Dermatologic Disorders PDF

Dermatologic Disorders Dermatology Anatomy and Physiology Select disorders ○ Psoriasis ○ Atopic Dermatitis ○ Acne Anatomy and Physiology Learning Objectives 1. Identify key skin structures 2. Describe the maturation process of keratin...

Dermatologic Disorders Dermatology Anatomy and Physiology Select disorders ○ Psoriasis ○ Atopic Dermatitis ○ Acne Anatomy and Physiology Learning Objectives 1. Identify key skin structures 2. Describe the maturation process of keratinocytes 3. Describe the role of keratinocytes, melanocytes, Langerhans cells 4. Identify and describe the function of skin appendages 5. Correlate skin structures with their role in the overall function of the skin Skin Structures  Epidermis Keratinocytes Keratinocytes -85% of epidermis ○ Produce keratin – protective protein Basal cells divide to make new keratinocytes Keratinocytes migrate upward; changing morphology Migration time = 20-30 days Stratum corneum – thickest layer; dead cells Epidermis Melanocytes Produce melanin = skin color Size of melanosomes (packaged melanin) dictates skin color ○ Darker color = larger Fixed to stratum basal Function: absorb and scatter ultraviolet rays Conditions ○ UV stimulates melanin ○ Albinism ○ Vitiligo Epidermis Langerhans Cells Antigen Presenting Cells Bind to antigens and migrate to lymph nodes Stimulate T-cells proliferation and cytokines  Dermis Collagen-based layer ○ Between epidermis and subcutaneous layer Nutrient supply Immune function ○ Macrophages ○ T-cells ○ Mast cells ○ Fibroblasts Highly innervated Dermis Appendages Hair follicle ○ Color ~ melansomes Sebaceous glands ○ Co-located with follicle ○ Not on palms/soles ○ Produce sebum (triglycerides, wax, cholesterol) Lubricate skin/hair Prevent moisture loss Sweat glands ○ Eccrine and apocrine types Regulate body temperature Nails Function of Skin Temperature regulation ○ SNS vasodilation/vasoconstriction ○ Sweat production Sensory ○ Pain, thermal, touch Maintain hydration Immunologic ○ Barrier to bacteria (bactericidal microfilm) ○ Langerhans cells (APC) ○ Mast cells, macrophages, T-cells Hormone synthesis ○ 7-dehydroxycholesterol  Cholecalciferol  Psoriasis SCOTT HANES, PHARMD ASSOCIATE PROFESSOR, COLLEGE OF PHARMACY Learning Objectives Identify the key immunologic factors associated with psoriasis development Identify important co-morbid conditions associated with psoriasis Identify the most common age ranges for onset of psoriasis Describe the key dermatologic features of psoriasis Identify the key immunologic Th cells implicated in the pathophysiology of psoriasis Identify the key mediators of keratinocyte proliferation Describe the most common dermatologic areas of the body affected by psoriasis Identify the most common variant form of psoriasis List potential co-morbid disease states that may be associated with psoriasis Identify risk factors that may trigger psoriasis exacerbation Recognize typical features of psoriatic onychodystrophy Psoriasis oDefinition ○ Immune mediated chronic skin condition ○ Commonly associated with systemic manifestations ○ Clinical manifestations are managed but not cured ○ Common to have remission and exacerbations of disease o2 – 7.5 million US adults but can affect children o 2% prevalence oOnset: bimodal o Most 20-40 y/o but second smaller peak 50-60 years o Median age of onset 25-28 years o 60-90% have family history of psoriasis o Identical twin: 80%  Pathophysiology Immune mediated ○ Inflammation T-lymphocytes Th1 and Th17 ○ Keratinocyte proliferation/differentiation Th17 Keratinocyte transit time shortened from 13 to 2 days Poor cell differentiation ○ Angiogenesis and vasodilation (endothelial cell proliferation) IL-22 Etiology Risk factors ○ Trauma Koebner phenomenon – new lesion with skin trauma ○ Infection (viral/streptococcal) –common with guttate type ○ Stress ○ Smoking ○ Obesity ○ Alcohol ○ Drugs (mechanisms poorly understood) Lithium, beta blockers (prolonged latency) TNF-antagonists – paradoxical (interferon mediated?) Hydroxychloroquine, Terbinafine (short latency) Rapid withdrawal of corticosteroid therapy (rebound)  Types of Psoriasis Variants of Psoriasis (https://www.psoriasis.com/about-psoriasis/psoriasis- types) ○ Plaque psoriasis (90%) –psoriasis vulgaris ○ Flexural/intertiginous ○ Erythrodermic ○ Localized (scalp, palms/soles) ○ Guttate (> pediatrics) ○ Generalized pustular ○ Seborrheic Clinical Presentation Dermatologic Features: ○ Pruritis ○ Scaling ○ Pain/inflammation (erythema) ○ Auspitz phenomenon Bleeding with mild skin disruption Plaque Psoriasis Lesions Scales (flaking) Erythematus, demarcated  Skin Distribution Local (elbows, knees, scalp are common) Scalp (50-80% of cases) ○ Can result in alopecia Nail involvement (80% of cases) Psoriatic onychodystrophy Generalized Severity ○ Mild < 5% BSA (80-90% of patients) ○ Moderate 5-10%, ≥ 8 PASI measurement (Psoriasis area severity index) ○ Severe > 10% BSA or PASI ≥ 10 Psoriatic onychodystrophy (80-90%) ○ Finger>toes ○ Pitting ○ Hyperkeratosis ○ Onycholysis: nail separation ○ Oil-droplet pattern Systemic Manifestations Psoriatic arthritis ○ Onset delayed but can be presenting sign Common to present 10 yrs after psoriasis diagnosis ○ More common in severe psoriasis (50%), presence of nail dystrophy, or intergluteal involvement ○ Typically asymmetric with distal interphalangeal joint involvement but 50% can have axial involvement (spondylitis, sacroiliitis) ○ Can be irreversible  Associated Co-morbidities Mental Health (depression, substance abuse, anxiety) ○ Impacts quality of life Metabolic syndrome ○ Obesity, dyslipidemia, hypertension, insulin resistance/glucose intolerance ○ Risk of diabetes 5x higher ○ Hypercoaguable, proinflammatory ○ Risk of MI/stroke 2-3x higher Especially among younger patient Crohn’s disease Malignancies ○ Cutaneous T-cell lymphoma ○ melanoma Psoriasis Treatment Options Topical anti-inflammatory agents: steroids (e.g. beclomethasone) Keratinolytics: Topical Vitamin D analogs; salicylates Biologic Response Modifiers ○ TNF inhibitors etanercept (Enbrel) – soluble TNF receptor (inactive) adalimumab (Humira) – Ab to TNF infliximab (Remicade) –Ab to TNF ○ IL-17 Secukinumab (Cosentex) – Ab to IL17 Ixekizumab (Taltz) – Ab to IL17 Brodalumab (Siliq) (IL17 receptor antagonist) ○ IL-12/IL-23p40 Ustekinumab (Stelara) – Ab to p40 subunit ○ IL-23p19 Guselkumab (Tremfya) – Ab to p19 subunit Atopic Dermatitis  Learning Objectives Describe key alterations in epithelial barrier, immune system, and skin microbes that contribute to atopic dermatitis Describe clinical features common to atopic dermatitis including dermatologic distribution Differentiate typical features of disease presentation for infants and adults Describe histamine’s role in pruritis in atopic dermatitis Atopic Dermatitis Atopic Dermatitis (Eczema) ○ Inflammatory skin disorder ○ IgE plays a role ○ Commonly co-associated with asthma, allergic rhinitis, and allergies ○ Most cases present by 5 years of age Characterized by: ○ Pruritis (itching) – key symptom ○ Promotes more lesion eruption ○ Dry skin Pathophysiology Skin barrier disruption Changes is skin microbes Immune dysfunction  Pathophysiology Skin barrier disruption ↑dermal H2O loss ↓dermal lipids ↑Epithelial permeability Mediated by: Th2 cytokine activity downregulating genes Filaggrin mutation ○ ↓ crosslinking of keratin filaments ○ ↑ pH Microbial dysbiosis Tsakok et al. Br J Derm 2018:DOI: 10.1111/bjd16934 Pathophysiology Microbial dysbiosis ↓diversity of microbes Staphylococcus aureus dominates Increased interaction bacterial and subdermal immune system ○ ↑Th2 activation ○ ↑dermal barrier disruption Pathophysiology Immune dysfunction ○ Th2 helper cells Interleukins IgE Inflammationedema erythema ○ Pruritis due to IL-31 and IL-4 >>histamine Tsakok et al. Br J Derm 2018:DOI: 10.1111/bjd16934  Clinical Presentation Differs by age ○ Infants/children Weeping vesicles Pruritis Crusting/excoriations Erythma, initiates on face (cheeks) and spreads Sparing the nosetip (headlight sign) ○ Adolescents/adults Dry, red patches Pruritis Chronic : leathery; lichenified skin knees, elbows, neck, hands commonly involved Common Atopic Dermatitis Skin Distribution Lancet 2020;396:345 Berke et al. Am Fam Phys 2012:86:35-42.  Atopic Dermatitis Treatment Skin moisturization (Emollients) Topical corticosteroids Topical calcineurin inhibitors (tacrolimus, pimicrolimus) Dupilumab – IL4 receptor antagonist (monoclonal antibody) Acne Vulgaris Learning Objectives Differentiate open and closed comedones Identify the key factor that causes increase sebum production Describe the factors involved in acne development Differentiate papules, pustules, nodules  Acne Vulgaris Inflammatory disorder of the pilosebaceous unit Contains: Hair/follicle Sebaceous gland (produces sebum) Sebum = mono-,di-, triglycerides + sterol/wax esters + squalene (lipid-like molecule) Dermal distribution - everywhere except palms and soles; most numerous on face back, chest. Glands increase in size and activity secondary to androgens Acne Vulgaris Acne terminology ○ Non-inflammatory ○ (Micro) Comedones-dilated hair follicles Open Blackheads – melanin containing sebum plugs Closed Whiteheads – pale raised papules ○ Inflammatory Papules - raised lesion < 5mm Pustules – have central core of pus Nodules - > 5mm; cysts Acne Vulgaris Papules Pustules Nodules ○ Inflammatory lesions Papules - raised lesion < 5mm Pustules – have central core of pus Nodules - > 5mm; cysts Zaenglein AL. NEJM 2018:379:1343-52.  Acne Vulgaris Precipitating factors ○ Hormones (androgens) Key factor  increases sebaceous glands and activity ○ Heat/humidity ○ Friction (hats/helmets/scrubbing/abrasive clothing) ○ Winter months ○ Stress/emotions Increases cortisol release augmenting androgens effect ○ Occlusion (make-up/hairspray) ○ Diet Dairy, whey protein, high-sugar Pathophysiology ↑Sebum production ○ Androgen induced sebaceous cell activity Colonization/proliferation of Cutibacterium (Propionibacterium) acnes Neutrophil infiltration of comedone Lipases break down free fatty acids  weakening follicular unit  rupture Inflammation ↑ proliferation of keratinizing epidermal cells that form sebaceous cells Plugged follicles Pathophysiology Acne Vulgaris Treatment