Presentation A 51-year-old Hispanic female with poorly controlled insulin-dependent diabetes mellitus (IDDM) presented with an ulcer on the left leg. The lesion developed one month prior to presentation as a mildly pruritic erythematous papule resembling an insect bite, which gradually increased in size and ruptured to form a crusted ulcer. Over the next few days, the area around the ulcer progressively became more red, swollen, and tender and developed a purulent discharge. Two weeks prior to consult, the patient developed a fever and chills and was admitted to the hospital for one day. She was sent home on oral levofloxacin and clindamycin and was advised to clean and dress the wound daily. The patient was diagnosed with IDDM in 1987 and has since been maintained on insulin injections and various oral hypoglycemics. Abnormally high serum glucose levels indicate poor blood sugar control (136–374mg/dL, normal=65–115mg/dL). The patient was previously hospitalized in November, 2003, at which time she presented with an ulcer on the right anterior leg associated with redness, pain, and swelling of the right lower extremity. She was afebrile and had a normal white blood cell count of 6.0. Her blood cultures, however, grew oxacillin-sensitive Staphylococcus aureus. She was started on clindamycin and levofloxacin and was discharged four days later with marked improvement. The patient has a history of frequent development of pustules and furuncles on various areas of the body including the shins, arms, buttocks, and axillae. These would sometimes heal to form hyperpigmented scars. Physical Examination Physical examination revealed an overweight, afebrile Hispanic woman. Her head, neck, chest, abdomen, back, and upper extremities were within normal limits. She had no lymphadenopathy. On cutaneous examination, a 2-cm round, well-defined, moderately deep ulcer (Figure 1) exuding a large amount of seropurulent discharge was noted on the lower anterolateral area of the left leg. The ulcer base was predominantly covered with yellowish fibrinous material admixed with thick, adherent, necrotic crusts. The ulcer margin was indurated, violaceous, and surrounded by erythema. Several coin-shaped hyperpigmented scars, approximately 1.5–2.5cm in diameter, were prominent on both anterior legs (Figure 2). Similar hyperpigmented patches were visible but not as prominent on the sacral area and left axilla. On the right forearm was a dry 3-mm pustule. Monofilament sensory testing revealed the patient was anesthetic bilaterally on the soles, extending to the distal half of the dorsa of the feet. Investigations Foot and leg x-rays were negative for osteomyelitis and gas collection. White blood cell count was 5.7 (normal=4–11). A fasting blood sugar level of 340 (normal=65–115) and the presence of glucose (3+) and ketones (1+) on urinalysis (normal=negative glucose and ketones) indicated poorly regulated blood sugar levels. Cultures of the wound and anterior nares were not performed, because the patient was receiving antibiotic therapy. Diagnosis The clinical history of a papular lesion similar to an insect bite on the lower leg that enlarges, suppurates, then ulcerates together with the physical findings on the lower extremities compounded with poorly controlled IDDM, frequent furunculosis, and previous bacteremia points to ecthyma. Discussion Gram-positive bacterial infections. The majority of primary and secondary cutaneous bacterial infections are usually caused by Staphylococcus aureus or group A streptococcus.1 S. aureus is an aggressive pathogen and the most common cause of primary pyodermas, soft-tissue infections, and secondary infections on disease-altered skin.1 Impetigo is the most common bacterial skin infection of children. It also occurs quite commonly in adults. Predisposing factors include poor hygiene, frequent skin trauma, and warm, humid conditions. Two types of impetigo are recognized: nonbullous impetigo and bullous impetigo. Nonbullous impetigo, also called impetigo contagiosa, is more prevalent, accounting for more than 70 percent of cases.2 Most often it is caused by S. aureus but can also be caused by S. pyogenes. The disease typically begins as 2–4-mm macules that evolve into vesicles and pustules that eventually rupture to form superficial erosions topped by “honey-colored” crusts. Sites of predilection include the face (especially the areas around the nose and mouth) and the extremities. In contrast, bullous impetigo is characterized by flaccid bullae containing clear, yellow, or turbid fluid that rupture easily, leaving a thin collarette of scale. Thick crusts, as seen in the nonbullous type, are notably absent. This disease mainly affects neonates and older infants with lesions occurring on the face, trunk, buttocks, perineum, or extremities. The etiologic agent is always S. aureus.2 Compared to both types of impetigo, ecthyma is a deeper epidermal infection and often occurs as a consequence of neglected impetigo.1 Some clinicians consider it an ulcerated form of nonbullous impetigo.2 It is caused by S. pyogenes and/or S. aureus. Lesions evolve from a superficial pyoderma, which extends into the dermis, or within a pre-existing dermatosis or site of trauma, such as insect bites or excoriations.1 The condition usually occurs on the lower extremities in children, neglected elderly patients, or individuals in immunocompromised states, such as patients with diabetes. Poor hygiene and minor trauma are contributory factors. A typical ecthyma lesion begins as a papule, vesicle, or vesico-pustule, which over the course of several days enlarges to 0.5–3cm in diameter and develops a crust. An ecthyma ulcer has a punched-out appearance and a purulent necrotic base.1 This matches the disease course and clinical description of the lesion in this patient. In addition, ecthyma lesions are slow to heal and produce scarring. This patient’s ulcer had been present for a month, and she had multiple scars on her anterior legs, probably secondary to past episodes of ecthyma and furunculosis. Several months ago, the patient’s blood culture grew S. aureus. S. aureus bacteremia occurs quite commonly in patients with diabetes with heavily infected open wounds.3 Diabetes mellitus and infections. Patients with diabetes have always been viewed, to some degree, as immunocompromised and, therefore, more prone to infections. Shah and Hux4 conducted the first study to quantify the risk of infectious disease for people with diabetes. The retrospective cohort study included over one million subjects. In comparing patients with diabetes versus patients without diabetes, their results showed that the risk ratio for contracting an infection was 1.21 (99% CI 1.20–1.22), the risk ratio for infection-related hospitalization was up to 2.17 (99% CI 2.10–2.23), and risk ratio for death attributable to infection was up to 1.92 (1.79–2.05). Many individual infections were also noted to be more common in patients with diabetes, especially serious bacterial infections. They concluded that diabetes confers an increased risk of developing and dying from an infectious disease. The susceptibility to infection in patients with diabetes has been attributed to immunopathy and associated defects in leukocyte function.5,6 Polymorphonuclear leukocyte chemotaxis and phagocytosis are energy-dependent processes that are impaired in the patient with diabetes.7 Some studies have documented an inadequate leukocytic response in severe foot infection, a clinical finding that can be found in up to 50 percent of such patients with diabetes.8,9 With correction of hyperglycemia in some patients with diabetes, leukocyte phagocytosis has been found to improve, and microbiocidal rates increase.10 In up to half of the cases, signs and symptoms often accompanying infections, such as fever and leukocytosis, may be absent because of diabetes-related immunosuppression.5,9 This patient was notably afebrile and had a normal white blood cell count despite a purulent ulcer with surrounding erythema and swelling. In these cases, the clinical appearance of the lesion and surrounding tissues would present the best means to assess the infection. Insulin deficiency and hyperglycemia contribute to poor wound healing.11 The quality and quantity of collagen formation is deficient and directly influences wound strength.12 In addition, hyperglycemia acts directly at the cellular level by decreasing phosphoinositide turnover in cell membranes, which in turn appears to cause abnormalities in matrix protein management.11 Microcirculatory abnormalities in patients with diabetes further impede healing by decreasing circulation capacity to deliver oxygen and nutrients to the wound.12 In an animal study, Liu, et al., suggested that the impaired healing response to bacteria in patients with diabetes may be partially caused by greater rates of fibroblast apoptosis, leading to reduced numbers of fibroblastic cells.13 This patient’s poorly controlled diabetes contributed to her risk of ecthyma. Management Important aspects of management of infected wounds in patients with diabetes include antimicrobial treatment of infection, drainage and debridement procedures, glycemic control, management of existing ischemia, relief of pressure over ulcerated areas, and patient education. Wound debridement is essential to reduce bacterial burden and promote rapid healing and is considered a critical factor in the management of infected wounds, since wound healing cannot take place until necrotic tissue is removed.14 In addition, if obligate anaerobes are present, the oxygen exposure that occurs during debridement kills these organisms and reduces bacterial load. Treatment The patient was treated with a two-week course of clindamycin and levofloxacin. In the outpatient clinic, surgical debridement was performed to remove the hardened purulent and necrotic materials overlying the ulcer. For wound care, the patient was sent home with instructions to clean the wound with water, apply a thin layer of papain cream (an enzymatic-debriding cream), and cover the wound with a nonadherent dressing daily. She was also instructed to apply mupirocin cream to her nostrils twice daily to reduce staphylococcus carriage.15 Ibuprofen 600mg every four to six hours as needed was prescribed for pain. Diabetic control was maintained with insulin (60 units in a.m. and 20 units in p.m.) and metformin (500mg 2x/day). Blood glucose levels were closely monitored in collaboration with her primary care physician. A two-week follow-up visit presented a significantly smaller, more superficial ulcer with a clean erythematous granulating base and minimal serous discharge (Figure 3). The wound dressing was changed to a hydrocolloid, and the patient was instructed to change the dressing every two to three days. One month after initial consult, the patient followed up with a completely epithelialized wound, which healed to form a dyschromic scar. No new lesions were noted.