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REMINDER-cell phones to vibrate mode please

Dermatologist Newbie?

That’s Greek for “not real

doctor”

Dermatology Emergencies?!? Really???

Dr Katherine ArmourConsultant Dermatologist

Canterbury District Health

Disclaimer

Not exhaustive (SSSS, immunobullous, Kawasaki’s disesase)

Approach to clinical scenarios

Conditions discussed are emergencies because they can lead to “acute skin failure” – i.e. Loss of thermoregulatory/metabolic/infection control mechanisms of skin

OverviewRecognition and clinical featuresAetiologyComplicationsManagement

Widespread pustulesGeneralised pustular psoriasisAcute generalised exanthematous pustulosisFolliculitis-bacterial/viral/eosinophilic/

pityrosporumDisseminated HSV (rarely)Neutrophilic dermatoses-Behcet’s/Sweet’s/PGIgA pemphigus(Exanthematous DE – often have a few

pustules of follicular origin)

Acute generalised pustular psoriasis

GPPAcute/subacte/chronic-superimposed on plaque type disease

or de novo after developing atypical, acral or flexural disease in later life

Acute form is an “emergency”= von Zumbusch variant

Clinical features: Warning signs – burning, tenderness,driness

Abrupt onset high fever and severe malaise

Pre-existing plaques become fiery and superimposed pustules

Sheets of erythema and waves of pustulation spread to involved previously normal skin, esp. Flexures and genitals

Remission days-weeks +/- erythroderma+/-relapse

Triggers for acute GPPIrritating topical therapy – tar/dithranolInfectionPregnancyHypocalcaemiaInfectionDrugs – salicylates, iodide, lithium,

terbinafineWithdrawal of systemic

corticosteroids/potent TCS/cyclosporin

Complications of Erythroderma“THE I NET +metabolic”Thermoregulation/ThrombosisHaemodynamic- renal

perfusion/CHF/pneumonia/oedemaEctropion Infection - cutaneous and respiratoryNutrition ( albumin)/nails/nodesEnteropathy - Fe/B12/folate/protein/fatTelogen effluviumMetabolic – electrolyte imbalance

Complications of acute GPP“THE I NET M”Low – albumin, calciumCholestatic jaundiceDVTSecondary Staph. aureus infectionInflammatory polyarthritisAmyloidosis (rare)Obstetric complicationsAcute telogen effluvium

Management acute GPPTreatment:Withdraw/treat provocative factorsAdmit to hospitalStrict bed restThromboprophylaxis +thermoregulation

(hypothermia)Fluid and nutritional support/electrolyte sAnalgesia and antihistamines

Management acute GPPTopical therapy: Bland emollients/wet

dressings/mild-moderate potency topical steroids.Tar and dithranol are contraindicated

Systemic therapy: Most require (difficult in pregnancy)

Acitretin = treatment of choiceMTX/CyA/TNF-α blockersOral steroids only when urgent control of

metabolic complications necessary/consider in pregnant patients

Acute generalised exanthematous pustulosis (AGEP)Acute febrile pustular eruption> 90% drug induced (other causes – HS to mercury,

enteroviral infection)Short time between drug and eruption <2- 4/7Drugs causing AGEP: “BAD FACE”-mostly penicillins and

macrolidesBactrimAntibiotics and

antifungals(Vanc/Penicillins/Cephalosporins/Macrolides/terbinafine/itraconazole)

DiltiazemFrusemideAllopurinol/antimalarialsCimetidineEpileptics

Small non-follicular pustules

AGEP – Clinical FeaturesHigh fever (usu. Onset same day as rash)Numerous small, primarily non-follicular,

sterile pustules arising within large areas of oedematous erythema +/- burning, pruritus

Lesions start face and flexures, then disseminate over a few hours

Other features: facial & acral oedema, erythema multiforme-llike lesions, vesicles, bullae, purpura, mucosal in 50%

Face, flexures, trunk, upper limbsFace, flexures, trunk, upper limbs

Lesions last 1-2 weeks; resolve with superficial desquamation

AGEP - TreatmentStop the offending drugSupportive measures – rest/bland

emollients/topical corticosteroids/occasionally prednisolone

• Fever• LAD• Elevated LFTs, eosin,

atypical lymphocytes

WellMild eosinophilia

DRESS (Drug reaction with eosinophilia and systemic symptoms), aka drug hypersensitivity syndrome

– Triad: fever, rash, internal organ involvement (hepatitis, lymphadenopathy, nephritis, pneumonitis, haematological, myocarditis, thyroiditis – atypical L, N, eos)

– Onset 1-8 wks– Prodrome: feverfever,, malaise, pharyngitis– Rash: morbilliform (usually), exfoliative,

erythrodermic, pustular, SJS, TEN– Onset rash usually face/upper trunk +extrem.– Features suggesting: facial oedema, eosinophilia

(90%), atypical lymphocytes (40%), deranged LFTs, lymphadenopathy

– Mortality 8%– Drug causes: “MATES”

Minocycline/allopurinol/ARV/terbinafine/epileptics/sulfas incl. dapsone

DDx of DRESSOther cutaneous drug reactionsViral infectionsIdiopathic hypereosinophilic syndromeLymphoma/pseudolymphoma

Investigations - DRESSFBC – eosinophilia and atypical

lymphocytosisUEC )Elevated hepatic enzymes ) close

monitoringCXR – pulmonary infiltratesBiopsy for H+E – Dense superficial dermal

lymphocytic infiltrate +eosinophils/dermal oedema+/-pseudolymphomatous (if chronic)

Treatment- DRESSStop the drug!Consult as per investigations for organ

involvementCorticosteroids first-line (good for skin,

heart and lungs, but less useful to treat renal and liver disease)

PNL may be need to be tapered over many months to avoid relapse

Emollients/antihistamines/TCS/wet dressings

ERYTHRODERMA

ErythrodermaPresence of erythema and scaling involving more

than 90% of skin surface (can be caused by any inflammatory skin condition)

Primary: erythema (often initially on trunk) extends within few days to weeks to involve whole skin surface. Followed by scaling

Secondary: generalisation of a preceding localized skin disease (e.g. psoriasis, atopic eczema)

Acute vs chronic

Causes of ErythrodermaDrug causes: DESIGN CHAMP

“Top 5” – “PEDLI”Psoriasis EczemaDrug eruptionsLymphomaIdiopathic

Diuretics (frusemide +thiazides)

EpilepticsSulfas Isoniazid (TB-RIPE)GoldNSAIDSCaptopril/ACEIHomeopathy/HerbsAllopurinol/antibioticsMalarialsPsychotics (anti) - lithium

Causes of Erythroderma-”PENCIILS GID”Psoriasis and variants - PRP/Seb. Derm/Reiter’sEczema-atopic/irritant/allergic/CADNeoplasia-lymphoma/CTCL/SS/leukaemia/solid organ CTD – LE/DM/Sjogren’sInfection – scabies/HIV/d’phyte(T.violaceum), SSSS,

TSSImmunobullous /acantholytic– PF/BP/Hailey-Hailey,

Darier’sLichen planus SarcoidosisGraft vs host disease

“PENCIILS GID”Ichthyosiform erythrodermas – lamellar

ichthyosis/Netherton’s syndrome/CIE/BIEDrugs- should improve within 2-6/52 off drug

unless DRESS

Erythroderma – clinical featuresRapidly extending erythema (may be

universal in 12-48 hrs – esp. rapid in primary eczema and lymphoma)

Fever, shivering, malaise- hypo>hyperthermia (low –reading thermometer)

Scale (fine/branny/large) –after 2-6 daysPruritus (90%) + tightness of skinLichenification

Erythroderma – clinical featuresLymphadenopathy-extent variable.

Dermatopathic (sl-mod. enlarged and rubbery) vs 2⁰ lymphoma

Weeks: Hair-diffuse, non-scarring alopecia (20% chronic)

Nails (40%)– “shiny” , discoloured, subungal hyperkeratosis, Beau’s lines, splinter hge’s

Multiple seborrhoiec keratoses

Oedema – lower legs/ankles

Clues – underlying skin disease

Complications of Erythroderma“THE I NET +metabolic”Thermoregulation/ThrombosisHaemodynamic- renal

perfusion/CHF/pneumonia/oedemaEctropion Infection - cutaneous and respiratoryNutrition ( albumin)/nails/nodesEnteropathy - Fe/B12/folate/protein/fatTelogen effluviumMetabolic – electrolyte imbalance

Erythroderma- InvestigationsDiagnosis: Biopsy – H+E/DIF (+/-)/TCR-GR Skin scrapings• Extent/Cx: Blood cultures if febrile• FBC – eosinophilia/lymphocytosis• UEC/Ca/Mg/PO4/LFTs/protein/albumin• MSU• Fe/B12/folate• Skin swabs• CXR-CHF/Ca/pneumonia• ECG – if elderly

Erythroderma- InvestigationsFor associated conditions:IgE and E⁰’s/patch/photo-patchFBC+film/TCR-GR/L⁰ subsets/LDH/Sezary cell

countLymph node/BMBxCXR/CT chest/abdo/pelvisImmunohistochemistry on skin biopsy CD3/4/5/7

+/- CD 30+SPE ESRCa-serum/urine ANA/ENA/C’/dsDNA/RhFPre-treatment investigations – QF-gold/Hep etc.

Erythroderma - TreatmentAdmit to hospital (if acute/unwell)

Management of fluid balance and temperature

Review medications (cease non-essential)

Topical (care re impaired barrier)Emollients, +/- mild/mod topical steroidsWet dressings

Erythroderma - TreatmentTreat infectionAntihistaminesSystemic steroids in some (not if ?psoriasis)ThromboprophylaxisReferrals – Nutrition/Cardiology

Treat the underlying disease!

Erythema multiforme-how do you tell that this isn’t a true emergency? (no risk of progression to TEN)Self-limited, but potentially recurrent diseaseAbrupt onset symmetrical, fixed red papules, some of

which evolve into typical/atypical papular target lesions

Typical targets- at least 3 different zonesAtypical – only 2 different zones and poorly-defined

border

Target lesions favour acrofacial sites; extremities and face

Painful/pruriticTargets may blister+/- mucous membranes

Dusky centres

Classic targets / iris – triphasic1) Central purple/ dusky area2) White oedematous concentric rim3) Red halo

EM minor vs majorEM minor EM majorTypical +/- atypical

papular targets Little or no mucosal

involvementNo systemic symptoms

In all EM, majority lesions will develop within 24 hr (all by 72 hr)

Duration episode approx. 2/52

Typical > atypical targets

Severe mucosal and systemic features

EM SJS TEN

Rash Typical targets

Acrofacial + limbs

Atypical targets, blisters widespread

SJS <10%; TEN > 30%

Mortality 5% SJS/30% TEN

Mucous membrane

Absent/

Mild (unless major)

Severe

Drug HSV >> drug Anticonvulsants, sulfonamides, allopurinol, NSAID, b-lactams

EM/SJS/TEN

Erythema Multiforme - aetiology

Infection:HSV(most common ), mycoplasmaMalignancyDrugs - sulphonamides, phenytoin,

barbiturates,penicillin, allopurinolImmunological – LE, RhA, DM, Behcet’sIdiopathic - 50%

Urticaria – ITCHY!Central zone is normal

skinLesions are transient,

lasting several hoursNew lesions appear dailyAssociated with oedema

hand and feet (angioedema)

Erythema multiformeCentral zone of

epidermal damage (dusky, bullous, crusted)

Lesions 'fixed' for at least 7 days

All lesions appear within first 72 hours

No oedema

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

SJS/TEN• Rare , acute life-threatening mucocutaneous

diseases• Overlapping features-both T-cell-mediated • Extensive keratinocyte cell death – separation

of skin at DEJ• Keratinocyte death via apoptosis – mediated

by interaction of the death receptor-ligand pair Fas-FasL

• Same precipitants-almost always DRUGS!!!• The more widespread, the more likely drug

cause (SJS 50% drug; TEN 90%)

PathogenesisGenetic susceptibility Failure to detoxify

reactive intermediate drug metabolites

Immune response to antigenic complex

Interaction between Fas (CD95) and its ligand on epidermal cells triggers apoptosis pathways and cell death

HLA-B12 ↑/HLA-B*5701, HLA-DR7

+HLA-DQ3 = 100% predictive TEN with abacavir

SJS and TEN• Spectrum of severity

– SJS < 10% epidermal detachment• ≥ 2 mucosal sites

– SJS / TEN overlap 10-30%– Toxic epidermal necrolysis >30%

• Large areas denuded skin• TEN: compared to SJS: extensive confluence, large areas of denuded

skin; poorly delineated red plaques;

• At risk:– Slow acetylators– HIV (1000x)– Lymphoma– SLE

SJSPrecipitants

Drugs 50% ≥ 14/7 (NSAIDS>sulfonamides, anticonvulsants, penicillins and tetracyclines)

Infections 50% Mycoplasma, Yersinia, TB, Syphilis, Chlamydia, Strep, Typhoid,

Pneumococcus; Coccidiodomycosis, Histoplasmosis; Enterov, Adenov, Measles, Mumps, Influenza

IBDVaccine

TENThe more widespread, the more likely drug cause (SJS

50% drug; TEN 90%). Other causes=infections and immunisations

Drugs causing TEN: “LOV THE SAND”Lamisil +other antifungalsOmeprazoleVancomycinTB drugsHIV drugs (esp. Nevirapine +abacavir)/herbsEpileptics (phenytoin/CBZ/lamotrigine)Sulphas (Bactrim,sulphasalazine), statinsAllopurinol (very common)/antibiotics (penicillins, Bactrim)NSAIDSDapsone

SJS /TEN clinical features• 1-3 weeks after exposure to drug• Prodrome (1-3 days)– malaise, fever, pharyngitis,

eye discomfort• Skin lesions: Usually first on trunk, then neck,

face and proximal upper extremities• Palms +soles may be involved early• Erythema and erosions of oral, ocular, genital

mucosae in >90%• Respiratory tract epithelium involved in 25%• GIT mucosal erosions• Skin and mucosal erosions tender and very

painful• Systemic manifestations: fever, LN, hepatitis,

cytopenias (neutropenia, lymphopenia,thromobcytopenia= poor prognosis)

SJS Haemorrhagic crusting

Denuded lip

Bullae

Bactrim

48M

amphetamines

Lesions initially erythematous, dusky or purpuric macules-tendency to coalesce+/- atypical targets

Positive Nikolsky sign

As necrosis becomes full-thickness, dusky –red macular lesions become grey (hours-days)

Necrotic epidermis then detaches, fluid fills space b/t epidermis and dermis flaccid blisters which break easily Tense blisters usu. only on palmoplantar surfaces

Raw and often bleeding dermis revealed.

Cephalexin

RIP 24 hours

ClinicalMucous membranes

90% mucosal lesionsErosions/erythema

GeneralPhotophobiaPainful micturitionFeverSevere painAcute renal failureErosions lower respiratory tract/gut-BOOP

SJS / TEN complications• Hypovolaemia, metabolic abnormalities,

secondary bacterial infection• Death

– infections (S. aureus, Pseudomonas aeruginosa)– ARDS – multiorgan failure/thromboembolism/GI hge

• Scarring – skin, joint contractures, cornea, conjunctiva, lacrimal ducts, oesophageal strictures, anal strictures, vaginal, urethral meatal stenosis (eye complications 40%)

• Mortality 1-5% SJS/25-35% TEN (+ more in elderly)

SJS / TEN complicationsSkin

Irregular pigmentationEruptive naeviNail dystrophySicca symptoms

SCORTEN severity-of-illness score

Sum Mortality %

Age >40 0-1 3.2

Malignancy 2 12.1

HR > 120/min 3 35.8

Initial >10% epidermal detachment

4 58.3

Urea > 10 mmol/L ≥5 90

Glucose > 14 mmol/L

Bicarbonate < 20 mmol/L

Important DDx’s for SJS/TEN• Paraneoplastic pemphigus/pemphigus vulgaris/ bullous

pemphigoid(including drug-induced) – DIF/IDIF

• Linear IgA disease (+drug-induced)-DIF/histology

• Bullous lupus erythematosus - ANA/DIF

• Stage IV acute GVHD-evolution

• Kawasaki’s disease (children)

• Staphylococcal scalded skin ∑ (frozen section/H+E)

• Acute generalised exanthematous pustulosis-self-limiting when cease drug

• SEE FEB. 2007 JAAD CME PAPER

Investigations in SJS/TENAs for erythrodermaCXR/UEC/LFT’s/Coags for systemic invltFBC – prognosis and evidence infectionSCORETEN – Day 1 and Day 3Biopsy – H+E/DIF +/- frozen sectionIndirect immunofluorescence – exclude PNP/PVANA/ENA/dsDNA (before give IVIg)Regular cultures – skin/blood/mucous membranesViral swabsIgA levels (before IVIg)

Early lesion: apoptotic keratinocytes Early lesion: separation of epidermis from dermis; full thickness necrosis +bulla formation; variable density dermal mononuclear infiltrate (mostly T Lₒ)

Management SJS/TENStop causative drug and all non-life-

sustaining drugsAdmit to hospital

Rapid initiation- a) Supportive b)Specific management – controversial and

evidence is still evolving

Management SJS/TEN-SupportiveAdmit Burns Unit/ICUCorrect/monitor fluid and electrolyte balanceNutrition – refer – replace calories/protein/etc Surveillance for infection- regular swabs mouth,

eyes, skin, sputum (treat based on culture results and when signs of sepsis – NOT PROPHYLACTICALLY)

Analgesia – Pain team reviewEye care – Consult Ophthalmology-lubricant

drops/steroid drops/chlorsigUrology/Gynae – IDC/manual exam or dermeze

tamponsMouth care – PMMW/xylocaine viscus 2%/Diprosone

OV ung/Daktarin oral gel/white soft paraffin lips

Management SJS/TEN-SupportivePhysio. to prevent contractures and

respiratorySkin care – gentle handling/no tapes on skin/air

mattress/non-adherent dressings (Bactigras and Acticoat)/biologic skin equivalents reported

Care to avoid pressure areas

Thromboprophylaxis

Medic Alert Bracelet/ADR notification/counsel relatives

Proton pump inhibitors for GIT prophylaxis

Management SJS/TEN-Specific/Adjunctive• CONTROVERSIAL! Complementary –

apoptosis is rapid + irreverisble once triggered so must be early (1st 4 days)

• Corticosteroids – deleterious effect in small studies/ possible benefit recent studies? Poor outcomes 2ₒ inadequate doses? (pulse dexa 1.5mg/kg/day for 3/7)

• CyA - ?anti-apoptotic via ↓regulation NF-κB (3-4mg/kg/day)

• Cyclophosphamide• Infliximab• Plasmapheresis +/- IVIg (remove

drug/metabolites/cytokines)

• IVIG high dose 2-4 g/kg

IVIG – autoantibodies against Fas receptor block Fas-FasL binding and thereby prevent (in vitro) apoptosis

IVIGIVIG

1g/kg for 3 days (total 3g/kg)

Miami group AAD 2011 – use 1g/kg for 4/7

Survival with every 1g/kg increment in dose (OR = 4.2)

No prospective controlled studies with sufficient numbers. Doses varied in previous studies

•HLA-B*1502 is strongly associated with carbamazepine-induced TEN/SJS – reported in several independent studies•Mostly observed in patients of South-East Asian descent

•This may also be seen in drugs with structural similarity to CBZ in patients with HLA-B*1502

•HLA-B*5801 associated with allopurinol-induced TEN/SJS

•Screening for HLA-haplotypes ideal before using these drugs in relevant patients

Eczema Herpeticum/Kaposi’s varicelliform eruptionWidespread cutaneous infection with a virus that

normally causes localised or mild vesicular eruptions – IN A PATIENT WITH PRE-EXISTING SKIN DISEASE

Majority of cases are HSV-1 in atopic eczema = eczema herpeticum

KVE = widespread infection with other viruses (coxsackie A16, VZV)

Children and young adults usually (2nd-3rd decade)In eczema herpeticum, majority are primary

infections, but can occur with endogenous recurrent infection (herpes labialis)

Risk factors Atopic dermatitis Parental /close contacts herpes labialis Other chronic skin disorders (pemphigus foliaceus, Darier’s,

Hailey-Hailey, MF, Sezary syndrome, ichthyosis vulgaris, CIE etc)

Clinical featuresIncubation period 10 daysUnderlying skin diseaseCrops of vesicles that rapidly become

pustules (new crops 5-7 days)Lesions begin in abnormal skin +/-

generalisePainful ‘punched out’ erosionsSecondary staph infectionMonomorphic 2-3mm haemorrhagic crusts =

clueFever onset 2-3 d after eruption –lasts 4-5/7+/- severe constitutional SxRegional lymphadenopathyProgression to potentially fatal systemic

infection rarely

Eczema herpeticum/KVE-clinical featuresLocalised mild infections – low-grade fever

and lymphadenopathy- usually self-limiting

Recurrences may be milder than initial episode/sometimes comparable severity

TreatmentOral (or IV antivirals)

Aciclovir/famciclovir/valaciclovir

+/- Anti-staph antibiotics

Aluminium acetate soaks

Treat underlying skin disorderRefer to Ophthalmology if periorbital

involvement

Any questions?