Skin Diseases & Musculoskeletal System Lecture Notes PDF

Musculoskeletal and Skin System (MSS) Pathology lectures (1,2, and 3) Skin Diseases and Tumors  Skin The skin is a the largest organ in the body, and has a protective function It is an active participant in immune responses: The dermis contain...

Musculoskeletal and Skin System (MSS) Pathology lectures (1,2, and 3) Skin Diseases and Tumors  Skin The skin is a the largest organ in the body, and has a protective function It is an active participant in immune responses: The dermis contains CD4+ helper and CD8+ cytotoxic T lymphocytes, memory T cells, regulatory T cells (Tregs), and occasional B cells. The epidermis contains intraepithelial lymphocytes, including γ/δ T cells. Responses involving these immune cells account for the morphologic patterns and clinical expressions of inflammatory and infectious skin disorders.  Skin Diseases Diagnosis of skin diseases requires: Clinical history Gross appearance (skin rash and lesions) Distribution of lesions Pathology findings  Skin Diseases Diagnosis of skin diseases requires: Clinical history Gross appearance (skin rash and lesions) Distribution of lesions Pathology findings Skin lesions: Macule: Circumscribed, flat lesion with discoloration, ≤5 mm in diameter Patch: Circumscribed, flat lesion with discoloration, > 5 mm in size.  Skin lesions Papule: Elevated dome-shaped or flat-topped lesion, ≤ 5 mm in diameter Nodule: Elevated dome-shaped lesion, > 5 mm in size. Skin pustule Plaque: Elevated flat-topped lesion, > 5 mm in diameter Pustule: Discrete, pus-filled, raised lesion Skin nodule Skin plaque  Skin lesions Vesicle: Fluid-filled raised lesion ≤ 5 mm in diameter. Bulla: Fluid-filled raised lesion >5 mm in diameter. Blister: common term for both lesions.  Skin lesions Wheal: Itchy, transient, elevated lesion with variable erythema (dermal edema) Scale: Dry, horny, plate-like excrescence Excoriation: Traumatic lesion breaking the epidermis (i.e., deep scratch); often self- inflicted Lichenification: Thickened, rough skin, usually the result of repeated rubbing Wheal Scale Excoriation Lichenification  Skin Diseases Diagnosis of skin diseases requires: Clinical history Gross appearance (skin rash and lesions) Distribution of lesions Pathology findings (after skin lesion biopsy is obtained)  Skin Diseases Diagnosis of skin diseases requires: Clinical history Gross appearance (skin rash and lesions) Distribution of lesions Pathology findings (after skin lesion biopsy is obtained) Normal Skin Histology  Pathology Terms Hyperkeratosis: Thickening of the stratum corneum, often associated with abnormality of the keratin. Parakeratosis: Retention of nuclei in the stratum corneum Acanthosis: Diffuse epidermal hyperplasia. Hyperkeratosis Parakeratosis Acanthosis  Pathology Terms Dyskeratosis: Abnormal, premature keratinization within cells below the stratum granulosum (apoptotic keratinocytes). Acantholysis: Loss of intercellular connections resulting in loss of cohesion between keratinocytes. Dyskeratosis Acantholysis  Pathology Terms Spongiosis: Intercellular edema of the epidermis Papillomatosis: Surface elevation caused by hyperplasia and enlargement of dermal papillae. Lentiginous: linear melanocyte proliferation within the epidermal basal cell layer; can occur as a reactive change or as part of a tumor of melanocytes.  Skin Inflammatory Diseases Acute inflammatory Skin Diseases Chronic inflammatory Skin Diseases Infectious Dermatosis Blistering (bullous) disorders Acute inflammatory Skin Diseases Days to several weeks in duration. Characterized by inflammation (mononuclear cells) and edema; NOT neutrophils. Some may persist, transitioning to a chronic phase, and others are self-limited. 1. Urticaria (Hives) 2. Acute Eczematous Dermatitis 3. Erythema Multiforme  Urticaria (Hives) Most 20- 40 years of age Mediated by localized mast cell degranulation:  Type 1 hypersensitivity rxn, in which antigens (foods, drugs & insect venom) bind IgE on mast cells.  Direct effect on mast cells (IgE-independent) such as opiates & some antibiotics. Approximately 75% of cases are idiopathic  Urticaria (Hives) PATHOGENESIS: Stimuli → mast cell degranulation → histamine and other proinflammatory mediators release → vasodilation and increased permeability of postcapillary venules to large plasma proteins→ transient skin or mucosal swellings due to plasma leakage Acute Urticaria Superficial dermal swellings are termed wheals (usually pruritic) Deep swellings of the skin or mucosa are termed angioedema (usually painful) Lesions might be localized or generalized Angioedema  Urticaria (Hives) Pathology Findings:  Mild superficial dermal edema  Dilatation of small blood vessels  Mild perivascular lymphocytic infiltrates with few eosinophils Treatment:  Antihistamines  Oral corticosteroids (only if angioedema)  Acute Eczematous Dermatitis Eczema is a clinical term Characterized by rash, pruritus and xerosis Clinical presentation is variable according to the phase of disease, age of patient, and changes during disease course Acute: ill defined, oozing, crusted, papules or vesicles Chronic: thickened, hyperpigmented or hypopigmented plaques, resulting from extensive irritation and rubbing; lichenified skin from scratching.  Acute Eczematous Dermatitis Allergic contact dermatitis: topical exposure to an allergen and is caused by delayed hypersensitivity reactions. Atopic dermatitis: genetic predisposition, susceptibility to it is often inherited, appears in early childhood. Patients often have asthma and allergic rhinitis Drug-related eczematous dermatitis Photoeczematous dermatitis Primary irritant dermatitis: results from exposure to substances that chemically, physically, or mechanically damage the skin  Acute Eczematous Dermatitis Microscopic features are variable depending on the chronicity of the lesion  Acute lesions show more marked spongiosis, also dermal edema with lymphocytic infiltrates -Eosinophils (prominent in drug cases)  Chronic lesions show hyperkeratosis, moderate to marked acanthosis and mild spongiosis  Erythema Multiforme Acute, self limited, hypersensitivity reaction to infections (ex. herpes simplex, histoplasmosis, leprosy, mycoplasma), drugs (ex. penicillin, phenytoin, salicylates), carcinoma/lymphoma, or collagen vascular disorders Affects skin and mucous membranes with target lesions Variable (multiform) lesions, including papules, macules, vesicles, bullae, target lesions Commonly in mucous membranes; also elbows, knees, extensor surface of extremities  Erythema Multiforme PATHOGENESIS The epithelial injury is mediated by CD8+ cytotoxic T lymphocytes that attack the basal cells of cutaneous and mucosal epithelia, presumably due to the recognition of unknown antigens. Erythema multiforme caused by drugs may progress to more serious eruptions, such as Stevens- Johnson syndrome or toxic epidermal necrolysis ( may cause Stevens- Johnson syndrome sloughing of large portions of the epidermis, resulting in fluid loss and infections).  Erythema Multiforme Pathology findings (can be variable): Interface dermatitis (lymphocytic infiltrate at the dermo-epidermal junction causing epidermal injury) Overlying epidermis often demonstrates liquefactive necrosis and degeneration, with dyskeratotic keratinocytes May also have dermoepidermal (subepidermal) bullae formation