Dermatology emergencies grand rounds


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  • Change order – pustules, DRESS, TEN, erythroderma
  • Subtypes of pustular psoriasis – Localised (palmoplantar, acrodermatitis continua of Hallopeau) Generalised (acute, of pregnancy, infantile and juvenile, circinate, localised - not hands and feet)
  • Occ agran, low plt, coombs+ h’lytic an, apl an, autoimmune thyroiditis after 2m
  • Fine in atopic dermatitis or dermatophytosis, branny in seb derm, crusted in PF, thicker in psoriasis. Skin hot to touch
  • Waxy orange PPKD, follicular horny plugs elbows+ knees and dorsal fingers and toes, islands of sparing+PRP, crusted erosions and flaccid bullae in PF, pre-existing nail changes such as pits etc in psoriasis, horizontal ridging in AD
  • Lichenification and excoriations
  • Islands of sparing, follicular accentuation
  • Complications?
  • Due to some clinical similarity, EM/SJS/TEN all previously considered to be spectrum. New concept that EM is a distinct disease entity on several levels (clinical, prognostic, aetiologic)
  • Concentric zones of colour change. Usually greater than 100 lesions. Recurrences are usual
  • What is the most common cause of EM?
  • HSV may be facial or genital. Mycoplasma is another common cause.
  • These two entities are frequently confused
  • TEN: compared to SJS: extensive confluence, large areas of denuded skin; poorly delineated red plaques;
  • Exfoliation due to extensive death of K’s mediated by interaction of the death receptor-ligand pair, Fas-Fas ligand on the surface of K’s
  • Drugs started 14+ days prior to onset. Genetic differences in detoxification likely to be responsible.
  • Recent report TEN secondary to beta-blocker eyedrops
  • Skin is extremely painful
  • Prognosis is highly correlated with extent of skin detachment. Prognosis also correlates with SCORTEN in which these 7 parameters are given equal weight
  • Biopsy needed to differentiate all. Vancomycin can induce both TEN and LAD – mucosal involvement is rare in DI-LAD. BMT pts receive many meds known to cause TEN and mucositis following chemo-induced neutropenia is common – folliculocentric, begins acrally and spreads proximally/TEN begins centrally and spreads periph
  • Fluid loss is significant Increased energy expenditure so hight caloric intake needed
  • By day 6-10 of admission, most of the skin erosions will re-epithelialise
  • IVIg remains preferred treatment in our unit – anecdotally good experience/helps combat infection
  • Diagnosis?
  • Dermatology emergencies grand rounds

    1. 1. All information about the condition, medical historyor treatment of patients disclosed at this clinicalmeeting is absolutely confidential.The Health Information Privacy Code (1994)applies to all present whether or not they areemployees of, visitors to, or studying at theCanterbury District Health Board or theUniversity of Otago, Christchurch.REMINDER-cell phones to vibrate mode please
    2. 2. DermatologyEmergencies?!?Really??? Dermatologist Newbie? That’s Greek for “not real doctor”
    3. 3. Dr Katherine Armour Consultant DermatologistCanterbury District Health
    4. 4. 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
    5. 5. OverviewRecognition and clinical featuresAetiologyComplicationsManagement
    6. 6. Widespread pustulesGeneralised pustular psoriasisAcute generalised exanthematous pustulosisFolliculitis-bacterial/viral/eosinophilic/pityrosporumDisseminated HSV (rarely)Neutrophilic dermatoses-Behcet’s/Sweet’s/PGIgA pemphigus(Exanthematous DE – often have a few pustules of follicular origin)
    7. 7. Acutegeneralisedpustularpsoriasis
    8. 8. GPPAcute/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
    9. 9. Triggers for acute GPPIrritating topical therapy – tar/dithranolInfectionPregnancyHypocalcaemiaInfectionDrugs – salicylates, iodide, lithium, terbinafineWithdrawal of systemic corticosteroids/potent TCS/cyclosporin
    10. 10. Complications of Erythroderma“THE I NET +metabolic”Thermoregulation/ThrombosisHaemodynamic- renal perfusion/CHF/pneumonia/oedemaEctropionInfection - cutaneous and respiratoryNutrition ( albumin)/nails/nodesEnteropathy - Fe/B12/folate/protein/fatTelogen effluviumMetabolic – electrolyte imbalance
    11. 11. Complications of acute GPP“THE I NET M”Low – albumin, calciumCholestatic jaundiceDVTSecondary Staph. aureus infectionInflammatory polyarthritisAmyloidosis (rare)Obstetric complicationsAcute telogen effluvium
    12. 12. Management acute GPPTreatment:Withdraw/treat provocative factorsAdmit to hospitalStrict bed restThromboprophylaxis +thermoregulation (hypothermia)Fluid and nutritional support/electrolyte sAnalgesia and antihistamines
    13. 13. Management acute GPPTopical 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 choiceMTX/CyA/TNF-α blockersOral steroids only when urgent control of metabolic complications necessary/consider in pregnant patients
    14. 14. Acute generalised exanthematouspustulosis (AGEP) Acute febrile pustular eruption > 90% drug induced (other causes – HS to mercury, enteroviral infection) Short time between drug and eruption <2- 4/7 Drugs causing AGEP: “BAD FACE”-mostly penicillins and macrolides Bactrim Antibiotics and antifungals(Vanc/Penicillins/Cephalosporins/Macrolides/terbinafine/i traconazole) Diltiazem Frusemide Allopurinol/antimalarials Cimetidine Epileptics
    15. 15. Small non-follicularpustules
    16. 16. AGEP – Clinical FeaturesHigh 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
    17. 17. Other features: facial & acral oedema, erythema multiforme-llike lesions,vesicles, bullae, purpura, mucosal in 50%
    18. 18. Face, flexures, trunk, upper limbsLesions last 1-2 weeks; resolve withsuperficial desquamation
    19. 19. AGEP - TreatmentStop the offending drugSupportive measures – rest/bland emollients/topical corticosteroids/occasionally prednisolone
    20. 20. • Fever Well• LAD Mild eosinophilia• Elevated LFTs, eosin, atypical lymphocytes
    21. 21. DRESS(Drug reaction with eosinophilia and systemic symptoms), aka drughypersensitivity syndrome – Triad: fever, rash, internal organ involvement (hepatitis, lymphadenopathy, nephritis, pneumonitis, haematological, myocarditis, thyroiditis – atypical ↑L∅, ↑N, ↑eos) – Onset 1-8 wks – Prodrome: fever, 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
    22. 22. DDx of DRESSOther cutaneous drug reactionsViral infectionsIdiopathic hypereosinophilic syndromeLymphoma/pseudolymphoma
    23. 23. Investigations - DRESSFBC – eosinophilia and atypical lymphocytosisUEC )Elevated hepatic enzymes ) close monitoringCXR – pulmonary infiltratesBiopsy for H+E – Dense superficial dermal lymphocytic infiltrate +eosinophils/dermal oedema+/-pseudolymphomatous (if chronic)
    24. 24. Treatment- DRESSStop the drug!Consult as per investigations for organ involvementCorticosteroids 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
    25. 25. ERYTHRODERMA
    26. 26. ErythrodermaPresence 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
    27. 27. Causes of Erythroderma Drug causes: DESIGN CHAMP“Top 5” – “PEDLI”  Diuretics (frusemide +thiazides)  EpilepticsPsoriasis  SulfasEczema  Isoniazid (TB-RIPE)Drug eruptions  Gold  NSAIDSLymphoma  Captopril/ACEIIdiopathic  Homeopathy/Herbs  Allopurinol/antibiotics  Malarials  Psychotics (anti) - lithium
    28. 28. Causes of Erythroderma-”PENCIILSGID”Psoriasis and variants - PRP/Seb. Derm/Reiter’sEczema-atopic/irritant/allergic/CADNeoplasia-lymphoma/CTCL/SS/leukaemia/solid organCTD – LE/DM/Sjogren’sInfection – scabies/HIV/d’phyte(T.violaceum), SSSS, TSSImmunobullous /acantholytic– PF/BP/Hailey-Hailey, Darier’sLichen planus SarcoidosisGraft vs host disease
    29. 29. “PENCIILS GID”Ichthyosiform erythrodermas – lamellar ichthyosis/Netherton’s syndrome/CIE/BIEDrugs- should improve within 2-6/52 off drug unless DRESS
    30. 30. Erythroderma – clinicalfeaturesRapidly 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 daysPruritus (90%) + tightness of skinLichenification
    31. 31. Erythroderma – clinicalfeaturesLymphadenopathy-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
    32. 32. Complications of Erythroderma“THE I NET +metabolic”Thermoregulation/ThrombosisHaemodynamic- renal perfusion/CHF/pneumonia/oedemaEctropionInfection - cutaneous and respiratoryNutrition ( albumin)/nails/nodesEnteropathy - Fe/B12/folate/protein/fatTelogen effluviumMetabolic – electrolyte imbalance
    33. 33. Erythroderma- InvestigationsDiagnosis: 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
    34. 34. Erythroderma- InvestigationsFor associated conditions:IgE and E⁰’s/patch/photo-patchFBC+film/TCR-GR/L⁰ subsets/LDH/Sezary cell countLymph node/BMBxCXR/CT chest/abdo/pelvisImmunohistochemistry on skin biopsy CD3/4/5/7 +/- CD 30+SPEESRCa-serum/urineANA/ENA/C’/dsDNA/RhFPre-treatment investigations – QF-gold/Hep etc.
    35. 35. Erythroderma - TreatmentAdmit 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 steroids Wet dressings
    36. 36. Erythroderma - TreatmentTreat infectionAntihistaminesSystemic steroids in some (not if ?psoriasis)ThromboprophylaxisReferrals – Nutrition/CardiologyTreat the underlying disease!
    37. 37. Erythema multiforme-how do you tell thatthis isn’t a true emergency? (no risk of progression to TEN) Self-limited, but potentially recurrent disease Abrupt onset symmetrical, fixed red papules, some of which evolve into typical/atypical papular target lesions Typical targets- at least 3 different zones Atypical – only 2 different zones and poorly-defined borderTarget lesions favour acrofacial sites; extremities and facePainful/pruriticTargets may blister+/- mucous membranes
    38. 38. Classic targets / iris – triphasic 1) Central purple/ dusky area 2) White oedematous concentric rim 3) Red halo Dusky centres
    39. 39. EM minor vs majorEM minor EM majorTypical +/- atypical papular Typical > atypical targets targets Severe mucosal and systemicLittle or no mucosal features involvementNo systemic symptomsIn all EM, majority lesions will develop within 24 hr (all by 72 hr)Duration episode approx. 2/52
    40. 40. EM/SJS/TEN EM SJS TENRash Typical Atypical targets, blisters widespread targets SJS <10%; TEN > 30% Acrofacial + Mortality 5% SJS/30% TEN limbsMucous Absent/ Severemembrane Mild (unless major)Drug HSV >> drug Anticonvulsants, sulfonamides, allopurinol, NSAID, b-lactams
    41. 41. Erythema Multiforme - aetiology Infection:HSV(most common ), mycoplasma Malignancy Drugs - sulphonamides, phenytoin, barbiturates,penicillin, allopurinol Immunological – LE, RhA, DM, Behcet’s Idiopathic - 50%
    42. 42. Urticaria – ITCHY! Erythema multiforme  Central zone is normal skin  Central zone of epidermal  Lesions are transient, lasting damage (dusky, bullous, several hours crusted)  New lesions appear daily  Lesions fixed for at least 7  Associated with oedema hand days and feet (angioedema)  All lesions appear within first 72 hours  No oedema
    43. 43. Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
    44. 44. 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%)
    45. 45. PathogenesisGenetic susceptibility HLA-B12 ↑/HLA-B*5701, HLA-DR7Failure to detoxify reactive +HLA-DQ3 = 100% predictive TEN with abacavir intermediate drug metabolitesImmune response to antigenic complexInteraction between Fas (CD95) and its ligand on epidermal cells triggers apoptosis pathways and cell death
    46. 46. 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
    47. 47. SJSPrecipitants 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 IBD Vaccine
    48. 48. TENThe 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
    49. 49. 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)
    50. 50. SJS Haemorrhagic crusting Denuded lip Bullae Bactrim
    51. 51. Lesions initiallyerythematous, dusky orpurpuric macules-tendency to coalesce+/- atypical targets48M Positive Nikolsky signamphetamines
    52. 52. As necrosis becomes full-thickness, dusky –redmacular lesions become grey (hours-days)
    53. 53. Necrotic epidermis then detaches, fluid fills spaceb/t epidermis and dermis flaccid blisterswhich break easily Tense blisters usu. only onpalmoplantar surfaces
    54. 54. Raw and often bleeding dermisrevealed.
    55. 55. CephalexinRIP 24 hours
    56. 56. ClinicalMucous membranes 90% mucosal lesions Erosions/erythemaGeneral Photophobia Painful micturition Fever Severe pain Acute renal failure Erosions lower respiratory tract/gut-BOOP
    57. 57. 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)
    58. 58. SJS / TEN complications Skin Irregular pigmentation Eruptive naevi Nail dystrophy Sicca symptoms
    59. 59. SCORTEN severity-of-illness score Sum Mortality %Age >40 0-1 3.2Malignancy 2 12.1HR > 120/min 3 35.8Initial >10% epidermal 4 58.3detachmentUrea > 10 mmol/L ≥5 90Glucose > 14 mmol/LBicarbonate < 20 mmol/L
    60. 60. 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
    61. 61. Investigations in SJS/TENAs for erythrodermaCXR/UEC/LFT’s/Coags for systemic invltFBC – prognosis and evidence infectionSCORETEN – Day 1 and Day 3Biopsy – H+E/DIF +/- frozen sectionIndirect immunofluorescence – exclude PNP/PVANA/ENA/dsDNA (before give IVIg)Regular cultures – skin/blood/mucous membranesViral swabsIgA levels (before IVIg)
    62. 62. Early lesion: apoptotic keratinocytes Early lesion: separation of epidermis from dermis; full thickness necrosis +bulla formation; variable density dermal mononuclear infiltrate (mostly T Lₒ)
    63. 63. Management SJS/TENStop causative drug and all non-life-sustaining drugsAdmit to hospitalRapid initiation-a) Supportiveb)Specific management – controversial and evidence is still evolving
    64. 64. Management SJS/TEN-SupportiveAdmit Burns Unit/ICUCorrect/monitor fluid and electrolyte balanceNutrition – 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 reviewEye care – Consult Ophthalmology-lubricant drops/steroid drops/chlorsigUrology/Gynae – IDC/manual exam or dermeze tamponsMouth care – PMMW/xylocaine viscus 2%/Diprosone OV ung/Daktarin oral gel/white soft paraffin lips
    65. 65. Management SJS/TEN-SupportivePhysio. to prevent contractures and respiratorySkin 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
    66. 66. 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
    67. 67. IVIGIVIG – autoantibodiesagainst Fas receptor blockFas-FasL binding andthereby prevent (in vitro)apoptosis 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
    68. 68. •HLA-B*1502 is strongly associated with carbamazepine-inducedTEN/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 toCBZ in patients with HLA-B*1502•HLA-B*5801 associated with allopurinol-induced TEN/SJS•Screening for HLA-haplotypes ideal before using these drugs inrelevant patients
    69. 69. Eczema Herpeticum/Kaposi’s varicelliformeruption Widespread 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 (2 nd-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)
    70. 70. Clinical featuresIncubation period 10 daysUnderlying skin diseaseCrops of vesicles that rapidly become pustules (new crops 5-7 days)Lesions begin in abnormal skin +/- generalisePainful ‘punched out’ erosionsSecondary staph infectionMonomorphic 2-3mm haemorrhagic crusts = clueFever onset 2-3 d after eruption –lasts 4-5/7+/- severe constitutional SxRegional lymphadenopathyProgression to potentially fatal systemic infection rarely
    71. 71. Eczema herpeticum/KVE-clinicalfeaturesLocalised mild infections – low-grade fever and lymphadenopathy- usually self-limitingRecurrences may be milder than initial episode/sometimes comparable severity
    72. 72. TreatmentOral (or IV antivirals) Aciclovir/famciclovir/valaciclovir+/- Anti-staph antibioticsAluminium acetate soaksTreat underlying skin disorderRefer to Ophthalmology if periorbital involvement
    73. 73. Any questions?