dermatology emergencies grand rounds
TRANSCRIPT
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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?