II. Epidemiology

  1. Outbreak 2022 spring globally (including U.S.) infected >16,000 in 75 countries
    1. Of cases studied, 98% of 528 were in Men who have Sex with Men
    2. Of these cases, 95% of transmission occurred during sex
    3. Thornhill (2022) N Engl J Med 387(8): 679-91 [PubMed]
  2. Outbreaks
    1. FIrst known human outbreak in Congo 1970
    2. Originally limited to Democratic Republic of Congo (and Refugees and Immigrants from that region)
    3. Cases seen primarily in Africa (e.g. Cameroon, Liberia, Nigeria, Sierra Leone) with rare reported cases in Europe
    4. Isolated outbreak occurred in U.S. in 2003, related to rodents imported from West Africa

III. Pathophysiology

  1. Virus in the Orthopoxvirus genus (same genus as Smallpox/Variola, and Cowpox/Vaccinia)
    1. Large enveloped virus
    2. Linear double stranded DNA Poxvirus
  2. Viral Infection whose natural hosts are primates and rodents
    1. First described in 1958, during an infectious outbreak in a research monkey colony
    2. Endemic primarily in the tropical forests of West and Central Africa (esp. Congo Basin)
    3. Animal reservoirs are mostly small rodents (tree squirrels, Gambian rats, prairie dogs)
  3. Zoonotic transmission to humans from animals is typically via bites or contact with the animal's blood
  4. Human to human transmission (much less common than with Smallpox)
    1. Respiratory transmission with prolonged, close face-to-face contact (primary route)
    2. Mucous membrane or body fluid contact with broken skin
      1. Sexually Transmitted Infection especially among Men who have Sex with Men
      2. Receptive anal intercourse appears to be a common mode of transmission
    3. Contact with infectious skin lesions (or contaminated clothing or bedding)
      1. Unlikely with brief contact (e.g. touching a doorknob or sitting on a toilet seat)
      2. Lesions are infectious until they re-epithelialize
  5. Course
    1. Incubation Period: 7 to 10 days (range 5 to 17 days)
    2. Duration: 2 to 4 weeks

IV. Types: Strains

  1. West African Monkeypox
    1. Milder illness with fewer deaths than with Central African Monkeypox
    2. Limited human-to-human transmission
  2. Central African Monkeypox Virus
    1. More severe cases with higher mortality
    2. Higher risk of person-to-person spread

V. Risk Factors

  1. Recent travel to endemic regions (esp. central and west african countries)
  2. Men who have Sex with Men (esp. multiple partners)
  3. HIV Infection
  4. Commercial sex workers
  5. Patients taking HIV PrEP

VI. Findings: Classic Prodrome

  1. General
    1. Classic MPox presentation is more common in children and young adults
    2. Classic prodrome may be absent in epidemic cases
  2. Onset up to 21 days after exposure
  3. Febrile Prodrome (duration 1 to 4 days)
    1. Fever
    2. Chills
    3. Malaise or Fatigue
    4. Headache
    5. Pharyngitis
  4. Marked Lymphadenopathy (generalized or localized)
    1. Less prominent in epidemic cases

VII. Findings: Mucocutaneous Lesions

  1. General
    1. Classic case lesions are in a similar state of progression
    2. Epidemic cases, in contrast, gradually develop lesions that lead to varying lesion age apperance
      1. Lesions may erupt in fulminant, widespread form
      2. Lesions may be pruritic or painful
  2. Common focal lesions in epidemic form are often sexually transmitted (oral sex, receptive anal sex)
    1. Tonsillitis
    2. Anogenital lesions (vessicle, Pustules, or firm well circumscribed ulcers)
    3. Proctitis
      1. May present with Rectal Pain and non-bloody Diarrhea
  3. Rash
    1. Characteristics
      1. Vesiculopustular rash (Blisters, Pustules)
      2. Deep seated, firm, well-circumscribed lesions that may be centrally umbilicated
      3. Lesion are larger than Shingles or HSV lesions
      4. Lesions are of similar size to one another and are typically in same stage in a particular body region
      5. Lesions are painful until they crust or scab and begin to heal, at which time they are pruritic
    2. Distribution: Generalizes over first 24 hours as Centrifugal Rash (trunk is more spared)
      1. Initial Lesions on Mucous membranes
        1. Tongue or mouth lesions or Tonsillitis (often related to oral sex)
        2. Perianal and genital regions (sexually transmitted, often related to receptive anal intercourse)
      2. Next: Face is often involved
      3. Next: Extremities (esp. Palms and soles)
        1. Less commonly involved in the epidemic form
    3. Lesions progress over a 2 to 4 week period
      1. Macule (1 to 2 days)
      2. Papule (1 to 2 days)
      3. Vesicles with clear fluid (1 to 2 days)
      4. Pustule with opaque fluid and Central DImple or umbilication (5 to 7 days)
      5. Crust or scab (7 to 14 days)
      6. Desquamation (lesions no longer contagious)
      7. Hypopigmentation, then Hyperpigmentation
      8. Resolve (2 to 3 weeks)
    4. Variations
      1. Lesion may coalesce into larger scabs
  4. Associated Symptoms
    1. Pruritus
    2. Myalgias

VIII. Labs

  1. General
    1. Obtain swabs of lesions and exudate
    2. Lesion skin biopsy may also be used
  2. Orthopoxvirus DNA PCR
    1. Preferred primary test in U.S.
  3. Orthopoxvirus Immunochemical stain
  4. Anti-Orthopoxvirus IgM
    1. Positive from day 5 to day 56 after rash onset

IX. Differential Diagnosis

  1. Varicella Zoster Virus (Chicken Pox, Shingles)
    1. Chicken Pox lesions are soft, fragile, thin-walled, clear-fluid filled (rarely on palms and soles), and heal within 14 days
    2. Mpox lesions are larger, deeper as well as more firm and Rubbery (more commonly affect palms and soles) and heal within 28 days
  2. Sexually Transmitted Infection
    1. Secondary Syphilis
    2. Herpes Simplex Virus
    3. Chancroid
  3. Scabies
  4. Cowpox
  5. Smallpox
    1. No natural outbreaks have occurred after 1978
    2. Associated with Influenza-like and gastrointestinal prodrome
    3. Lesions are widespread, and rapid onset within 36 hours

X. Complications

  1. Superimposed Cellulitis or other Bacterial Skin Infection (most common)
  2. Pneumonitis
  3. Keratitis
  4. Neuralgia
  5. Encephalitis or Seizures (rare)

XI. Management: General

  1. Most Mpox cases are mild and self-limited
  2. Supportive Care
    1. Analgesics (Ibuprofen, Acetaminophen)
    2. Maintain hydration (esp. Tonsillitis related Dysphagia)
    3. Antiemetics (e.g. Ondansetron) as needed
    4. Proctitis symptom relief (e.g. sitz baths, Stool Softeners)
  3. Consult with local public health regarding testing and treatment
    1. Rapid diagnosis and quarantine is critical to outbreak containment
  4. Isolation for 2 to 4 weeks until rash fully heals (lesions desquamate)
    1. When around others, mask and cover wound with dressing
    2. Avoid public transportation and other crowded palces
    3. Strict hygiene

XII. Management: Antivirals

  1. Background
    1. These agents were primarily developed for use in Smallpox, and efficacy in Monkeypox is unclear
    2. Antivirals may reduce disease severity, pain and swelling, abscess formation and scarring
  2. Indications (see prognosis below)
    1. Severe Disease
    2. Anogenital lesions or other sensitive sites (e.g. Tonsillitis)
    3. CNS or Eye lesions
    4. High risk of severe disease
      1. Immunocompromised
      2. Age <8 years
      3. Pregnancy
      4. Atopic Dermatitis
  3. Agents
    1. Tecovirimat (TPOXX, ST-246) - preferred in 2022 U.S.
      1. Blocks Orthopoxvirus envelope Protein vp37 (decreases cell to cell transmission)
      2. Dosing
        1. Oral: 600 mg orally every 12 hours for weight > 40 kg (every 8 hours for weight >120 kg)
        2. IV: 200 mg IV every 12 hours for weight >40 kg (300 mg IV if weight >120 kg)
          1. IV formulation is contraindicated in Creatinine Clearance <30 ml/min
      3. Adverse effects include Headaches, Nausea, Vomiting and Abdominal Pain (and uncommon Allergic Reactions)
      4. Unknown safety in pregnancy, but limited systemic absorption
      5. LoVecchio (2022) Crit Dec Emerg Med 36(10): 32
    2. Brincidofovir (CMX001, Tembexa)
      1. Consider as second-line adjunct to Tecovirimat for refractory cases
      2. Inhibits Orthopoxvirus DNA Polymerase (as with Cidofovir)
      3. Oral dosing only
      4. Adverse effects
        1. Increased liver transaminases and Bilirubin (obtain baseline hepatic panel before starting)
        2. Nausea and Vomiting
        3. Diarrhea
        4. Abdominal Pain
    3. Cidofovir (Vistide, primary indication is for CMV Retinitis)
      1. Consider as second-line adjunct to Tecovirimat for refractory cases
      2. Inhibits Orthopoxvirus DNA Polymerase (as with Brincidofovir)
      3. IV dosing
      4. Adverse effects
        1. Drug-induced Nephrotoxicity and Proteinuria
        2. Fever
        3. Decreased serum bicarbonate
        4. Neutropenia
        5. Iritis and Uveitis
    4. Vaccinia Immune Globulin Intravenous (VIGIV)
      1. FDA approved for Smallpox Vaccine complications
      2. Offers Mpox passive Immunity (from pooled samples of Smallpox immunized patients)
      3. Indications in Mpox
        1. Impaired Antibody response AND Mpox refractory to other treatments
      4. Adverse Effects
        1. Headache
        2. Nausea
        3. Rigors
        4. Dizziness

XIII. Prognosis: High Risk Patients for Severe Disease

  1. Immunocompromised State
    1. Human Immunodeficiency Virus Infection (HIV or AIDS)
    2. Generalized Malignancy
    3. Leukemia
    4. Lymphoma
    5. Solid Organ Transplantation
    6. Immunosuppressants (e.g. Alkylating Agents, antimetabolites, Tumor Necrosis Factor Inhibitors, high-dose Corticosteroids)
    7. Status Hematopoietic Stem Cell Transplant (<24 months post-transplant or =24 months with graft-versus-host disease)
    8. Other Immunodeficiency (e.g. Autoimmune Condition)
  2. Other factors
    1. Age <8 years old
    2. Atopic Dermatitis
    3. Active exfoliative skin conditions (e.g. Eczema, burns, Impetigo, VZV, HSV, severe acne, severe Diaper Dermatitis, Psoriasis)
    4. Women in pregnancy or Lactation
  3. Disease complications
    1. Secondary Bacterial Skin Infection
    2. Gastroenteritis with severe Nausea, Vomiting, Diarrhea or Dehydration
    3. Bronchopneumonia

XIV. Prevention

  1. Lesions are often outside of Condom protection
  2. Limit sexual partners
  3. Vaccination
    1. Preparations
      1. JYNNEOS Small Pox and Monkey Pox Vaccine
        1. Preferred (approved for Monkeypox)
        2. Third-Generation, Replication deficient live Vaccinia virus Vaccine
        3. Two dose Vaccine (28 days apart) with Immunity developed by 2 weeks after second dose
          1. Booster dose every 4 years as needed
      2. ACAM2000 (Smallpox Vaccine)
        1. Second Generation Smallpox, Live attenuated Vaccinia virus Vaccine
        2. Rare adverse effects include Myocarditis, Guillain-Barre Syndrome, Stevens-Johnson Syndrome
        3. Not recommended for Immunocompromised patients, pregnant or lactating patients, heart disease, Eczema
        4. One dose Vaccination by scarification (multiple skin punctures)
          1. Successful Vaccination is followed by open lesion formation at Immunization site within 28 days
          2. Booster dose every 3 years as needed
    2. Indications
      1. Occupational exposure (e.g. lab workers)
      2. Post-exposure Prophylaxis (sexual or other close contact)
        1. Ideal if within 4 days of exposure
        2. May be given up to 14 days after exposure
      3. High risk patients in regions of Monkey Pox outbreaks
        1. Men who have Sex with Men
        2. Multiple sexual partners
        3. Sex workers
        4. HIV Infection (esp. those on HIV PrEP)

XV. Resources

XVI. References

  1. (2022) Presc Lett 29(9): 49-50
  2. Gianuzzi (2023) Crit Dec Emerg Med 37(2): 4-10
  3. Marx (2022) Crit Dec Emerg Med 36(11): 12-3

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