The differential diagnosis of a patient with altered mental status and an elevated temperature is broad, and requires multiple simultaneous actions to manage properly. The practitioner must consider infectious, iatrogenic, and environmental causes, among others, and move decisively to stabilize and treat this serious presentation.

This chapter describes the normal maturation pattern of plasmacytoid dendritic cells (pDCs), as well as the dynamic antigenic changes during pDC differentiation. Common markers used to define the pDC lineage are included, with their advantages and limitations discussed. Key immunophenotypic features associated with neoplastic pDC proliferations (blastic plasmacytoid dendritic cell neoplasm, myeloid neoplasms with plasmacytoid dendritic cell differentiation, and mature plasmacytoid dendritic cell proliferation associated with myeloid neoplasm) are covered. Minimal residual disease evaluation of pDC neoplasms is also discussed. Finally, the differential diagnosis associated with pDC proliferations is addressed.

Fire-related injuries, including direct burns and inhalational injuries and related inhalation poisoning, require immediate lifesaving management through the rapid recognition of the extent of the injuries and appropriate resuscitation and prevention of further comorbidities. This case reflects patient exposure to indoor fire with facial, chest, and extremity burns. The case progresses, mandating rapid but focused patient assessment and prioritization of a variety of critical actions including recognition of the need for and performance of emergent intubation in the setting of facial and airway burns; aggressive resuscitation including utilization of the Parkland formula for burn patient management; high suspicion of carbon monoxide and concomitant cyanide poisoning requiring appropriate testing and treatment; and circumferential extremity burn requiring recognition of impending compartment syndrome requiring escharotomy.

nTFHL is a heterogenous group of mature T-cell lymphomas with follicular helper T-cell (TFH) immunophenotype. It is designated when at least two of the following markers are expressed: CD10, PD1 (CD279), ICOS, BCL6, CXCL13, CXCR5, SAP, MAF, or CD200. It is characterized by frequent loss of surface CD3, almost exclusively CD4, frequently diminished CD7, and retained CD2 and CD5. TFH markers studied by flow cytometry include CD10, PD1, CD200, ICOS, and CXCR5, but they can be expressed in reactive T-cells. nTFHL has three morphologic subtypes: angioimmunoblastic, follicular, and not otherwise specified. nTFHL angioimmunoblastic type or angioimmunoblastic T-cell lymphoma (AITL) is the prototype. All three subtypes share similar immunophenotypic characteristics, indistinguishable by flow cytometry. In nFFHL, lymphoma cells are frequently detected in blood and bone marrow by flow cytometry, often without morphologic involvement by lymphoma. The nTFHL immunophenotype is detailed and differential diagnoses are reviewed. Lymphocyte-variant hypereosinophilic syndrome and CD10-positive reactive T-cells in healthy individuals are discussed as immunophenotypic mimickers of nTFHLs.

Chimeric antigen receptor (CAR) T-cell therapy represents a revolution in cancer immunotherapy. Currently, seven FDA-approved CAR T-cell therapies target hematological malignancies such as B-cell lymphoblastic leukemia (B-ALL), B-cell lymphoma, and multiple myeloma. More than 250 ongoing clinical trials are exploring its application in various cancers. This rapid progress highlights the urgent need for dynamic and reliable monitoring of CAR T cells. Multiparameter flow cytometry (MFC) plays a critical role in quality control during manufacturing and also enables the detection of live CAR T cells after infusion in tracking and quantifying CAR T cells in vivo. By incorporating disease markers, MFC also provides a fast and accurate tool in addressing clinical concerns of disease relapse versus CAR T-cell proliferations. This chapter provides an overview of CART construction, recent developments, and clinical applications, followed by the introduction and illustration of CAR T by MFC tests as Laboratory Development Tests (LDT). Of the latter, we focus on CAR-CD19, CAR-BCMA, and allogeneic CART assays and discuss reagent choice, assay set-up, validations, and applications.

The chapter describes a case of a 28-year-old male with pain in the anal region, a history of Crohn’s disease, and a prior similar episode requiring surgery in the ED. The patient is examined, and it is found that he has an uncomplicated perianal abscess. The chapter details the primary and secondary surveys, history, action taken, results, diagnosis, critical actions, and pearls associated with perirectal abscesses. The critical actions include thorough examination, incision and drainage, and follow-up management. The chapter concludes by stating that antibiotics are not necessary unless the patient exhibits systemic involvement.

Rocky Mountain spotted fever is a tick-borne illness that peaks in the summer months. Classic presentation includes tick bite followed by fever, rash, nausea, vomiting, and headache. The classic maculopapular rash starts around the ankles and wrists then spreads toward the feet, legs, arms, hands, and torso. This rash can coalesce and become petechial with time. Historically, the rash starts several days after the fever. Classic laboratory findings include hyponatremia, thrombocytopenia, and transaminitis. Management with doxycycline or, less commonly, chloramphenicol, is imperative to treatment. Doxycycline can provide greater tick-borne coverage and decreases mortality. Chloramphenicol should only be used when doxycycline is contraindicated. It is crucial to elicit travel to an endemic area and participating in activity that might place a person in close contact with ticks, especially since people might not provide a history of tick bites.

The chapter describes a case of a 45-year-old female with type I diabetes who presented with severe diffuse abdominal pain for a day, fevers on and off since yesterday, and persistent nausea with vomiting. The physical exam revealed a mildly distended, diffusely tender abdomen, decreased bowel sounds, and rebound and guarding. The patient was diagnosed with diabetic ketoacidosis and urinary tract infection and was treated with IV fluid bolus, insulin drip, antibiotics, and ICU admission. The chapter provides pearls on the diagnosis and management of abdominal pain, including the importance of early blood glucose assessment, fluid replacement, insulin drip, and ICU admission for DKA, and early antibiotics, fluids, and surgical consultation for peritoneal signs.

This chapter covers a case of an ambiguous septic patient presenting with altered mental status. Sepsis is a common and life-threatening encounter faced by all emergency physicians. The management and timely treatment of sepsis, as well as recognition of the consequences of severe sepsis, is of utmost importance in emergency medicine. This case ensures that the emergency medicine physician does a full history and physical to find the culprit cause of sepsis as well as how to handle a rare and difficult acquired bleeding disorder that can occur with septic shock.

This is a case of newly diagnosed myasthenia gravis (MG). MG is an autoimmune disease where there is a marked decrease in the number and function of muscle fiber acetylcholine receptors (AChRs) due to autoantibodies. It is characterized by muscle weakness and fatigue, especially of proximal extremity, facial, and bulbar muscles. Ptosis and diplopia are also common presenting symptoms. During a myasthenic crisis, respiratory failure can occur due to extreme weakness in the muscles of respiration. A detailed history and physical examination are key to making the clinical diagnosis. The diagnosis is confirmed with bedside edrophonium testing. One must recognize that edrophonium testing may potentially cause profound respiratory weakness, and one must be prepared to provide ventilatory support. Depolarizing and nondepolarizing agents should be avoided, or used at half dose, since MG patients are extremely sensitive to these. MG treatment may involve administration of acetylcholinesterase inhibitors (pyridostigmine or neostigmine), corticosteroids, plasma exchange, IV immunoglobulin, or thymectomy.

A number of miscellaneous nodal and extranodal mature NK/T-cell lymphomas that are not included in other chapters are discussed in this chapter. Entities include peripheral T-cell lymphoma not otherwise specified (PTCL, NOS), nodal EBV+ NK/T-cell lymphoma, primary cutaneous T-cell lymphomas other than mycosis fungoides/Sezary syndrome, intestinal T-cell lymphoma (enteropathy associated T-cell lymphoma and monomorphic epitheliotropic intestinal T-cell lymphoma), and extranodal NK/T-cell lymphoma. The discussion focuses on the immunophenotypic features of each entity and how they aid in differential diagnosis.

This chapter discusses the diverse immunophenotypic features of acute myeloid leukemia (AML) with mutated TP53. It also addresses immunophenotypic shifts that may occur over the course of the disease.

An abdominal aortic aneurysm (AAA) is weakness in the wall of the aorta that causes dilation of the vessel. The dilation causes increased pressure at the wall, increasing the rate of stretch until a leak occurs. This condition tends to progress slowly over years, and the risk of rupture increases with the diameter of the vessel. The case highlights presentation of a patient who has an acute rupture and identifies risk factors for AAA, such as male gender and a significant smoking history. Elderly patients with back or flank pain should be evaluated for AAA. Hematuria is also common in patients with ruptured AAA, which can lead to the incorrect diagnosis of nephrolithiasis. Important early actions including administering IV fluids if hypotensive, obtaining a bedside ultrasound (US), consulting surgery, and advocating for the patient to go to the operating room are critical for management of aortic aneurysm. Bedside US is the preferred modality for imaging as it is technically adequate has close to 100% sensitivity for demonstrating an AAA.

A total of 85% of all diarrhea is infectious diarrhea, usually secondary to either bacterial or viral causes. Enteroinvasive diarrhea is a subset of infectious diarrhea where there is damage to the intestinal mucosa. Moderate to severe dehydration characterized by dry mucous membranes, low pressure, or tachycardia will benefit from isotonic fluid repletion. Severe cases are marked by fever, bloody diarrhea, or a toxic appearance, and antibiotic therapy should be considered in these patients. Fluoroquinolones, azithromycin, or rifaximin are all antibiotic choices, depending on a patient’s particular risk factors. Stool cultures should be part of the work-up for both treatment and diagnosis in infectious diarrhea, particularly in patients with a positive travel history or those who are immunocompromised or febrile or have severe, persistent abdominal pain. Special populations include those who have had recent antibiotic use and pediatric patients. If patients have been on antibiotics recently, C. difficileinfection should be considered. In pediatric populations, antibiotics should be carefully considered as pediatric patients are more likely to develop hemolytic uremic syndrome and thrombotic thrombocytopenic purpura when they are started on antibiotics.

The chapter discusses the diagnosis and critical actions for acute chest syndrome in patients. For acute chest syndrome, administration of oxygen, IV pain medications, and antibiotics are critical actions. Obtaining a CXR is key in this case, and albuterol should be given in patients with bronchospasm. Painful crises that are not typical of the patient’s usual symptoms should elicit a search for more serious complications of sickle cell disease.

This case concerns a patient with a spontaneous nontraumatic intracranial hemorrhage while on anticoagulation. Learners will have to determine the cause of the patient’s altered mental status using clues from the history and physical, order the applicable imaging and laboratory testing, and initiate the appropriate management of this condition. In addition, the patient’s use of anticoagulants and declining mental status will test learners’ knowledge of anticoagulation reversal and airway management.

This case describes a child with measles, a highly contagious infection caused by a paramyxovirus. This infection is classically characterized by fever, cough, coryza, conjunctivitis, and a characteristic rash that progresses craniocaudally. This case will review the clinical presentation, as well as testing and further management of this illness. We will also discuss the management of measles exposures.

Status epilepticus is defined as one seizure persisting for greater than 5 minutes, or two seizures within a 5-minute period without interval return to baseline. This condition is characterized by intractable seizure and represents a true medical emergency, as it poses a severe threat of anoxic brain injury that increases with duration of seizure. Status epilepticus has widely varied causes, including but not limited to hypoglycemia, electrolyte abnormalities, substance withdrawal, medications/toxins, new-onset primary seizure disorders, malignancy, and trauma. Following the classic primary survey, management should focus on cessation of seizure activity through administration of benzodiazepines, with progression to phenytoin/fosphenytoin and even barbiturates should seizures remain refractory. Airway protection should be actively maintained given the often-high doses of these medications. Work-up should include basic laboratory panels, including CBC, BMP, LFTs, coags, UA, serum tox, ABG, and ECG; imaging should include CXR and CT head. A thorough history should be obtained from patient/family/bystanders if possible following stabilization, and neurology consult should be considered.