Introduction
The skin is a complex organ, and yet the largest among other organs. The skin has various functions related to its composition. The division of the skin includes the epidermis, dermis, and hypodermis. The maturation of keratinocytes begins in an ascending order from basal cell layer to topmost corneal layer.
The epidermis consists of keratinocytes; melanocytes; dendritic Langerhans cells; Merkel cells. The keratinocytes synthesize keratin filaments to protect the skin. Melanocytes produce brown pigments to protect against sun ray. Langerhans cells provide cellular innate immune response; Merkel cells serve as mechanoreceptors and provide neuroendocrine functions.
Dermis consists of hair follicles; sebaceous glands; sweat glands; mast cells; small vessels; lymphatic vessels; nerves; dermal dendritic cells; fibroblasts. Hair follicles produce hair shafts, and also contain epithelial stem cells. Sweat glands assist in thermoregulation.
In the hypodermis-the final layer, there is the adipose, and loose connective tissue. When there is a disturbance in the homeostasis of skin tissue, skin pathologies develop.
Terminologies for describing skin pathologies
Macule: A flat, colored skin lesion <0.5cm.
Patch: A flat, colored skin lesion >0.5cm.
Papule: An elevated skin lesion <0.5cm.
Nodule: An elevated skin lesion >0.5cm.
Plaque: Fused papular skin lesion >0.5cm.
Vesicle/blister: An elevated fluid-filled skin lesion <0.5cm.
Bulla/blister: An elevated fluid-filled skin lesion >0.5cm
Excoriation: An epidermal lesion with a linear mark or deep scratch.
Lichenification: An area of thick & rough skin.
Pustule: An elevated pus-filled lesion.
Scale: A dry, hard area of skin.
Wheal: A temporary, itchy, red area on a skin due to edema.
Acantholysis: Loss of intercellular keratinocyte cohesion.
Acanthosis: Diffuse hyperplasia of the epidermis resulting in thickening.
Hyperkeratosis: Corneal layer thickening.
Parakeratosis: keratinization with retained nuclei in skin which is abnormal.
Freckle
Freckles are pigmented tan-red or light brown macular skin lesions that occur after sun exposure in light skin people. They begin in childhood, appearing in summer and fading in winter. They result from high amounts of melanin pigment in basal keratinocytes.
Lentigo
Lentigines are round, tan-brown patches or macular mucocutaneous lesions. They appear due to linear hyperplasia of melanocytes that secrete pigments in basal cell layer. Cause is unknown & unlike freckles, lesions don’t appear after sunlight exposure.
Melanocytic nevus/mole
Melanocytic nevi are brown, uniformly pigmented maculopapular benign lesions, with symmetrically well-defined round borders. Among other types are junctional & compound nevi.
Junctional nevi consist of aggregates/nests of melanocytic cells along dermo-epithelial junction. Compound nevi consist of nests or cords of melanocytic cells within the dermis, which are extensions from junctional nevi.
Pathogenesis: The reason stems from an acquired mutation in either BRAF or NRAS that encode Mitogen Activated Protein Kinases (MAP), RAF, RAS respectively. The activated mutation causes normal melanocyte proliferation, which is then followed by arrest of cell growth. Hence, why melanocytic nevi are rarely malignant.
Melanoma
The is a malignant tumor of melanocytes >1cm in diameter that usually affects sun-exposed skin areas. Other sites including eyes; esophagus; meninges & anogenital mucosal surfaces are also affected. They are highly invasive with metastasis to regional lymph nodes.
Gross presentation: They appear as shades of black, brown, dark blue, red lesions with irregular, rough borders.
Microscopic presentation: Malignant cells are larger than normal melanocytes with large nuclei that have irregular borders. Chromatins aggregate at nuclear periphery, and tumor cells aggregate to form nodules as they invade dermis.
Tumors may proliferate horizontally or vertically in which case, we measure their risk of metastasis using, Breslow thickness (depth of tumor invasion measuring distance from epidermal to intradermal layer).
Favorable prognostic factors: Breslow thickness <1.7mm; female gender; no/very fewer mitosis; active tumor-infiltrating lymphocyte response; absence of regression; location on extremity.
Predisposing factors: sun exposure; weak pigmentation gene (MC1R which encodes melanocortin 1 receptor; TYR-encodes tyrosine); Retinoblastoma gene (tumor suppressor) mutation. Risks are higher in light skin persons.
Clinical manifestations: asymptomatic (usually); pain and itching. Lesions appear on upper back in men, back and legs in females.
Seborrheic keratosis, Dermatosis papulosa nigra
These are round, tan to dark brown, coin-like plaques with granular surfaces. They affect individuals 40 years & above. Dermatosis papulosa nigra presents as multiple, small similar lesions on the face, especially in dark skin people.
Histologically, the skin is hyperkeratotic. Here, groups of small cells resembling basal cells (basaloid cells), contain much keratin to form a “horn” cyst. When these cysts communicate with a hyper-keratinized epidermal external surface, they form ‘’pseudo-horn’’ cysts.
Diagnosis: Inspection with a hand lens reveals pore-like surfaces on skin impacted by keratinized surface plugs.
Causes: They are caused by activating mutation in fibroblast growth factor-receptor-3 gene. These lesions are found around trunk (usually); extremities; head & neck.
Acanthosis Nigrans
A thick, hyperpigmented skin lesion with a soft, smooth or relatively rough texture. It may be an autosomal dominant trait seen in childhood or puberty. It can be seen in association with obesity, diabetes, pituitary & pineal tumors, gastrointestinal adenocarcinomas.
Histologically, the basal cell layer shows proliferation, hyperkeratosis, & hyperpigmentation. They are common in skin folds of axillae, anogenital, neck, & groin.
Cylindroma, Trichoepithelioma, & Syringoma
These are benign tumors affecting supporting structures of the skin including hair follicules, & sweat glands. They are flesh-colored, single or multiple papular/nodular lesions.
Cylindromas are composed of proliferating glandular-like basaloid cells with apocrine or eccrine differentiation found on the scalp & forehead.
Trichoepitheliomas consist of nests of proliferating basaloid cells (basal-cell looking) that form structures similar to early hair follicles. They often occur around perinasal regions. Syringomas occur around the lower eyelids and they show eccrine features.
Actinic keratosis, Actinic cheilitis
This is a premalignant lesion of the epidermis affecting sun exposed areas including face, dorsum of hand, arm, lip. It is actinic cheilitis when it affects outer lips.
Predisposing factors: sunlight; therapeutic radiation; industrial hydrocarbons & arsenics.
Signs: It appears as tan-brown, red lesion <1cm in diameter, with a rough sandpaper-like consistency.
Histologically, there is hyperplasia of basal cell keratinocytes with abnormal keratinization making them atypical cells. These atypical cells are associated with hyperkeratosis & parakeratosis. In contrast to basal cell carcinoma, cell bridges are visible.
Squamous cell carcinoma, Keratoacanthoma
Squamous cell carcinoma is the 2nd most common invasive skin cancer, common in older people. It affects sun exposed areas of face, lip, arm, dorsum of hand, legs, cutaneous head & neck region & very few metastasize to regional lymph nodes.
Sign: It appears as a sharply defined, red, scaling plaque in non-invasive carcinoma in-situ (affecting epidermal full thickness). In an invasive lesion, it is nodular, & scaly with ulceration.
Histologically, tumor cells may vary from well differentiated keratinized polygonal cells to anaplastic keratinocytes.
Risk factors: sunlight (damages DNA); p53 mutation (defective DNA repair) immunosuppression; HPV 5 & 8; industrial tars & oils; chronic skin ulcers; old burn scars; ingestion of arsenicals; ionizing radiation; tobacco & chewing betel nuts (for oral squamous cancers).
Keratoacanthoma is benign lesion that is cup-shaped, with central depression filled with keratin debris they heal spontaneously. Results from abnormal proliferation of epidermal cells. Histologically, the squamous cells are hyper-keratinized with corneum abnormally retaining nucleus.
Basal cell carcinoma
These are the most common invasive & slow growing skin cancer that rarely metastasize. They appear as pearly shaped papules or nodular lesions with dilated subepidermal blood vessels. It may be associated with xeroderma pigmentosa.
Predisposing factors: p53 gene mutation; sunlight; immunosuppression.
Histologically, cells are composed of nests of basaloid cells within the dermis, separated from adjacent stroma by a thin space.
Ichthyosis
This skin disorder results from excess build-up of keratin on the epidermis resulting in a fish-like scale. This condition may result from a defective desquamation process, which causes corneocytes (dead keratinocytes) to stick together continuously.
Histologically, there is the loss of basket weave pattern of the stratum corneum, resulting in a much-compacted pattern.
Urticaria, Angioedema
Urticaria is an acute inflammatory skin response that results from mast cell degranulation and dermal vascular hyperpermeability. Lesion lats <24 hrs. & may have persistent episodes.
Signs: wheals (small pruritic papules or edematous plaques), which may come in ring, arch, or linear forms. It often affects trunk, extremities, ear.
Predisposing factors: IgE-dependent exposure to pollen, dust, food, insect venom, drugs; IgE-independent exposure to certain antibiotic, contrast agents, opiates; inherited deficiency of C1 inhibitor results in overactivation of complement system.
Histologically, epithelium is normal. There is edema in the superficial dermis & spaces exist between collagen bundles.
Angioedema is a tissue edema affecting both the dermis and hypodermis from various inflammatory stimuli. Predisposing factors is same as in urticaria. The face and upper extremities are often affected.
Eczematous dermatitis
This is an acute skin reaction that presents as red, papulovesicular oozing, crusting lesion, which overtime becomes a scaling plaque. It may be pruritic sometimes.
Causes & predisposing factors: irritants (poison ivy/oak; detergents; jewelries; soaps); allergens (dust mites; pollens; food; drugs); sunlight.
Histologically, edema from the superficial dermis, extends into the epidermis, separating apart keratinocytes, especially in the stratum spinosum.
Erythema multiforme (EM); Steve-Johnson syndrome; Toxic epidermal necrolysis
Erythema multiforme is an acute self-limiting hypersensitivity reaction that frequently affects extremities, & may be found around the body. It is associated with infections, drugs, malignancies & connective tissue diseases.
Predisposing factors: mycoplasmal infections; herpes simplex; histoplasmosis; coccidioidomycosis; typhoid; leprosy; sulfonamides; penicillin; barbiturates; hydantoins; antimalarials; carcinomas; lymphomas; SLE; dermatomyositis; polyarteritis nodosa.
Signs: It presents as an erythematous macule or papule with a pale, vesicular or eroded center.
Steven-Johynson syndrome is an extensive form of EM that often affects children. In addition, there is fever, erosion and hemorrhagic crust affecting mucosa of lips & mouth, including other body parts.
Toxic epidermal necrolysis which is also another form of EM, presents as a more extensive necrosis, & shedding of the mucocutaneous membrane.
Psoriasis
This is a chronic inflammatory reaction that most often affects cutaneous areas of elbow, knee, scalp, intergluteal cleft, glans penis, & lumbosacral region. It is sometimes associated with arthritis; spondylitic joint disease; enteropathy; AIDS.
Predisposing factors: HLA-C allele; trauma-induced local inflammatory reaction (Koebner phenomenon). Individuals with HLA-C allele are hypersensitive, which causes skin infiltration by inflammatory T-cells, cytokines (TNF) & growth factor production.
Signs: well-demarcated pinkish-orange plaque covered by loosely adherent silver-white scale. Nail changes include yellow-brown discoloration; pitting; onycholysis.
Histologically, there is increase in epidermal cell turnover, causing epidermal hyperplasia and thickening with parakeratotic scale.
Seborrheic dermatitis
This is a chronic inflammatory lesion presenting as a reddish-yellow and greasy lesion with macules, papules, scaling and crusting. It often affects the scalp, nasolabial folds, forehead, retro auricular areas, external auditory canal.
When the scalp is affected in infants it is called cradle cap, and >1 year of age, it is called dandruff.
Predisposing factor: Malassezia fur (a yeast)
Lichen planus
This is a self-limiting chronic inflammatory lesion that affects the oral mucosa and the skin. The cause is unknown, but there are lymphocyte infiltrates in the dermo-epidermal junction, & Langerhans cells hyperplasia.
Signs: They appear as pruritic, flat, purple, papular plaques with white lacelike patterns or fine white dots called Wickham striae. Lesions may be dark-brown in persons with dark complexion.
Pemphigus vulgaris
This is the most common blistering disorder that affects the oral mucosa & skin including scalp, face, groin, axilla, extremities. It affects persons between 30 & 60 yrs.
Signs: It presents as superficial vesicles & bullae that over time, rupture and crusts. Treatment requires immunosuppressive agents.
Causes: IgG against desmoglein (protein component of desmosome), that holds epidermal cells together.
Histologically, there is acantholysis- breakdown of intercellular adhesion among squamous epithelium immediately above basal cell layer. This allows for intraepidermal fluid accumulation (blisters).
Bullous pemphigoid
This is also a blistering disorder which may affect the skin and oral mucosa. It usually affects people older than 70, & inner thigh surfaces, anterior forearm, lower abdomen, axilla, groin are regions affected most.
Signs: It presents as a relatively stiff bulla >0.5cm to about 8cm, containing clear fluid. On applying minimal pressure, the bullae don’t rupture easily & hardly ulcerate unless secondarily infected.
Causes: IgG reaction against Bullous Pemphigoid Antigen (BPAG-2)-a protein component of hemidesmosome that connects basal cells to basement membrane.
Histologically, there is subepidermal cleft, basal membrane damage, subepidermal blisters & superficial dermal edema.
Dermatitis herpetiformis
This is a blistering disorder that mainly affects male btw. 30 & 40 yrs & is associated with celiac disease. The lesion is bilaterally symmetrical in extensor surfaces of forearm, elbows, knees, buttocks & upper back.
Signs: They present as a pruritic erythematous vesicles & plaques that erode after blister ruptures.
Causes: IgA cross-reacts with reticulin- a component of anchoring fibrils that attach epidermal basement membrane to superficial dermis. Histologically, there is subepidermal blister formation.
Acne vulgaris
This is an epidermal lesion commonest among adolescents, due to physiologic androgenic hormonal changes & alterations in hair follicles & sebaceous glands. There are inflammatory or non-inflammatory acne.
In non-inflammatory acne, there are open & closed comedones. Open comedones are follicular papules with a central black keratin plug. It results from keratinization of follicular infundibulum and blockage of sebaceous gland duct by keratin plugs.
Closed comedones are follicular papules without any visible keratin plugs. Possibly due to increased activity of sebaceous gland.
In an inflammatory acne, there is an erythematous papule or nodule with pustules, due to Propionibacterium acnes (colonizes hair follicles).
Predisposing factors: drugs including: corticosteroids; adrenocorticotropic hormone; gonadotropins; contraceptives; trimethadione; iodides; bromides. Other factors may include tropical climates; heavy clothing; cosmetics.
Severe acne can be treated with isotretinoin (a Vit. A derivative).
Rosacea
This is a chronic inflammatory disorder of the hair follicle and sebaceous gland. It usually affects females 40 years and above on the face.
Causes: It results from inappropriate activation of the innate immune system by high cutaneous cathelicidin-an antimicrobial peptide.
Signs: flushing, persistent erythematous skin area with papules, pustules, & rhinophyma. Rhinophyma is a thickening of nasal skin due to merging papules & follicular erections.
Verruca vulgaris; Verruca plana; Verruca palmaris; Verruca plantaris; Venereal wart
These are lesions caused by Human papilloma viruses, and transmission occurs by contact, or self-infection. HPV 6 & 11 cause mainly the venereal warts. HPV 16 increases risk for genital cancer.
Verruca vulgaris is common on the dorsal surfaces of hands. It presents as a gray-white to tan flat or convex papule btw 1mm & 10mm with a rough surface.
Verruca plana is common on the face or dorsal surfaces of the hands. It presents as a smooth surfaced, flat, tan papule smaller than vulgaris.
Verruca palmaris & plantaris affect the palms and soles respectively. They present as rough, scaly, tan papules between 1mm & 20mm in diameter that may merge together.
Venereal warts affect urethra, perianal areas, rectum, penis, female genitalia. They present as soft tan cauliflower masses.
Histologically, superficial epidermal cells undergo verrucous or papillomatous hyperplasia, with a perinuclear halo in individual cells (koilocytosis). Koilocytosis is seen is HPV infections.
Impetigo
This is a superficial bacterial infection of the skin by staphylococcus aureus. It usually affects children, and occasionally adults. The skin of face and hands are commonly affected.
Signs: It presents as a honey-colored crust (an erythematous macule, with several pustules which break to leave a crust).
Tinea capitis; Tinea corporis; Tinea cruris; Tinea pedis; Onychomycosis
These are superficial infections, limited to stratum corneum caused primarily by the fungus, dermatophytes.
Tinea capitis is the infection of the scalp commonly seen in children. It presents as areas of hairless patches of skin, with mild erythema, scales and crusts.
Tinea corporis is the infection of body surfaces, that commonly affects children and occasionally people of other ages. It presents as an expanding, round, mildly erythematous plaque with an elevated scaling border.
Predisposing factors of tinea corporis include: include heat; high humidity; chronic dermatophytosis of feet/nails; contact with infected animals.
Tinea cruris is the infection of the inguinal area amongst higher-weight individuals. They present as moist, red patches with elevated scaly borders. Predisposing factors include heat, friction.
Tinea pedis is the infection of the foot, around the web spaces with a secondary bacterial infection. It presents as an area of diffuse erythema and scaling.
Onychomycosis is the infection of the nails & presents as discoloration, deformation, & thickening of nail plate.
Tinea versicolor
This is a yeast infection by Malassezia furfur. It usually affects the upper trunk and presents as a macule that is lighter or darker than surrounding skin.