Monkeypox (Mpox) Workup

Updated: Nov 29, 2022
  • Author: Mary Beth Graham, MD, FIDSA, FACP; Chief Editor: William D James, MD  more...
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Diagnostic Criteria

The diagnostic criteria are summarized below; refer to the current criteria established by the CDC at Monkeypox: Clinical Recognition.

Confirmed case

Meets 1 or more of the following laboratory criteria:

  • Isolation of the monkeypox (mpox) virus in culture from a sample obtained from the patient

  • Demonstration of the monkeypox virus on PCR in a specimen obtained from the patient

  • Demonstration of the orthopox virus by electron microscopy in samples obtained from the patient in the absence of exposure to other orthopoxviruses

  • Demonstration of the monkeypox virus by immunohistochemical methods in samples obtained from the patient in the absence of exposure to another orthopoxvirus

Probable case

This is contact that meets current epidemiologic criteria per the CDC. It is the occurrence of fever and vesicular-pustular rash, with the onset of the first sign or symptom at most 21 days after the last exposure, meeting the epidemiologic exposure.

Suspected case

This is contact that meets current epidemiologic criteria per the CDC. It the occurrence of fever or unexplained rash and 2 or more other signs or symptoms, with the onset of the first sign or symptom at most 21 days after exposure, meeting the epidemiologic criteria. Symptoms are as follows:

  • Chills and/or sweats

  • Lymphadenopathy

  • Sore throat

  • Cough

  • Shortness of breath

  • Headache

  • Backache


Laboratory Studies

On November 15, 2002, the US FDA issued an EUA for the cobas MPXV to detect monkeypox (mpox) virus DNA in swabs from human monkeypox lesions in patients with suspected monkeypox cases. [17]

Information regarding procurement and disposition of specimens for the CDC may be obtained at Laboratory Testing of Human and Animal Specimens.

A viral culture should be obtained from an oropharyngeal or nasopharyngeal swab. A skin biopsy specimen of the vesiculopustular rash or a sample of the roof of an intact vesiculopustule should be analyzed.

Tissue for PCR of DNA sequence-specific for the monkeypox virus may be obtained. [42]

Paired sera for acute and convalescent titers may be analyzed. Serum collected more than 5 days for IgM detection or serum collected more than 8 days after rash onset for IgG detection was most efficient for the detection of the monkeypox virus infection. [25]

A Tzanck smear can help differentiate monkeypox from other nonviral disorders in the differential diagnosis. However, a Tzanck smear does not differentiate a monkeypox infection from smallpox or herpetic infections.

A pilot of the Tetracore Orthopox BioThreat Alert provided promising results using lesion specimens from acute Orthopoxvirus infections. This assay correctly identified 5 of 6 clinical specimens tested. Although not specific for monkeypox virus, this assay could be used in monkeypox-endemic areas for Orthopoxvirus confirmation by proxy. [43]


Histologic Findings

Histologically, papular lesions show acanthosis, individual keratinocyte necrosis, and basal vacuolization. This is accompanied by a superficial and deep perivascular, lymphohistiocytic infiltrate in the dermis. Lesions in the vesicular stage demonstrate spongiosis with reticular and ballooning degeneration. Multinucleated epithelial giant cells may be seen. Pustular lesions are characterized by epidermal necrosis with numerous eosinophils and neutrophils, many displaying karyorrhexis. Necrosis may extend through full-thickness epidermis with sharp lateral demarcation from adjacent intact epidermis. The associated perivascular infiltrate includes eosinophils and neutrophils in addition to lymphocytes and histiocytes. Petechial lesions demonstrate secondary vasculitis. Amphophilic intranuclear structures suggestive of viral inclusions may be seen in keratinocytes.

Immunohistochemistry staining for orthopox viral antigens can be performed in a reference laboratory. With electron microscopy, intracytoplasmic, round-to-oval inclusions with sausage-shaped structures centrally, measuring 200-300 µm, are observed. [44] Inclusions are consistent with orthopox viruses, permitting differentiation from parapox and herpes viruses.