Differentials

Chickenpox

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SIGNS / SYMPTOMS

Most common in children <10 years of age.

Lacks history of chickenpox or varicella vaccination.

Vesicles appear in crops (monkeypox lesions are all of a similar stage of evolution), are shallow (easily break, unlike deep-seated monkeypox lesions), and located mainly on the trunk (centripetal, the reverse of the centrifugal monkeypox rash).

Rash is usually polymorphic and generally evolves more quickly (<24 hours), and lesions on palms or soles are rare.[149]

Prodromal fever is uncommon (mild, if present).[149]

Lymphadenopathy is usually not present.[149]

No differentiating signs or symptoms if severe disease.

Co-infection is possible. Patients with co-infections were more likely to report symptoms than varicella zoster-alone cases, and less likely than monkeypox-alone cases. Significantly higher lesion counts have been observed with co-infection cases compared with varicella zoster-alone cases, but less than monkeypox-alone cases.[187]

INVESTIGATIONS

Polymerase chain reaction of vesicle fluid: positive for varicella-zoster virus DNA.

Usually performed automatically by reference laboratory as part of poxvirus screening.

Disseminated herpes zoster

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SIGNS / SYMPTOMS

May occur in severely immunocompromised patients.

Vesicular rash involves several dermatomes, and visceral involvement may occur.

Co-infection is possible. Patients with co-infections were more likely to report symptoms than varicella zoster-alone cases, and less likely than monkeypox-alone cases. Significantly higher lesion counts have been observed with co-infection cases compared with varicella zoster-alone cases, but less than monkeypox-alone cases.[187]

INVESTIGATIONS

Polymerase chain reaction of vesicle fluid: positive for varicella-zoster virus DNA.

Herpes simplex

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

May occur in severely immunocompromised patients.

Rash is not generalised and is not deep-seated.

INVESTIGATIONS

Polymerase chain reaction of vesicle fluid: positive for herpes simplex DNA.

Usually performed automatically by reference laboratory as part of poxvirus screening.

Syphilis

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SIGNS / SYMPTOMS

Generalised rash of secondary syphilis does not vesiculate; it may extend to the palms and soles.

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Syphilis serology (e.g., rapid plasma reagin, Treponema pallidum particle agglutination [TPPA] test): positive.

Rapid plasma reagin: non-specific but reflects disease activity.

TPPA test: specific, but remains positive after effective treatment.

Chancroid

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SIGNS / SYMPTOMS

Painful genital papules in early stages, which then pustulate and ulcerate. Ulcers are soft and painful without induration. Buboes form in later stages.

Other symptoms may include urethritis, vaginal discharge, dysuria, dyspareunia, rectal pain or bleeding, and extra-genital ulcers.

INVESTIGATIONS

Culture or polymerase chain reaction of ulcer swabs or bubo aspirates: positive for Haemophilus ducreyi. Gram stain may be useful and shows gram-negative coccobacilli or slender bacilli in railroad or chaining pattern.

Disseminated gonococcal infection

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

Lesions may be papules, haemorrhagic pustules, bullae, petechiae, or necrotic, and are usually on the extremities.

Severe joint pain or polyarthritis.

Note: urogenital symptoms of gonorrhoea may be absent in disseminated gonococcal infection.

INVESTIGATIONS

Polymerase chain reaction or culture: positive for gonorrhoea.

Lymphogranuloma venereum (LGV)

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SIGNS / SYMPTOMS

Painful unilateral inguinal or femoral lymphadenopathy ('groove sign of Greenblatt' may be seen) during secondary stage.

Non-specific symptoms of proctocolitis (e.g., anorectal pain, rectal bleeding, mucopurulent discharge).

May be present in tertiary stages: genital elephantiasis; oedema; saxophone penis; esthiomene; or anogenital sinus tracts, strictures, or fistulae.

Erythema nodosum is occasionally present.

INVESTIGATIONS

Polymerase chain reaction of fluid or swab: positive for LGV-specific Chlamydia trachomatis genovars.

Hand-foot-and-mouth disease

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SIGNS / SYMPTOMS

Most common in children <10 years of age.

Vesicles generally confined to the oral mucosa with small lesions on the hands and feet. Illness generally only lasts a few days if no complications.

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Typically a clinical diagnosis.

Virus isolation (from faeces, throat swab, urine, or cerebrospinal fluid) is very labour-intensive.

Serological tests are prone to cross reactivity and generally only allow retrospective diagnosis.

Viral RNA can be detected by reverse transcription-polymerase chain reaction but this is not routinely available.

Drug reaction

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SIGNS / SYMPTOMS

Cutaneous drug reactions may be vesiculobullous, but the lesions are rarely uniform.

Rash is usually generalised.

History of exposure to a new drug.

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Clinical diagnosis.

Eczema vaccinatum

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SIGNS / SYMPTOMS

Inoculation with the live smallpox vaccine can cause a generalised vesicular rash in the presence of eczema.[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@10eeefba

History of vaccination or recent exposure to someone who has been vaccinated on a background of known eczema.

INVESTIGATIONS

Polymerase chain reaction of vesicle fluid: positive for vaccinia DNA but negative for monkeypox DNA.

Usually performed automatically by reference laboratory as part of poxvirus screening.

Disseminated (generalised) vaccinia

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

Self-limiting viraemic illness from exposure to vaccinia (either deliberate or through contact with a vaccine).

Additional lesions subsequent to and distant from the original inoculation site.

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Clinical diagnosis that may be confirmed by the demonstration of vaccinial DNA in distant lesions.

Erythema multiforme

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SIGNS / SYMPTOMS

Vesicular, pleomorphic, often with large vesicles. Often associated with conjunctivitis, stomatitis, and urethritis (Stevens-Johnson syndrome).

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Clinical diagnosis.

Usually there are no specific diagnostic tests for erythema multiforme, but sometimes the underlying precipitant may be identified (e.g., mycoplasma infection).

Meningococcal septicaemia

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

Purpuric lesions.

INVESTIGATIONS

Polymerase chain reaction of ethylenediamine tetra-acetic acid (EDTA) blood: detection of meningococcal DNA.

Isolation of gram-negative diplococci from blood culture subsequently proven to be Neisseria meningitidis.

Measles

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

Widespread blotchy rash that does not vesiculate.

Occurs in the context of coryza and conjunctivitis.

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Raised anti-measles IgM in serum.

Isolation of measles virus from throat swab or urine.

Tanapox

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

Single or a few localised and slowly evolving lesions that do not pustulate.

Zoonosis found mainly in Kenya and Zaire.

May be preceded by a mild febrile prodrome.

INVESTIGATIONS

Polymerase chain reaction of DNA from lesional material: positive for tanapox DNA.

Usually performed automatically by reference laboratory as part of poxvirus screening.

Orf

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SIGNS / SYMPTOMS

Usually solitary lesions, not associated with systemic illness.

Patient systemically well.

History of exposure to sheep and/or farms.

INVESTIGATIONS

Polymerase chain reaction of DNA from lesional material: positive for orf (parapox) DNA.

Insect bites

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SIGNS / SYMPTOMS

Usually bites do not vesiculate or appear as monomorphic lesions (an exception might be sudden exposure to bed bugs).

Absence of prodromal illness or systemic symptoms.

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Clinical diagnosis.

Acne

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SIGNS / SYMPTOMS

Lesions can form pustules typically involving the face, occasionally the trunk, and rarely the limbs.

Prolonged history of acne in the absence of any prodromal illness.

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Clinical diagnosis.

Oral aphthous ulcers

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SIGNS / SYMPTOMS

Risk factors may be present (e.g., local trauma).

Absence of lesions on other parts of the body (particularly perineal/perianal and genital areas).

Absence of systemic symptoms (e.g., fever, myalgia, headache, lymphadenopathy).

INVESTIGATIONS

Clinical diagnosis.

Polymerase chain reaction: negative for monkeypox virus DNA.

Behcet's syndrome

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

Family history may be present.

Common in young people 20-40 years of age.

Diagnosis is based on defined clinical criteria.

Clinical manifestations may involve various organs (e.g., eye, gastrointestinal, vascular, pulmonary, central nervous system).

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Laboratory testing and imaging are not useful but may play a role in ruling out alternative diagnoses.

Polymerase chain reaction: negative for monkeypox virus DNA.

Molluscum contagiosum

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

Most common in children, young adults, and immunocompromised people.

Localised papular lesions that may show central umbilication but not vesiculation caused by the poxvirus molluscum contagiosum.

Commonly affects face and genitals, but can occur anywhere.

May be widespread in the immunosuppressed.

Does not cause systemic illness.

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Clinical diagnosis that may be confirmed by standard histology.

Electron microscopy (not usually performed): reveals typical poxvirions.

Scabies

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

Symmetrical erythematous papules, vesicles, and excoriations of the web spaces, axillae, areola, periumbilical areas, and male genitalia; typically spares the face in adults.

Presence of burrows is pathognomonic.

Thick crusted lesions with dystrophic nails may be seen in Norwegian scabies.

Does not cause systemic illness.

Positive ink burrows test.

INVESTIGATIONS

Ectoparasite prep shows presence of mites, eggs, or faecal material of mites.

Eczema herpeticum

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

Severe skin infection caused by herpes simplex virus in patient with eczema.

Characteristic lesions are grouped vesicles or pustules, and may later progress to 'punched out' ulcerations.

May affect multiple organs.

INVESTIGATIONS

Clinical diagnosis.

Vesicular fluid polymerase chain reaction testing: positive for herpes simplex DNA.

Rickettsialpox

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

Rash is usually macular or papular in rickettsial diseases but is vesicular in some infections (e.g., rickettsialpox due to Rickettsia akari).

Eschar may be present.

INVESTIGATIONS

Serology is positive for antibodies to Rickettsia species.

Polymerase chain reaction is positive for R akari DNA.

Smallpox

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

Smallpox has been eradicated so it is very unlikely, unless the patient has a history of contact with a known smallpox repository or is a laboratory worker who accidentally encounters the variola virus while disposing of archival material, or there has been a deliberate release.

Lymphadenopathy is usually absent.

More severe illness and more numerous lesions.

INVESTIGATIONS

Polymerase chain reaction of lesion material or exudate: positive for smallpox DNA.

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