Asplenia and fever

Abstract

A 45-year-old-man presented with the abrupt onset of a fever over 30 years after surgical splenectomy. He presented with symptoms and findings that seemed consistent with influenza. He rapidly developed fulminant meningitis that resulted in his death.

Pneumococcal meningitis remains a devastating illness with high mortality and morbidity despite all of the advances in medical care. Pneumococcal meningitis has been found in some studies to be over four times deadlier than other causes of bacterial meningitis in adults, and over six times more likely to cause other poor outcomes (1). Survivors of meningitis frequently are left with chronic neurologic deficits. Streptococcus pneumoniae, otherwise known as pneumococcus, is an encapsulated bacterial organism. Individuals who lack a functional spleen are at higher risk for infection from encapsulated organisms. A person without a functional spleen is at risk for postsplenectomy sepsis (PSS) and overwhelming infection, including pneumococcal meningitis. They are also more likely to have a devastating outcome despite current treatment options. Physicians and caregivers in the outpatient clinic setting will rarely, if ever, see a patient presenting with PSS. As such, primary caregivers are less familiar with the best practice guidelines associated with PSS than caregivers in the hospital setting.

CASE DESCRIPTION

A 45-year-old man who had a history of a splenectomy at age 13 secondary to idiopathic thrombocytopenic purpura presented with the abrupt onset of a high fever, myalgias, fatigue, loose stools, and headache. He had received an influenza vaccine about 2 months earlier. His temperature was 102.3°F and blood pressure, 110/74 mm Hg. He appeared sick, answered questions appropriately, and had no nuchal rigidity; head, ear, eye, nose, or throat abnormalities; rales or rhonchi; abdominal abnormalities; or evidence of dermal cellulitis. A rapid influenza test was negative. He was sent home on oseltamivir with instructions to call back if his clinical situation changed. The next day his temperature was 99.4°F. He still had myalgias and mild diarrhea and had developed a “puffiness” in his hands.

He became confused that night at home and was taken to the emergency department. His blood pressure was 129/80 mm Hg and heart rate, 76 beats per minute. He was in distress, moaning, combative, and not following commands, but had reactive pupils, a supple neck, and no other abnormalities. Computed tomographic scan of the head revealed no apparent disease. A lumbar puncture was described by the emergency room physician as having high opening pressure with cloudy fluid, and specifically that the cerebrospinal fluid (CSF) “flew 3 feet with patient lying on side.” The CSF had a protein of 425 mg/dL and a glucose of <5 mg/dL. Gram stain revealed Gram-positive cocci in pairs. Pneumococcal antigen was present.

Intravenous antibiotics (vancomycin and cephtriaxone) were immediately started. He experienced respiratory arrest nearly 6 hours after arrival to the emergency department. He was intubated and ventilated, but cardiac arrest occurred. After several rounds of cardiopulmonary resuscitation and the addition of multiple cardiac vasopressor medications, his pulse was stable. He was given ventilator support and intensive therapy, but never regained consciousness and died 3 days later.

DISCUSSION

Streptococcus pneumoniae is the most common bacteria implicated in overwhelming PSS. Some studies have suggested it might be responsible for as many as 90% of these devastating infections (2). The initial infection leading to pneumococcal meningitis usually presents with vague symptoms such as fever, chills, malaise, headache, and various gastrointestinal symptoms. Bacterial meningitis often presents with only one of the classic meningitis triad: a) fever, b) neck stiffness (i.e., nuchal rigidity), and c) altered mental status. A delay in diagnosis and treatment of meningitis can be devastating and fatal. Studies have shown a triphasic progression to bacterial meningitis: from a nonspecific illness phase to a bacteremic phase to finally bacteremic seeding of the CNS and the meningitic phase (3). Bonadio explained:

Symptoms characterizing each phase can be heterogenous, can vary in type and duration, and are often of a ‘nonspecific’ nature (e.g. fever, vomiting, alterations in behavior and activity) that can mimic those indicative of less serious, nonmeningitic illnesses. The relatively more ‘specific’ symptoms of meningitis (e.g. nuchal rigidity, bulging fontanelle, altered mental status/neurologic deficit) are not invariably present, especially early in the course of the infection (3).

These phases can progress more rapidly in patients without a functional spleen, sometimes over the course of a few hours rather than days. Our patient presented with only one symptom of the classic meningitis triad (fever). He began showing mental status changes about 36 hours after initial presentation. He was never reported to have nuchal rigidity.

The patient was initially thought to have influenza. The presentation of a variety of infections can mimic influenza, especially in early phases. If the patient has not received an influenza vaccine or has a positive rapid influenza test, one can be more confident of the diagnosis; however, the absence of either of these two does not rule out influenza as the causative agent. The influenza vaccine's effectiveness against influenza A and B varies from 50% to 90%. The rapid influenza antigen tests that are used in most primary care offices range in sensitivity from 10% to 70%. The Centers for Disease Control and Prevention stated:

Negative results of [rapid influenza diagnostic tests] do not exclude influenza virus infection in patients with signs and symptoms suggestive of influenza. Therefore, antiviral treatment should not be withheld from patients with suspected influenza, even if they test negative. While influenza vaccine is the best way to prevent influenza, a history of influenza vaccination does not rule out influenza virus infection in an ill patient with clinical signs and symptoms compatible with influenza (4).

Our patient had a splenectomy as a child, increasing his risk of serious infection in the setting of a febrile illness. PSS is most common in the first few years after a splenectomy, but may appear even decades later. Current recommendations for vaccines prior to a splenectomy call for a patient to receive a 13-valent pneumococcal conjugate vaccine (PCV13) 8 weeks prior, and then a pneumococcal polysaccharide vaccine (PPSV23) at least 14 days prior to the surgery. A Haemophilus influenza type b vaccine (Hib) and a quadrivalent meningococcal conjugate vaccine (MenACWY) should be given at least 14 days prior to the procedure in those who have not previously been vaccinated for either of these organisms. It is also recommended that both children and adults without a functional spleen be reimmunized 5 years after their initial vaccination with a PPSV23, and again at the age of 65 (5). The MenACWY should be repeated every 5 years after the splenectomy (5). Yearly influenza immunizations are recommended. Asplenic adults are not recommended to take prophylactic antibiotics, but should have antibiotics available to them to “be taken at the first sign of infection (increase in body temperature, malaise or shivering) if the patient is unable to obtain prompt medical attention. However, in such situations medical help should still be sought without delay” (6). “Prompt” medical attention is defined as less than 2 hours (5).

In an emergency room or hospital setting, appropriate evaluation and treatment for an asplenic febrile patient should include a complete blood count with differential, blood culture with Gram stain, arterial blood gas analysis, chest x-ray, and consideration for lumbar puncture with CSF studies. None of these evaluations should delay the initiation of appropriate broad-spectrum intravenous antibiotics. The Surviving Sepsis Campaign guidelines state that antibiotics should be administered in a patient suspected of sepsis within 1 hour of presentation (7). Delay in starting antibiotics for any reason is associated with a poor outcome.

There is fairly clear understanding of the risks to asplenic patients and of PSS among hospital specialists and hospital-based physicians, most likely because of the frequency with which they encounter these patients. Conversely, in the primary care setting, experience and familiarity with these patients is lower. A study published in the Journal of Clinical Pathology “suggests a continuing broad failure to attain currently accepted best practice in the management of asplenic patients” (8). Primary care literature has published very few articles reviewing the risks to asplenic patients and of PSS. A review of the New England Journal of Medicine and the Journal of the American Medical Association found only two articles related to PSS published in the last 10 years (5, 9). The overwhelming majority of articles related to these topics are published in surgical or specialty literature. In this time of avoiding the overuse of antibiotics due to the development of resistance, it is important to know this important exception.