Controversies in the Diagnosis and Management of Cellulitis
You’re moonlighting in the local ED one afternoon, when you encounter Mrs. X, a 40-year-old woman with rheumatoid arthritis, for which she takes Methotrexate. She was gardening three days prior to presentation when she suffered a small cut to her left ankle from a misplaced spade. the following day, there was some milk erythema around the wound, which has progressed. She now has redness, warmth, and mild swelling to the lateral ankle and distal calf, with no signs of lymphangitis and no fluctuance. The ankle joint moves easily and without pain. As she is afebrile and well appearing, you discuss with her PMD and send her out on Bactrim and Keflex, to cover both Strep species and MRSA.
The very next patient you meet is Mr. Y, a 50-year-old obese male with CHF. He has had swelling in both legs for quite some time, chalked up in the past to chronic lymphedema and CHF, but now has redness and pain to both ankles and lower legs. Given the severity of the redness and swelling, you elect to treat the patient for cellulitis and order vancomycin, then place an admission order. The hospitalist muses that perhaps the patient has venous stasis dermatitis, but admits that it’s probably wort treating for potential cellulits.
Thinking back to both patients later in the day, you begin to worry about your treatment plans. Should the immunosuppressed woman have been admitted for her cellulitis? What factors make patients more prone to treatment failure? Do you always need to prescribe both Bactrim and Keflex for cellulitis (see IDSA guidelines for SSTIs)? And finally, could the second patient have had stasis dermatitis, and if so, did he really need antibiotics and admission? You decide to look into the evidence to try to answer these questions, and dive right into the literature.
Given the nature of the journal club this month, no specific PICO questions was devised. Instead, we looked at several controversial issues surrounding the management of cellulitis, including diagnostic accuracy, antibiotic selection, risk factors for treatment failure, and prescribing practices
Again, due to the nature of the journal club, no specific search strategy was undertaken. Recent high-impact articles were selected from the medical literature, some due to their highly controversial nature.
Article 1: Peterson D, McLeod S, Woolfrey K, McRae A. Predictors of failure of empiric outpatient antibiotic therapy in emergency department patients with uncomplicated cellulitis. Acad Emerg Med. 2014 May;21(5):526-31
Article 2: Pallin DJ, Camargo CA Jr, Schuur JD. kin infections and antibiotic stewardship: analysis of emergency department prescribing practices, 2007-2010, West J Emerg Med. 2014 May;15(3):282-9.
Article 3: Weng QY, Raff AB, Cohen JM, Gunasekera N, Okhovat JP, Vedak P, Joyce C, Kroshinsky D, Mostaghimi A. Costs and Consequences Associated With Misdiagnosed Lower Extremity Cullulitis. JAMA Dermatol. 2016 Nov 2
Article 4: Moran GJ, Krishnadasan A, Mower WR, Abrahamian FM, LoVecchio F, Steele MT, Rothman RE, Karras DJ, Hoagland R, Pettibone s, Talan DA. Effect of Cephalexin Plus Trimethoprim-Sulfamethoxazole vs Cephalexin Alone on Clinical Cure of Uncomplicated Cullulitis: A Randomized Clinical Trail. JAMA. 2017 May 23;317(20):2088-2096
Cellulitis, a common skin infection, results in around 2.3 million ED visits in the US annually. This number has risen over the years with the increasing prevalence of community-acquired MRSA (CA-MRSA) (Pallin 2008). Despite these rising numbers, there remains significant controversy regarding the diagnosis and management of this common condition, in part due to the lack of objective diagnostic criteria, the presence of several hard to distinguishes mimics (Weng 2016), and difficulties in determining the bacterial etiology in the majority of cases (Jeng 2010).
The most recent guidelines from the Infectious Diseases Society of America (IDSA) do not recommend adding MRSA coverage for the management of mild or moderate on-purulent skin and soft-tissue infections (i.e. cellulitis and erysipelas). The PGY-4 paper (Moran 2017) found that among patients treated as an outpatient for cellulitis, cephalexin alone resulted in similar cure rates to cephalexin plus trimethroprim-sulfamethoxazole, supporting the IDSA recommendations. However; it should be noted that this recommendation does not apply to patients with fever or leukocytosis, or in immunocompromised patients. In our PGY-2 paper (Pallin 2014), the authors determined, among other things, that 63% of patients with cellulitis were given antibiotic regimens that included CA-MRSA coverage. Unfortunately, they did not attempt to determine how many of these patients had criteria that would exclude them from the IDSA recommendation, but instead insinuate that nearly all of them were being treated inappropriately. They even go so far as to recommend using this as a reported quality measure for Medicare’s Physician Quality Reporting System, a suggestion that is both premature and potentially dangerous.
Our PGY-3 article (Went 2016) went a step further, attempting to determine the costs associated with misdiagnosis of lower extremity cellulitis in the US. They report that 30.5% of patients admitted to the hospital with lower extremity cellulitis in their study were misdiagnosed, and that the maority of these patients did not require hospital admission. using a literature review, they therefore determined that such misdiagnoses cost between $195 and $515 million dollars annually throughout the US. Unfortunately, all of these conclusion are based on a highly methodologically flawed retrospective study in which final diagnosis was determined by char review out to thirty days post-discharge. It is quite likely that the retrospective conclusion of misdiagnosis was, in many cases, itself a misdiagnosis. Additionally, the authors offer no direction on how to avoid such proposed misdiagnosis, failing to consider the amount the amount of data available 30 days after presentation that would not be available to the ED physician at the time of presentation (e.g. response to treatment), and fail to note that among misdiagnosed patients who were deemed not to require hospital admission at all (determined retrospectively by dermatologists), the mean length of stay was over 4 days! This information suggests that either these patients did, in fact, need to be admitted, or that the abiliy to differentiate cellulitis from “pseudocellulitis” did not become evident until several days of observation had passed. An editorial written in response to this review notes many of these issues, but also calls for improved diagnostic capabilities and discussion between the ED and admitting physicians (Moran 2017), which seems more than reasonable.
Our PGY-1 paper (Peterson 2014) found that fever (odds ratio [OR] 4.3), chronic leg ulcers (OR 2.5), chronic edema or pymphedema (OR 2.5), prior cellulitis in the same area (OR 2.1), and cellulitis at the wound site (OR 1.9) were all predictors failure of outpatient management of cellulitis.
All of this evidence suggests that cellulitis can be difficult diagnosis fraught with controversy. Care should be taken when diagnosing lower extremity cellulitis, as there are many mimics that do not require antibiotics. Care should also be taken in those patients with risk factors for failed outpatient therapy, with close follow-up and good return precautions given to such patients. Additionally, improved ahjerence to current IDSA guidelines would likely result in use of fewer antibiotics with fewer adverse effects.