VACCINE UPDATE
Fatal purpura fulminans and septic shock in asplenic patient with Streptococcus pneumoniae bacteremia Cyle White, Anthony J. Guarascio, and Heather M. Draper
Case report A 43-year-old white man presented to the emergency department by private vehicle complaining of left anterior chest pain, shortness of breath, and inability to feel his extremities, along with a 3-day history of fatigue, mild fever, loss of appetite, and nausea. His previous medical history was important for hypertension, nephrolithiasis, and chronic abdominal pain, and his past surgical history was noteworthy for lithotripsy and splenectomy during childhood secondary to trauma. The patient’s home medication regimen did not consist of any antibiotic or immunosuppressive agents. He stated a tobacco use history of one pack per day. Of note, the patient received typical childhood vaccinations, reportedly including pneumococcal vaccination, but had not received pneumococcal vaccination as an adult. Initial vital signs were noteworthy for tachycardia, tachypnea, hypotension, and a pulse oximetry of 60% on room air. During physical examination, the patient‘s skin appeared pale and diaphoretic with areas of mottling and cyanosis in the upper and lower extremities. Fluid resuscitation began, and the patient was placed on oxygen. The patient remained hypotensive and was initiated on vasopressor therapy in addition to broad, empiric antimicrobial therapy. Analysis of the laboratory and physical findings obtained in the emergency department resulted in a diagnosis of septic shock and acute renal failure. The patient was admitted to the intensive care unit for management of sepsis with multiple organ dysfunction syndrome, and aggressive resuscitation was continued. 88 JAPhA | 5 4 : 1 | JAN/F EB 2014
Shortly upon arrival to the intensive care unit, the patient reported diffuse pain in the upper and lower extremities. Upon routine inspection, nursing staff noted what was initially described as severe, worsening mottling of the skin. During the next 2 hours, purple discoloration of the extremities was noted, followed by rapid progression to include involvement of the skin of the fingers, toes, nose, ears, and abdomen, which was determined to be purpura fulminans. Shortly thereafter, preliminary blood culture results revealed gram-positive cocci in pairs and chains. Final culture results revealed Streptococcus pneumoniae that was susceptible to penicillin, cephalosporins, and fluoroquinolones, at which time penicillin G intravenous continuous infusion was implemented. Approximately 16 hours after initial presentation, the patient developed respiratory failure requiring mechanical ventilation. Purpura fulminans continued to spread proximally from the extremities to the trunk, affecting nearly 100% of the body surface area over the course of the hospital stay. Fresh frozen plasma, packed red blood cells, intravenous vitamin K, and low-dose heparin infusion were administered for disseminated intravascular coagulopathy (DIC).
Despite ongoing, aggressive resuscitation, continued deterioration left few options for treatment. After discussion with the family regarding the extremely poor prognosis, the family elected to withdraw support, and the patient was referred to palliative care. The patient expired on hospital day 3, approximately 76 hours after initial presentation, due to cardiopulmonary arrest attributed to the complications of sepsis and purpura fulminans secondary to invasive pneumococcal infection.
Discussion Asplenia may result from surgical splenectomy or functional hyposplenia as a result of conditions such as sickle cell anemia, celiac disease, and bone marrow transplant. These patients are at increased risk of infection from several infectious pathogens, particularly encapsulated bacteria such as S. pneumoniae, Haemophilus influenzae, and Neisseria meningitidis.1 Overwhelming postsplenectomy infection (OPSI) is a relatively rare complication, occurring in approximately 0.5% of patients, that can occur at any time, both immediately after surgery/ diagnosis or years later, resulting in a high mortality rate (from 40% up to 70% in some reports).1 Sepsis is of particular concern, as this population is not only at substantially increased risk for developing sepsis—more than 50 times that of the general population2—but also is at increased risk for mortality.1 Acute infectious purpura fulminans is a rare and life-threatening condition characterized by peripheral thrombosis caused by DIC
Send your immunization questions to the JAPhA Contributing Editors who coordinate the Vaccine Update column: ❚
❚
ja p h a .org
Mary S. Hayney, PharmD, BCPS, Associate Professor of Pharmacy, School of Pharmacy, University of Wisconsin, Madison (mshayney@pharmacy. wisc.edu) John D. Grabenstein, PhD, Director of Scientific Affairs, Merck Vaccine Division ([email protected])
Journal of the American Pharmacists Association
VACCINE UPDATE
and cutaneous purpuric hemorrhage and necrosis.3 Meningococcal sepsis is the most common cause of infectious purpura fulminans, followed by S. pneumoniae, though purpura fulminans has been reported in association with both viral and bacterial infections caused by numerous other pathogens, including group A and B Streptococci, Staphylococcus aureus, Escherichia coli, H. influenzae, and varicella. In the acute phase, purpura fulminans resulting from sepsis is associated with a high mortality rate (estimated 50%); patients who survive the acute phase ultimately face major morbidity due to progressive skin necrosis and secondary cutaneous infections.4 Our patient developed overwhelming pneumococcal sepsis resulting in the additional complications of DIC and purpura fulminans and eventually bilateral cutaneous gangrene. Purpura fulminans due to S. pneumoniae sepsis in an asplenic host has rarely been reported in the literature.4,5 Pneumococcal septicemia causing purpura fulminans has been reported even more rarely in asplenic patients who have previously been vaccinated5 and in patients with a normal spleen.6 Of important note, the majority of these cases have been described in patients with predisposition for an immunocompromised state. Our patient was a healthy adult without any known immunocompromised state other than asplenia.
Despite rare incidences of vaccine failure or inadequate serological response to immunization, pneumococcal vaccination in high-risk adult patients has been shown to significantly reduce the incidence of sepsis and potential subsequent purpura fulminans due to S. pneumoniae infection.7 In addition, patient counseling regarding awareness of increased risk of infection and the need for a clear vaccination history are necessary interventions. Of particular concern, current best practice preventive measures in asplenic patients are not being implemented.8 Practitioners must be cognizant of the immunizations needed to decrease morbidity and mortality in immunocompromised adults, including those with anatomic or functional asplenia. The 13-valent pneumococcal conjugate vaccine (PCV13) is now recommended for use in immunocompromised adult patients as part of a regimen during their next pneumococcal vaccination opportunity. Patients who have not been previously vaccinated should receive PCV13 first, followed by the 23-valent pneumococcal polysaccharide vaccine (PPSV23) at least 8 weeks later. Those who have been previously vaccinated with PPSV23 should be administered PCV13 1 year or later following PPSV23 vaccination. In addition, patients with immunocompromising conditions or asplenia requiring a second PPSV23 vaccination at a 5-year interval should
receive the PPSV23 vaccination again consistent with previous recommendations.9 Asplenic patients also should receive meningococcal and H. influenzae type b vaccine (Table 1), in addition to all other applicable vaccinations (e.g., annual influenza vaccination, tetanus, diphtheria, pertussis).10 Specific recommendations for meningococcal vaccination in patients with asplenia include administration of the meningococcal conjugate vaccine every 5 years after a two-dose primary series in adults aged 19 through 55 years. Unlike others receiving meningococcal vaccination at 56 years or older, the Advisory Committee on Immunization Practices recommends vaccination with the conjugate vaccine rather than the polysaccharide vaccine among patients with asplenia who were previously vaccinated with the meningococcal conjugate vaccine.11 If splenectomy is planned, these vaccinations should be given at least 2 weeks before surgery.12
Conclusion This case report describes a rare occurrence of OPSI due to S. pneumoniae that resulted in refractory septic shock, purpura fulminans, and ultimately death in an otherwise healthy patient decades following surgical splenectomy. Although OPSI is a relatively rare complication, morbidity and mortality remain high despite prompt, aggressive treatment. This case
Table 1. Supplementary ACIP vaccine recommendations for adults with asplenia Vaccine Pneumococcal PCV13 PPSV23
Dose
Route
Vaccination/revaccination schedule
0.5 mL 0.5 mL
Intramuscular Intramuscular/ subcutaneous
Pre/postasplenia at next vaccination opportunity Pre/postasplenia 8 weeks following PCV13, revaccinate 5 years after first dose of PPSV23, revaccinate at ≥65 years of age if ≥5 years since previous vaccination
Meningococcal MCV4
0.5 mL
Intramuscular (deltoid)
Pre/postasplenia, revaccinate 2 months following first dose of MCV4, revaccinate every 5 years
Haemophilus Influenzae Hib
0.5 mL
Intramuscular
Consider pre/postasplenia if not previously received
Abbreviations used: ACIP, Advisory Committee on Immunization Practices; Hib, Haemophilus influenzae type B; MCV4, quadrivalent meningococcal conjugate vaccine; PCV13, 13-valent pneumococcal conjugate vaccine; PPSV23, 23-valent pneumococcal polysaccharide vaccine. Journal of the American Pharmacists Association
j apha.org
JA N /FEB 2014 | 54:1 |
JAPhA 89
VACCINE UPDATE
fundamentally serves as a sober reminder for the critical importance of preventive measures, including vaccination and education of asplenic patients and awareness of the potentially fatal complications that arise if these measures are not instituted. Pharmacists, in collaboration with other health professionals, must take an active role as vaccination advocates and deliver sustained efforts to reduce preventable disease in these high-risk patients. Cyle White, PharmD, BCPS Pharmacotherapy resident University of Tennessee Medical Center Knoxville Anthony J. Guarascio, PharmD, BCPS Assistant Professor College of Pharmacy University of Tennessee Health Science Center Knoxville [email protected] Heather M. Draper, PharmD, BCPS Clinical Pharmacist, Emergency Medicine Mercy Health Saint Mary’s Grand Rapids, MI doi: 10.1331/JAPhA.2014.14505
90 JAPhA | 5 4 : 1 | JAN/F EB 2014
References 1. Di Sabatino A, Carsetti R, Corazza GR. Post-splenectomy and hyposplenic states. Lancet. 2011;378(9785):86–97. 2. Hansen K, Singer DB. Asplenic-hyposplenic overwhelming sepsis: postsplenectomy sepsis revisited. Pediatr Dev Pathol. 2001;4(2):105–21. 3. Betrosian AP, Berlet T, Agarwal B. Purpura fulminans in sepsis. Am J Med Sci. 2006;332(6):339–45. 4. Ward KM, Celebi JT, Gmyrek R, Grossman ME. Acute infectious purpura fulminans associated with asplenism or hyposplenism. J Am Acad Dermatol. 2002;47(4):493–6. 5. Minhas KM, Bashir S, Sarwari AR, Parker J. Pneumococcal purpura fulminans successfully treated with activated protein C. South Med J. 2008;101(10):1046–8.
8. Waghorn DJ. Overwhelming infection in asplenic patients: current best practice preventive measures are not being followed. J Clin Pathol. 2001;54(3):214–8. 9. Centers for Disease Control and Prevention. Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2012;61(40):816– 9. 10. ACIP Adult Immunization Work Group. Advisory Committee on Immunization Practices (ACIP) recommended immunization schedule for adults aged 19 years and older: United States, 2013. MMWR Surveill Summ. 2013;62(suppl 1):9–19.
6. Bramley PN, Shah P, Williams DJ, Losowsky MS. Pneumococcal Waterhouse-Friderichsen syndrome despite a normal spleen. Postgrad Med J. 1989;65(767):687–8.
11. Cohn AC, MacNeil JR, Clark TA, et al. Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2013;62(RR-2):1–28.
7. Shatz DV, Schinsky MF, Pais LB, et al. Immune responses of splenectomized trauma patients to the 23-valent pneumococcal polysaccharide vaccine at 1 versus 7 versus 14 days after splenectomy. J Trauma. 1998;44(5):760–5.
12. National Center for Immunization and Respiratory Diseases. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011;60(2):1–64.
ja p h a .org
Journal of the American Pharmacists Association
Fatal purpura fulminans and septic shock in asplenic patient with Streptococcus pneumoniae bacteremia Cyle White, Anthony J. Guarascio, and Heather M. Draper
Case report A 43-year-old white man presented to the emergency department by private vehicle complaining of left anterior chest pain, shortness of breath, and inability to feel his extremities, along with a 3-day history of fatigue, mild fever, loss of appetite, and nausea. His previous medical history was important for hypertension, nephrolithiasis, and chronic abdominal pain, and his past surgical history was noteworthy for lithotripsy and splenectomy during childhood secondary to trauma. The patient’s home medication regimen did not consist of any antibiotic or immunosuppressive agents. He stated a tobacco use history of one pack per day. Of note, the patient received typical childhood vaccinations, reportedly including pneumococcal vaccination, but had not received pneumococcal vaccination as an adult. Initial vital signs were noteworthy for tachycardia, tachypnea, hypotension, and a pulse oximetry of 60% on room air. During physical examination, the patient‘s skin appeared pale and diaphoretic with areas of mottling and cyanosis in the upper and lower extremities. Fluid resuscitation began, and the patient was placed on oxygen. The patient remained hypotensive and was initiated on vasopressor therapy in addition to broad, empiric antimicrobial therapy. Analysis of the laboratory and physical findings obtained in the emergency department resulted in a diagnosis of septic shock and acute renal failure. The patient was admitted to the intensive care unit for management of sepsis with multiple organ dysfunction syndrome, and aggressive resuscitation was continued. 88 JAPhA | 5 4 : 1 | JAN/F EB 2014
Shortly upon arrival to the intensive care unit, the patient reported diffuse pain in the upper and lower extremities. Upon routine inspection, nursing staff noted what was initially described as severe, worsening mottling of the skin. During the next 2 hours, purple discoloration of the extremities was noted, followed by rapid progression to include involvement of the skin of the fingers, toes, nose, ears, and abdomen, which was determined to be purpura fulminans. Shortly thereafter, preliminary blood culture results revealed gram-positive cocci in pairs and chains. Final culture results revealed Streptococcus pneumoniae that was susceptible to penicillin, cephalosporins, and fluoroquinolones, at which time penicillin G intravenous continuous infusion was implemented. Approximately 16 hours after initial presentation, the patient developed respiratory failure requiring mechanical ventilation. Purpura fulminans continued to spread proximally from the extremities to the trunk, affecting nearly 100% of the body surface area over the course of the hospital stay. Fresh frozen plasma, packed red blood cells, intravenous vitamin K, and low-dose heparin infusion were administered for disseminated intravascular coagulopathy (DIC).
Despite ongoing, aggressive resuscitation, continued deterioration left few options for treatment. After discussion with the family regarding the extremely poor prognosis, the family elected to withdraw support, and the patient was referred to palliative care. The patient expired on hospital day 3, approximately 76 hours after initial presentation, due to cardiopulmonary arrest attributed to the complications of sepsis and purpura fulminans secondary to invasive pneumococcal infection.
Discussion Asplenia may result from surgical splenectomy or functional hyposplenia as a result of conditions such as sickle cell anemia, celiac disease, and bone marrow transplant. These patients are at increased risk of infection from several infectious pathogens, particularly encapsulated bacteria such as S. pneumoniae, Haemophilus influenzae, and Neisseria meningitidis.1 Overwhelming postsplenectomy infection (OPSI) is a relatively rare complication, occurring in approximately 0.5% of patients, that can occur at any time, both immediately after surgery/ diagnosis or years later, resulting in a high mortality rate (from 40% up to 70% in some reports).1 Sepsis is of particular concern, as this population is not only at substantially increased risk for developing sepsis—more than 50 times that of the general population2—but also is at increased risk for mortality.1 Acute infectious purpura fulminans is a rare and life-threatening condition characterized by peripheral thrombosis caused by DIC
Send your immunization questions to the JAPhA Contributing Editors who coordinate the Vaccine Update column: ❚
❚
ja p h a .org
Mary S. Hayney, PharmD, BCPS, Associate Professor of Pharmacy, School of Pharmacy, University of Wisconsin, Madison (mshayney@pharmacy. wisc.edu) John D. Grabenstein, PhD, Director of Scientific Affairs, Merck Vaccine Division ([email protected])
Journal of the American Pharmacists Association
VACCINE UPDATE
and cutaneous purpuric hemorrhage and necrosis.3 Meningococcal sepsis is the most common cause of infectious purpura fulminans, followed by S. pneumoniae, though purpura fulminans has been reported in association with both viral and bacterial infections caused by numerous other pathogens, including group A and B Streptococci, Staphylococcus aureus, Escherichia coli, H. influenzae, and varicella. In the acute phase, purpura fulminans resulting from sepsis is associated with a high mortality rate (estimated 50%); patients who survive the acute phase ultimately face major morbidity due to progressive skin necrosis and secondary cutaneous infections.4 Our patient developed overwhelming pneumococcal sepsis resulting in the additional complications of DIC and purpura fulminans and eventually bilateral cutaneous gangrene. Purpura fulminans due to S. pneumoniae sepsis in an asplenic host has rarely been reported in the literature.4,5 Pneumococcal septicemia causing purpura fulminans has been reported even more rarely in asplenic patients who have previously been vaccinated5 and in patients with a normal spleen.6 Of important note, the majority of these cases have been described in patients with predisposition for an immunocompromised state. Our patient was a healthy adult without any known immunocompromised state other than asplenia.
Despite rare incidences of vaccine failure or inadequate serological response to immunization, pneumococcal vaccination in high-risk adult patients has been shown to significantly reduce the incidence of sepsis and potential subsequent purpura fulminans due to S. pneumoniae infection.7 In addition, patient counseling regarding awareness of increased risk of infection and the need for a clear vaccination history are necessary interventions. Of particular concern, current best practice preventive measures in asplenic patients are not being implemented.8 Practitioners must be cognizant of the immunizations needed to decrease morbidity and mortality in immunocompromised adults, including those with anatomic or functional asplenia. The 13-valent pneumococcal conjugate vaccine (PCV13) is now recommended for use in immunocompromised adult patients as part of a regimen during their next pneumococcal vaccination opportunity. Patients who have not been previously vaccinated should receive PCV13 first, followed by the 23-valent pneumococcal polysaccharide vaccine (PPSV23) at least 8 weeks later. Those who have been previously vaccinated with PPSV23 should be administered PCV13 1 year or later following PPSV23 vaccination. In addition, patients with immunocompromising conditions or asplenia requiring a second PPSV23 vaccination at a 5-year interval should
receive the PPSV23 vaccination again consistent with previous recommendations.9 Asplenic patients also should receive meningococcal and H. influenzae type b vaccine (Table 1), in addition to all other applicable vaccinations (e.g., annual influenza vaccination, tetanus, diphtheria, pertussis).10 Specific recommendations for meningococcal vaccination in patients with asplenia include administration of the meningococcal conjugate vaccine every 5 years after a two-dose primary series in adults aged 19 through 55 years. Unlike others receiving meningococcal vaccination at 56 years or older, the Advisory Committee on Immunization Practices recommends vaccination with the conjugate vaccine rather than the polysaccharide vaccine among patients with asplenia who were previously vaccinated with the meningococcal conjugate vaccine.11 If splenectomy is planned, these vaccinations should be given at least 2 weeks before surgery.12
Conclusion This case report describes a rare occurrence of OPSI due to S. pneumoniae that resulted in refractory septic shock, purpura fulminans, and ultimately death in an otherwise healthy patient decades following surgical splenectomy. Although OPSI is a relatively rare complication, morbidity and mortality remain high despite prompt, aggressive treatment. This case
Table 1. Supplementary ACIP vaccine recommendations for adults with asplenia Vaccine Pneumococcal PCV13 PPSV23
Dose
Route
Vaccination/revaccination schedule
0.5 mL 0.5 mL
Intramuscular Intramuscular/ subcutaneous
Pre/postasplenia at next vaccination opportunity Pre/postasplenia 8 weeks following PCV13, revaccinate 5 years after first dose of PPSV23, revaccinate at ≥65 years of age if ≥5 years since previous vaccination
Meningococcal MCV4
0.5 mL
Intramuscular (deltoid)
Pre/postasplenia, revaccinate 2 months following first dose of MCV4, revaccinate every 5 years
Haemophilus Influenzae Hib
0.5 mL
Intramuscular
Consider pre/postasplenia if not previously received
Abbreviations used: ACIP, Advisory Committee on Immunization Practices; Hib, Haemophilus influenzae type B; MCV4, quadrivalent meningococcal conjugate vaccine; PCV13, 13-valent pneumococcal conjugate vaccine; PPSV23, 23-valent pneumococcal polysaccharide vaccine. Journal of the American Pharmacists Association
j apha.org
JA N /FEB 2014 | 54:1 |
JAPhA 89
VACCINE UPDATE
fundamentally serves as a sober reminder for the critical importance of preventive measures, including vaccination and education of asplenic patients and awareness of the potentially fatal complications that arise if these measures are not instituted. Pharmacists, in collaboration with other health professionals, must take an active role as vaccination advocates and deliver sustained efforts to reduce preventable disease in these high-risk patients. Cyle White, PharmD, BCPS Pharmacotherapy resident University of Tennessee Medical Center Knoxville Anthony J. Guarascio, PharmD, BCPS Assistant Professor College of Pharmacy University of Tennessee Health Science Center Knoxville [email protected] Heather M. Draper, PharmD, BCPS Clinical Pharmacist, Emergency Medicine Mercy Health Saint Mary’s Grand Rapids, MI doi: 10.1331/JAPhA.2014.14505
90 JAPhA | 5 4 : 1 | JAN/F EB 2014
References 1. Di Sabatino A, Carsetti R, Corazza GR. Post-splenectomy and hyposplenic states. Lancet. 2011;378(9785):86–97. 2. Hansen K, Singer DB. Asplenic-hyposplenic overwhelming sepsis: postsplenectomy sepsis revisited. Pediatr Dev Pathol. 2001;4(2):105–21. 3. Betrosian AP, Berlet T, Agarwal B. Purpura fulminans in sepsis. Am J Med Sci. 2006;332(6):339–45. 4. Ward KM, Celebi JT, Gmyrek R, Grossman ME. Acute infectious purpura fulminans associated with asplenism or hyposplenism. J Am Acad Dermatol. 2002;47(4):493–6. 5. Minhas KM, Bashir S, Sarwari AR, Parker J. Pneumococcal purpura fulminans successfully treated with activated protein C. South Med J. 2008;101(10):1046–8.
8. Waghorn DJ. Overwhelming infection in asplenic patients: current best practice preventive measures are not being followed. J Clin Pathol. 2001;54(3):214–8. 9. Centers for Disease Control and Prevention. Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2012;61(40):816– 9. 10. ACIP Adult Immunization Work Group. Advisory Committee on Immunization Practices (ACIP) recommended immunization schedule for adults aged 19 years and older: United States, 2013. MMWR Surveill Summ. 2013;62(suppl 1):9–19.
6. Bramley PN, Shah P, Williams DJ, Losowsky MS. Pneumococcal Waterhouse-Friderichsen syndrome despite a normal spleen. Postgrad Med J. 1989;65(767):687–8.
11. Cohn AC, MacNeil JR, Clark TA, et al. Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2013;62(RR-2):1–28.
7. Shatz DV, Schinsky MF, Pais LB, et al. Immune responses of splenectomized trauma patients to the 23-valent pneumococcal polysaccharide vaccine at 1 versus 7 versus 14 days after splenectomy. J Trauma. 1998;44(5):760–5.
12. National Center for Immunization and Respiratory Diseases. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011;60(2):1–64.
ja p h a .org
Journal of the American Pharmacists Association
