Inflammatory Skin Diseases PDF

Inflammatory skin diseases Function barrier for microorganisms limit water loss thermoregulation immune regulation protection against ultraviolet light Histology Epidermis composed of a multilayered sheet of keratin-producing cells keratinocytes Histology Histology Histology Melanocytes a...

Inflammatory skin diseases Function barrier for microorganisms limit water loss thermoregulation immune regulation protection against ultraviolet light Histology Epidermis composed of a multilayered sheet of keratin-producing cells keratinocytes Histology Histology Histology Melanocytes are dendritic cells of neural crest origin Langerhans cells carry antigenic cargo to regional lymph nodes and initiate immune responses Merkel cells are specialized cells in the skin that are important for proper neural encoding of light touch stimuli Nomenclature of skin lesions-Macroscopic Excoriation: Traumatic lesion breaking the epidermis and causing a raw linear area (i.e., deep scratch); often self-inflicted Nomenclature of skin lesions-Macroscopic Lichenification: Thickened, rough skin usually the result of repeated rubbing lichen on a rock Nomenclature of skin lesions-Macroscopic Macule, patch: Circumscribed, flat lesion distinguished from surrounding skin by color. macule ≤ 5 mm patch > 5 mm Nomenclature of skin lesions-Macroscopic Papule, nodule: Elevated dome-shaped or flat-topped lesion papule ≤ 5 mm nodule > 5 mm Nomenclature of skin lesions-Macroscopic Plaque: Elevated flat-topped lesion, usually greater than 5 mm in diameter (may be formed by coalescence of papules) Scale: Dry, horny, plate like excrescence; usually the result of imperfect cornification Nomenclature of skin lesions-Macroscopic Pustule: Discrete, pus-filled, raised lesion Wheal: Itchy, transient, elevated lesion with variable blanching and erythema formed as the result of dermal edema Nomenclature of skin lesions-Macroscopic Vesicle, bulla, blister: Fluid-filled raised lesion. Blister is the common term for both lesions. vesicle ≤ 5 mm bulla > 5 mm Nomenclature of skin lesions-Microscopic Acanthosis: Diffuse epidermal hyperplasia Hyperkeratosis: Thickening of the stratum corneum Parakeratosis: nuclei (+) Orthokeratosis: nuclei (-) Nomenclature of skin lesions-Microscopic Dyskeratosis: Abnormal, premature keratinization within cells below the stratum granulosum Nomenclature of skin lesions-Microscopic Spongiosis: Intercellular edema of the epidermis Acantholysis: Loss of cohesion between keratinocytes PART I ACUTE INFLAMMATORY DERMATOSES Acute inflammatory dermatoses last days to weeks characterized by inflammation, edema, and sometimes epidermal, vascular, or subcutaneous injury some may persist, transitioning to a chronic phase; others are selflimited Acute inflammatory dermatoses-1-Urticaria Clinical features: common disorder 20-40 years of age lesions usually develop and fade within hours episodes can persist for days or even months small, pruritic papules to large, edematous, erythematous plaques localized or generalized most cases respond to antihistamines, but may require treatment with leukotriene antagonists, monoclonal antibodies or immunosuppressive drugs Acute inflammatory dermatoses-1-Urticaria Pathogenesis: Type 1 hypersensitivity rxn Antigens include viruses, pollens, foods, drugs, and insect venom IgE-independent urticaria can result from exposure to substances that directly incite mast cell degranulation, such as opiates and certain antibiotics In the vast majority of cases, no clinical cause is discovered even with extensive investigation Acute inflammatory dermatoses-1-Urticaria Morphology: Often subtle Sparse superficial infiltrate of mononuclear cells, rare neutrophils, and sometimes eosinophils Superficial dermal edema Acute inflammatory dermatoses-2-Acute eczematous dermatoses «Eczema» is a clinical term that embraces a number of conditions with varied underlying etiologies. «spongiotic dermatitis» is a histopathologic term that encompass all «eczematous dermatoses» Acute inflammatory dermatoses-2-Acute eczematous dermatoses Clinical features: new lesions take the form of erythematous papules, often with overlying vesicles with persistence, these lesions coalesce into raised, scaling plaques nature and degree of these changes vary among the clinical subtypes Acute inflammatory dermatoses-2-Acute eczematous dermatoses Allergic contact dermatitis: topical exposure to an allergen and is caused by «delayed hypersensitivity reactions». Atopic dermatitis: formerly attributed to allergen exposure, now thought to often stem from defects in keratinocyte barrier function, defined as skin with increased permeability to substances to which it is exposed, such as potential antigens Drug-related eczematous dermatitis: hypersensitivity reaction to a drug Photoeczematous dermatitis: appears as an abnormal reaction to UV or visible light Primary irritant dermatitis: exposure to substances that chemically, physically, or mechanically damage the skin Acute inflammatory dermatoses-2-Acute eczematous dermatoses While atopic dermatitis reflects a genetic predisposition and can persist for years or decades, other forms of eczematous dermatitis resolve completely when the offending stimulus is removed or exposure is limited, stressing the importance of investigating the underlying cause. Acute inflammatory dermatoses-2-Acute eczematous dermatoses Susceptibility to atopic dermatitis is often inherited Usually appears in early childhood and remits spontaneously as patients mature into adults. Children with atopic dermatitis often have asthma and allergic rhinitis. Acute inflammatory dermatoses-2-Acute eczematous dermatoses Pathogenesis: Allergic contact dermatitis is triggered by exposure to an environmental contact-sensitizing agent, that chemically reacts with self-proteins, creating neoantigens that can be recognized by the T cell arm of the adaptive immune system. The self-proteins are processed by epidermal Langerhans cells, which migrate to draining lymph nodes and present the antigen to naïve T cells. This sensitization event leads to memory; on reexposure to the antigen, the activated memory CD4+ T lymphocytes migrate to the affected skin sites during the course of normal circulation. There they release cytokines that recruit additional inflammatory cells and also mediate epidermal damage, as in any «delayed-type hypersensitivity» reaction. Acute inflammatory dermatoses-2-Acute eczematous dermatoses Morphology: Spongiosis: edema splays apart keratinocytes, intercellular bridges are stretched and become more prominent superficial perivascular lymphocytic infiltrate, dermal edema eosinophils may be present in general the histologic features are similar regardless of cause, emphasizing the need for careful clinical correlation. Acute inflammatory dermatoses-3-Erythema multiforme Clinical features: uncommon, usually self-limited wide array of lesions, including macules, papules, vesicles, and bullae (hence the term «multiforme»). well-developed lesions have a characteristic “targetoid” appearance Acute inflammatory dermatoses-3-Erythema multiforme has a broad range of severity forms associated with infection (most often herpesvirus) are less severe Erythema multiforme caused by medications may progress to more serious eruptions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis. These forms can be life-threatening, as they may cause sloughing of large portions of the epidermis, resulting in fluid loss and infections complications similar to those seen in burn-injured patients. Acute inflammatory dermatoses-3-Erythema multiforme Pathogenesis: appears to be a hypersensitivity response to certain infections and drugs Infections: herpes simplex, mycoplasma, and some fungi Drugs: sulfonamides, penicillin, salicylates, hydantoins, and anti-malarials Characterized by epithelial injury mediated by skin-homing CD8+ cytotoxic T lymphocytes. The cytotoxic T cell attack is focused on the basal cells of cutaneous and mucosal epithelia, presumably due to recognition of still unknown antigens. Certain human lymphocyte antigen (HLA) haplotypes are associated with the disease. Acute inflammatory dermatoses-3-Erythema multiforme Morphology: Early lesions: superficial perivascular lymphocytic infiltrate lymphocytes along the dermoepidermal junction «interface dermatitis» apoptotic keratinocytes dermal edema Acute inflammatory dermatoses-3-Erythema multiforme With time; discrete, confluent zones of basal epidermal necrosis appear, with concomitant blister formation Acute inflammatory dermatoses-3-Erythema multiforme More severe forms: Steven’s Johnson Syndrome (10% of the skin is involved) and toxic epidermal necrolysis (30% of skin is involved) necrosis extends through the full thickness of the epidermis PART II CHRONIC INFLAMMATORY DERMATOSES Chronic inflammatory dermatoses Chronic inflammatory dermatoses are persistent skin conditions that exhibit their most characteristic features over many months to years, although they may begin with an acute stage. The skin surface in some chronic inflammatory dermatoses is roughened as a result of excessive or abnormal scale formation and shedding. Chronic inflammatory dermatoses-1-Psoriasis Clinical features: common chronic inflammatory dermatosis 1% to 2% of individuals in USA associated with an increased risk for heart attack and stroke, a relationship that may be related to a chronic inflammatory state also associated in up to 10% of patients with arthritis Chronic inflammatory dermatoses-1-Psoriasis well-demarcated, pink to salmon– colored plaque covered by loosely adherent silverwhite scale elbows, knees, scalp, lumbosacral areas, intergluteal cleft, glans penis, and vulva. nail changes occur in 30% of cases. mostly limited in distribution, but it can be widespread and severe. clinical subtypes are defined by pattern of involvement and severity. Chronic inflammatory dermatoses-1-Psoriasis lesions can be induced in susceptible individuals by local trauma (Koebner phenomenon) Genome-wide association studies have linked an increased risk for psoriasis to polymorphisms in HLA loci and genes affecting antigen presentation, TNF signaling, and skin barrier function. Chronic inflammatory dermatoses-1-Psoriasis Pathogenesis: a T cell-mediated inflammatory disease, presumed to be autoimmune in origin, although the antigens are not well described. Both genetic (HLA types and other susceptibility loci) and environmental factors contribute to the risk. It is unclear whether the inciting antigens are self-antigens, environmental antigens, or some combination of the two. Chronic inflammatory dermatoses-1-Psoriasis Sensitized populations of T cells home to the dermis, including CD4+ TH17 and TH1 cells and CD8+ T cells, and accumulate in the epidermis. These cells secrete cytokines and growth factors that induce keratinocyte hyperproliferation, resulting in the characteristic lesions. Chronic inflammatory dermatoses-1-Psoriasis Morphology: marked epidermal thickening (acanthosis), with regular downward elongation of the rete ridges increased epidermal cell turnover and lack of maturation results in loss of the stratum granulosum and extensive parakeratosis Chronic inflammatory dermatoses-1-Psoriasis Kogoj microabscess: neutrophils within epidermis Munro microabscess: neutrophilic aggregates in stratum corneum Chronic inflammatory dermatoses-1-Psoriasis thinning of the epidermal cell layer overlying the tips of dermal papillae dilated and tortuous blood vessels within the papillae. these vessels bleed readily when the scale is removed, giving rise to multiple punctate bleeding points (Auspitz sign) Chronic inflammatory dermatoses-2-Lichen Planus Clinical Features: “Pruritic, purple, polygonal, planar papules, and plaques” these papules are highlighted by white dots or lines termed Wickham striae. middle-aged adults multiple lesions, usually symmetrically distributed Hyperpigmentation Chronic inflammatory dermatoses-2-Lichen Planus extremities, wrists and elbows, vulva and glans penis. 70% of cases also involve the oral mucosa, where the lesions manifest as white papules with a reticulate or netlike appearance lesions usually resolve spontaneously within 1 to 2 years, but the oral lesions may persist Chronic inflammatory dermatoses-2-Lichen Planus Pathogenesis: may result from a CD8+ T cell–mediated cytotoxic response against antigens in the basal cell layer and the dermoepidermal junction that are produced by unknown mechanisms, perhaps as a consequence of a viral infection or drug exposure. Chronic inflammatory dermatoses-2-Lichen Planus Morphology: prototypical interface dermatitis the inflammation and damage are concentrated at the interface of the squamous epithelium and papillary dermis. lymphocytes are intimately associated with basal keratinocytes Civatte (colloid) bodies: Anucleate, necrotic basal cells Chronic inflammatory dermatoses-2-Lichen Planus well-developed changes of chronicity: acanthosis, hypergranulosis, hyperkeratosis dermoepidermal interface has a zigzag contour=sawtoothing basal cells looks like more mature cells of the stratum spinosum= squamatization Chronic inflammatory dermatoses-3-Lichen simplex chronicus Clinical Features: lesions often are raised, erythematous, and scaly and can be mistaken for keratinocytic neoplasms manifests as roughening of the skin, which takes on an appearance reminiscent of lichen on a tree. is a response to local repetitive trauma, usually from rubbing or scratching nodular forms exist that are referred to as prurigo nodularis Chronic inflammatory dermatoses-3-Lichen simplex chronicus Pathogenesis: not understood, but the trauma probably induces epithelial hyperplasia and eventual dermal scarring. Lichen simplex chronicus can be superimposed on and mask another (often pruritic) dermatosis. It is therefore important to rule out an underlying cause while recognizing that the lesion may be entirely trauma-related. Chronic inflammatory dermatoses-3-Lichen simplex chronicus Morphology: acanthosis, hyperkeratosis, and hypergranulosis elongation of the rete ridges, fibrosis of the papillary dermis, and a dermal chronic inflammatory infiltrate these lesions are similar in appearance to normal volar (palms and soles) skin, in which skin thickening serves as an adaptation to repetitive mechanical stress. Summary: • Many specific inflammatory dermatoses exist and can be mediated by IgE antibodies (urticaria), antigen-specific T cells (eczema, erythema multiforme, and psoriasis), or trauma (lichen simplex chronicus). • Underlying genetic susceptibility plays a role in atopic dermatitis and psoriasis. • Clinical correlation is essential to diagnose specific skin diseases, since many have overlapping, nonspecific histologic features. Part III INFECTIOUS DERMATOSES Infectious dermatoses-Bacterial infections Numerous bacterial infections occur in skin. These range from superficial infections known as impetigo, to deeper dermal abscesses associated with puncture wounds that are caused by bacteria such as Pseudomonas aeruginosa. Infectious dermatoses-Bacterial infections Impetigo: Clinical features: one of the most common bacterial infections of the skin, is seen primarily in children causative organism is usually Staphylococcus aureus or, less commonly, Streptococcus pyogenes Infectious dermatoses-Bacterial infections Impetigo: Clinical features: typically acquired through direct contact with a source often begins as a single small macule, usually on the extremities or the face near the nose or the mouth, which rapidly evolves into a larger often with a honey-colored crust of dried serum Individuals who are colonized by S. aureus or S. pyogenes are more likely to be affected. less common bullous form of childhood impetigo may mimic an autoimmune blistering disorder. Infectious dermatoses-Bacterial infections Impetigo: Morphology: accumulation of neutrophils beneath the stratum corneum, subcorneal pustule nonspecific reactive epidermal alternation superficial dermal inflammation accompany these findings. Bacterial cocci in the superficial epidermis can be demonstrated by Gram stain. Infectious dermatoses-Fungal infections range from superficial infections with Tinea or Candida spp. to life-threatening Aspergillus spp. infections in immunosuppressed individuals can be superficial (stratum corneum, hair, and nails), deep (dermis or subcutis), or systemic, the last type arising through hematogenous spread, often in an immunocompromised patient. Infectious dermatoses-Fungal infections Clinical Features: superficial infections usually produce erythematous macules with superficial scale that can be pruritic superficial fungal infections may have an annular appearance; also may induce lesions that mimic other psoriasiform or eczematous dermatoses, so it is important to consider the possibility of fungal infection when these conditions are in the differential diagnosis Infectious dermatoses-Fungal infections deeper infections such as those seen with Aspergillus spp. are erythematous and often nodular and sometimes associated with local hemorrhage Infectious dermatoses-Fungal infections Morhology: histologic appearance varies depending on the organism, host response, and degree of superinfection. superficial infections are often associated with a neutrophilic infiltrate in the epidermis. Periodic acid–Schiff (PAS) and Gomori methenamine silver stains are helpful in identifying the fungal organisms. Infectious dermatoses-Fungal infections Deep fungal infections produce greater tissue damage and often elicit a granulomatous response. Aspergillus can be angioinvasive. Infectious dermatoses-Verrucae (Warts) proliferative lesions of squamous epithelial cells that are caused by human papillomavirus (HPV). most common in children and adolescents, but may be encountered in any age group. HPV infection usually stems from direct contact with an infected individual or autoinoculation. Verrucae generally are self-limited, most often regressing spontaneously within 6 months to 2 years. Infectious dermatoses-Verrucae (Warts) Pathogenesis: cutaneous warts are mainly caused by low-risk HPV subtypes that lack transforming potential. Different kinds of warts are identified on the basis of their gross appearance and location and generally are caused by distinct HPV subtypes. Infectious dermatoses-Verrucae (Warts) Verruca plantaris and verruca palmaris occur on the soles and palms, respectively. These rough, scaly lesions can reach 1 to 2 cm in diameter and may coalesce to form a surface that can be confused with ordinary calluses. Condyloma acuminatum (venereal wart) occurs on the penis, female genitalia, urethra, and perianal areas. Infectious dermatoses-Verrucae (Warts) Clinical features: Verruca vulgaris: can occur anywhere but is found most frequently on the hands, a gray-white to tan, flat to convex, 0.1- to 1-cm papule with a rough, pebble like surface. Verruca plana (flat wart): common on the face or dorsal surfaces of the hands . Infectious dermatoses-Verrucae (Warts) Pathogenesis: Like high-risk HPV, low-risk viruses express viral E6 and E7 oncoproteins that lead to dysregulated epidermal cell growth and increased survival. Because the growth of warts is normally halted by the immune response, immunodeficiency is associated with more numerous and larger verrucae. Infectious dermatoses-Verrucae (Warts) Morphology: epidermal hyperplasia; verrucous or papillomatous epidermal hyperplasia cytoplasmic vacuolization (koilocytosis) Infected cells also may demonstrate prominent keratohyalin granules and jagged eosinophilic intracytoplasmic protein aggregates as a result of impaired maturation Part IV BLISTERİNG/BULLOUS DISEASES Blistering/Bullous diseases vesicles and bullae (blisters) occur as secondary phenomena in several unrelated conditions (e.g., herpesvirus infection, spongiotic dermatitis), a group of disorders in which blisters are the primary and most distinctive feature, blistering in these diseases tends to occur at specific levels within the skin, a morphologic distinction that is critical for diagnosis Blistering/Bullous diseases-Pemphigus (Vulgaris and Foliaceus) an uncommon autoimmune blistering disorder resulting from loss of normal intercellular attachments within the epidermis and the squamous mucosal epithelium three major variants: • Pemphigus vulgaris (the most common type) • Pemphigus foliaceus • Paraneoplastic pemphigus Blistering/Bullous diseases-Pemphigus (Vulgaris and Foliaceus) Pathogenesis: Pemphigus vulgaris and pemphigus foliaceus are autoimmune diseases caused by antibody-mediated (type II) hypersensitivity reactions. The pathogenic antibodies are IgG autoantibodies that bind to intercellular desmosomal proteins (desmoglein types 1 and 3) found in the skin and mucous membranes. The antibodies disrupt the intercellular adhesive function of desmosomes and may activate intercellular proteases. Blistering/Bullöz hastalıklar -Pemphigus (Vulgaris and Foliaceus) Blistering/Bullous diseases- Pemphigus (Vulgaris and Foliaceus) The distribution of desmoglein proteins within the epidermis determines the location of the lesions. By direct immunofluorescence study, lesional sites show a characteristic fishnet-like pattern of intercellular IgG deposits. As with many other autoimmune diseases, pemphigus is associated with particular HLA alleles. Blistering/Bullous diseases-Pemphigus (Vulgaris and Foliaceus) Morphology: Pemphigus vulgaris involves both mucosa and skin, especially on the scalp, face, axillae, groin, trunk, and points of pressure. The lesions are superficial flaccid vesicles and bullae that rupture easily, leaving deep and often extensive erosions covered with a serum crust. Blistering/Bullous diseases- Pemphigus (Vulgaris and Foliaceus) Pemphigus foliaceus, a rare, milder form of pemphigus, results in bullae that are mainly confined to the skin, with only infrequent involvement of mucous membranes. The blisters in this disorder are superficial, such that more limited zones of erythema and crusting of ruptured blisters are seen Blistering/Bullöz hastalıklar -Pemphigus (Vulgaris and Foliaceus) Acantholysis: lysis of the intercellular adhesive junctions between neighboring squamous epithelial cells that results in the rounding up of detached cells Blistering/Bullöz hastalıklar -Pemphigus (Vulgaris and Foliaceus) Pemphigus vulgaris: acantholysis involves the layer of cells immediately above the basal cell layer= suprabasal acantholytic blister Variable superficial dermal infiltrates composed of lymphocytes, macrophages, and eosinophils accompany all forms of pemphigus. Blistering/Bullöz hastalıklar -Pemphigus (Vulgaris and Foliaceus) In pemphigus foliaceus, acantholysis selectively involves the superficial epidermis at the level of the stratum granulosum. Blistering/Bullöz hastalıklar -Pemphigus (Vulgaris and Foliaceus) Blistering/Bullous diseases-Bullous Pemphigoid Bullous pemphigoid is another distinctive acquired blistering disorder with an autoimmune basis. Bullous pemphigoid and pemphigus vulgaris are caused by similar pathogenic mechanisms, but differ in their clinical presentation and course due to variation in the location of the target antigen (hemidesmosomes in bullous pemphigoid, desmosomes in pemphigus). Blistering/Bullous diseases-Bullous Pemphigoid Clinical features: The lesions of bullous pemphigoid do not rupture as readily as in pemphigus and, if uncomplicated by infection, heal without scarring. The disease tends to follow a remitting and relapsing course and responds to topical or systemic immunosuppressive agents. Gestational pemphigoid (also known as herpes gestationis, a misnomer since there is no viral etiology) is a clinically distinct subtype that appears suddenly during the second or third trimester of pregnancy. It also is caused by autoantibodies against bullous pemphigoid antigen. Gestational pemphigoid typically resolves after childbirth, but may recur with subsequent pregnancies. Blistering/Bullous diseases-Bullous Pemphigoid Pathogenesis: Blistering in bullous pemphigoid is triggered by the linear deposition of autoreactive IgG antibodies and complement in the epidermal basement membrane. Reactivity also occurs in the basement membrane attachment plaques (hemidesmosomes), where most bullous pemphigoid antigen (most commonly type XVII collagen) is located. The proteins that are recognized by the autoantibodies have structural roles in dermoepidermal adhesion. IgG autoantibodies to hemidesmosome components fix complement and cause tissue injury by recruiting neutrophils and eosinophils. Blistering/Bullous diseases-Bullous Pemphigoid Blistering/Bullous diseases-Bullous Pemphigoid Morphology: tense subepidermal bullae filled with clear fluid epidermis characteristically lacks acantholysis blister roof consists of full-thickness epidermis with intact intercellular junctions, a key distinction from the blisters seen in pemphigus. Blistering/Bullous diseases-Bullous Pemphigoid Early lesions show variable numbers of eosinophils at the dermal-epidermal junction, occasional neutrophils, superficial dermal edema, and associated basal cell layer vacuolization. Blistering/Bullous diseases -Dermatitis Herpetiformis Dermatitis herpetiformis is an autoimmune blistering disorder associated with gluten sensitivity that is characterized by extremely pruritic grouped vesicles and papules. The disease affects predominantly males, often in the third and fourth decades of life. Up to 80% of cases are associated with celiac disease; conversely, only a small fraction of patients with celiac disease develop dermatitis herpetiformis. like celiac disease, dermatitis herpetiformis responds to a gluten-free diet. lesions of dermatitis herpetiformis are bilateral, symmetric, and grouped and preferentially involve the extensor surfaces, elbows, knees, upper back, and buttocks . Blistering/Bullous diseases -Dermatitis Herpetiformis Pathogenesis: Genetically predisposed individuals develop IgA antibodies to dietary gluten (derived from the wheat protein gliadin) as well as IgA autoantibodies that cross-react with endomysium and tissue transglutaminases, including epidermal transglutaminase expressed by keratinocytes. Blistering/Bullous diseases -Dermatitis Herpetiformis direct immunofluorescence, the skin shows discontinuous, granular deposits of IgA selectively localized in the tips of dermal papillae. resultant injury and inflammation produce a subepidermal blister. Blistering/Bullous diseases -Dermatitis Herpetiformis Morphology: Initially, neutrophils accumulate selectively at the tips of dermal papillae, forming small microabscesses The basal cells overlying these microabscesses show vacuolization and focal dermoepidermal separation that ultimately coalesce to form a true subepidermal blister. Acne Vulgaris • Virtually universal in the middle to late teenage years, • Affects both males and females, although males tend to have more severe disease. • is seen in all races but is usually milder in people of Asian descent. • may be induced or exacerbated by drugs (corticosteroids, adrenocorticotropic hormone, testosterone, gonadotropins, contraceptives, trimethadione, iodides, and bromides), occupational exposures (cutting oils, chlorinated hydrocarbons, and coal tars), and conditions that favor occlusion of sebaceous glands, such as heavy clothing, cosmetics, and tropical climates. • Some families seem to be particularly prone to acne, suggesting a hereditary component. Acne Vulgaris • Acne is divided into noninflammatory and inflammatory types, although both types may coexist. Noninflammatory acne may take the form of open and closed comedones. • Open comedones are small follicular papules containing a central black keratin plug. This color is the result of oxidation of melanin pigment (not dirt). • Closed comedones are follicular papules without a visible central plug. Because the keratin plug is trapped beneath the epidermal surface, these lesions are potential sources of follicular rupture and inflammation. Acne Vulgaris • The pathogenesis of acne is incompletely understood and is likely multifactorial. • At least four factors contribute to its development: (1) keratinization of the lower portion of the follicular infundibulum and development of a keratin plug that blocks outflow of sebum to the skin surface, (2) hypertrophy of sebaceous glands during puberty under the influence of androgens, (3) lipase-synthesizing bacteria (Propionibacterium acnes) colonizing the upper and midportion of the hair follicle, converting lipids within sebum to proinflammatory fatty acids, and (4) secondary inflammation of the involved follicle Acne Vulgaris • Inflammatory acne is marked by erythematous papules, nodules, and pustules . • Severe variants (e.g., acne conglobata) result in sinus tract formation and dermal scarring. • Depending on the stage of the disease, open or closed comedones, papules, pustules, or deep inflammatory nodules may develop. • Open comedones have large, patulous orifices, whereas those of closed comedones are identifiable only microscopically . • Variable infiltrates of lymphocytes and macrophages are present in and around affected follicles, and extensive acute inflammation accompanies follicular rupture. • Dermal abscesses may form in association with rupture and lead to scarring. Acne Vulgaris Rosacea • Rosacea is a common disease of middle age and beyond, affecting up to 3% of the US population, with a predilection for females. • Four stages are recognized: • • • • (1) flushing episodes (pre-rosacea), (2) persistent erythema and telangiectasia, (3) pustules and papules, and (4) rhinophyma—permanent thickening of the nasal skin by confluent erythematous papules and prominent follicles. Rosacea • Pathogenesis. • Individuals with rosacea have high cutaneous levels of the antimicrobial peptide cathelicidin, an important mediator of the cutaneous innate immune response. Panniculitis • Erythema Nodosum and Erythema Induratum Panniculitis • Panniculitis is an inflammatory reaction in the subcutaneous adipose tissue that may preferentially affect (1) the lobules of fat, or (2) (2) the connective tissue that separates fat into lobules. Panniculitis often involves the lower legs. Erythema nodosum is the most common form Erythema nodosum • poorly defined, tender, erythematous plaques and nodules that may be more readily palpated than seen. • often associated with infections, drug administration, sarcoidosis, inflammatory bowel disease, and certain malignant neoplasms, but many times a cause cannot be identified. • Fever and malaise may accompany the cutaneous signs. • considered to be caused by a delayed hypersensitivity reaction to microbial or drug related antigens. In some cases immune complexes have been implicated but in many cases the pathogenesis remains mysterious. • Over the course of weeks, lesions usually flatten and become bruiselike, leaving no residual clinical scars, while new lesions develop. • Biopsy of a deep wedge of tissue to generously sample the subcutis is usually required for histologic diagnosis. Erythema induratum • Erythema induratum is an uncommon type of panniculitis that affects primarily adolescents and menopausal women. • Although the cause is not known, most observers regard this as a primary vasculitis of deep vessels supplying the fat lobules of the subcutis; the associated vascular compromise leads to fat necrosis and inflammation. • Erythema induratum presents as an erythematous, slightly tender nodule that usually goes on to ulcerate. • Originally considered a hypersensitivity response to tuberculosis, erythema induratum today most commonly occurs without an associated underlying disease. Panniculitis • Many other types of panniculitis have also been described: • Weber-Christian disease (relapsing febrile nodular panniculitis) is a rare form of lobular, nonvasculitic panniculitis seen in children and adults. It is marked by crops of erythematous plaques or nodules, predominantly on the lower extremities, created by deep-seated foci of inflammation containing aggregates of foamy macrophages admixed with lymphocytes, neutrophils, and giant cells. • Factitial panniculitis is a form of secondary panniculitis caused by self-inflicted trauma or injection of foreign or toxic substances. • Rare types of T-cell lymphoma home to fat lobules, producing fat necrosis and superimposed inflammation that mimics panniculitis. • Lupus erythematosus may occasionally cause inflammation of the subcutis and an associated panniculitis MOLLUSCUM CONTAGIOSUM • Molluscum contagiosum is a common, self-limited viral disease of the skin caused by a poxvirus. • The virus is the largest pathogenic poxvirus in humans and one of the largest viruses in nature. • Infection is usually spread by direct contact, particularly among children and young adults. MOLLUSCUM CONTAGIOSUM • Multiple lesions may occur on the skin and mucous membranes, with a predilection for the trunk and anogenital areas. • Individual lesions are firm, often pruritic, pink to skin-colored umbilicated papules, generally ranging in diameter from 0.2 cm to 0.4 cm. • Rarely, “giant” forms occur measuring up to 2 cm in diameter. • A curd-like material can be expressed from the central umbilication. Smearing this material onto a glass slide and staining with Giemsa often shows diagnostic molluscum bodies. • On microscopic examination, lesions show cuplike verrucous epidermal hyperplasia. The diagnostically specific structure is the molluscum body, which occurs as a large (up to 35 µm), ellipsoid, homogeneous, cytoplasmic inclusion in cells of the stratum granulosum and the stratum corneum. • In the hematoxylin and eosin stain, these inclusions are eosinophilic in the blue-purple stratum granulosum and acquire a pale blue hue in the red stratum corneum. Numerous virions are present within molluscum bodies. MOLLUSCUM CONTAGIOSUM MOLLUSCUM CONTAGIOSUM