CHAPTER 30 Intrinsic diseases and uncommon cutaneous wounds
1. Differentiate between staphylococcal scalded skin syndrome and toxic epidermal necrolysis (TEN) and between graft-versus-host disease (GVHD) and pyoderma gangrenosum in terms of manifestations and etiology.
2. Describe the process of tissue damage and treatment options for vasculitis, calciphylaxis, epidermolysis bullosa (EB), GVHD, frostbite, and TEN.
3. Discriminate among the patient populations at risk for calciphylaxis, frostbite, TEN, and extravasation.
4. Compare and contrast the role of debridement in necrotizing fasciitis, TEN, extravasation, and frostbite.
5. Describe the distinguishing features of a chronic wound with malignant transformation.
6. Identify four conditions that require a tissue biopsy for diagnosis.
Infectious etiology
Staphylococcal scalded skin syndrome
Staphylococcal scalded skin syndrome (SSSS) is a superficial blistering skin disorder caused by the exfoliative toxins of some strains of Staphylococcus aureus. Initially an infection is present most commonly in the oral or nasal cavities, neck, axillae, groin, or umbilicus (King and de Saint Victor, 2009). The toxins produced by the infecting organism are transferred through the bloodstream to a site remote from the original infection where significant erythema will develop, followed by separation of the superficial epidermis (i.e., desquamation). The primary lesions are superficial bullae. Secondarily, lesions develop superficial scales. The skin may have a sandpaper feel. Significant pain is unusual for SSSS and, if present, suggests another diagnosis, such as toxic epidermal necrolysis (TEN), a drug-induced necrosis of the epidermis.
Although SSSS has been reported in adults, it most commonly occurs in healthy children 6 years or younger and in neonates (Habif et al, 2005; King and de Saint Victor, 2009). Mortality in children is very low (1%–5%) unless SSSS is associated with sepsis or a coexisting serious medical condition. SSSS, when it develops in adults, occurs in adults who are chronically ill, immunocompromised, or with renal failure. The mortality rate in adults is substantial (50%–60%), although this may be attributable to the overall health status of the adults rather than the SSSS (King and de Saint Victor, 2009).
Once SSSS is diagnosed, treatment consists of supportive care and elimination of the primary infection. Debridement and antibiotics are essential to manage the infection. Topical management of the desquamated skin should address exudate management, pain control, and maintenance of a moist environment. Foam dressings, superabsorbent dressings, sheet hydrogels, and alginates are preferred dressing options; adhesives should be avoided. Steroids may worsen immune function, and nonsteroidal antiinflammatory drugs (NSAIDs) should be avoided because they potentially can reduce renal function (King and de Saint Victor, 2009). When massive tissue loss is apparent, the wound should be managed according to the principles for burn therapy as outlined in Chapter 32.
Toxic shock syndrome
Toxic shock syndrome is caused by a toxin produced by certain types of Staphylococcus bacterial infections. The most common pathogen for this serious infection is S. aureus. Acute onset consists of a widespread macular erythematous eruption (within 1–3 days) that extends to include the soles of the feet and the palms of the hands. Desquamation of the skin is highly characteristic of toxic shock syndrome. It occurs 10 days to 3 weeks after onset and primarily includes the fingertips and plantar surfaces of the palms and feet. Additional clinical manifestations include edema of the hands and feet (50%), petechiae (27%), conjunctival injection (85%), oropharyngeal hyperemia (90%), and genital hyperemia (100%) (Habif et al, 2005).
Diagnosis is based on a constellation of symptoms: fever (>102°F), hypotension, rash progressing to desquamation, and mucosal membrane involvement (mouth, eyes, vagina). In addition, the condition must be multisystem as evidenced by impaired functioning of at least three organs (muscular, gastrointestinal, central nervous system, renal, hepatic, hematologic, cardiopulmonary, metabolic) (Habif et al, 2005; Smith, 2008). A skin biopsy is indicated to exclude TEN as a diagnosis.
The goal of treatment of toxic shock syndrome is preventing organ damage through supportive care and aggressive antibiotic therapy; the mortality rate of toxic shock syndrome ranges from 3% to 12% (Habif et al, 2005). Local wound management is based on wound needs (e.g., exudate absorption), and topical dressings should be nonocclusive and nonadhesive.
Necrotizing fasciitis
Necrotizing fasciitis is an uncommon but serious subcutaneous tissue infection that spreads rapidly along the superficial fascial plane. The overall mortality rate from this very rapidly spreading condition is variable: 20% in pediatric cases and anywhere from 6% to 73% in adults (Anaya and Dellinger, 2007). Necrotizing fasciitis is characterized by widespread necrosis of the fascia and deep subcutaneous tissue, with thrombosis of nutrient vessels and sloughing of overlying tissue (Plate 59). It usually occurs in the extremities after a minor operation or injury. The clinical markers of necrotizing fasciitis are a rapidly spreading erythema in the skin around the wound and subcutaneous crepitus that may be visible on radiograph. Additional signs of necrotizing fasciitis are pain (considered to be out of proportion for the extent of the skin damage), swelling at the site of the wound, chills, fever, and toxemia. The skin may initially appear normal over the cellulitis, but as the infectious process compromises blood supply the skin becomes erythematous, edematous, and reddish-purple to patchy blue gray. Bullae form within 3 to 5 days from onset and progress to necrosis of the skin, sloughing, and frank cutaneous gangrene (Anaya and Dellinger, 2007). Tendon sheaths and muscle will liquefy when infected; in the operating room, “dishwater fluid” is the hallmark of liquefactive necrosis.
Necrotizing fasciitis can be detected by its dramatic clinical presentation and by probing the wound. When the affected area is probed with a hemostat through a limited incision, the instrument passes easily along a plane of superficial to deep fascia. This examination helps to distinguish necrotizing fasciitis from cellulitis. This infection is most often polymicrobial with group A streptococci or S. aureus predominating. A subset of necrotizing soft tissue infections caused by Clostridium species are monomicrobial and associated with a significantly worse prognosis (Anaya and Dellinger, 2007).
The presence of necrotizing fasciitis requires aggressive surgical debridement; any nonviable or questionably viable tissue must be removed. Because the infection spreads subcutaneously, a wound may need to be extended to allow access to and debridement of all necrotic tissue (Attinger et al, 2006). Despite aggressive local control, necrotizing fasciitis has a 24% to 50% mortality rate secondary to persistent wound sepsis or systemic sepsis (Martin et al, 2008). Local wound care consists of close monitoring for further dissection, which indicates progression of the infection. Topical dressing recommendations are largely based on expert opinion or preference. Dressings should be used that meet the needs of the wound (e.g., fill dead space, absorb exudate), allow for frequent monitoring of the wound, and are nonadhesive and nonocclusive.
Spider bites
Only 60 of the 20,000 species of spiders in the world are capable of inflicting a bite, and only four can cause significant injury; evidence of that tissue damage is documented for only two spiders: the brown recluse and the black widow. The brown recluse spider is one of five species of spiders within the genus Loxosceles. This spider is about the size of a U.S. quarter, is yellow to brown in color, and has a distinctive fiddle-shaped mark on its back (Rhoads, 2007). The brown recluse spider usually is shy and nocturnal. It tends to avoid humans and seek shelter in abandoned or infrequently used buildings, attics, and basements. Bites generally occur when a person disturbs a pile of wood or rocks, moves boxes that have been stored, or dresses in clothes that have been stored for a long period of time. The most common site for a Loxosceles spider bite is on the extremities, but they also can occur on the buttocks or genitalia.
The venom of the brown recluse spider is a mixture of enzymes that destroy cellular membranes, resulting in damage to the surrounding skin, fat, nerves, and blood vessels. Manifestations of a brown recluse spider bite can range from small lesions with erythema to full-thickness necrotic wounds (known as necrotic arachnidism). Fewer than 10% of patients develop severe skin necrosis or other systemic reaction (e.g., loxoscelism, which is characterized by fever, nausea, hemolysis, and thrombocytopenia) (Schwartz, 2009; Zeglin, 2005). Severity of the reaction depends on the amount of venom injected, the site of the bite, and host susceptibility. However, it is the accumulation of activated neutrophils that is responsible for the cutaneous necrosis (Schwartz, 2009). Accumulation of neutrophils occurs 24 to 72 hours before skin necrosis and ulceration. The very young, the elderly, and individuals in poor physical condition are at highest risk for serious illness from a spider bite.
After a spider bite, the person may experience a mild burning sensation or may experience no discomfort at all. Within 6 to 12 hours, itching, pain, a central papule, and erythema may develop. Wounds that progress usually begin to do so within 48 to 72 hours of the bite. As the tissue damage progresses, the characteristic “red, white, and blue” sign of a brown recluse bite develops; the sign consists of a ring of blanched skin (due to vasoconstriction) surrounded by erythema with gray-to-red-purple bullae at the site of the bite (Schwartz, 2009; Zeglin, 2005) (Plate 60). Severe necrosis is more likely when the bite is located in an area with significant adipose tissue, such as the thighs and buttocks. When the bite remains localized with a central blister, resolution occurs within 3 weeks. Severe bites that develop necrosis heal over a 2- to 3-month time span (Rhoads, 2007).
The standard treatment of spider bite lesions is (1) thorough cleansing, (2) rest, (3) application of ice, (4) compression, and (5) elevation. Oral antiinflammatory medications, an antihistamine, and tetanus vaccine also may be given. If cellulitis appears to be developing, an antibiotic such as erythromycin is indicated (Zeglin, 2005). Treatment of severe necrotic lesions is controversial; however, the goals are to (1) maintain skin integrity, (2) prevent spread of infection, and (3) maintain circulatory status. The following interventions are indicated (Smith et al, 1997): (1) ice pack on the affected area (no heat) to lessen tissue damage, (2) empiric antibiotics to treat cellulitis, (3) NSAIDs to relieve inflammation and pain, (4) tetanus toxoid, and (5) nonocclusive topical dressings to provide a moist environment, fill dead space, and absorb exudate. The site should be monitored for signs of deterioration and cellulitis (Rhoads, 2007).
Patients with severe and rapidly progressing lesions may be given dapsone (Avlosulfon) therapy, which is an inhibitor of neutrophil function. However, it must be administered within hours of a bite to be effective. By inhibiting the spread of neutrophils, dapsone is believed to minimize tissue necrosis (Zeglin, 2005). However, dapsone can have multiple moderate to severe adverse effects. Alternative interventions include hyperbaric oxygenation, nitroglycerin patches, electric shock therapy, and heparin therapy, although no evidence is conclusive for the effectiveness of these treatments. Systemic reactions and complications from the bite of a recluse spider include renal failure and coagulation disorders such as thrombocytopenia and disseminated intravascular coagulopathy (Zeglin, 2005).
Pyoderma gangrenosum
Pyoderma gangrenosum (PG) is a chronic neutrophilic inflammatory disease that most likely represents an aberrant immune response to an as yet unidentified antigen; alterations of neutrophils and interleukins through action of tumor necrosis factor (TNF)-α cytokines have been reported (Brooklyn et al, 2006). The pathogenesis of PG may be related to abnormal T-cell responses and production of a powerful proinflammatory cytokine (TNF-α) (Reguiaii˜ and Grange, 2007). Histologically, the presence of numerous polymorphonuclear leukocytes creates a dense infiltrate of the dermis that can extend from the superficial dermis to the subcutaneous tissue.
These painful lesions have been associated with underlying systemic diseases, such as inflammatory bowel disease in 30% of cases and rheumatoid arthritis with seropositive increase of the rheumatoid factor in 25% of cases (Box 30-1). Approximately 40% to 50% of cases occur in patients with no known associated systemic disease and are idiopathic (Snyder, 2008; Wollina, 2007). When PG accompanies a systemic disease, it does not necessarily parallel the underlying disease and instead be triggered by trauma (Paparone et al, 2009).
PG has several different manifestations, but generally these extremely painful lesions begin with a nodule, pustule, or bulla that develops significant induration and erythema and proceeds to ulceration. The three clinically distinct variations of PG are classic, atypical, and peristomal. The most common presentation is the classic ulcerative form. This particular variation is characterized by ulcers that usually occur on the lower extremities but may also occur on the abdomen, genitalia, trunk, head, and neck. It is commonly associated with inflammatory bowel disease (particularly Crohn’s disease) and rheumatoid arthritis and may occur before, during, or after the disease (Callen and Jackson, 2007).
Atypical PG is commonly associated with myeloproliferative disease, refractory anemias, and myelogenous leukemia (Callen and Jackson, 2007). These are superficial ulcerations or deep erosions primarily located on the hands, arms, face, head, or neck that begin as pustules and extend into plaques. This particular variation of PG is commonly misdiagnosed as cellulitis.
Peristomal PG consists of lesions around a stoma commonly associated with inflammatory bowel disease. These lesions are similar to those typical of classic PG. Although rare, extracutaneous manifestations of PG can involve the lungs, bones, cornea, liver, spleen, heart, skeletal muscles, and central nervous system (Callen and Jackson, 2007).
Common characteristics of the ulcerative PG lesion include irregularly shaped wound edges that are elevated and violaceous (Plate 61). Ulcers are exudative and extremely tender. The wound base is often filled with yellow slough and/or islands of necrosis; wound edges are undermined. A band of erythema may extend from the wound edge, which defines the direction in which the ulcer will extend. Healing may be present along one edge of the ulcer while enlargement occurs along another edge. Ulcers heal slowly and leave an atrophic, irregular scar. A common and notable characteristic of PG is a phenomenon known as pathergy, which is the abnormal and exaggerated inflammatory response to noxious stimuli. Patients often report the lesion developing after minor trauma, such as a bump against a piece of furniture. Minor trauma preceding the development of the ulcer is an important piece of information to obtain during the patient interview (Paparone et al, 2009).
PG is difficult to diagnose; it is essentially a diagnosis by exclusion. It can be misdiagnosed as venous, arterial, neuropathic disease, vasculitis (i.e., polyarteritis nodosa), thrombophilic disease (livedoid vasculitis, antiphospholipid syndrome), neoplasia (squamous cell carcinoma, cutaneous lymphoma, metastatic carcinoma), or infection (cellulitis, herpes, cutaneous tuberculosis) (Callen and Johnson, 2007). Diagnosis is based on clinical manifestations and a thorough examination in which other ulcerative skin disorders (e.g., vasculitis, infections) and psychosomatic illnesses have been excluded. A history and physical examination, skin biopsy for histology and microbiology, and an investigation for an associated illness constitute a thorough workup (Box 30-2). The histopathologic findings are not specific for PG; however, they are supportive of the disease. A biopsy of the ulcer is essential, even though it may enlarge the size of the ulcer through the process of pathergy. The biopsy must be obtained from the erythematous margin of the wound for accurate histopathologic findings, which will assist in ruling out vasculitic, vasoocclusive, and infectious causes (Callen and Jackson, 2007). Laboratory tests for antineutrophilic cytoplasmic antibodies (ANCAs) and antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant, rapid plasma reagin [RPR]) are important to exclude other diseases that could account for these lesions. The diagnosis of PG is reached only after this workup is complete.
BOX 30-2 Proposed Diagnostic Criteria for Pyoderma Gangrenosum
Minor criteria
1. History suggestive of pathergyd or clinical finding of cribriform scarring
2. Systemic diseases associated with pyoderma gangrenosume
3. Histopathologic findings (sterile dermal neutrophilia ± mixed inflammation ± lymphocytic vasculitis)
4. Treatment response (rapid response to systemic glucocorticoid treatment)f
Adapted from Su WPD et al: Pyoderma gangrenosum: clinicopathologic correlation and proposed diagnostic criteria, Int J Dermatol 43:790–800, 2004. From Callen JP, Jackson JM: Pyoderma gangrenosum: an update, Rheum Dis Clin North Am 33:793, 2007.
Treatment of PG consists of a combination of systemic therapy and local wound care. Of the several treatments that have been used to manage PG, the most consistent, effective results have been obtained with immunosuppression with corticosteroids and cyclosporine. Large, orally administered doses of prednisolone (60–120 mg) are given daily until the disease is under control as demonstrated by the reduction in pain and presence of granulation tissue. Although PG is not an infectious disease process, it can be complicated by infections. In fact, patients may receive treatment with antibiotics for cellulitis and may not improve because an initial biopsy was not obtained (Callen and Jackson, 2007; Wollina, 2007). Dapsone has been useful in controlling the wound bioburden, particularly during the diagnostic workup. Researchers are reporting the effectiveness of anti–TNF-α therapy for PG associated with inflammatory bowel disease, with complete ulcer healing within 7 to 21 days (Reguiai˜ and Grange, 2007).
Topical wound management should address wound needs, which include exudate management, protection from trauma, a moist wound environment, and pain control. Typically, management of the wound is necessary before its cause is known. Because of the extreme pain that typifies PG, nonadhesive dressings are preferred. Debridement is achieved only through autolysis and regression of the disease process itself. Aggressive sharp debridement is contraindicated because it will lead to extension of the disease through the process of pathergy. In fact, local care should be delivered with great caution because of the tendency for pathergy to occur. Skin grafts also are to be avoided due to pathergy (Paparone et al, 2009). Antibacterial topical dressings are often warranted to manage the wound bioburden and potential secondary bacterial infections (Callen and Jackson, 2007).
Vasculitis and connective tissue disorders
Vasculitis comprises a group of disorders that have in common the pathologic features of inflammation of the blood vessels, endothelial swelling, and necrosis. Vessels of any size can be affected, so any organ or system may be involved, resulting in a wide array of symptoms and clinical presentations. Vasculitis ulcers usually are the sign of a complex process and may indicate a systemic disorder such as rheumatoid arthritis or lupus. However, vasculitis ulcers also can occur as a primary condition (Anderson, 2008; Armitage and Roberts, 2004). Most vasculitic syndromes are believed to have an immunologic etiology.
Specific diseases that may have vasculitis as a prominent feature include rheumatoid arthritis, systemic lupus erythematosus, polyarteritis nodosa, hypersensitivity vasculitis, Wegener granulomatosis, Sjögren syndrome, cryoglobulinemia, scleroderma, and dermatomyositis (Hunter et al, 2002; Rubano and Kerstein, 1998).
The general signs and symptoms of vasculitis are fever, myalgias, arthralgias, and malaise. Patients sometimes describe a vague, flulike illness. Peripheral neuropathy may be present. Other symptoms depend on the organ involved, which is determined by the specific disease. For example, cryoglobulinemic vasculitis likely will be associated with renal and skin problems, Wegener granulomatosis may lead to respiratory as well as renal involvement, and the vasculitis associated with Sjögren syndrome attacks the brain, lungs, and skin (Jennette and Falk, 1997).
Cutaneous features of vasculitis can vary depending on the disease, but certain characteristics are common. The lesions can range from erythematous, nonblanching macules and/or nodules to hemorrhagic vesicles and palpable purpura, to necrotic lesions and ulceration. Skin biopsy is critical and is best taken from early lesions. Two or three sites might be needed to obtain the correct diagnosis (Roenigk and Young, 1996). Skin ulcers associated with vasculitis are frequently located on the lower extremities, making them difficult to distinguish from venous ulcers (Plate 62).
The goal of treatment of vasculitis ulcers is control of the underlying disease process. Bed rest and administration of antihistamines, corticosteroids, and immunosuppressive agents often are necessary (Hunter et al, 2002). Plasmapheresis might be necessary in cases associated with circulating immune complexes. Topical therapy includes debridement of necrotic tissue, prompt identification and treatment of infection, maintenance of a moist wound base, absorption of excess exudate, packing of any dead space, insulation, and protection from further trauma.
The various vasculitis syndromes have many similarities but also have specific differences unique to some of the diseases. The unique features of rheumatoid arthritis, systemic lupus erythematosus, and polyarteritis nodosa are listed in Table 30-1.
TABLE 30-1 Characteristics of Skin Lesions with Vasculitic Disorders
| Vasculitic Disorder | Description | Ulcer Characteristics |
|---|---|---|
| Rheumatoid arthritis | Not well understood Associated with high levels of rheumatoid factor (RF) (Ikeda et al, 1998; Yamamoto et al, 1995) Evidence of venous insufficiency (McRorie et al, 1998) Limited ankle movement contributes to poor calf muscle pump function and may place patient at risk for venous ulcer development | Begin as palpable purpura and ecchymosis May progress to ulceration Shallow, well-demarcated, painful, slow to heal May require addition of compression therapy (McRorie et al, 1998) |
| Systemic lupus erythematosus (SLE) | Chronic immune disorder Characterized by periods of exacerbation and remission Affects multiple organs (skin, serosal surfaces, central nervous system, kidneys) and red blood cells Circulating immune complexes and autoantibodies cause tissue damage and organ dysfunction No single cause; influenced by environment, host immune responses, hormones Common symptoms include fatigue, weight loss, fever, malaise Butterfly rash (facial edema over cheeks, nose) is typical Potential manifestations include seizures, hemiparesis, pericarditis, pleuritis, renal failure, nausea, vomiting, abdominal pain, arthralgias | Present as palpable purpura Progress to ulceration Occur on malleolar area Present as round lesions with erythematous borders Wound may have atrophy and loss of pigmentation |
| Polyarteritis nodosa (PAN) | Medium- and small-vessel vasculitis Necrotizing arteritis affecting small- and medium-sized arteries of most organs Involved organs commonly include kidney, liver, intestine, peripheral nerves, skin, muscle Characterized by fresh and healing lesions Clinical manifestations include anorexia, weight loss, fever, fatigue Organ-specific manifestations include abdominal pain, myalgia, arthralgia, paresthesia Subcutaneous painful nodules of lower extremities may develop | Skin involvement occurs in approximately 40% of patients Lesions have “punched out” appearance Painful Lesions may begin as purpura with urticaria before progressing to ulceration May have “starburst” pattern extending from ulcer Painful subcutaneous nodules present |
Drug-induced vasculitis
In approximately 10% of patients with vasculitis, the cause is a drug reaction rather than a disease process. Drug-induced vasculitis usually is confined to the skin and appears about 1 week after administration of the drug. The drug binds to serum proteins, causing an immune-complex vasculitis (Jennette and Falk, 1997). The typical presentation is purpura and ulceration involving the lower extremities. Once systemic disease has been ruled out, treatment involves removal of the precipitating drug and symptomatic treatment. Antihistamines and NSAIDs are most often prescribed. Corticosteroids may be added for more severe symptoms. Wound care is based on wound needs, and ulcers resolve spontaneously once the drug is removed.
Epidermolysis bullosa
Epidermolysis bullosa (EB) is the name given to a group of similar skin conditions with various defects in the epidermal basement membrane. Manifestations include a tendency to develop blisters and erosions in the skin, and sometimes in mucous membranes, after mild mechanical trauma (Ly and Su, 2008). EB is most often inherited, although there is a noninherited form (EB acquisita). There are many types of EB, and symptoms can range from mild, seasonal blistering to life-threatening skin erosions (Schober-Flores, 2003). EB can affect every epithelial structure in the body, including the eyelids, conjunctivae, corneas, bowels, skin, and gums.
Inherited EB is rare, affecting 100,000 people, mostly children (Pillay, 2008). It is classified as one of three types: EB simplex, junctional EB, and dystrophic EB. At least 23 distinctive phenotypes of EB have been identified. Differences between the three types are based on ultrastructural levels of the skin within which the blisters develop. Immunofluorescence or electron microscopic studies of skin specimens are most reliable in establishing the diagnosis. Distinctive characteristics of EB are listed in Box 30-3.
BOX 30-3 Characteristics of Epidermolysis Bullosa by Category
Recessive dystrophic epidermolysis bullosa (rdeb)
• Dystrophic scarring is distinctive feature that serves as clinical marker
• Separation at basement membrane zone deep to basement membrane
• Blister formation results from even minimal mechanical trauma
• Blisters eventually rupture to form slow-to-heal superficial ulcers that continue to be exposed to minimal mechanical trauma
• Healing always involves scarring, so skin has atrophic and wrinkled appearance
• Elbows, knees, hands, feet are sites of repeated trauma
Dominant dystrophic eb (ddeb)
• Formation of blisters below basement membrane
• Autosomal dominant inheritance
• Trauma-induced blisters form at birth or shortly thereafter
• Blisters heal with scar formation but usually are less extensive than in recessive form
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