What is the DDx of a new-onset rash?

Assuming an adult with a new-onset rash and no prior confirmed dermatological diagnosis.

First: the “can’t miss” causes

These are the ones to prioritise because they can deteriorate quickly:

• Non-blanching petechiae/purpura: think meningococcaemia, sepsis, DIC, vasculitis, thrombocytopenia. A purpuric rash is a red flag, especially with fever, lethargy, hypotension, abdominal pain, haematuria, headache, or meningism. [1][2]
• Painful rash with mucosal involvement, blistering, skin sloughing: think SJS/TEN, DRESS, AGEP, bullous drug eruption, erythema multiforme major. NICE specifically highlights painful rash, mucosal erosions, blistering, epidermal detachment, fever as features of severe drug reactions. [3]
• Hot, tender, rapidly spreading unilateral erythema: cellulitis/erysipelas; if the pain is out of proportion, worry about necrotising fasciitis. [2]
• Wheeze, hypotension, tongue/lip/throat swelling with rash: anaphylaxis/angioedema. [3]

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Core differential diagnosis of a new rash

1) Urticaria ± angioedema

What it looks like: transient, raised wheals; individual lesions usually come and go, often within hours.
Why it matters: common, but can be part of drug allergy, infection-related urticaria, or an allergic reaction.
Clues: intense itch, migratory lesions, no scale, no persistent fixed plaque. If there is angioedema without wheals, think bradykinin-mediated causes such as ACE-inhibitor angioedema. [1][3]

2) Eczematous dermatitis

Includes atopic eczema, irritant/allergic contact dermatitis, and nummular/discoid eczema.
What it looks like: erythema, dryness, scale, excoriation, sometimes oozing/crusting in acute flares.
Clues: itch is prominent; distribution often gives the answer — flexural, exposed areas, or a pattern matching contact with an irritant/allergen. Contact dermatitis is often asymmetrical or in an odd shape. [1][2]

3) Drug eruption

This is one of the most important causes of a new rash in adults.
Common forms:

• Morbilliform/exanthematous eruption: symmetric pink-red macules/papules, often 1–2 weeks after a new drug.
• DRESS: rash plus fever, lymphadenopathy, eosinophilia, and organ involvement, usually 2–6 weeks after exposure.
• SJS/TEN: painful rash, fever, mucosal erosions, blistering/detachment, usually 7–14 days after first exposure.
• AGEP: pustular eruption with fever and neutrophilia, often 3–5 days after drug exposure.
• Fixed drug eruption: recurrent, sharply demarcated lesion(s) at the same site, often leaving hyperpigmentation.
  Clues: new medication in the last days to 8 weeks, OTCs included; think antibiotics, anticonvulsants, allopurinol, NSAIDs, sulfonamides, etc. [3]

4) Viral exanthem

What it looks like: generalised maculopapular rash, often with a viral prodrome.
Examples: parvovirus B19, EBV/CMV, measles, rubella, roseola, varicella.
Clues: fever, coryza, sore throat, cough, conjunctivitis, malaise, lymphadenopathy; in adults, remember that “childhood viruses” still happen and can be clinically messy. [2]
If the rash is annular/spreading after a tick bite, consider erythema migrans from Lyme disease; UKHSA notes that a rash which develops after a tick bite and enlarges is a key clue, while other mimics include insect bites, cellulitis, tinea corporis, granuloma annulare, erythema multiforme, and nummular eczema. [4]

5) Bacterial/toxin-mediated infection

What it looks like: depends on organism, but usually more toxic/ill-looking than simple eczema.
Examples: cellulitis, erysipelas, impetigo, scarlet fever, staphylococcal scalded skin syndrome, necrotising soft tissue infection.
Clues: fever, pain, warmth, tenderness, rapid spread, crusting, bullae, or systemic upset. Unilateral leg erythema strongly suggests cellulitis/erysipelas. [2]

6) Scabies / arthropod-bite reactions

What it looks like: intensely itchy papules, sometimes eczematous or excoriated; burrows may be visible, especially in finger webs/wrists.
Clues: nocturnal itch, household contacts with itch, lesions in finger webs, wrists, axillae, groin, genitalia; secondary infection can obscure the classic pattern. In outbreaks, particularly in institutional settings, this is easy to miss. [5]

7) Psoriasis

What it looks like: well-demarcated red scaly plaques; can be guttate, plaque, pustular, or erythrodermic.
Clues: extensor surfaces, scalp, nails; guttate psoriasis can follow streptococcal infection; pustular/erythrodermic disease can look acutely unwell and needs urgent review. [6]

8) Pityriasis rosea

What it looks like: often starts with a herald patch, then a more widespread oval scaly eruption in a cleavage-line pattern.
Clues: usually self-limited; often trunk-predominant; can be mistaken for tinea or a drug eruption early on. [2]

9) Dermatophyte infection / tinea corporis or faciei

What it looks like: annular lesion with a scaly advancing edge, often asymmetrical.
Clues: itch, central clearing, steroid use making it atypical (“tinea incognito”), contact with pets or other affected people. It is a frequent mimic of erythema migrans and eczema. [4][1]

10) Herpes zoster / HSV

What it looks like: grouped vesicles; zoster is classically dermatomal and unilateral, HSV tends to recur in a more localised pattern.
Clues: pain/burning more than itch, dermatomal restriction, all lesions at a similar stage early on. [2]
If there is widespread erosive disease with mucosal involvement, re-think SJS/TEN or eczema herpeticum rather than simple zoster.

11) Erythema multiforme

What it looks like: target lesions; may be localised or more widespread.
Clues: often follows HSV, but can also follow drugs or infections; if mucosae are involved or the patient is very unwell, distinguish from SJS/TEN carefully. [3][2]

12) Vasculitic rash

What it looks like: palpable purpura, petechiae, sometimes urticarial-appearing lesions that persist >24 hours or leave bruising.
Clues: lower limbs, arthralgia, abdominal pain, haematuria, renal involvement, recent infection or drug exposure. Skin biopsy is often needed if the diagnosis is uncertain. [1][3]

13) Photosensitive / photodistributed eruption

What it looks like: rash on sun-exposed skin, often sparing creases, under the chin, eyelids, or hair-bearing areas.
Clues: new drug, new topical exposure, outdoor exposure, connective tissue disease, or a photodermatosis; distribution is the key discriminator. [1]

14) Systemic inflammatory / autoimmune / haematological disease

What it looks like: variable — can be urticarial, purpuric, papulosquamous, or erythrodermic.
Clues: fever, weight loss, arthralgia, oral ulcers, ocular symptoms, lymphadenopathy, hepatosplenomegaly, night sweats, or recurrent episodes. If the rash is persistent or unexplained, broaden to lupus, dermatomyositis, Behçet’s, Sweet syndrome, lymphoma, or other systemic disease. [1]

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Practical “pattern recognition” shortcut

If I were structuring the DDx on the ward, I’d sort it like this:

• Itchy + transient wheals → urticaria / angioedema
• Itchy + dry/oozy/scaly → eczema / contact dermatitis / scabies
• Scaly, well-demarcated plaques → psoriasis / tinea / pityriasis rosea
• Painful or burning → zoster, cellulitis, drug reaction, SJS/TEN, nec fasc
• Purpuric or non-blanching → vasculitis, sepsis/meningococcaemia, thrombocytopenia, DIC
• Vesicles/blisters + mucosa → SJS/TEN, bullous drug eruption, pemphigoid/pemphigus, HSV/VZV
• Sun-exposed distribution → photosensitivity, lupus, drug reaction
• Dermatomal → zoster
• After a tick bite / expanding annulus → Lyme erythema migrans [4]

If you want, I can turn this into a one-page acute rash algorithm or a morphology-based differential table for clinic use.