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Purpura-Producing Streptococcus pneumoniae

Crum, Nancy F. MD, MPH*; Lederman, Edith R. MD

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Infectious Diseases in Clinical Practice: September 2004 - Volume 12 - Issue 5 - p 288-290
doi: 10.1097/01.idc.0000143977.32716.43
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An 18-year-old male presented with a 3-week history of rhinorrhea that progressed to fevers, a dry cough, and chills over the 4 days before admission. The patient noted a rash that began on both ankles and spread proximally to his distal thighs 2 days before admission. The rash was not painful or pruritic. He denied headache, confusion, dyspnea, or chest pain. He was without any significant past medical or surgical history and was on no medications. He had moved to San Diego, CA, from Texas one month before presentation after enlisting in the US Marines. He reported no exposures to ticks or animals. Standard Basic Training-related immunizations 1 month before admission included the pneumococcal and meningococcal vaccines. On examination, his temperature was 38.2°C, pulse of 78 beats per minute, blood pressure 110/59 mm Hg, respiratory rate of 20 breaths per minute, and oxygen saturation of 99%. He was ill-appearing. His lungs had decreased breath sounds in the left lower lobe with accompanying crackles. Skin examination showed a nonblanching, nonpalpable, purpuric rash extending from both ankles to his thighs (Fig. 1). He had no other cutaneous findings, and the remainder of his examination was normal.

Nonpalpable purpura symmetrically distributed on the lower extremities due to Streptococcus pneumoniae.

Laboratory values included a white blood cell count of 15,100 cells/mm3, hemoglobin of 13.2 mg/dL, platelets 263,000, and a normal chemistry panel. Liver function tests were normal except for an albumin of 2.6 mg/dL. International Normalized Ratio was elevated at 1.4 with a prothrombin time of 13.8 seconds, and partial thromboplastin time of 34.3 seconds; a disseminated intravascular coagulation panel was negative. The elevated INR resolved over 48 hours without any specific therapy. Chest radiograph demonstrated a left lower lobe infiltrate without effusion or adenopathy.

The patient was treated with ceftriaxone 2 g intravenously and levofloxacin 500 mg daily for community-acquired pneumonia. He continued to have temperatures of up to 39.1°C for the first 36 hours and then became afebrile. Given the possibility of Neisseria meningitidis, 80 men who slept in the same room in the barracks received a single dose of levofloxacin (500 mg).

A workup for the etiology of the patient's illness included 2 sets of blood cultures; Chlamydia pneumoniae and Mycoplasma pneumoniae IgM and IgG serologies; viral cultures for adenovirus, respiratory syncytial virus, influenzae, and parainfluenzae (Rhinoprobe); an antistreptolysin O titer; and throat culture for group A streptococcus and N. meningitidis. All of these tests were negative. The patient was unable to produce a sputum sample despite multiple attempts. A polymerase chain reaction for N. meningitidis on acute serum was negative at the Naval Health Research Center, San Diego. The urine pneumococcal antigen (Binax NOW) was positive. The patient was discharged after 4 days of hospitalization to complete a 10-day course of levofloxacin. At follow-up 10 days after discharge, his cough and purpuric rash had completed resolved, and he returned to military training. No other cases of Streptococcus pneumoniae-induced purpuric rashes have occurred among colocated military trainees.


Although S. pneumoniae is the most common cause of community-acquired pneumonia, causing approximately 200 cases per 100,000 persons,1 clinical infections in which this organism induces purpura are rare.2-4 We report the first case of S. pneumoniae benign purpura in the setting of uncomplicated community-acquired pneumonia.

The pathogenesis of S. pneumoniae purpura formation involves the hydrolysis of the muramic acid-alanine bonds of the cell wall by its own autolysin (N-acetylmuramyl-L-alanine amidase) which produces a heat-labile glycan-teichoic acid fragment, named the "purpura-producing principle." Purpura-producing principle was first described in the 1920s5 and has subsequently been elucidated by Chetty and Kreger6,7 as a heat-stable glycan-teichoic acid fragment of the bacterial cell wall with a molecular weight of about 2.6×107. The introduction of purpura-producing principle in animal models can induce purpura within 6 to 8 hours; the skin findings occur alone without other evidence of clinical disease, and the purpura usually resolves in 4 to 6 days.6,8 Host susceptibility also plays a role in purpura formation; not all mice injected with purpura-producing principle developed purpura, just as most humans with S. pneumoniae infections do not develop skin manifestations. The exact underlying host factors or genetics have not been elucidated.

The differential diagnosis of purpura due to an infectious agent includes meningococcemia, group A and B streptococci, rickettsiae, varicella zoster virus, and Gram-negative sepsis. Purpura due to S. pneumoniae usually occurs in the setting of purpura fulminans, characterized by ecchymotic skin lesions, fever, hypotension, bacteremia, disseminated intravascular coagulation, and potentially extremity loss due to gangrene; the mortality rate is 35%.9 The first description of purpura fulminans is attributed to Henoch during the 1880s with subsequent classification as a generalized Shwartzman phenomenon.3 The mechanism of purpura during these infections is most often a manifestation of underlying disseminated intravascular coagulation, stimulated by endotoxin-induced immune complexes or complement activation.2,10 Most cases of purpura fulminans due to S. pneumoniae infections occur in asplenic or immunocompromised patients11-13; cases among immunocompetent persons are less common.3,14-19 Purpura as the sole manifestation of S. pneumoniae has been reported only once before in an immunocompetent 4-month old who presented with purpura without other clinical manifestations; blood cultures grew pneumococcus, and the patient had an uneventful recovery.20 Petechiae have also been associated with a wide range of febrile infections in children including S. pneumoniae.21,22

Our case describes benign purpura occurring with an uncomplicated community-acquired pneumonia due to S. pneumoniae. We established the diagnosis using the Binax NOW antigen test, which identifies the S. pneumoniae C polysaccharide antigen in urine and has a specificity of 97%.23,24 Urine antigen testing may be useful, since 75-90% of S. pneumoniae cases have sterile blood cultures. An additional advantage is that the test is not affected by prior antibiotic administration. We acknowledge that our diagnosis is presumptive since cultures from sterile sites (ie, blood) were negative; an extensive workup for other etiologies was negative. Unlike most previously described purpura fulminans associated with pneumococcal infections, our case had nonpalpable purpura in the absence of disseminated intravascular coagulation or septic shock. S. pneumoniae should be considered among patients presenting with purpura and pneumonia, sepsis, or meningitis, regardless of vaccination status. Empiric antibiotic therapy of such cases should cover both S. pneumoniae and N. meningitidis, with consideration of the current resistance patterns for these organisms.1 Novel therapies, such as protein C concentrate, are promising for the treatment of purpura fulminans.25


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