Correspondence

Monkeypox without Exanthem

N Engl J Med 2007; 356:2112-2114May 17, 2007

Article

To the Editor:

We report on two unvaccinated adult patients from the same household who had strikingly divergent clinical presentations after monkeypox infection. Although readily identifiable disease symptoms developed in both patients, one of them presented with a disseminated skin eruption that included more than 100 pocks, whereas the other had no evident eruption suggestive of monkeypox. Analysis of the findings in the latter patient revealed a rare, specific description of monkeypox without exanthem1 and illustrates the difficulty of relying on clinical algorithms alone for the diagnosis of atypical or vaccine-modified orthopoxvirus infections.

Patient 1 (whom Reed et al. refer to as Patient 4 in their study2) initially presented with a nodular lesion at a puncture site on his wrist after being bitten by a prairie dog; a generalized skin eruption developed during hospitalization. His condition appeared to be a zoonotic infection, and his initial symptoms did not trigger the use of the smallpox-detection algorithm,3 even though he had a febrile prodrome followed by the eruption of smallpoxlike lesions on his limbs. After an earlier case of monkeypox was diagnosed by electron microscopy,2 confirmatory testing of biopsy samples from this patient was performed. In contrast to Patient 1, Patient 2 (whom Reed et al. refer to as Patient 52) had had clear and significant exposure to monkeypox and had seven of eight diagnostic symptoms of the disease; however, she did not have the classic diffuse skin eruption. As a result, Patient 2 was listed as having suspect disease that could not be confirmed by virologic analysis.2

We compared the immune responses of Patient 1 and Patient 2 with those of other unvaccinated adults with primary monkeypox, in whom the infection had triggered readily detectable antiviral antibody titers and orthopoxvirus-specific CD4 and CD8 T-cell responses, as reported by Hammarlund et al.4 (Table 1Table 1Immunologic and Other Characteristics of the Patients.). Patient 2 had normal virus-specific antibody and CD4 T-cell responses but had a substantially stronger antiviral CD8 T-cell response than did other patients with monkeypox. This factor may have played a role in preventing viral replication at distant sites, such as the skin and mucosal surfaces.

Diagnosis of both smallpox and monkeypox on the basis of the clinical presentation can be difficult, as illustrated by an emergency drill in which 6 of 13 patients with simulated smallpox (46%) were discharged with diagnoses that included West Nile virus and upper respiratory infection.5 Furthermore, vaccine-modified infection may result in few or no skin lesions,4 making diagnosis even more problematic. The apparent unreliability of clinical recognition, combined with the difficulty observed in confirming monkeypox during the 2003 U.S. outbreak, suggests the need for caution, since smallpox and monkeypox elicit a range of clinical symptoms that can differ substantially, depending on the underlying health and vaccination status of the infected person.

Matthew W. Lewis, M.S.
Oregon Health and Science University, Beaverton, OR 97006

Mary Beth Graham, M.D.
Medical College of Wisconsin, Milwaukee, WI 53226

Erika Hammarlund, M.S.
Jon Hanifin, M.D.
Mark K. Slifka, Ph.D.
Oregon Health and Science University, Beaverton, OR 97006
slifkam@ohs.edu

Dr. Slifka reports being president and chief scientific officer of Najít Technologies and having an equity interest in the company. Ms. Hammarlund also owns stock in Najít Technologies, which may have a commercial interest in the results of this research and technology. This potential conflict of interest has been reviewed by Oregon Health and Science University and the Integrity Program Oversight Council. This work was supported in part by a grant (R41-AI063675) from the Public Health Service and a grant (RR000163, to Dr. Slifka) from the Oregon National Primate Research Center. No other potential conflict of interest relevant to this letter was reported.

5 References

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   Reed KD, Melski JW, Graham MB, et al. The detection of monkeypox in humans in the Western Hemisphere. N Engl J Med 2004;350:342-350
   Full Text | Web of Science | Medline

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   Hammarlund E, Lewis MW, Carter SV, et al. Multiple diagnostic techniques identify previously vaccinated individuals with protective immunity against monkeypox. Nat Med 2005;11:1005-1011
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Citing Articles (3)

Citing Articles

1. 1

   Melissa E. Dubois, Erika Hammarlund, Mark K. Slifka. (2012) Optimization of Peptide-Based ELISA for Serological Diagnostics: A Retrospective Study of Human Monkeypox Infection. Vector-Borne and Zoonotic Diseases120104061731004
   CrossRef

2. 2

   Kristina E. Rehm, Rachel L. Roper. (2011) Deletion of the A35 gene from Modified Vaccinia Virus Ankara increases immunogenicity and isotype switching. Vaccine 29:17, 3276-3283
   CrossRef

3. 3

   E HAMMARLUND, M LEWIS, J HANIFIN, E SIMPSON, N CARLSON, M SLIFKA. (2008) Traditional smallpox vaccination with reduced risk of inadvertent contact spread by administration of povidone iodine ointment. Vaccine 26:3, 430-439
   CrossRef