Blistering Skin Eruptions Jill Tichy, PGY III February 15 th, 2010

Causes of Vesicles/Bullae Primary Cutaneous Disease: Pemphigus, Bullous Pemphigus, Dermatitis Herpatiformis, Contact Dermatitis, Erythema Multiforme, Stevens-Johnson syndrome, Toxic Epidermal Necrolysis, VZV, HSZ, Hand-foot-and-mouth disease, Staphylococcal scalded-skin syndrome, Scarlet Fever, Toxic Shock Syndrome, Exfoliative Erythroderma Syndrome Systemic Diseases: Paraneoplastic pemphigus, Porphyria Cutanea Tarda, Porphyria Variegata

Nikolsky’s Sign Staphylococcal Scalded Skin Syndrome SJS/TENS Positive when slight rubbing of the skin results in exfoliation of the skin's outermost layer A "positive" Nikolsky's sign is associated with pemphigus vulgaris. pemphigus vulgaris Nikolsky's sign is useful in differentiating between pemphigus vulgaris (where it is present or positive) and bullous pemphigoid (where it is absent)bullous pemphigoid

Toxic Epidermal Necrolysis Bullae that arise on the widespread areas of erythema and then slough The result is large areas of denuded skin Sepsis and Respiratory Failure Involvement of mucous membranes and intestinal tract Drugs are primary offenders (95%): phenytoin, barbituates, tegretol, sulfonamides, PCN, steroids

TEN-cont’d

TEN- cont’d. SCORTEN A score of 0-1 indicates a mortality risk of 3.2%; score of 2, 12.1%; score of 3, 35.3%; score of 4, 58.3%; and a score of 5 or more, 90%. Each of the following independent prognostic factors is given a score of one: Age older than 40 years Heart rate of greater than 120 beats per minute Cancer/hematologic malignancy Involved body surface area of greater than 10% Serum urea level of more than 10 mmol/L Serum bicarbonate level of less than 20 mmol/L Serum glucose level of more than 14 mmol/L

Mechanism of TENS Delayed Hypersensitivity Antigen native drug Accumulation of interstitial fluid under necrotic epidermis; T lymphocytes that are able to kill autologous lymphocytes and keratinocytes in a drug specific, HLA- restricted mediated pathway Epidermis overexpresses TNF-alpha  stimulates cytotoxic T lymphocytes  Apoptosis

Tegretol and TEN Strongly associated with HLA-B*1502 Commonly reaction seen within two months of drug initiation However can be seen in long-term use

Steven-Johnson Syndrome Widespread dusky macules and mucosal involvement Due to drugs Limited to < 10% of BSA SJS/TENs overlap 10-30% BSA TEN > 30% BSA

SJS and TEN Acute symptoms, painful skin lesions, fever > 39, pharyngitis, visual impairment Mortality 10-30% No treatment of proven efficacy Early diagnosis, immediate discontinuation of any offending drug No RCT exist but IVIG is second line G-CSF if leukopenia exists (again no data) Early retrospective studies suggested that corticosteroids increased hospital stays and complication rates.

Erythema Multiforme “Dusky” violet color or petechiae in the center of the lesions Target or iris lesions Symmetric on palms, soles, knees, elbows Mycoplasma, HSV, idiopathic, rarely drugs; PCN, sulfa, phenytoin May involve of mucous membranes, Hemorrhagic crusts of the lips (SJS, HSV, PV, Paraenoplastic) Fever, malaise, myalgias, sore throat, and cough may accompany the eruption Resolve over 3-6 weeks but may recur Can follow vaccinations, XRT, exposure to environmental toxins

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) Widespread erythematous eruption Fever, facial/periorbital edema, tender generalized lymphadenopathy (atypical lymphocytes and eosinophils), leukocytosis, hepatitis, nephritis, pneumonitis Eruption recur with re-challenge Onset 2-8 weeks after drug is started and lasts longer Mortality 10%

Staphylococcal Scalded Skin Syndrome (SSSS) Redness or tenderness of the face, trunk, intertriginous zones Short lived flaccid bullae and a slough of superficial epidermis Crusted areas develop around the mouth Distinguishing features: young age group (infants), more superficial, no oral lesions, shorter course Associated with Staph exfoliative toxin Lesions are sterile vs bullous impetigo Conjuctivitis, rhinorrhea, Otitis media, pharyngitis

SSSS

Porphyria Cutanea Tarda Sun exposed areas mainly hands and face Skin is fragile which leads to tense vesicles => milia => epidermoid inclusion cysts Hypertrichosis Porphyria Variegata: PCT + systemic findings Drug-induced psuedoporphyria: Naproxen, Lasix, tetracycline, Tegretol is porphyrinogenic Attacks can be precipitated by infections, surgery, ETOH

Blistering Metabolic Disorders Comatose patients and decreased cutaneous blood flow; pressure points Diabetes Mellitus; distal extremities

References Harrison’s Internal Medicine 17 th ed. Google Images