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Surgery_Schwartz. F. Genome engineering using the CRISPR-Cas9 system. Nat Protoc. 2013;8(11):2281-2308. 47. Deveau H, Garneau JE, Moineau S. CRISPR/Cas system and its role in phage-bacteria interactions. Annu Rev Microbiol. 2010;64:475-493. 48. Ma Y, Zhang L, Huang X. Genome modification by CRISPR/Cas9. FEBS J. 2014;281(23):5186-5193. 49. Lu XJ, Xue HY, Ke ZP, Jin-Lian C, Li-Juan J. CRISPR-Cas9: a new and promising player in gene therapy. J Med Genet. 2015;52(5):289-296. 50. Saleh-Gohari N, Helleday T. Conservative homologous recom-bination preferentially repairs DNA double-strand breaks in the S phase of the cell cycle in human cells. Nucleic Acids Res. 2004;32(12):3683-3688. 51. Farboud B. Targeted genome editing in Caenorhabditis elegans using CRISPR/Cas9. Wiley Interdiscip Rev Dev Biol. 2017;6(6). 52. Liu J, Zhou Y, Qi X, et al. CRISPR/Cas9 in zebrafish: an effi-cient combination for human genetic diseases modeling. Hum Genet. 2017;136(1):1-12. 53. Ren X, Holsteens K, Li H, et al. Genome editing in


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Surgery_Schwartz. J, Zhou Y, Qi X, et al. CRISPR/Cas9 in zebrafish: an effi-cient combination for human genetic diseases modeling. Hum Genet. 2017;136(1):1-12. 53. Ren X, Holsteens K, Li H, et al. Genome editing in Dro-sophila melanogaster: from basic genome engineering to the multipurpose CRISPR-Cas9 system. Sci China Life Sci. 2017;60(5):476-489. 54. Chadwick AC, Musunuru K. Treatment of dyslipidemia using CRISPR/Cas9 genome editing. Curr Atheroscler Rep. 2017;19(7):32. 55. Zou Q, Wang X, Liu Y, et al. Generation of gene-target dogs using CRISPR/Cas9 system. J Mol Cell Biol. 2015;7(6):580-583. 56. Niu Y, Shen B, Cui Y, et al. Generation of gene-modified cyno-molgus monkey via Cas9/RNA-mediated gene targeting in one-cell embryos. Cell. 2014;156(4):836-843. 57. Krishan K, Kanchan T, Singh B. Human genome editing and ethical considerations. Sci Eng Ethics. 2016;22(2):597-599. 58. Ma H, Marti-Gutierrez N, Park SW, et al. Correction of a pathogenic gene mutation in human embryos. Nature. 2017;


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Surgery_Schwartz. genome editing and ethical considerations. Sci Eng Ethics. 2016;22(2):597-599. 58. Ma H, Marti-Gutierrez N, Park SW, et al. Correction of a pathogenic gene mutation in human embryos. Nature. 2017; 548(7668):413-419. 59. Ledford H. CRISPR fixes disease gene in viable human embryos. Nature. 2017;548(7665):13-14. 60. Ormond KE, Mortlock DP, Scholes DT, et al. Human germline genome editing. Am J Hum Genet. 2017;101(2):167-176.Brunicardi_Ch15_p0479-p0510.indd 50918/02/19 11:12 AM


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Surgery_Schwartz. The Skin and Subcutaneous TissuePatrick Harbour and David H. Song 16chapterINTRODUCTIONThe skin is a complex organ encompassing the body’s surface and is continuous with the mucous membranes. Accounting for approximately 15% of total body weight, it is the largest organ in the human body. Enabled by an array of tissue and cell types, intact skin protects the body from external insults. However, the skin is also the source of a myriad of pathologies that include inflammatory disorders, mechanical and thermal injuries, infec-tious diseases, and benign and malignant tumors. The intrica-cies and complexities of this organ and associated pathologies are reasons the skin and subcutaneous tissue remain of great interest and require the attention of various surgical disciplines that include plastic surgery, dermatology, general surgery, and surgical oncology.ANATOMY AND HISTOLOGYBackgroundIt is important that surgeons understand completely the cutane-ous anatomy and its variability as they


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Surgery_Schwartz. surgery, dermatology, general surgery, and surgical oncology.ANATOMY AND HISTOLOGYBackgroundIt is important that surgeons understand completely the cutane-ous anatomy and its variability as they play an enormous role in patient health and satisfaction. The skin is made up of tissues derived from both the ectodermal and mesodermal germ cell layers.1 Three distinct tissue layers comprise the organ, and differ in composition based on location, age, sex, and ethnicity, among other variables. The outermost layer is the epidermis, which is predominantly characterized by a protective, highly keratinized layer of cells. The next layer is the dermis, which is made up of an organized collagen network to support the numerous epider-mal appendages, neurovascular structures, and supportive cells within the skin. The fatty layer below the dermis is collectively known as the hypodermis and functions in body processes of thermoregulation and energy storage, among others. These three distinct layers


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Surgery_Schwartz. the skin. The fatty layer below the dermis is collectively known as the hypodermis and functions in body processes of thermoregulation and energy storage, among others. These three distinct layers function together harmoniously and participate in numerous activities essential to life.2EpidermisThe epidermis is the outermost layer of the cutaneous tissue, and consists primarily of continually regenerating keratinocytes. The tissue is also stratified, forming four to five histologically distinct layers, depending on the location in the body. These layers are, from deep to superficial, the stratum basale, stratum spinosum, stratum granulosum, stratum lucidum and stratum corneum (Fig. 16-1). The different layers of the epidermis represent layers of keratinocytes at differing stages of their approximately thirty-day life cycle. A minority of other cell types are found in different layers of the epidermis as well. Some of these cells are permanent residents, while others are visitors from


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Surgery_Schwartz. approximately thirty-day life cycle. A minority of other cell types are found in different layers of the epidermis as well. Some of these cells are permanent residents, while others are visitors from other parts of the body. All the epidermal appendages, such as sweat glands and pilosebaceous follicles, are derived from this tissue. The thickness of the epidermis is quite variable with regard to location and age, ranging from 75 to 150 µm in thin skin (eyelids) to 0.4 to 1.5 mm in thick skin (palms and soles).2 The epidermis lacks any vascular Introduction513Anatomy and Histology513Background / 513Epidermis / 513Epidermal Components / 514Epidermal Appendages / 515Dermal Components / 516Cells / 516Cutaneous Vasculature / 516Cutaneous Innervation / 517Hypodermis / 517Inflammatory Conditions517Hidradenitis Suppurativa / 517Pyoderma Gangrenosum / 517Epidermal Necrolysis / 517Injuries518Radiation-Induced Injuries / 518Trauma-Induced Injuries / 519Caustic Injury / 520Thermal Injury /


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Surgery_Schwartz. Suppurativa / 517Pyoderma Gangrenosum / 517Epidermal Necrolysis / 517Injuries518Radiation-Induced Injuries / 518Trauma-Induced Injuries / 519Caustic Injury / 520Thermal Injury / 521Pressure Injury / 523Bioengineered Skin Substitutes524Bacterial Infections of the Skin and Subcutaneous Tissue524Introduction / 524Uncomplicated Skin Infections / 524Complicated Skin Infections / 524Actinomycosis / 526Viral Infections with Surgical Implications526Human Papillomavirus Infections / 526Cutaneous Manifestations of Human Immunodeficiency Virus / 527Benign Tumors527Hemangioma / 527Nevi / 527Cystic Lesions / 527Keratosis / 528Soft Tissue Tumors / 528Neural Tumors / 528Malignant Tumors528Basal Cell Carcinoma / 528Squamous Cell Carcinoma / 529Melanoma / 530Merkel Cell Carcinoma / 534Kaposi’s Sarcoma / 535Dermatofibrosarcoma Protuberans / 535Malignant Fibrous Histiocytoma (Undifferentiated Pleomorphic Sarcoma and Myxofibrosarcoma) / 535Angiosarcoma / 535Extramammary Paget’s Disease /


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Surgery_Schwartz. Sarcoma / 535Dermatofibrosarcoma Protuberans / 535Malignant Fibrous Histiocytoma (Undifferentiated Pleomorphic Sarcoma and Myxofibrosarcoma) / 535Angiosarcoma / 535Extramammary Paget’s Disease / 536Conclusion536Brunicardi_Ch16_p0511-p0540.indd 51319/02/19 3:08 PM 514Hair shaftStratum corneumPigment ligamentStratum germinativumStratum spinosumStratum basaleArrector pili muscleSebaceous glandHair folliclePapilla of hairBlood andlymph vesselsNerve ÿberSweatporeDermalpapillaSensory nerve ending for touchEpidermisDermisSubcutis(hypodermis)VeinArteryPaciniancorpuscleSweatglandFigure 16-1. Schematic representation of the skin and its appendages. Note that the root of the hair follicle may extend beneath the dermis into the subcutis.structures and obtains all nutrients from the dermal vasculature by diffusion.3Epidermal ComponentsKeratinocytes. Keratinocytes typically make up about 90% of the cells of the epidermis. These cells have four to five distinct stages in their life cycle, each


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Surgery_Schwartz. by diffusion.3Epidermal ComponentsKeratinocytes. Keratinocytes typically make up about 90% of the cells of the epidermis. These cells have four to five distinct stages in their life cycle, each visibly different under light microscopy. The stratum basale, or germinative layer, is a deep, single layer of asynchronous, continuously rep-licating cuboidal to columnar epithelial cells and is the 1beginning of the life cycle of the keratinocytes of the epidermis. This layer is bound to its basement membrane by complexes made of keratin filaments and anchoring structures called hemidesmosomes. They are bound to other keratinocytes by structures called desmosomes. High mitotic activity and thus large nuclei and basophilic staining characterize the stratum basale on light microscopy. This layer also lines the epidermal appendages that reside largely within the substance of the der-mis and later serves as a regenerative source of epithelium in the event of partial thickness wounds.Key


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Surgery_Schwartz. layer also lines the epidermal appendages that reside largely within the substance of the der-mis and later serves as a regenerative source of epithelium in the event of partial thickness wounds.Key Points1 The epidermis consists of continually regenerating strati-fied epithelium, and 90% of cells are ectodermally derived keratinocytes.2 Pilosebaceous units are lined by the germinal epithelium of the epidermis and thus serve as an important source of epidermal regeneration after partial-thickness injury or split-thickness skin graft.3 Dermal fibers are predominantly made of type I and III collagen in a 4:1 ratio. They are responsible for the mechanical resistance of skin.4 The drugs most commonly associated with epidermal necrolysis include aromatic anticonvulsants, sulfonamides, allopurinol, oxicams (nonsteroidal anti-inflammatory drugs), and nevirapine.5 In wounds being allowed to heal secondarily, negative pressure wound therapy can increase the rate of granula-tion tissue


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Surgery_Schwartz. allopurinol, oxicams (nonsteroidal anti-inflammatory drugs), and nevirapine.5 In wounds being allowed to heal secondarily, negative pressure wound therapy can increase the rate of granula-tion tissue formation.6 Staphylococcus aureus is the most common isolate of all skin infections. Impetigo, cellulitis, erysipelas, folliculitis, furuncles, and simple abscesses are examples of uncompli-cated infections, whereas deep-tissue infections, extensive cellulitis, necrotizing fasciitis, and myonecrosis are exam-ples of complicated infections.7 Hemangiomas arise from benign proliferation of endothe-lial cells surrounding blood-filled cavities. They most commonly present after birth, rapidly grow during the first year of life, and gradually involute in most cases.8 Basal cell carcinoma represents the most common tumor diagnosed in the United States, and the nodular variant is the most common subtype. The natural progression of basal cell carcinoma is one of local invasion rather than distant


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Surgery_Schwartz. the most common tumor diagnosed in the United States, and the nodular variant is the most common subtype. The natural progression of basal cell carcinoma is one of local invasion rather than distant metastasis.9 Squamous cell carcinoma is the second most common skin cancer, and typically arises from an actinic keratosis precur-sor. Primary treatment modalities are surgical excision and Mohs microsurgery. Cautery and ablation, cryotherapy, drug therapy, and radiation therapy are alternative treatments.10 Tumor thickness, ulceration, and mitotic rate are the most important prognostic indicators of survival in melanoma. Sentinel lymph node biopsy is often used to stage indi-viduals with biopsy-proven high risk melanoma and clini-cally node-negative disease.Brunicardi_Ch16_p0511-p0540.indd 51419/02/19 3:08 PM 515THE SKIN AND SUBCUTANEOUS TISSUECHAPTER 16The next layer is the stratum spinosum, or “spiny” layer. This layer is from five to fifteen cells in thickness and is so named due


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Surgery_Schwartz. 51419/02/19 3:08 PM 515THE SKIN AND SUBCUTANEOUS TISSUECHAPTER 16The next layer is the stratum spinosum, or “spiny” layer. This layer is from five to fifteen cells in thickness and is so named due to the spinous appearance of the intercellular des-mosomal attachments under light microscopy. The production of keratin in this cell layer is responsible for their eosinophilic appearance on hematoxylin and eosin (H&E) staining.As the keratinocytes continue to migrate superficially, they begin to flatten and develop basophilic keratohyalin gran-ules. There are also structures called lamellar granules within these cells that contain the lipids and glycolipids that will ulti-mately undergo exocytosis to produce the lipid layer around the cells. It is in this layer that the keratinocytes manufacture many of the structures that will eventually serve to protect the skin and underlying tissues from environmental insult.4 At the super-ficial aspect of this layer, the keratinocytes begin to


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Surgery_Schwartz. many of the structures that will eventually serve to protect the skin and underlying tissues from environmental insult.4 At the super-ficial aspect of this layer, the keratinocytes begin to undergo programmed cell death, losing all cellular structures except for the keratin filaments and their associated proteins. In thick skin, such as that found on the palms and soles, there is a layer of flat, translucent keratinocytes called the stratum lucidum.The final stage of the keratinocyte life cycle results in the layer of the epidermis known as the stratum corneum, or cor-nified layer. The protein-rich, flattened keratinocytes are now anucleate and surrounded by a lipid-rich matrix. Together the cells and surrounding matrix of this layer serve to protect the tissue from mechanical, chemical, and bacterial disruption while preventing insensible water losses through the skin.4,5Langerhans Cells. Of the cells in the epidermis, 3% to 6% are immune cells known as Langerhans cells.6 Typically


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Surgery_Schwartz. and bacterial disruption while preventing insensible water losses through the skin.4,5Langerhans Cells. Of the cells in the epidermis, 3% to 6% are immune cells known as Langerhans cells.6 Typically found within the stratum spinosum, these mobile, dendritic cells inter-digitate between keratinocytes of the epidermis to create a dense network, sampling any antigens that attempt to pass through the cutaneous tissue. Through use of their characteristic rodor racket-shaped Birbeck granules, they take up antigens for pre-sentation to T-cells.7 These monocyte-derived cells represent a large part of the skin’s adaptive immunity. Because of the effec-tiveness of their antigen presentation, Langerhans cells could be utilized as vaccine vehicles in the future.8 The Langerhans cells are functionally impaired by UV radiation, specifically UVB radiation, and may play a role in the development of cutaneous malignancies after UV radiation exposure.9Melanocytes. Within the stratum basale are


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Surgery_Schwartz. impaired by UV radiation, specifically UVB radiation, and may play a role in the development of cutaneous malignancies after UV radiation exposure.9Melanocytes. Within the stratum basale are melanocytes, the cells responsible for production of the pigment melanin in the skin. These neural crest-derived cells are present in a density of four to ten keratinocytes per melanocytes, and about 500 to 2000 melanocytes per mm2 of cutaneous tissue. This density varies based on location in the body, but differences in skin pig-mentation are based on the activity of individual melanocytes and not the number of melanocytes. In darker-skinned ethnici-ties, melanocytes create and store melanosomes in keratinocytes at a higher rate, but still have a pale-staining cytoplasm on light microscopy. Hemidesmosomes also attach these cells to the basement membrane, but the intercellular desmosomal connec-tions are not present. The melanocytes interact with keratino-cytes of the stratum basale and spinosum


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Surgery_Schwartz. also attach these cells to the basement membrane, but the intercellular desmosomal connec-tions are not present. The melanocytes interact with keratino-cytes of the stratum basale and spinosum via long cytoplasmic extensions leading to invaginations in several keratinocytes. Tyrosinase is created and distributed into melanosomes, and these organelles travel along the dendritic processes to eventu-ally become phagocytized by keratinocytes and distributed in a supranuclear orientation. This umbrella-like cap then serves to protect the nuclear material from damage by radiation; this could explain why light-skinned ethnicities are more prone to the development of cutaneous malignancies.10,11 Melanocytes express the bcl-2 protein, S100 protein, and vimentin, which are important in the pathology and histologic diagnosis of disorders of melanocytes.Merkel Cells. Merkel cells are slow-adapting mechanorecep-tors of unclear origin essential for light touch sensation. Thus, they typically


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Surgery_Schwartz. and histologic diagnosis of disorders of melanocytes.Merkel Cells. Merkel cells are slow-adapting mechanorecep-tors of unclear origin essential for light touch sensation. Thus, they typically aggregate among basal keratinocytes of the skin in areas where light tactile sensation is warranted, such as the digits, lips, and bases of some hair follicles.12-14 They are joined to keratinocytes in the basal layer by desmosomes and have dense neurosecretory granules containing peptides. These neu-rosecretory granules allow communication with the CNS via afferent, unmyelinated nerve fibers that contact the basolateral portion of the cell via expanded terminal discs.3 The clinical significance of Merkel cells arises in the setting of Merkel cell carcinoma, a rare, but difficult-to-treat malignancy.Lymphocytes. Less than 1% of the cells in the epidermis are lymphocytes, and these are found primarily within the basal layer of keratinocytes. They typically express an effector memory T-cell


Surgery_Schwartz

Surgery_Schwartz. than 1% of the cells in the epidermis are lymphocytes, and these are found primarily within the basal layer of keratinocytes. They typically express an effector memory T-cell phenotype.15,16Toker Cells. Toker cells are found in the epidermis of the nip-ple in 10% of both males and females and were first described in 1970. While distinct from Paget’s cells, immunohistochemical studies have implicated them as a possible source of Paget’s disease of the nipple.17-20Epidermal AppendagesSweat Glands. Sweat glands, like other epidermal appendages, are derived from the embryologic ectoderm, but the bulk of their substance resides within the dermis. Their structure consists of a tubular-shaped exocrine gland and excretory duct. Eccrine sweat glands make up a majority of the sweat glands in the body and are extremely important to the process of thermoregu-lation. Solutes are released into the gland via exocytosis. They are present in greatest numbers on the palms, soles, axillae, and forehead.


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Surgery_Schwartz. and are extremely important to the process of thermoregu-lation. Solutes are released into the gland via exocytosis. They are present in greatest numbers on the palms, soles, axillae, and forehead. Collectively they produce approximately 10 L/d in an adult. These glands are the most effective means of temperature regulation in humans via evaporative heat loss.A second type of sweat gland, known as the apocrine sweat gland, is found around the axilla, anus, areola, eyelid, and external auditory canal. The cells in this gland undergo an excretion process that involves decapitation of part of the cell. These apocrine glands are typically activated by sex hormones and thus activate around the time of puberty. The secretion from apocrine glands is initially odorless, but bacteria in the region may cause an odor to develop. Pheromone production may have been a function of the apocrine glands, but this may now be vestigial. While eccrine sweat glands are activated by the cho-linergic system,


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Surgery_Schwartz. may cause an odor to develop. Pheromone production may have been a function of the apocrine glands, but this may now be vestigial. While eccrine sweat glands are activated by the cho-linergic system, apocrine glands are activated by the adrenergic system.There is also a third type of sweat gland called apoeccrine. This is similar to an apocrine gland but opens directly to the skin surface and does not present until puberty. 21 Both types of glands are surrounded by a layer of myoepithelial cells that can contract and assist in the excretion of glandular contents to the skin surface.Pilosebaceous Units. A pilosebaceous unit is a multicompo-nent unit made up of a hair follicle, sebaceous gland, an erector pili muscle, and a sensory organ. These units are responsible for the production of hair and sebum and are present almost entirely Brunicardi_Ch16_p0511-p0540.indd 51519/02/19 3:08 PM 516SPECIFIC CONSIDERATIONSPART IIthroughout the body, sparing the palms, soles, and mucosa. They


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Surgery_Schwartz. and sebum and are present almost entirely Brunicardi_Ch16_p0511-p0540.indd 51519/02/19 3:08 PM 516SPECIFIC CONSIDERATIONSPART IIthroughout the body, sparing the palms, soles, and mucosa. They are lined by the germinal epithelium of the epidermis and thus serve as an important source of epidermal regenera-tion after partial-thickness injury or split-thickness skin graft. The sebaceous glands secrete sebum into the follicle and skin via a duct. The lipid-secreting glands are largely influenced by androgens and become functionally active during puberty. They are present in greatest numbers on the face and scalp.Nails. The nails are keratinaceous structures overlying the dis-tal phalanges of the fingers and toes. The nail is made of three main parts. The proximal portion of the nail, continuous with the germinal nail matrix, is the nail root. The root is an adher-ence point for the nail. The nail plate is the portion of the nail that lies on top of the nail bed, the shape of which is


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Surgery_Schwartz. with the germinal nail matrix, is the nail root. The root is an adher-ence point for the nail. The nail plate is the portion of the nail that lies on top of the nail bed, the shape of which is determined by the underlying phalanx. The third part of the nail is the free edge, which overlies a thickened portion of epidermis known as the hyponychium. The nail functions to protect the distal digits and augment the function of the pulp of the digits as a source of counter-pressure.Dermal ComponentsArchitecture. The dermis is a mesoderm-derived tissue that protects and supports the epidermis while anchoring it to the underlying subcutaneous tissue. It consists primarily of three unique components: a fibrous structure, the ground substance that surrounds those fibers, and the cell population that is sup-ported by the dermis. In addition, the dermis houses the neuro-vasculature that supports the epidermis and facilitates interaction with the outward environment, as well as the epidermal


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Surgery_Schwartz. that is sup-ported by the dermis. In addition, the dermis houses the neuro-vasculature that supports the epidermis and facilitates interaction with the outward environment, as well as the epidermal append-ages previously described. The dermis varies in thickness based upon body region, thinnest in the eyelids and reaching a thick-ness of up to 4 mm on the back, and is composed of two distinct layers, the papillary layer and the reticular layer. The papillary layer is made up of papillae that interdigitate with the rete ridges of the deep portion of the epidermis. This structure increases the surface area between the dermis and epidermis, increasing the resistance to shear forces as well as facilitating greater diffusion of nutrients across the dermal-epidermal junction. The papil-lary layer is characterized by a greater density of cells, and the reticular layer is almost entirely made up of a coarse network of fibers and the ground substance that surrounds it.Fibers and Ground


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Surgery_Schwartz. layer is characterized by a greater density of cells, and the reticular layer is almost entirely made up of a coarse network of fibers and the ground substance that surrounds it.Fibers and Ground Substance. Ninety-eight percent of the dry weight of the dermis is made up of collagen, typically 80% to 90% type I collagen and 8% to 12% type III collagen. Collagen types IV and VII are also found in much smaller quantities in the dermo-epidermal junction. The structure of the fibers varies along the depth of the dermis. At the superficial part of the dermis, in the papillary layer, the collagen bundles are arranged more loosely and are primarily made up of type III collagen.22 Deeper in the reticular layer of the dermis, the col-lagen fibrils are larger in diameter and organized into interwo-ven bundles surrounded by elastic fibers all within the hydrated ground substance. In a healthy adult, these dermal fibers are in a constant state of breakdown and production, dictated by the activity


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Surgery_Schwartz. bundles surrounded by elastic fibers all within the hydrated ground substance. In a healthy adult, these dermal fibers are in a constant state of breakdown and production, dictated by the activity of matrix metalloproteases and fibroblasts, respectively. The activity of the MMPs is induced by UV radiation, thus lead-ing to increased degradation and disorganization of the collagen fibers, resulting in wrinkling and weakening of the dermis in sun-exposed areas.The retractile properties of skin are due in part to elas-tic fibers found throughout the dermis. These fibers, like the collagen fibers, are thinner and more perpendicularly oriented in the papillary dermis and become thicker and parallel in the reticular dermis. These elastic fibers are also produced by fibro-blasts, but they are unique in that they can stretch to twice their original length, and return to their original configuration. The elastic fibers are also in a constant state of turnover that can be negatively impacted by


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Surgery_Schwartz. in that they can stretch to twice their original length, and return to their original configuration. The elastic fibers are also in a constant state of turnover that can be negatively impacted by the effects of UV radiation.The fibrous network of the dermis lies within a hydrated amorphous ground substance made of a variety of proteoglycans and glycosaminoglycans, molecules that can contain up to 1000 times their weight in water. This ground substance facilitates the development of the structure of the dermis and cell migration within the dermis. It also assists in redistributing forces placed on the cutaneous tissues.CellsFibroblasts. Fibroblasts, like most cells in the dermis, are found in the loose, papillary layer, and are the fundamental cells of the dermis. They are responsible for producing all der-mal fibers and the ground substance within which those fibers reside. They are typically spindleor stellate-shaped and have a well-developed rough endoplasmic reticulum, typical of


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Surgery_Schwartz. producing all der-mal fibers and the ground substance within which those fibers reside. They are typically spindleor stellate-shaped and have a well-developed rough endoplasmic reticulum, typical of cells engaging in active protein production. The fibroblasts can also differentiate into myofibroblasts, cell types that harbor myofila-ments of smooth muscle actin and, more rarely, desmin, which help to decrease the surface area of the wound by contraction.23 Because of these fundamental functions of fibroblasts, they are the workhorses of wound healing, while macrophages are the orchestrators.Dermal Dendrocytes. Dermal dendrocytes are comprised of a variety of mesenchymal dendritic cells recognizable mainly by immunohistochemistry. They are responsible for antigen uptake and processing for presentation to the immune system, as well as the orchestration of processes involved in wound healing and tissue remodeling. They are typically found in the papillary dermis around vascular


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Surgery_Schwartz. for presentation to the immune system, as well as the orchestration of processes involved in wound healing and tissue remodeling. They are typically found in the papillary dermis around vascular structures as well as sweat glands and pilosebaceous units.Mast Cells. Mast cells are effector secretory cells of the immune system that are responsible for immediate type 1 hyper-sensitivity reactions. When primed with IgE antibodies, encoun-ter with a provoking antigen causes the release of histamine and cytokines, leading to vasodilation and dermatitis commonly seen in allergic reactions.Cutaneous VasculatureWhile the epidermis is void of any vasculature structures, the dermis has a rich supply of blood and nutrients supported by paired plexuses connected by a system of arteriovenous shunts. The superficial, subpapillary plexus is located between the papillary and reticular dermis and provides a vascular loop to every papilla of the papillary dermis.24 The deep dermal plexus is located at


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Surgery_Schwartz. superficial, subpapillary plexus is located between the papillary and reticular dermis and provides a vascular loop to every papilla of the papillary dermis.24 The deep dermal plexus is located at the junction of the reticular dermis and hypodermis, and it derives its blood supply from perforating arteries of larger vessels below the cutaneous tissues. The arteriovenous shunts connecting the two horizontal plexuses can divert blood flow to or away from the skin when necessary to conserve or release body heat, or to divert blood flow to vital organs when needed. Associated with the vascular loops of the dermal papillae are the blind-ended beginnings of lymphatic vessels, which serve to transport extravasated fluid and proteins from the soft tissues back into the venous circulatory system.23Brunicardi_Ch16_p0511-p0540.indd 51619/02/19 3:08 PM 517THE SKIN AND SUBCUTANEOUS TISSUECHAPTER 16Cutaneous InnervationThe skin is a highly specialized tool for interacting with our environment


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Surgery_Schwartz. 51619/02/19 3:08 PM 517THE SKIN AND SUBCUTANEOUS TISSUECHAPTER 16Cutaneous InnervationThe skin is a highly specialized tool for interacting with our environment and, as such, carries a rich network of nervous tis-sue to facilitate this purpose. An afferent component made up of free nerve endings and specialized corpuscular receptors is responsible for conveying to our brain information about the environment, while numerous functions of the cutaneous tis-sues, such as AV-shunting, piloerection, and sweat secretion are controlled by the myelinated and unmyelinated fibers of an efferent component of the CNS.25HypodermisThe hypodermis, or subcutaneous tissue, is a richly vascularized loose connective tissue that separates and attaches the dermis to the underlying muscle and fascia. It is made up primarily of pockets of lipid-laden adipocytes separated by septae that contain cellular components similar to the dermis, neurovas-cular structures supplying the cutaneous tissue, and the


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Surgery_Schwartz. is made up primarily of pockets of lipid-laden adipocytes separated by septae that contain cellular components similar to the dermis, neurovas-cular structures supplying the cutaneous tissue, and the deepest parts of sweat glands.26 The hypodermis serves multiple func-tions—namely insulation, storage of energy, and protection from mechanical forces, allowing the skin to glide over the underlying tissues.INFLAMMATORY CONDITIONSHidradenitis SuppurativaHidradenitis suppurativa, also known as acne inversa, is a pain-ful skin condition typically affecting areas of the body bear-ing apocrine glands—typically the axillae, perineum, and the inframammary and inguinal folds. It is characterized by tender, deep nodules that can expand, coalesce, spontaneously drain, and form persistent sinus tracts in some cases leading to sig-nificant scarring and hyperkeratosis. There can be superimposed bacterial infection during episodic flares of the disease as well. In women, flares often occur


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Surgery_Schwartz. tracts in some cases leading to sig-nificant scarring and hyperkeratosis. There can be superimposed bacterial infection during episodic flares of the disease as well. In women, flares often occur premenstrually.Hidradenitis suppurativa typically affects females (female to male ratio of 3:1), most commonly during the third decade of life and has demonstrated associations with smoking and obesity.27 While the etiology of hidradenitis is incompletely understood, it is thought to be the consequence of a genetic pre-disposition exacerbated by environmental factors. About one-third of affected patients endorse a family history of the disease. A specific gene locus has not been identified, but mutations in the γ-secretase gene have been linked to the disease in some familial cases.28 The histologic progression of the disease is characterized by atrophy of the sebaceous gland, followed by inflammation of the pilosebaceous unit from both the innate and adaptive immune systems, causing


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Surgery_Schwartz. histologic progression of the disease is characterized by atrophy of the sebaceous gland, followed by inflammation of the pilosebaceous unit from both the innate and adaptive immune systems, causing hyperkeratosis and eventual granuloma forma-tion.29 Some studies have shown involvement of the IL12-IL23 pathway and TNF-α, supporting the theory that the disease is at least in part caused by an inflammatory disorder.30,31The diagnosis of hidradenitis is clinical, and the presenta-tion is most commonly categorized by the Hurley classification system, divided into three stages. Single or multiple nodules or abscesses without any sinus tracts or scarring would be classi-fied as stage 1 disease. As abscesses recur and sinus tracts and scarring form, the disease is classified as Hurley stage 2. Stage 3 is the most advanced stage, with diffuse disease and intercon-nected sinus tracts and abscesses.Treatment is typically based on Hurley staging, with topi-cal and systemic antibiotics


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Surgery_Schwartz. 2. Stage 3 is the most advanced stage, with diffuse disease and intercon-nected sinus tracts and abscesses.Treatment is typically based on Hurley staging, with topi-cal and systemic antibiotics (typically clindamycin) being used for stage I and II disease,32 while radical excision, laser treat-ment, and biologic agents are reserved for more advanced stage II and III disease.33-36 Even with complete surgical resection, recurrence rates are still high, reaching up to 50% in the infra-mammary and inguino-perineal regions. Because of increased risks of recurrence with primary closure, it is preferable to pur-sue other methods of wound closure, like split-thickness skin grafting, local or regional flaps, and healing by secondary inten-tion. Topical antimicrobial creams should be used during the healing process.Pyoderma GangrenosumPyoderma gangrenosum is an uncommon inflammatory con-dition of the skin characterized by the development of sterile pustules which progress to painful,


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Surgery_Schwartz. during the healing process.Pyoderma GangrenosumPyoderma gangrenosum is an uncommon inflammatory con-dition of the skin characterized by the development of sterile pustules which progress to painful, ulcerating lesions with purple borders. This disease is typically diagnosed between the ages of 40 and 60 years and has a slightly higher prevalence in females. Although the exact etiology is currently unknown, it typically arises in individuals with a hematologic malignancy or inflammatory disorder, such as inflammatory bowel disease or rheumatoid arthritis. The most commonly affected sites are the legs, but lesions can occur anywhere. Extracutaneous mani-festations are also possible, and it can affect mucosal tissue and solid organs. While the initial pathology is sterile, it can easily become secondarily infected. The diagnosis of this condition is based upon history and clinical presentation after the exclu-sion of infectious etiologies. There are five distinct types of pyoderma


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Surgery_Schwartz. become secondarily infected. The diagnosis of this condition is based upon history and clinical presentation after the exclu-sion of infectious etiologies. There are five distinct types of pyoderma gangrenosum described: vegetative, pustular, peris-tomal, ulcerative, and bullous. The pathogenesis of this disease is incompletely understood, but it is thought to be a genetic predisposition that is triggered by an environmental influence. An inciting cutaneous injury can often be identified preceding the ulceration. Histopathologic studies have demonstrated sig-nificantly elevated levels of inflammatory cytokines, as well as neutrophils exhibiting aberrant chemotactic signaling.37-39 Treat-ment of pyoderma gangrenosum generally involves treatment of the underlying disorder (i.e., management of Crohn’s disease) as well as systemic anti-inflammatory medications such as steroids or immunosuppressants like calcineurin inhibitors. Patients with Crohn’s disease and PG treated with infliximab


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Surgery_Schwartz. of Crohn’s disease) as well as systemic anti-inflammatory medications such as steroids or immunosuppressants like calcineurin inhibitors. Patients with Crohn’s disease and PG treated with infliximab (tumor necrosis factor [TNF]-α inhibitor) and etanercept (TNF-α antagonist) had a marked improvement in their PG.40,41 In cases of peri-stomal pyoderma gangrenosum, topical calcineurin inhibitors have been shown to be useful.42 Concurrent treatment with sys-temic and topical antimicrobials, as well as local wound care, including the debridement of purulent exudate and devitalized tissue, is also beneficial. Surgical therapy without proper sys-temic treatment will generally result in recurrent disease. Final wound closure can be achieved with primary closure or grafts.Epidermal NecrolysisEpidermal necrolysis (EN) is a rare mucocutaneous disorder characterized by cutaneous destruction at the dermoepidermal junction. EN is commonly referred to as either Stevens-Johnson syndrome (SJS) or toxic


Surgery_Schwartz

Surgery_Schwartz. necrolysis (EN) is a rare mucocutaneous disorder characterized by cutaneous destruction at the dermoepidermal junction. EN is commonly referred to as either Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) depending on the extent of skin involvement present. SJS refers to cases in which <10% of total body surface area is involved, while cases with >30% involvement are considered TEN, with an SJS-TEN overlap syndrome referring to all cases in between. These two disorders are now considered to be the same clinical entity that vary simply on the extent of cutaneous involvement. Erythema multiforme was once considered as part of the clinical subgroup Brunicardi_Ch16_p0511-p0540.indd 51719/02/19 3:08 PM 518SPECIFIC CONSIDERATIONSPART IIFigure 16-2. Blisters on the forearm of a patient several days after exposure to vancomycin. Note the clear antishear dressing and the dark silver-impregnated antimicrobial dressing (Acticoat).encompassing SJS and TEN, but it is now


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Surgery_Schwartz. of a patient several days after exposure to vancomycin. Note the clear antishear dressing and the dark silver-impregnated antimicrobial dressing (Acticoat).encompassing SJS and TEN, but it is now thought to be a sepa-rate entity related to herpetic or Mycoplasma infections.The clinical presentation usually occurs within 8 weeks of initiation of a new drug treatment and is characterized by a macular rash beginning in the face and trunk and progressing to the extremities within hours to days. A positive Nikolsky sign is often present, in which lateral pressure on the skin causes separation of the epidermis from the dermis. (Fig. 16-2). The macular rashes then begin to blister and coalesce, forming bul-lae that eventually burst, leaving partial thickness wounds with exposed dermis. Mucous membrane involvement is seen in 90% of cases and can involve the oral, genital, and ocular mucosa, as well as the respiratory and gastrointestinal tracts. The cutaneous manifestations can also be


Surgery_Schwartz

Surgery_Schwartz. membrane involvement is seen in 90% of cases and can involve the oral, genital, and ocular mucosa, as well as the respiratory and gastrointestinal tracts. The cutaneous manifestations can also be associated with high fever and pain. It is important to distinguish EN from infectious etiologies like staphylococcal scalded skin syndrome due to their similar clini-cal presentation.While the etiology is not entirely clear, it is well docu-mented to be a reaction to various drugs. While over 100 drugs have been implicated as the inciting agent of EN,43,44 there are a handful of high-risk drugs that account for a majority of the cases.45 The drugs most commonly associated with EN include aromatic anticonvulsants, sulfonamides, allopurinol, oxi-cams (nonsteroidal anti-inflammatory drugs), and nevirap-ine. The pathophysiology is also incompletely understood, but it has generally been accepted that it involves cell-mediated cytotoxicity targeted at keratinocytes and the cytokine-induced


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Surgery_Schwartz. and nevirap-ine. The pathophysiology is also incompletely understood, but it has generally been accepted that it involves cell-mediated cytotoxicity targeted at keratinocytes and the cytokine-induced expression of “death-receptors” like Fas-L. Recently, studies have demonstrated greatly increased concentrations of granuly-sin, an apoptotic protein secreted by cytotoxic T cells, within EN lesions, and thus this protein may be implicated in the patho-genesis of EN.46 A genetic component may also exist, and genetic testing before carbamazepine treatment is recommended in people of Han Chinese ancestry to exclude carriers of HLA-B1502.47The prognosis of EN is generally related to the surface area affected and secondary complications of extensive cutane-ous damage, like secondary infections and loss of hemodynamic stability due to increased insensible losses and third spacing of fluid. Modern burnand ICU-care has decreased mortality 4significantly.48 The first principle of management of EN


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Surgery_Schwartz. loss of hemodynamic stability due to increased insensible losses and third spacing of fluid. Modern burnand ICU-care has decreased mortality 4significantly.48 The first principle of management of EN is dis-continuation of the offending agent, and in drugs with short half-lives, this can significantly increase chances of survival.49 Other management principles include maintenance of euvolemia, early enteral feeding, and measures to reduce risk of infection. This includes surgical debridement of devitalized tissue, the use of topical antibiotics or antimicrobial dressings, nonadherent dress-ings, or temporary biologic or synthetic grafts until the underly-ing dermis can reepithelialize. The cornea should regularly be inspected with a Wood’s lamp to evaluate for corneal sloughing. The use of systemic corticosteroids in the acute setting is con-troversial as there have been mixed results. Some studies have shown a slowed disease progression when corticosteroid therapy was administered


Surgery_Schwartz

Surgery_Schwartz. of systemic corticosteroids in the acute setting is con-troversial as there have been mixed results. Some studies have shown a slowed disease progression when corticosteroid therapy was administered early,50 while others showed increased rates of sepsis and overall mortality with no effect on disease progression. IVIG has also been used in an effort to inhibit the Fas-L cytotoxic pathway, with some mixed results. A 2007 meta-analysis of nine IVIG trials concluded that high-dose IVIG improves survival,51 while a large retrospective analysis in 2013 concluded that there was no mortality benefit.52 Other agents, like cyclosporine A, plasmapheresis and anti-TNF-α have been studied with mixed results.48 Recent guidelines out of the United Kingdom confirm that there is still no treatment with clearly demonstrated benefit in the management of EN.53 The cutaneous manifestations of EN generally progress for 7 to 10 days, while reepithelialization gen-erally occurs over 3


Surgery_Schwartz

Surgery_Schwartz. no treatment with clearly demonstrated benefit in the management of EN.53 The cutaneous manifestations of EN generally progress for 7 to 10 days, while reepithelialization gen-erally occurs over 3 weeks.INJURIESRadiation-Induced InjuriesRadiation injuries can result from exposure to electromag-netic radiation from industrial/occupation applications or, more commonly, from environmental exposure and medical treatments. This is especially true in the continually evolv-ing role of radiation therapy in the multidisciplinary approach to oncologic disease and other skin conditions. In addition to treatment for lymphomas, head and neck squamous cell car-cinomas, and prostate adenocarcinoma, it is often an adjuvant or neoadjuvant component of the surgical treatment of rectal, breast, esophageal, and cervical cancers. Although the new modalities and principles of radiation therapy have allowed for more precise administration of this therapy, there is still collateral damage in the cutaneous


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Surgery_Schwartz. and cervical cancers. Although the new modalities and principles of radiation therapy have allowed for more precise administration of this therapy, there is still collateral damage in the cutaneous and visceral tissues sur-rounding the treatment site.Environmental sources of radiation damage are typi-cally from UV radiation. UVC rays are filtered by the ozone layer, so the only UV rays that humans typically encounter are UVA (320–400 nm) and UVB (290–320 nm).54 The amount of exposure to UV radiation is dependent on seasonal, temporal, geographic and environmental variables. Ninety-five percent of the UV rays that reach the earth’s surface are UVA rays. This radiation is less energetic (longer wavelength) than UVB rays and affects the cutaneous tissues differently. UVA waves pen-etrate deeper into the tissues, with 20% to 30% reaching the deep dermis. UVB rays are mostly absorbed in the epidermis, with 70% reaching the stratum corneum, 20% reaching the deep epidermis, and only 10%


Surgery_Schwartz

Surgery_Schwartz. deeper into the tissues, with 20% to 30% reaching the deep dermis. UVB rays are mostly absorbed in the epidermis, with 70% reaching the stratum corneum, 20% reaching the deep epidermis, and only 10% reaching the papillary dermis. Major chromophores in the cutaneous tissue include nucleic acids, aro-matic amino acids, and melanin.The short-term effects of solar radiation include erythema and pigmentation. The resultant erythema peaks at 6 to 24 hours Brunicardi_Ch16_p0511-p0540.indd 51819/02/19 3:08 PM 519THE SKIN AND SUBCUTANEOUS TISSUECHAPTER 16after exposure. The pigmentation occurs differently for UVA and UVB rays. Pigmentation occurs because of photooxidation of melanin by UVA radiation. Partial fading of this pigment change occurs within an hour after exposure, but with higher and repeated doses of UVA, stable residual pigmentation is observed. UVB waves induce neomelanization, increasing the total amount of melanin in the epidermal tissues and resulting in an effect that is


Surgery_Schwartz

Surgery_Schwartz. repeated doses of UVA, stable residual pigmentation is observed. UVB waves induce neomelanization, increasing the total amount of melanin in the epidermal tissues and resulting in an effect that is observable 72 hours after exposure. The increase in melanin as a result of UVB exposure serves as a protective mechanism to defend the nuclei of the basal keratinocytes from further radiation-induced damage by absorbing the high-energy radiation in future exposures. Long-term effects of exposure to UV radiation can lead to chronic skin changes, such as irregular pigmentation, melasma, postinflammatory pigmentation, and actinic lentigines (sun spots). Lysozyme, an enzyme secreted by cells of the immune system, typically inhibits the activity of collagenase and elastase, playing a role in turnover of the elas-tin and collagen network of the dermis. Long-term exposure to UV radiation increases the activity of lysozyme, thus impairing the natural turnover of these fibers, resulting in a


Surgery_Schwartz

Surgery_Schwartz. turnover of the elas-tin and collagen network of the dermis. Long-term exposure to UV radiation increases the activity of lysozyme, thus impairing the natural turnover of these fibers, resulting in a disorganized accumulation of elastin, and an increase in the ratio of type III to type I collagen. This results in loss of firmness and resilience of the skin, leading to wrinkles and an aged appearance.The other major source of radiation injury that a surgeon will likely encounter is from therapeutic radiation. The vari-ous forms of radiation work to destroy the replicative potential of the target cells via damage to the nucleic acid structures in the cell. This is typically used to treat oncologic disease, but it can also be used to treat benign disease like eczema, psoria-sis, and keloid scarring at relatively low exposures. While this goal is accomplished, surrounding tissues are also affected and damaged. The most radiosensitive components of the cutane-ous tissue are the basal


Surgery_Schwartz

Surgery_Schwartz. scarring at relatively low exposures. While this goal is accomplished, surrounding tissues are also affected and damaged. The most radiosensitive components of the cutane-ous tissue are the basal keratinocytes, hair follicle stem cells, and melanocytes. Exposure to this intense radiation results in disorganized, uncontrolled cell death, leading to the release of reactive oxygen species and further damage and inflammation to the surrounding cellular network. Damage to the basal kera-tinocytes and fibroblasts hinders the replicative capacity of the epidermis and dermis, respectively.Acute skin changes to these structures manifest within weeks as erythema, edema, and alopecia. Permanent hyper-pigmentation, tightening, thickening, and fibrosis of the skin become apparent as the tissue attempts to heal. In severe radia-tion injury, there can be complete loss of the epidermis, resulting in partial-thickness wounds and fibrinous exudate. Reepitheli-alization typically occurs 14 days


Surgery_Schwartz

Surgery_Schwartz. attempts to heal. In severe radia-tion injury, there can be complete loss of the epidermis, resulting in partial-thickness wounds and fibrinous exudate. Reepitheli-alization typically occurs 14 days following initial injury, pro-vided other variables affecting wound healing are optimized (bacterial colonization, nutrition.) Long-term effects include compromise of the functional integrity of the skin secondary to thrombosis and necrosis of capillaries, hypovascularity, telangi-ectasia, ulceration, fibrosis, poor wound healing, and infection. These can present weeks to years after exposure.Treatment of minor radiation injury includes skin mois-turizers and local wound care when appropriate. Severe radia-tion injury may warrant surgical excision and reconstruction with free-tissue transfer from a part of the body unaffected by radiation.Trauma-Induced InjuriesMechanical Injury. Physical disruption of the skin can occur via numerous mechanisms. Treatment of the wound is depen-dent on the


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Surgery_Schwartz. a part of the body unaffected by radiation.Trauma-Induced InjuriesMechanical Injury. Physical disruption of the skin can occur via numerous mechanisms. Treatment of the wound is depen-dent on the size of the defect left behind by the insult, any exposed structures that remain in the wound bed, and the pres-ence of contaminating debris or infection. Clean, simple lacera-tions can be irrigated, debrided, and closed primarily. There is no systematic evidence to guide the optimal timing of closure within 24 hours,55 but many surgeons will close primarily within 6 hours of injury. Grossly contaminated or infected wounds should be allowed to heal by secondary intention or delayed primary closure.56 In wounds allowed to heal secondarily, nega-tive pressure wound therapy can increase the rate of granu-lation tissue formation.57 Tangential abrasions are treated similarly to burn wounds, with depth of injury dictating man-agement. Partial thickness injuries with preservation of the regenerative


Surgery_Schwartz

Surgery_Schwartz. tissue formation.57 Tangential abrasions are treated similarly to burn wounds, with depth of injury dictating man-agement. Partial thickness injuries with preservation of the regenerative pilosebaceous units can be allowed to heal on their own while maintaining a moist, antimicrobial wound environ-ment. Full thickness wounds may require reconstruction with splitor full-thickness skin grafting depending on the size of the defect and the need for future cosmesis and durability. In the setting of devitalization of full thickness tissue, the damaged tissue may be used as a full thickness graft, provided the wound is appropriately cleaned.Bite Wounds. Dog bites alone recently accounted for 4.5 million bites to humans in a single year. Bites from dogs, humans, and other animals can quickly lead to severe deep-tissue infections if not properly recognized and treated.58 The most com-mon location of bite wounds is the hand. This area is of particular importance, as the anatomy of the hand


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Surgery_Schwartz. lead to severe deep-tissue infections if not properly recognized and treated.58 The most com-mon location of bite wounds is the hand. This area is of particular importance, as the anatomy of the hand allows for rapid pro-gression of deep infection long relatively avascular structures and can lead to long term morbidity if not adequately treated.59 Bite bacteriology is influenced by normal mouth flora, as well as the content of the offending animal’s diet. Early presentation bite wounds yield polymicrobial cultures, while cultures from a late infection will typically exhibit one dominant pathogen. Common aerobic bacteria include Pasteurella multocida, Streptococcus, Staphylococcus, Neisseria, and Corynebacterium; anaerobic organisms include Fusobacterium, Porphyromonas, Prevotella, Propionibacterium, Bacteroides, and Peptostreptococcus. Capnocytophaga canimorsus bacteria after a dog bite are rare, and it appears that immunocompromised patients are most susceptible to this type of


Surgery_Schwartz

Surgery_Schwartz. Bacteroides, and Peptostreptococcus. Capnocytophaga canimorsus bacteria after a dog bite are rare, and it appears that immunocompromised patients are most susceptible to this type of infection and its complications. The bacterial load in dog bites is heavily influenced by the last meal of the animal, increasing with wet food and shorter time since the last meal60 (Fig. 16-3). Cat bite bacteriology is similar, with slightly higher prevalence of Pasturella species. Infections from Francisella tularensis (tularemia) and Yersinia pestis (human plague) have been reported.Bacteria colonizing human bites are those present on the skin or in the mouth. These include the gram-positive aerobic organisms Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus species, and anaerobes including Peptococ-cus species, Peptostreptococcus species, Bacteroides species, and Eikenella corrodens (facultative anaerobe). Human bites are characterized by a higher bacterial load (>105).


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Surgery_Schwartz. including Peptococ-cus species, Peptostreptococcus species, Bacteroides species, and Eikenella corrodens (facultative anaerobe). Human bites are characterized by a higher bacterial load (>105). Antibiotic prophylaxis after a human bite is recommended as it has been shown to significantly decrease the rate of infection.61 A course of 3 to 7 days of amoxicillin/clavulanate is typically used. Alter-natives are doxycycline or clindamycin with ciprofloxacin.There is controversy over the closure of bite wounds. Typically, in areas of aesthetic importance, the wound is thor-oughly irrigated and debrided and primarily closed with a short course of antibiotics and close follow-up to monitor for signs of infection. In areas that are less cosmetically sensitive and bites that look grossly contaminated or infected, the wounds 5Brunicardi_Ch16_p0511-p0540.indd 51919/02/19 3:08 PM 520SPECIFIC CONSIDERATIONSPART IIABCFigure 16-3. A. Dog bite to the face involving the lip. B. Primary multilayer


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Surgery_Schwartz. or infected, the wounds 5Brunicardi_Ch16_p0511-p0540.indd 51919/02/19 3:08 PM 520SPECIFIC CONSIDERATIONSPART IIABCFigure 16-3. A. Dog bite to the face involving the lip. B. Primary multilayer closure following debridement and irrigation. Closure was performed due to aesthetic and functional considerations. C. Follow up 1 week after injury following suture removal.are allowed to close secondarily. Special consideration should be paid to puncture wounds in areas like the hands, which have multiple small compartments. Some groups have found that as long as wounds are properly irrigated and cleansed with povidone iodine solution while a short course of antibiotics is prescribed, there is no difference in infection rates in dog bite wounds closed primarily.62Rabies in domestic animals in the United States is rare, and most cases are contracted from bat bites. In developing countries, dog bites remain the most common source of rabies. Management of this is beyond the scope of this


Surgery_Schwartz

Surgery_Schwartz. in the United States is rare, and most cases are contracted from bat bites. In developing countries, dog bites remain the most common source of rabies. Management of this is beyond the scope of this chapter.Caustic InjuryChemical burns make up to 10.7% of all burns but account for up to 30% of all burn-related deaths.63 The number of cases of industrial chemical burns is declining while chemical burns in the domestic setting is on the rise. The extent of tissue destruc-tion from a chemical burn is dependent on type of chemical agent, concentration, volume, and time of exposure, among other variables.Injuries from acidic solutions are typically not as severe as those from basic solutions. This is due to the mechanism of injury of each. Acidic injuries typically result in superficial eschar formation because the coagulative necrosis caused by acids limits tissue penetration. Acids can cause thermal injury in addition to the coagulative necrosis due to exothermic reactions. Without


Surgery_Schwartz

Surgery_Schwartz. formation because the coagulative necrosis caused by acids limits tissue penetration. Acids can cause thermal injury in addition to the coagulative necrosis due to exothermic reactions. Without treatment, acid injuries will progress to erythema and ulcers through the subcutaneous tissue. Injuries from basic solu-tions undergo liquefactive necrosis, unlike acids, and thus have no barrier preventing them from causing deeper tissue injury. Brunicardi_Ch16_p0511-p0540.indd 52019/02/19 3:08 PM 521THE SKIN AND SUBCUTANEOUS TISSUECHAPTER 16Figure 16-4. Self-inflicted alkali burn with cleaner fluid.(Fig. 16-4). Common examples of agents that often cause alka-line chemical burns are sodium hydroxide (drain decloggers and paint removers) and calcium hydroxide (cement).Treatment for acidic or alkaline chemical burns is first and foremost centered around dilution of the offending agent, typically using distilled water or saline for 30 minutes for acidic burns and 2 hours for alkaline


Surgery_Schwartz

Surgery_Schwartz. or alkaline chemical burns is first and foremost centered around dilution of the offending agent, typically using distilled water or saline for 30 minutes for acidic burns and 2 hours for alkaline injuries. Attempting to neutralize the offending agent is typically discouraged, as it does not offer an advantage over dilution and the neutralization reaction could be exothermic, increasing the amount of tissue damage. After removal of the caustic agent, the burn is treated like other burns and is based on the depth of tissue injury. Topical antimicrobials and nonadherent dressings are used for partial-thickness wounds with surgical debridement and reconstruction if needed for full-thickness injuries. Liposuction and saline dilution have been used in cases were injury to deeper structures was suspected.64 Prophylactic use of antibiotics is generally avoided.There are several chemical agents that have specific treat-ments, including the use of calcium gluconate for hydrofluoric acid burns


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Surgery_Schwartz. suspected.64 Prophylactic use of antibiotics is generally avoided.There are several chemical agents that have specific treat-ments, including the use of calcium gluconate for hydrofluoric acid burns and polyethylene glycol for phenol burns. These types of treatments are specific to the offending agent and out-side of the scope of this chapter.One type of caustic injury that is commonly seen in the hos-pital is extravasation injury, especially in the setting of chemo-therapeutic administration. Extravasation is estimated to occur in 0.1% to 0.7% of all cytotoxic drug administrations. Like other chemical burns, extravasation injuries depend on properties of the offending agent, time of exposure, concentration, and volume of drug delivered to the tissues. Extravasation injuries typically cause little damage, but they can cause significant morbidity in those with thin skin, fragile veins, and poor tissue perfusion, like neonates and the critically ill. (Fig. 16-5).Initial presentation of


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Surgery_Schwartz. little damage, but they can cause significant morbidity in those with thin skin, fragile veins, and poor tissue perfusion, like neonates and the critically ill. (Fig. 16-5).Initial presentation of extravasation injuries usually involves swelling, pain, erythema, and blistering. It may take days or longer for the extent of tissue damage to demarcate. Thorough evaluation to rule out injury to deeper tissues should be conducted. The treatment for extravasation injuries is usu-ally conservative management with limb elevation, but saline aspiration with a liposuction cannula in an effort to dilute and remove the offending agent has been used soon after injury pre-sentation.65 Infiltration of specific antidotes directed toward the offending agent has been described, but it lacks the support of randomized controlled trials, and no consensus in treatment has been reached.66 It is best to avoid cold or warm compression because the impaired temperature regulation of the damaged tissue may lead


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Surgery_Schwartz. randomized controlled trials, and no consensus in treatment has been reached.66 It is best to avoid cold or warm compression because the impaired temperature regulation of the damaged tissue may lead to thermal injury. After the wound demarcates, full-thickness skin death should be surgically debrided and man-aged like other wounds based on depth of injury.Thermal InjuryThermal injury involves the damage or destruction of the soft tissue due to extremes of temperature, and the extent of injury is dependent on the degree temperature to which the tissue is exposed and the duration of exposure. The pathophysiology and management are discussed in detail in a separate chapter. Briefly, the management of thermal wounds is initially guided by the concept of three distinct zones of injury. The focus of thermal injury that has already undergone necrosis is known as the zone of coagulation. Well outside the zone of coagulation is the zone of hyperemia, which exhibits signs of inflammation but


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Surgery_Schwartz. of thermal injury that has already undergone necrosis is known as the zone of coagulation. Well outside the zone of coagulation is the zone of hyperemia, which exhibits signs of inflammation but Brunicardi_Ch16_p0511-p0540.indd 52119/02/19 3:08 PM 522SPECIFIC CONSIDERATIONSPART IIABCFigure 16-5. A. Potassium chloride intravenous infiltrate in a critically ill patient on multiple vasopressors. B. Following operative debride-ment to paratenon layer. C. Temporary coverage with Integra skin substitute.will likely remain viable. In between these two zones is a zone of stasis with questionable tissue viability, and it is this area at which proper burn care can salvage viable tissue and decrease the extent of injury67 (Fig. 16-6).The mechanisms of injury in hypothermic situation dif-fer. Direct cellular damage can occur as a result of the crys-tallization of intracellular and extracellular components with resultant dehydration of the cell and disruption of lipid protein


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Surgery_Schwartz. dif-fer. Direct cellular damage can occur as a result of the crys-tallization of intracellular and extracellular components with resultant dehydration of the cell and disruption of lipid protein Brunicardi_Ch16_p0511-p0540.indd 52219/02/19 3:08 PM 523THE SKIN AND SUBCUTANEOUS TISSUECHAPTER 16complexes. During rewarming, further damage occurs because of the shifts of fluid in response to melting ice. Indirect effects of hypothermic injury include microvascular thrombosis and tis-sue ischemia. This, together with subsequent edema and inflam-mation upon rewarming, propagates tissue injury even further.68 Even so, the standard treatment of frostbite injury begins with rapid rewarming to 40°C to 42°C. In addition, further treatment includes debridement of all devitalized tissue, hydrotherapy, elevation, topical antimicrobials, topical antithromboxanes (aloe vera), and systemic antiprostaglandins (aspirin).Pressure InjuryA problem that all surgeons will encounter very early in their


Surgery_Schwartz

Surgery_Schwartz. elevation, topical antimicrobials, topical antithromboxanes (aloe vera), and systemic antiprostaglandins (aspirin).Pressure InjuryA problem that all surgeons will encounter very early in their careers is pressure necrosis. The development of pressure ulcers is increasingly being regarded as a marker of quality of care, and strategies aimed at prevention have been the source of recent study. Pressure ulcers are known to affect the critically ill (22% to 49% of all critically ill patients are affected), but pressure sources can also affect the chronically bedor wheelchair-bound, patients undergoing surgical procedures, and those with Foley catheters, artificial airways, or other medical equipment (Fig. 16-7).Pressure ulcers can present in several ways depending on the stage at presentation. They are typically grouped into 4 stages: stage 1, nonblanching erythema over intact skin; stage 2, partial-thickness injury with blistering or exposed dermis; stage 3, full-thickness injury


Surgery_Schwartz

Surgery_Schwartz. They are typically grouped into 4 stages: stage 1, nonblanching erythema over intact skin; stage 2, partial-thickness injury with blistering or exposed dermis; stage 3, full-thickness injury extending down to, but not including, fascia and without undermining of adjacent tissue; and stage 4, full-thickness skin injury with destruction Figure 16-6. Scald burn of upper arm, back, and buttock. Pink areas are superficial partial-thickness burn, whereas whiter areas are deeper burns in the dermis.ABFigure 16-7. A. Pressure wound after removal of a poorly padded cast. Stage cannot be determined until debridement but is at least a grade 2 lesion. B. Decubitus ulcer of the sacral region, stage 4, to the tendinous and bone layers.or necrosis of muscle, bone, tendon, or joint capsule. Tissue destruction occurs most easily at bony prominences due to the inability to redistribute forces along a greater surface area. The average perfusion pressure of the microcirculation is about 30 mmHg, and


Surgery_Schwartz

Surgery_Schwartz. occurs most easily at bony prominences due to the inability to redistribute forces along a greater surface area. The average perfusion pressure of the microcirculation is about 30 mmHg, and pressures greater than that cause local tissue isch-emia. In animal models, pressure greater than twice the capillary perfusion pressure produces irreversible tissue necrosis in just 2 hours. The most common areas affected are the ischial tuber-osity (28%), greater trochanter (19%), sacrum (17%), and heel (9%). Tissue pressures can measure up to 300 mmHg in the ischial region during sitting and 150 mmHg over the sacrum while lying supine.69 Tissues with a higher metabolic demand are Brunicardi_Ch16_p0511-p0540.indd 52319/02/19 3:09 PM 524SPECIFIC CONSIDERATIONSPART IItypically susceptible to insult from tissue hypoperfusion more rapidly than tissues with a lower metabolic demand. Because of this, it is possible to have muscle necrosis beneath cutaneous tis-sue that has yet to develop signs of


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Surgery_Schwartz. from tissue hypoperfusion more rapidly than tissues with a lower metabolic demand. Because of this, it is possible to have muscle necrosis beneath cutaneous tis-sue that has yet to develop signs of irreversible damage.Management of pressure sores first and foremost involves avoidance of prolonged pressure to at-risk areas. Strategies typically employed are pressure-offloading hospital beds or assist devices, patient repositioning every 2 hours, early mobilization, prophylactic silicone dressings, and nurs-ing education.70 From a wound healing perspective, patients should be nutritionally optimized and surgically debrided as appropriate.71,72 The presence of stage III or IV pressure ulcers is not necessarily an indication for surgery, and fevers in a patient with chronic pressure ulcers are often from a urinary or pulmonary source.73-75 Goals of surgical intervention are drain-age of fluid collections, wide debridement of devitalized and scarred tissue, excision of pseudobursa,


Surgery_Schwartz

Surgery_Schwartz. are often from a urinary or pulmonary source.73-75 Goals of surgical intervention are drain-age of fluid collections, wide debridement of devitalized and scarred tissue, excision of pseudobursa, ostectomy of involved bones, hemostasis, and tension-free closure of dead space with well-vascularized tissue (muscle, musculocutaneous, or fasciocutaneous flaps). Stage 2 and 3 ulcers may be left to heal secondarily after debridement. Subatmospheric pressure wound therapy devices (vacuum-assisted closure) play a role in wound management by removing excess interstitial fluid, promoting capillary circulation, decreasing bacterial coloniza-tion, increasing vascularity and granulation tissue formation, and contributing to wound size reduction.57BIOENGINEERED SKIN SUBSTITUTESThe management of soft tissue defects is more commonly including the use of bioengineered skin substitutes. These products are typically derived from or designed to imitate dermal tissue, providing a regenerative matrix or


Surgery_Schwartz

Surgery_Schwartz. tissue defects is more commonly including the use of bioengineered skin substitutes. These products are typically derived from or designed to imitate dermal tissue, providing a regenerative matrix or stimulating autogenous dermal regeneration while protecting the underly-ing soft tissue and structures. There are generally four types of skin substitutes: (a) autografts, which are taken from the patient and placed over a soft tissue defect (split-thickness and full-thickness skin grafts); (b) allografts, which are taken from human organ donors; (c) xenografts, which are taken from members of other animal species; and (d) synthetic and semisynthetic biomaterials that are constructed de novo and may be combined with biologic materials.76 Acellular dermal matrices are one type of skin substitute and are used quite often for wound healing and support of soft tissue reconstruction. They are from allogenic or xenogeneic sources and are com-posed of collagen, elastin, laminin, and


Surgery_Schwartz

Surgery_Schwartz. substitute and are used quite often for wound healing and support of soft tissue reconstruction. They are from allogenic or xenogeneic sources and are com-posed of collagen, elastin, laminin, and glycosaminoglycans. Tissue incorporation generally occurs within 1 to 2 weeks.77 Dermal matrices have been shown to be an effective bridge to split-thickness skin grafting for wounds that have exposed nerves, vessels, tendons, bones, or cartilage.78 Bilayered matri-ces can also be used to promote dermal regeneration in acute or chronic wounds. These products can be temporary, needing to be removed prior to grafting, or permanent, integrating into the host tissue and being grafted directly.BACTERIAL INFECTIONS OF THE SKIN AND SUBCUTANEOUS TISSUEIntroductionIn 1998, the Food and Drug Administration (FDA) categorized infections of the skin and skin structures for the purpose of clini-cal trials. A revision of this categorization in 2010 excluded spe-cific diagnoses such as bite wounds, decubitus


Surgery_Schwartz

Surgery_Schwartz. (FDA) categorized infections of the skin and skin structures for the purpose of clini-cal trials. A revision of this categorization in 2010 excluded spe-cific diagnoses such as bite wounds, decubitus ulcers, diabetic foot ulcers, perirectal abscesses, and necrotizing fasciitis. The general division into “uncomplicated” and “complicated” skin infections can be applied to help guide management.79 The agent most commonly responsible for skin and soft tissue infections is S aureus and is isolated in 44% of spec-imens.80 Less common isolates include other gram-positive bacteria such as Enterococcus species (9%), β-hemolytic strep-tococci (4%), and coagulase-negative staphylococci (3%). S aureus is more commonly responsible for causing abscesses. Patients with an impaired immune system (diabetic, cirrhotic, or neutropenic patients) are at higher risk of infection from gram-negative species like Pseudomonas aeruginosa (11%), Esche-richia coli (7.2%), Enterobacter (5%), Klebsiella (4%), and


Surgery_Schwartz

Surgery_Schwartz. cirrhotic, or neutropenic patients) are at higher risk of infection from gram-negative species like Pseudomonas aeruginosa (11%), Esche-richia coli (7.2%), Enterobacter (5%), Klebsiella (4%), and Serratia (2%), among others.Uncomplicated Skin InfectionsUncomplicated infections involve relatively small surface area (<75 cm2) and bacterial invasion limited to the skin and its appendages. Impetigo, erysipelas, cellulitis, folliculitis, and simple abscess fall into this category. Impetigo is a superficial infection, typically of the face, that occurs most frequently in infants or children, resulting in honey-colored crusting. Erysip-elas is a cutaneous infection localized to the upper layers of the dermis, while cellulitis is a deeper infection, affecting the deeper dermis and subcutaneous tissue. Folliculitis describes inflammation of the hair follicle, and a furuncle describes a fol-licle with swelling and a collection of purulent material. These lesions can sometimes coalesce into a


Surgery_Schwartz

Surgery_Schwartz. tissue. Folliculitis describes inflammation of the hair follicle, and a furuncle describes a fol-licle with swelling and a collection of purulent material. These lesions can sometimes coalesce into a carbuncle, an abscess with multiple different draining sinus tracts.It is recommended to culture infectious lesions to help identify the causative agent, but treatment without these studies is reasonable in typical cases. Minor infections can be safely treated with topical antimicrobials like 2% mupirocin to pro-vide coverage for methicillin-resistant S aureus (MRSA). Fol-liculitis generally resolves with adequate hygiene and warm soaks. Furuncles, carbuncles and other simple abscesses can be incised, drained, and packed, typically without the use of systemic antibiotics. The decision to use systemic antibiotics after incision and drainage of abscess should be made based upon presence or absence of systemic inflammatory response syndrome (SIRS) criteria.81For nonpurulent, uncomplicated


Surgery_Schwartz

Surgery_Schwartz. systemic antibiotics after incision and drainage of abscess should be made based upon presence or absence of systemic inflammatory response syndrome (SIRS) criteria.81For nonpurulent, uncomplicated cellulitis in which there is no drainable collection, systemic antibiotic coverage for β-hemolytic streptococcus is recommended. If there is no improvement in 48 to 72 hours or worsening of symptoms, antibiotic coverage should be added for MRSA. Systemic therapy for purulent cellulitis, which includes cutaneous abscesses, should cover MRSA, and empiric coverage for streptococcus is likely unnecessary. Antibiotic coverage for streptococcus is generally accomplished with β-lactam antibi-otics like penicillins or first-generation cephalosporins. MRSA coverage is accomplished with clindamycin, trimethoprim-sulfamethoxazole, linezolid, and tetracyclines. Clindamycin, trimethoprim-sulfamethoxazole, linezolid, or tetracycline combined with a β-lactam can all be used for dual coverage of


Surgery_Schwartz

Surgery_Schwartz. trimethoprim-sulfamethoxazole, linezolid, and tetracyclines. Clindamycin, trimethoprim-sulfamethoxazole, linezolid, or tetracycline combined with a β-lactam can all be used for dual coverage of streptococcus and MRSA.Complicated Skin InfectionsComplicated skin infections include superficial cellulitis encompassing a large surface area (>75 cm2) or deeper infec-tions extending below the dermis. Necrotizing soft tissue infec-tions (NSTIs), including necrotizing fasciitis, can rapidly cause extensive morbidity and mortality, thus their prompt diagnosis and appropriate management is crucial. A thorough history and 6Brunicardi_Ch16_p0511-p0540.indd 52419/02/19 3:09 PM 525THE SKIN AND SUBCUTANEOUS TISSUECHAPTER 16exam should be performed to elicit information (e.g., history of trauma, diabetes mellitus, cirrhosis, neutropenia, bites, IV or subcutaneous drug abuse) as well as physical findings such as crepitus (gas-forming organism), fluctuance (abscess), purpura (sepsis in streptococcal


Surgery_Schwartz

Surgery_Schwartz. mellitus, cirrhosis, neutropenia, bites, IV or subcutaneous drug abuse) as well as physical findings such as crepitus (gas-forming organism), fluctuance (abscess), purpura (sepsis in streptococcal infections), bullae (streptococci, Vibrio vulnificus), lymphangitis, and signs of a systemic inflammatory response.Extensive cellulitis is managed in a similar fashion as simple cellulitis. Initial treatment consists of intravenous anti-biotics that cover β-hemolytic streptococcus, such as ceph-alosporins, with the addition of MRSA coverage if there is no improvement in symptoms. Vancomycin is typically the first choice for MRSA coverage, but this drug is inferior to β-lactams for coverage of MSSA. Alternative antibiotics that are typically effective against MRSA are linezolid, daptomy-cin, tigecycline, and telavancin. Clindamycin is approved for use against MRSA, but resistance rates are increasing, and its use is discouraged if institutional rates of clindamycin resis-tance are


Surgery_Schwartz

Surgery_Schwartz. tigecycline, and telavancin. Clindamycin is approved for use against MRSA, but resistance rates are increasing, and its use is discouraged if institutional rates of clindamycin resis-tance are >15%.81Necrotizing soft tissue infections occur 500 to 1500 times a year in the United States82 and are frequently asso-ciated with diabetes mellitus, intravenous drug abuse, obe-sity, alcohol abuse, immune suppression, and malnutrition.83 Because NSTIs can often present initially with nonspecific findings, the physician should always have a high index of suspicion when evaluating a patient. The threshold for surgi-cal exploration and debridement should be low, particularly in a weakened host. Occasionally an inciting event or point of entry can be identified, but in 20% to 50% of cases, the exact cause is unknown. These infections are associated with a high mortality, ranging from 25% to 40%, with higher rates in the truncal and perineal cases.NSTIs are classified based on anatomic site,


Surgery_Schwartz

Surgery_Schwartz. cause is unknown. These infections are associated with a high mortality, ranging from 25% to 40%, with higher rates in the truncal and perineal cases.NSTIs are classified based on anatomic site, involved tis-sues, and the offending organisms. NSTIs commonly originate at the genitalia, perineum (Fournier’s gangrene), and abdomi-nal wall. Subcutaneous tissue, fascia and muscle can all be affected. Necrotizing fasciitis involves infection of the fascia, and the infection can quickly travel along the easily separable, avascular planes. There are three types of NSTIs when clas-sified by the offending agent. The most common is type 1, which is caused by a polymicrobial source including gram-positive cocci, gram-negative rods, and anaerobic bacteria, specifically Clostridium perfringens and C septicum. Type 2 is caused by a monomicrobial source of β-hemolytic Strepto-coccus or Staphylococcus species, with MRSA contributing to the increasing number of community-acquired NSTIs.84 A his-tory of


Surgery_Schwartz

Surgery_Schwartz. Type 2 is caused by a monomicrobial source of β-hemolytic Strepto-coccus or Staphylococcus species, with MRSA contributing to the increasing number of community-acquired NSTIs.84 A his-tory of trauma is often elicited and can be associated with toxic shock syndrome. Type 3 is a rare but fulminant subset result-ing from a V vulnificus infection of traumatized skin exposed to a body of salt-water.In addition to signs of SIRS, patients can present with skin changes like erythema, bullae, necrosis, pain, and crepitus. (Fig. 16-8). They may exhibit signs of hemodynamic instability, and gas within the soft tissues on imaging is pathognomonic. Patients can present with a range of symptoms, from minimal skin change to frank necrosis, and the time of progression to fulminant disease varies in each patient. Laboratory values are nonspecific and resemble values seen in sepsis. There have been attempts at creating scoring systems to assist in the diagnosis of NSTI. One study in 2000 used the


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Surgery_Schwartz. each patient. Laboratory values are nonspecific and resemble values seen in sepsis. There have been attempts at creating scoring systems to assist in the diagnosis of NSTI. One study in 2000 used the criteria of a white blood cell count >15,400 and a serum sodium level <135 mmol/L. This test was found to have a negative predictive value of 99%, but a positive predictive value of only 26%.85 In 2004, six criteria ABFigure 16-8. A. Initial presentation of necrotizing soft issue infec-tion in an obese, diabetic patient. B. Following operative debride-ment to muscle layer.were used and referred to as the Laboratory Risk Indicator for Necrotizing Fasciitis, or LRINEC, and included C-reactive protein (CRP), white blood cell (WBC) count, hemoglobin, plasma sodium, creatinine, and glucose.86 A score of 8 or greater Brunicardi_Ch16_p0511-p0540.indd 52519/02/19 3:09 PM 526SPECIFIC CONSIDERATIONSPART IIsuggested a high probability of NSTI, 6 or 7 an intermediate probability, and <5 a low


Surgery_Schwartz

Surgery_Schwartz. score of 8 or greater Brunicardi_Ch16_p0511-p0540.indd 52519/02/19 3:09 PM 526SPECIFIC CONSIDERATIONSPART IIsuggested a high probability of NSTI, 6 or 7 an intermediate probability, and <5 a low probability. This test was internally validated and found to have a PPV of 92% and an NPV of 96%. However, some have criticized this study because of its small sample size and over-reliance on CRP, which can be elevated in multiple other conditions. Blood cultures are not always posi-tive, and tissue samples will demonstrate necrosis, white blood cell infiltration, thrombosis, angiitis, and microorganisms. The use of cross-sectional imaging in the diagnosis of NSTI is lim-ited, and it should not delay appropriate surgical treatment.Three principles form the foundation of the management of NSTIs: (a) source control with wide surgical debridement, (b) broad-spectrum intravenous antibiotics, and (c) supportive care and resuscitation. As soon as the diagnosis is clear or the sus-picion is


Surgery_Schwartz

Surgery_Schwartz. NSTIs: (a) source control with wide surgical debridement, (b) broad-spectrum intravenous antibiotics, and (c) supportive care and resuscitation. As soon as the diagnosis is clear or the sus-picion is high, the patient should be taken for operative explo-ration and debridement. Incisions should be made parallel to neurovascular structures and through the fascial plane, removing any purulent or devitalized tissue until viable, bleeding tissue is encountered. On inspection, the tissue will appear necrotic with dead muscle, thrombosed vessels, the classic “dishwater” fluid, and a positive finger test, in which the tissue layers can be easily separated from one another. In Fournier’s gangrene, one should aim to preserve the anal sphincter as well as the testicles (blood supply is independent of the overlying tissue and is usually not infected). Return to the OR should be planned for the next 24 to 48 hours to verify source control and the extent of damage. Broad spectrum antibiotic therapy


Surgery_Schwartz

Surgery_Schwartz. the overlying tissue and is usually not infected). Return to the OR should be planned for the next 24 to 48 hours to verify source control and the extent of damage. Broad spectrum antibiotic therapy should be initiated as soon as possible, with the intent of covering gram positives (including MRSA), gram negatives, and anaerobic organisms. The Infec-tious Diseases Society of America recommends initiating ther-apy with intravenous vancomycin and piperacillin/tazobactam, unless a monomicrobial agent is identified, in which case more directed therapy would be appropriate.81 Antibiotic therapy should continue until the patient requires no further debride-ment, is clinically improving, and has been afebrile for 48 to 72 hours.Adjuncts to surgery include topical antimicrobial creams, subatmospheric pressure wound dressings, and optimization of nutrition. Controversial topics include the role of hyperbaric oxygen87 (may inhibit infection by creating an oxidative burst, with anecdotally fewer


Surgery_Schwartz

Surgery_Schwartz. pressure wound dressings, and optimization of nutrition. Controversial topics include the role of hyperbaric oxygen87 (may inhibit infection by creating an oxidative burst, with anecdotally fewer debridements required and improved survival, but limited availability) and IVIG (may modulate the immune response to streptococcal superantigens). Wound clo-sure is performed once bacteriologic, metabolic, and nutritional balances are obtained.ActinomycosisActinomycetes is a genus of gram positive rods that inhabit the oropharynx, gastrointestinal tract, and female genital tract. The most commonly isolated species causing disease in humans is A isrealii. The cervicofacial form of Actinomycetes infection is the most common presentation, representing 55% of cases, and typically presenting as an acute pyogenic infection in the submandibular or paramandibular area. Patients can also exhibit chronic soft tissue swelling, fibrosis, and sinus discharge of sulfur granules.88 Demonstration of


Surgery_Schwartz

Surgery_Schwartz. an acute pyogenic infection in the submandibular or paramandibular area. Patients can also exhibit chronic soft tissue swelling, fibrosis, and sinus discharge of sulfur granules.88 Demonstration of gram-positive filamentous organisms and sulfur granules on histological examination is strongly supportive of a diagnosis of actinomycosis.89 These infections are typically treated with high doses of intravenous followed by oral penicillin therapy. Surgical treatment is uti-lized if there is extensive necrotic tissue, poor response to anti-biotics, or the need for tissue biopsy to rule out malignancy.VIRAL INFECTIONS WITH SURGICAL IMPLICATIONSHuman Papillomavirus InfectionsHuman papillomaviruses represent a group of over 100 iso-lated types of small DNA viruses of the Papovavirus fam-ily that is highly host-specific to humans.90 These viruses are transmitted via cutaneous contact with individuals who have clinical or subclinical infection and occur more fre-quently in immunocompromised


Surgery_Schwartz

Surgery_Schwartz. is highly host-specific to humans.90 These viruses are transmitted via cutaneous contact with individuals who have clinical or subclinical infection and occur more fre-quently in immunocompromised individuals. The viruses are responsible for the development of verrucae, or warts. These are histologically characterized by nonspecific findings of hyperkeratosis, papillomatosis, and acanthosis, as well as the hallmark koilocytes (clear halo around nucleus). Clinically, these generally arise as slow-growing papules on the skin or mucosal surfaces. Regression of HPV lesions is frequently an immune-mediated, spontaneous event that is exemplified by the persistent and extensive manifestation of this virus in the immune-compromised patient.The subtypes are generally grouped, based on their pre-sentation, as cutaneous or mucosal. Cutaneous types most com-monly affect the hands and fingers. Verruca vulgaris, or common warts, are caused by HPV types 1, 2, and 4, with a prevalence of up to 33% in


Surgery_Schwartz

Surgery_Schwartz. as cutaneous or mucosal. Cutaneous types most com-monly affect the hands and fingers. Verruca vulgaris, or common warts, are caused by HPV types 1, 2, and 4, with a prevalence of up to 33% in school children and 3.5% in adults, and a higher prevalence in the immunosuppressed population.91 Plantar and palmar warts (HPV-1 and -4) typically occur at points of pres-sure and are characterized by a keratotic plug surrounded by a hyperkeratotic ring with black dots (thrombosed capillaries) on the surface. Plane warts occur on the face, dorsum of hands, and shins. They are caused by HPV-3 and -10 and tend to be multiple, flat-topped lesions with a smooth surface and light brown color. Cutaneous warts typically regress spontaneously in the immunocompetent patient. Epidermodysplasia verruci-formis is a rare, autosomal recessive inherited genetic skin dis-order that confers increased susceptibility to certain types of HPV. This presents with difficult-to-treat and often widespread verrucae that


Surgery_Schwartz

Surgery_Schwartz. is a rare, autosomal recessive inherited genetic skin dis-order that confers increased susceptibility to certain types of HPV. This presents with difficult-to-treat and often widespread verrucae that carry a higher risk of malignant transformation (30%–50% risk of squamous cell carcinoma), especially when caused by HPV types 5 and 8.92 A similar clinical picture has been described in human immunodeficiency virus (HIV) and transplant patients.93,94Mucosal HPV types cause lesions in the mucosal or geni-tal areas and behave like sexually transmitted infections. The most common mucosal types are HPV-6, -11, -16, -18, -31 and -33. These lesions present as condylomata acuminata, genital or veneral warts, papules that occur on the perineum, external genitalia, anus, and can extend into the mucosal surfaces of the vagina, urethra and rectum. These lesions are at risk for malig-nant transformation, with types 6 and 11 conferring low risk, and types 16, 18, 31 and 33 conferring a high risk. The


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Surgery_Schwartz. surfaces of the vagina, urethra and rectum. These lesions are at risk for malig-nant transformation, with types 6 and 11 conferring low risk, and types 16, 18, 31 and 33 conferring a high risk. The recently developed quadrivalent HPV vaccine, targeting HPV types -6, -11, -16, and -18, is now available to both males and females age 9 to 26 and is associated with an up to 90% reduction of infections from those HPV types.95Treatment is aimed at physical destruction of the affected cells. Children often require no treatment as spontaneous regres-sion is common. In cases causing physical or emotional discom-fort, or in cases of immunocompromise or risk of transmission, treatment may be indicated. Cryotherapy using liquid nitrogen is an effective treatment for most warts, but care must be taken not to damage underlying structures.96 Topical preparations of salicylic acid, silver nitrate, and glutaraldehyde may also be Brunicardi_Ch16_p0511-p0540.indd 52619/02/19 3:09 PM 527THE SKIN AND


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Surgery_Schwartz. not to damage underlying structures.96 Topical preparations of salicylic acid, silver nitrate, and glutaraldehyde may also be Brunicardi_Ch16_p0511-p0540.indd 52619/02/19 3:09 PM 527THE SKIN AND SUBCUTANEOUS TISSUECHAPTER 16used. Treatment of recalcitrant lesions includes a variety of ther-apeutic options aimed at physically destroying the lesions by electrodessication, cryoablation, and pulsed dye laser therapy. Additional modalities such as H2-antagonists and zinc sulfate may have a role in augmenting the immune response and reduc-ing recurrence rates.Cutaneous Manifestations of Human Immunodeficiency VirusThe HIV-infected patient is significantly more susceptible to infectious and inflammatory skin conditions than the rest of the population.97 These skin disorders may be due to the HIV infection itself or from opportunistic infections secondary to immunosuppression. During early stages, nonspecific cutane-ous manifestations may occur. Acute retroviral syndrome occurs following


Surgery_Schwartz

Surgery_Schwartz. HIV infection itself or from opportunistic infections secondary to immunosuppression. During early stages, nonspecific cutane-ous manifestations may occur. Acute retroviral syndrome occurs following inoculation in one-half to two-thirds of patients, and 30% to 50% of these patients can present with an acute viral exanthem.98 This is usually a morbilliform rash affecting the face, trunk, and upper extremities. Other skin changes, as well as common skin disorders with atypical features, can occur, including recurrent varicella zoster, hyperkeratotic warts, and seborrheic dermatitis. Condylomata acuminate and verrucae appear early; however, their frequency and severity do not change with disease progression.Late-presenting cutaneous manifestations include chronic herpes simplex virus (HSV), cytomegalovirus, and, to a lesser extent, molluscum contagiousum, which is typically treatable with imiquimod. HSV is the most common viral infection in the patient with HIV, and is more likely to


Surgery_Schwartz

Surgery_Schwartz. cytomegalovirus, and, to a lesser extent, molluscum contagiousum, which is typically treatable with imiquimod. HSV is the most common viral infection in the patient with HIV, and is more likely to display atypical fea-tures and less likely to spontaneously resolve in these patients.99 Mycobacterial infections and mucocutaneous candidiasis also occur. Bacterial infections such as impetigo and folliculitis may be more persistent and widespread.Malignant lesions such as Kaposi’s sarcoma occur in less than 5% of HIV-infected patients in the United States, although the worldwide prevalence in acquired immunodeficiency syn-drome (AIDS) patients exceeds 30%. Kaposi’s sarcoma is a vas-cular neoplasm that can affect cutaneous and visceral tissues. While the rates of Kaposi’s sarcoma development have sharply declined since the widespread use of antiretroviral therapy, the rates of other cutaneous malignancies have remained stable. The risk of an HIV-infected patient developing a cutaneous


Surgery_Schwartz

Surgery_Schwartz. have sharply declined since the widespread use of antiretroviral therapy, the rates of other cutaneous malignancies have remained stable. The risk of an HIV-infected patient developing a cutaneous malig-nancy is about 5.7%, with basal cell carcinoma being the most common type encountered.100With regard to general surgical considerations in HIV patients, contributing related morbidities such as malnutrition, decreased CD4 count, and presence of opportunistic infection may result in delayed and attenuated wound healing capacity.101BENIGN TUMORSHemangiomaHemangiomas are benign vascular tumors that arise from the proliferation of endothelial cells that surround blood-filled cavities. They occur in about 4% of children by 1 year of age. Their natural history is typically presentation shortly after birth, a period of rapid growth during the first year, and then gradual involution over childhood in more than 90% of cases. These hemangiomas are generally managed nonsurgically prior to


Surgery_Schwartz

Surgery_Schwartz. after birth, a period of rapid growth during the first year, and then gradual involution over childhood in more than 90% of cases. These hemangiomas are generally managed nonsurgically prior to involution. Occasionally, during the rapid growth phase, the lesions can obstruct the airway, GI tract, vision, and musculo-skeletal function. In these cases, surgical resection is indicated prior to the involution phase. Hemangiomas can sometimes con-sume a large percentage of cardiac output, resulting in high-output heart failure or a consumptive coagulopathy, which may also necessitate resection. These lesions characteristically express the GLUT-1 glucose transporter protein, which is absent in cells of the normal cutaneous vasculature.102 First-line ther-apy for these infantile hemangiomas is propranolol, which causes cessation of growth and, in most cases, actual regression of the lesions.103,104 Systemic corticosteroids and interferon-α can impede tumor progression, and laser therapy has