1. “Reactive” and Idiopathic Skin Diseases Rich Callahan MSPA, PA-C Fletcher Allen Dermatology Burlington, Vermont ICM I – Summer 2009

2. Overview Erythema Multiforme (EM) Erythema Nodosum (EN) Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (TEN) Urticaria/Angioedema Lichen Simplex Chronicus/Prurigo Nodularis Lichen Planus

3. 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

4. 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)

5. 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.

6. 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

7. 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!

8. 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.

9. 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

10. EN - Causes Infections Bacterial Fungal Viral GI parasites Drugs (esp. OCP’s) Cancer Concomitant Disease Sarcoidosis IBD Ulcerative Colitis Crohn’s Disease

11. 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.

12. 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.

13. 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.

14. 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.

15. 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

16. 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

17. 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.

18. 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%

19. 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.

20. 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.

21. 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.

22. 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

23. 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

24. 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

25. 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