SAEM Clinical Images Series: A Rash You Don’t Want to Miss

rash

A 54-year-old female with a past medical history of diabetes presented to the Emergency Department (ED) for evaluation of unresponsiveness. The patient was found unresponsive by her spouse, who notes she had missed several doses of insulin over the past few days. EMS notes the glucometer read ‘HIGH’ on fingerstick. The patient remains unresponsive on presentation and is unable to contribute further history.

Vital Signs: BP 148/105; HR 120; RR 24; Pulse Oximetry 98% on room air; Temperature 97.7°F

Constitutional: Patient is morbidly obese, unresponsive, and toxic-appearing.

Cardiovascular: Regular rhythm with tachycardia. No murmur.

Pulmonary: Pulmonary effort is normal. Lungs clear to auscultation bilaterally.

Abdomen: Abdomen is soft and non-distended. Unable to assess for tenderness given unresponsiveness.

Skin: Cool, pale, mottled. Large gangrenous, draining, foul-smelling wound on proximal left thigh. There is necrotic, malodorous, black skin noted over the left lower abdomen and left upper thigh.

Neurological: Unresponsive. GCS 3.

White blood cell (WBC) count: 20.5

Comprehensive metabolic panel (CMP): K 5.8; Cr 2.06; BUN 86; Glucose >600

Venous blood gas (VBG): pH<7; lactate 3.4; bicarbonate 7

These photographs show advanced Fournier’s Gangrene, a form of necrotizing fasciitis located in the genitals, perineum, or perianal region. Rapid involvement of our surgical colleagues is crucial, as these patients will not recover without the debridement of affected tissues. Aggressive fluid resuscitation and broad-spectrum antibiotics can be initiated after a surgical consult is made.

This patient presented with impressive visual evidence of advanced disease including severe ecchymosis, but our clinical suspicion must be high as Fournier’s is rapidly progressing and carries a high mortality rate (may be upwards of 30%). Earlier symptoms are genital or perineal pain which may be associated with itching, lethargy, or fever. The biggest exam finding to keep in mind is ‘pain out of proportion to the exam’ as up to 40% of these patients may present without localized symptoms. Advanced disease, as seen in this patient, can present with crepitus and severe ecchymosis of tissue involved. This patient was also found to be in DKA, as evidenced by her laboratory findings. This case should serve as a reminder that it is vital to perform a proper skin examination in patients presenting with hyperglycemia. Ultimately in this case, the patient was intubated for airway protection and started on vasopressors for cardiovascular support in the setting of septic shock. She went into VTach arrest and was successfully defibrillated before further decompensating and becoming asystolic.

Take-Home Points

  • The first task after suspected diagnosis of Fournier’s Gangrene is a page to your surgery service for evaluation and emergent debridement in the OR (depending on your institution this may be general surgery, urology, or both). After your patient is on the path to definitive management, you can begin aggressive fluid administration and broad-spectrum antibiotics (gram-positive, gram-negative, and anaerobic coverage needed).
  • Fournier’s Gangrene is a clinical diagnosis. Imaging may assist in atypical or borderline cases, but should never result in delay of surgical evaluation and treatment. Crepitus and ecchymotic tissue are very late findings; have high clinical suspicion inpatients with signs of swelling, erythema, and pain.

  • Shyam DC, Rapsang AG. Fournier’s gangrene. Surgeon. 2013 Aug;11(4):222-32. doi: 10.1016/j.surge.2013.02.001. Epub 2013 Apr 8. PMID: 23578806.
  • Ustin JS, Malangoni MA. Necrotizing soft-tissue infections. Crit Care Med. 2011 Sep;39(9):2156-62. doi: 10.1097/CCM.0b013e31821cb246. Erratum in: Crit Care Med. 2011 Nov;39(11):2592. Dosage error in article text. PMID: 21532474.
  • Harbrecht BG, Nash NA. Necrotizing Soft Tissue Infections: A Review. Surg Infect (Larchmt). 2016 Oct;17(5):503-9. doi: 10.1089/sur.2016.049. Epub 2016 Aug 2. PMID: 27483003.
  • Singh A, Ahmed K, Aydin A, Khan MS, Dasgupta P. Fournier’s gangrene. A clinical review. Arch Ital Urol Androl. 2016 Oct 5;88(3):157-164. doi: 10.4081/aiua.2016.3.157. PMID: 27711086.
  • Sarani B, Strong M, Pascual J, Schwab CW. Necrotizing fasciitis: current concepts and review of the literature. J Am Coll Surg. 2009 Feb;208(2):279-88. doi: 10.1016/j.jamcollsurg.2008.10.032. Epub 2008 Dec 12. PMID: 19228540.
  • Tintinalli JE, Ma O, Yealy DM, Meckler GD, Stapczynski J, Cline DM, Thomas SH. eds. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9e. McGraw Hill; 2020. p.592- 593.

SAEM Clinical Image Series: Eye Pain

necrotizing

A 59-year-old gentleman experiencing homelessness with a history of hepatocellular carcinoma, hepatitis C, alcohol use disorder, and tobacco dependence presented to the emergency department (ED) with severe, worsening right eye pain, blurry vision, swelling, redness, and purulent discharge after scraping his upper face on concrete during a mechanical fall two weeks prior. Of note, his partner presented to the ED at the same time with a necrotic infection of the breast as well as multiple skin lesions reportedly due to insect bites.

Vitals: T 102.4°F; HR 108; BP 121/94

Head: Lice nits visible in his hair

Eye: Unable to open right eye without assistance; eyelids crusted and necrotic with underlying orbicularis oculi muscle visible; EOM full but painful in all fields of gaze; visual acuity 20/60 in each eye; pupils 2 mm, equal and minimally reactive.

White blood cell (WBC) count: 27,600/μl

Comprehensive metabolic panel (CMP): Na 121; K 2.8; Cl 83; AST 113; ALT 45

Wound culture: Positive for MRSA, Streptococcus pyogenes, Enterobacter cloacae, and Staphyloccocus epidermis

This patient’s presentation is consistent with periorbital necrotizing fasciitis complicated by severe sepsis.

This patient had type 1 necrotizing fasciitis given the polymicrobial source of infection with both aerobic and anaerobic organisms growing from his wound culture. Type 2 necrotizing fasciitis is attributable to streptococcal and/or staphylococcal infection alone. Group A strep is the most common organism responsible for necrotizing fasciitis, found in about 50% of cases.

Independent risk factors for necrotizing fasciitis include advanced age, diabetes mellitus, heart disease, liver cirrhosis, alcohol use disorder, and trauma. Furthermore, persons who experience homelessness are at risk of skin lesions due to insect bites, burns, and physical trauma which predispose them to secondary bacterial infections because of inadequate hygiene resources.

A systematic review of periorbital necrotizing fasciitis showed that 35% of cases were triggered by trauma, while 14% were caused by other infections such as acute dacryocystitis, sinus infections, and infections of the parotid glands.  Thus, it is likely that the patient’s contact with his partner who had a necrotic soft tissue infection secondary to insect bites, as well as his recent trauma to the eye, predisposed his development of this condition.

Initiation of broad-spectrum intravenous (IV) antibiotics with vancomycin, piperacillin/tazobactam, and clindamycin, as well as IV fluids.

In this case, the patient received the above antibiotics, underwent operative debridement, frequent wound care including dilute hypochlorous acid, local vancomycin administered via intra-orbital catheter, as well as lid reconstruction with glabellar flap. He was ultimately discharged on a two-week course of oral moxifloxacin and linezolid, healing well at his one-month follow-up appointment.

 

Take-Home Points

  • Skin problems are a common reason that persons experiencing homelessness seek medical care, given their risk factors for both primary insults and subsequent superinfection.
  • Common sources of infection for periorbital necrotizing fasciitis include trauma, surgery, and other infections of the upper face.
  • The standard of care for periorbital necrotizing fasciitis consists of IV and local antibiotics, and operative debridement.

  • Amrith S, Hosdurga Pai V, Ling WW. Periorbital necrotizing fasciitis — a review. Acta Ophthalmol. 2013 Nov;91(7):596-603. doi: 10.1111/j.1755-3768.2012.02420.x. Epub 2012 Apr 20. PMID: 22520175.

 

Oral Antivirals for Treatment of Mild-Moderate COVID-19 Infection

Background

Two new oral agents were given Emergency Use Authorization to be used in patients with mild-moderate COVID-19 at high risk of progression to severe infection, molnupiravir and nirmatrelvir/ritonavir (Paxlovid) [1,2]. Prior to this authorization, most evidence-based COVID therapies were parenteral and required significant healthcare resources to coordinate and administer.

Comparison

Nirmatrelvir/ritonavir [3]Molnupiravir [4]
Mechanism

Protease inhibitor leadings to interruption of viral replication

Ritonavir has no role in treating COVID-19, it is only included to boost levels of nirmatrelvir via CYP3A4 inhibition

Increased frequency of RNA mutations and impaired replication [5]
Efficacy vs Placebo (Hospitalization or Death)0.8% vs 6.3% (CI -7.21 to -4.03)6.8% vs 9.7% (CI -5.9 to -0.1)
Drug InteractionsCYP3A4 inducers, inhibitors, and substrates

May decrease efficacy of hormonal contraceptives, non-hormonal contraceptives should be considered

Contraindicated medications include: amiodarone, carbamazepine, clozapine, colchicine, dihydroergotamine, dronedarone, flecainide, lovastatin, ranolazine, sildenafil, simvastatin

Many other important interactions exist so care should be taken to assess all medication interactions

N/A
Cost*Patient: $0

US government: $530 [6]

Patient: $0

US Government: $700 [7]

Dose300 mg/100 mg BID for 5 days

Must be started within 5 days of symptom onset

800 mg BID for 5 days

Must be started within 5 days of symptom onset

NotesApproved for patients ≥ 12 years old AND ≥ 40 kg

Not approved for inpatient initiation

If patient is hospitalized, continuation is up to the discretion of the provider

Not used as pre-/post-exposure prophylaxis

Approved for patients ≥ 18 years

Not approved for inpatient initiation

If patient is hospitalized, continuation is up to the discretion of the provider

Not used as pre-/post-exposure prophylaxis

Renal/Hepatic Dose AdjustmentseGFR  ≥30 to <60 mL/min: 150 mg/100 mg BID

eGFR <30 mL/min: Not recommended

Child-Pugh class C: Not recommended

None

*Note: The US federal government has purchased 10 million doses of nirmatrelvir/ritonavir and 3 million doses of molnupiravir [8,9]. These supplies will be allocated to states and territories as needed and will be available to patients at no charge. 

Evidence:

Nirmatrelvir/ritonavir (Paxlovid)

Paxlovid was evaluated in the EPIC-HR trial, which is not fully published at this time [3]. This was a phase 2/3, double-blinded, randomized placebo controlled trial including nonhospitalized, unvaccinated patients adults with mild-moderate COVID-19 within 5 days of symptom onset with at least 1 risk factor for development of severe illness from COVID-19. Exclusion criteria included patients with a history of COVID-19 infection or COVID vaccination. Patients were given Paxlovid 300 mg/100 mg or placebo BID for 5 days. The primary outcome was hospitalization or death at day 28. The modified intention-to-treat1 (mITT1) group excluded patients who did not receive nor were expected to receive COVID-19 mAb treatment. In the mITT1 group, the primary outcome occurred in 0.8% of patients receiving Paxlovid vs 6.3% of patients in the placebo group (8/1039 vs 66/1046, CI -7.21 to -4.03).

These results appear quite robust with a fragility index of 37. Additionally, in patients with detectable COVID antibodies there was less of an impact of the study medication. However, these patients still appeared to have some benefit (0.2% vs 1.5%, CI -2.45 to -0.23) which suggests that vaccinated patients may still benefit from Paxlovid.

Risk factors for progression to severe disease: BMI >25, chronic lung disease, asthma, chronic kidney disease, current smoker, immunosuppressive disease or immunosuppressive treatment, cardiovascular disease, hypertension, sickle cell disease, neurodevelopmental disorders, active cancer, medically-related technological dependence, or age >60 years

Molnupiravir 

Molnupiravir was evaluated in the MOVe-OUT trial [10]. This was a phase 3, double-blinded, randomized, placebo controlled trial including nonhospitalized, unvaccinated adults with mild-moderate COVID-19 within 5 days of symptom onset with at least 1 risk factor for development of severe illness from COVID-19. Exclusion criteria included anticipated hospitalization within 48 hours, eGFR <30 or dialysis dependent, pregnancy, and COVID vaccination. Patients were able to receive steroids but not monoclonal antibodies (mAbs) nor remdesivir. Patients were given molnupiravir 800 mg or placebo BID for 5 days. The primary outcome was hospitalization or death at 29 days. In the mITT population, the primary outcome occurred in 6.8% of patients in the study group vs 9.7% in the placebo group (48/709 vs 68/699, CI -5.9 to -0.1). Death occurred in 1 patient on molnupiravir and in 9 patients on placebo (0.1% vs 1.3%, RRR 89%, CI 14 to 99).

Despite the above results, this may not be the positive trial it initially appears. First of all, for the primary outcome, the fragility index is 0, meaning that if 1 more patient in the study group experienced the primary outcome then it would have changed the statistical significance. Additionally, when the mITT analysis was adjusted for sex, the absolute risk reduction remained 2.8% but the confidence interval was not significant (-5.7 to 0.1). Lastly, in the subgroup analysis, there was no benefit in patients that had positive COVID antibody tests and there was a slight preference towards placebo over molnupiravir (3.7% vs 1.4%, ARR 2.3, CI -1.7 to 7.1). This suggests that vaccinated patients may not benefit from this therapy as much (or at all) as compared to unvaccinated patients.

Risk factors for progression to severe disease: age >60 years, active cancer, chronic kidney disease, COPD, BMI ≥30, heart failure, coronary artery disease, cardiomyopathy, or diabetes mellitus

Note: Both the EPIC-HR and MOVe-OUT studies were funded by their respective pharmaceutical company.

Bottom Line:

  • Nirmatrelvir/ritonavir (Paxlovid) and molnupiravir are approved under FDA EUAs for patients with mild-moderate COVID infection at high risk of severe disease within 5 days of symptom onset
  • Both medications appear to reduce death or hospitalization within a month, with most benefit likely to be experienced by unvaccinated patients
  • Nirmatrelvir/ritonavir (Paxlovid) appears to be more effective but also has many more drug interactions and contraindications

Want to learn more about EM Pharmacology?

Read other articles in the EM Pharm Pearls Series and find previous pearls on the PharmERToxguy site.

References:

  1. O’Shaughenessy J. Food and Drug Administration. Molnupiravir Emergency Use Authorization 108. December 23, 2021. https://www.fda.gov/media/155053/download
  2. O’Shaughenessy J. Food and Drug Administration. Nirmatrelvir/ritonavir Emergency Use Authorization 105. December 22, 2021. https://www.fda.gov/media/155049/download
  3. Nirmatrelvir/ritonavir. Package insert. Pfizer, Inc. 2021. https://www.fda.gov/media/155050/download
  4. Molnupiravir. Package insert. Merck Sharp & Dohme Corp. 2021. https://www.merck.com/eua/molnupiravir-hcp-fact-sheet.pdf
  5. Kabinger F, Stiller C, Schmitzová J, et al. Mechanism of molnupiravir-induced SARS-CoV-2 mutagenesis. Nat Struct Mol Biol. 2021;28(9):740-746. doi: 10.1038/s41594-021-00651-0. PMID: 34381216.
  6. Mishra M. U.S. to buy 10 mln courses of Pfizer’s COVID-19 pill for $5.3 bln. Reuters. Accessed January 12, 2022. https://www.reuters.com/business/healthcare-pharmaceuticals/us-govt-buy-10-mln-courses-pfizers-covid-19-pill-529-bln-2021-11-18/
  7. Willyard C. How antiviral pill molnupiravir shot ahead in the COVID drug hunt. Nature. Published online October 8, 2021. doi: 10.1038/d41586-021-02783-1. PMID: 34625735.
  8. Paxlovid (nirmatrelvir/PF-07321332 and ritonavir). U.S. Department of Health & Human Services: Office of the Assistant Secretary of Preparedness and Response. Updated: January 12, 2022. Accessed January 12, 2022. https://www.phe.gov/emergency/events/COVID19/investigation-MCM/Paxlovid/Pages/default.aspx
  9. Molnupiravir (MK-4482). U.S. Department of Health & Human Services: Office of the Assistant Secretary of Preparedness and Response. Updated: January 12, 2022. Accessed January 12, 2022. https://www.phe.gov/emergency/events/COVID19/investigation-MCM/molnupiravir/Pages/default.aspx
  10. Jayk Bernal A, Gomes da Silva MM, Musungaie DB, et al. Molnupiravir for oral treatment of covid-19 in nonhospitalized patients. N Engl J Med. Published online December 16, 2021. doi: 10.1056/NEJMoa2116044. PMID: 34914868.

Dose Order Matter? Which Antibiotic to Give First for a Bloodstream Infection

Background

Early antibiotics are recommended for treatment of many infections, including patients with sepsis or septic shock [1]. Critically-ill patients and those with a suspected infection at risk for severe illness are generally administered two (or more) empiric antibiotics in the emergency department (ED) which cover a wide range of potential pathogens. A typical approach includes utilizing a broad-spectrum antibiotic (frequently a beta-lactam such as cefepime or piperacillin-tazobactam) plus an anti-MRSA agent (typically vancomycin).

Early in the patient’s hospital stay they may have limited IV access, so the question often arises as to which antibiotic to give first, the broad-spectrum antimicrobial or the anti-MRSA agent. Additionally, though the overall risk of an allergic reaction is relatively low with most antimicrobials, when multiple agents are given simultaneously it can be difficult to ascertain which one may have caused a reaction and lead to incorrectly documented allergies, so it can be important to consider if the initial doses should be administered separately. However, there isn’t strong data to guide practice in terms of giving the initial antibiotics concurrently vs consecutively, from an allergy perspective. To further complicate the issue, patients may also develop delayed reactions so a strong causal relationship cannot always be determined. In practice, there are times (increasingly so with rising ED patient volumes) when we give antibiotics one at a time simply for logistical reasons. So that begs the question, which antibiotic should be given first?

Evidence

In patients with sepsis or septic shock, early antibiotics significantly decrease mortality [1]. This relationship is strongest for patients with septic shock, where the odds of in-hospital mortality was increased by 1.04-1.16 for each hour antibiotics were delayed [2-4]. Notably, broad spectrum antibiotics are deemed such as they cover both gram positive and gram negative pathogens, therefore the addition of an anti-MRSA agent contributes a relatively smaller amount of coverage and is primarily targeted at resistant gram-positive bacteria. Additionally, gram-negative pathogens tend to cause a higher degree of illness and mortality, so it would be reasonable to give the broad-spectrum antibiotic first [5-7]. As both cefepime and piperacillin-tazobactam are recommended to be infused over 30 minutes (though this can vary based on institutional policies) and vancomycin is typically infused over 1 hour for each gram, if vancomycin is administered first, patients may wait hours to receive a broad spectrum agent.

A recent study now supports this practice. This is an observational trial which evaluated 3,376 patients with a blood stream infection, 2,685 patients received a beta-lactam first and 691 patients received vancomycin first [8]. They found that patients who received a beta-lactam prior to vancomycin had significantly improved 48-hour and 7-day mortality. Further review of this article may be found on the JournalFeed blog post.

Bonus tip: Having antibiotics stocked on the unit reduces time to administration [9].

Bottom Line

  • Antibiotic delays lead to increased mortality, especially in patients with septic shock.
  • For patients with a suspected bloodstream infection, administering the broad-spectrum antibiotic first, instead of the anti-MRSA agent, has the potential to reduce mortality at 48 hours and 7 days. This should be the general approach for treatment of all infections when two or more antimicrobial agents are indicated.

Want to learn more about EM Pharmacology?

Read other articles in the EM Pharm Pearls Series and find previous pearls on the PharmERToxguy site.

References

  1. Evans L, Rhodes A, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Crit Care Med. 2021;49(11):e1063-e1143. PMID: 34605781. doi: 10.1097/CCM.0000000000005337.
  2. Seymour CW, Gesten F, Prescott HC, et al. Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med. 2017;376(23):2235-2244. PMID: 28528569. doi: 10.1056/NEJMoa1703058.
  3. Liu VX, Fielding-Singh V, Greene JD, et al. The timing of early antibiotics and hospital mortality in sepsis. Am J Respir Crit Care Med. 2017;196(7):856-863. PMID: 28345952. doi: 10.1164/rccm.201609-1848OC.
  4. Peltan ID, Brown SM, Bledsoe JR, et al. Ed door-to-antibiotic time and long-term mortality in sepsis. Chest. 2019;155(5):938-946. PMID: 30779916. doi: 10.1016/j.chest.2019.02.008.
  5. Abe R, Oda S, Sadahiro T, et al. Gram-negative bacteremia induces greater magnitude of inflammatory response than Gram-positive bacteremia. Crit Care. 2010;14(2):R27. PMID: 20202204. doi: 10.1186/cc8898.
  6. Alexandraki I, Palacio C. Gram-negative versus Gram-positive bacteremia: what is more alarmin(G)? Crit Care. 2010;14(3):161. PMID: 20550728. doi: 10.1186/cc9013
  7. Morgan MP, Szakmany T, Power SG, et al. Sepsis patients with first and second-hit infections show different outcomes depending on the causative organism. Front Microbiol. 2016;7:207. PMID: 26955367. doi: 10.3389/fmicb.2016.00207.
  8. Amoah J, Klein EY, Chiotos K, Cosgrove SE, Tamma PD, CDC Prevention Epicenters Program. Administration of a β-lactam prior to vancomycin as the first dose of antibiotic therapy improves survival in patients with bloodstream infections. Clin Infect Dis. Published online October 4, 2021:ciab865. PMID: 34606585. doi: 10.1093/cid/ciab865.
  9. Lo A, Zhu JN, Richman M, Joo J, Chan P. Effect of adding piperacillin-tazobactam to automated dispensing cabinets on promptness of first-dose antibiotics in hospitalized patients. Am J Health Syst Pharm. 2014;71(19):1663-1667. PMID: 25225451. doi: 10.2146/ajhp130694.

SAEM Clinical Image Series: Pediatric Rash

pediatric rash

A previously healthy 8-year-old female presents to the pediatric emergency department due to a rash. Her symptoms started three days prior to presentation with a painful rash on her lower extremities. The rash subsequently spread to the buttocks and upper extremities, and she developed intermittent diffuse abdominal pain, a nonproductive cough, and pharyngitis. The patient denies subjective fever. Known sick contacts include the patient’s mother, who tested positive for COVID-19 two and a half weeks prior.

 

Vitals: T 98.5°F; HR 93; BP 115/68; RR 16; O2 sat 100% on room air

Constitutional: Well-developed and in no acute distress

HEENT: Normocephalic, atraumatic; moist mucus membranes; no conjunctival injection; posterior pharyngeal erythema without exudates; tonsils are three bilaterally; lips are not cracked; no “strawberry tongue”;

Neck: Normal range of motion; no lymphadenopathy

Cardiovascular: Regular rate and rhythm; normal heart sounds and pulses

Pulmonary: Effort is normal; normal breath sounds; no wheezing

Abdominal: Abdomen is flat; minimal tenderness to palpation without guarding; no organomegaly

Skin: Diffuse petechial rash and painful, palpable, nonblanching purpura in the dependent regions (most notable on the buttocks and lower extremities)

COVID-19: Detected

Complete blood count (CBC): WBC 10K, hemoglobin 13, platelets 469

Comprehensive metabolic panel (CMP): Na 138, K 4.1, Cl 103, CO2 26, BUN 7, Cr 0.38, Glucose 94, ALT 23, AST 26, Albumin 4.5

Lipase: 10

Urinalysis (UA): Normal

C-reactive protein (CRP): 3.4

Erythrocyte sedimentation rate (ESR): 24

Procalcitonin: 0.03

Fibrinogen: 363

BNP: <10

Troponin: 0.00

Ferritin: 83

Triglycerides: 37

 

  • COVID-19-Associated Multisystem Inflammatory Syndrome in Children (MIS-C): According to CDC criteria, patients must be under 21 years of age, with a fever higher than 38°C/subjective fever for longer than 24 hours, laboratory evidence of inflammation, severe illness requiring hospitalization, and two or more organ systems involved (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic, or neurologic), with no alternative plausible diagnoses and recent COVID-19 infection.
  • Immunoglobulin A Vasculitis (Henoch-Schönlein Purpura): According to the EULAR/PRINTO/PRES criteria, symptoms must include cutaneous findings (palpable purpura or petechiae without the presence of thrombocytopenia), plus at least one of the following: diffuse abdominal pain with acute onset, arthritis/arthralgia, renal involvement in the form of proteinuria or hematuria, or deposition of Immunoglobulin A seen on renal histology.
  • Kawasaki Disease: The diagnostic criteria include fever for five days or longer and four of the following: bilateral conjunctival injection, cervical lymphadenopathy, polymorphous rash, oral mucous membrane changes (including fissured lips, pharyngeal erythema or strawberry tongue), peripheral extremity changes (edema of the hands/feet or desquamation).

Immunoglobulin A (IgA) Vasculitis.

This patient presented with palpable purpura and petechiae without the presence of thrombocytopenia, as well as diffuse abdominal pain. The majority of cases of IgA Vasculitis are preceded by a respiratory pathogen, with the most common being streptococcus, staphylococcus, and parainfluenza virus. Although not well-documented due to its recent conception, COVID-19 is likely to be the cause of this patient’s vasculitis. Usual management of IgA Vasculitis is supportive care, with admission and specialty referral for complications including intussusception and glomerular involvement. Given the severity of the differential diagnoses, this patient was admitted to the hospital for observation and discharged the following day with close follow-up

Take-Home Points

  • COVID-19 can cause a variety of rashes in the pediatric population, and appropriate workup including inflammatory markers, complete blood count, and comprehensive metabolic panel must be initiated to rule out severe disease. Consider obtaining a troponin, EKG, chest x-ray, echocardiogram, ferritin, prothrombin time, partial thromboplastin time, international normalized ratio, fibrinogen, urinalysis and cultures to assess for end-organ damage. If positive, and the patient appears ill, consider Multisystem Inflammatory Syndrome in Children (MIS-C).
  • IgA Vasculitis is usually caused by a respiratory pathogen. Keep it on your differential when assessing children who test positive for Covid-19.
  • Complications of IgA vasculitis include intussusception, heme-positive stool, microscopic hematuria, and periarticular disease.

  • Centers for Disease Control and Prevention, Health Alert Network. (2020). Case Definition for Multisystem Inflammatory Syndrome in Children (MIS-C). [online] Available at: https://emergency.cdc.gov/han/2020/han00432.asp.
  • Trnka P. Henoch-Schönlein purpura in children. J Paediatr Child Health. 2013 Dec;49(12):995-1003. doi: 10.1111/jpc.12403. Epub 2013 Oct 18. PMID: 24134307.
  • Ozen S, Pistorio A, Iusan SM, Bakkaloglu A, Herlin T, Brik R, Buoncompagni A, Lazar C, Bilge I, Uziel Y, Rigante D, Cantarini L, Hilario MO, Silva CA, Alegria M, Norambuena X, Belot A, Berkun Y, Estrella AI, Olivieri AN, Alpigiani MG, Rumba I, Sztajnbok F, Tambic-Bukovac L, Breda L, Al-Mayouf S, Mihaylova D, Chasnyk V, Sengler C, Klein-Gitelman M, Djeddi D, Nuno L, Pruunsild C, Brunner J, Kondi A, Pagava K, Pederzoli S, Martini A, Ruperto N; Paediatric Rheumatology International Trials Organisation (PRINTO). EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria. Ann Rheum Dis. 2010 May;69(5):798-806. doi: 10.1136/ard.2009.116657. PMID: 20413568.
  • Royle J, Burgner D, Curtis N. The diagnosis and management of Kawasaki disease. J Paediatr Child Health. 2005 Mar;41(3):87-93. doi: 10.1111/j.1440-1754.2005.00555.x. PMID: 15790316.

 

SAEM Clinical Image Series: A Rapidly Spreading Rash

spreading rash

A 40-year-old male with a past medical history of HIV presented for evaluation of a non-pruritic rash. Six days ago, he suddenly felt a stinging sensation at the back of his head and neck similar to a bug bite. He then noticed bumps were starting to form and developed a shock-like pain in the area. Three days ago, the rash spread from the back of his head towards his chest. Yesterday, the rash spread further and now extends medially and upwards covering most of his left neck and ear. The pain continued to worsen, at which point the patient shaved the left side of his head in an attempt to help the rash. Today, the pain became unbearable, which prompted his visit to the emergency department for further evaluation and management.

Head: Normocephalic, atraumatic; left side of patient’s head is shaved.

Eye: Pupils equal, round, reactive to light; extraocular movements intact; no corneal ulcers or dendritic lesions with fluorescein staining.

Visual acuities: Right 20/25, left 20/25, baseline 20/25

Ear, nose, throat: Mucous membranes are dry; oral thrush and tonsillar erythema appreciated; localized erythema, crusting and blistering rash of varying sizes and ages along with the outer ear including the tragus, antihelix, and antitragus; helix mildly swollen. On otoscopy, the tympanic membranes appear pearly grey, shiny, translucent with no bulging, and without cerumen impaction.

Neck: Full range of motion appreciated but both horizontal and vertical movement is slow secondary to pain; no lymphadenopathy.

Neurological: Awake, alert, and oriented to date, place, and person; moves all extremities; cranial nerves II through XII grossly intact; strength 5/5 in all extremities; gait steady; no ataxia, dysmetria, or dysarthria.

Skin: Erythematous, localized, crusted, blistering vesicular rash of various sizes and ages appreciated along the left V3 distribution, C3 to T3 dermatomes anteriorly, and C2 to C6 dermatomes posteriorly.

HIV-1 antibody: positive

CD4 helper t-cells: 48 (L)

HIV-1 RNA PCR: 36,490

The lesions can be characterized as vesicles in various stages of healing. Some lesions are crusted, others are bullous, and a few are pustular. The C2-C6 dermatomes are affected posteriorly, and the C2-T3 dermatomes are involved anteriorly.

The diagnosis is Disseminated Herpes Zoster. The rash in reactivation varicella zoster virus (VZV) is preceded by tingling, itching, or pain, and begins as maculopapular then progresses to vesicles, pustules, and bullae. The rash typically involves a single dermatome and does not cross the midline. Rash present in multiple dermatomes (>3) or a rash that crosses the midline signifies disseminated disease. Hutchinson’s sign is a lesion on the lateral dorsum and tip of the nose indicating the involvement of the nasociliary branch of the ophthalmic division of the trigeminal nerve. The nasociliary branch innervates the eye, thus these lesions are highly suspicious for herpes zoster ophthalmicus. Herpes zoster ophthalmicus on fluorescein examination appears as pseuododendritic lesions with no terminal bulbs (not to be confused with herpes simplex virus (HSV) keratitis, which has dendritic lesions with terminal bulbs). Vesicles in the auditory canal (herpes zoster oticus) may be a part of Ramsay Hunt syndrome with ear pain and paralysis of the facial nerve.

The patient is immunocompromised and requires hospitalization for intravenous (IV) antiviral therapy and pain management. VZV primary infection results in viremia, diffuse rash, and seeding of sensory ganglia where the virus establishes latency. Herpes zoster is the result of viral reactivation with spread along the sensory nerve in that dermatome. Antiviral therapy aids in the resolution of lesions, reduces the formation of new lesions, reduces viral shedding, and decreases the severity of acute pain, but does not affect the development of post-herpetic neuralgia.

Immunocompetent patients may receive Valacyclovir 1 g PO q8hrs (preferred) or Acyclovir 800 mg PO 5x/day x 7d if the onset of rash is <3 days or >3 days with the appearance of new lesions.

Immunocompromised, transplant, and cancer patients are all at high risk for dissemination, chronic skin lesions, acyclovir-resistant VZV, and multi-organ involvement. Immunocompromised patients and patients with disseminated zoster require aggressive multimodal treatment, admission to the hospital, and IV antiviral therapy regardless of the time of onset of rash. Recommended therapy is Acyclovir 10 mg/kg IV q8h or Foscarnet 40 mg/kg IV q8h for acyclovir-resistant VZV. All patients require adequate analgesia, typically with non-steroidal anti-inflammatory drugs, opioids, Gabapentin, Nortriptyline, and Lidocaine patches on intact skin.

Take-Home Points

  • Disseminated herpes zoster is defined as reactivation of VZV in three or more dermatomes. It requires admission, IV antiviral therapy, and pain control.
  • If VZV reactivation involves the face, one must evaluate for herpes zoster ophthalmicus and oticus.
  • Perform a thorough neuro exam including evaluation of cranial nerves V, VII, and VIII.
  • VZV requires airborne precautions.
  1. Cohen JI. Clinical practice: Herpes zoster. N Engl J Med. 2013 Jul 18;369(3):255-63. doi: 10.1056/NEJMcp1302674. PMID: 23863052; PMCID: PMC4789101.

 

 

 

One-Time Vancomycin Doses in the Emergency Department

Background

A previous ALiEM post from 2013 by an EM pharmacist colleague argued the case against one-time vancomycin doses in the ED prior to discharge. The take-home points from this post were:

    1. No evidence that a one-time vancomycin has any benefit
    2. This practice is not recommended by the Infectious Diseases Society of America (IDSA)
    3. May extend the patient’s ED stay by at least an hour for the IV infusion, depending on the dose
    4. Increases the cost of the ED visit (e.g., IV line, medication, RN time)
    5. Pharmacokinetically 1 dose of vancomycin doesn’t make sense
      • Vancomycin 1 gm IV x1 provides sub-therapeutic levels for patients with normal renal function
      • Efficacy is based on overall exposure (e.g., AUC/MIC) achieved with repeated dosing over several days
    6. Subtherapeutic vancomycin concentrations lead to development of resistance

Despite the above points, a one-time dose of vancomycin prior to the patient being discharged on an oral regimen is a common practice [1].

Evidence

As stated above, a single dose of vancomycin is unlikely to provide a therapeutic benefit and may only serve to reassure clinicians. The 2020 consensus guidelines regarding vancomycin monitoring for serious MRSA infections reinforce the recommendation of achieving an AUC0-24/MIC ratio of ≥400, as a ratio <400 increases resistance and has inferior efficacy [2]. Since the AUC is dependent on overall time of exposure plus concentration, a single dose for an average patient with normal renal function is not adequate (Figure 1). The graph below also demonstrates how long it generally takes for vancomycin to reach steady state when patients receive a dose every 8 hours.

 

*The estimated AUC above assumes a 30 yo male that weights 70kg and is 6′ tall with a serum creatinine of 1.0 mg/dL.

A randomized trial conducted at Christiane Care Health System compared patients who received a vancomycin loading dose of 30 mg/kg or 15 mg/kg [3]. Just twelve hours after this initial dose, 34.6% of patients who received 30 mg/kg had vancomycin levels in the therapeutic range (trough >15 mg/L) vs. 3% of patients who received 15 mg/kg (p < 0.01).

Bottom Line

Even large vancomycin loading doses rarely achieve therapeutic levels after one dose. Therefore, if the plan is to discharge, skip the one-time dose altogether and choose an antimicrobial regimen that will be continued in the outpatient setting (e.g., doxycycline or sulfamethoxazole/trimethoprim if concerned for MRSA or cephalexin for most other patients).

Want to learn more about EM Pharmacology?

Read other articles in the EM Pharm Pearls Series and find previous pearls on the PharmERToxguy site.

References

  1. Mueller K, McCammon C, Skrupky L, Fuller BM. Vancomycin use in patients discharged from the emergency department: a retrospective observational cohort study. J Emerg Med. 2015;49(1):50-57. doi: 10.1016/j.jemermed.2015.01.001. PMID: 25802166.
  2. Rybak MJ, Le J, Lodise TP, et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant staphylococcus aureus infections: a revised consensus guideline and review by the american society of health-system pharmacists, the infectious diseases society of america, the pediatric infectious diseases society, and the society of infectious diseases pharmacists. Am J Health Syst Pharm. 2020;77(11):835-864. doi: 10.1093/ajhp/zxaa036. PMID: 32191793.
  3. Rosini JM, Laughner J, Levine BJ, Papas MA, Reinhardt JF, Jasani NB. A randomized trial of loading vancomycin in the emergency department. Ann Pharmacother. 2015;49(1):6-13. doi: 10.1177/1060028014556813. PMID: 25358330.
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