Immune-Mediated Epithelial Diseases Lecture Notes PDF

Vitiligo Vitiligo: Predisposition and Symptoms • • • • Affects all races and genders equally Affects 2% of the population (2-5 million Americans) Usually develops in early adulthood (10-30 years, <40 yoa) May run in families (esp. those with premature graying of hair and those with autoimmune dis...

Vitiligo Vitiligo: Predisposition and Symptoms • • • • Affects all races and genders equally Affects 2% of the population (2-5 million Americans) Usually develops in early adulthood (10-30 years, <40 yoa) May run in families (esp. those with premature graying of hair and those with autoimmune disease) • Rapid pigment loss on several areas of the skin • Most commonly affects sun-exposed skin and body folds (e.g., armpits), prior sites of injury, around moles or body openings • Can also affect eyelids and hair • Once lost, pigment rarely returns • Not physically painful, but can be emotionally damaging • Vitiligo appears in one of three patterns: – Focal pattern – one or few areas of depigmentation – Segmental pattern – depigmentation on one side of the body – Generalized pattern – depigmentation symmetrically – *most common* Pathogenesis of Vitiligo • Basis of disease – autoAb against melanocytes • Mechanism – destruction by C’-mediated lysis or ADCC • Process: ‒ Skin damage (e.g., sunburn, trauma) occurs ‒ Melanocyte-specific Abs are formed and isotype switch to IgG ‒ Ab binds to melanocyte ‒ Classical C’ pathway activate, and MAC is formed ‒ Ab binds NK cell FcγR, then binds melanocyte through Fab ‒ ADCC and perforin/granzyme pathways activated in NK cell ‒ Melanocyte is lysed Diagnosis and Treatment of Vitiligo • Diagnosis ‒ Physical exam ‒ Documented history of sun exposure (sunburn), rash, or skin trauma 2-3 months prior to the depigmentation ‒ Signs of stress or illness ‒ Premature hair graying (<35 yoa) ‒ Family history of autoimmune disease • Treatment ‒ No known way to prevent vitiligo ‒ Repigmentation treatments (long-term: 6-18 months): o Cosmetics (to conceal depigmentation) o UV light therapy (e.g., UV-B) or PUVA – photochemotherapy (drug + UV-A) o Corticosteroid creams o Autologous skin grafting or melanocyte transplant o Micropigmentation (tattooing) o OR… depigmentation of unaffected skin areas Study Guide: Immune-Mediated Epithelial Diseases Immune-Mediated Epithelial Disease Atopic Dermatitis Pemphigus foliaceus Pemphigus vulgaris Psoriasis Vitiligo See from Musculoskeletal Autoimmune Syndromes: Lupus (SLE) Scleroderma Demographics Associations Polymorphisms HLA Pathology Clinical Presentation Treatments Recall: Systemic Lupus Erythematosus Recall: Key Points of SLE • Chronic immune-mediated disease that manifests in multiple organ systems, esp. skin, kidneys, joints, and lungs; a type III hypersensitivity reaction • Multifactorial disease ‒ Sex/race (non-Eur. female), genetics (MHC along with others related to defects in macs, phagocytosis, and C’ activation), and environmental factors (UV exp., infections, drugs, smoking) • Symptoms ‒ Organ-dependent – malar (butterfly rash), mucosal ulcers, joint pain, other organ-specific symptoms ‒ Rarely fatal unless kidneys are involved (glomerulonephritis) • Pathophysiology (see next slide too) ‒ Triggering event damages tissue, then delayed clearance of apoptotic bodies leads to autoAb response ‒ Ag-Ab immune complexes deposited in vasculature, leading to C’ activation, PMN recruitment, microthrombi formation – all increasing inflammatory response • Diagnosis – SLICC criteria – at least 1 clinical and at least 1 immunologic criterion • Treatments – vary from behavioral (avoid sun, smoking) to non-biologic immunosuppressants The Picture of SLE Scleroderma Recall: Key Points of Scleroderma • Chronic immune-mediated disease characterized by fibrosis and vasculopathy of skin • Multifactorial disease ‒ Sex (females) and environmental factors (CMV, organic solvents) ‒ More severe outcome if other organs (besides skin) are involved • Symptoms ‒ First swollen fingers and hands, progressing to thickened/scarred skin with possible discoloring, scaliness, and flexion contractures ‒ Raynaud’s phenomenon – >90% of patients • Pathophysiology (see next slide too) ‒ Triggering event damages epithelium and initiates a CMI response → autoAg = endothelial nuclei ‒ Perivascular edema with mononuclear perivascular cuffing and T cell production of IL-2 and TGF-β ‒ Leads to fibroblast activation and fibrosis (collagen and extracellular matrix deposited) • Diagnosis – ANA antibodies • Treatments – NSAIDs, immunosuppressants, calcium channel blockers for Raynaud’s The Presentation of Scleroderma Top 10 Takeaways SEE NOTES!! 1. Atopic dermatitis is a type I allergic response seen primarily in children. 2. Symptoms of atopic dermatitis are itchy red skin that cannot retain moisture, lichenification, ichthyosis, atopic pleat. 3. Atopic dermatitis is caused by mutation of filaggrin + physical damage to skin allows allergens in, causing IgE/mast cell response. 4. Pemphigus is a rare painful blistering autoimmune disease of skin – foliaceous is superficial (IgG4 autoantibody vs. desmoglein-1); vulgaris is deep (IgG4 autoantibody vs. desmoglein-3). 5. Nikolsky’s sign, presence of acanthocytes, and Tzanck smear help to diagnose pemphigus. 6. Scleroderma is chronic immune-mediated attack of endothelial cells, causing edema, fibrosis, atrophy. May also cause telangiectasia, calcinosis, flexion contractures, and digital ischemia-Raynaud’s phenomenon. 7. Lupus is a multisystemic type III hypersensitivity/autoimmune disease that causes malar rash, alopecia and mucosal ulcers. Genetic and environmental factors may trigger lupus. 8. Review SLICC criteria for diagnosis of lupus. 9. Psoriasis has bimodal distribution for onset, is Th1, Th17 hyperproliferation response, and has 5 cardinal signs (1. Red raised plaques 2. Well circumscribed margins 3. Bright salmon red color 4. Silvery micaceous scale 5. Symmetric distribution) and don’t forget Koebner phenomenon. 10. Vitiligo is a focal, segmental or generalized immune-mediated destruction of melanocytes mediated by autoAbs that activate C’ and NK cells, causing patchy lightened areas of skin and hair. No gender or ethnic predisposition.