42 year-old male with fever, vomiting and diarrhea

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1 42 year-old male with fever, vomiting and diarrhea Morbidity & Mortality Case Presentation Michael J. Burns, MD FACEP FACP FIDSA Professor of Emergency Medicine Professor of Medicine, Division of Infectious Diseases UC Irvine School of Medicine

2 A Patient with Acute Vomiting and Diarrhea (This is a real case exactly as it happened) 42 year-old male walked into ED Triage at 2100 hr, accompanied by his wife Chief complaint at triage: vomiting and diarrhea for one day Vital signs at triage: T F (39.2 C), Pulse 112, R 20, BP 112/68, Pulse ox 99% RA Chief complaint to the physician: abdominal pain

3 History of Present Illness Diffuse abdominal pain for 1½ days with N/V, diarrhea 4-5x/day Pain constant, increasing in severity No chest or back pain, cough, SOB, bloody or dark stools, hematemesis, dysuria, hematuria Illness started a few days after he stopped Vicodin and started celecoxib (Celebrex) His young daughter has a confirmed RSV infection diagnosed in the past few days

4 Past Medical History Chronic L shoulder pain, anxiety disorder, panic attacks, blunt head injury 3 yrs ago due to MVA causing 1 yr of disability Negative for: diabetes, cardiovascular, liver or kidney disease, pancreatitis, gallstones, peptic ulcer Surgery: Auto accident 21 yrs ago with laparotomy and splenectomy; numerous knee and shoulder surgeries; cervical spine fusion; sinus surgery

5 Additional History Current Medications: celecoxib, diphenhydramine, diazepam, trazodone, Vicodin (just stopped) Allergies: penicillin, ampicillin, cephalexin, sulfa, tramadol (Ultram), naproxen Social History: smokes 2 PPD; former alcoholic, stopped 1 yr ago; former IVDA; negative HIV (last tested 8 yrs ago); construction worker, works fulltime, several children, including a recent child with his new wife He has a primary internist with an office next to the hospital where he has been getting care for many years; has always had excellent medical insurance through his union

6 Physical Exam (exactly as documented by ED physician) Vital signs: listed earlier; repeat temp 104 F (40 C) Patient in moderate distress, retching HEENT: benign Neck: supple Lungs: scattered rhonchi Heart: tachycardia Abdomen: soft, diffuse tenderness, no guarding or rebound, positive bowel sounds Back: nontender (Rectal: not done) Neuro: alert, oriented Extr: tender L shoulder (chronic, no change, per patient) (Skin: exam not documented)

7 Initial Treatment in ED IV fluids (normal saline) IV morphine, promethazine, prochlorperazine Oral acetaminophen Reevaluated 2 hrs later, after lab tests were back: mild improvement

8 Diagnostic Testing in ED CBC: WBC 8000 (PMN 69, bands 21, L 5, M 4), H/H 14.5/41.7, platelets 204k Glucose 114, Na 141, K 3.7, Cl 105, CO2 21, BUN 11, creatinine 1.3, calcium 9.5 (anion gap 15) Serum lipase normal; LFT s not done UA: spec grav 1.015, ph 5, protein 1+; gluc, ketones, leuk esterase, nitrite, bili, blood--all neg; WBC <5, RBC <2, epi 2-5, bacteria none, casts 0-2 Acute abdominal series: negative per ED MD chart documentation No cultures ordered

9 Reevaluation 5 Hrs after ED Arrival T 99.7 F (37.6 C), P 98, R 20, BP 120/54 Patient now able to take small sips of fluids and feels better

10 Course in Clinical Decision Unit Patient admitted to CDU about 2 AM for observation and more symptomatic therapy, with plan to get a CT scan of abdomen if not better Repeat vital signs at 0700 hr (10 hrs after arrival to ED): P 69, R 25, BP 154/73, Rectal temp F (38.9 C) Still complaining of diffuse abdominal pain Abdomen diffusely tender CT scan ordered and surgeon called to consult at same time with plan for surgeon to see patient right after the CT scan

11 CDU Course The surgeon reviewed the AAS and CT scan with the radiologist just prior to coming to the ED to see the patient The surgeon made a presumptive diagnosis that later proved correct, requested more lab tests and an urgent change in treatment, and admission to the medical intensive care unit What was the surgeon s diagnosis?

12 Repeat Lab Tests Repeat lab tests after patient returned from CT scan (requested by the surgeon): WBC 29.6k (PMN 54, bands 39, L 1, M 6); H/H 16.3/47.1; platelets 27k Na 140, K 4.6, Cl 107, CO2 16, BUN 23, creat 3.4, calcium 7.7, (anion gap 17), magnesium 1.2, phosphorus 3.7, total bilirubin 5.0, AST 167, ALT 56, alk phos 141, total protein 6.0, albumin 2.9

13 Radiographic Findings The acute abdominal series performed the previous evening and read by the EM doc as normal was read by radiologist: LLL infiltrate consistent with pneumonia, nonspecific bowel gas pattern, no free air CT abd/pelvis: small LLL infiltrate; abnormal appearance of the kidneys bilaterally with lack of excretion, consistent with acute tubular necrosis; absent spleen; no other abnormalities

14 Hospital Course Blood cultures were obtained in the ED Antibiotics given in ED (recommended by the surgeon) (patient had multiple allergies) vancomycin, clindamycin, and gentamicin Admitted to MICU Later that evening, widespread purpuric lesions developed and GI bleeding occurred; septic shock developed

15 Hospital Course Blood cultures grew Streptococcus pneumoniae, penicillin-sensitive After a long and complicated hospital course, the patient survived, but lost all his fingers and toes and his nose, which had all necrosed Final diagnosis: Overwhelming post-splenectomy sepsis due to Streptococcus pneumoniae

16 Review of Prior Outpatient Records Review of his outpatient records prior to this event was done He had been under the care of the same medical group of board-certified internists for over 15 years and had never been offered or given pneumococcal polysaccharide vaccine despite a history of splenectomy repeatedly documented in the outpatient records

17 Final Outcome The patient later sued the emergency physician and his primary physician s medical group The case did not go to trial but was settled in favor of the plaintiff (the patient) for a total amount well over $1 million dollars, with the largest amount paid by the primary physician, a board-certified internist, for not providing the patient with pneumococcal vaccine

18 Infections and Infectious Disease Emergencies Associated with Splenectomy, Hyposplenia, and Functional Asplenia

19 Functions of the Spleen Primary site for IgM synthesis Opsonin production in the spleen facilitates phagocytosis of bacteria by macrophages Patients without a spleen have decreased production of neutrophils, NK cells, and immunomodulating cytokines. Spleen filters complement- and antibody-coated bacteria from the bloodstream, an especially important mechanism of killing of bacteria having a capsular polysaccharide Spleen is the principal site of clearance of Streptococcus pneumoniae from the blood

20 Anatomic or functional hyposplenism may be recognized on peripheral blood smear by the presence of what structures in red blood cells?

21 Howell-Jolly Bodies William Henry Howell Justin Marie Jolly

22 Howell-Jolly Bodies

23 Howell-Jolly Bodies Named for William Henry Howell and Justin Marie Jolly Howell-Jolly bodies: nuclear remnants in RBC s, seen when the spleen does not function to remove inclusions in RBC s. Seen routinely in moderate to severe hyposplenism, but may not be present if only mild impairment of splenic function. The more Howell-Jolly bodies seen, the worse the splenic dysfunction/impairment.

24 Beware the Howell-Jolly Bodies!!

25 Howell Jolly Bodies on Wright-stained peripheral blood smear

26 Pappenheimer Bodies abnormal granules of iron within RBCs, irregular in shape and frequently multiple in an RBC; also seen in splenectomized patients

27 RBC Inclusions

28 Infections Associated with Splenectomy and Functional Asplenia Fulminant infections with encapsulated bacteria Streptococcus pneumoniae * Haemophilus influenzae Neisseria meningitidis Capnocytophaga canimorsus (after dog bites) E. coli Klebsiella Anaplasmosis (Rickettsia-like) Human granulocytic anaplasmosis (formerly ehrlichiosis); Anaplasma phagocytophilum transmitted by Ixodes scapularis (deer tick) and on the West Coast, the western blacklegged tick (Ixodes pacificus) Protozoan Babesia microti: malaria-like parasite transmitted by tick bite in the northeastern coastal U.S.; severe, often fatal hemolysis Malaria * 50-90% of cases

29 Overwhelming Postsplenectomy Sepsis Uncommon Annual incidence of serious bacterial infection following splenectomy derived from cohort studies 0.42% in 1 study; 0.23% in another study Lifetime risk of overwhelming infection is about 5% Risk greater in children than adults Risk highest in first few years after splenectomy but persists for life Highest risk is seen in: Splenectomy for hematologic disorder or lymphoma Functional asplenia from sickle cell, thalassemia major Lower risk after splenectomy for trauma, probably due to splenic implants or accessory spleens High mortality rate of 50-70% is independent of the indication for spleen removal

30 Risk for severe infection is lower for patients taking prophylactic penicillin and after pneumococcal and other vaccines, but these patients are still at increased risk!

31 Changes in the Bacteriology of Post-Splenectomy Sepsis Most data on the bacteria associated with severe infections in asplenic or hyposplenic patients were obtained before widespread use of prophylactic antibiotics or conjugated vaccines against these agents. More recent data obtained from in Australia and from in Israel report that gram-negative bacilli and Staphylococcus aureus were the most common causes of postsplenectomy infections The current increasing use of S. pneumoniae vaccines among adults, as well as the widespread use of protein-conjugated S. pneumoniae and H. influenzae vaccines in children, may modulate both the rates of post-splenectomy sepsis and the spectrum of the implicated bacteria.

32 Some Conditions Associated With Functional Hyposplenism Sickle cell hemoglobinopathies: SS, SC, S-β thalassemia Hemophilia CML Non-Hodgkin s lymphoma Sarcoidosis Amyloidosis Rheumatoid arthritis Systemic lupus erythematosus Celiac disease Crohn s disease Ulcerative colitis Biliary cirrhosis Grave s disease Hashimoto s thyroiditis Mixed connective tissue disease Dermatitis herpetiformis Alcoholism

33 Underlying cause of splenic deficiency in 688 episodes of postsplenectomy sepsis

35 Risk of Postsplenectomy Sepsis Related to Splenectomy Cause (Cases/100 Patient-Years) Low Attack Rate Risk Incidental surgical 1.17 ITP 2.03 Trauma 2.07 Intermediate Attack Rate Spherocytosis 3.15 Hodgkin s disease 6.15 Portal hypertension 6.72 High Attack Rate Thalassemia 11.6 Autoimmune lymphoproliferative syndrome 31.3

37 Post-splenectomy sepsis in patients with HIV infection Markedly increased incidence of severe bacterial infections, especially S. pneumoniae, in persons with HIV infection and a history of splenectomy, even in those on HAART Severe infections occurred a mean of 9.7 years after splenectomy Much higher risk than HIV infection without splenectomy, or splenectomy without HIV infection. Polizzotto: The influence of splenectomy on the infectious complications and outcomes of people with HIV: marked, sustained elevation in risk of severe infection with bacteria including Streptococcus pneumoniae. J Acquir Immune Defic Syndr (Melbourne, Australia)

38 Clinical Presentations Prodromal symptoms occur for 1-2 days Fever, rigors, malaise, body aches, headache, pharyngitis, vomiting, diarrhea Patients seen at this stage may be misdiagnosed as viral illness, gastroenteritis, food poisoning An asplenic individual may walk into a health care facility complaining of fever and diarrhea, appear to be stable, only to be in shock within a few hours Abrupt deterioration occurs over a few hours, with rapid progression to septic shock, DIC, purpura, multiorgan dysfunction May also present with a focal illness (meningitis, pneumonia) and rapidly deteriorate Mortality rate is 50-70% even with appropriate antimicrobial therapy and intensive medical support Of those who die, 80% die within 48 hrs of symptom onset

39 Pneumococcal sepsis more than 20 years after splenectomy for trauma

40 Purpura in patient with pneumococcal sepsis after splenectomy

41 Purpura fulminans with necrosis of digits

42 Fever, chills, and a generalized seizure occurred in a 57 yearold man who had undergone splenectomy for stage IV non- Hodgkin s lymphoma 3 years earlier

43 The images are typical of symmetric peripheral gangrene associated with S. pneumoniae bacteremia in a patient whose spleen has been removed. The patient survived.

44 Early Diagnosis High index of suspicion for febrile presentations in patients with asplenia or functional hyposplenism In patients with fever and hx of splenectomy, ask for manual review of peripheral blood smear CBC blood smear: if lab reports Howell-Jolly bodies or Pappenheimer bodies in a febrile patient, take urgent measures Blood cultures Gram or Wright stain of blood may show organisms Aspirate, culture of purpuric lesions CSF exam if meningitis is suspected, especially in children Obtain blood smear for malaria and babesiosis if epidemiologic history suggests these possibilities

45 Treatment for Fever in Patient with Splenectomy/Functional Asplenia Immediate blood cultures Give ceftriaxone + vancomycin right away Alternatives if serious penicillin-allergy Levofloxacin or moxifloxacin Add vancomycin in areas where penicillinresistance is prevalent No waiting for results of lab tests, x-rays before administering antibiotic

46 Pneumococcal Vaccination in Adults with Functional or Anatomic Asplenia Includes sickle cell disease and other hemoglobinopathies, congenital or acquired asplenia, splenic dysfunction, or splenectomy All adults 19 to 64 yrs of age with these conditions should receive the PPSV23 pneumococcal vaccine to prevent invasive pneumococcal disease Revaccination: a second dose of PPSV23 is recommended 5 years after the first dose for persons aged years with functional or anatomic asplenia and for persons with immunocompromising conditions. ACIP does not recommend multiple revaccinations because of insufficient data regarding clinical benefit, particularly the degree and duration of protection, and safety Elderly: all persons should be vaccinated with PPSV23 at age 65 years. Those who received PPSV23 before age 65 years for any indication should receive another dose of the vaccine at age 65 years or later if at least 5 years have passed since their previous dose. Those who receive PPSV23 at or after age 65 years should receive only a single dose. From: Updated Recommendations for Prevention of Invasive Pneumococcal Disease among Adults Using the 23-Valent Pneumoccoccal Polysaccharide Vaccine (PPSV23). MMWR. September 3, 2010 / 59;

47 Pneumococcal Vaccination in Children with Functional or Anatomic Asplenia Complete the primary series using the 13-valent pneumococcal conjugate vaccine (PCV13) Schedule for vaccination using 23-valent polysaccharide vaccine (PPSV23) after 13-valent pneumococcal conjugate vaccine (PCV13) for children aged 2 years with underlying medical conditions 1 dose of PPSV23 administered at age 2 yrs and 8 weeks after last indicated dose of PCV13 Revaccination with PPSV23: 1 dose 5 years after the first dose of PPSV23 From: Prevention of Pneumococcal Disease Among Infants and Children --- Use of 13-Valent Pneumococcal Conjugate Vaccine and 23-Valent Pneumococcal Polysaccharide Vaccine. MMWR. December 10, 2010 / 59;1-18.

48 Prevention of Infection Asplenic persons should be immunized against S. pneumoniae H. influenzae type B N. meningitidis Influenza Oral penicillin/amoxicillin prophylaxis Children up to age 5, and 1-2 years after splenectomy Long term prophylaxis is not recommended Standby oral antibiotics at home (amoxicillinclavulanate, levofloxacin, or moxifloxacin) with instructions to self-administer at first sign of infection Medical alert bracelet; carry card listing an emergency plan to be given to medical providers

49 Strategies to Prevent Severe Infections in Splenectomized Patients

50 Lack of Awareness Among Patients Low level of knowledge about PSS exists Only 16% of asplenic patients in North Carolina were aware of any health precautions in one study White KS et al: Patient awareness of health precautions after splenectomy. Am J Infect Control 1991;19:36

51 Quiz A 27-year-old male presents to the ED with acute onset of fever, chills, headache, myalgias, vomiting, mild abdominal cramping, and diarrhea for 8 hours. A splenectomy was performed 15 years earlier when he was treated for lymphoma, which has been in remission since then. He is not taking any medications and has been well. Vital signs are pulse 125 beats/minute, blood pressure 110/60, respiratory rate 20/minute, and temperature 39.5 C. His mental status is normal and he has mild generalized abdominal tenderness. What is the most appropriate treatment for this patient at this time?

52 A. Lumbar puncture. Quiz Choose the single best answer B. Hydration, antipyretic, antiemetic, and observation in the ED. C. Immediate hospital admission with observation and frequent abdominal exams. D. Stool testing for occult blood and fecal leukocytes. E. Blood cultures followed by immediate administration of ceftriaxone, with or without vancomycin.

53 Quiz Answer Answer: E. This patient is at high risk for overwhelming postsplenectomy sepsis, usually caused by Streptococcus pneumoniae. Persons who have undergone splenectomy for a hematolgic disorder or lymphoma are at much higher risk for overwhelming postsplenectomy infection than are those undergoing splenectomy for trauma. The initial prodromal symptoms may be misdiagnosed as a viral illness, gastroenteritis, or food poisoning, before there is abrupt deterioration with development of septic shock with disseminated intravascular coagulation, purpura, and multiorgan dysfunction.. After blood cultures are obtained, he should immediately receive antimicrobials active against pneumococci, meningococci, and Haemophilus influenzae. He can be investigated for other possible etiologies of his symptoms after this initial critical action is taken.

CARE OF THE PEDIATRIC ASPLENIC PATIENT. Michael Siegenthaler, MD and Nadine Khouzam, MD

CARE OF THE PEDIATRIC ASPLENIC PATIENT Michael Siegenthaler, MD and Nadine Khouzam, MD CASE OVERVIEW 11-year-old Arabic speaking female who recently immigrated from Jordan presented to the office as a