“Reactive” and Idiopathic Skin Diseases

Rich Callahan MSPA, PA-C

Fletcher Allen Dermatology

Burlington, Vermont

ICM I – Summer 2009

Overview

• Erythema Multiforme (EM)• Erythema Nodosum (EN)• Stevens-Johnson Syndrome/Toxic

Epidermal Necrolysis (TEN)• Urticaria/Angioedema• Lichen Simplex Chronicus/Prurigo

Nodularis• Lichen Planus

EM – What is it?

• An acute, common skin rash associated with a number of causative factors, although 50% of the time a precipitating cause is not found.

• Classified as a reactive, inflammatory process of the skin, or “Hypersensitivity syndrome.”

• Reactive change in dermal vasculature with overlying epidermal changes

EM – Epidemiology/Causative Factors

• Can be caused by drugs, infections (Herpes,) pregnancy, internal malignancy, acute URI, atypical pneumonia

• ~50% idiopathic• Mostly see in younger patients, most

common age range is 20-40 years• I have seen several patients who develop

EM after HSV outbreaks (cold sores)

EM – Clinical Presentation

• Characteristic erythematous, target-shaped, urticarial papules, vesicles and bullae

• Affects trunk, extremities, mucous membranes, palms/soles.

• Lesions appear quickly in a symmetric pattern, usually first on dorsal hands/feet, then migrating along extensor extremities, then to trunk in severe cases.

• Can be asymptomatic, pruritic or painful.• Occassionally, will manifest only as oral bullae and

ulcerations.

EM – Clinical Presentation

• Eruption evolves over several days, may be preceded by prodromal symptoms including malaise, fever or burning/itching at sites where EM will later develop.

• Presentation can be entirely non-diagnostic at first, then later dx’ed as EM when classic “target lesions” develop.

• Entire course of disease usually 1 month or less. • Rarely life-threatening with extensive mucous

membrane involvement, patches of vesiculation, etc

EM - Diagnosis

• EM is a clinical diagnosis based on patient history and disease presentation.

• Skin biopsy seldom helpful in my experience as histologic findings can be non-specific at early stages of disease, which is when it tends to get biopsied.

• Biopsy of target lesions generally diagnostic, but seldom biopsied as is an easy clinical diagnosis by that point!

EM - Treatment

• Mild cases do not require treatment.• Moderate cases respond well to a 1-3 week

course of oral steroids (prednisone.)• Severe cases treated with IV steroids.• In recurrent cases with positive HSV

association, I have used prophylactic therapy with oral antiviral meds (Valtrex) with good success.

Erythema Nodosum – EN – What is it?

• An acute panniculitis of the lower extremities with diverse causes

• Considered a delayed hypersensitivity reaction to a number of possible antigens, I.e., it is a reaction to a concurrent disease or condition.

• Most common cause today is streptococcal infection.

• Can be precipitated by drugs, infections, sarcoidosis, misc. inflammatory disorders

EN - Causes

• Infections• Bacterial• Fungal• Viral• GI parasites• Drugs (esp. OCP’s)

• Cancer• Concomitant Disease• Sarcoidosis• IBD• Ulcerative Colitis• Crohn’s Disease

EN - Epidemiology

• Women >> men. Female: Male ratio is 5:1

• Peak ages of incidence are 18 – 35 years.

• Extremely rare in the elderly.

• Historically, much less common in the modern area with advent of antibiotic drugs.

EN – Clinical Presentation

• Presents as development of painful red nodules, patches and plaques, usually on lower legs, over a period of 1-2 weeks.

• Often preceded by prodromal symptoms of fever, malaise, arthritis and arthralgias.

• Individual lesions begin as reddish, swollen papules on shins bilaterally, then grow into violaceous, indurated, tender patches and plaques which resolve in 1-2 weeks.

• Eruption can recur in crops for months to years.

EN - Treatment

• Usually resolves spontaneously w/o treatment.

• Symptomatic relief with rest and/or NSAID’s.

• SSKI (supersaturated potassium iodide.)• Prednisone• ID and treatment of precipitating cause if

possible.

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis – What is it?

• Both names represent a spectrum of disease with SJS being the less severe end.

• A life-threatening condition characterized by large scale and widespread necrosis and detachment of epidermis, affecting both skin and mucosal surfaces of eyes (conjunctivae,) nares, mouth, anorectal/genital areas.

• One of the few truly acute medical emergencies in Dermatology.

SJS/TEN

• Pathophysiology not entirely understood, but thought to be reaction in keratinocytes where cells accumulate foreign antigen and are stimulated to apoptosis (cell death) by T-cells.

• Large areas of epidermis become necrotic and slough off in sheets

• Results in massive transcutaneous water loss and usually secondary bacterial infection

SJS/TEN - Causes

• Most often caused by drugs, then infections, then rarely by a malignancy.

• Drugs include: Sulfonamides, Bactrim/Septra, Quinolones, Cephalosporins, acetaminophen, phenobarbital, NSAID’s, cocaine, ginseng, allopurinol, fluconazole, many others.

• Infections include influenza, HSV, Epstein-Barr virus, Cat-Scratch disease, histoplasmosis

• Malignancies include carcinomas and lymphomas

SJS/TEN Spectrum of Disease

• Grade I - SJS: Less than 10% of Body Surface Area (BSA) affected.

• Grade II - SJS/TEN Overlap: Between 10% and 30% BSA affected.

• Grade III – TEN: Greater than 30% BSA affected.

SJS/TEN Epidemiology/Morbidity/Mortality

• Usually seen in Caucasians, male:female ration is 2:1.

• Average patient is 20-40 years old, although occasionally seen in infants/elderly.

• If BSA involvement 10% or less, mortality is 1-5% of cases. 30% or higher BSA involvement has mortality rate between 25% and 35%

• Overall mortality for entire SJS/TEN spectrum of disease is 15%

SJS/TEN – Clinical Presentation

• Clinically manifests as erythematous and purpuric macules and target lesions, distributed over trunk, palms, soles and mucosal areas. Blister formation and sloughing/necrosis of skin follow.

• Nikolsky Sign: Pushing down on blisters causes them to spread laterally with little resistance

• Skin rash preceded by cough/URI symptoms. • Patients have fever, electrolyte imbalances,

eye/mucous membrane involvement, pain, occassional lung involvement.

SJS/TEN – Clinical Presentation

• Mucosal lesions lead to widespread epidermal sloughing and crust formation.

• Extensive disease can lead to scarring, stricture formation and partial loss of funcion of organ system involved.

• Eye involvement includes corneal ulcerations and conjunctival injury which can lead to scarring and blindness.

SJS/TEN - Treatment• Most often a reaction to drugs, so look for

offending cause in all cases: Usually the newest drug on a patient’s list, within 1 to 4 weeks of starting it

• Treatments are supportive, although oral prednisone is often used in an attempt to shorten duration of illness.

• Other treatments include oral antihistamines, lidocaine gargles, liquid/soft diet, Burrow’s compresses, topical steroids to non-eroded areas, ophthalmology consult, antibacterial therapy for secondary infections.

Urticaria/Angioedema

• Urticaria presents as groups of itchy, pink/flesh-colored wheals

• Caused by edema, or fluid accumulation in epidermis/superficial dermis

• Papillary vascular plexus

• Angioedema presents as broad, poorly-defined areas of swelling

• Caused by edema of dermis and subcutis

• Deep vascular plexus

Urticaria/Angioedema

• Wide Variety of Causes:

• 50-60% of cases idiopathic

• Allergies• Drugs• Contact urticaria• Autoimmune and

immunologic mediated

• Physical Urticaria – Angioedema

• Infections• Treatment usually

with antihistamines and/or prednisone

LSC/Prurigo Nodularis

• Lichenification of skin in direct reaction to repeated rubbing and scratching of skin

• Skin becomes thickened with accentuation of skin markings

• Scratching becomes pleasurable to patient

• Dome-shaped, hyperpigmented papules and nodules in areas of lichenification

• Often deeply excoriated

• Hyperplasia of cutaneous nerves leads to enhanced sensitivity and pruritis

Lichen Planus (LP)

• Idiopathic eruption defined by the 4 P’s:• Pruritic, purple, polygonal papules• Tends to affect wrists, flexor extremities,

lumbar areas, genitals, mucosa• Tends to last 6 months to one year• Leaves behind deep, long-lasting

hyperpigmentation• Presence of Wickham’s striae diagnostic