EM and SCARs Dan

Question 1

what are triggers for eyrthema multiforme

Answer 1

No cause found in 50%
HSV most common, mycoplasma second
Other infections; many inc VZV, CMV and HIV, bacterial infections and histoplasmosis
Drusg; esp sulfa drugs and antiepileptics
topical drugs and chemicals
vaccinations
XRT
diseases inc malignancies eg. LE, PMLE, sarcoid, PAN, Carcinoma, lymphoma, leaukaemia

Question 2

T/F

50% of cases of EM are EM minor

Answer 2

F
80% minor
20% major

Question 3

what is difference between EM major and minor?

Answer 3

Minor;
No prodrome
skin limited only or mild mucosal involvement esp oral/genital
Major;
May be short prodrome of fever, rigors, malaise, arthralgia for 1-14 days
One or more mucosal sites significantly affected
Skin lesions widespread
Rarely can affect only mucosae

Question 4

what is the onset and resoluton time for EM?

Answer 4

Eruption develops over 2-3 days resolves in 2-3 weeks

Question 5

T/F

EM is photoaggravated

Answer 5

T

Question 6

T/F

vesiculobullous EM is a type of EM Major

Answer 6

F
although som elsions may be bullous in EM major, vesiculobullous EM is an intermediate type
Red plaques with central bulla and marginal ring of vesicles; ‘herpes iris of Bateman’ . Usually in acral sites but only few lesions Looks like linear IgA disease
Mucous membranes often involved.

Question 7

What is histo of EM?

Answer 7

Lichenoid reaction pattern
w/ true Interface dermatitis
Upper dermal perivascular lymphocytic infiltrate and dermal oedema
apoptotic keratinocytes can be high in epi
Sometimes spongiosis
May be epidermal necrosis but no large sheets
May be parakeratosis

Question 8

What is management of EM?

Answer 8

Sun avoidance (sun can trigger HSV attacks) if recurrent try daily high SPF lip balm.
Symptomatic Rx only if mild.
Treat underlying condition if symptomatic – mycoplasma etc (does not improve the EM) or stop the causative drug.
Early ophth r/w if eyes involved
Oral lesions – topical steroid and anaesthetic agents, may need pain relief.
If severe consider steroids – pred at 0.5mg/kg reducing over 1-4 wks (debate about benefit).
If due to HSV, antivirals usually not useful even if started early but benefit if recurrent EM due to HSV
Recurrent cases – Azathioprine, thalidomide (also cyclosporine, dapsone, MMF but less evidence)

Question 9

T/F

prophylactic antivirals can help recurent EM even if no viral cause found

Answer 9

T

Question 10

what is erythroderma?

Answer 10

Red inflammation of 90% or more of BSA

exfoliative dermatitis means the smae thing but there is not always alot of exfoliation

Question 11

causes of erythroderma?

Answer 11

Idiopathic (about 10%)
Eczema (40%) – includes endogenous + other subtypes;
- contact dermatitis – irritant or allergic
- stasis dermatitis generalization
- seb derm generalization
Psoriasis (25%)
PRP
Sezary syndrome/erythrodermic MF (15%)
blistering diseases esp pemphigus folleaceus
Rare derm causes – HOSTING Lovely Ladies Double Ds;
Hailey-Hailey
Ofuji
sarcoidosis
Toxic shock syndrome
Icthyoses
Norwegian scabies
GvHD
Lupus
Lichen planus
Dermatophyte
Dermatomyositis
non derm causes
Drugs (10%);
Includes erythodermic DRESS or AGEP or exanthematous drug eruption
Esp; mercury, arsenic gold and CASA;
Carbamazepine/phenytoin
Allopurinol
Sulphasalazine
Ampicillin/penicillin
Hypereosinophilic syndrome
Systemic Lymphomas or leukaemias
HIV seroconversion

Question 12

what are causes of erythroderma in a neonate?

Answer 12

Infection – SSSS, TSS, candidiasis, HSV, syphilis
Immunodeficiency – Omenn’s, SCID, Leiner’s
Ichthyoses – NBIE, BIE, Conradi HH, Netherton’s
Metabolic – Gaucher’s, biotin defcy
Drugs – ceftriaxone, vanc
Other – infantile seb derm, atopic derm, psoriasis, PRP, generalised mastocytosis

Question 13

what are complications of erythroderma?

Answer 13

Hypothermia
High output cardiac failure
Fluid loss
Hypoalbuminaemia - Reduced synthesis + protein loss due to chronic exfoliation
Altered immune response

Question 14

T/F

TCS should be avoided in erythoderma

Answer 14

F
mild TCS are fine unless cause is supected to be psoriasis then should avoid
Avoid irritants like tar, sal acid or UV

Question 15

what is Papuloerythroderma of Ofuji?

Answer 15

Very pruritic rare type of papular erythroderma
over 50s esp men
brown-red, flat-topped papules on trunk and limbs
Spares face and flexures – deck chair sign
Can be koebnerising
Lesions become confluent
May be hyperkeratosis and fissuring of palms and soles, may be lymphadenopathy
Raosed eos and IgE - Remember eOfujE
Rx w/ emollients, antihistamines and topical or oral steroids
Reports of PUVA, AZA, CsA, etretinate
Persists for many years
o May remit spontaneously

Question 16

T/F

AGEP onset is usually about 24 hrs after exposure to drug

Answer 16

T

few hrs – 48hrs

Question 17

what is natural clinical Hx of AGEP?

Answer 17

Starts on face or in groin or axilla – confluent erythema with many small (38
20% get systemic features
After stoppingd rug skin starts to settle within a few days
Skin eruption lasts 1-2 wks and heals with superficial desquamation
illness settles in 15 days classically

Question 18

Drug causes of AGEP?

Answer 18

Do My Pits Pus Today?
Diltiazem
Macrolides
Penicillins/beta lactams
Plaquenil
Terbinafine and azole antifungals

Question 19

What are major DDs for AGEP?

Answer 19

Infection - v important to r/o as pt has fever and neutrophilia
Acute pustular psoriasis (von Zumbusch type)
Exanthematous drug eruption - if pustules present usually will be follicular
SJS/TEN
Sweets
DRESS
Subcorneal IgA dermatosis/Sneddon Wilkinson

Question 20

What does histo of AGEP look like?

Answer 20

Spongiosis 
Pustules in epi - most classically non-spongiform and subcorneal or intraepidermal
papillary oedema
perivasc infiltrate of neuts + some eos 
neutrophil exocytosis +/- eos exocytosis

Question 21

What investigations should be performed in suspected AGEP?

Answer 21

Biopsy skin for H+E
swab pustules - should be sterile
FBC - neutrophilia typical, eosinophilia in 30%
ELFT - liver or renal impairment
CRP - may be inc esp if systemic organ involvement
Calcium - may be low
Blood cultures - do full septic screen as infection major DD
urine for MC+S and protein
CXR - effusions, septic screen

Question 22

How is diagnosis of AGEP made?

Answer 22

Can use EuroSCAR group criteria - based on clinicla findings and histo;
Need 8 points;
typical appearing rash in typical distribution = 6
fever 38 or greater = 1
neutrophil count 7 x 10to the9/L or greater = 1
post pustular desquamation = 1
Typical histo = 3
can lose points if factors against the diagnosis or gain less points if non-typical findings

Question 23

T/F

AGEP histo looks unusual if pt has psoriasis so hard to distinguish from pustular pso

Answer 23

F

AGEP histo usually the same regardless of whether pt has Hx of psoriasis

Question 24

T/F

Pso pts with a pustular eruption are much more likely to have pustular pso than AGEP

Answer 24

F

people with Pso at higher risk of AGEP than others so don’t assume pustular psoriaisis just because pt has Pso

Question 25

What is management of AGEP?

Answer 25

Stop drug – skin settles within a few days, illness settles in 15 days classically Supportive cares Condys baths Dressings if required Antibiotics only if superadded infection Emollients to preserve skin barrier Topical steroids for itch/inflammation – potent TCS can reduce time in hospital No evidence for systemic steroids Analgesia if required Mortality

Question 26

what 3 factors are important in the aetiology of DRESS?

Answer 26

Impaired metabolism of drug reactivation of HHV6 and sometimes HHV7 specific HLA associations to rcns to certain drugs

Question 27

T/F | Phenytoin is the most common cause of DRESS

Answer 27

F carbamazepine is most common phenytoin classical - DRESS used to be called phenytoin hypersensitivity syndrome

Question 28

T/F | DRESS typically starts in first 15-50 days on a drug

Answer 28

F | 14-40 days

Question 29

T/F | fever over 38 degrees is typical of both AGEP and DRESS

Answer 29

T

Question 30

T/F | 25% of cases of DRESS have no rash

Answer 30

T | best called Drug induced Hypersensitivity syndrome (DiHS)

Question 31

What are features of DRESS other than typical rash?

Answer 31

``` Dress FOR SALE Fever Oedema Red sore throat, dry mouth, stomatitis Systemic disease Arthralgia Lymphadenopathy Erythroderma - if drug not stopped ```

Question 32

What is the characteristic rash of DRESS like?

Answer 32

Starts on face, upper trunk and arms Starts as morbilliform eruption then becomes oedematous w/ follicular accentuation Can be vesicles, bullae, Follicular or non-follicular pustules, purpura or erythroderma Oedema of face is a common feature May progress to erythroderma or superficial peeling esp if drug not stopped

Question 33

What are the organ/systems that may be affected in DRESS? | what is the time frame?

Answer 33

Liver most common (70%) Interstitial nephritis (10%) Myocarditis Interstitial pneumonitis Thyroiditis Encephalitis – limbic types, can be SIADH Gastroenteritis/colitis Rarely – Heamophagocytic syndrome, pancreatitis, parotid gland enlargement Can occur early but onset can be weeks into disease so caution needed New visceral involvement can occur late in the course even after a steroid taper

Question 34

What is the major cause of death in DRESS?

Answer 34

fulminant hepatitis is biggest cause of death

Question 35

T/F | colitis causing GI bleeding is a feature of allopurinol induced DRESS

Answer 35

T

Question 36

What is histo in DRESS?

Answer 36

perivascular lymphocytic infiltrate in superficial dermis usually Eos but not always dermal oedema If persists/drug not stopped; can develop loose granulomas can get dense infiltrate like pseudolymphoma

Question 37

T/F | In DRESS, PCR may detect HHV-6 or other viral DNA in skin samples

Answer 37

T

Question 38

Whta tests should be ordered for suspected DRESS?

Answer 38

Skin biopsy FBC - eosinophilia, inc lymphcytes, anaemia, low plts ELFT - liver, kidney derangement TFTs - thyroiditis lipase - high if pancreatitis CK - myocarditis or myositis LDH - may be raised Ferritin - may be raised esp very high in haemophagocytic syndrome triglycerides - may be raised esp if severe liver inflammation or in haemophagocytic syndrome calcium, PTH - can be very low calcium coags - can get derangement, DIC esp if haemophagocytic syndrome EPP - Hypogammaglobulinaemia CRP - often high PCR serum for HHV6 + 7, EBV, CMV - reactivation blood culture - septic screen as unwell w/ temp fasting BSL - pre steroids Urinalysis 24hr – protein and urinary eosinophils FOBTs x 3 - colitis ECG, Echo, CXR, RFTs, liver USS, echocardiogram, Troponin etc as indicated to investigate visceral involvement paired serum and urine osmolarity - exclude SIADH from CNS inflammation Consider CT head, LP if CNS signs To rule out other causes; Hep A, Hep B, Hep C, ANA, Blood cultures, Chlamydia + Mycoplasma serology

Question 39

What tests should be monitored regularly during DRESS?

Answer 39

``` FBC, ELFT LDH, ferritin, triglycerides, calcium Coags HHV6 + 7, EBV, CMV urine protein others as indicated by disease ```

Question 40

What tests can be used to confirm drug trigger of DRESS?

Answer 40

Patch test Lymphocyte transformation test – negative up to 3 wks after onset but may turn positive at 5-7 wks NB Patch testing often +ve if carbamazpine cause but not if allopurinol – others variable

Question 41

what are diagnostic criteria for DRESS?

Answer 41

STAMPER - 7 diagnostic, 6 possible; Symptoms persist >2 wks after stopping drug Temp >38 degrees ALT >100; hepatitis or other visceral inflammation Maculopapular rash >3wks after starting drug Palpable LNs Eosinophilia or high WCC or raised atypical lymphocytes >5% Re activation of HHV6 ``` Or RegiSCAR – need at least 3 of; Hospitalisation Reaction suspected to be drug related Acute skin rash Fever above 38 C Enlarged lymph nodes at two sites Involvement of at least one internal organ Blood count abnormalities such as low platelets, raised eosinophils or abnormal lymphocyte count ```

Question 42

What is the management of DRESS?

Answer 42

stop drug – slow recovery not rapid like AGEP If mild – close monitoring + TCS, emollients and antihistamines may be sufficient If severe - Prednisolone 1mg/kg/day - wean over 6-8 weeks If signs of life threatening organ failure – transfer to ICU, IVIg 2g/Kg over 5 days Plasma exchange or Rituximab or combination of these are alternatives If viral reactivation in mod-severe disease give antiviral (valganciclovir) in addition to prednisone Consult other specialists as required

Question 43

What is prognosis and sequele of DRESS?

Answer 43

10% mortality mainly due to fulminant hepatitis but also from myocarditis, colitis or hepatic necrosis Can get autoimmune diseases with onset up to 4 years after resolution of DRESS – possibly due to depletion of Treg cells; Type 1 diabetes Autoimmune thyroid disease Sclerodermoid GvHD SLE BP

Question 44

whta re the causes of SJS/TEN?

Answer 44

Mostly drugs; SATAN; Sulpha drugs – co-trimoxazole, sulphonamides Allopurinol – esp if dose >200mg/day or if renal impairment Tetracyclines Anticonvulsants - barbiturates, phenytoin, lamotrigine, carbamazepine NSAIDs (esp COX2 & oxicams), Nevirapine Also; Vaccinations – DTP, measles, polio, smallpox, ‘flu. Also – radiological contrast media, vaginal pessary, eye drops

Question 45

What is the timing of onset of SJS/TEN?

Answer 45

Onset 2-3 wks after starting drug but up to 6 weeks Very unlikely if drug first given in last 24 hrs or if more than 3 weeks ago Except antiepileptics which may still be cause up to 8 weeks after starting

Question 46

What is the prodrome of SJS/TEN?

Answer 46

URTI + eye symptoms; sore throat or rhinitis, fever, malaise and conjunctivitis for 1-3 days or sometimes weeks

Question 47

What are the clinical features of SJS?

Answer 47

EM-like or bullous or pustular (rare) lesions may be localised or extensive New crops appear for 10 days – 4 weeks Less than 10% BSA blisters/ skin detachment - if 10-30% maximum BSA desquamation then some classify as SJS/TEN overlap At least 2 mucous membranes significantly involved - oral mucosa almost always, then eyes then genitals severe conjunctivitis, corneal ulceration common Less common features; Lung inflammation bladder/urethra inflammation - can be AROU diarrhoea polyarthritis paronychia, nail shedding otitis media

Question 48

What are the clinical features of TEN?

Answer 48

initial rash may be ‘burning’ maculopapular, urticarial or EM-like eruption with purpuric macules or atypical targets. May start on face and upper chest then extend rapidly or may be more confluent erythema. Often worsens in groin and axilae first Blistering and skin peeling starts in crops then becomes sheet-like desquamation High fever persists during acute phase. This lasts 8-12 days with waves of sloughing of skin every 3-5 days and total BSA over 30% Pressure areas often badly affected wheres necrotic epidermis may remain intact on palms and soles Mucosal erosion may include eyes, oropharynx, oesophagus, nasal, bronchial, pharyngeal, perianal urethra and vagina surfaces; intestinal involvement is rare Often urethritis - 2/3 of cases - and can be AROU In 10% of cases the whole body is affected within 24 hours spares hairy scalp

Question 49

T/F | in up to 1/3 of TEN, membrane involvement precedes skin by up to 3 days

Answer 49

T

Question 50

what are the laboratory findings in TEN?

Answer 50

``` 50% get rise in transaminases 10% overt hepatitis Amylase often raised in first few days ?due to salivary gland involvement Anaemia and lymphopenia 30% get neutropenia 15% get low platelets Eosinophilia is very rare Urea and creatinine are raised glucose high hosphate is low Subclinical interstitial oedema on CXR ```

Question 51

what are the acute complications of SJS/TEN?

Answer 51

``` Massive fluid and electrolyte losses with hypovolaemia and organ failure - shock Pneumonia or pneumonitis in 30% Hepatitis pancytopenia, DIC, ARDS AKI (pre-renal), GIT bleeding sepsis (staph aureus or pseudomonas, sometimes candida or gram negs) MOF Hypothermia VTE GI bleed Death most often from ARDS and MOF triggered by sepsis, usually staph or pseudomonas, also PE or GI bleed. ```

Question 52

What is Ankylosymblepharon?

Answer 52

fusion of eyelids to each other and globe | can follow TEN if eyes not cared for or if infection

Question 53

what are the long term complications of SJS/TEN?

Answer 53

``` Ocular complications - conjunctivitis, ectropion, entropion or corneal scarring/opacities/vascularisation/ulceration, symblepharon, sicca syndrome/ xerophthalmia due to duct obstruction or watery eyes, blindness. post-TEN ocular syndrome, Ankylosymblepharon Xerostomia oesophageal stricture phimosis, vaginal synechiae orogenital ulcers, wound infections nail dystrophy pigment changes hypohidrosis contractures scarring alopecia melanocytic naevi, milia ```

Question 54

T/F | mucosal and eye complications occur in a minority of TEN survivors

Answer 54

F | 70-80% of those with eye or mucosal involvement have long term complications of these

Question 55

What is post-TEN ocular syndrome?

Answer 55

punctuate keratitis and a corneal pannus causing photophobia, burning eyes and visual impairment.

Question 56

How is SJS/TEN managed?

Answer 56

STOP THE DRUG Must be admitted to Burns unit or ICU (Burns unit -> reduced morbidity & mortality) FBC, ELFT, bicarb, ABG if any sign of resp symptoms, skin biopsy inc DIF (negative), urine dip for protein, clotting screen, CXR, BSL + ANA/ENA/dsDNA to exclude bullous lupus Bacterial and viral swabs Consider mycoplasma urinalysis Biopsy and perilesional IMF to aid diagnosis Pt and family need full explanation and support Don’t forget acute and ongoing psychological care Nurse on air-fluidised mattress Reverse isolation and sterile handling (reverse barrier nursing) Analgesia, IV fluid, nutritional support, warming, skin care and mucous membrane cares may need catheter for AROU or fluid balance Monitor temperature with low-reading thermometer (as risk of hypothermia) frequent culture of swabs and tips Ophthalmology, ENT, gynaecology, urology and intensivists should all be involved from the outset

Question 57

How is BSA % estimated?

Answer 57

Wallace’s rule of 9s | or for kids use Lund and Browder charts

Question 58

What are specific recommendations for IV fluid and temperature in TEN?

Answer 58

Initial IVF is 2mls/kg/%BSA + daily losses as crystalloid or crystalloid + 5% human albumin to maintain urine output at 0.5-1ml/kg/hr Room temp should be 28-32˚C

Question 59

what are vulvovaginal cares in TEN with vulvovaginal erosions?

Answer 59

betnovate cream BD for vulva betnovate oint BD for vagina via dilator both 3/7 on and 4/7 off + regular antifungal + use of soft vaginal mold as much as possible + menstrual supression

Question 60

whta re recommendations/guidelines for IVIg in TEN?

Answer 60

1g/kg/day for 3 days Minimum total dose 2mg/kg but 3mg/kg recommended Ideally should be started in first 24 hrs of disease onset Australian national blood authority qualifying criteria for IVIg in SJS/TEN; Used for TEN or SJS/TEN overlap if; - Diagnosed by a dermatologist. AND; - BSA of 10% or more. AND; - Evidence of rapid evolution (not specified) Also should be in first 24 hrs of diagnosis Urgent skin biopsy should be performed but should not delay IVIg Adverse Drus Reactions Advisory Committee should be notified of the responsible medication Should not be used for SJS alone (

Question 61

Should steroids be given in TEN?

Answer 61

controversial currently unclear evidence for effectiveness and may increase risk of infection and mortality. Some studies suggest some benefit if given early but not enough data to support this at present. If used give Dexamethasone 1.5mg/kg pulse therapy for 3 days

Question 62

T/F | broad spectrum antibiotics should be given prophylacticaly in TEN

Answer 62

F

Question 63

Apart from IVIg and steroids what systemics have been suggested in TEN?

Answer 63

Cyclophosphamide Cyclosporin anti-TNFα drugs (infliximab and etanercept) plasmapheresis N-acetylcysteine Use of these is advocated in some recent reviews NB CsA has been used at 3mg/kg/day for 10 days tapered over one month

Question 64

what dressings are used in TEN?

Answer 64

non-adherent paraffin gauze (xeroform, vasgauze, jelonet) or hydrogel Can use Bactigras (0.5% chlorhex in paraffin gauze) but chlorhex can be irritating use with dermeze+++ some recommend silver dressing but some say silver can be a trigger for TEN and should be avoided

Question 65

What is prognosis of SJS/TEN?

Answer 65

Healing occurs by re-epithelialization Rapid on chest/abdo, slower on pressure and intertiginous areas Takes 3-4 weeks for skin, longer for mucosae and up to 2/12 on glans penis Mortality; SJS 5%. SJS/TEN overlap 10-15% TEN 30-40% - can stratify with SCORTEN Almost ¼ of TEN die after discharge from hospital. worse prognosis if; drug has a long half life Older age Extensice disease Delay in specialist Rx thrombocytopenia Early empirical antibiotic treatment given NB; Early withdrawal of causative drug improves prognosis – reduces risk of death by up to 30%

Question 66

What is SCORTEN? how is it scored? what are the associated mortalities?

Answer 66

``` Assess SJS/TEN pts for SCORTEN after 24hrs in hospital using highest scores and again on day 3. 1 point each; ABC PUSH; Age over 40 Bicarbonate below 20 mmol/L Cancer Percent BSA >10% initially and reaches >30% Urea over 10 mmol/L Sugar - BGL over 14 mmol/L Heart rate over 120 ``` ``` Predicted mortality; 0-1 - 3% 2 - 12% 3 - 36% 4 - 60% 5-7 - >90% ```

Question 67

What are the complications of skin emergencies?

Answer 67

THE INET + Metabolic Thermoregulation + Thrombosis Haemodynamic – ARF, CHF/high output cardiac failure, odema Ectropion + other eye complications Infection – skin, pneumonia etc Nutrition, Nails & Nodes (low albumin marker of poor protein status) Enteropathy (iron, B12, folate, protein and fat malabsorption and deficiency) Telogen effluvium Metabolic - electrolyte imbalance