline should be started immediately to avoid the increase in mortality that is associated with delayed treatment.