Fever and a rash

Acute presentation of an unwell patient

Fever most commonly indicates bacterial or viral infection. If there is no systemic sepsis, localised rashes associated with infection tend to cause fewer systemic symptoms than generalised rashes associated with infection. Mucosal involvement is common. There are some acute auto-inflammatory disorders than mimic infection due to neutrophil activation, the neutrophilic dermatoses.

Consider performing the following tests:

• Swab for bacterial and viral culture if blisters, erosions, pustules or crusts
• Blood culture if high fever
• CBC, CRP
• Coagulation screen if purpura or very sick patient
• PCR and serology for specific bacteria or viruses
• Echocardiography if septic emboli suspected
• Skin biopsy of fresh skin lesions for histology, culture

Treatment depends on the cause. Consider referral to the emergency department if you are suspicious of a serious infection or the patient is very unwell.

Differential diagnosis

Consider:

• Is the rash localised or generalised? What is its distribution? Are mucosal sites involved?
• The severity of symptoms
• Predominant morphology: is/are there erythema, blisters/erosions, pustules/crusts, purple/black areas?

Fever and localised rash

Painful red, hot skin

• Cellulitis
  • Unilateral swelling/induration
  • Spreads over hours to days
  • May have associated wound or skin disease

Cellulitis 

• Erysipelas
  • Unilateral large plaques with sharp, stepped edge
  • Large blisters
  • Face, lower legs or anywhere
  • Spreads over hours to days
  • May have associated lymphangitis (red streak to local lymph nodes)
  • Culture Streptococcus pyogenes

Erysipelas 

• Erythema nodosum
  • Tender subcutaneous nodules
  • Usually on lower legs

Erythema nodosum 

• Panniculitis – other
  • Many causes
  • Often associated with underlying disease

Panniculitis 

Prominent blisters/erosions

• Hand, foot and mouth
  • Mainly young children
  • Symmetrical vesicles mainly hands, feet and mouth
  • Can extend to limbs and buttocks
  • Culture/PCR enterovirus

HFM in an adult 

• Herpes simplex
  • Monomorphic, umbilicated vesicles, erosions, crust
  • Culture/PCR Herpes simplex

Herpes simplex 

• Herpes zoster
  • Dermatomal
  • Painful
  • Monomorphic vesicles (early), erosions, crust and ulceration (late)
  • Culture/PCR Herpes varicella-zoster

Herpes zoster 

• Impetigo
  • Crusted plaques, vesicles, bullae, pustules
  • Culture Staphylococcus aureus +/- Streptococcus pyogenes

Impetigo 

Pustules

• Folliculitis/furunculosis
  • Based on hair follicle
  • Fever if multiple boils or secondary cellulitis
  • Culture Staphylococcus aureus, Pseudomonas

Folliculitis/furunculosis 

• Neutrophilic dermatosis of dorsal hands
  • Dorsum hands
  • Culture negative
  • Biopsy confirmatory

Neutrophilic dermatosis of dorsal hands 

Purple/black areas

• Ecthyma
  • Not very unwell
  • Eschar
  • Small deep ulcers
  • Culture Staphylococcus aureus +/- Streptococcus pyogenes

Ecthyma 

• Meningococcal disease
  • Rapid deterioration in status
  • Purpura of extremities and more generally in extremis (purpura fulminans due to disseminated intravascular coagulation)
  • Neck stiffness
  • Eyes sensitive to light
  • Obtunded
  • Blood culture/PCR Neisseria meningitidis

Purpura fulminans 

• Necrotising spider bite
  • Endemic venomous spiders
  • Spider must be observed to make this diagnosis
  • Central punctum with purpura/necrosis, surrounding erythema and induration

Necrotising spider bite 

• Necrotising fasciitis
  • Very sick; septic shock
  • Rapid spread of cellulitis with purpura/blistering
  • Fournier gangrene is necrotising fasciitis affecting genitalia
  • Anaesthetic areas in early lesions
  • Bacterial culture essential

Fournier gangrene 

• Vascular occlusion
  • Cholesterol emboli
    • Recent vascular/cardiac procedure

Cholesterol emboli 

• • Septic emboli
    - Endocarditis, arthritis

Septic emboli 

• • Calciphylaxis
    - Renal dialysis, diabetes

Calciphylaxis 

Fever and generalised rash

Redness

• Drug hypersensitivity syndrome
  • Morbilliform (maculopapular) eruption or other rash
  • Drug within 8 weeks of onset
  • Other organs affected (renal, hepatic, respiratory, haematological)
  • May have eosinophilia

Drug hypersensitivity syndrome 

• Erythema infectiosum / fifth disease
  • Child > adult
  • Slapped red cheek appearance
  • Relapsing reticulate rash on arms
  • Serology/PCR Parvovirus B19

Erythema infectiosum / fifth disease 

• ­Erythema marginatum
  • Rheumatic fever
  • Evanescent annular/polycyclic rash with elevated border with temperature spike
  • Evidence of streptococcal infection

­Erythema marginatum 

• Erythroderma (red rash affecting > 90% body surface)
  • Pre-existing atopic eczema, psoriasis
  • New onset: drug eruption, pityriasis rubra pilaris, lymphoma

Erythroderma 

• Kawasaki disease
  • Young child with red skin and mucosal surfaces
  • Swollen hands and feet
  • Peeling is a late feature
  • Lymphadenopathy
  • Cardiac artery aneurysms
  • Other organ involvement leads to a variety of signs
  • No specific diagnostic test

Kawasaki disease 

• Measles
  • Red eyes, red tongue, Koplik spots
  • Coryza, cough
  • Rash has bronze hue
  • Serology/RT-PCR measles

Measles 

• Nonspecific exanthem
  • Upper respiratory symptoms

Nonspecific exanthem 

• Roseola / erythema subitum
  • Infant
  • High fever + upper respiratory symptoms
  • Rash is brief
  • Serology for herpes virus 6 and 7 is not generally available
• Scarlet fever (Streptococcus pyogenes)
  • Strawberry tongue
  • Scarlatiniform rash: tiny red macules or rough papules
  • Swollen then peeling hands
  • Evidence of streptococcal infection

Scarlet fever 

• Rare infections
  • Arbovirus (recent travel)
  • Rubella (unvaccinated)
  • Typhoid fever
• Rare inflammatory disorders
  • Various auto-inflammatory syndromes
  • Often, genetic markers present

Blisters/erosions

• Acute febrile neutrophilic dermatosis
  • Neck, limbs, upper trunk
  • Pseudovesicular plaques, blisters, pustules, purpura, or ulceration
  • Disease associations: rheumatoid arthritis, inflammatory bowel disease, autoimmune arthritis, myeloid dysplasia
  • Biopsy suggestive (neutrophils)

Acute febrile neutrophilic dermatosis 

• Bullous drug eruption
  • Blistering form of drug hypersensitivity syndrome
  • Drug within 8 weeks of onset
  • Other organs affected
  • May have eosinophilia

Bullous drug eruption 

• Enterovirus infection
  • Mild systemic symptoms
  • Vesicular eruption
  • Often followed by nail shedding
  • PCR/serology enterovirus
• Erythema multiforme
  • Mainly hands, feet, face
  • Target lesions
  • Often preceded by herpes simplex, orf, vaccination, drug etc

Erythema multiforme 

• Mycoplasma
  • Erythema multiforme or Stevens Johnson syndrome–like eruption
  • May or may not have pneumonia
  • Serology Mycoplasma pneumoniae

Mycoplasma 

• Staphylococcal scalded skin
  • Infant or elderly, diabetic or renal impairment
  • Discomfort is mild
  • Develops from localised bullous impetigo
  • Culture Staphylococcus aureus

Staphylococcal scalded skin 

• Stevens-Johnson / toxic epidermal necrolysis
  • Patient very unwell
  • Nearly always drug-induced
  • Red skin comes off in sheets

Stevens-Johnson / toxic epidermal necrolysis 

• Varicella (chickenpox)
  • More itch than pain
  • Mainly scalp, face, trunk
  • Culture/PCR Herpes varicella zoster

Varicella 

Pustules/crusts

May involve mucosal surfaces

• Acute generalised exanthematous pustulosis (AGEP)
  • Drug eruption
  • Biopsy suggestive

Acute generalised exanthematous pustulosis 

• Eczema herpeticum
  • Prior eczema or rarely, other skin disease
  • Clustered monomorphic, umbilicated vesicles, pustules or crusts
  • Culture/PCR Herpes simplex

Eczema herpeticum 

• Generalised pustular psoriasis (Zombusch)
  • May or may not have history of plaque psoriasis
  • Symmetrical eruption of numerous superficial pustules on red skin
  • Often annular, flexural
  • Associated with hypocalcaemia
  • Biopsy suggestive

Generalised pustular psoriasis 

• Varicella (late stage)
  • More itch than pain
  • Mainly scalp, face, trunk
  • Culture/PCR Herpes varicella zoster

Varicella 

Widespread purple/black areas

• Purpura fulminans / disseminated intravascular coagulation
  • Usually due to meningococcal disease (neck stiffness, photophobia)
  • Rapid deterioration in mental status
  • Purpura initially affects extremities
  • Blood cultures/meningococcal PCR may reveal cause

Purpura fulminans / disseminated intravascular coagulation 

• Vasculitis
  • Palpable purpura
  • Recent infection or drug or underlying chronic disease
  • Biopsy confirmatory

Vasculitis