Overview Pathogenesis of Acne Vulgaris Inflammatory Diseases of the skin: Acne, Rosacea, Psoriasis, Atopic Dermatitis Sebum production by the sebaceous gland Infections: Zoster P. acnes follicular colonization Pre-malignant and malignant neoplasms: Actinic Alteration in the keratinization process Keratoses, Basal Cell Carcinoma, Squamous Cell Carcinoma, Melanoma Release of inflammatory mediators into the skin, i.e. role of sebaceous lipids and inflammatory mediators including MMPs. Inflammatory Acne Papules Comedones Pustules Open (Blackheads) Closed (Whiteheads) Acne Scarring Nodules Cysts Strategic Approach to Acne Therapy Role of retinoids Topical/Systemic antibiotics have no role as monotherapy Treatment of Acne Oral isotretinoin should be considered as first line in severe acne Azeleic acid is useful in pregnancy and patients with hyperpigmentation Moderate Inflammatory Acne Oral Contraceptives and Acne Treatment Hormonal Therapy Norgestimate-ethinyl estradiol Oral contraceptives may be helpful in some women Norethindrone acetate-ethinyl estradiol May take 3 months to see improvement. Drospirenone-ethinyl estradiol Spiranolactone useful in some. If acne is accompanied by irregular menses, female Use with topicals patterned hair loss or hirsutism, consider endocrine workup. As effective as oral antibiotics at 6 months Severe Nodulocystic, Scarring Isotretinoin-Before and After or Resistant Acne Isotretinoin Synthetic oral retinoid 16-20 week course Regular laboratory evaluation and contraceptive counseling for females Registration with iPledge Program required Acne and Diet Rosacea Powell NEJM 352;8 Feb 2005 High Glycemic index diet causes hyperinsulinemia leading to increase in IGF-1 Causes keratinocyte and sebocyte proliferation, lipogenesis Cascade of events activates androgens Subtype 1 Subtype 3 Observational studies suggest milk consumption imparts increased risk for acne Subtype 2 Subtype 4 Rosacea Rosacea Rosacea Rosacea Variants Papule and pustules Opthalmic Rosacea- treatment of choice: oral antibiotics Telangiectasias Steroid Rosacea- resulting from long term topical or systemic Flushing and blushing steroid use Sebaceous hyperplasia Perioral Dermatitis- triggered or aggravated by steroid use Triggers: cold, heat, UV, irritation, emotions, alcoholic beverages, spicy foods, hot beverages Rosacea Treatments Rosacea Topical: clindamycin, erythromycin, metronidazole, sulfur-based lotions, azelaic acid, sunscreens, ivermectin oxymetazoline hydrochloride cream 1%, brimonidine- facial erythema Systemic: tetracyclines, erythromycin, isotretinoin Psoriasis Psoriasis An immune dysregulatory disease secondary to T-cell activation, release of TH1 based cytokines. Cytokines cause keratinocytic proliferation and recruitment of inflammatory cells into the skin 2% of the U.S. population Bimodal incidence: peaks at ages 29 and 55 Early onset associated with increased severity and family history Generalized plaque psoriasis Guttate psoriasis . scattered scaly papules . trunk and proximal extremities . can be associated with streptococcal infection . can be seen as first sign of disease in children or acute exacerbation in adults Inverse psoriasis Nail Findings . nail pits . yellowish discoloration . commonly involves axilla, groin, umbilicus beneath nail plate . may not see much scaling . higher risk of secondary infection National Psoriasis Foundation Recommends: Triggers BP, pulse, BMI every 2 years Streptococcal infection (Guttate) HIV Fasting blood glucose, lipid levels every 5 years if no additional Drugs: Lithium, steroids, Beta-blockers, Interferons, ACE risk factors, every 2 years with risk factors inhibitors, G-CSF Joint status every visit- 5-8% of patients with psoriasis also suffer from PsA Psoriasis Treatment-Topical Systemic Therapy Anthralin PUVA Vitamin D3 Analogues Methotrexate Tazarotene Cyclosporine Tar Retinoids- Acitretin Topical glucocorticoids Biologic Agents- Etanercept, Efaluzimab, Adalumimab, Alefacept, Infliximab, Secukinumab Apremilast Biologics and Psoriasis TNF-alpha Safety Warnings • 8 FDA approved biologics for psoriasis • Serious infections • New targets in development in response to advancements in basic • Malignancies science • Demyelinating disease • Therapies targeting IL-17 and IL-23 exhibit promising potential • Congestive heart failure thus far • Hepatitis B • Further study is necessary to elucidate the long term efficacy and • Hematologic safety characteristics of these categories of drugs • Autoimmunity Rubbert-Roth A. Rheumatology. • Live vaccines 2012;51:v38-47 Bioloigics-Clinical Pearls Biologics -Psoriasis • Adalimumab • Guselkumab –-q8-12 weeks • Etanercept • Brodalumab • Apremilast • Ixekizumab • Certolizumab - doesn’t cross placenta • Secukinumab – not associated with TB reactivation • Tildrakizumab- takes time to work (several mos) • Ustekinumab – safe in adolescents • Tofacitinib –JAK1 inhibitor for vitiligo, concomitant with light • Risankizumab/Mirikizumab Atopic Dermatitis Atopic Dermatitis Pruritus Facial/ Extensor involvement in pediatrics Flexural lichenification in adults Personal/ Family History of atopy Atopic Dermatitis- Associated Features Atopic Dermatitis and Food Xerosis Prenatal and postnatal probiotic supplementation decreases risk Cutaneous infections- S. aureus, Herpes, Molluscum Restriction diets helpful only if oral food challenge is positive Keratosis Pilaris Pityriasis Alba Nipple Eczema Elevated Serum IgE Orbital darkening Fig 2 Atopic Dermatitis- Management Crisaborole ointment Emollients are key part of treatment Topical glucocorticoids Topical calcineurin inhibitors Antihistamines Phototherapy Systemic immunosuppression in severe disease Novel therapy: Crisaborole ointment (PDE4 inhibitor) Dupilumab acetyl dipeptide cream Journal of the American Academy of Dermatology 2016 75, 494-503.e4DOI: (10.1016/j.jaad.2016.05.046) Copyright © 2016 American Academy of Dermatology, Inc. Terms and Conditions Novel Therapy- Atopic Dermatitis Atopic Dermatitis: Advances in Therapy Dupilumab-a monoclonal antibody that targets both interleukin-4 and interleukin-13 Dupilumab Dupilumab therapy provides clinically meaningful improvement in patient-reported outcomes (PROs): A phase IIb, randomized, placebo-controlled, clinical trial in adult patients with moderate to Phosphodiesterase 4 inhibitors severe atopic dermatitis (AD) Crisaborole ointment 2% Eric L. Simpson, MD, MCR et al JAK inhibitors Journal of the American Academy of Dermatology Emerging therapies Volume 75, Issue 3, Pages 506-515 (September 2016) DOI: 10.1016/j.jaad.2016.04.054 Monoclonal Ab against IL 13 and IL 31 RA TRPV1 antagonists T-cell inhibitors Copyright © 2016 American Academy of Dermatology, Inc. Terms and Conditions Zoster/ Shingles •May involve multiple dermatomes or may be generalized in immunosuppressed patients Zoster/ Shingles Zoster Varicella-zoster Virus 5% with non-specific prodromal symptoms 2/3 of patients are over 50 years of age Preceded by pain, paresthesia in the involved dermatome Risk factors: advanced age, malignancy, immunosuppression, xrt, Pain may mimic acute abdomen or MI HIV May involve multiple dermatomes or may be generalized in Reactivation of the virus in the sensory ganglia immunosuppressed patients Consider if pt complains of pain in dermatomal distribution for more than 24-48 hrs even in the absence of skin lesions Zoster Zoster- Therapy Diagnosis may be confirmed by: Treatment Tzanck smear –most rapid, non-specific Ideally initiate within 48-72 hours of rash Direct antigen detection – rapid, specific Oral antiviral agents: Viral culture Acyclovir 800mg five times/day x 7-10 days Valacyclovir 1gm TID x 7d Famciclovir 500mg TID x 7d IV Acyclovir for immunosuppressed patients Zoster- Pain Management Zoster Prevention Treatment of Acute Pain: Treatment of Post-Herpetic Decrease number of new cases of Zoster NSAIDs Neuralgia: Decrease severity of Zoster outbreaks Short course of Opiates Oral Tricyclics +/- Systemic corticosteroids Capsaicin cream Decrease long-term consequences i.e. post-herpetic neuralgia Pain usually improves over weeks to Topical Anesthetics Acceptable cost/benefit ratio months Nerve blocks Gabapentin 1800mg-3600 mg/d Pregabalin 150-600 mg Shingles Prevention Study Contraindications Conclusions: Risk of Zoster reduced by 51% compared to Any patient with a history of acquired or primary immunodeficiency states placebo such as: Leukemia/lymphoma Effect greatest in 60-69 y/o AIDS FDA approved for people aged 50 years and older High dose corticosteroids Active unrelated tuberculosis Reduced burden of illness by 61% Pregnancy Reduced incidence of PHN by 66.5% Active Zoster Reduced incidence of HZ by 51% History of anaphylactic reaction to gelatin, neomycin, or other vaccine component Actinic Actinic Keratoses Keratoses Actinic Keratosis Actinic Keratosis- Therapy Common, pre-cursors to Squamous Cell Carcinoma- .025%- Cryotherapy 16%/yr progress to SCC Topical 5-Fluorouracil Risk factors: age, male gender, fair skin, immunosuppression, Imiquimod lifetime sun exposure, albinism/ xeroderma pigmentosum Diclofenac- NSAID UVB triggers genetic mutations in keratinocytes Ingenol Mebutate P53 most altered tumor suppressor gene in AK/ SCC Photodynamic therapy Clinical: sun exposed areas, flat, erythematous, rough scale (better Dermabrasion/ chemical peels/ laser felt than seen) Systemic retinoids- transplant Actinic