The Infection—Inflammation Challenges to Skin and Wound Care

Happy New Year and welcome to 2025! The Clinical Management Extra (CME) article featured in this issue was stimulated by one of wound care’s great mentors, scientists, and innovators: Dr Gregory Schultz. Dr Schultz led the international advisory board on wound bed preparation (WBP) in 2002 and further elaborated the scientific basis for WBP with over 70 patents for new innovations. He was keen on disseminating the molecular/cellular evidence that provided barriers to healing in chronic wounds. The paradigm shift of WBP with the mnemonic TIME (Tissue management, Inflammation/infection, Moisture balance, wound Edge) became a living enabler for clinicians to identify and decide on possible interventions based on the wound characteristics and goals of care. Just as a wound changes, WBP is a dynamic concept that has changed and evolved over the years.1 Twenty-one years later, Dr Schultz collaborated with co-Editors-in-Chief Drs Ayello and Sibbald at the Mexican national wound care meeting in September 2023. We combined our three plenaries and staged an interprofessional collaboration of a scientist, nurse, and doctor. During this meeting, Drs Schultz and Sibbald continued to discuss the therapeutic index, which compares published data on topical antiseptics. It compares the mean cytotoxic concentration in mammalian cells to the mean minimum bactericidal concentration of bacterial species. The higher the number, the higher the safety protocol for the topical antiseptic agent. However, this is only one factor to consider when choosing a cleansing agent. The accompanying Practice Points article, “Connecting Wound Bed Preparation 2024, Therapeutic Index, and Covert and Overt Infection” interprets the CME article for everyday practice. For patients with healable wounds (adequate blood supply, the cause has been treated) and bacterial balance (contaminated or colonized), the wound can be cleansed with saline or potable water. For a maintenance or nonhealable wound, bacterial burden is often more important than tissue toxicity. The best antiseptic agent for the wound may relate to the predominate bacterial species in the wound; tissue toxicity is then less important. Remember that antiseptic agents are often present for a short duration on the wound surface and will be often neutralized with exudate and other debris. When local or covert2 infection is present (defined by the presence of three or more of the five NERDS criteria), antimicrobial dressings are indicated. In the Practice Points model, a soup bowl represents deep and surrounding (overt) infection. Four of the STONEES criteria are in the side of the soup bowl and three (probe/ exposed bone, increased exudate, and smell) are in the bottom of the bowl. If three or more criteria are met, a systemic antimicrobial is required. Severe infections (eg, osteomyelitis) are often treated with systemic antimicrobial agents with more severe infections requiring IV antibiotics. The OVIVA (Oral Vs Intra-Venous Antibiotics) trial published in the New England Journal of Medicine in 20193 concluded that oral antibiotics were not inferior to IV antibiotics for most cases of bone and joint infections. In some patients, higher doses of oral antibiotics are needed. This is a very important addition to the use of oral antibiotics for diabetic foot-related osteomyelitis in remote, isolated areas such as Northern and Indigenous communities across Canada and the US state of Alaska. Three factors could increase local capacity for treating leg and foot ulcers: (1) increased use oral antibiotics, (2) equipping clinics with a toolkit containing an 8 MH Doppler to measure/document arterial circulation, and (3) use of USD $25 plantar pressure redistribution shoes. Interprofessional remote education has been facilitated through the Ontario Skin and Wound ECHO program (Extension for Community Healthcare Outcomes) with virtual skills teaching to potentially increase capacity for low-resource communities. In this issue of Advances, adjunctive hyperbaric oxygen (HBO) therapy was studied for chronic refractory osteomyelitis. Lead author J. Benjamin Jackson III concluded that patients who completed HBO therapy had 7.76 times the odds of improvement (P = .015), but HBO did not significantly impact resolution of the osteomyelitis (including potential amputations), especially if the patient had diabetes, peripheral arterial disease, or congestive heart failure. Chronic inflammation can be associated with skin changes and these disorders often have a negative effect on wound healing. Two unusual conditions are explored in this issue of Advances: calciphylaxis and scleredema. Calciphylaxis (calcific uremic arteriolopathy) is a life-threatening disorder (up to 80% mortality) that is most frequently associated with end stage renal disease as outlined in a three-patient case series by Kochhar and podiatry colleagues. These patients develop calcification of the medial layer of the arterioles and subintimal fibrosis that led to thrombotic occlusion of the arterial vessels and subsequent cutaneous necrosis (large black areas of gangrenous lesions of variable size). Punch biopsies were recommended by the authors from the edge of the lesions but in clinical practice, I (RGS) prefer a wedge biopsy of the skin at the edge of the necrosis. Plates of calcification can extend beyond the edges of the necrotic margins. Intravenous sodium thiosulfate is often beneficial along with tight control of the renal disease with dialysis; control of secondary parathyroid dysfunction; and discontinuing calcium, vitamin D3, and vitamin K antagonist therapy. Some patients benefit from HBO to increase oxygenation of the damaged skin regions. Aggressive wound management should remove necrotic tissue early in the course of the necrotic skin changes to promote healing and prevent secondary infections. A variant of calciphylaxis is Martorell hypertensive ischemic leg ulcers, which should be recognized by wound healers. This is a very painful condition with necrotic lesions developing on the posterior gaiter area. It is most common in 50- to 70-year-old women with poorly controlled hypertension. Early surgical excision is optimal when possible, but control of the hypertension and pain along with regular debridement can also result in successful outcomes. This condition is not associated with claudication or other signs of peripheral arterial disease. Scleredema is a progressive symmetric thickening of the skin on the upper back predominantly but can involve the neck, face, and proximal extremities. It differs from scleroderma by not having any distal involvement of the extremities or Raynaud phenomena. Skin biopsies can identify extra deposition of collagen and glycosaminoglycans. There are three subtypes of this disorder. Type I is postinfectious (55% of cases), usually streptococcus. The primary infection needs to be identified and treated, and the scleredema usually resolves in 2 to 6 months. In this issue of Advances, Dr Priyanka Hemrajani and colleagues linked scleredema with COVID-19 infection. Type II (25% of cases) is associated with malignancy including monoclonal gammopathies and paraproteins. Laboratory screening should include serum protein electrophoresis and immunoelectrophoresis. Type III scleredema is due to poorly controlled insulin-dependent diabetes (20% of cases); these cases persist indefinitely and are difficult to resolve. Uncommon inflammatory conditions are often missed, or the diagnosis is delayed. Consider expert consultation when skin conditions are not responding as expected. It is also important for wound healers to differentiate when to use antisepsis versus saline or potable water for wound cleansing. Infections should be diagnosed based on clinical criteria. Covert (local) infection can be treated with topical antimicrobial dressings but deep and surrounding (overt) infections require systemic treatment. In the infectious disease world, there is an increased use of oral antimicrobials with some patients starting with a short 1-week course of intravenous therapy. Thank you, Dr Greg Schultz, for your contributions to improving wound care and acting as the catalyst for exploring the therapeutic index.R. Gary Sibbald, MD, Med, FRCPC (Med Derm), FAAD, MAPWCA, JMElizabeth A. Ayello, PhD, MS, RN, CWON, MAPWCA, FAAN

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