What are the signs and symptoms of monkeypox?

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Last updated: December 25, 2025View editorial policy

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Signs and Symptoms of Monkeypox

Monkeypox presents with a characteristic biphasic illness beginning with a prodromal phase of fever, severe headache, lymphadenopathy, myalgia, and fatigue, followed 1-3 days later by a centrifugal rash that progresses through distinct stages from macules to pustules to scabs. 1, 2

Prodromal Phase (Initial Symptoms)

The illness begins after an incubation period of 5-21 days (typically 7-14 days) with non-specific systemic symptoms: 1, 3, 4

  • High fever - often the first presenting symptom 1, 2
  • Severe headache - a prominent feature distinguishing it from other viral illnesses 1
  • Lymphadenopathy - swollen lymph nodes, which is a key distinguishing feature from smallpox 1, 2, 4
  • Myalgia - muscle aches and widespread body pain 1, 3
  • Fatigue and malaise - profound exhaustion 1, 5
  • Back pain - characteristic complaint 5
  • Chills - accompanying the fever 2, 4

Rash Phase (Eruptive Stage)

The characteristic skin lesions typically appear 1-3 days after fever onset: 1

Distribution Pattern

  • Centrifugal distribution - the rash is more concentrated on the face and extremities (including palms and soles) rather than the trunk 1
  • Face is typically most heavily affected 1
  • Extremities show prominent involvement 1

Lesion Progression

The rash follows a predictable Jennerian progression through distinct stages: 4

  • Macules - flat, discolored spots appear first 4
  • Papules - raised lesions develop 4
  • Vesicles - fluid-filled blisters form 4
  • Pustules - lesions become pus-filled 4
  • Crusts/scabs - lesions eventually scab over and heal 4

Important Clinical Features

  • All lesions in a given area tend to be in the same stage of development simultaneously, unlike varicella (chickenpox) where lesions are in different stages 1
  • Lesions are often painful 2
  • The rash can involve oral mucosa 1

Recent Outbreak Variations (2022-Present)

The 2022 outbreak has shown atypical presentations that differ from classic descriptions: 2

  • Anogenital lesions have emerged as the predominant feature in many cases 2
  • Some patients present with localized rather than disseminated rash 2
  • The typical centrifugal distribution may not always be present 2

Clinical Course and Duration

  • Symptoms typically last 2-4 weeks 1
  • The disease is usually self-limiting in immunocompetent individuals 1, 2
  • Patients remain infectious until all scabs have separated 1

Critical Diagnostic Pitfall

Monkeypox can be difficult to distinguish from other pox-like infections based on clinical presentation alone, particularly in atypical cases, making laboratory confirmation essential for definitive diagnosis. 3, 5 The key distinguishing feature from smallpox is the presence of lymphadenopathy, which occurs in monkeypox but not in smallpox. 1, 2

References

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

Diagnosis of monkeypox virus - An overview.

Travel medicine and infectious disease, 2022

Research

Monkeypox: Past, Present, and Future.

Advances in experimental medicine and biology, 2024

Research

The monkeypox diagnosis, treatments and prevention: A review.

Frontiers in cellular and infection microbiology, 2022

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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