Pneumococcal sepsis can usually be traced back to a primary site that was left untreated, facilitating spread of the infection into the bloodstream. Most patients have predisposing factors, such as splenectomy, recent surgery, or other immunocompromised states. Typically the blood is seeded from pneumonia or meningitis. Cases of primary pneumococcemia resulting in death within 4 hours of presentation in a patient who had not had splenectomy and with no significant medical history are exceedingly uncommon.

Case Presentation

A 46-year-old woman was brought to the emergency department by a basic life support ambulance. She was triaged with a chief complaint of "leg burning." Vital signs on arrival were: blood pressure, 119/51 mm Hg; heart rate, 84 beats/min; respiratory rate, 20 breaths/min; temperature, 36.8 F; oxygen saturation, 98% on room air. The patient was awake, alert, and oriented to person, place, and time. Physical examination showed mottled, nonblanching skin, which was worst on her abdomen and extremities, and petechiae on the trunk and back. Her hands and feet were pale and cool, although the distal pulses were intact. No cellulitis, skin abscess, or cervical or inguinal lymphadenopathy were evident. Her lips and mucous membranes were cyanotic but moist. The rest of the examination was unremarkable.

Her primary complaint was bilateral burning in her anterior thighs and numbness in her feet, which began 3 hours before presentation. She had traveled to New Jersey from San Francisco for business and was staying at a local hotel. She denied any other recent travel, including outside of the United States. She reported she had a few episodes of vomiting and diarrhea, with chills but without fever, the previous night. She had no other significant medical history.

The initial presumed diagnosis was meningococcemia, and she was immediately given intravenous (IV) vancomycin 1 g and IV ceftriaxone sodium 2 g. After an emergent consult with the infectious diseases attending physician, the patient was given hydrocortisone sodium succinate 100 mg IV. Two large-bore IV lines were also placed in the antecubital region.

An immediate spinal tap was performed, during which the patient remained awake and alert, with stable vital signs, although she did have a transient nosebleed after the procedure. Because of disseminated intravascular coagulation, 4 units of fresh frozen plasma were ordered, along with 2 units of packed red blood cells (RBCs). The cerebrospinal fluid (CSF) Gram's stain showed no white blood cells or organisms. The underlying cause of illness remained unclear.

A Foley catheter was placed, with no urine output returned. Her heart rate increased to 110 beats/min, and her blood pressure decreased to 100 mm Hg systolic, but she remained neurologically intact. The patient continued to complain of severe, bilateral, burning pain in the thighs and was given morphine sulfate IV in 2-mg increments. Her hands and feet were becoming paler, and her skin appeared more mottled.

The patient was moved to the intensive care unit (ICU) before the laboratory results arrived. An emergent hematology consult was obtained in the ICU, and a peripheral smear showed no evidence of schistocytes. Bone marrow aspiration was not done because of the patient's acute deterioration. A renal consult was immediately obtained to evaluate the anuria. Laboratory test results were returned at this time (Table 1).

During the next 30 minutes, the patient became increasingly tachycardic and hypotensive and then went into cardiac arrest. Advanced cardiac life support measures were performed, but she was pronounced dead 2 hours after arriving at the hospital. The following day, blood and CSF cultures grew Streptococcus pneumoniae. Autopsy did not reveal a focal site of infection or any other pathology.

Discussion

Pneumococcal sepsis
S pneumoniae is an encapsulated gram-positive coccus. The capsule helps the bacteria escape phagocytosis and leads to a decreased inflammatory response by naïve hosts. In contrast, some immunity is provided to those who have been previously exposed to S pneumoniae. As a result, infection rarely causes invasive disease in healthy adults; when it does, immunodeficiency should be suspected.

Many conditions predispose to pneumococcal infection, including asplenia, splenectomy, complement disorders, and defective antibody formation (often the result of HIV infection, lymphoma, leukemia, or hypogammaglobulinemia).

Our case is unique in that an otherwise healthy woman, with no known medical problems, presented with pneumococcal sepsis that proved to be rapidly fatal. Another unusual aspect of this case is the presentation of purpura fulminans.

Purpura fulminans
Purpura fulminans is characterized by widespread ecchymosis and ischemic infarction of the skin. The lesions can progress to hemorrhagic bullae and skin necrosis and are usually seen on the extremities, buttocks, and abdomen; the chest, face, scalp, and mucous membranes are typically spared. Although the lesions of purpura fulminans are normally confined to the skin, any organ system can be affected, including the kidneys, brain, gastrointestinal tract, and lungs. Patients are often acutely ill at presentation, with high fever, tachycardia, and shock. Other clinical manifestations can include hypotension and disseminated intravascular coagulation.

Laboratory findings often indicate a consumptive coagulopathy, with a low platelet count, low concentrations of fibrinogen and clotting factors, and increased fibrin degradation products.

The management of purpura fulminans remains controversial. Treatment modalities range from reversing the precipitating cause and providing supportive care to administering fresh frozen plasma, antibiotics, steroids, hyperbaric oxygen therapy, heparin, and IV low-molecular-weight dextran. Despite this, the mortality rate is approximately 18%.¹

Purpura fulminans is often secondary to a bacterial, fungal, or viral illness, most often meningococcemia, varicella, or scarlet fever. Patients with pneumococcemia are more vulnerable to developing purpura fulminans if they have one of the following conditions²:

• An underlying medical condition, such as HIV infection, sickle-cell anemia, alcoholism, hypogammaglobulinemia, upper respiratory tract infection, or diabetes mellitus
• Undergone splenectomy or any recent surgery
• A history of recent childbirth.

Our patient presented with purpura fulminans, secondary to widespread sepsis from S pneumoniae. The ecchymotic and purpuric rash was observed over her trunk, back, and extremities; her face was spared, but the lips and mucous membranes were cyanotic. Although she appeared to have disseminated intravascular coagulation, laboratory workup for this condition was not processed. Despite treatment with fresh frozen plasma, fluids, packed RBCs, and IV antibiotics, she rapidly decompensated and died. She had no underlying conditions, such as HIV infection or malignancy, which are normally associated with a presentation of overwhelming pneumococcal sepsis.

Similar cases
Several similar reported cases involve women of different ages (Table 2). One case is a 43-year-old woman who had pneumococcal sepsis complicated by purpura fulminans after she had a cut on her finger that was infected with pneumococcus.³ This patient's course of illness progressed more slowly. Within 24 hours, she developed thrombocytopenia and had an increased blood urea nitrogen/creatinine ratio and elevations in alanine aminotransferase, total bilirubin, prothrombin time, and partial thromboplastin time. She later became disoriented, confused, afebrile, jaundiced, and anuric, and she had respiratory failure. Despite this, the woman survived after treatment with IV antibiotics, dialysis, and plasma exchange. Although no identifiable source of infection was found, she had a more indolent course of illness and survived with supportive therapy.³ With the exception of plasma exchange, our patient received the same initial treatment.

Another case of pneumococcal sepsis complicated by purpura fulminans involved a 50-year-old patient who had a prodrome of upper respiratory tract infection, with fevers, headache, and a nonproductive cough.⁴ This woman also rapidly decompensated, presented the next morning with nausea, vomiting, bowel and bladder incontinence, confusion, and purple discoloration of her skin. She rapidly went into shock, was intubated, and developed cold, mottled extremities with ecchymosis extending to the extremities, face, and trunk. She died rapidly, despite supportive treatment with fresh frozen plasma, platelet transfusion, dopamine, IV antibiotics, and mechanical ventilation.⁴

Despite some similarities, that patient differed significantly from ours, except for her prodrome. She was elderly, had a history of fevers before admission, and had a more protracted course, dying 36 hours after admission. In addition, postmortem examination revealed diffuse interstitial and alveolar edema with hemorrhagic exudate, hemorrhagic necrosis of the adrenal glands, and hemorrhagic gastritis, consistent with acute respiratory distress syndrome (ARDS) and Waterhouse-Friderichsen syndrome.⁴ Our patient had only mild ARDS on autopsy; she was younger, afebrile, and had no known medical conditions.

Perhaps most similar in initial presentation to our patient was a case involving a 15-month-old girl.⁵ Like our patient, the girl had prodromal symptoms of nausea, vomiting, and fatigue. However, 2 days after she began vomiting, she was unresponsive and had an erythematous, nonblanching, perioral rash. At the time of presentation to the emergency department, the child had a diffuse petechial and purpuric rash over her face and trunk; her legs and arms were cool. This child also had leukocytosis, thrombocytosis, and elevated liver enzymes. However, CSF culture grew S pneumoniae within 24 hours. Despite treatment with IV ceftriaxone sodium and vancomycin, mechanical ventilation, fluid resuscitation, peritoneal dialysis, and blood product transfusion, her pupils became fixed and dilated, and she developed hypertension within 9 hours of presentation. Life support was withdrawn the next day. The cause of death was determined to be meningitis, with edema and cerebellum tonsillar herniation, sepsis, and disseminated intravascular coagulation.⁵

Another case of S pneumoniae sepsis with purpura fulminans involved a woman who had undergone bariatric surgery 1 year earlier.⁶ This 63-year-old patient had a more indolent course of illness than our patient. She had lost 57 kg during the year after her surgery. She presented with severe dehydration and diarrhea, and a stool culture was positive for Clostridium difficile. On her third hospital day, the patient became dyspneic, and was diagnosed with deep-vein thrombosis and pulmonary embolism. At that time, her blood cultures grew S pneumoniae. The following day she became hypotensive, hypoxic, and azotemic; a petechial rash appeared over her feet, and she was diagnosed with disseminated intravascular coagulation. She continued to receive IV antibiotics, and dopamine and drotrecogin alfa were added to her regimen. She was also started on vitamins A, C, and D replacement therapy, because she was believed to be malnourished as a result of the diarrhea. This patient eventually recovered and became fully ambulatory.⁶

It is postulated that she was more susceptible to illness because of her malnutrition; she continued to take the vitamin supplementation. Unlike our patient, this woman was malnourished and had been hospitalized for 4 days before developing purpura fulminans, during which time she also developed a pulmonary embolus, which she survived. In contrast, our patient, who was younger and did not have any premorbid medical conditions, died 2 hours after arriving at the hospital.

Conclusion

Primary pneumococcal sepsis is unusual in adults without predisposing factors, such as HIV infection, splenectomy, lymphoma, and immunocompromised states. Purpura fulminans is a focal ischemic skin manifestation often seen secondary to bacterial, viral, and fungal infections. Our case is unusual in that it involved a young woman who rapidly decompensated, despite supportive treatment. Although she was later found to have overwhelming sepsis from S pneumoniae, no primary site was ever identified. In addition, no underlying medical conditions were found, which could have made her more susceptible to pneumococcal sepsis and purpura fulminans.

References

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