Infectious Disease

Tales from LBJ Tropical Medical Center: A Viral Febrile Illness

Presentation and History

A previously healthy 11-year-old female presents to the emergency department with three days of oral mucosal bleeding. One week prior to presentation, the patient developed a fever associated with generalized body aches, headache, anorexia, and malaise. The fever lasted for three days and then resolved. Since then has had daily bleeding from her gums as well as one episode of epistaxis. She reports continued fatigue. She denies abdominal pain, nausea, vomiting, or diarrhea. She denies hematuria, bloody or dark stools. There is no family history of bleeding disorders or blood dyscrasias.  There is no history of trauma.

Initial Workup

Image 1: Diffuse, oozing venous hemorrhage of the gingival mucosa

Image 1: Diffuse, oozing venous hemorrhage of the gingival mucosa

On arrival, the patient is noted to be afebrile, with a heart rate of 77, respirations 20, blood pressure 117/69, and oxygen saturation of 99% on room air. On physical examination, the patient is alert and oriented to person, place and time.  She appears fatigued but non-toxic. She is noted to have diffuse, oozing venous hemorrhage of her gums. The posterior oropharynx is clear and there are no palatal petechiae. The neck is supple and non-tender without lymphadenopathy. The lungs are clear to auscultation bilaterally and respirations are even and unlabored. The cardiac exam is regular rate and rhythm with no murmur, rub or gallop. The abdomen is soft, non-tender and non-distended with normoactive bowel sounds and no organomegaly. The extremities are warm and well-perfused with no edema or cyanosis. A faint macular rash is noted on the arms and legs.  She has no focal neurological deficits.

A tourniquet test is performed at the bedside and is positive for >10 petechiae per square inch. A CBC demonstrates a white blood cell count of 7.0, hemoglobin of 14.1, and thrombocytopenia with a platelet count of 39. LFTs are notable for an elevation of AST of 107. The BMP and coagulation profile are within normal limits. A rapid Dengue test returns positive for NS1 antigen, Dengue IgM and Dengue IgG.


Image 2 Tourniquet Test.jpg
Image 2 Tourniquet Applied.jpg

Image 2: A tourniquet test is a marker of capillary fragility and is performed by inflating a blood pressure cuff midway between the patient’s systolic and diastolic blood pressures and leaving it inflated for 5 minutes. The cuff is released and after two minutes the number of petechiae below the antecubital fossa are counted. The test is considered positive if there are more than 10 petechiae present within a square inch on the patient’s arm. The WHO criteria considers a positive test as one of the diagnostic criteria for the presumptive diagnosis of Dengue. It is important to note that while this test may be clinically helpful in specific situations, systemic reviews have found the tourniquet test to be neither sensitive nor specific for Dengue virus infection.


ED Course and Disposition

The patient is diagnosed with dengue virus infection with warning signs and is started on IV hydration with normal saline at a rate of 5cc/kg/hr. Two peripheral IVs are placed, and the patient is cross-matched for 2u pRBCs in anticipation of further hemorrhage or clinical decline. She remains stable during the course of her ED stay. She is evaluated by pediatrics and admitted to the ICU for hemodynamic monitoring, IV fluids and serial blood counts.

Dengue Virus Infection

Dengue is a febrile illness caused by a viral infection transmitted to humans through mosquitos. The incidence of Dengue has grown dramatically around the world in recent decades with an estimated 390 million Dengue infections per year, and the disease is now endemic in more than 100 countries in tropical and subtropical regions. Dengue virus infection should be on the differential diagnosis for all patients who present with fever and a history of recent travel to an endemic area.

Clinical features and diagnosis

Dengue virus infection can be asymptomatic, or it can present with a broad range of clinical findings from a mild febrile illness to life-threatening dengue shock syndrome (DSS). Thus, the emergency provider must be aware of the diagnostic criteria and warning signs that distinguish the mild cases from those who are at risk of rapid and potentially fatal clinical deterioration. There are four distinct serotypes of the virus; thus patients who have been previously exposed to one serotype are still vulnerable to infection by another serotype. To complicate matters further, Dengue virus often coexists with several other mosquito-borne viruses including Zika and Chikungunya, which often have overlapping clinical features.

While serologic testing through viral PCR and antigen detection yields a more definitive diagnosis, physicians in endemic areas must often rely upon the history and physical exam findings when evaluating the febrile patient with possible Dengue.

The 2009 WHO criteria breaks down Dengue virus infection into Dengue without warning signs, Dengue with warning signs, and Dengue with severe features. According to this criteria, A presumptive diagnosis of Dengue can be made when a high fever (40C/140F) or history of fever is accompanied by two or more of the following signs or symptoms:

  • Headache, eye pain, myalgias, arthralgias
  • Nausea and vomiting
  • Rash
  • Leukopenia
  • Positive tourniquet test
Image 3: a close-up view of the patient’s antecubital fossa. There are clearly greater than 10 petichiae within a square inch on this patient’s arm, thus making a “positive” tourniquet test.

Image 3: a close-up view of the patient’s antecubital fossa. There are clearly greater than 10 petichiae within a square inch on this patient’s arm, thus making a “positive” tourniquet test.

“Warning signs” serve to highlight patients who are at high risk of clinical deterioration and include:

  • Abdominal pain or tenderness
  • Persistent vomiting
  • Clinical fluid accumulation (pleural effusions, ascites, edema)
  • Mucosal bleeding
  • Lethargy or restlessness
  • Hepatomegaly >2 cm
  • Increased hematocrit concurrent with a rapid decrease in platelet count

Severe dengue includes one or more of the following features:

  • Plasma leakage leading to shock or fluid accumulation with respiratory distress
  • Severe bleeding
  • Severe end-organ involvement (AST or ALT >1000 units/L, impaired consciousness, other organ failure)

Dengue virus infection presents in three distinct clinical phases: the febrile, critical and recovery or convalescent phase. The febrile phase lasts for three to seven days and is characterized by high-grade fever and the clinical features noted above. The critical phase occurs around the time of defervescence (days 3-7 of illness) and lasts for 24-48 hours. It is during this phase that a small proportion of patients will progress to develop a systemic capillary leak syndrome that can lead to hemorrhage, shock, end-organ failure and death. The convalescent or recovery phase lasts two to four days and is characterized by resolution of plasma leakage and hemorrhage, normalization of vitals and resorption of accumulated fluids. Patients may experience significant and debilitating fatigue that can last for weeks after their initial infection.

Management and disposition

Patients without warning signs or comorbidities (extremes of age, pregnancy, immunocompromise, poor social situation) can be discharged home with careful return precautions and close outpatient follow up. Dengue patients should not be prescribed NSAIDs for fever or pain given their risk of bleeding.

Patients with warning signs should be considered at risk for impending shock and admitted for hemodynamic monitoring and serial blood counts. Care must be given to not fluid overload these patients as they are at high risk of third-spacing. If they can tolerate PO fluids and are not significantly volume depleted, patients do not need IV hydration. If IV fluids are administered, isotonic crystalloid should be administered in a stepwise fashion starting at 5-7cc/kg/hr and gradually titrated down based upon clinical reassessment and serial hematocrits. If the hematocrit rapidly rises or the patient’s vital signs worsen, this signals worsening systemic capillary leak and the rate of IVF should be increased to 5-10 cc/kg/hr followed by serial monitoring of the hematocrit and vitals.

Patients with severe dengue should be admitted to an ICU setting for ongoing resuscitation. If a patient is in hypotensive shock, they should immediately be given a 20cc/kg bolus of isotonic crystalloid. The provider must then determine whether the shock is being driven primarily by systemic capillary leak, hemorrhage, or both. If hemodynamics fail to improve with isotonic crystalloid administration and the hematocrit is rising, this suggests systemic capillary leak and the patient should receive a 10-20/cc/kg bolus of colloid in order to increase the intravascular oncotic pressure to counteract this leak. If the hematocrit is falling, this suggest hemorrhage is driving the shock and the patient should be given 5-10cc/kg of packed RBCs or 10-20cc/kg of whole blood. In some cases, patients may require both blood and colloid administration, and even vasopressors if they develop refractory shock.

Currently, there is no effective vaccine for Dengue virus infection. Travelers to endemic areas should take appropriate precautions including wearing long sleeves, bug repellent, mosquito nets, and avoiding areas with large concentrations of mosquitos (standing water, swamps, etc.). 

Case Conclusion

The patient’s platelet count reached a nadir of 39,000 and then recovered. She developed mild peripheral edema that gradually reabsorbed without intervention. Her symptoms improved and she was discharged home on hospital day 5 without further complications. 

Faculty Reviewer: Alexis Kearney, MD

References

Jose Grande, A et al. “Tourniquet test for Dengue diagnosis: systematic review and meta-analysis of diagnostic test accuracy.” PLOS Neglected Tropical Diseases. Aug 3 2016. 

Simmons, C.P. et al. “Dengue.” N Engl J Med 2012; 366:1423-1432. 

Thomas, S. et al. “Dengue virus infection: clinical manifestations and diagnosis.” UpToDate. <http://www.uptodate.com/>

Thomas, S. et al. “Dengue virus infection: prevention and treatment.” UpToDate. <http://www.uptodate.com/>

“Dengue: guidelines for diagnosis, treatment, prevention and control.” World Health Organization and The Special Programme for Research and Training in Tropical Diseases.” 2009 <http://www.who.int/>

“Dengue case management for clinicians.” Centers for Disease Control and Prevention. <http://www.cdc.gov/>

Approach to the Pediatric Limp

Case:

A 4 year old otherwise healthy boy presents to the ED with left leg pain and limp with decreased ability to bear weight. The symptoms started yesterday after watching a movie, with moderate improvement after Motrin. Mom denies any trauma or fall. Notably, he has been afebrile, but has had a mild coryzal illness over the past 3-5 days.

On presentation to the ED, his vital signs are recorded as: T 36.9 C, pulse 120, BP 100/60, RR 22, SpO2 100%. He is alert, active, and non-toxic in appearance. He is lying on the bed, with his hip flexed, abducted, and in external rotation. There is no overlying erythema of the hip, knee, or ankle. The left hip has mild restriction in abduction in comparison the right hip. With the left leg fully extended, the patient exhibits no involuntary muscle guarding or obvious discomfort with log-rolling of the left lower extremity. He additionally has a nontender lumbar spine and ipsilateral knee, ankle, and tibia/fibula. The patient is able to bear weight, but has an antalgic gait without exhibiting toe walking or circumduction. Plain radiographs of the pelvis and left hip are obtained which reveal medial joint space widening in comparison to the right hip.

What is the most likely cause of his symptoms?

A.   Toddler’s fracture

B.   Septic arthritis

C.   Transient synovitis

D.   Osteomyelitis

E.   Limb length discrepancy

C: Transient synovitis

Background:

Limp accounts for approximately 4/1000 visits to the Emergency Department, with the location of the pain not always reflecting the location of pathology. Problems in the hip can cause knee pain, and similarly, back problems can refer pain to the lateral thigh or posterior leg.

Differential:

Minor trauma is the most common etiology for a limp, with the median age being 4 years, boys outnumbering girls 2:1, and localization typically to the hip. In those that deny history of trauma, the most common diagnosis is transient synovitis, with 77% having a benign cause without requiring surgical intervention or hospital admission.

PEM Playbook has a great mnemonic: STOP LIMPING

S: Septic arthritis (hip>knee)

T: Toddler’s fracture (1-3 years, minor fall with rotational component)

O: Osteomyelitis (2% of those children presenting with limp)

P: Perthes disease (Legg-Calve-Perthes disease, an idiopathic AVN, affecting children 3-12 years old)

L: Limb length discrepancy

I: Inflammatory (transient synovitis, 3-6 years of age after viral illness)

M: Malignancy

P: Pyomyositis (possible viral cause such as influenza, often with tender calves)

I: Iliopsoas abscess

N: Neurologic (stroke, will often have underlying pathology such as cardiac lesion, sickle cell disease, metabolic history; ataxia can present with a reported ‘limp’)

G: Gastrointestinal (appendicitis), genitourinary (testicular/ovarian torsion)

One of the ‘can’t-misses’ is the pediatric septic hip, which typically results from three sources: hematogenous spread, local spread (osteomyelitis), direct inoculation (trauma, surgery). S. aureus is the most common causative organism in all age groups, with Salmonella considered in sick cell disease patients, and N. gonorrhea in sexually active patients.

Evaluation:

CBC, ESR, CRP are indicated in an acutely limping child in whom infectious etiology is a possible cause. Also consider Lyme if living in an endemic area, and there are no abnormalities on plain radiography.

If suspicion for septic arthritis remains high despite negative plain radiographs, recent studies have show utility in ultrasonography to identify effusions. Unfortunately, US cannot differentiate between septic arthritis and toxic/transient synovitis as both will result in effusions and mild widening of the joint space, as seen in this patient. MRI is favored over radionuclide scanning for osteomyelitis, stress fracture, and early avascular necrosis. MRI is also indicated if spinal pathology is suggested. Computed tomography (CT) is rarely useful in the patient with a limp, but can diagnose appendicitis, deep soft tissue infections of the paraspinal and retroperitoneal regions.

American College of Radiology Appropriateness Criteria

Traumatic – XR

Atraumatic, no signs of infection – XR, if negative then US hip

Atraumatic, signs of infection – US hip, if negative consider XR, if negative and still concerned for septic arthritis consider MRI

Disposition:

Patients with high concern for bone or joint infection require orthopedic consultation, emergent bone or joint aspiration, and early initiation of antibiotic therapy. A child with an oncologic process requires admission for staging workup and initiation of treatment. Most children have a benign etiology. Afebrile children with normal radiographs are suitable to followup with PCP, after discharging with NSAIDs. Ambulatory febrile children, with normal radiography and blood studies can also be followed up as an outpatient. If the patient remains febrile and unable to bear weight, have a low threshold to pursue joint aspiration. If the patient is afebrile, but unable to bear weight despite an adequate dose of analgesia, consider observation for MRI if early osteomyelitis, AVN, or spinal pathology is high on your differential.

Any unstable patient requires treatment as presumed sepsis, with fluid resuscitation and initiation of empiric antibiotics, orthopedics consultation for source control, and consideration of ultrasonography or MRI. One antibiotic regimen includes nafcillin 50 mg/kg, ceftriaxone 50 mg/kg; consider adding vancomycin 10 mg/kg if concerned for MRSA or sepsis.

Kocher’s criteria:

Our orthopedic colleagues utilize the Kocher criteria to determine the probability of whether the pediatric patient has a septic arthritis. The four elements include:

  • Erythrocyte sedimentation rate >40
  • WBC >12
  • Non-weight bearing on the affected joint
  • Fever >38.5 C

If elements are present, the probability of septic arthritis was determined to be:

  • 0/4 = 0%
  • 1/4 = 3%
  • 2/4 = 40%
  • 3/4 = 93%
  • 4/4 = >99%

HIGH pretest probability? – Kocher's criteria predictive value is HIGH

LOW pretest probability? – Kocher's criteria predictive value is LOW

A 2011 ACEP News Release confirms that Kocher’s criteria remains the best method for EM providers to differentiate transient synovitis and septic arthritis. If 2 or more criteria are present, talk with your orthopedic colleagues.

Takeaways:

  • Assume that any child with a fever who presents with refusal to walk has septic arthritis or osteomyelitis until proven otherwise. Transient synovitis is a diagnosis of exclusion!
  • 2 or more Kocher criteria should prompt orthopedic consultation for consideration of joint aspiration.
  • Discuss care with PCP for prompt re-evaluation if patient’s ED examination is improving and they are stable for discharge.

References:

Brady M. The child with a limp. J Pediatr Health Care. 1993:7:226.

Singer J. The cause of gait disturbance in 425 pediatric patients. Pediatr Emerg Care. 1985;1:7.

Chung S. Identifying the cause of acute limp in childhood. Clin Pediatr. 1974;13:769.

Fischer S, Beattie T. The limping child: epidemiology, assessment and outcome. J Bone Joint Surg Br. 1999;81:1029.

Pediatric Emergency Playbook. Please, just stop limping! Available at: http://pemplaybook.org/podcast/please-just-stop-limping/. Accessed April 3, 2017.

Leet A, Skaggs D. Evaluation of the acutely limping child. Am Fam Physician. 2000;61:1011.

Huttenlocher A, Newman T. Evaluation of the erythrocyte sedimentation rate in children presenting with limp, fever, or abdominal pain. Clin Pediatr. 1997;36:339.

American College of Radiology ACR Appropriateness Criteria. Limping child – ages 0-5 years. Available at: https://acsearch.acr.org/docs/69361/Narrative/. Accessed April 3, 2017.

ACEP News. Kocher criteria still the best way to ID septic arthritis in children. Available at: https://www.acep.org/MobileArticle.aspx?id=82236&coll_id=716&parentid=740. Accessed April 3, 2017.

Kocher M, Zurakoski D, Kasser J. Differentiating between septic arthritis and transient synovitis of the hip in children: an evidence-based clinical prediction algorithm. J Bone Joint Surg Am. 1999;81(12):1662.

Kocher M, Mandiga R, Zurakoski D, et al. Validation of a clinical prediction rule for the differentiation between septic arthritis and transient synovitis of the hip in children. J Bone Joint Surg Am. 2004;86:1629.

Clinical Image 21: A Sparkle in the Eye

WELCOME BACK TO ANOTHER CLINICAL IMAGE FROM THE CASE FILES OF THE BROWN EM RESIDENCY!

Case:

HPI/ROS: 49-year-old female with a history of hypothyroidism and asthma  presents to the ED with right eye swelling and pain. She reports that four days ago she initially developed a severe right-sided headache, which progressed to right eye swelling, redness and pain with movement. She was seen at an urgent care center and diagnosed with conjunctivitis and treated with topical antibiotics[am1] . Today, she awoke with a new rash on her scalp as well as chills, nausea, and watery discharge from the eye. She denies visual changes or fevers.  

Vital Signs: T: 98.6, HR: 91, BP: 123/73, R: 16, SpO2: 99% on room air

Visual Acuity: R 20/25 L 20/25

Physical Examination: The patient is alert and oriented. Normocephalic, atraumatic head. Tympanic membranes are clear. Oropharnyx clear and moist. Cranial nerves II-XII are intact. Pupils are 4 mm and reactive bilaterally. Extra-ocular movements are intact. Peripheral vision is intact. Patient accommodates appropriately. Neck is supple. Lungs are clear to auscultation. Heart is regular rate and rhythm without murmurs, rubs, or gallops. Abdomen is soft, non-tender, non-distended. A rash is appreciated above the right eye with some associated mild peri-orbital swelling (see image 1). There is conjunctival injection. Slit lamp examination is performed as well (see image 2). No other pertinent exam findings.

Image 1: Rash appreciated above the right eye.

Image 1: Rash appreciated above the right eye.

Image 2: Slit lamp examination findings

Image 2: Slit lamp examination findings

What’s the diagnosis?

Herpetic Zoster Ophthalmicus (HZO)

Here are some quick facts:

  • Herpetic Zoster Ophthalmicus (HZO) is a vision threatening condition secondary to Varicella Zoster Virus (VZV) reactivation, “shingles”, within the trigeminal ganglion, specifically the first division (V1).
  • Up to one-half of all patients with VZV V1 reactivation experience direct ocular involvement.
  • Typical prodromal symptoms include headache, malaise, fever, pain and photophobia in the affected eye and surrounding dermatome.
  • Upon eruption of vesicular lesions within the trigeminal dermatome, patients will likely experience hyperemic conjunctivitis, blurred vision, and/or lid droop. The rash typically does not cross the midline.
  • Two thirds of patients will develop corneal involvement (keratitis), which can either manifest as punctate (our patient) or dendritic lesions on slit lamp examination.
  • The anterior chamber can show cells and flare if deeper structures are affected (iritis).
  • Lesions on the nose are fairly specific for HZO due to involvement of the nasociliary branch of the trigmeninal nerve, which also innervates the eye.  
  • Early diagnosis is critical and management involves oral anti-retrovirals and adjunctive topical steroid drops to reduce the inflammatory response. Associated conjunctivitis can be treated with topical erythromycin ointment. Pain reduction can be achieved with topical cycloplegic agents.
  • If the patient is immunocompromised or systemically ill, consider admission with IV acyclovir.
  • Prompt ophthalmological follow up is warranted as well.

Case Conclusion:

This patient was discharged home on oral acyclovir and topical steroid drops. She had follow up with ophthalmology the following day.

Faculty Reviewer:

Dr. Alyson McGregor

References:

Albrecht, Mary. Clinical Manifestations of Varicella-Zoster Virus Infection: Herpes Zoster. UptoDate. 2017.

Tintinalli, et. al. Emergency Medicine. 8th Edition. 2016. 1061-1062.   

The contents of this case were deliberately altered to protect the identity of the patient. All content in this report are for educational purposes only. The patient consented to the use of these images.