Spotlight

1. Spotlight Pitfalls in Diagnosing Necrotizing Fasciitis

2. Source and Credits • This presentation is based on the July/August 2014AHRQ WebM&M Spotlight Case • See the full article at http://webmm.ahrq.gov • CME credit is available • Commentary by: Terence Goh, MBBS, Department of Plastic Surgery, Singapore General Hospital and Lee Gan Goh, MBBS, Division of Medicine, National University Health System, Singapore • Editor, AHRQ WebM&M: Robert Wachter, MD • Spotlight Editor: Bradley A. Sharpe, MD • Managing Editor: Erin Hartman, MS

3. Objectives At the conclusion of this educational activity, participants should be able to: • State the epidemiology of necrotizing fasciitis • Appreciate the high mortality associated with necrotizing fasciitis • Explain the pathophysiology of necrotizing fasciitis • Describe the main challenges in the diagnosis of necrotizing fasciitis • List steps which can be taken to avoid errors in the diagnosis of necrotizing fasciitis

4. Case: Diagnosing Necrotizing Fasciitis A 49-year-old previously healthy man presented to the emergency department (ED) after falling at work 3 days before. He had presented to a different ED one day prior with diffuse pain on his left side (the side of impact) and was given non-steroidal anti-inflammatory medications and sent home. He presented to this new ED with persistent and worsening left arm, chest, abdomen, and thigh pain. On physical examination, he was afebrile but tachycardic. He had diffuse, tender ecchymosesinvolving his left shoulder, upper chest, lateral abdomen, and thigh. Although ED physicians felt he had simple bruising from the fall, they noted that he was in severe pain requiring intravenous opiates and that he was unable to independently ambulate.

5. Case: Diagnosing Necrotizing Fasciitis (2) Because of these symptoms, blood tests were obtained and results showed a white blood cell count of 2.8 x 109/L (normal range: 3.5–10.5 x 109/L) and acute renal insufficiency with a creatinine of 1.4 mg/dL (normal range: 0.6–1.2 mg/dL). A CT scan of the abdomen and pelvis showed ʺinduration in the left quadriceps muscle and fluid layering in the abdominal wall.ʺ He was seen by the trauma surgical service, who felt the findings were due to diffuse bruising. The patient was admitted to an internal medicine service. Due to ED crowding, he remained in the ED overnight, receiving only intravenous fluids and intravenous opiates for his pain.

6. Case: Diagnosing Necrotizing Fasciitis (3) Overnight, his pain worsened and he had persistent tachycardia. Early morning lab results showed a white blood cell count of 1.6 x 109/L, a creatinine of 1.6 mg/dL, a creatine kinase of 2650 U/L (normal range 55-170 U/L) (evidence of muscle breakdown), and a lactate of 6.2 mg/dL (normal range 0.5−2.2 mmol/L) (evidence of tissue hypoxia). He was seen by the internal medicine team mid-morning and diagnosed with rhabdomyolysis from trauma and acute renal failure. He continued to receive intravenous fluids. His pain had become so severe that he was switched to dilaudid, administered through a patient-controlled analgesia (PCA) pump.

7. Case: Diagnosing Necrotizing Fasciitis (4) Later that day, the patient had progressive respiratory distress and developed septic shock. He was re-evaluated by the surgical service and felt to have probable necrotizing fasciitis with pyomyositis. He was urgently taken to the operating room, where he required debridement of 7300 cm/sq (an area roughly 2 feet by 4 feet) of skin and soft tissue from his left arm and axilla, anterior chest wall, abdominal wall, thigh, and leg. After surgery, he was progressively hypotensive despite multiple vasopressors. He developed multi-organ dysfunction and ultimately, after discussions with his family, care was withdrawn and he died peacefully. He underwent autopsy, which showed necrotizing fasciitis with pyomyositis secondary to methicillin-resistant Staphylococcus aureus (MRSA).

8. Skin and Soft Tissue Infections Skin and soft tissue infections (SSTIs) are incredibly common in both pediatric and adult medicine SSTIs involve suppurative bacterial or fungal invasion of the epidermis, dermis, or subcutaneous tissues SSTIs can range in severity from benign to very serious (as in this case)

9. Background • An expert panel has classified skin infections into 4 classes to help guide treatment: • Afebrile and healthy, other than cellulitis • Febrile and ill appearing, no unstable comorbidities • Toxic appearance, or at least one unstable comorbidity, or a limb-threatening infection • Sepsis syndrome or life-threatening infection (e.g., necrotizing fasciitis)

10. Background (2) This unfortunate case provides an opportunity to focus on necrotizing fasciitis (NF) NF is the most severe SSTI and the diagnosis is often missed or delayed Delay in diagnosis can have devastating consequences, as with this patient

11. History and Features Hippocrates first alluded to a clinical condition of ʺnecrotizing erysipilasʺ in the 5th century BC as a complication of erysipelas Since then, numerous terms have been applied to this condition—phagedenagangrenosum, hospital gangrene, Meleney gangrene, and Fournier gangrene Dominant feature is inflammation and necrosis of subcutaneous fat and deep fascia, with sparing of muscle, leading to severe systemic toxicity

12. Epidemiology • Necrotizing fasciitis is a rare disease • The incidence of NF progressively increases among patients aged 50 years and older • Necrotizing fasciitis generally affects patients with chronic illnesses • More than half of patients have pre-existing medical conditions and 35% have at least two • Despite improved recognition, NF continues to be associated with a high mortality—in the past decade, reported to be between 15% to 45%

13. Pathophysiology of NF • Microbial invasion of the subcutaneous tissues occurs either through: • External trauma • Direct spread from a perforated viscus • From a hematogenoussource • NF can affect any part of the body; extremities and the perineum are most commonly affected

14. Pathophysiology of NF (2) As infection progresses, the skin becomes more tense and red with indistinct margins Local pain is replaced by numbness (from compression or infarction of nerves) Next, skin becomes pale, then mottled and purple looking, and finally gangrenous If gas-forming bacteria are present, air under the skin (crepitus) may be palpated

15. Evolution of Physical Signs in NF A clinical staging of the disease has been proposed based on cutaneous signs (see below) Symptoms may occur over hours to days and patients may present with sepsis or septic shock

16. Microbiology of NF • Historically, group A–beta-hemolytic streptococcus has been identified as the major cause of this infection • More recently, researchers report NF is usually polymicrobial (Type I NF) rather than monomicrobial (Type II NF) • Patient in case had NF secondary to methicillin-resistant Staphylococcus aureus (MRSA) • Though not particularly common, community-acquired MRSA causing NF is an emerging clinical entity

17. Early Diagnosis of NF • Early diagnosis and adequate debridement within 24 hours are the most important factors impacting survival • Patients who receive surgery in the first 24 hours have mortality rate of 4.2%−6.7% • Delaying surgery more than 24 hours is associated with mortality rates of 23%−75% • Thus the relative risk of death is increased by more than 9 times

18. Challenges in Diagnosis • Early diagnosis of necrotizing fasciitis (NF) is notoriously difficult and misdiagnosis is common • In one study, NF was initially misdiagnosed 71.4% of the time

19. Challenges in Diagnosis (2) • Multiple factors contribute to missed or delayed diagnosis: • NF is a rare disease and many practitioners may be encountering it for the first time • NF initially can present similarly to other common soft tissue infections (as in this patient where it appeared he had simple bruising after his fall) • The cutaneous signs of NF usually lag behind disease pathology • Systemic signs of NF may not correlate with the cutaneous signs and vice versa; patients with extensive infection may not be systemically ill

20. Challenges in Diagnosis (3) • The ʺhard signsʺ (e.g., bullae, numbness, crepitus, and skin necrosis) may be absent • In one study, they were present in only 43% of patients with NF • Fever may not be present • In one review, only 32%−56% of patients with NF had a fever • In addition, initial symptoms of NF can be mild until the patient rapidly deteriorates and develops septic shock

21. Strategies to Improve Diagnosis • Multiple specific strategies may help prevent missing a diagnosis of NF • Recognize pain out of proportion to the skin manifestations is a consistent feature of NF • In this case, the patient's severe pain requiring increasing intravenous opiates and a PCA pump should have been a sign that this was a more serious infection • Recognize NF often has rapid progression of infection with migration of the margins of erythema and skin induration despite use of antibiotics • This extension can progress over the course of hours

22. Strategies to Improve Diagnosis (2) • Three other cutaneous features can serve as diagnostic clues: • Margins may be indistinct and poorly defined • Tenderness may extend beyond the apparent involved area of skin • Lymphangitis (inflammation of lymphatics, seen as streaking along skin) is rarely seen in NF • Use of clinical pathways may also help aid in diagnoses • Institutions should involve multidisciplinary teams (often including surgeons, infectious disease specialists, and wound care experts) • Education of frontline clinicians is also crucial

23. This Case • Patient in this scenario presented with a history of trauma • Based on initial clinical exam and diagnostic tests, it appeared to be a simple bruise • Over time, the patient exhibited a cardinal sign of NF—pain out of proportion to working diagnosis • The need for escalating intravenous opiates should have raised concerns for NF and prompted further diagnostic testing

24. Take-Home Points Early diagnosis of necrotizing fasciitis and early debridement is crucial to survival and reduction in morbidity and need for amputation Early presenting signs of necrotizing fasciitis can be non-specific Pain out of proportion to what one would expect for simple cellulitis should ring alarm bells and prompt physicians to expand the differential diagnosis to include NF There is an evolution of clinical signs of necrotizing fasciitis—from early to late stages A keen sense of suspicion and constant review of a patient are the only ways to reliably detect necrotizing fasciitis at an early stage