Tag Archives: meningitis

Must Know Antimicrobial Regimens – Adults

Authors: Marina N. Boushra, MD (EM Resident Physician, Vidant Medical Center) and Cassandra Bradby, MD (EM Attending Physician, Vidant Medical Center) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit)

A 75-year-old man with a history of diabetes, hypertension, and dementia presents to the emergency department with a complaint of altered mental status. His nursing home caretaker endorses a dry cough for one week that has recently become productive and fevers with a Tmax of 38.9 ºC. She notes that he is not “acting like himself,” and elaborates that he is sleeping more, talking less, and has had multiple episodes of urinary incontinence, which is unusual for him. His vitals on arrival are T 38.5º C, HR 110, RR 30, BP 100/70. His exam is notable for somnolence, increased work of breathing with accessory muscle use, coarse rales at the base of the right lung, tachycardia, and dry mucus membranes.

Bacterial infections are a common diagnosis in the emergency department, and emergency physicians are often tasked with providing antibiotics for outpatient management or beginning antibiotics prior to admission. Antibiotic treatment is not without side effects, and treatment started in the emergency department is frequently empiric. Therefore, an understanding of the most likely causative organisms as well as local patterns of susceptibility and resistance is paramount to adequate treatment, appropriate antibiotic selection, and responsible antibiotic stewardship. Important historical details to elicit include allergies, recent antibiotic use, prior antibiotic failure, dialysis use, use of immunosuppressants or history of immunocompromise, culture results of prior infections, and contact with healthcare facilities, including recent hospitalization, living in a care facility, or recent invasive procedures such as ureteral catheterizations or intubation. These details offer vital information regarding possible bacterial resistance or the presence of opportunistic infection. Because multiple empiric regimens exist for infectious disease in the emergency department, contacting the hospital pharmacy about the local antibiogram may help tailor the empiric regimen to local microbial susceptibilities. Please keep this in mind with the recommendations discussed in each table. The following is a discussion of the most common or most emergent ED-diagnosed bacterial infections, their most likely causative organisms, and current recommendations for empiric treatment.


Pneumonia is infection of the pleural parenchyma and can be broadly divided into community-acquired (CAP) and hospital-acquired pneumonia (HAP). A third category of pneumonia, healthcare-associated pneumonia, is discussed in more detail later in this paper. The majority of pneumonia is community-acquired but historical details such as recent hospitalization, intubation, or ventilator dependence should raise concern for HAP and multi-drug resistant organisms (MDROs). Travel history may be important for more rare causes of pneumonia. In patients with known or suspected HIV or AIDS, pneumocystis pneumonia should be strongly considered.

Community-Acquired Pneumonia (CAP)

CAP can be caused by a variety of pathogens, with the most common bacterial cause being Streptococcus pneumonia1–3. Other common organisms include respiratory viruses, Haemophilus influenza, and Mycoplasma pneumoniae1–3. In patients requiring ICU admission, S. pneumoniae is still common, but there is increased prevalence of Legionella pneumophila, Staphylococcus aureus, gram-negative bacilli, and influenza4. It is important to remember these differences in etiology and to cover adequately for these serious organisms in patients requiring ICU admission. Patients with risk factors for aspiration pneumonia should receive additional anaerobic coverage. Treatment for CAP has become increasingly more complicated due to rising resistance to antibiotics. Risk factors for drug resistance include age >65, alcoholism, medical comorbidities, immunosuppressive illness or medication use, and use of beta-lactam, macrolide, or fluoroquinolone antibiotics in the last 3-6 months5,6.

Treatment should be initiated as soon as a diagnosis of CAP is made to prevent decompensation. CAP can often be treated on an outpatient basis. Studies have shown that physicians often use inconsistent criteria when making the decision to admit patients for the treatment of CAP and overestimate short-term patient mortality, leading to an increased rate of unnecessary hospitalizations7. The 2007 guidelines for the Infectious Disease Society of America (IDSA) and the American Thoracic Society (ATS) recommend using the CURB-65 score or Pneumonia Severity Index (PSI), both well validated prediction rules and decision aids, to aid in the risk stratification of patients and making the decision to admit for inpatient treatment7–9. Interestingly, a recent article investigating oral vs. intravenous fluoroquinolones for non-critically ill patients with CAP showed no difference in mortality, ICU transfers, or need for vasopressors or intubation10. Studies have shown shorter time to treatment and shorter hospital stays for patients started on oral rather than intravenous antibiotics11. As such, it is important to consider oral therapy in non-critically ill patients with CAP who are being admitted for treatment but are able to tolerate oral medication.

Studies have shown similar efficacy in CAP for fluoroquinolones and macrolides plus a penicillin or cephalosporin12. Importantly, there is a high rate of macrolide resistance in S. pneumoniae in the United States; as such, macrolides should not be used as empiric monotherapy in areas where resistance to macrolides is >25%5,13–15. Recommended regimens are outlined in the Table 1 below. The IDSA is expected to publish new guidelines for the treatment of CAP that better reflect current trends in resistance in the summer of 2017.

Hospital-Acquired (nosocomial) Pneumonia (HAP)

Pneumonia patients with recent hospitalizations present a challenge in antibiotic selection. While the pneumonia may be caused by an MDRO picked up in the healthcare environment, it is also possible that the patient has a simple community-acquired organism. The multi-drug resistant (MDR) score assesses a particular patient’s risk for infection with an MDRO16,17. Patients with a high MDR score should be presumed to have a pneumonia due to a resistant organism and treated accordingly with broad-spectrum coverage as outlined in Table 1 below. Patients with low MDR scores can be treated with the more narrow-spectrum coverage used for CAP, with the possibility of widening the spectrum in the event of treatment failure. The Shorr score is a similar scoring tool to assess the risk of infection by an MDR and tailor empiric coverage appropriately18.  Antibiotic treatment for presumed HAP should cover for Staphylococcus aureus and Pseudomonas aeruginosa19. Local antimicrobial prevalence and susceptibility, especially within the hospital, is helpful to determining a regimen, but can often be deferred to the judgement of the admitting team. Empiric regimens as recommended in the 2016 IDSA/ATS guidelines for empiric management of HAP are outlined in Table 1 below.

Healthcare-Associated Pneumonia (HCAP)

Healthcare-associated pneumonia (HCAP) refers to pneumonia that may have been acquired in healthcare facilities such as nursing homes and dialysis centers. It was formerly grouped with HAP due to presumed increased susceptibility to MDROs. Several studies, however, have shown no increased susceptibility to MDROs in patient with HCAP, and it is conspicuously missing from the IDSA/ATS guidelines on the management of HAP19–24. As such, in the absences of other historical susceptibilities to MDROs such as comorbidities or severe illness, patients with HCAP may be treated as CAP19–24.

Table 1: Empiric Treatment of Pneumonia based on type, setting, and patient-specific factors8,19

Type Setting Patient Factors Regimen
CAP Outpatient No recent antibiotics, co-morbidities, high-rate of resistance -Doxycycline 100mg bid for five days

-Azithromycin 500mg on day 1 followed by 250mg for four days.*

-Clarithromycin 500mg bid for seven days*

Recent antibiotics, co-morbidities, high-rate of resistance -Levofloxacin 750mg daily for five days

-Moxifloxacin 400mg daily for five days

-Gemifloxacin 320mg daily for five days

-Combination therapy with a beta-lactam (amoxicillin 1g tid, amoxicillin-clavulanate 2g bid, cefpodoxime 200mg bid, or cefuroxime 500mg bid) PLUS either a macrolide (azithromycin 500mg on day 1, followed by 250mg for four days, or clarithromycin 500mg bid for five days) or doxycycline 100mg bid for five days.

Inpatient Mild-Moderate disease, managed on general floor -Levofloxacin 750mg IV or po

-Moxifloxacin 400mg IV or po

-Combination therapy with a beta-lactam (cefotaxime 1-2g, ampicillin-sulbactam 1.5-3g, ceftriaxone 1-2g) PLUS a macrolide (azithromycin 500mg IV, or clarithromycin 500mg orally)

Severe disease requiring ICU admission -Combination therapy with a beta-lactam (cefotaxime 1-2g, ampicillin-sulbactam 1.5-3g, ceftriaxone 1-2g) PLUS a respiratory fluoroquinolone (levofloxacin 750mg IV, or moxifloxacin 400mg IV) OR azithromycin 500mg IV.

-If penicillin allergic, a respiratory fluoroquinolone PLUS aztreonam 1g

-If MRSA suspected, add vancomycin 15-20mg/kg IV

HAP Inpatient Combination therapy is warranted, with one from each of the following 3 categories:

1) Piperacillin-tazobactam 4.5 g IV, Cefepime 2 g IV, Ceftazidime 2g IV, Imipenem/cilastatin 500mg IV

2) Azithromycin 500mg IV, Ciprofloxacin 400mg IV, Levofloxacin 750mg IV, or Gentamicin 5-7mg/kg IV

3) Vancomycin 15-20mg/kg IV, Linezolid 600mg IV

*Macrolide antibiotics should not be used as empiric monotherapy in areas of known S. pneumoniae resistance >25% to macrolides. If such resistance exists, pair with a beta-lactam as shown in the table above.

Urinary Tract Infection

Urinary tract infections can involve the lower urinary tract (cystitis) or the upper tract (pyelonephritis). Urinary tract infections are very common in women, with sexually active women being at higher risk. Risk factors for urinary tract infections include recent sexual intercourse, prior urinary tract infections, and recent spermicide use25. When present in men, urinary tract infections are typically associated with underlying anatomical anomalies, recent catheterization, or other risk factors. While not all urinary tract infections in males are necessarily complicated, a search for these risk factors should be conducted when a male is diagnosed with a urinary tract infection.

Uncomplicated Cystitis

Urinary tract infections in women begin by bacterial colonization of the vagina by fecal bacteria, which may ascend via the urethra to infect the bladder and kidneys. Uncomplicated cystitis and pyelonephritis in women is typically caused by Escherichia coli, though Proteus mirabilis, Klebsiella pneumoniae, and Streptococcus saprophyticus are occasionally found26,27. Empiric treatment for uncomplicated urinary tract infections is best tailored to the regional E. coli sensitivities and is outlined in Table 328. Of note, this table may be modified based on local resistance patterns. Sterile pyuria should raise concern for a possible sexually-transmitted infection (STI) and patients who fail to improve despite appropriate antibiotic treatment should be tested for STI.

Complicated Urinary Tract Infection

A complicated urinary tract infection is one which is associated with a condition that increases the risk for therapeutic failure, as outlined in Table 2. The microbial spectrum of complicated UTI is more broad, including not only the typical organisms associated with uncomplicated UTI but also more varied and resistant pseudomonal, staphylococcal, and Serratia species as well as fungi29,30. Complicated lower urinary tract infections may be managed as an outpatient, but indications for hospitalization include inability to tolerate oral therapy or suspected/ documented infection with a resistant organism such as extended-spectrum beta-lactamase producing organisms (ESBLs). Complicated pyelonephritis is the progression of infection resulting in emphysematous pyelonephritis, corticomedullary or perinephric abscess, or papillary necrosis. Complicated pyelonephritis is an indication for admission and intravenous antibiotic treatment.

Table 2: Conditions that increase the risk of treatment failure in UTI (complicated UTI)

Renal failure
Hospital-acquired infection
Renal transplantation
Anatomic abnormality of the urinary tract
Symptoms >7 days prior to presentation
Presence of an indwelling foreign body (ureteral catheter, nephrostomy tube, ureteral stent)
Ureteral calculus

UTI and Asymptomatic Bacteriuria in the Pregnant Patient

Urinary tract infection and colonization in pregnant patients are worth special mention. While asymptomatic bacteriuria in a non-pregnant female does not warrant treatment, studies have shown a high rate of progression to symptomatic cystitis and pyelonephritis in pregnant patients31. As such, current recommendations suggest that any bacteriuria in a pregnant patient should be treated with antibiotics32. Additionally, although urinary tract infection in a pregnant woman is, by definition, complicated, fluoroquinolones, the first-line treatment for complicated cystitis, are a pregnancy class C medication and should be avoided33. Mild urinary tract infections in pregnant females are treated similarly to uncomplicated UTIs, as shown in Table 3 below. Follow-up cultures for resolution are important in this patient population34.

Table 3: Empiric treatment of uncomplicated and complicated urinary tract infections28,31,35.

Urinary Tract Infection Recommended regimen
Uncomplicated cystitis -Nitrofurantoin 100mg bid for five days*

-Trimethoprim-sulfamethoxazole 160/800mg bid for three days

-Cephalexin 500mg BID for 3-7 days

-Fosfomycin 3g in a single dose*

-Ciprofloxacin 250mg bid or Levofloxacin 250mg once per day for three days**

Complicated cystitis Outpatient:

-Ciprofloxacin 500mg bid or 1000mg daily for five to ten days

-Levofloxacin 750mg daily for five to ten days


-Levofloxacin 500mg IV

-Ceftriaxone 1g IV

-Ertapenem 1g IV

-Gentamicin 3-5mg/kg IV +/- ampicillin 1-2g every 4-6 hours***

-Tobramycin 3-5mg/kg IV +/- ampicillin 1-2g every 4-6 hours***

Uncomplicated Pyelonephritis




-Ciprofloxacin 500mg po bid for seven days or 1000mg daily for seven days

-Levofloxacin 750mg po daily for five to seven days


-Levofloxacin 500mg IV

-Ceftriaxone 1g IV

-Ertapenem 1g IV

-Gentamicin 3-5mg/kg IV

-Tobramycin 3-5mg/kg IV

Complicated Pyelonephritis – Inpatient, mild-moderate disease:

-Ceftriaxone 1g IV

-Ciprofloxacin 400mg IV

-Levofloxacin 750 mg IV

-Aztreonam 1g IV

Inpatient, severe disease:

-Cefepime 2g IV

-Ampicillin 1g IV four times per day plus Gentamicin 5mg/kg IV daily

-Piperacillin-tazobactam 3.375g IV

-Meropenem 500mg IV

-Imipenem 500mg IV

-Doripenem 500mg IV

Asymptomatic bacteriuria and acute cystitis in the pregnant patient -Nitrofurantoin 100mg po bid for five to seven days (in second or third trimester)*

-Trimethoprim-sulfamethoxazole 160/800 mg po bid for three days****

-Fosfomycin 3g po in a single dose*

-Amoxicillin-clavulanate 500mg po tid for three to seven days

-Cephalexin 500mg po bid for three to seven days

-Cefpodoxime 100mg po bid for three to seven days

*Fosfomycin and nitrofurantoin should be avoided if there is concern for early pyelonephritis.

**Fluoroquinolones, if possible, should be reserved for other important uses to avoid resistance against this class of antibiotics.

***Adding ampicillin provides Enterococcus coverage

****Should be avoided in first trimester and at term

Cellulitis and Soft-Tissue Infection

Cellulitis and Erysipelas

Cellulitis and erysipelas are bacterial skin infections that differ in that erysipelas involves the upper dermis and superficial lymphatics while cellulitis involves the deeper dermis and subcutaneous fat tissue. Both manifest with localized skin erythema, edema, warmth, and pain. Because of the more superficial nature of erysipelas, these lesions are typically more raised and better demarcated than cellulitis. Erysipelas also presents more acutely and with more systemic symptoms such as fevers and chills. The most common pathogens in cellulitis are beta-hemolytic streptococci and S. aureus, including methicillin-resistant S. aureus (MRSA)36–38. Beta-hemolytic streptococci are the most common cause of erysipelas36,39.

Lesions consistent with cellulitis should be examined closely for the presence of a drainable abscess. History is particularly important in the patient with possible cellulitis as cellulitis associated with human or animal bites or with water exposure needs different coverage than uncomplicated cellulitis. The presence of an indwelling device near the region of cellulitis is also important, as it is an indication of device infection.

The treatment of uncomplicated cellulitis is based on whether or not there is associated purulence. Current guidelines group erysipelas with non-purulent cellulitis in terms of treatment, as the lesions are often difficult to distinguish from each other and are caused by a similar spectrum of organisms. Patients with purulent cellulitis should receive empiric coverage for MRSA pending culture results40. Patients with non-purulent cellulitis or erysipelas should receive empiric coverage for beta-hemolytic streptococcus and MSSA, although patients with systemic symptoms, recurrent infection, or prior infection with MRSA should receive additional MRSA coverage36. Cellulitis can typically be managed as an outpatient; patients with signs of systemic toxicity, rapid progression, indwelling devices, or failure of outpatient management should be admitted for parenteral antibiotics. In addition to antibiotics, elevation of the affected area is an important aspect of treatment as it helps promotes drainage of edema and inflammatory substances, speeding symptomatic improvement36.

Table 4: Empiric treatment of cellulitis and erysipelas36

Infection Recommended regimen
Uncomplicated nonpurulent cellulitis without MRSA risk factors or erysipelas Outpatient -Dicloxacillin 500mg po qid for 5-10 days

-Cephalexin 500mg po qid for 5-10 days

-Clindamycin 450mg po tid for 5-10 days

Inpatient -Cefazolin 1-2g IV tid

-Ceftriaxone 1g IV every 24 hours

-Oxacillin or nafcillin IV every 4 hours

-Clindamycin 600-900mg IV tid

Uncomplicated purulent cellulitis or nonpurulent cellulitis with MRSA risk factors


Outpatient -Clindamycin 300-450mg po 3-4 times per day for 5-7 days

-Trimethoprim/sulfamethoxazole 1-2 DS tablets po bid for 5-7 days

-Doxycycline 100mg bid for 5-7 days

Inpatient -Vancomycin 15-20mg/kg/dose IV bid

-Clindamycin 600mg IV tid 

-Linezolid 600mg IV two times per day

-Daptomycin 4mg/kg/dose IV once daily

Skin abscesses

Skin abscesses are most commonly due to S. aureus (MRSA or MSSA), although polymicrobial infection with flora from the skin or adjacent mucosal tissues is also common36,40–42. Risk factors for MRSA infection include recent hospitalization or antibiotic use, contact with healthcare environments, institutionalization, HIV infection, intravenous drug use, and diabetes. Source control, in the form of warm compresses to promote drainage or incision and drainage, is important. The role of antibiotics following source control is debated. Studies have shown a slightly increased cure rate with the use of antibiotics following incision and drainage of uncomplicated abscesses, but also a higher rate of diarrhea and adverse effects43,44. Antibiotics should be started for large (>2cm) or multiple abscesses, extensive surrounding cellulitis, systemic symptoms, immunocompromise or co-morbidities, the presence of an indwelling device, or in cases where incision and drainage alone fails to achieve adequate clinical response36. Hospitalization and parenteral antibiotics should be considered for patients with extensive skin involvement or signs of systemic toxicity.

Table 5: Empiric antibiotic treatment of abscesses following source control36

Outpatient If suspicion for MRSA:

-Clindamycin 300-450mg po 3-4 times per day for 5-7 days

-Trimethoprim/sulfamethoxazole 1-2 DS tablets po bid for 5-7 days

-Doxycycline 100mg po bid for 5-7 days

If no suspicion for MRSA:

-Dicloxacillin 500mg po bid for 5-7 days

-Cephalexin 500mg po bid for 5-7 days

Inpatient -Vancomycin 15-20mg/kg/dose IV bid

-Clindamycin 600mg IV tid 

-Linezolid 600mg IV two times per day

-Daptomycin 4mg/kg/dose IV once daily

Sexually-Transmitted and Vulvovaginal Infections

Sexually transmitted infections (STI) are a diagnosis of immense public health importance. While the results of lab testing are often not available in the emergency department, physicians should have a low threshold for the initiation of treatment in patients with presentations consistent with STI. Treatment for common STIs is outlined in Table 6 below45. Counseling patients about safe sex practices and urging them to inform their partners is paramount to infection control.

Pelvic Inflammatory Disease

Pelvic inflammatory disease (PID) is infection of the upper genital tract (uterus, endometrium, fallopian tubes, ovaries) in women. PID may extend to involve adjacent structures, causing periappendicitis, pelvic peritonitis, and perihepatitis (Fitz-Hugh-Curtis syndrome). The majority of PID is caused by ascending sexually-transmitted infections (STI), with Neisseria gonorrhea and Chlamydia trachomatis being the most commonly implicated pathogens in PID45. The diagnosis of PID is often a presumptive one based on presentation. Due to the risk for tubal scarring leading to infertility or risk of ectopic pregnancy, even minimal symptoms without an alternative diagnosis warrant the start of antibiotic therapy to reduce the risk of serious complications due to delay of therapy. Mild to moderate disease can be treated as an outpatient. Indications for hospitalization and intravenous antibiotics include pregnancy, clinically severe disease, complicated PID (pelvic abscess), and intolerance to, noncompliance with, or failure of oral antibiotics. Empiric coverage for inpatient and outpatient management of pelvic inflammatory disease are outlined in Table 646,47.

Table 6: Recommended treatment regimens for select genitourinary infections45–47

Chlamydia -Azithromycin (1g po in one dose)

-Doxycycline (100mg bid for 7 day)

Gonorrhea* -Ceftriaxone (250mg IM or IV in one dose) plus azithromycin (1g po in one dose) or doxycycline (100mg bid for 7 days)
Trichomonas -Metronidazole (2g po in a single dose or 500mg bid for seven days)

-Tinidazole (2g po in a single dose)

Bacterial Vaginosis -Metronidazole (500mg  po bid for seven days)

-Metronidazole vaginal gel 0.75% (5g intravaginally for five days)

-Clindamycin vaginal gel 2% (5g intravaginally for seven days)

Candida Vulvovaginitis Fluconazole (150mg po in one dose)
Pelvic Inflammatory


Outpatient management -Ceftriaxone (250mg IM in one dose) plus doxycycline (100mg po bid for 14 days)

-Cefoxitin (2g IM) with probenecid (1g orally) plus doxycycline (100mg po bid for 14 days)

Inpatient management -Ceftriaxone (250mg IM in one dose) plus doxycycline (100mg po bid for 14 days)

-Cefoxitin (2g IM) with probenecid (1g orally) plus doxycycline (100mg po bid for 14 days)

*Patients with gonorrhea should also be treated for chlamydia due to high rates of concomitant infection.

Bacterial meningitis

While meningitis is not as common an emergency department diagnosis as the bacterial infections discussed above, patients with meningitis are often quite ill, and knowledge of appropriate antibiotic coverage can speed time to therapy. The most common causes of community-acquired meningitis in adults in developed countries are Streptococcus pneumoniae, Neisseria meningitidis, and, in older adults, Listeria monocytogenes48,49. Empiric treatment should be initiated as soon as meningitis is suspected. Empiric regimens should include ceftriaxone (2g every 12 hours) or cefotaxime (2g every 4-6 hours) for coverage of N. meningitidis and S. pneumoniae as well as vancomycin due to increasing rates of S. pneumoniae resistance to third-generation cephalosporins50,51. In patients >50 years of age or with immunocompromise, ampicillin (2g every 4 hours) should be added to provide coverage for L. monocytogenes49.

Adverse Effects of Antibiotic Use

A discussion of antibiotic use in the emergency department would be remiss without mention of the adverse effects of antibiotics commonly used in the ED. While the use of certain antibiotics may be unavoidable due to patient allergies or susceptibility patters, knowledge of the adverse effects of antibiotics may help guide therapeutic choices and inform or temper patient expectations.

Clostridium difficile infection should always be a consideration when starting antibiotics. Clindamycin is the most common culprit in antibiotic-associated C. difficile infection, but cephalosporins, penicillins, and fluoroquinolones are also common causes52–56. Aminoglycosides, tetracyclines, metronidazole, and vancomycin are rarely associated with C. difficile infection, though any antibiotic use increases the risk for C. difficile infection57. Other important adverse effects include QT prolongation with arrhythmia associated with macrolide and fluoroquinolone use and the risk of peripheral neuropathy and (the uncommon, but oft-cited) tendon rupture with fluoroquinolone use. Common or serious side effects of antibiotics used in the emergency department are summarized in Table 7 below.

Table 7: Common and serious adverse effects of commonly used antibiotics

Antibiotic Common Adverse Effects Serious Adverse Effects Comments
Beta-lactams C. diff infection, diarrhea Hypersensitivity reactions High risk of C. diff, especially with broader coverage and with ampicillin
Macrolides Diarrhea, nausea, vomiting, abdominal pain QT prolongation (especially with erythromycin)
Clindamycin C. diff infection, diarrhea Serious hypersensitivity reactions Most common cause of C. diff
Fluoroquinolones Anorexia, nausea, vomiting, abdominal pain Tendon rupture, peripheral neuropathy, QT prolongation High C. diff risk
Tetracyclines Nausea, diarrhea, photosensitivity Inhibition of bone growth and tooth discoloration (a concern in children) Low C. diff risk
Vancomycin Abdominal pain, nausea Nephrotoxicity, ototoxicity, Red man syndrome, hypotension Red man syndrome can be prevented with pretreatment with antihistamines
Aminoglycosides Nephrotoxicity, ototoxicity Need frequent monitoring of drug levels
Metronidazole Headache, dizziness, metallic taste Disulfiram-like reaction Low C. diff risk
  • Summary

Table 8: Common and serious bacterial infections and recommended empiric treatment

Infection Important organisms to cover Recommended Regimens
Community-acquired pneumonia S. pneumoniae CAP outpatient: doxycycline, macrolide +/- penicillin or cephalosporin

CAP inpatient, mild: respiratory fluoroquinolone, macrolide + penicillin or cephalosporin

S. pneumoniae, L. pneumophila, S. aureus CAP inpatient, severe: penicillin or cephalosporin+ fluoroquinolone OR azithromycin
Hospital-acquired pneumonia S. pneumoniae, MRSA, P. aeruginosa HAP inpatient: anti-pseudomonal penicillin or cephalosporin, or fluoroquinolone, or carbapenem + vancomycin/linezolid
Uncomplicated cystitis E. coli Nitrofurantoin or fosfomycin or TMP/SMX or ciprofloxacin


Complicated cystitis or uncomplicated pyelonephritis E. coli, Pseudomonas sp., Staphylococcus sp. Outpatient: Fluoroquinolone

Inpatient: Fluoroquinolone or aminoglycoside or third-generation cephalosporin or carbapenem

Complicated pyelonephritis E. coli, Pseudomonas sp., Staphylococcus sp. Inpatient, mild-moderate: third-generation cephalosporin or monobactam

Inpatient, severe: anti-pseudomonal penicillin or cephalosporin, carbapenem

Asymptomatic bacteriuria or simple cystitis in the pregnant patient E. coli Nitrofurantoin or TMP/SMX or fosfomycin, or penicillin or cephalosporin with gram-negative coverage
Nonpurulent cellulitis or abscess without MRSA risk factors, erysipelas Beta-hemolytic streptococcal species, MSSA Outpatient and inpatient: staphylococcal penicillin or cephalosporin
Purulent cellulitis, nonpurulent cellulitis or abscess with MRSA risk factors Beta-hemolytic streptococcal species, MSSA, MRSA Outpatient: Clindamycin or TMP/SMX or doxycycline

Inpatient: Vancomycin or clindamycin

Chlamydia C. trachomatis Azithromycin or doxycycline
Gonorrhea N. gonorrhea AND C. trachomatis Ceftriaxone plus azithromycin or doxycycline
Trichomonas Trichomonas vaginalis Metronidazole or tinidazole
Bacterial vaginosis Polymicrobial, anaerobic gram-negative rods Metronidazole oral or intravaginal gel or clindamycin
Candida Vulvovaginitis C. albicans, C. glabrata Fluconazole
Pelvic Inflammatory Disease N. gonorrhea, C. trachomatis Inpatient and outpatient: third generation cephalosporin plus doxycycline
Bacterial meningitis S. pneumoniae, N. meningitidis, L. monocytogenes (if >50 years or immunocompromised) Vancomycin plus third generation cephalosporin +/- ampicillin if age >50 or immunocompromised


 References / Further Reading

  1. Johansson, N., Kalin, M., Tiveljung-Lindell, A., Giske, C. G. & Hedlund, J. Etiology of community-acquired pneumonia: increased microbiological yield with new diagnostic methods. Clin. Infect. Dis. 50, 202–9 (2010).
  2. Jain, S. et al. Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults. N. Engl. J. Med. 373, 415–27 (2015).
  3. Gadsby, N. J. et al. Comprehensive Molecular Testing for Respiratory Pathogens in Community-Acquired Pneumonia. Clin. Infect. Dis. 62, 817–23 (2016).
  4. Cillóniz, C. et al. Microbial aetiology of community-acquired pneumonia and its relation to severity. Thorax 66, 340–6 (2011).
  5. Vanderkooi, O. G. et al. Predicting antimicrobial resistance in invasive pneumococcal infections. Clin. Infect. Dis. 40, 1288–97 (2005).
  6. Ramsdell, J., Narsavage, G. L. & Fink, J. B. Management of Community-Acquired Pneumonia in the Home: An American College of Chest Physicians Clinical Position Statement. Chest 127, 1752–1763 (2005).
  7. Fine, M. J. et al. The hospital admission decision for patients with community-acquired pneumonia. Results from the pneumonia Patient Outcomes Research Team cohort study. Arch. Intern. Med. 157, 36–44 (1997).
  8. Mandell, L. A. et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin. Infect. Dis. 44 Suppl 2, S27-72 (2007).
  9. Lim, W. S. et al. Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax 58, 377–82 (2003).
  10. Belforti, R. K. et al. Association Between Initial Route of Fluoroquinolone Administration and Outcomes in Patients Hospitalized for Community-acquired Pneumonia. Clin. Infect. Dis. 63, 1–9 (2016).
  11. Cyriac, J. M. & James, E. Switch over from intravenous to oral therapy: A concise overview. J. Pharmacol. Pharmacother. 5, 83–7 (2014).
  12. Ruhe, J. & Mildvan, D. Does Empirical Therapy with a Fluoroquinolone or the Combination of a β-Lactam Plus a Macrolide Result in Better Outcomes for Patients Admitted to the General Ward? Infect. Dis. Clin. North Am. 27, 115–132 (2013).
  13. Low, D. E. What Is the Relevance of Antimicrobial Resistance on the Outcome of Community-Acquired Pneumonia Caused by Streptococcus pneumoniae? (Should Macrolide Monotherapy Be Used for Mild Pneumonia?). Infect. Dis. Clin. North Am. 27, 87–97 (2013).
  14. Daneman, N., McGeer, A., Green, K., Low, D. E. & Toronto Invasive Bacterial Diseases Network. Macrolide resistance in bacteremic pneumococcal disease: implications for patient management. Clin. Infect. Dis. 43, 432–8 (2006).
  15. Jones, R. N., Sader, H. S., Moet, G. J. & Farrell, D. J. Declining antimicrobial susceptibility of Streptococcus pneumoniae in the United States: report from the SENTRY Antimicrobial Surveillance Program (1998-2009). Diagn. Microbiol. Infect. Dis. 68, 334–6 (2010).
  16. Park, S. C. et al. Validation of a scoring tool to predict drug-resistant pathogens in hospitalised pneumonia patients. Int. J. Tuberc. Lung Dis. 17, 704–709 (2013).
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Thunderclap Headache – Pearls and Pitfalls

Authors: Drew A. Long, BS (@drewlong2232, Vanderbilt University School of Medicine) and Brit Long, MD (@long_brit, EM Attending Physician at SAUSHEC) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)

You are working in the ED and see that your next patient is a 38 y/o female complaining of headache.  As soon as you enter the room, you notice the patient appears to be in pain, holding her hand to her left temple and wincing.  She states she was going on a run about an hour earlier when she experienced a 10/10 intensity headache.  When you ask about the onset of the headache, she states “One moment I was running, and suddenly I was bent over in pain.”  She also complains of dizziness, nausea, and tingling and numbness of her left hand and foot.  The patient has no history of headaches and no pertinent past medical history.  She recently gave birth 6 weeks prior via spontaneous vaginal delivery.  Her vitals include HR 110, RR 16, BP 173/100, oxygen saturation of 98%, and a normal temperature.  As you gather the rest of the history and move to the physical examination, what must you consider in this patient?

What is a thunderclap headache?

A thunderclap headache (TCH) has been defined as a “headache that reaches 7 (out of 10) or more in intensity within less than one minute.”1 TCH is often unexpected and not preceded by any warning signs or symptoms.  While the duration and location of the headache are important parts of the history, they do not have a role in defining TCH and are nonspecific for TCH.1 When evaluating a patient with a headache, it is vital the Emergency Physician (EP) determine both the intensity and time it took the headache to reach maximum severity.  The EP must keep in mind that a normal neurological exam and absence of any associated symptoms does not exclude a serious cause in a patient with a TCH, and the patient still requires a diagnostic workup for potentially deadly pathologic conditions.1 Additionally, pain relief with treatment does not exclude a serious cause.2-4

The classic teaching in medical school is that a “thunderclap” headache is pathognomonic for subarachnoid hemorrhage (SAH) from a ruptured intracranial aneurysm.  However, only 11-25% of TCHs are due to SAH.5,6 What else should the EP think of when a patient presents with a TCH?

Differential Diagnosis

Table 1 depicts conditions that may manifest as a TCH.1,7,8

Subarachnoid Hemorrhage
Cerebral Venous Thrombosis
Cervical Artery Dissection
Acute Hypertensive Crisis/

Posterior Reversible Encephalopathy Syndrome

Ischemic Stroke
Intracranial Hypotension
Pituitary Apoplexy
Retroclival Hematoma
Third Ventricle Colloid Cyst
Temporal Arteritis
Reversible Cerebral Vasoconstriction Syndrome

Subarachnoid Hemorrhage

Most cases of SAH occur from a ruptured cerebral aneurysm (about 85% of cases), which occur most commonly at branch points in the Circle of Willis.9 The typical presentation of SAH is a sudden, severe headache that the patient describes as “the worst headache of my life.”  A headache will be the primary symptom of SAH in 70% of patients, of which 50% will present with a TCH.6,10-12 The headache usually lasts for several days and very rarely resolves within a few hours.13 Accompanying signs and symptoms include loss of consciousness (one third of patients), seizures (6-9%), delirium (16%), stroke, visual disturbances, N/V, dizziness, neck stiffness, and photophobia.14-16

As TCH is a common presentation of a SAH, any patient that presents with TCH must be evaluated for SAH due to high morbidity and mortality.  According to literature, the average fatality rate of SAH is 51%.17 About 10% of patients with aneurysmal SAH die prior to hospital arrival, 25% die within the first 24 hours of SAH onset, and 45% die within 30 days.18

In evaluating for SAH it is helpful to consider a sentinel headache.  A sentinel headache is a headache that occurs days or weeks prior to a ruptured cerebral aneurysm.  This is thought to arise from a small leak of blood into the subarachnoid space.8 About 10-43% of patients with aneurysmal SAH report a prior similar warning headache.19 Importantly, signs often accompanying SAH, such as a stiff neck, altered mental status, and focal neurological deficits, are usually absent in a sentinel headache.7 However, even if these signs are absent the patient still requires evaluation for a SAH.  For more on evaluation of SAH, see http://www.emdocs.net/controversies-in-the-diagnosis-of-subarachnoid-hemorrhage/.

Cerebral Venous Thrombosis

A headache occurs in 75-95% of patients with cerebral venous thrombosis (CVT).20,21 While the onset of headache in CVT is usually gradual, about 2-13% of patients experience a TCH as the primary symptom.22 Additionally, patients may experience accompanying neurological symptoms from several vascular territories.  Other signs and symptoms include seizures (more commonly focal), papilledema, altered mental status, and focal neurological deficits.7,8 The symptoms can be associated with thrombus location.23,24 Importantly, patients with CVT presenting with TCH as their main symptom are clinically indistinguishable from patients with SAH presenting with TCH.7

While CVT is a relatively rare disorder, 80% of patients with CVT are younger than 50.23,25,26 CVT is more common in women, especially in the peripartum period and in patients with recent surgery.27 CVT is also associated with hypercoagulable states including the use of oral contraceptives, hematologic disorders, factor V Leiden, protein C or S deficiency, and anti-thrombin III deficiency.25,28

For more information about CVT, check out a previous post here:  http://www.emdocs.net/cerebral-venous-thrombosis-pearls-and-pitfalls/

Cervical Artery Dissection

A cervical artery dissection can result in an ischemic stroke, transient ischemic attack, or more rarely a SAH.8 Carotid or vertebral artery dissections are an especially important cause of strokes to consider in young and middle aged patients.29-32 A significant risk factor is a history of neck trauma, which can be minor (e.g. manipulation therapy of the neck or sports-related trauma).33 Other risk factors include connective tissue disease, large vessel arteriopathies, hypertension, and a history of migraines.34-36

Headaches are reported in 60-95% of patients with carotid artery dissections and 70% of patients with vertebral artery dissections.36 While headache onset is typically gradual, TCH occurs in about 20% of patients with a cervical artery dissection.38,39 According to the International Headache Society’s diagnostic criteria, headaches from cervical artery dissection must be ipsilateral to the dissected artery.40 The typical first symptom of a cervical artery dissection is unilateral headache (68%), neck pain (39%), or facial pain (10%).41 The headache from a carotid artery dissection is found most commonly in the frontotemporal region.42 Additionally, about 25% of patients will experience a partial Horner’s syndrome (miosis and ptosis).43 A vertebral artery dissection presents with neck pain (66%) and headache (65%), which can be unilateral or bilateral.44 The headache is more commonly posterior in location.  Many other symptoms may be present, including facial paresthesia, dizziness, vertigo, nausea/vomiting, visual disturbances (such as diplopia), ataxia, limb weakness or numbness, dysarthria, and hearing loss.42

Acute Hypertensive Crisis/Posterior Reversible Encephalopathy Syndrome

Two case reports describe patients who presented with TCH from either a hypertensive crisis or posterior reversible encephalopathy syndrome (PRES).45,46 In a hypertensive emergency, while the diastolic pressure is often ≥ 120 mmHg, there is no specific threshold, as different patients will manifest signs of end-organ damage at varying blood pressures.47 While about 20% of patients with hypertensive crises have associated headaches, most of these are not a TCH but rather a throbbing headache.48 Additionally, a hypertensive crisis may present with symptoms in addition to headache consistent with end-organ damage.  These may include dizziness, dyspnea, vision change, chest pain, psychomotor agitation, change in urine output, fluid overload state, or focal neurological deficits.8

Posterior reversible encephalopathy syndrome (PRES) is a clinical syndrome with radiographic findings that presents with headache, seizures, and visual loss often with extreme hypertension.49 Other symptoms include nausea/vomiting, focal neurological signs, or altered mental status.49,50 Specific radiographic findings are necessary for the diagnosis, most commonly symmetric white matter edema in the posterior cerebral hemispheres.51 The headache associated with PRES generally has an acute onset.7 PRES may occur in conjunction with other disorders including eclampsia, thrombotic thrombocytopenic purpura or hemolytic uremic syndrome, and immunosuppressive therapy.52

It is important to determine whether a patient with TCH is hypertensive due to a stress response to the severe headache or if the TCH is the result of the hypertension.  In patients with TCH and extreme hypertension, it is vital to evaluate for signs of end-organ damage suggesting an acute hypertensive crisis and to consider PRES in patients presenting with headache, seizures, and visual loss.

Ischemic Stroke

About 25-34% of patients with stroke develop an associated headache.53,54 In 50% of these patients, the headache precedes any other neurological signs or symptoms.54 Typically, the headache is throbbing and ipsilateral to the side of the stroke.54  TCH associated with stroke is rare, but several case reports document patients presenting with TCH due to stroke.5,55,56

Spontaneous Intracranial Hypotension

The most common cause of spontaneous intracranial hypotension is CSF leakage from spinal meningeal defects or dural tears.57 This most commonly occurs after lumbar puncture, but can occur from minor trauma such as falls, lifting, coughing, or sports.1,7 Most commonly intracranial hypotension presents with a positional headache that improves after lying down and worsens when upright.58 However, 15% of patients will present with TCH.59,60  Other symptoms associated with spontaneous intracranial hypotension are nausea/vomiting, dizziness, auditory changes, diplopia, visual blurring, interscapular pain, or upper extremity pain.7,8


Meningitis can very rarely present with TCH.  A prospective study of patients presenting with TCH found 2.7% to have an infectious etiology.6 Consider meningitis if the patient is febrile, at increased risk for infection (immunocompromised), or has features of meningitis (e.g. stiff neck).

Pituitary Apoplexy

Pituitary apoplexy occurs with hemorrhage or infarction of the pituitary gland.1,7,8 This most commonly occurs in the setting of a pituitary adenoma, but may occur in association with pregnancy, general anesthesia, bromocriptine therapy, or pituitary irradiation.61 Pituitary apoplexy usually presents with a combination of acute headache, ophthalmoplegia, decreased visual acuity, reduction in visual fields, and altered mental status.62 The headache is usually sudden and severe.62

Retroclival hematoma

A retroclival hematoma is usually seen as a rare manifestation of severe head and neck injuries in which there is atlantoaxial dislocation.63,64 Patients with retroclival hematomas may present with TCH, which has been described in several patients.65,66

Third Ventricle Colloid Cyst

A colloid cyst of the third ventricle can impede the flow of CSF leading to obstructive hydrocephalus.  Third ventricle colloid cysts account for 0.5% of intracranial tumors and are most commonly diagnosed between the third and fifth decades of life.67 The most common symptom is headache, which occurs in 68-100% of patients.68 The headache of a third ventricle colloid cyst usually begins abruptly, lasts for seconds up to one day, and resolves quickly.69 The headache may be relieved with a supine position. Additionally, 50% of patients have associated nausea/vomiting.  They can also experience loss of consciousness, altered mental status, seizures, coma, or death.68

Temporal Arteritis

Temporal arteritis is a very rare cause of TCH.  Temporal arteritis should be suspected in older patients (>50) complaining of a new onset headache, temporal pain, visual symptoms, or jaw claudication.  It is also associated with polymyalgia rheumatica, which occurs in 40-50 percent of patients with temporal arteritis.70 For more information on temporal arteritis, check out this previous post:  http://www.emdocs.net/can-giant-cell-arteritis-be-ruled-out-in-the-ed/.

Reversible Cerebral Vasoconstriction Syndrome

Reversible Cerebral Vasoconstriction Syndrome (RCVS) includes conditions associated with TCH and diffuse, segmental, reversible vasospasm.71,72 RCVS is thought to account for most cases of TCH that are termed “benign,” or unexplained.1 Risk factors for RCSV include the postpartum period, history of migraine, and use of pharmacologic agents including ergotamine, triptans, SSRIs, pseudoephedrine, cocaine, amphetamines, ecstasy, cannabis, and bromocriptine.73-81 Half of RCVS cases occur during the postpartum period or after exposure to serotoninergic agents, adrenergic agents, or cannabis.81-83

The hallmark of RCVS is multiple thunderclap headaches that recur every day or every few days.  These headache recurrences can occur for up to four weeks.72,81 Other symptoms include altered mental status, motor or sensory deficits, seizures, visual changes, ataxia, speech abnormalities, and N/V.7

While RCVS is usually self-limiting, it is not always benign.  A minority of patients can experience residual effects including seizures or strokes.72,82,84

Other causes of TCH

Other conditions that have been reported in association with TCH include complicated sinusitis; cluster headache; primary cough, exertional, and sexual headaches; and primary TCH.1,7,8


What is the workup of TCH?

Every patient with TCH must be assumed to have a life-threatening intracranial condition.  Management of patients presenting with TCH starts with the ABCs.  Once the patient is stabilized, diagnostic evaluation is initiated beginning with specific evaluation for SAH.  Schwedt, Matharu, and Dodick proposed an algorithm for TCH evaluation in 2005, beginning with head CT:7


Figure 1.  Diagnostic Evaluation of TCH.7 (CVST:  cerebral venous sinus thrombosis; SIH:  spontaneous intracranial hypotension; PRES:  posterior reversible encephalopathy syndrome; RCVS:  reversible cerebral vasoconstriction syndrome)

The initial imaging modality is a noncontrast head CT.  CT scan has a high sensitivity and specificity for SAH.  When conducted within 6 hours of onset of TCH, CT has a specificity of 98% and sensitivity nearing 100%.11 As time from headache onset increases, the sensitivity of CT for SAH declines:  86% on day two, 76% after two days, and 58% after five days.85 However, these numbers are based on head CTs interpreted by neuroradiologists, and the scanners utilized were at least third generation.

Unfortunately, CT can miss many causes of TCH including SAH (especially if after 12 hours), CVT, CVA dissection, acute hypertensive crisis/PRES, intracranial hypotension, meningitis, pituitary apoplexy, and retroclival hematoma.  For CVT, the initial CT may be normal in up to 25-30% of patients.86 In a patient with CVA dissection without an ischemic stroke, head CT is usually normal.1,7 Similarly, CT is typically unrevealing in patients with acute hypertensive crisis, intracranial hypotension, meningitis, pituitary apoplexy, and retroclival hematoma.1,7,8 For patients with an acute hypertensive crisis or PRES, while neuroradiographic changes may be apparent on CT, they are best visualized on MRI.87,88

Some authors recommend always performing a CTA or MRA after negative CT noncontrast.1,7,72,89 If the patient has a SAH, a CTA can detect a ruptured aneurysm.  One method is for the TCH patient to receive a CT and CTA, as CTA will additionally further evaluate for SAH or an aneurysm, CVA dissection, stroke, and RCVS.

An LP with opening pressure can aid in diagnosis.  LP is the gold standard for the diagnosis of SAH, especially if the patient presents after 12 hours of headache onset.11,89,90 CSF studies including glucose, protein, white cells, and differential are used for diagnosing viral and bacterial meningitis.  Additionally, opening pressure can be utilized to detect increased or decreased pressures.  CVT may be associated with an elevated opening pressure, while intracranial hypotension is associated with a low opening pressure.1,22 Finally, the CSF should be visually inspected for xanthochromia.

The majority of evidence states that conventional angiography is not necessary in patients with a normal head CT and LP.91 Angiography has a small risk of transient and permanent neurological complications.92 In evaluating patients with TCH and normal head CT and LPs, prospective studies have found no subsequent development of SAH or sudden death in patients with normal head CT and normal LP, supporting the viewpoint that conventional angiography may be more harmful than helpful.93-96

The role of MRI for imaging of the brain and cerebral vasculature has not yet been defined in patients with TCH, especially in the setting of the Emergency Department.  Schwedt, Matharu, and Dodick in 2005 recommended that patients presenting with TCH and a normal head CT and LP receive further evaluation with MRI.7 An MRI can help further evaluate for CVT, pituitary apoplexy, PRES, or intracranial hypotension.7 If MRI is normal, Schwedt et al. recommends evaluation with either an MRA or MRV.  Ducros and Bousser in 2012 have similar recommendations and state that all patients with TCH and a normal head CT and LP should receive a CTA or MRA.1 If these are normal, they recommend a brain MRI for further evaluation.

Even with a thorough workup, studies estimate that a diagnosis is made in only 27-71% of patients with TCH.5,6,10,95 The most common diagnosed cause of TCH is SAH.5,6,10,95 Other vascular causes are the second most common diagnosed cause, which includes cervical artery dissection, CVT, and RCVS.1,97

In determining workup of patients with TCH, the patient history is essential in determining the necessary diagnostic evaluation.  Table 2 provides several suspicious features associated with TCH that may help an Emergency Physician suspect a specific diagnosis.  While the physical exam is useful, patients with TCH and a normal exam (specifically a neurological exam) may still have a deadly intracranial condition.  The decision to pursue further measures beyond a head CT and/or LP should be made in conjunction with a neurologist, so early consultation is warranted. Neurosurgery may also need to be on board.  The ideal mechanism of imaging for each potential condition is shown in Table 3.

Table 2.  Features of TCH that aid with diagnostic evaluation1,7,8,42

Diagnosis Suspect with…
Subarachnoid Hemorrhage Any patient with TCH; also a/w neck stiffness, transient loss of consciousness, and focal neurological symptoms
Cerebral Venous Thrombosis Nonanatomic neurologic deficits, women in peripartum period, recent surgical history, clotting disorders, use of OCPs
Cervical Artery Dissection Young/middle-age patient presenting with stroke S/S, neck trauma
Acute Hypertensive Crisis/

Posterior Reversible Encephalopathy Syndrome

-Hypertensive Crisis:  extreme HTN with S/S of end-organ damage

-PRES:  extreme HTN with headache, seizures, and visual loss

Ischemic Stroke Patients with risk factors for stroke with focal neurological S/S in anatomic distribution
Intracranial Hypotension S/P lumbar puncture or mild trauma with orthostatic headache
Infectious Patient with fever, immunocompromise, or S/S of meningitis
Pituitary Apoplexy Patient with hx of pituitary adenoma, or currently pregnant, with headache, visual S/S, and AMS
Retroclival Hematoma Severe head and neck injury
Third Ventricle Colloid Cyst TCH that resolves quickly, pain often relieved with supine position
Temporal Arteritis Older patient with HA, pain in temporal distribution, visual sx, or jaw claudication.  A/w PMR
Reversible Cerebral Vasoconstriction Syndrome Recurrent TCH over several weeks; history of migraine; postpartum; or use of ergotamine, triptans, SSRIs, pseudoephedrine, cocaine, amphetamines, ecstasy, cannabis, or bromocriptine

Table 3.  Gold-Standard Diagnostic Modality for Conditions resulting in TCH1,7,8,42

Diagnosis Gold-standard diagnosing modality
Subarachnoid Hemorrhage Head CT and Lumbar Puncture
Cerebral Venous Thrombosis MR Venography
Cervical Artery Dissection Brain MRI with MRA or head CT with CTA
Acute Hypertensive Crisis/

Posterior Reversible Encephalopathy Syndrome

Brain MRI
Ischemic Stroke Brain MRI
Intracranial Hypotension Brain MRI
Infectious LP
Pituitary Apoplexy Brain MRI
Retroclival Hematoma MRI
Third Ventricle Colloid Cyst CT or brain MRI
Temporal Arteritis Temporal Artery Biopsy
Reversible Cerebral Vasoconstriction Syndrome CTA or MRA

Case Conclusion

Upon further questioning, the patient remembers that she was in a minor car accident several days prior.  She states she was not injured other than minor neck pain from “whiplash.”  However, the pain had been decreasing over the past several days and was barely noticeable prior to today.  When asked about neck pain, she admits she is experiencing left sided neck pain, but not nearly as severe as her headache.  Now suspicious for a CVA dissection, you order a head CT and CTA.  CTA demonstrates a left sided vertebral artery dissection, revealing the cause of this patient’s thunderclap headache.


A thunderclap headache (TCH) is a headache that reaches 7 (out of 10) or more in intensity within less than one minute.  Every patient presenting with TCH must be assumed to have a life-threatening intracranial condition.  As many conditions can present with TCH (most commonly SAH or RCVS), a thorough history is essential in evaluating for risk factors for other conditions.  The Emergency Physician must keep in mind that the absence of associated symptoms and a normal physical and neurological exam does not exclude a serious cause in a patient with a TCH; the patient still requires a diagnostic workup.  Due to the high morbidity and mortality of subarachnoid hemorrhage, any patient that presents with TCH must be evaluated for SAH.  A noncontrast head CT has a sensitivity for SAH nearing 100% if performed within 6 hours of headache onset.  We recommend TCH patients to receive a CTA with the initial head CT, as this will further evaluate for an aneurysm, cervical artery dissection, stroke, or RCVS.  Decisions on further imaging and diagnostic evaluation should be made in conjunction with neurology and possibly neurosurgery.


References/Further Reading:

  1. Ducros A, Bousser MG. Thunderclap Headache.  BMJ 2013 Jan 8;346:e8557.
  2. Pope JV, Edlow JA. Favorable Response to Analgesics does not predict a benign etiology of headache.  Headache 2008;48:944-950.
  3. Rosenberg JH, Silberstein SD. The Headache of SAH responds to Sumatriptan.  Headache 2005;45:597-598.
  4. Seymour JJ, Moscati RM, Jehle DV. Response of headaches to nonnarcotic analgesics resulting in missed intracranial hemorrhage.  Am J Emerg Med 1995;13:43-45.
  5. Landtblom AM, Fridriksson S, Boivie J, et al. Sudden onset headache:  a prospective study of features, incidence and causes.  Cephalalgia 2002;22:354-60.
  6. Linn FJ, Wijdicks EF, van der Graff Y, Weerdesteyn-van Vliet FA, Bartelds AI, van Gijn J. Prospective study of sentinel headache in aneurysmal subarachnoid hemorrhage.  Lancet 1994:344:590-93.
  7. Schwedt TJ, Matharu MS, Dodick DW. Thunderclap headache.  Lancet Neurol 2006 Jul;5(7):621-31.
  8. Schwedt TJ, Dodick DW. Thunderclap Headache.  UpToDate 2014 Dec 10.
  9. van Gijn J, Rinkel GJ. Subarachnoid hemorrhage:  diagnosis, causes and management.  Brain 2001;124:249-78.
  10. Linn FJ, Rinkel GJ, Algra A, van Gijn J. Headache characteristics in subarachnoid hemorrhage and benign thunderclap headache.  J Neurol Neurosurg Psychiatry 1998;65:791-3.
  11. Edlow JA, Caplan LR. Avoiding pitfalls in the diagnosis of subarachnoid hemorrhage.  N Engl J Med 2000;344:29-36.
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What’s that Rash? An approach to dangerous rashes based on morphology

Author: Jamie Santistevan, MD (ED Quality and Administrative Fellow, University of Wisconsin, @jamie_rae_EMdoc) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)

A wide range of benign and dangerous pathology can present with a rash. It is wise to develop a systematic approach to rashes in the ED, one that helps you recognize the deadly causes of rash while narrowing the differential diagnosis.

Key elements from the history include the distribution and progression of the skin lesions, recent exposures (sick contacts, foreign travel, sexual history and vaccination status), and any new medications. On physical exam, pay specific attention to vital signs. A rash associated with fever or hypotension should make you worry about potentially deadly diagnoses. Perform a careful physical exam, including undressing the patient to fully examine the trunk and the extremities as well as the palms, soles and mucous membranes. Touch the skin with a gloved hand to determine if the lesions are flat or raised and press on lesions to see whether they blanch. Rub erythematous skin to see if it sloughs. Historical and physical “red flags” in a patient with an unknown rash include:[1]

  • Fever
  • Toxic appearance
  • Hypotension
  • Mucosal lesions
  • Severe pain
  • Very old or young age
  • Immunosuppressed
  • New medication

For an organized approach to dangerous rashes, this post will focus on four broad categories based on visual and tactile characteristics:[2]

  • Petechial/Purpuric
  • Erythematous
  • Maculopapular
  • Vesiculobullous

Next, rashes in each category will be further categorized based on clinical features such as the presence or absence of fever. This post will focus on life threatening causes of rash, but you may notice some benign etiologies in the flow diagrams pictured.

Petechial/purpuric rashes

Petechiae are small, red lesions caused when capillaries leak blood into the skin. They do not blanch when pressure is applied and usually begin on the dependent areas of the body, such as the legs. Petechiae larger than 0.5 cm are purpura. Sometimes these lesions will be raised (palpable). Palpable petechiae and purpura are a result of either perivascular inflammation (vasculitis) or infection. Non-palpable petechiae usually occur in low platelet states such as ITP and DIC.

petechiae purpura

There are two defining features that help narrow the diagnosis for patients with a petechial rash. The most important is whether or not the patient is febrile or toxic appearing. To further narrow the diagnosis, ask yourself, is the rash palpable or flat?

petechiael rashes highlight

Approach to the petechial/purpuric rash[2]

Febrile & Palpable: Patients with a petechial rash plus fever or toxic appearance should be considered sick because the rashes in this category are life threatening. In fact, fever plus petechial/purpuric rash equals meningococcemia until proven otherwise and the patient should be placed on respiratory and contact isolation immediately.

  • Meningococcemia and meningococcal meningitis: are caused by Neisseria meningitidis, an encapsulated gram-negative diplococcus. Meningococcemia is disseminated infection whereas meningitis is infection of the CNS. Untreated, both are fatal and even with treatment mortality remains between 10-20%.[1] Patients present with fever, chills, malaise, myalgias, headaches, nausea, and vomiting. The rash is initially erythematous, maculopapular and appears first on the wrist and ankles, then becomes palpable petechiae, mimicking Rocky Mountain spotted fever. The rash quickly spreads to the rest of the body coalescing into palpable purpura. Diagnosis is confirmed by positive cultures of the skin, blood or CSF. Treatment should begin immediately with ceftriaxone if suspecting this disease. Vancomycin should be added to cover resistant strep pneumoniae. Prophylaxis is necessary for anyone potentially exposed to respiratory secretions with Rifampin, Ciprofloxacin or Ceftriaxone.
  • Rocky Mountain spotted fever (RMSF): is a tick-borne illness caused by Rickettsia rickettsii. Mortality exceeds 30% and increases when untreated or when treatment is delayed. The skin lesions begin as a maculopapular rash on wrists and ankles before becoming palpable petechiae and then spreads to the rest of the body. Patients are febrile and toxic appearing and often have a history of travel to southeastern or south central US. Patients complain of fever, headaches, myalgias, and malaise. Calf and abdominal pain is also common. A patient with a history of travel to an endemic area between April to September who presents with fever, headaches, and a rash should be treated for RMSF.[2] Treatment is with doxycycline in all non-pregnant patients, even children.[3]
  • Endocarditis: is an infection of the heart valves commonly caused by streptococcus viridans or staphylococcus aureus. Patients present with vague constitutional symptoms that mimic other common infections. Symptoms include fever, malaise, fatigue and a new heart murmur. Skin findings include palpable petechiae, splinter hemorrhages (nail bed lesions), Janeway lesions (painless, macular spots on the palms and soles) and Osler’s nodes (painful, purple nodules on the pads of the finger and toes). Diagnosis is confirmed by finding valvular vegetations on ultrasound and positive blood cultures. If suspecting endocarditis, obtain at least three sets of blood cultures.

endocarditis skin

Skin Findings in Endocarditis

  • Disseminated gonococcal infection: is caused by widespread infection with Neisseria gonorrhoeae. It typically causes urethritis and cervicitis but can also cause pharyngitis, proctitis, and conjunctivitis. If untreated, the infection can disseminate, occurring in about 3% of patients.[4] Systemic infection can lead to septic arthritis alone without a rash, or the triad of tenosynovitis, polyarthritis and rash.[5] Patients generally complain of fever, chills, arthralgias, and malaise. The rash consists of few skin lesions only, usually on the distal extremities, and may be missed. The lesions begin as petechial macules which progress to form papules and pustules as microabscesses form around embolized bacteria. They later develop a necrotic center. Diagnosis is made with positive cultures of blood, cervical or urethral secretions or skin lesions. Cultures of synovial fluid may also be positive in the case of septic arthritis. Patient should be tested for other sexually transmitted infections. Treatment is with IV Ceftriaxone for 7 days and add Azithromycin or Doxycycline to cover for Chlamydia.[4]

dissem gc findings

Skin Findings in Disseminated Gonorrhea

  • Henoch-Schonlein Purpura (HSP): is an autoimmune vasculitis that primarily affects children causing palpable purpura, GI hemorrhage and nephritis. HSP is an acute, self-limited disease characterized by IgA and C3 deposition preceded by an infection or drug exposure. Patients usually present with palpable purpura on the legs and buttocks and complain of joint and abdominal pain. Some children will develop intussusception as a complication and may appear toxic. Nephritis (hematuria and proteinuria) occurs in about 40% of patients, but only 1% will develop end-stage renal disease.[6] Most patients require admission and consultation with a nephrologist, and treatment is with corticosteroids and/or IVIG.

Febrile & Nonpalpable: Patients in this category are also likely to have a life-threatening diagnosis. Again, beware fever plus petechial rash!

  • Thrombotic Thrombocytopenic Purpura (TTP): is a disease of abnormal platelet aggregation and activation leading to micro-thrombus formation, hemolysis and end organ damage. Consumption of platelets and subsequent thrombocytopenia leads to a nonpalpable, petechial rash. The classic pentad is fever, thrombocytopenia, hemolytic anemia, renal failure, and altered mental status. However, the occurrence of the entire pentad is rare. The combination of thrombocytopenia plus hemolytic anemia is sufficient to suspect TTP and initiate treatment.[2,7] Unlike patients with DIC, patients with TTP will have normal PT, PTT and fibrin levels. Hematology consultation is warranted and treatment is with plasmapheresis. Without treatment mortality exceeds 90%.[2] Platelets should not be transfused because they will precipitate additional thrombus formation.
  • Disseminated Intravascular Coagulation (DIC): is a pathologic activation of the coagulation cascade leading to thrombin and fibrin clot formation, microvessel occlusion and end organ damage. This is followed by activation of the fibrinolytic system, including endogenous TPA, and subsequent bleeding. Patients are toxic appearing, often with fever and shock and develop a non-palpable petechial/purpuric rash. Laboratory findings include thrombocytopenia, increased PT and PTT, increased D-dimer and fibrin degradation products and decreased fibrinogen. Causes include pregnancy, massive trauma, transfusion reactions, or sepsis from Gram-negative bacteremia. Treat the underlying cause and reverse coagulopathy with FFP, platelets, cryoprecipitate and RBCs as needed. Patients require emergent hematologic consultation and ICU admission.
  • Purpura fulminans: is basically end-stage DIC. Patients develop shock and rapid subcutaneous hemorrhage often forming large purpura, hemorrhagic bullae, tissue necrosis, widespread bleeding from multiple sites and multi-organ failure.

Afebrile & Palpable: Patients with palpable petechiae or purpura who are not febrile nor toxic appearing are more likely to be suffering from some form of vasculitis.

  • Autoimmune vasculitis: is a disease in which the blood vessels come under attack of the immune system. Involvement of the small, cutaneous vessels leads to inflammation and capillary leakage producing palpable petechiae. There are many rheumatologic causes, including systemic lupus erythematosus (SLE), rheumatoid arthritis and Sjogren’s syndrome. Systemic vasculitides include Wegener’s granulomatosis, Churg-Strauss syndrome or microscopic polyangiitis. Other causes include chronic hepatitis C or B and medications such as penicillins, cephalosporins, sulfonamides, phenytoin and many more.

Afebrile & Nonpalpable: patients who are not febrile nor toxic appearing with a non-palpable petechial rash are likely suffering from isolated thrombocytopenia.

  • Idiopathic thrombocytopenic purpura (ITP): is a syndrome of isolated thrombocytopenia, which leads to bleeding diathesis. Most commonly, it occurs in children and is self-limited. Often, patients report a preceding viral illness. Rarely, intracranial hemorrhage can occur, often when platelets drop below 10 x 10 ^3/uL and happens in 0.5-1% of cases.[8] The rash of ITP develops as nonpalpable petechiae first in dependent areas such as the ankles or buttocks and can spread to the rest of the body. Patients may have petechiae of the face after coughing or vomiting, but are generally well appearing. Labs show thrombocytopenia but with normal coagulation studies. Treatment is with steroids.

 Erythematous Rashes

Erythematous rashes are characterized by diffuse red skin from capillary congestion, mimicking a bad sunburn. These rashes can occur in a variety of inflammatory and infectious conditions, some of which can be rapidly fatal.

diffuse erythroderma

When evaluating the bright red patient, first try applying lateral pressure to the skin and see if it sloughs (Nikolsky’s sign). Then to further narrow the differential, consider wither or not the patient is febrile or toxic in appearance. Patients with an erythematous rash plus fever are also at high risk for having a deadly diagnosis.

erythematous diagram highlight

Approach to the erythematous rash[2] 


Febrile & Positive Nikolsky’s Sign: Patients in this group have the potential to be sick (Fever + Rash= Badness). But thy also have the potential to lose large amounts of skin which lead to fluid loss and electrolyte imbalances!

  • Staphylococcal Scalded Skin Syndrome (SSSS): occurs in children <5 years old and presents as a red rash with eventual sloughing of the epidermis. It is caused by certain strains of Staphylococcus aureus, which release an exfoliative toxin.[9] Symptoms include abrupt fever, diffuse, blanching skin erythema usually beginning on the neck, axillae and groin associated with skin tenderness. Mucous membranes are NOT involved. Patients may develop flaccid, loose bullae, but because epidermal cleavage is very superficial, these fragile bullae often are not intact at the time of presentation. If suspecting SSSS, cultures should be obtained from blood, urine, nasopharynx, umbilicus or any suspected focus of infection. Culture from fluid within any intact bullae will not be helpful as they contain sterile fluid. Treatment includes antistaphylococcal antibiotics (nafcillin or oxacillin), and Vancomycin in areas with a high prevalence of CA-MRSA. Patients will require diligent fluid and electrolyte management and wound care, generally in a burn unit.
  • Toxic Epidermal Necrolysis (TEN): TEN is a serious drug reaction commonly associated with sulfa drugs, anticonvulsants and antivirals, but other drugs may be involved. Other causes include Mycoplasma pneumonia and CMV infections.[10] TEN presents with sudden onset diffuse erythema with painful skin and eventual sloughing. Patients are usually febrile and toxic appearing. Skin cleavage is full thickness and occurs in massive large sheets and the mucous membranes will have painful, erosive and crusting lesions. Mortality is as high as 30-35%.[2] Treatment includes discontinuation of offending medication and IV fluid management and wound care, usually in a burn unit.

Febrile & Negative Nikolsky’s Sign: Patients in this group still have potential to be sick. Again, Fever + Rash = Badness. Although their skin is diffusely red, it will not slough with lateral pressure. Patients in this group can have eventual sloughing of the skin, but this is generally isolated to the hands and feet.

  • Toxic shock syndrome: TSS is a toxin-mediated illness, which occurs secondary to staph or strep infection. The majority of cases are due to methicillin-susceptible aureus (MSSA), but TSS due to methicillin-resistant S. aureus (MRSA) is increasing.[11] Classically TSS has been associated with high absorbent tampon use, however nasal packing, surgical wounds, postpartum infection and abscesses are other causes. Patients are febrile and toxic appearing and have hypotension refractory to fluids due to massive vasodilation. They have a diffuse erythematous rash, which eventually desquamates on the hands and feet. Treatment involves rapid removal of the infected material, IV antibiotics (Clindamycin and Vancomycin), and hemodynamic resuscitation with fluids often requiring vasoactive medications and ICU admission.
  • Kawasaki disease: is a vasculitis of unknown etiology that manifests in childhood. Patients present with diffuse red rash and fever with lymphadenopathy, strawberry tongue, conjunctivitis, edema of the extremities and peeling skin of the fingers and toes. Symptoms generally follow a nonspecific respiratory or GI illness. Other nonspecific symptoms can also occur including abdominal pain, joint pain, cough, vomiting, irritability or decreased PO intake. The worrisome complication is development of coronary artery aneurysm and myocardial infarction. Treatment is with high dose aspirin and IVIG.
Fever lasting at least five days without any other explanation combined with at least four of the five following criteria:
Bilateral conjunctivitis
Oral mucous membrane changes: red, fissured lips or strawberry tongue
Peripheral extremity changes: erythema of palms or soles, edema of hands or feet, and periungual desquamation
Polymorphous rash
Cervical lymphadenopathy (at least one lymph node >1.5 cm in diameter)

Table 1: Diagnostic criteria for Kawasaki Disease[12]

Kawasaki pics

Mucocutaneous Findings Kawasaki’s Disease

Afebrile & Negative Nikolsky Sign: Most rashes in this category are benign, including scombroid, medication side effect (Vancomycin, Niacin) and alcohol use, but there is one that you don’t want to miss!

  • Anaphylaxis: is a life threatening, generalized allergic reaction. The diagnosis should be highly suspected in an acute illness (developing over minutes to hours) involving the skin and mucosal tissue. The patient may have diffuse hives, pruritus or generalized skin flushing, swollen mucous membranes (lips, tongue, or uvula) and at least one of the following: respiratory compromise (dyspnea, wheezing, stridor, hypoxia) OR symptoms of hypoperfusion (hypotension, syncope, altered mental status). Patients may also have abdominal pain and vomiting as signs of GI tract involvement. Treatment is with prompt delivery of epinephrine, volume resuscitation and management of airway compromise or respiratory distress. Adjunctive agents (antihistamines and glucocorticoids) may be given, but should NOT be used as initial or sole treatment because they do not relieve respiratory tract obstruction, hypotension, or shock and are NOT life saving.[13]

Maculopapular Rashes

The most common types of rashes are maculopapular and they have the broadest differential diagnosis. They are usually seen with viral illnesses but can also be seen in certain bacterial infections, drug reactions, and immune-mediated syndromes. These rashes are characterized by a combination of two types of lesions: macules, which are flat, red splotches and papules, which are solid, raised lesions.


To narrow the differential, first ask yourself if this patient looks ill (febrile and toxic appearing). Then ask where the lesions are concentrated. Are they central (chest, abdomen or back) or peripheral (on the extremities)?

maculopapular diagram highlight

Approach to the maculopapular rash[2] 

Febrile/Toxic & Central: This category generally encompasses viral exanthems, but Lyme disease should also be considered.

  • Lyme disease: is a tick-borne illness caused by Borrelia burgdorferi. Initially patients will have a large, targetoid lesion with central clearing at the site of the tick bite (erythema migrans). This initial lesion characterizes early, localized Lyme disease and is often found in the axilla, inguinal region, popliteal fossa, or at the belt line. It is not particularly painful, although the lesion may burn or itch, and is hot to the touch. Over the next few weeks, patients may develop systemic symptoms such as diffuse dermatitis, meningitis, fever, AV nodal blocks, arthralgias and myalgias (early disseminated Lyme disease). Late Lyme disease is typically associated with intermittent or persistent arthritis involving one or a few large joints and rare neurologic problems, primarily a subtle encephalopathy or polyneuropathy. Serologic testing for antibodies to burgdorferi should be seen as an adjunct to the clinical diagnosis and can neither establish nor exclude the diagnosis of Lyme disease. A positive or negative serologic test for Lyme disease simply changes the probability of actually having the disease. The use of serologic testing in populations with a low pre-test probability of Lyme disease results in a greater likelihood of false positive test results than true positive test results.[14] Doxycycline is the first line treatment in nonpregnant adults and children can be treated with amoxicillin. Patients with EM who reside in or have recently traveled to an endemic area should be treated for Lyme disease without serologic testing.
Serologic testing should be performed in patients who meet all of the following criteria:
A recent history of having resided in or traveled to an area endemic for Lyme disease AND
A risk factor for exposure to ticks AND
Symptoms consistent with early disseminated disease or late Lyme disease (eg, meningitis, radiculopathy, mononeuritis, cranial nerve palsy, arthritis, carditis)
Serologic testing for Lyme disease should NOT be performed in the following settings:
In patients with an erythema migrans (EM) rash.
For screening of asymptomatic patients living in endemic areas.
For patients with non-specific symptoms only (eg, fatigue, myalgias/arthralgias)

Table 2: Indications for serologic testing for Lyme disease.[14]

Febrile/Toxic & Peripheral: Patients in this group can be further differentiated based on the presence or absence of characteristic targetoid lesions. It is important to note that patients who are febrile with peripheral maculopapular lesions that aren’t targetoid require emergent evaluation for meningococcemia and RMSF because both of these infections can begin with rashes that are in the maculopapular form before becoming petechial.

  • Erythema Multiforme (EM): is a condition that can either present as a self-limited rash (EM minor) or progress to include the mucous membranes and become life threatening (EM major). EM is an autoimmune process that follows infection with herpes simplex, mycoplasma or fungal diseases or drug exposure such as sulfa drugs, anticonvulsants and antibiotics.[15] EM minor presents as pruritic targetoid lesions on the extremities that then resolve in 1-2 weeks. Target lesions involve the palms, soles, dorsa of hands and feet, face, extensor surfaces of the extremities. EM minor requires only symptomatic treatment. EM major, on the other hand, is life threatening and is defined by mucous membrane involvement. EM major requires discontinuing the offending agent and fluid management, analgesics, wound care. Although often given, systemic steroids are of unproven benefit. Dermatology consult should be obtained and diagnosis is confirmed with skin biopsy.

EM skin

Mucocutaneous findings in Erythema Multiforme

  • Stevens-Johnson Syndrome (SJS): is a mucocutaneous reaction triggered by medications characterized by detachment of the epidermis. SJS and TEN are in one disease continuum and are distinguished by severity. SJS involves <10% body surface area whereas TEN involves >30%. Patients with skin detachment of 10-30% are described as having “SJS/TEN overlap syndrome”.[16] There are two different ways that these patients present: either with macular (flat), targetoid lesions, which coalesce into large erythematous areas, OR with sudden, diffuse skin erythema and pain (as described above for TEN). The mucous membranes are involved patients have sloughing of large areas of skin. Patients are febrile and may complain of general malaise and other constitutional symptoms. Treatment involves discontinuation of the offending medication and optimizing fluid and electrolyte levels. The use of steroids is controversial.

Afebrile/Nontoxic: Patients with a maculopapular rash, whether central or peripheral, who are afebrile and well appearing are much less likely to have a life threatening diagnosis. Things to consider in these patients are drug reactions, pityriasis, scabies, eczema and psoriasis.

Vesiculobullous rashes

Vesiculobullous disorders are characterized by involvement of the dermal-epidermal junction causing fluid-filled lesions to form. Vesicles are small, <1cm, in size whereas bullae are larger than 1cm.


As with the other forms of rashes, you must first consider whether or not the patient has a fever or is toxic appearing, because this points to a deadly diagnosis. Next look at the distribution of the lesions: are they diffuse or concentrated to a single area of the body?

vesiculobullous dagram highlight

Approach to the vesiculobullous rash[2] 

Febrile and Diffuse: As always, fever and rash should get your attention. In this category of vesucolobullous rashes, one disease is  common in childhood and the other is basically extinct.

  • Varicella: is an infection primarily in children caused by Varicella-Zoster Virus (a herpesvirus) and is transmitted by aerosolized droplets from nasal secretions. The illness begins with a prodrome of fever, malaise and pharyngitis followed by a generalized vesicular rash. The rash appears in crops over several days. The lesions are initially macular, but evolve to become papular, vesicular and then eventually crust over. Lesions have an erythematous base and are present in a variety of stages at one time. Since the introduction of the varicella vaccine in 1995, the overall incidence of complications has declined. The most common complications include: soft tissue infections (42%), dehydration (11%) and neurologic complications such as encephalitis and Reye syndrome (9%).[17]
  • Smallpox: is a deadly disease caused by variola virus and is highly contagious. If you are seeing Smallpox in your emergency department, then we are all doomed, because the disease was pronounced eradicated in 1979 (one of the greatest achievements of modern medicine).[18] However, it is considered among the highest priority agents for biological weapons. Category A agents (including smallpox and anthrax) are of concern because they can be grown easily in large quantities, are resistant to destruction and well-suited for airborne dissemination allowing for infection of large numbers of people.[19] Smallpox presents with sudden onset high fever, headache, malaise and myalgias followed by the development of mucous membrane lesions and cutaneous rash. The rash begins as papules then develops into vesicles involving the face, proximal extremities and trunk then spreading distally. A key finding is skin lesions that are all at the same stage of development. Unvaccinated patients had a mortality rate of 30-50%, but vaccination decreased mortality rate to <1%.[20]

Febrile and localized: Ppatients with localized skin blistering can have a variety of diagnoses, but remember, if they have a fever or look sick, they probably are.

  • Necrotizing fasciitis: is a severe soft tissue infection characterized by tissue destruction, systemic toxicity and high morbidity and mortality. It can occur anywhere on the body but most commonly affects the extremities, perineum and genitalia and rarely arises on the trunk.[21] Early in the infection, skin findings may be mild. About one third of patients are misdiagnosed as having cellulitis.[22] Symptoms that should heighten your suspicion include fever, hypotension or toxic appearance, pain out of proportion to the skin findings, pain beyond the margins of erythema, indistinct margins of involvement and edema beyond the margins of erythema.[23] Later in the course of the disease more ominous signs can appear including skin bullae, skin necrosis and crepitus. Aggressive resuscitation and broad-spectrum antibiotics should be given, but definitive treatment is with immediate surgical debridement.
  • Hand foot and mouth (HFM) disease: is an illness affecting children, which presents with fever, oral vesicles and skin lesions. The oral vesicles are present on the buccal mucosa and tongue. On the skin, small blistering lesions are distributed on the hands and feet but also can occur on the buttocks and less commonly on the genitalia.[24] The infection is spread by contact with nasal discharge, saliva, blister fluid or stool. Coxsackie A is the etiologic agent. Management is primarily supportive consisting of oral analgesics and encouraging adequate fluid intake.

HFM findings

Mucocutaneous findings in Hand Foot and Mouth Disease

Afebrile and Diffuse: There are only two rashes in this category to consider and both are caused by auto-antibodies.

  • Bullous pemphigoid: is an autoimmune disease characterized by skin blisters and occurring in the elderly (age 65 and older). Patients present with prodrome phase lasting weeks to months characterized by eczematous, papular or urticarial skin lesions. Following this phase, tense blisters and bullae develop most commonly on the trunk, extremity flexures and axillary and inguinal folds. It is the tense quality of the bullae, which differentiate bullous pemphigoid from pemphigus vulgaris. Mucosal lesions are present in 10-30% of patients.[25] First line treatment is with topical or oral corticosteroids with the addition of other immunosuppressive therapies if needed.[26]
  • Pemphigus vulgaris: is also an autoimmune, blistering skin disease, but with an average age of onset between 40-60 years old.[27] In PV, bullae are flaccid and superficial and they coalesce to produce large areas of skin sloughing. Positive Nikolsky sign can also be elicited on physical exam and painful mucosal erosions will be present. Patients may require fluid and electrolyte control similar to burn care, requiring pain control, prevention of secondary infection, treatment with steroids and occasionally other immunosuppressant medications.

Afebrile and localized: The patients in this group generally do not have a life threatening diagnosis. Localized burns and contact dermatitis to are included in this category. But there is one important diagnosis to consider.

  • Herpes Zoster: also known as shingles, is caused by varicella-zoster virus and results from reactivation of latent VZV infection in the sensory nerve ganglia. The rash is characterized by a painful eruption of vesicular lesions that do not cross midline and are localized to a single dermatome (most commonly the thoracic and lumbar). Severe pain associated with the acute neuritis may actually precede the rash.[28] The rash begins as erythematous papules, which then progress into grouped vesicles on an erythematous base. There are a number of complications associated with herpes zoster in immunocompetent hosts, the most common of which is postherpetic neuralgia (about 8% of patients).[29] Other complications include bacterial skin infection (2.3%), uveitis or keratitis (1.6%), motor neuropathy (about 1%), meningitis (0.5%) and herpes zoster oticus (0.2%).[29] In immunocompromised patients, those with HIV, organ transplant recipients, those on chemotherapy or with congenital immunodeficiency, VZV can cause severe complications including cutaneous dissemination or end organ involvement. Cutaneous dissemination presents with generalized vesicular skin lesions affecting multiple dermatomes, which do cross the midline. Visceral organ involvement can present as pneumonia, hepatitis or VZV meningoencephalitis. Additionally, pregnant patients are at risk for congenital varicella syndrome (limb hypoplasia, skin lesions, neurologic abnormalities and structural eye damage). All patients with suspected VZV infection should be placed on droplet precautions.

Well that’s all for now. I hope you enjoyed this review on an approach to dangerous rashes. Remember, all patients with a rash who also have fever have the potential to have a life threatening condition, but further differentiating the causes can be done by categorizing the rash into one of four morphologies to help narrow your diagnosis.

References / Further Reading

  1. Nguyen T and Freedman J. Dermatologic Emergencies: Diagnosing and Managing Life-Threatening Rashes. Emergency Medicine Practice. September 2002 volume 4 no 9.
  2. Murphy-Lavoie H and Leigh LeGros T. Emergent Diagnosis of the Unknown Rash: An Algorithmic Approach. Emergency Medicine Magazine. March 2010. emedmag.com
  3. American Academy of Pediatrics. Rocky Mountain Spotted Fever. In: Red Book: 2012 Report of the Committee on Infectious Diseases, 29th ed, Pickering LK. (Ed), American Academy of Pediatrics, Elk Grove Village, IL 2012.
  4. Goldenberg D and Sexton D. Disseminated gonococcal infection. This topic last updated: Jun 11, 2015. Accessed June 19, 2016 at https://www-uptodate-com.ezproxy.library.wisc.edu/contents/disseminated-gonococcal-infection?source=machineLearning&search=disseminated+gonorrhea&selectedTitle=1%7E150&sectionRank=2&anchor=H6#H6
  5. O’Brien JP, Goldenberg DL, Rice PA. Disseminated gonococcal infection: a prospective analysis of 49 patients and a review of pathophysiology and immune mechanisms. Medicine (Baltimore). 1983;62(6):395.
  6. Scheinfeld NS. Langman CB (Ed). Henoch Schonlein purpura. eMedicine. http://emedicine.medscape.com/article/984105-overview. Last updated Sept 28, 2016. Accessed June 20, 2016
  7. George JN and Cuker A. Acquired TTP: Clinical manifestations and diagnosis. This topic last updated: Nov 25: 2015. Accessed July 7, 2016 at https://www-uptodate-com.ezproxy.library.wisc.edu/contents/acquired-ttp-clinical-manifestations-and-diagnosis?source=search_result&search=ttp&selectedTitle=1%7E150#H10434276
  8. Kessler CM, and Nagalla S (ED). Immune Thrombocytopenic Purpura. eMedicine. http://emedicine.medscape.com/article/202158-overview
  9. Patel GK, Finlay AY. Staphylococcal scalded skin syndrome: diagnosis and management. American Journal of Clinical Dermatology. 2003;4(3):165
  10. Mukasa Y, Craven N. Management of toxic epidermal necrolysis and related syndromes. Postgrad Med J. 2008;84(988):60-65.
  11. Durand G, Bes M, Meugnier H, Enright MC, Forey F, Liassine N, Wegner A, Kikuchi K, Lina G, Vandenesch F, Etienne J. Detection of new methicillin-resistant Staphylococcus aureus clones containing the toxic shock syndrome toxin 1 gene responsible for hospital- and community-acquired infections in France. Journal of Clinical Microbiology. 2006;44(3):847.
  12. Ayusawa M, Sonobe T, Uemura S, Ogawa S, Nakamura Y, Kiyosawa N, Ishii M, Harada K. Revision of diagnostic guidelines for Kawasaki disease (the 5th revised edition). Kawasaki Disease Research Committee. Pediatric Int. 2005;47(2):232.
  13. Campbell RL and Kelso JM. Anaphylaxis: Emergency treatment. This topic last updated Jun 07, 2016. Retrieved on July 16, 2016 from https://www-uptodate-com.ezproxy.library.wisc.edu/contents/anaphylaxis-emergency-treatment?source=search_result&search=anaphylaxis&selectedTitle=1%7E150#H30
  14. Wormser GP, Dattwyler RJ, Shapiro ED et al. The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43(9):1089.
  15. French LE, Prins C. Erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. In: Dermatology, Bolognia JL, Jorizzo JL, Rapini RP (Eds), Elsevier Limited, 2008. p.287.
  16. Nirken MH, High WA and Roujeau JC. Stevens-Johnson syndrome and toxic epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis. This topic last updated: Aug 20, 2015. Retrieved on July 16, 2016 from https://www-uptodate-com.ezproxy.library.wisc.edu/contents/stevens-johnson-syndrome-and-toxic-epidermal-necrolysis-pathogenesis-clinical-manifestations-and-diagnosis?source=search_result&search=sjs&selectedTitle=1%7E150
  17. Marin M, Watson TL, Chaves SS et al. Varicella among adults: data from an active surveillance project, 1995-2005. J Infect Dis. 2008;197 Suppl 2:S94.
  18. The global eradication of smallpox: Final report of the global commission for the certification of smallpox eradication. History of International Public Health, No. 4. Geneva: World Health Organization, 1980.
  19. Biological and chemical terrorism: strategic plan for preparedness and response. Recommendations of the CDC Strategic Planning Workgroup. MMWR Recomm Rep 2000; 49:1.
  20. Friedman, HM and Isaacs SN. The epidemiology, pathogenesis, and clinical manifestations of smallpox. This topic last updated: Sep 11, 2015. Retrieved on July 16, 2016 at https://www-uptodate-com.ezproxy.library.wisc.edu/contents/stevens-johnson-syndrome-and-toxic-epidermal-necrolysis-pathogenesis-clinical-manifestations-and-diagnosis?source=search_result&search=sjs&selectedTitle=1%7E150
  21. Goh T, Goh LG, Ang CH, Wong CH. Early diagnosis of necrotizing fasciitis. Br J Surg.2014 Jan;101(1):e119-25. PMID: 24338771
  22. Hakkarainen TW, Kopari NM, Pham TN, Evans HL. Necrotizing soft tissue infections: Review and current concepts in treatment, systems of care, and outcomes. Curr Probl Surg. 2014 Aug;51(8): 344–362. PMID: 25069713
  23. Sudarsky LA, Laschinger JC, Coppa GF, Spencer FC. Improved results from a standardized approach in treating patients with necrotizing fasciitis. Ann Surg. 1987;206(5):661. PMID: 3314752
  24. Adler JL, Mostow SR, Mellin H, Janney JH, Joseph JM. Epidemiologic investigation of hand, foot, and mouth disease. Infection caused by coxsackievirus A 16 in Baltimore, June through September 1968. Am J Dis Child. 1970;120(4):309.
  25. Kasperkiewicz M, Zillikens D, Schmidt E. Pemphigoid diseases: pathogenesis, diagnosis, and treatment. Autoimmunity. 2012;45(1):55.
  26. Murrell DF, Ramirez, M. Management and prognosis of bullous pemphigoid. This topic last updated: Sep 18, 2014. Retrieved on July 16, 2016 from https://www-uptodate-com.ezproxy.library.wisc.edu/contents/management-and-prognosis-of-bullous-pemphigoid?source=machineLearning&search=bullous+pemphigoid&selectedTitle=1%7E71&sectionRank=1&anchor=H24368221#H1643371716
  27. Joly P, Litrowski N. Pemphigus group (vulgaris, vegetans, foliaceus, herpetiformis, brasiliensis). Clin Dermatol. 2011 Jul;29(4):432-6.
  28. Dworkin RH, Johnson RW, Breuer J et al. Recommendations for the management of herpes zoster. Clin Infect Dis. 2007;44 Suppl 1:S1.
  29. Yawn BP, Saddier P, Wollan PC, et al. A population-based study of the incidence and complication rates of herpes zoster before zoster vaccine introduction. Mayo Clin Proc. 2007;82(11):1341.