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Acute Drug Reaction SJS/TEN - Department of Health · Steven Johnson syndrome Toxic Epidermal...

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Acute Drug Reaction Acute Drug Reaction SJS/TEN SJS/TEN Dr B Dr B Parag Parag
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Page 1: Acute Drug Reaction SJS/TEN - Department of Health · Steven Johnson syndrome Toxic Epidermal Necrolysis SJS/TEN overlap syndrome. Epidemiology ... Stevens‐Johnson Syndrome ‐Less

Acute Drug ReactionAcute Drug ReactionSJS/TENSJS/TEN

Dr B Dr B ParagParag

Page 2: Acute Drug Reaction SJS/TEN - Department of Health · Steven Johnson syndrome Toxic Epidermal Necrolysis SJS/TEN overlap syndrome. Epidemiology ... Stevens‐Johnson Syndrome ‐Less

History

45 yr old female – RVD postive CD4 238, clin. stage 1Pulmonary TB on treatment for 2/52

p/w ‐ sore throat‐ septic mucocutaneous lesions‐ pustules involving the 

upper and lower lips, purulent eye discharge, blisters over the feet, diffuse hyperpigmentation of the skin

‐ fever ‐ generalised body pains

HxPC: initially diagnosed with PTB in February 2007.commenced on TB treatment and subsequently developed a rash a month later. Rx was stopped and not re‐challenged(4 sputum samples taken were negative). 

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She then presented in Manzini with constitutional symptoms of TB 5mths later. Sputum was + and treatment was commenced.INH was given for 3 days and thereafter full TB treatment wasgiven together with streptomycin. 2/52 she had developed SJSand sent to greys hospital.

PmedHx: Hypertensive on Hctz 12.5 mg dailyDrug hx: also on bactrim prophylaxisNo other significant hx of note

O/E general‐ septic oral lesions involving both the upper and lower lip, purulent eye discharge, diffuse hyperpigmentation ofthe skin, blisters over the feet. Swelling of the ankles and knees.Pyrexial.

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No lymphadenopathy, no pallorRESP:  chest clear,  CVS: s1 s2 normal, no murmursABD: SNT, no organomegalyCNS: fully orientated to person,place,time

no focal signsENT: purulent otitis media

Assesment:Stevens Johnson syndrome secondary to TB treatment/ bactrim induced.

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NaNa 138138 HbHb 8.28.2 AlpAlp 4646 CaCa 2.402.40

KK 4.864.86 WCCWCC 5.65.6 TbilTbil 88 MgMg 0.800.80

ClCl 109109 PltPlt 358358 AlbAlb 2020 PO4PO4 0.900.90

HCO3HCO3 22.922.9 GGTGGT 4747

UreaUrea 6.46.4 ALTALT 2020

CreatCreat 8181

GlucGluc 5.15.1

INRINR 0.980.98

Sputum : TB auramine stain positive.,CXR‐ NAD, sensitivity: INH resistant.HSV serology‐ neg

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ManagementDermatology: Hydocortisone 200mg TDS for 3 days

wait for lesions to completely healskin lesions treated with flamazine dressings

Rechallenge TB treatment

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Acute Drug Eruption

Steven Johnson syndrome

Toxic Epidermal Necrolysis

SJS/TEN overlap syndrome

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Epidemiology

Incidence: 2 cases per million people per yearSJS: TEN‐ 3:1

Mean age: 25‐47 ( SJS), 46‐63( TEN)Sex‐M=FFemales: 33‐ 62%(SJS), 60%(TEN)

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Pathogenesis

‐Incompletely understood‐Immunological process‐ T‐ lymphocyte (cell mediated  cytotoxicreaction against epidermal cells).  ‐Role for reactive drug metabolites‐ slow N acetylation‐other: mixed drug‐induced, immune‐mediated phenomenon,

role of fas and fas ligand in apoptosis of keratinocytes(absence of substantial dermal inflammation): Perforin,TNF‐a, granzyme B‐ non apoptotic cell death

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Stevens‐ Johnson Syndrome

‐Less severe‐ prodrome‐ fever and malaise, influenza like sympt( 1‐3 days)‐ rapid onset of erythematous/purpuric macules and plaques‐ epidermal necrosis and sloughing‐< 10% body surface‐mucosal involvement: 92‐100%, 2‐3 distinct sites( ocular , oral,genital)

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Stevens Johnson syndrome

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Toxic  Epidermal Necrosis

‐prodrome: fever( temp higher than in SJS‐ >39C), malaise 1‐3 days

‐Skin lesions: widely distributed erythematous macules and patches, 50% may begin with diffuse erethema‐early stages: skin pain‐Full thickness epidermal necrosis ‐>30% body surface (“ extensive thermal injury”‐mucous membrane involvement‐ almost all cases

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Toxic Epidermal Necrolysis

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SJS/TEN Overlap Syndrome

‐>10% by < 30 % body surface 

Erythema Multiforme

‐ Previously used to describe SJS‐Typical “target” lesions , distal extremities incl. palms & soles‐ reaction to infection, most commonly herpes simplex virus/mycoplasma

‐benign clinical course

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Erythema Multiforme

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Presentation

‐All three –SJS, TENS, SJS/TENS‐ acute onset( 1‐3 weeks, avg 14 days), re‐exposure – <48hrs‐Skin tenderness, photophobia, conjuctival itching/burning  ‐ early symptoms‐Painful(burning )skin lesions‐ begin on the face and thorax, scalp spared, palms and soles less involved‐Fever ‐Sore throat‐Visual impairment( mucous membrane and ocular involvement)‐Transcutaneous fluid loss‐ prerenal failure

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Skin lesions‐ill defined erythematous macules with purpuric centres‐Occasional target lesions on SJS‐Symmetrically distributed‐Vesicles  flacid bullae‐Sloughing

Mucous membrane: painful crusts and erosions, includesGenitalia, GI tract and respiratory tract

Ophthalmic: conjuctival lesions‐ 85%‐ simple hyperaemiaand congestion of vessels, scarringLong term: photophobia, visual impairment, trichiasis,neovascularization of the cornea, keratitis, corneal scarringleading  to blindness

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SevereTEN“burns”

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Mucosal lesion- oral

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Ocular involvement- presence of pseudomembranein the lower cul de sac

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Late stage: cornea -symblepharon formation

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Early signs of potentially serious reaction

Confluent erythemaFacial oedema/ central facial involvementSkin painPalpable purpuraSkin necrosisBlisters/epidermal detachmentMucous membrane erosions and crustingUrticariaSwelling of the tongue

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Differential Diagnosis

Erythematous drugs eruptionsPustular drug eruptionsPhototoxic eruptionsStaphylococcal scalded skin syndromeToxic shock syndromeAcute generalized exanthematous pustulosis

(skin biopsy to exclude above causes)

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Staphtlococcal TSS

Staphylococcal scaleded skin syndrome

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Aetiology

Medication( 30‐ 50%SJS, 80%TENS): Antibiotics:  penicillins , sulphonamides, cephalosporinNSAIDSTB medication‐ Rifampicin and EthambutolCough cold remediesAntipsychoyticslamotrigineAromatic anticonvulsants‐ carbamazepineOxicamAnti‐ gout agents‐allopurinol

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Aetiology

Infection( 15 % SJS, rare TEN)‐ Herpes Simplex, MycoplasmaRare causes: vaccinations, systemic disease, chemical exposure,herbal medication, foods

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Risk Factors

Certain HLA typesLower N‐ acetylation capacity ( slow acetylators)Immunosuppression‐malignancyViral infections Physical stimuli‐ UV light and radiation therapy

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Laboratory Abnormalities

Anaemia(TEN)Lymphopaenia(TEN)Neutropaenia( 1/3 )Mild inc ALT, AST (2‐3 times normal) 50% TENHepatitis‐ 10% TEN

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Management( KEH Protocol)-Stop TB treatment-Supportive management-Topical agents: avoid soap, use aqueous cream to bath, topicalsteroid- Advantan, emoliants

-IV fluids and correct electrolyte imbalance-monitor for sepsis- avoid urinary catheter,CVP,NG tube-do not use sulphur containing antibiotics -wound management: flamazine dressing, bactroban, salinewash, glycothymol mouth wash-Multidisciplinary: ophthalmology, dietician, psychologist-Desensitization: 1/3 dose IRPE for 3 days (monitor for

2/3 dose IRPE 3 days rash,pyrexia)full dose

Steroids: 1mg/kg for 3 days only- prevent dissemination of TBand other oppurtunistic infections

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Treatment

‐stop offending medication‐burn unit, sterile handling‐fluid management‐ocular care‐ ophthalmology consult‐temperature management and environmental support‐monitor for superimposed infection‐ staph aureus‐routine cultures of skin, blood , catheters, gastric tubes‐no benefit from prophylactic oral antibiotics‐topical antibiotics‐ 0.5% silver nitrate( avoid topical sulphur agent)‐corticosteroids‐IV gammaglobulin

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Treatment

PlasmapheresisThalidomide‐ increase mortality in TENS –not usedPatient education

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TreatmentTreatment Observations in SJSObservations in SJS Observations in TENObservations in TEN

Systemic Systemic corticosteroids (short corticosteroids (short term, high dose)term, high dose)

Results mixed: Results mixed: possible benefit, possible benefit, possible harmpossible harm

Possible harm due to Possible harm due to increased rates of increased rates of sepsis and impaired sepsis and impaired rere--epithelializationepithelialization

Intravenous Intravenous immunoglobulinimmunoglobulin

Possible benefitPossible benefit

No significant evidence No significant evidence of harmof harm

Possible benefitPossible benefit

PlasmapheresisPlasmapheresis No dataNo data Possible benefitPossible benefit

No evidence of harmNo evidence of harm

ThalidomideThalidomide No dataNo data HarmfulHarmful

ContraindicatedContraindicated

Summary of reported treatments for SJS and TEN

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Resolution

‐2‐4 weeks in the absence of complicaitons‐re‐ epithelialization ‐ several days after onset, usually 2‐3wks‐Remaining skin may peel, nails may  detach

Long term sequele

‐scarring, irregular pigmentation, eruptive naevi , abnormal regrowth of nails, alopecia.

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Prognosis

Poor: intestinal and pulmonary involvementolder ageneutropaeniaincreased % denuded skinDrug withdrawn late

Mortality

SJS: 5%TEN: 30%

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Independent prognosis factorsIndependent prognosis factors WeightWeight

AgeAge 40 years40 years 11

Malignancy*Malignancy* YesYes 11

Body surface area Body surface area detacheddetached

10%10% 11

TachycardiaTachycardia 120/min120/min 11

Serum ureaSerum urea > 10 > 10 mmol/lmmol/l 11

Serum glucoseSerum glucose > 14 > 14 mmol/lmmol/l 11

Serum Serum bicarbonatebicarbonate

< 20 < 20 mmol/lmmol/l 11

SCORTEN#SCORTEN# 77

SCORTEN schema

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HIV Infected Patients

‐3 times increased risk for SJS/TEN‐40 fold increased risk for SJS/TEN due to Bactrim( benefit outweighs risk)‐related to the degree of immunosuppression‐? Exposure to multiple medications, including sulphonamides, “slow acetylation” status, immune dysregulation, presence of concomitant  infections‐Bactrim , sulfadiazine, dapsone, amino penicillins‐Abacavir, Efavirenz, nevirapine, ‐strong association between herpes virus infections and EM, SJS is more associated with exogenous agents(drugs)

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Case‐Recommenced on modified TB treatment ‐INH commenced for 3 days, stopped due to temp spike and re‐occurrance of mucosal lesions‐1/52 later pyrazinamide and rifampicin commenced at full dose, Rifampicin stopped‐ itchy  skin and pyrexia‐Pyrazinamide continued‐11 days later Ethambutol commenced at low dose and increased after 3 day interval to maximum dosage according to weight.‐sensitivity – INH resistant‐7 days later ciprobay commenced at ½ full dose, increased to full dosage after 3 days‐repeat auramine negative ‐currently due to commence on HAART

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THE END


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