Does the monkeypox rash differ from the smallpox (variola) rash?

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Last updated: April 23, 2025View editorial policy

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From the Guidelines

Monkeypox rash differs from smallpox rash in several key aspects, although the provided evidence primarily describes smallpox symptoms. The symptoms of smallpox, as described in the study 1, begin with a prodrome of high fever, malaise, and prostration, followed by a maculopapular rash that progresses through various stages, including papules, vesicles, pustules, and scab lesions. Key characteristics of smallpox rash include:

  • Deeply embedded lesions in the dermis
  • Firm, round objects embedded in the skin
  • Appearance first on the oral mucosa, face, and forearms, then spreading to the trunk and legs
  • Potential for lesions on the palms and soles
  • Pitted scarring as the skin lesions heal In contrast, monkeypox rash is not explicitly described in the provided evidence, but based on general medical knowledge, it is known to have distinct features, such as:
  • A fever preceding the rash
  • Lesions that develop at the same time and appear similar in size and stage throughout the body
  • A tendency to start on the face and extremities before spreading to other parts of the body
  • Deeper skin lesions that may become umbilicated
  • Significant lymph node swelling These differences are crucial for accurate diagnosis and appropriate treatment, as the management and isolation requirements for monkeypox and smallpox differ.

From the Research

Monkeypox Rash Characteristics

  • The rash associated with monkeypox tends to be more localized on the face and extremities than on the trunk 2.
  • The skin lesions typically erupt within 1-3 days of the onset of fever 2.
  • Monkeypox lesions are all in the same stage and evolve with the same rate, unlike varicella where lesions can be identified in various stages including macular, papular, vesicular, pustular, and crusts 3.

Comparison with Smallpox Rash

  • Smallpox, caused by the variola virus, has been eradicated since the 1980s, but its relationship to monkeypox is a concern due to their shared virus family 4.
  • The rash-causing disorders, including monkeypox, smallpox, and chickenpox, can be distinguished by their distinctive symptoms, despite similar manifestations such as fever, rash, myalgia, chills, and headache 3.
  • Diagnostic tests can be useful in differentiating between these skin diseases, which can be mistaken for one another due to similar symptoms 3.

Clinical Diagnosis and Treatment

  • The clinical diagnosis of monkeypox infection is commonly made based on the occurrence pattern of its skin rash 3.
  • Currently, no specific medication is available for monkeypox, but anti-viral agents approved for smallpox infection, such as tecovirimat, cidofovir, and brincidofovir, can be used 2, 5, 6.
  • Tecovirimat has demonstrated efficacy in animal studies and is FDA-approved for treating smallpox, with its use for monkeypox treatment permitted only through an FDA-regulated Expanded Access Investigational New Drug (EA-IND) mechanism 5, 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Monkeypox: Virology, Pathophysiology, Clinical Characteristics, Epidemiology, Vaccines, Diagnosis, and Treatments.

Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques, 2022

Research

Smallpox and monkeypox: Looking back and looking ahead.

Cleveland Clinic journal of medicine, 2023

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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