CHAPTER EIGHT: Atypical Wounds

At the end of this chapter, the learner will be able to:

1. Recognize signs of an atypical wound.

2. Categorize an atypical wound into a basic pathology.

3. Determine the appropriate medical specialist for a given wound.

4. Develop an evidence-based care plan for an atypical wound.

5. Educate the patient and family about the wound diagnosis.

Most wounds are diagnosed as arterial, venous, pressure, neuropathic, surgical, or burn and are treated according to the principles that have been discussed in the previous chapters. If a wound has a different appearance or does not respond to standard care, the clinician is challenged to determine either the factors that are inhibiting healing or to consider a different diagnosis. This chapter reviews the basic morphology of skin disease, red flags of atypical wounds, and characteristics of different diagnostic categories. The pathophysiology, clinical presentation with photographs, differential diagnosis, medical management, and wound management of each wound category are provided to assist the clinician in making sound clinical decisions.

The first signal that a wound is atypical is that little signal in the clinician’s instinct that says, “This is just not quite what it looks to be.” And usually it behooves the clinician to follow those instincts, to at least rule out an atypical diagnosis, and at most to make a differential diagnosis that completely changes the care plan and results in wound healing. TABLE 8-1 provides a list of characteristics that suggest a wound does not fall into the typical categories.^1,2

Many diseases will cause changes in the skin that are predictable and/or suggestive of a certain diagnosis. TABLE 8-2 provides a list of terms and definitions of integumentary characteristics (based on size, texture, and color) that are used to describe abnormal skin appearance.² These terms are used in the following descriptions of atypical wound clinical presentations.

Allergic Reactions

Allergic reactions can be either contact (the offending substance touches the skin) or systemic (the offending substance is injected or ingested). In either case, the substance, termed an antigen, causes an immunological response that results in the production of antibodies and a subsequent inflammatory response.

The reaction can actually cause wounds to develop, or in the case of existing wounds, prevent healing from progressing.

Contact Dermatitis

Pathophysiology

Dermatitis can be either contact or irritant, depending on the host immune system and the concentration of the irritant.³ In contact allergies, the irritant reacts with the skin barrier to initiate an immune response—the allergen binds to the carrier protein and creates a sensitizing antigen, the Langerhans cells carry the antigen to the T cells, and the T cells cause the release of cytokines. Thus develops the inflammatory symptoms of erythema, rash, itching, and sometimes vesicular lesions (FIGURES 8-1, 8-2). The allergic response can be either immediate or delayed, and can involve both the skin and the subcutaneous tissue. Usually the response increases in severity after repeated exposures due to increased numbers of antibodies.

The irritant type of contact dermatitis is not an immunological response, but a reaction to a caustic substance and depends on the concentration of the substance, for example, a chemical or topical liquid.

Patients with chronic leg wounds have an increased susceptibility to allergic contact dermatitis,⁴ especially if they are being treated with compression therapy. This condition is sometimes referred to as stasis dermatitis. If contact dermatitis is suspected or if the patient reports a history of allergies to other substances, patch testing can be performed to confirm the diagnosis. TABLE 8-3 provides a list of common allergens for patients who have wounds.

Clinical Presentation

Signs of dermatitis include erythema, weeping, scaling of the periwound area, and itching. It can occur at any age; however, in the older population it can easily be misdiagnosed. In severe cases, shiny skin and alopecia may develop. A visible determining factor is that the symptoms occur only in areas of direct contact with the irritating material.

Differential Diagnosis

• ▪ Cellulitis

• ▪ Vasculitis

Medical Management

The most important component of treating any dermatitis is the identification and discontinuation of the medication, dressing, or other substance that might be responsible for contact dermatitis. Low-dose topical steroids may help decrease inflammation and discomfort; systemic steroids may be beneficial if there is an extensive area of contact dermatitis.

Wound Management

Patients usually require only supportive care and discontinuation of the irritating topical agent and, in the case of an existing wound, substitution of a dressing that has fewer or no allergens. Nonadherent hypoallergenic dressings are recommended for care of open lesions. Most products that are used for wound care are available in latex-free forms, as both patients and clinicians can suffer from latex allergies. The skin will usually heal in 2 to 3 weeks.

Drug-Induced Hypersensitivity Syndrome

Pathophysiology

Drug-induced hypersensitivity syndrome (DIHS) is an immunologic response to a drug received either orally, by injection, or by IV. Although not fully understood, the process is similar to what occurs with skin allergies except that the immune response is activated by the causative agents and their metabolites rather than by a direct effect on the keratinocytes.⁵ There are numerous syndromes based on severity, types of lesions and underlying diseases processes; however, all of them produce generalized (rather than localized) skin lesions and systemic symptoms (TABLE 8-4).

Clinical Presentation

Symptoms include generalized rash (with or without vesicles) and any of the following: local eruptions, fever, lymphedema, mucosal lesions, conjunctivitis, and epidermal sloughing (FIGURE 8-3). Onset is usually 1 to 3 weeks after the first exposure to the offending drug, beginning with a fever or sore throat and progressing to the cutaneous/mucosal involvement. In the younger adult population (20 to 40 years), the syndrome is termed erythema multiforme.

Differential Diagnosis

• ▪ Infection

• ▪ Vasculitis

• ▪ Contact dermatitis

Medical Management

Medical management begins with identification and cessation of the causative agent, which is usually the last one that the patient has initiated taking. Depending on the severity of the symptoms, corticosteroids are used to prevent progression and relieve symptoms, and supportive care is provided in an intensive care unit or a burn unit for more severe cases.

Wound Management

In minor cases, cessation of the medication may be sufficient to reverse symptoms and no wound care is needed. In more severe cases with epidermal sloughing, treatment is similar to that of a deep superficial burn except that debridement of the detached epidermal tissue is usually not advisable. Nonadherent antimicrobial dressings are recommended to help prevent infection and to avoid further skin tearing with dressing changes. Prevention of fluid loss and infection is paramount, and as the patient improves, dressings to promote reepithelialization are advised.

Autoimmune Disorders

Vasculitis

Vasculitis is an inflammatory disorder of blood vessels, which can ultimately result in organ damage, including the skin. The etiology is often idiopathic—it is a reaction pattern that may be triggered by certain comorbidities including underlying infection, malignancy, medication, and connective tissue diseases such as systemic lupus erythamatosus (FIGURE 8-4). Circulating immune complexes (antibody/antigen) deposit in the blood vessel walls, causing inflammation that may be segmental or involve the entire vessel. At the site of inflammation, varying degrees of cellular inflammation and resulting necrosis or scarring occur in one or more layers of the vessel wall, and inflammation in the media of the muscular artery tends to destroy the internal elastic lamina. ^6–7

Leukocytoclastic vasculitis, a histopathologic term used to describe findings in small-vessel vasculitis, refers to the breakdown of inflammatory cells that leaves small nuclear fragments in and around the vessels. Vasculitic inflammation tends to be transmural, rarely necrotizing, and nongranulomatous. Resolution of the inflammation tends to result in fibrosis and intimal hypertrophy, which in combination with secondary clot formation, can narrow the arterial lumen and account for the tissue ischemia or necrosis.⁸ Clinical symptoms (ie, tissue loss) depend on the artery or arteries that are involved and the extent of lumen occlusion. Cutaneous vasculitis usually occurs in the lower extremities and feet.

Clinical Presentation

Clinical presentation, which varies depending on the arterial involvement, includes palpable purpura, livedo reticularis, pain, skin lesions with or without nodules, and tissue necrosis. It may present as one large necrotic lesion or several small lesions, but all are full thickness after debridement. Systemic systems may also be present and usually relate to kidney, lung, or gastrointestinal tract involvement. On some occasions, signs of vasculitis in other organs may appear at the same time that skin lesions appear (FIGURES 8-5, 8-6). One very distinctive characteristic for differential diagnosis from chronic venous wounds is the exquisite pain that occurs with vasculitis, making the initial local treatment very tedious.

Differential Diagnosis (TABLE 8-5)

• ▪ Giant cell arteritis

• ▪ Primary angiitis of the CNS

• ▪ Takayasu arteritis

• ▪ Churg-Strauss syndrome

• ▪ Immune complex–associated vasculitis

• ▪ Microscopic polyangiitis

• ▪ Polyarteritis nodosa

• ▪ Rheumatoid arthritis

• ▪ Wegener granulomatosis

• ▪ Henoch-Schönlein purpura

• ▪ Chronic venous wounds

Medical Management

Treatment of any vasculitis depends on the etiology, extent, and severity of the disease. For secondary vasculitic disorders, treating the underlying comorbidity (eg, infection, drug use, cancer, or autoimmune disorder) is crucial.

Remission of life- or organ-threatening disorders is induced by using cytotoxic immunosuppressants (eg, cyclophosphamide) and high-dose corticosteroids, usually for 3 to 6 months, until remission occurs or until the disease activity is acceptably reduced. Adjusting treatment to maintain remission takes longer, usually 1 to 2 years. During this period, the goal is to eliminate corticosteroids, reduce the dosage, or use less potent immunosuppressants as long as needed. After tapering or eliminating corticosteroids, methotrexate or azathioprine can be substituted to maintain remission.

Wound Management

Initial treatment of wounds caused by vasculitis is extremely difficult because of the pain. The principles of standard wound care (debride necrotic tissue, treat inflammation and infection, apply moist wound dressings, nurture the edges, and ensure optimal oxygen supply, termed TIMEO₂)⁹ are recommended. Topical lidocaine helps reduce pain during treatments, noncontact low-frequency ultrasound helps mobilize cellular activity and interstitial fluids, and compression therapy helps manage the edema that occurs in the lower extremities as a result of the inflammation and decreased mobility. Nonadherent dressings that promote autolysis of the necrotic tissue (eg, X-Cell, Medline, Mundelein, IL) are excellent initially, especially in reducing pain levels with dressing changes. Silicone-backed foam dressings are helpful in absorbing exudate as well as in reducing pain. If the patient is on steroids, local vitamin A can be used to negate the effects of steroids. As the acute inflammation recedes, pain levels decrease, and wound healing progresses to proliferation, treatment can be more aggressive.

Antiphospholipid Syndrome

Pathophysiology

The antiphospholipid syndrome (APS) is characterized by elevated titres of different antiphospholipid antibodies. It consists of arteriole thrombosis (and in pregnancy, fetal demise) associated with various autoimmune antibodies directed against one or more phospholipid-binding proteins (eg, anti-β2-glycoprotein I, anticardiolipin, and lupus anticoagulant).¹⁰ These proteins normally bind to phospholipid membrane constituents and protect them from excessive coagulation activation. The autoantibodies displace the protective proteins and thus produce procoagulant endothelial cell surfaces and cause arterial or venous thrombosis. In vitro clotting tests may paradoxically be prolonged because the antiprotein/phospholipid antibodies interfere with coagulation factor assembly and with activation on the phospholipid components that are added to plasma to initiate the tests.

The lupus anticoagulant is an antiphospholipid autoantibody that binds to protein-phospholipid complexes. It was initially recognized in patients with SLE; however, these patients now account for a minority of patients with the autoantibody. The lupus anticoagulant is suspected if the PTT is prolonged and does not correct immediately upon 1:1 mixing with normal plasma but does return to normal upon the addition of an excessive quantity of phospholipids (done by the hematology laboratory). Antiphospholipid antibodies in patient plasma are measured by immunoassays of IgG and IgM antibodies that bind to phospholipid-β2-glycoprotein I complexes on microtiter plates.¹⁰

Clinical Presentation

The arteriole thrombosis results in venous swelling, creating the typical livedo reticularis skin appearance. In addition, the lower extremities may have superficial thrombophlebitis with cutaneous infarcts. As the disease progresses, skin necrosis may occur (FIGURE 8-7).

Differential Diagnosis

• ▪ Disseminated intravascular coagulation

• ▪ Infective endocarditis

• ▪ Thrombotic thrombocytopenic purpura

Medical Management

Asymptomatic individuals in whom blood test findings are positive do not require specific treatment.

Prophylactic therapy involves elimination of other risk factors such as oral contraceptives, smoking, hypertension, or hyperlipidemia. For patients with SLE, hydroxychloroquine, an anti-inflammatory which may have intrinsic antithrombotic properties, may be useful. Statins are beneficial for patients with hyperlipidemia. If the patient has a thrombosis, full anticoagulation with intravenous or subcutaneous heparin followed by warfarin therapy is recommended.^10,11,12

Based on the most recent evidence, a reasonable target for the international normalized ratio (INR) is 2.0 to 3.0 for venous thrombosis and 3.0 for arterial thrombosis. Patients with recurrent thrombotic events, while well maintained on the above regimens, may require an INR of 3.0 to 4.0. For severe or refractory cases, a combination of warfarin and aspirin may be used. Treatment for significant thrombotic events in patients with APS is generally lifelong.

Wound Management

Conservative wound care is recommended for patients with skin lesions, keeping the wound moist and following wound bed preparation principles. Healing of wounds caused by other etiologies, eg. trauma or spider bites, will be delayed.

Pemphigus

Pathophysiology

Pemphigus is an autoimmune blistering disease resulting from loss of normal intercellular attachments in the skin and oral mucosal membrane. Circulating antibodies attack the cell surface adhesion molecule desmoglein at the desmosomal cell junction in the suprabasal layer of the epidermis, resulting in the destruction of the adhesion molecules (acantholysis) and initiating an inflammatory response that causes blistering. There are three major forms of pemphigus: pemphigus foliaceus (FIGURE 8-8) and pemphigus vulgaris that have IgG autoantibodies against desmoglein 1 and desmoglein 3, respectively; and paraneoplastic pemphigus that has IgG autoantibodies against plakins and desmogleins (FIGURE 8-9).

Clinical Presentation

Pemphigus vulgaris, the most common type, involves the mucosa and skin, especially of the scalp, face, axilla, groins, trunk, and points of pressure. Patients usually present with painful oral mucosal erosions and flaccid blisters, erosions, crusts, and macular erythema in areas of skin involvement.^10,12 The primary cell adhesion loss is at the deeper suprabasal layer. (Refer to Chapter 1 for a review of the skin anatomy.) Pemphigus foliaceus is a milder form of the disease, with the acantholysis occurring more superficial in the epidermis and usually on the face and chest. Paraneoplastic pemphigus, in addition to having different autoantibodies, occurs exclusively on patients who have some type of malignancy, usually a lymphoproliferative disorder (FIGURE 8-9). Because of the malignancy, mortality is high in this type of pemphigus.¹³

Differential Diagnosis

Diagnosis is confirmed by using immunofluorescence to demonstrate the IgG autoantibodies against the cell surface of intraepidermal keratinocytes.

Medical Management

Medical treatment of all three types consists of systemic corticosteroids and immunosuppressive therapy.

Wound Management

Wound management is conservative with the goal of preventing infection and promoting reepithelialization if denuding occurs with the blistering. Flat antimicrobial dressings (eg, Acticoat Flex, Smith & Nephew, Largo, FL) are useful over open areas, and hydrotherapy is beneficial when the disease is widespread and in the crusty phase. Secondary dressings are required for most areas, and can include surgical or fish-net garments. Silicone-backed foam dressings without adhesive borders are also recommended for easy removal of loose necrotic tissue without causing painful skin tears.

Bullous Pemphigoid

Pathophysiology

Bullous pemphigoid (BP) is associated with tissue-bound and circulating autoantibodies directed against BP antigen 180 and BP antigen 230, both components of the basement membrane.¹² An immune reaction is initiated by the formation of IgG autoantibodies that target dystonin, a component of the hemidesmosomes, resulting in the infiltration of immune cells to the area. The consequence is separation of the dermal/epidermal junction with fluid collection and blistering or bullae.

Clinical Presentation

BP occurs most commonly among the elderly, and the most common sites of involvement include inner aspects of thighs, flexor aspects of forearms, axilla, groin, and oral cavity. The extremities can also become involved. Clinically, patients can present with urticarial plaques with intense pruritis to widespread tense bulla filled with clear fluid (FIGURE 8-10).

Differential Diagnosis

Histologically, BP is the prototype of a subepidermal bullous disease along with eosinophilic spongiosis. The dermis shows an inflammatory infiltrate composed of neutrophils, lymphocytes, and eosinophils. Diagnosis is confirmed by the presence of linear deposits of IgG and/or C3 along the dermal-epidermal junction on direct immunoflouroscence.^10,12

Medical Management

Medical options include systemic corticosteroids and immunosuppressive therapy.

Wound Management

Wound management recommendations are the same as for pemphigus, with the goal of minimizing pain, preventing infection, and promoting reepithelialization.

Cryoglobulinemia

Pathophysiology

Cryoglobulins are abnormal proteins (immunoglobulins), and cryoglobulinemia is the presence of these proteins in the blood. They coagulate or become thick and gel-like in temperatures below body temperature (37° C), thereby clogging the small blood vessels and causing hypoxic skin changes, ischemic wounds, or other organ damage (TABLE 8-6). The symptoms are reversible if the environmental temperature is warmed. The disorder is grouped into three main types, depending on the type of antibody that is produced: Type I is most often related to cancer of the blood or immune system, for example, multiple myeloma. Types II and III, also referred to as mixed cryoglobulinemia, most often occur in people who have a chronic inflammatory condition, for example, hepatitis C or systemic lupus erythematosus. Type II is the most common type, and most of these patients also have hepatitis C.^1,10,12

Clinical Presentation

Symptoms vary depending on the type of cryoglobulinemia present and the organs that are affected. Systemic signs may include difficulty breathing, fatigue, glomerulonephritis, joint pain, and muscle pain. Integumentary signs may begin with purpura and Raynaud phenomenon (FIGURE 8-11). Meltzer triad, associated with Types II and III, includes arthralgia, purpura, and weakness.¹⁴ See TABLE 8-6 for a list of cryoglobulinemia symptoms.

Differential Diagnosis

• ▪ Antiphospholipid syndrome

• ▪ Chronic lymphocytic leukemia

• ▪ Churg-Strauss syndrome

• ▪ Cirrhosis

• ▪ Giant cell arteritis

• ▪ Systemic lupus erythematosus

Medical Management

Treatment of mild or moderate cryoglobulinemia depends on the underlying cause, and treating the cause will often treat the cryoglobulinemia as well. Mild cases can be treated simply by avoiding cold temperatures. Standard hepatitis C treatments usually work for patients who have hepatitis C and mild or moderate cryoglobulinemia. However, the condition can return when treatment stops. NSAIDs may be used to treat mild cases that involve arthralgia and myalgia. Severe cryoglobulinemia (involving vital organs or large areas of skin) is treated with corticosteroids, immunosuppressants, interferon, or cytotoxic medications. Plasmapheresis may be indicated if the complications are life threatening.¹⁵

Wound Management

Wound care involves treatment of infection and pain management, especially in the early stages. Nonadherent dressings such as X-Cell (Medline, Mundelein, IL), hydrogel, Acticoat (Smith & Nephew, Largo, FL), and petrolatum gauze help minimize pain with dressing changes and promote autolytic debridement. A topical anesthetic is advised 10 to 15 minutes before initiating any sharp debridement; enzymatic debridement may also be beneficial but can cause stinging and burning upon application. Absorbent dressings are advised if there is wound drainage, and modified compression (eg, with short stretch bandages) helps reduce edema that occurs with chronic inflammation, immobility, and lower extremity dependency. Compression bandages also help keep the extremities warm and facilitate vasodilation. If edema is not severe, warm hydrotherapy can help reduce precipitation of the cryoglobulins and relieve ischemic pain. Patient education regarding avoidance of cold or wearing warm clothing such as thermal socks is a crucial component of long-term management.

Pyoderma Gangrenosum

Pathophysiology

Pyoderma gangrenosum (PD) is an autoimmune disorder of unknown etiology that leads to painful skin necrosis. PD is commonly associated with other inflammatory diseases such as Crohn disease, inflammatory bowel disease, arthritis, and hematologic malignancy.¹⁵ Pathergy, the development of skin lesions in the area of trauma or the enlargement of initially small lesions, is commonly seen with PD, especially if debridement of necrotic tissue is attempted. Neutrophilic dermatosis occurs with altered neutrophilic chemotaxis and is thought to be part of the pathology.¹⁶

Clinical Presentation

PD ulcers usually begin as small pustules or blisters and become larger with a violaceous border and surrounding erythema. The first lesion may be at the site of minor trauma, but will progress and enlarge rapidly. They are painful, necrotic, and usually recurring. Sometimes PD will appear in groups of lesions at different stages of formation or healing. They do not respond to standard care if diagnosed as another wound type, and indeed may worsen if the standard TIMEO₂ care is administered (FIGURES 8-12 to 8-14).

Differential Diagnosis

As there is no diagnostic test to confirm PD and multiple other conditions that resemble PD, a correct diagnosis relies on clinical presentation and exclusion of other causes. TABLE 8-7 lists the systemic diseases most often associated with PD. Further differentiation is made into these four subgroups: ulcerative, pustular, bullous, and vegetative.^12,17

Medical Management¹⁸

Systemic management includes treatment of any underlying disease; systemic steroids are recommended for severe or widespread disease. Other therapies that have been used in patients with PD include antibiotics (dapsone and minocycline), cyclosporine, clofazimine, azathioprine, methotrexate, chlorambucil, cyclophosphamide, thalidomide, tacrolimus, mycophenolate, mofetil, IV immunoglobulin, plasmapheresis, and infliximab.^10,12,19

Wound Management

Topical steroids, topical tacrolimus, nicotine patches, and intralesional steroids have been used for mild or moderate disease. Debridement of adhered tissue is contraindicated and may cause pathergy; however, as the necrotic tissue loosens with reepithelialization, it may be gently removed with sterile forceps. Keeping the lesions covered with a nonadherent mesh or silicone-backed wicking foam that will allow drainage to escape to a secondary dressing can help alleviate the pain associated with PD wound care. Split-thickness skin grafts, along with concurrent immunosuppressive therapy to reduce the risk of pathergy, have been reported.

Necrobiosis Lipoidica Diabeticorum

Pathophysiology

Necrobiosis Lipoidica diabeticorum (NLD) is a disease of unknown etiology that is usually seen in morbidly obese patients with a strong family history of diabetes. Different pathological mechanisms have been proposed and include microangiopathic and neuropathic processes, abnormal collagen degeneration, abnormal immune mechanisms, and abnormal leukocyte function. NLD also results in thickening of the blood vessel walls and fat deposition, making the integumentary symptoms similar to vasculitis. The disease tends to be chronic with recurrent lesions and scarring.¹⁹

Clinical Presentation

Lesions usually are bilateral but asymmetric on the tibial surface of the lower leg, and begin as a rash or 1 to 3 mm slightly raised spots. They progress to irregular ovoid reddish-brown plaques with shiny yellow centers and violaceous indurated borders. The edges may be raised and purple, and the wound bed may have good granulation tissue but no epithelial migration. Pain and edema are also usually present. Remodeling is characterized by round patches of hyperpigmentation (FIGURE 8-15).^10,12,20

Differential Diagnosis

• ▪ Pyoderma gangrenosum

• ▪ Calciphylaxis

• ▪ Vasculitis

• ▪ Diabetic wound with peripheral vascular disease

Medical Management

Systemic steroids or other immunotherapy can be given in patients with severe disease. Blood thinners such as pentoxifylline and aspirin may be helpful in facilitating cell migration to the damaged tissue.

Wound Management

Topical and intralesional steroids can be beneficial in treating mild to moderate cases. Other reported treatments include 0.1% topical tacrolimus ointment,²⁰ collagen matrix dressings,²¹ and phototherapy.²² A combination of low-frequency noncontact ultrasound, topical steroid ointment, saline-impregnated cellulose dressings, and multilayer compression wraps, in conjunction with pentoxifylline, was a successful combination used by the editor for a patient with chronic lesions of more than 1 year duration.

Scleroderma

Pathophysiology

Scleroderma (systemic sclerosis) is a chronic disease that causes the skin to become thick and hard (sclerotic) with a buildup of scar tissue, resulting in loss of skin elasticity, joint range of motion, muscle strength, and mobility. Patients with scleroderma usually have proliferation of fibroblasts and excessive collagen proteins. There is also damage to internal organs such as the heart and blood vessels, lungs, stomach, kidneys, heart, and other organs. Scleroderma is an autoimmune disorder of unknown etiology that usually affects women between the age of 30 and 50 and results in extensive scarring and disfigurement as it progresses.²³

The sequence of scleroderma involves the following: arteriole endothelial cells die by apoptosis and are replaced by collagen; inflammatory cells infiltrate the arteriole and cause more damage, resulting in the scarred fibrotic tissue that is the hallmark of scleroderma.^10,12

Clinical Presentation

The two main types of scleroderma are localized and systemic. Localized is further differentiated into morphea with discolored patches on the skin, and linear with streaks or bands of thick hard skin on the arms and legs. Localized scleroderma only affects the skin and not the internal organs. Systemic scleroderma can be limited (affecting only the arms, hands, and face) or diffuse (rapidly progressing, affecting large areas of the skin and one or more organs). Thirty-five percent of the patients with scleroderma develop skin ulcers that are painful, refractory, and over bony prominences (FIGURE 8-16). CREST, a limited systemic form of scleroderma, is described in TABLE 8-8. In addition, patients may experience joint pain, fatigue, depression, reduced libido, and altered body image. A third type is scleroderma sine sclerosis, which includes Raynaud phenomenon and internal involvement without sclerotic skin.²⁴

Differential Diagnosis

Other systemic autoimmune diseases, for example, systemic lupus erythematosus and rheumatoid arthritis.

Medical Management

Because the etiology is unknown, treatment of scleroderma centers on alleviating symptoms, preserving skin integrity with protective strategies, and preventing infection. D-penicillamine, colchicine, PUVA, relaxin, cyclosporine, and omega-oil derivatives have been used to treat the skin fibrosis. Immunosuppressive agents such as methotrexate and cyclosporine have been used to treat the systemic disease. Plasmapheresis can be used in severe cases. ^1,16

Wound Management

Local wound care is tedious because of the high-pain levels associated with open wounds on sclerotic skin, and wound healing is impeded by the scarring of the subcutaneous tissue and the immunosuppressive medications. Enzymatic debridement with collagenase may be helpful with painful wounds, as well as occlusive dressings to help with autolytic debridement. Nonadherent dressings are advised both to minimize pain and avoid tearing skin upon removal. Silicone-backed foam dressings are useful as secondary dressings. Patient education regarding protective measures for skin is crucial, for example, using gloves when doing housework, avoiding caustic liquids, wearing warm clothes to avoid Raynaud phenomenon, and using moisturizers to avoid dry skin. As the disease progresses, custom shoes with molded inserts to accommodate changes in the shape of the feet can help maintain independent ambulation.

Herpes Virus

Pathophysiology

Varicella is a virus that presents in three different ways: herpes simplex Type 1 (oral or cold sores), herpes simplex Type 2 (genital herpes), and herpes zoster (varicella-zoster or shingles). Herpes simplex, commonly referred to as “cold sores,” is caused by recurrent infections with herpes simplex virus (HSV), a DNA virus that invades the cell nucleus and replicates, thereby producing partial thickness wounds on the mouth and lips (FIGURE 8-17). Chicken pox is a childhood disorder caused by the varicella-zoster virus (VZV). The virus enters through the respiratory system and infects the tonsillar T cells. The infected T cells carry the virus to the reticuloendothelial system where the major replication occurs and to the skin where the rash appears (FIGURE 8-18).²⁶

The VZV can remain latent in the nerve ganglion and reactivate in later years, usually during a period of stress or immunosuppression, as herpes varicella-zoster or “shingles” (FIGURE 8-19). Vesicles can involve the corium and dermis, with degenerative changes characterized by ballooning, multinucleated giant cells, and eosinophilic intranuclear inclusions. Infection may involve localized dermal blood vessels, resulting in necrosis and epidermal hemorrhage.¹⁰ Individuals who are immunosuppressed can have more severe cases of herpes, with the incidence of herpes zoster more than 14 times higher in adults with HIV.

Clinical Presentation

Herpes simplex usually occurs initially in childhood and progresses through the stages of prodrome, erythema, papule, vesicle, ulcer, hard crust, and residual dry flaking and swelling. Lesions can become secondarily infected by Staphylococcus or Streptococcus. Individuals tend to have recurrent eruptions. Nonulcerative lesions tend to last 3 days; full-blown ulcerative lesions may last 7 to 10 days.

Chicken pox usually presents with prominent fever, malaise, and a pruritic rash that starts on the face, scalp, and trunk and spreads to the extremities. The rash is initially maculopapular and rapidly progresses to vesicles, then pustules that rupture, and then to crusts.

Herpes varicella-zoster presents as an eruption of grouped vesicles on an erythematous base usually limited to a single dermatome. Initial symptoms include dermatologic tingling or pain in the affected dermatome 48 to 72 hours before the onset of lesions, which can appear for 3 to 5 days. Lesions develop quickly into vesicles, then rupture, ulcerate, and dry out. They usually resolve in 10 to 15 days, although the pain may remain as postherpetic neuralgia. In patients with advanced HIV, the herpetic infection may develop into chronic ulcers and fissures with a substantial degree of edema.

Differential Diagnosis

History and clinical presentation are often all that is necessary to establish the diagnosis of herpes; therefore, confirmatory tests such as the Tzanck smear preparation, biopsy, or viral culture are rarely necessary. Other differential diagnoses include

• ▪ Small pox—lesions are deeper and painful; all lesions occur at the same stage

• ▪ Disseminated HSV—usually occurs in the setting of a skin disorder

• ▪ Meningococcemia—presents with petechiae, purpura, sepsis

• ▪ Atopic dermatitis

• ▪ Atypical measles

• ▪ Poison ivy

• ▪ Spinal nerve compression (pain)

Medical Management

Chicken pox will usually heal in less than 2 weeks without medical intervention.

Uncomplicated herpes varicella-zoster is treated for 7-10 days with acyclovir (Zovirax), famciclovir (Famvir), or valacyclovir (Valtrex). These oral antiviral medications reduce the duration and severity of adult symptoms. Oral prednisone may decrease the risk of postherpetic neuralgia. VariZIG may prevent complications in immunocompromised and pregnant patients. Antihistamines may help reduce the itching, and Zostrix may help reduce severe neuralgia. If the lesions have not healed in 3 to 4 weeks, the patient may have a drug-resistant virus that may require treatment with IV foscarnet.

Wound Management

Herpes simplex can be treated with topical acyclovir and mild corticosteroid ointment²⁵ or with a thin hydrocolloid dressing.²⁶ Moisture retentive dressings such as hydrogels, hydrocolloids, transparent films, or alginates may be helpful to facilitate autolytic debridement of necrotic tissue and healing of herpes-varicella wounds.

Infected Wounds

Necrotizing Fasciitis

Pathophysiology

Necrotizing fasciitis (NF) is a deep-seated infection of the subcutaneous tissue that progresses rapidly along fascial planes with severe systemic toxicity and 40% mortality. NF can lead to progressive destruction of fascia and fat without initial skin involvement. Bacteria enter the skin through cut or scratch. NF can be monomicrobial or polymicrobial, and the most common offenders are Group A streptococcus (Streptococcus pyogenes), Staphylococcus aureus, Clostridium perfringens, Bacteroides fragilis, Aeromonas hydrophila. The bacteria release toxins that produce an exotoxin that in turn activates T cells. This process produces increased cytokines that lead to severe systemic symptoms known as toxic shock syndrome, which can be fatal if the initial necrosis is not immediately controlled.^1,10

Risk factors for NF include IV drug use, diabetes, peripheral vascular disease, obesity, and malnutrition. A 50% mortality rate is associated with any combination of three or more risk factors.

Clinical Presentation

NF is frequently preceded by a minor skin trauma that serves as a portal for the causative bacteria. This is followed by a sequence of the following clinical manifestations:

• ▪ Low-grade fever

• ▪ Pain, usually out of proportion to the initial clinical findings

• ▪ Swelling with massive, “sausage-like” edema

• ▪ Erythema with bullous skin changes

• ▪ Lack of adenopathy, misses immune recognition

• ▪ Skin necrosis with hypesthesia or anesthesia

• ▪ Striking indifference to one’s clinical state

• ▪ Toxic-shock appearance with rapid demise

Basic antigen testing may identify Streptococcus, but does not establish a diagnosis. A basic rapid strep test is helpful, and PCR testing identifies streptococcal pyrogenic exotoxin genes (SPE=B).

Differential Diagnosis

Cellulitis—all of the signs of NF may not be present initially, leading to an early misdiagnosis of cellulitis. Gas gangrene—See detailed description on page 240.

Medical Management

Medical management includes appropriate antibiotics, aggressive surgical debridement of all infected subcutaneous and dermal tissue (the saying is that the patient goes straight from the ER to the OR), medical stabilization as needed, and adjunctive hyperbaric oxygen therapy²⁷ (discussed in more detail in Chapter 18).

Wound Management

Wound management depends on the amount of debridement done surgically, as well as the amount and quality of the residual soft tissue. If there is concern about continued infection, antimicrobial dressings are used, for example, nanocrystalline silver, half or quarter strength Dakin solution (unless there is granulation tissue), or acetic acid washes for pseudomonas. Once the wounds are more than 70% clean, negative pressure wound therapy is used to facilitate wound contraction and angiogenesis in preparation for skin grafts or flaps.²⁸ Pain management during wound care is essential, and if the wounds are extensive, rehabilitation services and/or psychological care may be needed.²⁹

Fournier Gangrene

Fournier gangrene is an aggressive form of necrotizing infection of the perineum that may extend to the anterior abdominal wall, gluteal muscles, and in males, to the penis and scrotum. The causative organisms are a mixed collection of aerobic gram-negative bacteria, enterococci, and anaerobes, including bacteroides and peptostreptococci.³⁰

Myonecrosis (Gas Gangrene)

Pathophysiology

Myonecrosis, also known as gas gangrene, occurs after a deep penetrating injury compromises the blood supply, thus creating the anaerobic conditions ideal for infection.^10,12 The majority of the infections in this situation are caused by Clostridium perfringens, although other species of Clostridium have been implicated. C. perfringens produce multiple toxins (including bacterial proteases, phospholipases, and cytotoxins) that cause aggressive necrosis of the skin and muscles.³¹ The same bacteria can cause clostridial cellulitis, which also occurs after trauma or surgery.

Clinical Presentation

The patient presents with severe pain, and the skin changes color from pale to bronze to purplish-red with bullae formation. Gas in the tissue is evident from physical examination as crepitus upon palpation or by radiography. TABLE 8-9 presents a detailed list of integumentary signs and symptoms associated with gas gangrene (FIGURE 8-20). In addition, renal failure may occur as a result of hemoglobinuria and myoglobinuria, as well as bacteremia and hemolysis. The patient may rapidly progress to shock and multiorgan failure with toxic psychosis.

Medical Management

Medical management of gas gangrene is predicated on debridement of all devitalized and infected tissue and appropriate IV antibiotics. Hyperbaric oxygen therapy may also be helpful in decreasing the infection and promoting new tissue growth.

Wound Management

Initial local wound care is packing or covering with antiseptic or antimicrobial dressings using aseptic precautions. When healthy tissue is visible, the principles of moist wound healing are followed and may include the use of negative pressure wound therapy to help decrease the size of tissue defect caused by surgical debridement.

Actinomycosis

Pathophysiology

Actinomycosis is caused by a gram positive, nonspore forming anaerobic bacilli, the most common being Actinomycosis israelii. The most common locations are cervicofacial, abdominal, or thoracic and may occur after radiation for malignant tumors. Several reports of actinomycosis on the foot have also been reported.^32-33 The infection is usually accompanied by the presence of some other bacteria that facilitates its invasion of tissue.³⁴

Clinical Presentation

The clinical presentation of actinomycosis, which is usually chronic and difficult to eliminate, varies with the location. Cervicofacial actinomycosis develops slowly; the area becomes markedly indurated and the overlying skin becomes reddish or cyanotic. In addition, the wound may produce particles (similar to sulfur particles) that carry the bacteria, frequently into adjacent soft tissue and bone (FIGURE 8-21). Thoracic actinomycosis involvement begins with fever, cough, and sputum production. Other signs include night sweats, weight loss, and pleuritic pain. Abdominal actinomycosis usually causes pain in the ileocecal region, spiking fever and chills, vomiting, and weight loss.³⁵ This type may be confused with Crohn disease.

Differential Diagnosis

• ▪ Nocardiosis

• ▪ Madura Foot

• ▪ Cellulitis

Medical Management

Surgical excision is usually required for actinomycosis, and IV or oral antibiotics (eg, ampicillin, penicillin, or amoxicillin) are recommended for 6 months. Doxycycline and sulfonamides may also be used; however, medical treatment is slow.³⁵

Wound Management

Actinomycosis is treated locally with antibiotic solutions or with local antibiotic cream or anti-infective agents.

Mycobacteria

Pathophysiology

Mycobacteria can be typical or atypical, and the bacteria are neither gram positive nor gram negative. Atypical strains were not reported as human pathogens until the 1950s. Mycobacterial cutaneous infections usually result from exogenous inoculations, and predisposing factors include a history of preceding trauma, immunosuppression, or chronic disease, especially diabetes. TABLE 8-10 presents a list of mycobacteria, as well as their clinical presentations and treatments.^36,37

Clinical Presentation

The cutaneous lesions vary depending on the causative agent and may present as granulomas, small superficial ulcers, sinus tracts, abscesses, or large ulcerated lesions localized in exposed areas. The appearance is very similar to lesions seen in leprosy and may be difficult to differentiate. Tissue cultures are required to make an accurate diagnosis of any mycobacterial infection.

Medical Management

The primary medical treatment of mycobacterial infections is specific chemotherapy, the major ones being INH and RMP. Other first-line medications are pyrazinamide, ethambutol, and streptomycin.^38,39 Drug resistance is a global problem and numerous second-line defense medications have been presented in the literature.

Wound Management

Wound management is based on use of antimicrobial dressings, management of exudate, and use of aseptic technique to prevent further infection, and use of airborne precautions if the strain is tuberculin.

Sporotrichosis

Pathophysiology

Sporotrichosis is a subacute or chronic fungal infection caused by the fungus Sporothrix schenckii, which occurs as a consequence of traumatic implantation of the fungus into the skin. It is usually seen in nursery workers, florists, and gardeners who have exposure to soil, sphagnum moss, or decaying wood.⁴⁰

Clinical Presentation

The patient usually presents with nontender, red maculopapular granulomas, usually 2 to 4 mm in diameter, which may ulcerate (FIGURE 8-22). The primary lesion is typically painless and may be surrounded by raised erythema.⁴¹ It is often associated with lymphangitis; less often inhalation of the fungus can lead to pulmonary infection and subsequently spread to the bones, eyes, central nervous system, and viscera.

Differential Diagnosis

• ▪ Other fungal infections

• ▪ Brown recluse spider bite

Medical Management

Sporotrichosis is usually treated with systemic medications, including saturated solution of potassium iodide, itraconazole, fluconazole, terbinafine, and amphotericin B.

Wound Management

Local wound management includes topical antifungal agents, topical application of saturated solution of potassium iodide, and topical application of heat (the sporotrichosis organism grows at low temperatures).

Fungal Infections

Pathophysiology

Tinea infections are specific fungal infections caused by dermatophytes that locate exclusively in keratin (eg, stratum corneum, hair, nails).⁴² The most common tinea infections are caused by epidermophyton, trichophyton, or microsporum.⁴³

Clinical Presentation

Clinical signs of fungal infections are scaly skin, erythematous plaques, and annular plaques. A definitive fungal odor may sometimes be present. Rarely are the lesions vesicular or pustular. The specific disorder is named according to the body part infected as follows: tinea capitis (scalp), tinea barbae (beard), tinea corporis (body), tinea cruris (genital area), tinea pedis (feet), and tinea unguium or onychomycosis (nail). Onychomycosis is characterized by thick, yellow nails with surrounding scaly skin, and is frequently observed on the diabetic foot (FIGURES 8-23 to 8-25).

Differential Diagnosis

Histological features of tinea infections include neutrophils in the stratum corneum, often with parakeratosis and a variable inflammatory response in the dermis. The organisms are best visualized by PAS, and potassium hydroxide (KOH) prep may show branching septate hyphae.¹²

Medical Management

Systemic treatment with antifungal agents such as fluconazole is used for severe cases only. Oral itraconazole and terbinafine are recommended for onychomycosis.

Wound Management

The mainstay of treatment for fungal infections is topical antifungal creams, for example, imidazoles, triazoles, and allylamines. They are applied twice daily and need to be used for a week after symptoms have resolved. Topical treatment of onychomycosis may take several months before visible changes in the nail can be observed.

Spider Bites

Pathophysiology

More than 50 spider species in the United States have been implicated in causing significant medical conditions; however, there are two main species that are most known for causing skin necrosis and open wounds: Loxosceles reclusa (brown recluse) and Latrodectus (black widow). In both cases, the wound severity depends on the venom load and the host immune response. The venom responsible for skin necrosis is a water-soluble substance that contains eight enzymes, including sphingomyelinase D, which destroys the tissue it invades. Approximately 10% of spider bites progress to necrosis. The brown recluse is so named because it tends to reside in dark, secluded places such as closets, attics, and wood piles, and is not aggressive. It bites only when it is disturbed and requires counterpressure to inject the venom.⁴⁴

Clinical Presentation

Because most spiders are not seen at the time of the bite (80%), making a definitive diagnosis can be difficult. Only about 12% of the victims are able to bring the spider to the medical facility after the bite. The initial response is minor stinging or burning. If there is sufficient venom or the host is immunosuppressed, the bite may progress to severe inflammation with a “bull’s-eye” appearance, followed by a red, white, and blue sign as the lesion enlarges (FIGURES 8-26, 8-27). If the tissue becomes anoxic, necrosis with an eschar will develop. Viscerocutaneous loxoscelism or systemic signs may include rash, fever, chills, nausea, vomiting, malaise, arthralgia, and myalgia. In severe rare cases, renal failure may occur with hemolysis, hemoglobulineria, leukocytosis, leukopenia, or thrombocytopenia.^45,46

Differential Diagnosis

• ▪ Foreign body reaction

• ▪ Infections (mainly MRSA)

• ▪ Trauma

• ▪ Vasculitis

• ▪ Pyoderma gangrenosum

• ▪ Squamous cell carcinoma

• ▪ Lyme disease

Diagnosis is made by positive identification of the spider, complete blood count if there are systemic effects, urinalysis if there is renal failure, and ELISA (enzyme-linked immunosorbent assay), which can check for the specific antigen.⁴⁷

Medical Management

Treatment of spider bites may begin with excision of the bite location. Dapsone administered within 24 hours is advised to inhibit neutrophil migration (except in the case of G6PD deficiency), and systemic steroids may prevent enlargement of the necrotic area. Other medical interventions include oral antihistamines, glucocorticoids, and antivenom. Surgical debridement of necrotic tissue may be indicated if the tissue loss is extensive, and antibiotics are indicated for immunosuppressed victims.

Wound Management

Initial first aide includes cooling the bite site to prevent spreading of the venom. If tissue necrosis occurs, debridement and moist wound principles are indicated. Hyperbaric oxygen therapy may also be useful, especially if the patient has marginal oxygen supply due to peripheral arterial disease.

Calciphylaxis

Pathophysiology

Calciphylaxis is a potentially fatal condition characterized clinically by progressive cutaneous necrosis, which frequently occurs in patients with end-stage renal disease. Calciphylaxis is seen in 1% of patients with chronic renal failure and in 4.1% of patient receiving hemodialysis. In addition, it usually occurs in patients with Type 2 diabetes and end-stage renal disease who have been on hemodialysis for more than 10 years.⁴⁸ Estimated 1-year survival rate of patients with calciphylaxis is approximately 46%.

The pathogenesis of calciphylaxis is still poorly understood. Patients who are on long-term dialysis usually develop abnormal calcium-phosphorus products, which in turn lead to tertiary hyperparathyroidism. This results in elevated calcium-phosphate products and the development of vascular calcification that in turn leads to tissue death. Histology shows calcification of the intima and media of small and medium vessels in the dermis and subcutaneous tissue.^49,50

Clinical Presentation

The cutaneous manifestations of calciphylaxis begin as sudden-appearing red or violaceous mottled plaques in a livedo reticularis pattern. The early ischemic lesions often progress to gangrenous, poorly defined, black plaques. With time, the plaques ulcerate and become exquisitely tender. Usually ulcers are bilateral, symmetric, and may extend deep into muscle (FIGURES 8-28, 8-29).

Differential Diagnosis

• ▪ Pyoderma gangrenosum

• ▪ Coumadin-induced skin necrosis

• ▪ Necrotizing fasciitis

• ▪ Pressure-induced tissue loss

Medical Management

Multiple approaches to medical management of calciphylaxis are recommended to prevent infection, manage pain, and optimize outcomes by chelating arterial calcium. Treatment strategies include the following:

• ▪ Systemic antibiotics

• ▪ Opioid pain medication (morphine can cause hypotension and slow blood flow in the arterioles)

• ▪ Phosphate binders such as sevelamer

• ▪ Sodium thiosulfate as a chelating agent for calcium deposits in the tissue

• ▪ Biophosphonate therapy to help remove arterial calcification

• ▪ Low calcium hemodialysis for patients with ESRD

• ▪ Cinacalcet to lower parathyroid levels and improve calcium-phosphorus homeostasis

• ▪ Hyperbaric oxygen therapy to increase local tissue oxygen perfusion

• ▪ Low calcium diet to optimize nutrition and provide adequate calorie and protein intake for wound healing⁵¹

In the past, parathyroidectomy was performed in an effort to increase calcium uptake; however, this procedure has not been shown to be significantly effective. Also, systemic corticosteroids are not recommended as they may exacerbate arteriolar calcification.

Wound Management

Debridement of necrotic tissue and calcified vessels is needed for reversal of the inflammatory response to calciphylaxis; however, this is difficult to perform bedside if the necrosis is extensive because of the intense pain levels associated with the disease. Surgical debridement followed by negative pressure wound therapy is the most expeditious approach if the patient is medically stable for surgery. This is complemented by skin grafting with either autologous or tissue-engineered skin. Electrical stimulation and hyperbaric oxygen therapy may be beneficial adjunct therapies. In addition to the meticulous wound care (using aseptic technique to prevent infection), nutritional supplements and monitoring is advised because patients may have difficulty eating sufficient calories for wound healing given the amount of pain medicine required to manage the anoxic pain.

Coumadin-Induced Skin Necrosis

Pathophysiology

Coumadin-induced skin necrosis is a rare complication of anticoagulation therapy that leads to skin necrosis. Although the exact pathogenesis is unknown, it is understood that protein C deficiency, protein S deficiency, and antithrombin III deficiency can lead to Coumadin-induced skin necrosis, usually between the 3rd and 10th days after starting anticoagulation therapy.⁵² Sometimes postpartum women have reduced levels of free proteins S during antepartum and immediate postpartum periods.⁵³

Clinical Presentation

Skin changes usually appear within the first week of starting warfarin (Coumadin) therapy, and usually appear on the trunk. Manifestations include ecchymoses and purpura; hemorrhagic necrosis; maculopapular, vesicular, urticarial eruptions; and purple toes (FIGURE 8-30).

Differential Diagnosis

• ▪ Necrotizing fasciitis

• ▪ Gangrene

• ▪ Calciphylaxis

• ▪ Pyoderma gangrenosum

Medical Management

The most important aspect of treatment is discontinuation of the anticoagulant, along with pain management and infection prevention.

Wound Management

Wound management includes debridement (surgical, sharp, or autolytic, depending on the depth and amount of necrotic tissue), moist wound therapy, skin grafts, and/or bioengineered skin. If surgical debridement involves loss of subcutaneous tissue, negative pressure wound therapy may assist in wound bed preparation for surgical closure.

Sickle Cell Wounds

Pathophysiology

Sickle cell ulcers are a complication of sickle cell anemia, an inherited genetic disorder in which the red blood cells have a sickle shape, rendering them incapable of binding hemoglobin. This leads to hypoxia that can cause severe pain crises and can also deprive injured tissue of the oxygen necessary for healing. The patient with the homozygous form of sickle cell disease is most likely to develop a sickle cell ulcer. Studies have shown that males are more likely to develop leg ulcers due to sickle cell disease than females.⁵⁴

In sickle cell disease, the abnormal hemoglobin molecule in the red blood cell causes a change in the shape of the RBC. In addition, when cells are in the sickled shape, they tend to increase blood viscosity. This causes slowing of the blood flow in small vessels, which also contributes to ischemia of tissue and organs. Over time, the patient suffers repeated episodes of pain, tissue damage, and eventually, organ failure. Although the exact cause of sickle cell ulcers is not clear, they have been associated with trauma, infection, severe anemia, warm temperatures, and venous insufficiency.⁵⁵

Clinical Presentation

Sickle cell ulcers are found on the lower third of the leg, usually over the medial and/or lateral malleoli of the ankle (FIGURE 8-31). They are exquisitely painful and can have a thick layer of fibrinous tissue, slough, or biofilm. The edges tend to be even like an arterial wound, and the wound bed is slow to granulate. Because of the chronic inflammatory state and reduced ankle function due to pain, lower extremity edema may be present and thus complicate the healing process.

Differential Diagnosis

• ▪ Venous insufficiency ulcers

• ▪ Vasculitis

Medical Management

Treating patients who have wounds and sickle cell anemia requires a combination of therapies in order to optimize healing. Medical management of the sickle cell disorder includes oral zinc sulfate (200 mg three times/day)⁵⁶ and a combination of L-methylfolate calcium, pyridoxal-5- phosphate, and methylcobalamin (Metanx). The goal is to decrease endothelial cell homocysteine levels and raise nitric oxide levels, resulting in improved wound healing. It also helps reduce pain associated with sickle cell ulcers and increase blood flow in the microcirculation at the wound margin.^57,58

Transfusion therapy is advised with a goal of keeping the hematocrit level between 30 and 35 and the level of normal hemoglobin (hemoglobin A) greater than 70% of the total. The transfusions are continued until the ulcers heals or for 6 months at which time they are discontinued.⁵⁴ In conjunction with transfusions, deferasirox is administered to chelate the excess iron that accumulates with transfusions.⁵⁹

IV Arginine butyrate can also help change the concentration of abnormal hemoglobin, thus facilitating wound healing.⁵⁷ Pentoxifylline (Trental) is a vasodilator used to treat peripheral arterial disease that may also help increase the peripheral tissue perfusion.

Wound Management

Basics of good wound care include debridement of devitalized tissue, control of infection, assurance of adequate circulation, and maintenance of a moist wound environment.⁶⁰ Specific strategies that have been included in the literature include the following:⁶¹

• ▪ Negative pressure wound therapy

• ▪ Antibiotics

• ▪ Biofilm

• ▪ Compression therapy

• ▪ Topical growth factor (granulocyte macrophage-colony—stimulating factor)

• ▪ Honey-based dressing

• ▪ Bioengineered skin⁶²

• ▪ Split thickness skin graft

• ▪ Hyperbaric oxygen therapy

• ▪ Electrical stimulation or electromagnetic therapy

Malignant Wounds

Basal Cell Carcinoma

Pathophysiology

Basal cell carcinoma is the most common type of skin cancer affecting one in every six Americans. The neoplasm arises from damaged undifferentiated basal cells as a result of prolonged exposure to ultraviolet (sun) light. The UV exposure leads to the formation of thymine dimers, a form of DNA damage. BCC occurs when the DNA damage is greater than what the cells can naturally repair.⁶³

Clinical Presentation

BCC presents as a small scaly wound that outgrows its blood supply, eventually erodes, and subsequently ulcerates. Other characteristics include rolled edges, slightly raised, painless, and slow growing. BCC usually occurs on the head, neck, back, or chest where there has been sun exposure. Multiple variants include superficial, infiltrative, and nodular basal cell carcinoma (with papules present) (FIGURE 8-32).

Differential Diagnosis

• ▪ Squamous cell cancer

• ▪ Vasculitis

Medical Management

Treatment consists of biopsy to confirm the diagnosis and excision of the lesion with curettage, electrodesiccation, or Mohs micrographic surgery.⁶⁴ Close follow-up with full-body skin inspection by a dermatologist or other medical specialist is advised for additional lesions that may occur.

Wound Management

Wound management is not usually indicated unless an excision becomes infected or for some other reason fails to heal. In such a case, moist wound healing is recommended. Cleansing with hydrogen peroxide is contraindicated as it is cytotoxic, has no antibacterial properties, and can instead prevent wound closure.

Patient education regarding avoidance of sun exposure is necessary for prevention of further lesions.

Squamous Cell Carcinoma

Pathophysiology

Squamous cell carcinoma (SCC), the second most common form of skin cancer, is a malignant neoplasm of the keratinizing epidermal cells. The development of SCC has been reported in chronic wounds secondary to burns, trauma, hidradenitis suppurativa, radiotherapy, diabetes, and draining sinus tracts of chronic osteomyelitis. Risk factors for SCC include the following: exposure to ultraviolet A and B light, fair skin and blue eyes, radiation therapy, and antirejection medications after organ transplant.

If the SCC occurs in the area of a previous wound, for example, a burn, venous ulcer, or traumatic wound, years after the initial wounding, it is termed a Marjolin ulcer. This type of SCC is usually very aggressive and requires excision beyond its margins and radiation therapy. ^65,66

Clinical Presentation

SCC usually presents as a red papule, nodule, or plaque. The edges are poorly defined and the surrounding skin is scaly. It is commonly hyperkeratotic or ulcerated and may metastasize and grow rapidly (FIGURES 8-33, 8-34).

Differential Diagnosis

• ▪ Basal cell cancer

• ▪ Vasculitis

Medical Management

If the SCC metastasizes, chemotherapy and radiation therapy are indicated, as well as excision of nodules and any regional lymph nodes that are involved. Fine needle aspiration can be used to diagnose any potential problematic areas.

Wound Management

Because of the chemotherapy and radiation of affected tissue, wounds are not uncommon after excision of SCC. Supportive wound care is required, including infection control, pain management, lymphedema management, and frequent inspection for new lesions. Cavity wounds in areas such as the axilla after node removal may be managed with pulsed lavage with suction to reduce the bacterial load and antimicrobial filler dressings.

Melanoma

Pathophysiology

Melanoma, the most lethal form of skin cancer, is a tumor of the melanocytes of the epidermis. TABLE 8-11 lists the different types of melanoma and TABLE 8-12 presents Breslow depth scale, which is used as a prognostic indicator. The scale indicates how deeply the tumor cells have invaded the epidermis/dermis in micrometers.⁶⁷ The cause of melanoma is exposure to ultraviolet light in the sun and from tanning beds.

Clinical Presentation

• ▪ Melanomas are best described by the ABCDE presentation (FIGURE 8-35).

• ▪ Asymmetry of the discolored area

• ▪ Borders that are uneven and distinct

• ▪ Color that is dark brown or black

• ▪ Diameter more than 1 cm

• ▪ Evolution to larger, darker lesion

Medical Management

The first treatment of melanoma is excision, then depending on the depth of tissue involved, chemotherapy and radiation may be necessary.^68,69

Wound Management

Wound care is not indicated unless there is failure of the incisional wound to heal.

Kaposi Sarcoma

Pathophysiology

Kaposi sarcoma (KS) is a malignant tumor of the lymphocytic and endothelial cells linked to the herpetic viruses and HIV (FIGURE 8-36). The pathogenesis of KS has now been identified as human herpes virus type 8.⁷⁰ Four clinical variants have been identified:

• ▪ Localized, slowly progressing form in older men (classical KS)

• ▪ Endemic African KS

• ▪ Immunosuppressive KS, usually associated with organ transplant recipients

• ▪ Rapidly progressive form associated with HIV or AIDS⁷¹

Clinical Presentation

KS lesions can appear anywhere on the body, including the mucous membranes. The lesions are slightly raised, elongated with poorly demarcated edges and may have rust or purple-red maculae or patches. They progress slowly into firm necrotic plaques with underlying nodules.⁷¹ Marked edema may develop when the tumors involve the lymphatic vessels, leading to diffuse edema and subsequent skin breakdown.

Differential Diagnosis

• ▪ Diabetic wounds

• ▪ Venous wounds

• ▪ Pyogenic granuloma

• ▪ Squamous cell carcinoma

• ▪ Melanoma

Medical Management

KS associated with AIDS is treated with highly active antiretroviral therapy (HAART). Surgical excision, local radiation therapy, and cryotherapy are used for isolated cutaneous lesions. For immunosuppressed patients, rapamycin or reduction of immunosuppressive therapy is recommended.⁷¹

Wound Management

Immediate treatment of KS may include topical application of 9-cis-retinoic acid (alitretinoin gel), which has been proven superior to previously used vehicle gel.⁷⁰

Because of the radiation, lymphatic involvement, and edema, chronic wounds may develop (especially if the lesion is on the lower extremity) even years after the tumor has been eliminated. Standard wound care with the TIMEO₂ principles and compression therapy is recommended, and adjunctive therapies such as HBOT and electrical stimulation may be beneficial if there are no signs of malignant cells.

Merkel Cell Carcinoma

Pathophysiology

Merkel cell carcinoma (MCC), involving the Merkel cells in the epidermis, is a skin cancer associated with UV exposure that tends to occur in older individuals who are also immunosuppressed. It has recently been shown to contain a polyomavirus. MCC can progress rapidly into the lymph nodes, therefore, needs early diagnosis and interventions.

Clinical Presentation

Initial MCC presentation is much like a cyst, often resulting in misdiagnosis (FIGURE 8-37). MCC can be identified using the acronym AEIOU as defined in TABLE 8-13 and if three of the five characteristics are present, there is a high probability of MCC and a biopsy is recommended.⁷²

Medical Management

Medical management begins with surgical excision, preferably with Mohs technique, followed by radiation and chemotherapy (especially for palliative care of advanced disease or for patients who cannot undergo surgery).⁷²

Wound Management

Prior to surgery, exudate can be managed with absorbent dressings. After surgery, any excision wounds can be managed with standard wound care.

Cutaneous Lymphoma

Pathophysiology

Although lymphomas generally originate in the lymph nodes or collections of lymphatic tissue in organs, such as stomach or intestines, the skin may also be affected. Cutaneous lymphomas represent clonal proliferation of neoplastic B cells or T cells that migrate to the skin and cause progressive lesions. TABLE 8-14 presents a list of primary cutaneous lymphomas, the most common being mycosis fungoides (FIGURE 8-38).

Clinical Presentation

Cutaneous lymphoma may present as various types of skin lesions, but rarely as an open wound. Mycosis fungoides begin as patches of scaly erythema and progress to plaques of sharply demarcated, scaly, elevated lesions that are dusky red to violet. The next, most severe stage is nodular in which the malignant cells cause formation of reddish-brown or purplish-red and smooth-surfaced nodules, which often ulcerate and may become secondarily infected. Ulcerative cutaneous lymphomas are associated with poor prognosis; they are increasingly observed in severely immune-compromised patients.

Medical Management

Spot radiotherapy is used to treat isolated cutaneous lesions; topical chemotherapy can be useful for patches and plaques. Chemotherapy is used for diffuse lesions or systemic disease. Psoralen+UVA (PUVA) phototherapy is used for long-term maintenance therapy of patches and plaques.

Wound Management

Supportive wound care is indicated for any nonhealing ulcerated lesions.

Factitious Wounds

Pathophysiology

As with many psychiatric illnesses, the pathophysiology of factitious disorder is unclear. Case reports of abnormalities on MRIs of the brains of patients with chronic factitious disorder suggest that brain biology may play a role in some cases. Factitious disorder is similar to somatic symptom disorder, another mental disorder that involves the presence of skin lesions that are not due to actual physical illnesses. Rather the wounds are self-inflicted and not allowed to heal because of patient interference with care.^1,12

Clinical Presentation

Factitious wounds usually have geometric edges and healthy granulation tissue (FIGURE 8-39).

Differential Diagnosis

Differential diagnosis of factitious wounds is dependent on diagnosis of an underlying psychological or psychiatric disorder (eg, delusional disorder, depression, schizophrenia) once the clinician is suspicious that a nonhealing wound is the result of self-inflicted behavior.

Medical Management

Medical management includes treatment of the underlying psychiatric disorder, any comorbidities, and other complications that may arise from the induced illness.

Wound Management

Standard wound care, supportive emotional care, and close observation for signs of distress are required for the clinician caring for a patient with factitious wounds. Adherence to treatment strategies will need continuous reinforcement for both the patient and family/care givers.

When wounds have an unusual appearance or fail to respond to standard care, further evaluation is required to determine the diagnosis of what is termed atypical wounds. Signs of atypical wounds include unusual location, unusual age, poor or friable granulation tissue, overgrowth, red or purple periwound skin, or history of diseases that suggest other wound diagnoses. Atypical wounds can be generally categorized into allergic reactions, infections (bacterial or fungal), autoimmune disorders, malignancies, or factitious behavior. Successful treatment of the wound is predicated on making the correct diagnosis of underlying diseases as well as the wound or integumentary disorder. Referral to the appropriate medical specialist is also an integral part of caring for the patient with an atypical wound.