Description

Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

I'm Pradip Kamat and I'm Rahul Damania and we are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

Welcome to our Episode of a 16 year old with fever and a rash.

Here's the case:

A 16 year old F presents to the PICU with generalized weakness, fever and a diffuse rash**.** Three days prior to admission she stated that she was feeling lightheaded and the day after she started having frequent non-bloody diarrhea. She states that she has otherwise been healthy, no sick contacts or travel, and the only change in her life was her menstrual cycle which ended a few days before her symptoms started. She says that about two weeks ago, she went to her primary care physician to get an in-grown toe nail drained, but was able to recover after some analgesia and antibiotics for a week. On day of admission her mother brings her into the ED as she says her rash continues to progress. Her mother states that the rash looks like a sunburn. Mother noticed on day of admission that her daughter now had red injected eyes bilaterally without discharge, and was becoming increasingly confused with her fevers. Of note, the patient has also has had decreased oral intake as she says her mouth quote hurts when she swallows. She has had no sore throat, congestion, dysuria, or headache. She presents to the ED febrile to 39 C and tachycardic to 130 bpm. She is ill appearing and has orthostatic vital signs. Her exam is notable for palpable diffuse myalgia, oropharyngeal hyperemia, diffuse erythroderma, and conjunctival injection. She is noted to have a hyperdynamic precordium and faint crackles bilaterally. Her L toe is mildly erythematous with no discharge, necrosis or pain to palpation. Acute resuscitation and diagnostics are begun and patient is transferred to the pediatric intensive care unit.

To summarize key elements from this case, this patient has:

• Hx of a fever and multisystem involvement including GI manifestations, myalgias, confusion, mucositis, and rash
• This is in the setting of a local drainage procedure and course of antibiotics.
• In addition, she presents now with fever, hypotension, and tachycardia.
• These elements so far bring up a broad differential but for now we can agree that it seems that she has signs of acute inflammation or infection throughout her body.

nsition into some history and physical exam components of this case.

1. If we take a step back, what are key history features in a child who presents with fever & rash?

• Understanding the characteristics of the rash, the evolution, and progression of the rash is important.
• In the setting of myalgias, fever, headache, and rash you should think of assessing for any recent travel as tick-borne illnesses commonly present with this symptomatology.
• You also want to assess for recent antibiotic exposures, sexual history, and surgical history - in our case, our patient had a recent procedure on her toe

1. Are there some red-flag symptoms or physical exam components which you could highlight?

• Absolutely, when a child presents with fever and a rash, it is important to stratify two major elements:

1. You want to assess the degree of toxicity in relation to the symptomatology:
2. Lethargy, irritatbility, altered sensorium, poor perfusion, pallor or cyanosis may indicate serious illness.
3. Understanding the duration of fever in the setting of suspected total body inflammation is important, however the importance of the heigh of fever in predicting the risk of serious illness is unclear.
4. We will visit a differential a bit later in this podcast, however I do want to highlight that the presence of tachycardia and tachypnea in any patient with fever and rash suggests the possibility of sepsis.
5. When you notice these red-flag symptoms it is important to focus on resuscitation and treatment rather than pursuing diagnostics.

• To continue with our case, our patients labs were consistent with:
• An AKI - with her creatinine being three times the upper limit of normal.
• A transaminitis and indirect hyperbilirubinemia.
• Thrombocytopenia
• Pyuria on UA with negative LE or nitrites.
• And finally, an elevated CPK at 2000 units/L.
• Looking ahead in this case, our patient had negative serologies for RMSF, leptospirosis, measles.

Ok, to summarize, we have:

• 16 yo F who presents with fever, diffuse erythroderma, signs of systemic inflammation, and multi-organ dysfunction all of which bring up concern for Toxic Shock Syndrome, the topic of our discussion today.
• Let's start with a short multiple choice question:
• A patient presents with fever and rash and concern for Staphylococcal Toxic Shock Syndrome. Which of the following describes the mechanism of pathogenesis behind this diagnosis?
• A. Increased TLR-4 binding with LPS.
• B. Endotoxin production.
• C. Increased MHC II binding with T-cell receptor.
• D. Cytokine release of TGF-beta and IL-10.
• The answer is C. Increased MHC II binding with T-cell receptor. Staphylococcal Toxic Shock Syndrome characteristically has a TSST-1 exotoxin which is present in all of menstrual cases toxic shock syndrome and about half the non-menstrual cases of toxic shock syndrome. The interaction and stabilization between the antigen presenting cells and T-cell receptors cause a massive cytokine storm and thus this superAg can be one of the major virulence factors behind the multi-system involvement we see in toxic-shock-syndrome. Interestingly, one of the cytokines which is released in this syndrome is TNF and this inhibits neutrophil function. Data suggests that TSST-1 in addition to TNF do not engender Staph to have a purulent response and this may be due to lack of PMN recruitment.
• As you think about our case, what would be your differential?
• This is an interesting differential however given her symptomatology and disease progression I would focus my differential to infectious entities first. These include but are not limited to:
• Disseminated Meningococcemia ( type of rash, lack of meningismus)
• Rocky Mountain Spotted Fever (type of rash, exposure/travel history)
• Leptospirosis (type of rash/ exposure to rodents feces and urine)
• Dengue fever (bleeding besides arthralgias and rash)
• Typhoid fever
• Now Staph Scalded skin syndrome may have similar nomenclature and pathogenesis as TSS however they are slightly different. A review article published in Clinical Infectious Diseases in 2006, highlighted key differences between SSS and TSS. These included:
• Age — as patients with TSS are older with a median age of 12...