Complications

Complication
Timeframe
Likelihood
short term
high

Secondary bacterial skin infections have been reported in 19% of unvaccinated patients.[149] Secondary fungal infections have also been reported.[100] The vesicular skin rash results in a breach of the integrity of the cutaneous barrier to bacterial skin infection, especially when scratched or otherwise traumatised. Necrotising soft-tissue infections and pyomyositis can occur.[14] Soft-tissue abscesses and cellulitis have also been reported.[140][205][229] Infection of hand lesions may lead to paronychia and lymphangitis.[229][230]

Antibiotic treatment should be administered. Surgery may be required for necrotising soft-tissue infection, cellulitis, paronychia, or pyomyositis. Some cases in the current ongoing outbreak have required extensive surgical debridement or amputation of an affected extremity.[100]

Permanent pitted scarring and discoloration secondary to infection is a common long-term sequelae.[5][149]

short term
high

Patients with a heavy rash burden may develop exfoliation, similar to partial thickness burns in severe cases. Minimise insensible fluid loss and promote skin healing. Ensure adequate hydration and nutrition. Debridement may be needed. Skin grafting may be required rarely.[14]

short term
high

Can occur in up to 86% of cases with lymphadenopathy. When combined with multiple oropharyngeal lesions, patients may be at risk of retropharyngeal abscess or respiratory compromise. Corticosteroid treatment may be required.[14]

short term
medium

Identification of sepsis should be done rapidly using established criteria. Management follows the same principles as for bacterial sepsis and should include: broad-spectrum empirical antibiotic therapy, ideally given within 1 hour of recognition; rapid intravenous fluid resuscitation with assessment of response; vasoactive therapy; appropriate airway management and oxygen administration.[228]

short term
medium

Frequent in severe disease because intravascular fluid tends to be lost through fever, rash, and capillary leak. The accompanying systemic inflammatory response syndrome may cause hypotension as well. This combination of factors reduces renal blood flow and promotes acute kidney injury. Early recognition by monitoring urine output and blood biochemistry will indicate whether intravenous fluids are necessary.

short term
medium

Patients are at risk of bacterial pneumonia.[5] Broad-spectrum antibiotic treatment should be given. Severe pneumonia will cause hypoxia requiring oxygen therapy and possibly mechanical ventilation in an intensive care unit.

Pulmonary involvement with nodular lesions has been reported.[100]

short term
medium

Hypotension may also be exacerbated by superadded bacterial sepsis and possible viral myocarditis. Hypotension unresponsive to adequate fluid replacement will require treatment with inotropes. If superadded bacterial sepsis is suspected, broad-spectrum antibiotics should be given intravenously.

short term
low

Cases of myocarditis and myopericarditis have been reported in the current ongoing outbreak. Cases have been self-limiting and required supportive care.[39][141][231][232][233]

Myocarditis has been documented after administration of ACAM2000® smallpox vaccine, which may be used for post-exposure vaccination of contacts in some countries. The risk of myocarditis after third-generation smallpox vaccines is currently unknown. Myocarditis and pericarditis are also associated with COVID-19 vaccines, and recent COVID-19 vaccination may be relevant.

A case of pericarditis with pericardial effusion has also been reported in the current ongoing outbreak.[234]

short term
low

Ocular infections may result in corneal ulcer/scarring and permanent vision loss.[149][235][236] Ocular complications can result from autoinoculation. Approximately <1% of patients have had ocular involvement in the current ongoing outbreak.[237]

Patients may present with conjunctivitis, blepharitis, keratitis, subconjunctival nodules, or periorbital cellulitis.[229][238][239][240][241][242][243]

Ophthalmic consultation is recommended in patients with ocular involvement. Slit-lamp examination and dilated funduscopic examination may be helpful for determining whether anterior or posterior segment structures are involved.[237]

Vitamin A supplementation is recommended. Eye lubrication and saline-soaked eye pads may be helpful. Ophthalmic antibiotics/antivirals may be required for co-infection.[14]

Topical antiviral agents are recommended. The topical antiviral agent trifluridine (also known as trifluorothymidine) has been used for the treatment of ocular vaccinia, and may be used to hasten resolution of symptoms and prevent long-term damage from scarring.[244] Trifluridine is recommended for the management of monkeypox keratitis, in consultation with an ophthalmologist. It may also be used prophylactically in certain patients with lesions near the eye to prevent autoinoculation; however, the risk of corneal epithelial toxicity with prolonged use must be taken into account. Topical corticosteroids should be avoided as they may cause corneal damage or viral persistence.[237]

Tecovirimat should be considered for all patients with severe disease, which includes ocular manifestations. See Treatment algorithm.

Vaccinia immunoglobulin may be considered on a case-by-case basis in consultation with an infectious disease specialist. However, caution is recommended in people with active keratitis, as increased corneal scarring was observed in an animal model study.[237] See Emerging.

short term
low

Tonsillar complications were not previously known to be a typical feature of monkeypox. However, they have been reported rarely in the current ongoing outbreak (e.g., tonsillitis, peritonsillar cellulitis, tonsillar/peritonsillar abscess, necrotising tonsillitis), likely as a consequence of practising oral-receptive sex.[39][140][145][245][246][247] Airway management, antibiotic therapy, and surgery may be required depending on the presentation. 

[Figure caption and citation for the preceding image starts]: Right tonsillar enlargement with an overlying pustular lesion and yellow-green exudate with slight deviation of the uvulaBMJ. 2022 Jul 28;378:e072410; CC-BY-NC 4.0 licence [Citation ends].com.bmj.content.model.Caption@5da4569b

short term
low

Epiglottitis has been reported rarely in the current ongoing outbreak.[39] Urgent management, particularly of the airway, may be required.

short term
low

Paraphimosis/phimosis has been reported rarely in the current ongoing outbreak as a consequence of lesions causing severe penile oedema.[140][145][160] Paraphimosis is a medical emergency and surgery may be required if there is evidence of ischaemia or necrosis.

[Figure caption and citation for the preceding image starts]: Progression of penile lesions and penile oedemaBMJ. 2022 Jul 28;378:e072410; CC-BY-NC 4.0 licence [Citation ends].com.bmj.content.model.Caption@7d913d3e

short term
low

Perianal/groin abscesses and rectal perforation have been reported rarely in the current ongoing outbreak.[140][145] Bowel lesions may be exudative and cause significant tissue oedema leading to obstruction. Lesions may lead to bowel strictures and scarring.[100] Antibiotic therapy and surgery may be required. A case complicated by anal abscess relieved by colostomy has been reported.[248]

short term
low

Urinary retention (e.g., due to severe penile oedema or urethritis) has been reported rarely in the current ongoing outbreak.[140][160] Catheterisation may be required. Lesions may lead to urethral strictures and scarring.[100]

short term
low

Patients with severe disease are at risk of encephalitis, transverse myelitis, and seizures.[5][100][250][251] Few neurological complications have been reported with the current ongoing outbreak.[251] However, cases of encephalomyelitis have been reported. The complication developed within 5 and 9 days of illness onset.[252] It is unknown whether this is a result of direct viral invasion of the central nervous system, or whether it is a parainfectious autoimmune process triggered by systemic infection. Treatment is primarily supportive. There may be a role for antiviral agents but there is no supportive evidence. Antibiotics/antivirals may be indicated for co-infections. Anticonvulsants should be administered if required.[14]

variable
low

A case of acute arthritis has been reported in a HIV-positive man in the current ongoing outbreak.[249] No cases of monkeypox-related arthritis or osteomyelitis have been previously described in the literature. 

variable
low

Inoculation with traditional vaccinia may cause a generalised vesicular rash in the presence of eczema called eczema vaccinatum. A history of vaccination or recent exposure to someone who has been vaccinated on a background of known eczema is key for diagnosis. A polymerase chain reaction of vesicle fluid will be positive for vaccinia DNA but negative for monkeypox DNA. Eczema vaccinatum should be distinguished from generalised vaccinia (see below). Tecovirimat is approved in Europe for the treatment of complications following vaccinia vaccination. Other antiviral drugs may also be recommended. Vaccinia immunoglobulin is licensed in the US for the treatment of complications due to vaccinia vaccination.

[Figure caption and citation for the preceding image starts]: Eczema vaccinatum skin lesions on the torso of a smallpox vaccine recipientCDC/Moses Grossman, MD/California Emergency Preparedness Office (Calif/EPO) [Citation ends].com.bmj.content.model.Caption@69c6be91

variable
low

Generalised (disseminated) vaccinia is a self-limiting illness consequent upon vaccinia viraemia occurring in the absence of pre-existing skin disease. Tecovirimat is approved in Europe for the treatment of complications following vaccinia vaccination. Other antiviral drugs may also be recommended. Vaccinia immunoglobulin is licensed in the US for the treatment of complications due to vaccinia vaccination.

variable
low

Progressive vaccinia starts as a localised but relentlessly progressive spread of vaccinia at the inoculation site and is potentially fatal. It occurs in the markedly immunosuppressed (e.g., congenital immunodeficiencies, cytotoxic chemotherapy, advanced HIV disease). Progressive vaccinia is rare, but fatal if untreated. Tecovirimat is approved in Europe for the treatment of complications following vaccinia vaccination. Other antiviral drugs may also be recommended. Vaccinia immunoglobulin is licensed in the US for the treatment of complications due to vaccinia vaccination.

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