Sections

Workup

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.

Treatment & Management

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Media Gallery

Vesicular rash on the dorsal aspect of the hand. Vesicopustules are seen; some have a central umbilication.
Umbilicated papule on the lower part of the leg. This smaller lesion still shows the typical umbilicated morphology.
Lymphadenopathy in monkeypox. Large nodes in the mandibular, cervical, or inguinal region are commonly seen in monkeypox. The presence of significant lymphadenopathy helps differentiate monkeypox from smallpox and chickenpox.

of 3

Author

Mary Beth Graham, MD, FIDSA, FACP Professor of Medicine and Surgery (With Tenure), Associate Chief, Division of Infectious Disease, Medical Director, Infection Prevention and Control, Froedtert Hospital, Medical College of Wisconsin

Mary Beth Graham, MD, FIDSA, FACP is a member of the following medical societies: American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Coauthor(s)

Janet Fairley, MD Professor and Head, Department of Dermatology, University of Iowa, Roy J and Lucille A Carver College of Medicine

Janet Fairley, MD is a member of the following medical societies: American Academy of Dermatology, American Federation for Medical Research, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Juliet L Aylward, MD, FAAD, FACMS Clinical Professor of Dermatology, Nelson M Hagan Class of 1929 Chair, Section Chief, Mohs and Dermatologic Surgery, Department of Dermatology, University of Wisconsin School of Medicine and Public Health

Juliet L Aylward, MD, FAAD, FACMS is a member of the following medical societies: American Academy of Dermatology, American College of Mohs Surgery, American Medical Association, American Society for Dermatologic Surgery, Wisconsin Medical Society, Women's Dermatologic Society

Disclosure: Nothing to disclose.

Specialty Editor Board

David F Butler, MD Former Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Association of Military Dermatologists, Phi Beta Kappa, Texas Dermatological Society

Disclosure: Nothing to disclose.

Jeffrey P Callen, MD Professor of Medicine (Dermatology), Chief, Division of Dermatology, University of Louisville School of Medicine

Jeffrey P Callen, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, American College of Rheumatology

Disclosure: Received income in an amount equal to or greater than $250 from: Biogen US (Adjudicator for study entry cutaneous lupus erythematosus); Priovant (Adjudicator for entry into a dermatomyositis study); IQVIA (Serono - adjudicator for a study of cutaneous LE) <br/>Received honoraria from UpToDate for author/editor; Received royalty from Elsevier for book author/editor; Received dividends from trust accounts, but I do not control these accounts, and have directed our managers to divest pharmaceutical stocks as is fiscally prudent from Stock holdings in various trust accounts include some pharmaceutical companies and device makers for these trust accounts for: Stocks held in various trust accounts: Allergen; Amgen; Pfizer; 3M; Johnson and Johnson; Merck; Abbott Laboratories; AbbVie; Procter and Gamble;; Celgene; Gilead; CVS; Walgreens; Bristol-Myers Squibb.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD<br/>Served as a speaker for various universities, dermatology societies, and dermatology departments.

Additional Contributors

Julie R Kenner, MD, PhD Private Practice, SkinHappy MD

Julie R Kenner, MD, PhD is a member of the following medical societies: American Academy of Dermatology, American Society for Dermatologic Surgery

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors, Michael W. Peterson, DO, and Juliet L. Gunkel, MD, to the development and writing of this article.

Monkeypox (Mpox) Workup

Diagnostic Criteria

Laboratory Studies

Histologic Findings

References

Tables

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