STRUCTURE, FUNCTION, AND DISORDERS OF THE INTEGUMENT

Epidermis

The epidermis grows continually by shedding the superficial layer of stratum corneum, which is formed primarily of keratinocytes and melanocytes. These cells are named for the substances they produce. Keratinocytes produce keratin, a scleroprotein that provides protection from mechanical stress. Keratin is the main constituent of skin, hair, and nail cells. The thickness of the epidermis varies from 0.3 mm on the eyelids to 1.5 mm on the palms of the hands and soles of the feet. New cells (keratinocytes) formed in the basal layer (stratum basale) move upward and differentiate, forming the spinous layer (stratum spinosum). Together they form the germinative layer (stratum germinativum). The cells enlarge and then become flattened, stacked, and cornified (stratum corneum) as they ascend to the skin surface. Cornification, or keratinization, prevents dehydration of deeper skin layers. The average turnover of the epidermis is about 30 days.

The epidermis has three additional types of cells that facilitate its functional characteristics: melanocytes, Langerhans cells, and Merkel cells. The melanocytes are usually located near the base of the epidermis. They synthesize and secrete the pigment melanin with exposure to UV light in response to melanocyte-stimulating hormone (MSH). Melanin in the epidermis provides a shield against UV radiation and determines skin color. Langerhans cells migrate to the epidermis from the bone marrow. Langerhans cells (a type of dendritic cell) and dermal dendritic cells initiate an immune response by presenting processed antigen to T cells, thus providing a defense against environmental antigens.¹ Merkel cells are associated with touch receptors and function as slowly adapting mechanoreceptors when stimulated by deformation of the epidermis.

Dermis

The dermis is 1 to 4 mm thick and is composed of three types of connective tissue: (1) collagen, (2) elastin and reticulin, and (3) a gel-like ground substance. The haphazard arrangement of connective tissue allows the skin to be mobile and to stretch and contract with body movement. Hair follicles, sebaceous glands, sweat glands, blood vessels, lymphatic vessels, and nerves are contained in the dermis. The conelike projections of the papillary dermis interface with the epidermis. The papillae provide texture to the surface of the skin by forming rete pegs.

The cells of the dermis include fibroblasts, mast cells, and macrophages. Fibroblasts secrete the connective tissue matrix and collagen. Mast cells release histamine and play a role in hypersensitivity reactions in the skin. Macrophages are phagocytic and participate in immune responses. Histiocytes are macrophages that reside in loose connective tissue and phagocytize pigments and the debris of inflammation.

Dermal Appendages

The dermal appendages include the nails, hair, sebaceous glands, and the eccrine and apocrine sweat glands. The nails are protective keratinized plates that appear at the ends of fingers and toes. Each nail is composed of four structural units: (1) the proximal nail fold, (2) the matrix from which the nail grows, (3) the hyponychium (nail bed), and (4) the nail plate (Figure 44-2). Nail growth is continuous throughout life at a rate of 1 mm or less per day.

Hair follicles and sebaceous glands are integrated units (see Figure 44-1). Hair color, density, grain, and pattern of distribution have considerable variability and depend on age, gender, and race. Hair follicles arise from the matrix (or bulb) located deep in the dermis. They extend from the dermis at an angle and have an erector pili muscle attached near the mid-dermis that straightens the follicle when contracted, causing the hair to stand up. Hair growth begins in the bulb, with cellular differentiation of stem cells occurring as the hair progresses up the follicle.^3,4 Hair is fully hardened, or cornified, by the time it emerges at the skin surface. Hair growth is cyclic, with periods of growth and rest that vary over different body surfaces.

The sebaceous glands open onto the surface of the skin through a canal. They are found in greatest numbers on the face, chest, and back; modified glands are found on the eyelids, lips, nipple, glans penis, and prepuce. Sebaceous glands secrete sebum that is composed primarily of lipids; sebum oils the skin and hair and prevents drying. Growth of sebaceous glands is stimulated by androgens, and their enlargement is one of the early signs of puberty.

The eccrine sweat glands are distributed over the body, with the greatest numbers in the palms of the hands, soles of the feet, and forehead. These secretions are important in thermoregulation and cooling of the body through evaporation. The apocrine sweat glands are fewer in number and are located in the axillae, scalp, face, abdomen, and genital area and have very limited proven function.

Blood Supply and Innervation

The blood supply to the skin is limited to the papillary capillaries, or plexus, of the dermis. These capillary loops arise from a subpapillary plexus that is supplied by a deeper horizontal cutaneous arterial plexus. Branches from the deep plexus supply hair follicles and sweat glands. A subpapillary network of veins drains the capillary loops. Arteriovenous anastomoses in the dermis facilitate the regulation of body temperature. Heat loss can be regulated by varying blood flow through the skin by opening and closing the arteriovenous anastomoses in conjunction with evaporative heat loss of sweat. The sympathetic nervous system regulates vasoconstriction and vasodilation through α-adrenergic receptors. The lymphatic vessels arise in the papillary dermis and drain into larger subcutaneous trunks, removing cells, proteins, and immunologic mediators.

Lesions

Lesions of the skin are readily observable and easily assessed for distribution and structure. Identification of the morphologic structure and appearance of the skin in combination with a health history is necessary to identify the underlying pathophysiology. Table 44-3 describes and illustrates the basic lesions of the skin. Special skin lesions are described in Table 44-4.

Pruritus

Pruritus, or itching, is the most common symptom associated with many primary skin disorders, such as eczema, psoriasis, or lice infestations, or it can be a manifestation of systemic disease (e.g., xerosis, chronic renal failure, cholestatic liver disease, thyroid disorders, iron deficiency) or drug reactions. Pruritus may be localized or generalized and may move from one location to another.³⁶ Central and peripheral nerve pathways are activated.³⁷

Significant progress has been made in understanding the pathophysiology of itch. Studies show that peripheral itch mediators include neuropeptides, serotonin, prostaglandins, bradykinin, histamine, substance P, and acetylcholine and that the itch sensation is carried by specific unmyelinated C-nerve fibers.^38,39 These nerve fibers may also interact with dermal mast cells.⁴⁰

Itching also has been linked to pain because many stimuli that induce pain produce itching at lower intensities. Central nervous system mechanisms also can modulate itching, which is less perceptible when the mind is concentrating on other things. How the central nervous system influences the itch sensation is unclear. Neuropathic itch is related to pathology along an afferent pathway (i.e., postherpetic neuropathy). Psychogenic itch is associated with psychologic disorders (i.e., depression and obsessive-compulsive disorder).⁴¹

Chronic itching is an unpleasant sensation relieved by scratching—often done so intensely that trauma to the skin occurs, resulting in infection and scarring. Some individuals become so distraught with the constant irritation that they apply heat with enough intensity and duration to produce burns.

Management of localized itching depends on the cause, and the primary condition must be treated. Symptomatic relief may be obtained from antihistamines, which also have a sedative effect. Minor tranquilizers, such as promethazine, may be effective for some causes of pruritus. Itching related to dry, rough skin (xerosis) can be managed with applications of emollients and increased environmental humidity. Topical steroids are immediately effective with some occurrences of pruritus; however, in some instances, pruritus is resistant to any type of therapy. New topical treatment therapies are being developed, as are the use of phototherapy treatment with narrow band UVB and vagal nerve stimulation⁴² and cutaneous field stimulation.⁴³ Analgesics used to treat neuropathic pain also can be effective for treating pruritus.⁴⁴

Allergic Contact Dermatitis

Allergic contact dermatitis is a common form of T-cell mediated or delayed hypersensitivity (type IV).⁴⁶ (See Chapter 8 for various types of allergic responses.) Allergens (e.g., microorganisms, chemicals, foreign proteins, drugs, metals, latex) can form the sensitizing antigen; contact with poison ivy is a common example (Figure 44-5). The response is a reaction to irritants with release of cytokines, chemokines, and cytotoxins from keratinocytes, dendritic cells (Langerhans cells), and natural killer cells. When the allergen comes into contact with the skin the allergen is bound to a carrier protein, forming a hapten-specific sensitizing antigen. Langerhans cells process the antigen and carry it to T cells that then become sensitized to the antigen releasing cytokines and chemokines leading to leukocyte infiltration and inflammation.⁴⁷ Latex allergy can be either a type IV hypersensitivity to chemicals used in latex rubber processing or a type I immediate hypersensitivity with IgE antibodies formed in response to latex rubber protein.⁴⁸

In delayed hypersensitivity, several hours pass before an immunologic response is apparent. The T cells play an important role because they differentiate and secrete lymphokines that affect macrophage movement and aggregation, coagulation, and other inflammatory responses (see Chapter 8). Sensitization usually develops with first exposure to the antigen, and symptoms of dermatitis occur with reexposure.

The manifestations of allergic contact dermatitis include erythema and swelling with pruritic (itching) vesicular lesions in the areas of allergen contact. The pattern of distribution provides clues to the source of the antigen (e.g., hands exposed to chemical solutions or boundaries from rings and bracelets). Patch tests with specific antigens may assist with diagnosis. Removal of the allergen is necessary for resolution of the inflammatory response and tissue repair. Topical or systemic steroids, as well as other symptomatic treatment, may be required depending on the severity of the lesion.⁴⁷

Atopic Dermatitis

Atopic dermatitis (allergic dermatitis) is more common in infancy and childhood; however, some individuals are affected throughout life. A family history of asthma, allergic rhinitis, dry skin, food allergy, and eczema often accompanies this disorder. During adolescence and childhood the lesions are usually localized to the hands and feet or flexor surfaces (i.e., antecubital fossa, popliteal space) of the arms and legs (Figure 44-6). The erythema, scaling, and lichenification (thickened and leather-like skin) are exacerbated by scratching because the lesions manifest by itching. The scratching increases susceptibility to infections from Staphylococcus aureus and predisposition to cutaneous dissemination of viruses, particular herpes simplex. The pathogenesis and treatment of atopic dermatitis in adults are similar to that in children⁴⁹ and are discussed in detail in Chapter 45.

Stasis Dermatitis

Stasis dermatitis usually occurs on the legs as a result of venous stasis and edema. The disorder is associated with varicosities (incompetent venous valves), phlebitis, and vascular trauma. Pooling of venous blood traps leukocytes that may release proteolytic enzymes. Increased venous pressure widens interendothelial pores with deposition of fibrin and other macromolecules making them unavailable for repair.⁵⁰ Edema evolves to erythema and pruritus and progression to scaling, petechiae, and hyperpigmentation. Progressive lesions become ulcerated (stasis ulcers), particularly around the ankles and tibia (Figure 44-7).

Treatment includes elevating the legs as often as possible, not wearing tight clothes around the legs, and not standing for long periods. Defined infections are treated with antibiotics. Chronic lesions with ulceration are treated with moist dressings, external compression, and vein ablation surgery.^51,52

Irritant Contact Dermatitis

Irritant contact dermatitis is a common nonimmunologically mediated inflammation of the skin. The intensity of the inflammation is related to the concentration of the irritant, exposure time, and disruption of the skin barrier.⁵³ Irritation can occur from almost anything, especially if the epidermal barrier is compromised in any way (Box 44-1). The skin lesions are similar in appearance to allergic contact dermatitis. Removing the source of irritation and use of topical agents (i.e., corticosteroids and petroleum-based emollients) and non-irritating soaps constitute effective treatment.

Seborrheic Dermatitis

Seborrheic dermatitis is a common chronic inflammation of the skin involving the scalp, eyebrows, eyelids, ear canals, nasolabial folds, axillae, chest, and back (Figure 44-8). In infants it is known as cradle cap. The cause is unknown, but genetic predisposition an immunologic response to yeasts from the genus Malassezia have been implicated.⁵⁴ The lesions appear from infancy to old age, with periods of remission and exacerbation. The lesions appear as greasy, scaly, white, or yellowish inflammatory plaques in sebaceous areas with mild pruritus. Mild cases are treated with shampoos containing sulfur, salicylic acid, or tar. Ketoconazole has antifungal and anti-inflammatory effects and has been used with success.⁵⁵ Topical calcineurin inhibitors have also been effective and corticosteroid applications are useful for suppression of severe symptoms but should not be used for maintenance therapy.^54a

Psoriasis

Psoriasis is a chronic, relapsing, proliferative skin disorder that involves the skin, scalp and nails and can occur at any age. The disease affects about 2% of the population.⁵⁶ Psoriasis is a T-cell mediated autoimmune disease. Inflammatory cytokines (i.e., tumor necrosis factor [TNF], interferon-gamma [IFN-γ], IL-6, IL-12, IL-15, IL-17, IL-22, IL-23) from activated T cells, B cells, and macrophages cause the skin changes and comorbidities occurring in psoriasis.⁵⁷ The onset is generally established by 20 years of age. A family history of psoriasis is common. The genetic mechanisms are complex and the human leukocyte antigen (HLA)-Cw6 allele (PSORS1) is a major susceptibility gene.⁵⁸

The dermis and epidermis are thickened, with cellular hyperproliferation, altered keratinocyte differentiation, expanded dermal vasculature, infiltration of neutrophils and lymphocytes, and inflammation.⁵⁹ The turnover time for shedding the epidermis is decreased from the normal 26 to 30 days to 3 to 4 days. There are increased numbers of germinative cells and an increase in transit time of cells through the dermis. The rapid cellular proliferation does not allow time for cell maturation and keratinization to occur, resulting in a thickened epidermis and plaque formation. The loosely cohesive keratin gives the lesion a silvery, scaly appearance. There is often capillary dilation and increased vascularization to accommodate the increased cell metabolism. The increased vascularity causes erythema.

The types of psoriasis include plaque (psoriasis vulgaris), inverse, guttate, pustular, and erythrodermic. Plaque psoriasis is the most common and affects 80% to 90% of individuals with psoriasis. The disease can be mild, moderate, or severe, depending on the size, distribution, and inflammation of the lesions. Early onset psoriasis is an inflammatory lesion with epidermal hyperproliferation and the presence of activated T lymphocytes.⁵⁷ The typical lesion of plaque psoriasis is a well-demarcated, thick, silvery, scaly, erythematous plaque surrounded by normal skin (Figure 44-9). Initial lesions usually develop insidiously as small erythematous papules that enlarge and coalesce into larger inflammatory lesions. The lesions are commonly located on the scalp, elbows, and knees and at sites of trauma. The scales are usually loosely adherent and may cause small bleeding points when removed. Inverse psoriasis involves lesions that develop in skinfolds (i.e., axilla or groin). They are large, smooth, dry, and deep red. The progress of psoriasis is characterized by remissions and exacerbations. Antimalarial drugs, lithium, nonsteroidal anti-inflammatory drugs, and beta-blockers, tend to exacerbate existing psoriasis.

In guttate psoriasis, small papules (1 to 10 mm) appear suddenly on the trunk and extremities (Figure 44-10). The lesions may appear a few weeks after a streptococcal respiratory infection and are more common in children. Guttate psoriasis may resolve spontaneously in weeks or months. Pustular psoriasis appears as blisters of noninfectious pus (collections of neutrophils) that develop over areas of plaque psoriasis. Erythrodermic (exfoliative) psoriasis is often accompanied by itching or pain with widespread red, scaling lesions that cover a large area of the body.

Psoriatic arthritis and ankylosing spondylitis are associated with the proinflammatory cytokines that cause psoriatic skin lesions. Joints of the hands, feet, knees, and ankles are involved, and 5% to 50% of individuals with psoriasis have seronegative joint involvemment.⁶⁰ Psoriatic nail disease can occur in all psoriasis subtypes with pitting, onycholysis, subungual hyperkeratosis, and nail plate dystrophy. Psoriasis is also a risk factor for a number of comorbidities including inflammatory bowel disease, metabolic syndrome, including hypertension, insulin resistance, dyslipidemias, and abdominal obesity, and increased risk for atherosclerosis and myocardial infarction that is independent of traditional risk factors for these diseases.

Treatment is individualized and related to reducing epidermal cell turnover. Mild lesions are usually treated with emollients, keratolytic agents, and corticosteroids. Moderate lesions may respond to UV light, tar preparations, or a combination of both, and to methotrexate, cyclosporine A, and acitretin. Vitamin D₃ (calcitriol) is used to reduce epidermal proliferation. Moderate to severe disease is the indication for biologic treatment, including drugs that inhibit the activation and number of T lymphocytes (alefacept), drugs that block T-cell adhesion (efalizumab), or TNF-α inhibitors (adalimumab, etanercept, infliximab).⁵⁶

Pityriasis Rosea

Pityriasis rosea is a benign self-limiting inflammatory disorder that occurs more often in young adults, usually during winter months. The cause is unknown but is thought to be associated with a virus because of the timing and clustering of the outbreaks.⁶¹ Pityriasis rosea begins as a single lesion known as a herald patch (Figure 44-11) that is circular, demarcated, salmon-pink, approximately 3 to 4 cm in diameter, and usually located on the trunk. Early lesions are macular and papular; secondary lesions develop within 14 to 21 days and extend over the trunk and upper part of the extremities. Lesions are rarely located on the face. They emerge as small erythematous papules that expand into characteristic oval lesions. There may be few or hundreds of lesions. The pattern of distribution follows the skin lines around the trunk and resembles a drooping pine tree. As scales flake off from the margin of the lesions, a collarette pattern is formed. Itching is the most common symptom. Headache, fatigue, or sore throat may precede the development of the lesions.⁶²

The diagnosis of pityriasis rosea is made by the clinical appearance of the lesion. It can be confused with secondary syphilis, psoriasis, or seborrheic dermatitis. The disorder is usually self-limiting and resolves in a few months with symptomatic treatment for pruritus. UV light, antihistamines, or topical corticosteroids may be used to control itching, and erythromycin may control the rash.⁶³ Sun exposure facilitates resolution of the lesions.

Lichen Planus

Lichen planus is a benign, autoimmune inflammatory disorder of the skin and mucous membranes. The cause is unknown, but T cells, adhesion molecules, inflammatory cytokines, perforin, and antigen-presenting cells are involved.⁶⁴ The infiltrate of T cells mediates immunoreactivity against basal layer keratinocytes, which have altered surface antigens and adhesion molecules.⁶⁵ Lichen planus is also linked to hepatitis C virus.⁶⁶ Some individuals develop lichenoid lesions after exposure to drugs or film-processing chemicals. The age of onset is usually between 30 and 70 years. The disorder begins with nonscaling, violet-colored pruritic papules, 2 to 4 mm in size, usually located on the wrists, ankles, lower legs, and genitalia (Figure 44-12). The papules are flat topped and have a polygonal shape. New lesions are pale pink and evolve into a dark violet. Persistent lesions may be thickened and red, forming hypertrophic lichen planus. The lesions often involve the oral mucous membranes, appearing as lacy white rings that must be differentiated from leukoplakia or oral candidiasis.⁶⁷ Fine white lines, known as Wickham striae, can be seen throughout the oral lesions on magnification. These lesions also can develop on the penis and vulvovaginal area. More commonly, oral lesions do not ulcerate, but localized or extensive painful ulcerations do, and frequently occur. Chronic ulcerated lesions become malignant in 1% of individuals with the disease. Thinning and splitting of nails are common, and part or all of the nail may be shed.

Pruritus is the most distressing symptom. The lesions are self-limiting and may last for months or years, with an average duration of 6 to 18 months. Postinflammatory hyperpigmentation is a common consequence of the lesion. Approximately 20% of individuals have a recurrence. Diagnosis is commonly made by the clinical appearance of the lesion. Treatment is individualized. Antihistamines are given for itching, and topical or systemic corticosteroids may be used to control inflammation. Mucous membrane lesions are treated with topical steroids, topical tacrolimus, or pimecrolimus.⁶⁸

Acne Vulgaris

Acne vulgaris is an inflammatory disorder of the pilosebaceous follicle (the sebaceous gland contiguous with a hair follicle). It occurs most commonly during adolescence. Details of this disorder are presented in Chapter 45.

Acne Rosacea

Acne rosacea is an inflammation of the skin that develops in middle-age adults. The disease is chronic with episodes of exacerbation. The most common lesion types are erythematotelangiectatic, papulopustular, phymatous, and ocular.⁶⁹ They occur in the middle third of the face, including the forehead, nose, cheeks, and chin (Figure 44-13). The cause is unknown, but immune-mediated inflammation may be a factor.⁷⁰ The lesions are associated with chronic, inappropriate vasodilation resulting in flushing and sensitivity to the sun. Sebaceous hypertrophy, fibrosis, and telangiectasia may be severe enough to produce an irreversible bulbous appearance of the nose, known as rhinophyma. Disorders of the eye often accompany rosacea, particularly conjunctivitis and, more rarely, keratitis, which can result in visual impairment.⁷¹ Facial application of fluorinated topical steroids may precipitate rosacea-like lesions that are difficult to treat. There is controversy regarding the association between Demodex folliculorum (mites), Helicobacter pylori infection, and rosacea.^72,73

Hot drinks or alcohol should be taken cautiously because the heat and vasodilation accentuate erythema. Tetracycline, though photosensitizing, continues to be the drug of choice for treatment, and a low-maintenance dose may be required after the most severe lesions are controlled. Daily use of photoprotection, including sunscreens, is recommended; 1% topical metronidazole and 15% azelaic acid gel may be effective.^74,75 Surgical excision of excessive tissue may be required for rhinophyma.

Lupus Erythematosus

Lupus erythematosus is an inflammatory, autoimmune, systemic disease with cutaneous manifestations. Discoid (or cutaneous) lupus erythematosus (DLE) is limited to the skin and can lead to systemic lupus erythematosus (SLE) in approximately 5% of individuals. DLE may be described as a subset of SLE, with cutaneous manifestations as the only symptom⁷⁶ (Figure 44-14). (SLE, a diffuse, multisystem disease, is discussed in Chapter 8.)

Pemphigus

Pemphigus (meaning to blister or bubble) is a rare autoimmune blistering disease of the skin and oral mucous membranes caused by circulating autoantibodies directed against the cell surface adhesion molecule, desmoglein, at the desmosomal cell junction in the suprabasal layer of the epidermis. Immunoglobulin G (IgG) autoantibodies and C3 complement bind to the desmoglein adhesion molecules resulting in the destruction of cell-to-cell adhesion (acantholysis) in the epidermis with fluid accumulation and the resulting symptom of blister formation. A subset of autoantibodies may block keratinocyte acetylcholine receptors, disrupting keratinocyte cohesion.⁸² IgA autoantibodies have been found in some individuals.⁸³ Pemphigus can occur in all age groups but is more prevalent between 40 and 50 years of age. There is a genetic predisposition as well as environmental triggers.⁸⁴

Pemphigus presents in varying forms. Pemphigus vulgaris is the most common form with acantholysis at the suprabasal level. Oral lesions precede the onset of skin blistering, which is more prominent on the face, scalp, and axilla. The blisters rupture easily because of the thin, fragile overlying portion of epidermis. Pemphigus vegetans is a variant of pemphigus vulgaris with large blisters occurring in tissue folds of the axilla and groin. Pemphigus foliaceus is a milder form of the disease and involves acantholysis at the subcorneal level with blistering, erosions, scaling, crusting, and erythema usually of the face and chest. Oral mucous membranes are rarely involved. Pemphigus erythematosus is a subset of pemphigus foliaceus often associated with systemic lupus erythematosus with positive antinuclear antibodies. The lesions are generally less widely distributed.

The diagnosis of pemphigus is made from the clinical manifestations and histologic examination of the skin. Immunofluorescence demonstrates the presence of antibodies at the site of blister formation. The clinical course of the disease may range from rapidly fatal to relatively benign. The primary treatment for pemphigus is systemic corticosteroids, usually in high doses during acute episodes or when there is widespread involvement. Adjuvant immunosuppressive therapy also may be used and decreases the steroid dosage requirement. Newer methods of treatment and a clearer understanding of the pathogenesis have improved the prognosis and decreased mortality.⁸⁵

Bullous Pemphigoid

Bullous pemphigoid (BP) is a more benign disease than pemphigus vulgaris, with the presence of serum and bound IgG and blistering of the subepidermal skin layer.⁸⁶ Autoantibodies have been found to hemidesmosomal proteins designated BP 180 and BP 230. Loss of dermal-epidermal adhesion is caused by proteinases released by granulocytes.⁸⁷ The lesions of pemphigoid begin with localized erythema or as pruritic plaques that extend and become edematous. The plaques turn reddish-purple by 2 to 3 weeks, with vesicles and bullae emerging on the surface (Figure 44-15). The bullae do not extend with pressure. The blisters rupture within 1 week and heal rapidly. BP occurs more commonly after 60 years of age.

Diagnosis is by skin biopsy and immunofluorescent examination. The presence of subepidermal blistering and eosinophils distinguishes pemphigoid from pemphigus. Treatment usually includes hydroxyzine (Atarax) for itching and prednisone with an immunosuppressive drug to control blistering. Individuals who respond to treatment with sulfapyridine or dapsone do not require prednisone.

Erythema Multiforme

Erythema multiforme is not a single disease but rather a syndrome characterized by inflammation of skin and mucous membranes. It often is associated with a T-cell mediated immunologic reaction to microorganisms (e.g., Mycoplasma pneumoniae, herpes simplex virus) or a toxic reaction to drugs in which TNF-α causes tissue damage.⁸⁸ Overall, it is relatively rare and can occur at any age but is more common between 20 and 40 years of age. Immune complex formation and deposition of complement (C3), IgM, and fibrinogen around the superficial dermal blood vessels, basement membrane, and keratinocytes are found in most individuals with erythema multiforme. Edema develops in the superficial dermis, leading to the formation of vesicles and bullae. The lesions vary in clinical presentation and may involve the skin or mucous membranes or both. The characteristic “bull’s-eye” or “target” lesions occur on the skin surface with a central dusky region surrounded by concentric rings or alternating edema and inflammation.⁸⁹ The lesions usually occur suddenly in groups over 2 to 3 weeks. Urticarial plaques, 1 to 2 cm in diameter, can develop without the target lesion. A vesiculobullous form is characterized by mucous membrane lesions and erythematous plaques over elbows and knees. Single or multiple vesicles or bullae may arise on a part of the plaque, accompanied by pruritus and burning. In the minor form there may be ten to hundreds of lesions.⁹⁰ The lesions heal within 3 to 4 weeks (Figure 44-16).

The most common severe forms in children and young adults are Stevens-Johnson syndrome (severe bullous form) and toxic epidermal necrolysis, in which there are numerous erythematous bullous lesions on the skin and mucous membranes. These diseases may have a different etiology than erythema multiforme.⁹¹ The cause is unknown, but an immune mechanism related to drug administration is involved.⁹² Bursts of nitric oxide formation have been proposed as the cause of epidermal apoptosis and necrosis.⁹³ There is destruction of the epidermis in toxic epidermal necrolysis. Cytotoxic lymphocytes (early) and monocytes-macrophages (late) are involved in this severe blistering disease.⁹⁴

Prodromal symptoms of fever, headache, malaise, sore throat, and cough develop in approximately one third of cases. The bullous lesions form erosions and crusts when they rupture. The mouth, air passages, esophagus, urethra, and conjunctiva may be involved. Blindness can result from corneal ulcerations. Difficulty with eating, breathing, and urinating may develop with severe manifestations. The disease can involve the kidneys and extend from the upper respiratory passages into the lungs. Severe forms of the disease can be fatal.

Diagnosis is made by medication history, recognition of the target lesion, or by skin biopsy if the target lesion is absent. Mild acute forms of the disease last 10 to 14 days. Mild forms of the disease, usually self-limiting, require no treatment. Any ongoing drug therapy should be withdrawn or reevaluated and underlying infections treated. Fluid and electrolyte balance should be monitored in severe forms of the disease, and mucous membranes must be carefully managed with a bland diet, warm saline eyewashes, topical anesthetics, or corticosteroids to maintain comfort and prevent infection. Use of systemic steroids is controversial.⁹⁵ Cutaneous blisters can be treated with wet compresses of nanocrystalline silver. Ophthalmic, kidney, and lung involvement requires special care. Resolution occurs in 8 to 10 days, usually without scarring. Mucosal lesions may take 6 weeks to heal.

Bacterial Infections

Most bacterial infections of the skin are caused by local invasion of pathogens. Coagulase-positive S. aureus and, less often, beta-hemolytic streptococci are the common causative microorganisms.⁹⁷ Community-acquired methicillin-resistant Staphylococcus aureus (C-MRSA) is also a cause of serious skin infection (Box 44-2).

Viral Infections

Fungal Infections

The fungi causing superficial skin infections are called dermatophytes, and they thrive on keratin (stratum corneum, hair, nails). Fungal disorders are known as mycoses; when caused by dermatophytes, the mycoses are termed tinea (dermatophytosis or ringworm).

Cutaneous Vasculitis

Vasculitis (angiitis) is an inflammation of the blood vessels of the skin. The vasculitis is often idiopathic or can be triggered by infection, decreased blood flow (i.e., venous stasis), drugs, or autoimmune disorders. The initiating site of inflammation may be the blood, the vessel wall, or the adjacent tissue. Small vessels are usually affected. Immune complexes, which initiate an uncontrolled inflammatory response, are often the cause of damage, and the lesions are often polymorphic.

Cutaneous vasculitis develops from the deposit of immune complexes in small blood vessels as a toxic response to drugs (phenothiazines, barbiturates, sulfonamides) or allergens as a response to streptococcal or viral infection or as a component of systemic vasculitic syndromes. The precise mechanism is not known, but the deposit of immune complex activates complement, which is chemotactic for polymorphonuclear leukocytes and other mediators of inflammation which disrupt adhesion molecules and the vessel wall. The cutaneous form usually resolves in a few weeks and is treated with steroids.

The disorder is also known as allergic vasculitis and occurs primarily in adults. A systemic form (cutaneous systemic vasculitis) can involve other organs, including the kidneys, lungs, and gastrointestinal tract.¹²² The extremities are the chief sites, primarily the lower legs and feet. The lesions appear as palpable purpuras (from the leakage of blood from damaged vessels) and progress to hemorrhagic bullae with necrosis and ulceration from occlusion of the vessel (Figure 44-22). Lesions appear in clusters and remain from 1 to 4 weeks. Recurrences are common. Biopsy may disclose the presence of complement or immunoglobulins in the vessel walls.

Identifying and removing the antigen (chemical, drug, or source of infection) is the first step of treatment. Corticosteroids and other drugs may be used when symptoms are severe.¹²³

Urticaria

Urticaria (hives) is a circumscribed area of raised erythema and edema of the superficial dermis. Urticarial lesions are most commonly associated with type I hypersensitivity reactions to drugs (e.g., penicillin, aspirin), certain foods (e.g., strawberries, shellfish), systemic diseases (e.g., intestinal parasites, lupus erythematosus), physical agents (e.g., heat, cold), or complement-mediated reactions (see Chapter 8). The lesions are mediated by IgE-stimulated release of histamine, bradykinin, kallikrein from mast cells or basophils, or both, which causes the endothelial cells of skin blood vessels to contract.¹²⁴ Other inflammatory mediators such as serotonin, leukotrienes, prostaglandins and kinins may also be mediators of urticaria. The leakage of fluid from the vessels appear as wheals, welts, or hives and may be a few leaks or many leaks distributed over the entire body (Figure 44-23). Most lesions resolve spontaneously within 24 hours, but new lesions may appear. All possible causes should be removed. Antihistamines (H₁ antagonists) usually reduce hives and provide relief of itching. Epinephrine or corticosteroids and α-adrenergic agonists may be required for treatment of severe attacks (i.e., angioderma). Chronic urticaria (recurrent wheals for more than 6 weeks) is either an autoimmune or idiopathic disease.¹²⁵

Scleroderma

Scleroderma means sclerosis of the skin, and the disease is associated with immune dysregulation and several autoantibodies.¹²⁶ The disease is more prominent in women. Genetic predisposition, autoimmunity, and an immune reaction to a toxic substance are possible initiating mechanisms of the disease. Impaired regulation of growth factors, collagen gene expression by fibroblasts, probably underlies the persistent fibrosis.¹²⁷ Systemic scleroderma (sclerosis) involves the connective tissues of many organs, including the kidney, heart, peripheral nervous system, gastrointestinal tract, and lungs.¹²⁸ Only a few organs are involved in some individuals. The cutaneous lesions are most often on the face and hands, neck, and upper chest. The entire skin can be involved, however.

There are massive deposits of collagen with fibrosis, accompanied by inflammatory reactions, vascular changes in the capillary network with a decrease in the number of capillary loops, dilation of the remaining capillaries, enhanced expression of adhesion molecules, endothelial injury and dysfunction, perivascular infiltrates, and ischemia.¹²⁹ Fibrosis occurs in the papillary and reticular dermis and in the subcutaneous tissue and deep fascia. The skin is hard, hypopigmented, taut, shiny, and tightly connected to the underlying tissue. The tightness of the facial skin projects an immobile masklike appearance, and the mouth may not open completely. The nose may assume a beaklike appearance. The hands are shiny and sometimes red and edematous (Figure 44-24). The fingers become tapered and flexed, often with depressed scars and loss of fingertips from atrophy. Raynaud phenomenon with episodic arteriolar vasoconstriction of the fingers contributes to ulcer formation and gangrene.¹³⁰ The nails may be shed. Calcium deposits develop in the subcutaneous tissue and erupt through the skin. Progression to body organs may occur, and death is caused by subsequent respiratory failure, renal failure, cardiac dysrhythmias, or esophageal or intestinal obstruction or perforation.

Suitable clothing and a warm environment are essential to protecting the hands. Trauma and smoking should be avoided. Vasodilator drugs (i.e., angiotensin-converting enzyme inhibitors) or sympathectomy rarely has lasting effects. Symptomatic treatment is required for involved organs (e.g., intestinal resection for obstruction, antibiotics for pneumonitis, and regulation of hypertension).¹³¹ There is no specific treatment, and progression of the disease is variable. Broad-spectrum immunosuppression and hematopoietic bone marrow or stem cell transplantation may be used early in the disease.^128,132 Fifty percent of individuals die within 5 years of the onset of scleroderma.

Ticks

Ticks are significant vectors of transmitted diseases, including Rocky Mountain spotted fever and other rickettsial diseases, tularemia, and Lyme disease.¹³³ Ticks vary from 1 cm to about the size of a comma on this printed page. They embed their heads in the skin to obtain blood. As they gorge themselves on blood, they enlarge to many times their normal size and may release toxins or transmit microorganisms during feeding. In most instances, there is no consequence from a tick bite, with the exception of papular urticaria at the site of the bite. If mouthparts remain in the skin when the tick is removed, a persistent nodule remains that may require excision; ideally the tick should be removed completely intact. Irritant substances, such as camphor, soft wax, or heat from a match, may stimulate the tick to withdraw its head. Wearing protective clothing and applying tick repellant, such as diethyltoluamide (DEET), butopyronoxyl (Indalone), or benzylbenzoate, helps prevent tick bites.

Lyme disease is a multisystem inflammatory disease caused by the spirochete Borrelia burgdorferi transmitted by tick bites and is the most frequently reported vector-borne illness.¹³⁴ The highest incidence is among children (50% of infected individuals are symptom free). An immune response to B. burgdorferi may contribute to the pathogenesis of the disease.¹³⁵ The microorganism is difficult to culture and it escapes immunodefenses through antigenetic diversity, blocks complement-mediated killing, and hides in tissue.^136,137

Symptoms of the disease occur in three stages.¹³⁴ Localized infection occurs soon after the bite with erythema migrans (rash), fever, fatigue, malaise, myalgias, and arthralgias. Within days to weeks after the onset of the illness, there is disseminated infection with secondary erythema migrans, arthralgias, meningitis, neuritis, or cardiovascular symptoms. Late persistent infection can continue for years with arthritis, encephalopathy, or polyneuropathy (see Chapter 16). The diagnosis of Lyme disease is based on the clinical presentation and history of tick bite, if known. Serologic tests often are used to confirm the diagnosis.¹³⁸ Antibiotics (i.e., doxycycline [not used in children younger than 8 years] or amoxicillin) are used for treatment.¹³⁴ Reinfection can occur. Vaccines are in development, and personal protection is important to disease prevention.¹³⁹

Mosquitoes and Flies

There are thousands of species of mosquitoes throughout the world. Species from the Culicidae family are responsible for malaria, yellow fever, dengue fever, filariasis, and St. Louis encephalitis. Several different species of mosquitoes can carry the West Nile virus which causes encephalitis (see Chapters 9 and 17). Mosquitoes can bite through thin, loose clothing and are attracted by warmth and sweat. The edema, pruritus, and papular lesions of the mosquito bite are caused by the disruption of the skin from the insertion of a blood tube by a female mosquito. Irritating salivary secretions also contain anticoagulants. Reactions vary depending on the sensitivity of the victim.

Several species of flies are blood suckers. The black fly (Simuliidae) is usually found in swarms—near moving bodies of water in the late spring and early summer—and is a vicious biter. The initial bite is painless because the fly injects an anesthetic with the bite. Subsequent lesions are painful and accompanied by significant swelling of surrounding tissues. Systemic reactions, such as fever, headache, and nausea, are common.

Very small flies of the Ceratopogonidae family, also known as “no-see-ums,” “midges,” “punkies,” or sand fleas, are also blood suckers. The bite of the female is particularly miserable and produces immediate pain, erythema, and vesicles. Itching and vesicular reactions may persist for weeks.

The fiercest blood-sucking flies are the Tabanidae, or horseflies, deerflies, gadflies, greenheads, and clegs. These flies vary in size from 1 to 5 cm and produce painful, bleeding bites because of their large mouthparts. The bites produce urticaria that may be accompanied by weakness, dizziness, and wheezing.

Wounds produced by biting insects should be cleansed with soap and water, and a local antiseptic should be applied. Local applications of steroid creams or antihistamine will reduce symptoms. Systemic reactions may require more specific medical care.

Seborrheic Keratosis

Seborrheic keratosis is a benign proliferation of cutaneous basal cells that produces smooth or warty elevated lesions. The pathogenesis is unknown. They are usually seen in older people and occur as multiple lesions on the chest, back, and face. The color varies from tan to waxy yellow, flesh colored, or dark brown-black. Lesion size varies from a few millimeters to several centimeters, and they are often oval and greasy appearing with a hyperkeratotic stuck-on scaly appearance (Figure 44-25). Cryotherapy with liquid nitrogen or electrocautery are effective treatments, and the lesions usually slough 2 to 3 weeks after treatment.

Keratoacanthoma

A keratoacanthoma is a benign self-limiting tumor of squamous cell differentiation arising from hair follicles. It usually occurs on sun-damaged skin of older adults and smokers; the incidence is high in males. The most commonly affected sites are the face, back of the hands, forearms, neck, and legs (Figure 44-26). The lesion develops over a period of 1 to 2 months and has a histology resembling a well-differentiated squamous cell carcinoma as follows¹⁴⁰:

Although the lesions resolve spontaneously, they can be removed by curettage or excision to improve cosmetic appearance. Intralesional methotrexate also has been effective.¹⁴²

Actinic Keratosis

Actinic keratosis is a premalignant lesion found on skin surfaces exposed to the UV radiation of the sun. The prevalence is highest in individuals with unprotected light-colored skin. Actinic keratosis is rare in black skin. The lesions appear as rough or scaly, poorly defined pink to reddish or reddish- brown papules that are felt more than seen (Figure 44-27) and are considered an early in situ squamous cell carcinoma.¹⁴³ Surrounding areas may have telangiectasia. Treatment options include ablative and topical therapies. The lesions should continue to be evaluated for progressive squamous cell carcinoma.¹⁴⁴ Protection from the sun with clothing or a sunblock to prevent lesions from developing elsewhere is advised.

Nevi

Nevi (moles) are pigmented or nonpigmented lesions that form from melanocytes beginning at ages 3 to 5 years. During the early stages of development, the cells accumulate at the junction of the dermis and epidermis and are macular lesions. Over time the cells move down into the dermis and the nevi become nodular and palpable. Nevi may appear on any part of the skin, and vary in size. They occur singly or in groups and are not considered disfiguring. Nevi may undergo transition to malignant melanomas (see p. 1670). Nevi irritated by clothing can be excised.

Basal Cell Carcinoma

Basal cell carcinoma is a surface epithelial tumor of the skin originating from undifferentiated basal or germinative cells. The tumors grow upward and laterally or downward to the dermal epidermal junction (Figure 44-28). They usually have depressed centers and rolled borders. Early tumors are so small that they are not clinically apparent.

Basal cell carcinoma is the most common type of skin cancer in whites and is thought to be caused by UV radiation exposure.¹⁴⁸ Lesions are seen most often on people who live in regions with intense sunlight and on those areas of the skin most exposed—namely, the face and neck. Dark-skinned persons and those avoiding sunlight are significantly less likely to develop these malignant tumors. In dark-skinned persons, basal cells contain the pigment melanin, a protective factor against sun exposure. Basal cell carcinoma arises as a consequence of UV-associated mutation in the TP53 tumor-suppressor gene, leading to loss of keratinocyte repair functions and apoptosis resistance of DNA-damaged cells.¹⁴⁹ Other factors also are implicated: arsenic from groundwater wells¹⁵⁰ (alters DNA repair and causes mutation in TP53 tumor-suppressor gene), autosomal dominant nevoid basal cell carcinoma syndrome with mutation in the PTCH1 gene that has tumor-suppressor activity, and alteration in the Sonic Hedgehog signaling pathway genes (important for cell growth and differentiation).^151,152

The lesion starts as a nodule (greater than 5 mm across) that is pearly or ivory in appearance and slightly elevated above the skin surface; it has small blood vessels on the surface. As the lesion grows, it often ulcerates, develops crusting, and becomes firm to the touch. If left untreated basal cell lesions invade surrounding tissues and, over months or years, can destroy a nose, an eyelid, or an ear (for treatment, see Box 44-3). Metastatic spread is rare because these tumors do not invade blood or lymph vessels.

Squamous Cell Carcinoma

Squamous cell carcinoma is a tumor of the epidermis characterized by two types: in situ (Bowen disease) and invasive. Areas affected are the head and neck (75%) and the hands (15%), with 10% of squamous cell carcinomas occurring elsewhere on the body. These tumors are more predominant in countries where arsenic is found in higher rates in drinking water. Gamma rays and x-rays are also associated with squamous cell carcinoma. In addition, patients who are immunosuppressed experience a greater occurrence of this carcinoma.

UV exposure causes squamous cell carcinoma, particularly with mutation of the TP53 gene.¹⁵³ It is unclear how UV light produces alterations in DNA, and DNA repair.¹⁵⁴ Invasive squamous cell carcinoma can arise from premalignant lesions of the skin. It rarely arises from normal-appearing skin or de novo. The premalignant lesions include sun-damaged skin or dysplasias (actinic dermatitis); leukoplakia, or whitish, discolored areas; scars; radiation-induced keratosis; tar and oil keratosis; and chronic ulcers and sinuses. The invasive type grows more rapidly than basal cell carcinomas and can spread to regional lymph nodes with metastasis. These tumors are firm and increase in elevation and diameter. The surface may be granular and bleed easily (Figure 44-29).

In situ squamous cell carcinoma is usually confined to the epidermis (intraepidermal) but may extend into the dermis. Common premalignant skin lesions associated with in situ squamous cell carcinomas are actinic (solar) keratosis and Bowen disease. Actinic keratosis is a white, scaly, keratotic (horny) lesion on the exposed areas of the body (see p. 1668). Bowen disease is a dysplasia of the basal layer of the dermis or carcinoma in situ. It often is found on unexposed areas of the body and is demonstrated by flat, reddish, scaly patches. These lesions may enlarge to more than 1 cm in diameter, rarely invading surrounding tissue and almost never metastasizing. Other cellular components in the skin (sweat glands, hair follicles, etc.) can give rise to skin cancer, but these cancers are relatively uncommon.

Malignant Melanoma

Melanoma is a malignant tumor of the skin originating from melanocytes, or cells that synthesize the pigment melanin. The incidence of melanoma is increasing, and young to middle-age adults are at highest risk. Risk factors implicated in melanoma induction include genetic predisposition, exposure to ultraviolet light (solar and artificial), steroid hormone activity, fair hair, light skin with a propensity to sunburn, moles, and susceptibity genes^155,156 (see What’s New? Melanoma, UVA Exposures and Cutaneous Vitamin D₃).

Melanomas arise as a result of malignant degeneration of melanocytes located either along the basal layer of the epidermis or in a benign melanocytic nevus. The pathogenesis of malignant melanoma is complex and a number of proto-oncogenes have been identified.¹⁵⁷

A nevus, or mole, is an aggregation of melanocytes (Figure 44-30). These clusters of cells may not be apparent until puberty, when the pigmentation process is initiated by steroid

hormones. The relationship between nevi and melanoma makes it important for the clinician to understand the various neval forms (Table 44-8). Most nevi never become suspicious; however, suspicious pigmented nevi should be removed.158 Indications for biopsy include color change, size change, irregular notched margin, itching, bleeding or oozing, nodularity, scab formation, ulceration, or an unusual pattern of presentation. The ABCDE rule is used as a guide: Asymmetry, Border irregularity, Color variation, Diameter larger than 6 mm, and Elevation which includes raised appearance or rapid enlargement.¹⁵⁸ Clinical characteristics are summarized in Table 44-9.

Staging of melanoma is determined from tissue biopsy, by assessing the thickness of the lesion using the Breslow microstage, and the Clark levels of tumor invasion¹⁵⁹ (Figure 44-31). The clinical classifications of cutaneous melanoma include lentigo malignant melanoma (LMM) (Figure 44-32), superficial spreading melanoma (SSM) (Figure 44-33), primary nodular melanoma (PNM), and acral lentiginous melanoma. A melanotic melanoma is the rarest subtype and is a nonpigmented melanoma.¹⁶⁰ Efforts are in progress to refine the morphologic classifications by adding subgroups that include molecular markers for proto-oncogene mutations and specific signaling pathways.^161,162 Early recognition of cutaneous melanomas can have a major effect on surgically curing this disease.

Treatment of melanoma with no evidence of metastatic disease involves surgical excision to the primary site and regional lymph nodes. The extent of surgery is determined by the staging of disease. Lesions of the extremities have the best prognosis; head and neck lesions and trunk lesions have the poorest prognosis. Survival rate for advanced disease is very low. Immunotherapy is advancing and vaccines and gene therapy are under investigation.^163,164

Kaposi Sarcoma

Kaposi sarcoma (KS) is a vascular malignancy with four different presentations:

Kaposi-associated herpesvirus 8 is found in all four forms of KS and may be a common etiology for all types of KS through the development of an angiogenic-inflammatory state.¹⁶⁵ Immunosuppression allows for opportunistic infections and malignancy. Proliferation of the tumor depends on the presence of platelet-derived and other growth factors.¹⁶⁶

The human immunodeficiency virus (HIV) and CMV have been proposed as cofactors in the development of KS.¹⁶⁷ The endothelial cell is thought to be the progenitor of KS but the specific origin is elusive. The lesions emerge as purplish- brown macules and develop into plaques and nodules. They tend to be multifocal rather than spreading by metastasis. The lesions initially appear over the lower extremities in the classic form (Figure 44-34). The rapidly progressive form associated with AIDS tends to spread symmetrically over the upper body, particularly the face and oral mucosa. The lesions are often pruritic and painful. About 75% of individuals with epidemic KS have involvement of lymph nodes, particularly in the gastrointestinal tract and lungs. Organ involvement is much less common in the classic form. The rapidly progressive form has a poor prognosis and shorter survival rates than the classic form. (See Chapter 9 for a further discussion on AIDS.)

Diagnosis is by skin biopsy, with a high index of suspicion for those with immunodeficiency. The disease is incurable. Local lesions can be excised. Multiple disseminated lesions may be treated with a combination of immunomodulator, cytotoxic, and antiviral drugs. The new, highly active antiretroviral therapy (HAART) for AIDS treatment is decreasing the incidence of KS, but new treatments are needed.¹⁶⁸

First degree: Superficial, characterized by a numb central white area surrounded by erythema and edema and including partial skin freezing without blistering

Second degree:. Full-thickness skin freezing with blistering surrounded by edema and hyperemia

Third degree: Deep, characterized by full-thickness skin and subcutaneous freezing with tissue necrosis and hemorrhagic vesicles

Fourth degree: Deep tissue freezing with full-thickness necrosis and gangrene

Male-Pattern Alopecia (Androcentric Alopecia)

Alopecia means loss of hair. Localized hair loss in men is not a disease but rather a genetically predisposed response to androgens. The mechanism of inheritance is unknown. Within the distribution of hair over the scalp, androgen-sensitive hair follicles are on top and androgen-insensitive follicles are on the sides and back. In genetically predisposed men, the androgen-sensitive follicles are transformed into vellus follicles. The normal hair is shed and replaced by fine, light, short hair. Male-pattern baldness begins with frontotemporal recession and progresses to loss of hair over the top of the scalp. Minoxidil may be used to stimulate hair growth and finasteride may decrease the effect of androgens on hair follicles.¹⁷⁴ Affected men may choose to wear wigs or have hair transplants.

Female-Pattern Alopecia

Some women in their 20s and 30s experience progressive thinning and loss of hair over the central part of the scalp.¹⁷⁵ Contrary to male-pattern baldness, no loss of hair occurs along the frontal hairline. Many of these women have elevated levels of serum adrenal androgen dehydroepiandrosterone sulfate (DHEAS), and treatment with antiandrogens can be effective.^176,177 In rare instances a male-pattern baldness develops. Laboratory evaluation of serum androgenic hormones shows elevations, and some women have decreased hair loss when treated with daily doses of spironolactone.

Alopecia Areata

Alopecia areata is an autoimmune T-cell–mediated chronic inflammatory disease directed at hair follicles that results in baldness.¹⁷⁸ Hair loss occurs in multiple areas of the scalp, usually in round patches.¹⁷⁹ The eyebrows, eyelashes, beard, and other areas of the body are rarely involved. The cause is unknown, but stressful events, cell-mediated immune factors, and genetic susceptibility are linked to hair loss. Metabolic disorders, such as Addison disease, thyroid disease, and lupus erythematosus, also are associated with alopecia areata.¹⁸⁰

The affected areas of skin are smooth or may have short shafts of hair. The hair shaft is poorly developed and breaks at the surface. Regrowth occurs within 1 to 3 months, but hair loss may recur at the same site. Permanent regrowth of hair usually occurs. Total loss of hair (alopecia totalis) occurs in some young people; the long-term prognosis for total hair regrowth is poor.

Diagnosis is made by observation of the pattern of hair loss. Biopsy may show a lymphocytic infiltrate around the follicle. There are several treatments for alopecia areata including corticosteroids and topical immunotherapy.¹⁸¹

KEY TERMS

Acne rosacea 1659

Acne vulgaris 1659

Actinic keratosis 1668

Allergic contact dermatitis 1655

Alopecia 1673

Alopecia areata 1674

Apocrine sweat gland 1646

Atopic dermatitis 1656

Basal cell carcinoma 1669

Basal layer (stratum basale) 1644

Bullous pemphigoid 1661

Candidiasis 1665

Carbuncle 1663

Cellulitis 1663

Clawlike prolongation 1654

Condylomata acuminata 1664

Cutaneous vasculitis 1666

Dermal appendage 1646

Dermis 1645

Discoid (cutaneous) lupus erythematosus (DLE) 1659

Eccrine sweat gland 1646

Eczema 1655

Epidermis 1644

Erysipelas 1663

Erythema multiforme 1661

Erythrodermic (exfoliative) psoriasis 1658

Flies 1668

Folliculitis 1662

Frostbite 1673

Furuncle 1662

Germinative layer (stratum germinativum) 1644

Guttate psoriasis 1658

Hair follicle 1646

Herald patch 1658

Herpes simplex virus (HSV) 1663

Herpes zoster 1664

Hirsutism 1674

Hypertropic scar 1654

Hyphae 1665

Impetigo 1663

Inverse psoriasis 1657

Irritant contact dermatitis 1656

Kaposi sarcoma (KS) 1672

Keloid 1654

Keratin 1644

Keratinocytes 1644

Keratoacanthoma 1668

Langerhans cell 1645

Lichen planus 1658

Lupus erythematosus 1659

Lyme disease 1667

Melanocyte 1645

Melanoma 1670

Merkel cell 1645

Mosquito 1668

Myofibroblast 1654

Nail 1646

Nevi (sing., nevus; also known as a mole) 1669

Onychomycosis 1674

Papillary capillary 1646

Papulosquamous disorder 1657

Paronychia 1674

Pemphigus 1660

Pityriasis rosea 1658

Plaque psoriasis 1657

Proteoglycan 1654

Pruritus 1654

Psoriasis 1657

Psoriatic arthritis 1658

Psoriatic nail disease 1658

Pustular psoriasis 1658

Scleroderma 1667

Sebaceous gland 1646

Seborrheic dermatitis 1656

Seborrheic keratosis 1668

Spinous layer (stratum spinosum) 1644

Squamous cell carcinoma 1670

Stasis dermatitis 1656

Stevens-Johnson syndrome 1661

Stratum corneum 1644

Systemic scleroderma (sclerosis) 1667

Tinea capitis 1664

Tinea corporis (ringworm) 1664

Tinea infection 1664

Tinea pedis 1664

Toxic epidermal necrolysis 1661

Urticaria 1666

Urticarial lesion 1666

Varicella 1664

Wart 1664