A Case of Acute Purpura Fulminans Caused by Streptococcus pneumoniae

AUTHORS:
Pinky Jha, MD, MPH, and Sierra Jin, BS

CITATION:
Jha P, Jin S. A case of acute purpura fulminans caused by Streptococcus pneumoniae. Consultant. 2016;56(11):1010-1012.

A 60-year-old woman with history of chronic obstructive pulmonary disease presented to the emergency department with concern for progressive shortness of breath, productive cough, myalgia, and fever for 2 to 3 days.

On arrival, she was in respiratory distress and febrile. Her heart rate was 120 beats/min, respiratory rate was 30 breaths/min, blood pressure was 85/50 mm Hg, and oxygen saturation was 85% on room air. On physical examination, the patient was lethargic and tachypneic using accessory muscles. Lung auscultation revealed bibasilar crackles with scattered wheezes.

Laboratory investigations revealed the following values: hemoglobin, 13.2 g/dL; hematocrit, 40.8%; white blood cell (WBC) count, 1500/µL (bands, 39%; neutrophils, 32%; lymphocytes, 18%); platelet count, 131 × 10³/µL; blood urea nitrogen, 39 mg/dL; creatinine, 2.4 mg/dL; lactate, 41.4 mg/dL; anion gap, 19 mEq/L; aspartate aminotransferase, 454 U/L; alanine aminotransferase, 150 U/L; bilirubin, 1.7 mg/dL; and alkaline phosphatase, 240 U/L.

An electrocardiogram revealed sinus tachycardia. Chest radiography and computed tomography (CT) of the chest showed bilateral lower lobe pneumonia and emphysema.

She was admitted to the intensive care unit (ICU) for acute respiratory failure and septic shock with multiorgan failure. In the ICU, she was intubated and started on broad-spectrum intravenous antibiotics, fluids, and vasopressors. She also required continuous renal replacement therapy (CRRT) for acute renal failure. Blood culture tests were positive for Streptococcus pneumoniae. Based on culture sensitivity, the patient was switched to intravenous moxifloxacin. She was stabilized in the ICU and was extubated on day 3 of the hospitalization.

On day 5, the patient’s extremities were noted to be cool; she then rapidly developed well-demarcated, dark, mottling purpura on her forearms and legs bilaterally (Figures 1 and 2). Laboratory investigations revealed the following values: hemoglobin, 6.4 g/dL; hematocrit, 20%; WBC count, 4500/µL (neutrophils, 74%; lymphocytes, 19%; monocytes, 1%); platelet count, 38 × 10³/µL. Results of a peripheral blood smear showed schistocytes.

Figure 1. Bullae and vesicles on the patient’s hand, with gangrene of the fingers.

Figure 2. Areas of blue-black hemorrhagic necrosis with a surrounding erythematous border on the patient’s legs.

The vascular and plastic surgery teams were consulted for management of dry gangrene of the limbs. Biopsy of the lesion was done by the dermatology team. The hematology team was consulted to assess for potential disseminated intravascular coagulopathy (DIC), thrombocytopenic thrombotic purpura (TTP), and heparin-induced thrombocytopenia (HIT). Because of the high clinical suspicion for TTP, she was started on methylprednisolone and a 5-day course of plasmapheresis.

DIC and HIT subsequently were ruled out with a normal fibrinogen level and negative platelet factor 4 test results, and heparin was initiated for anticoagulation. TTP also was ruled out with normal haptoglobin levels and mildly diminished ADAMTS13 levels. Therefore, plasmapheresis was stopped, and tapering of methylprednisolone was initiated.

Histopathologic examination of the skin lesions showed the presence of perivascular inflammatory infiltrate in the dermis with microthrombi in the dermal vessels. The results of tests for antiphospholipid antibodies, lupus anticoagulant, antinuclear antibodies, antineutrophil cytoplasmic antibodies, myeloperoxidase, proteinase 3, anti–double-stranded DNA, VDRL, antistreptolysin O titer, hepatitis panel, cryoglobulin, and serum protein electrophoresis were negative. Stevens-Johnson syndrome/toxic epidermal necrolysis and angioinvasive organisms subsequently were ruled out by punch biopsy test results.

Based on the typical clinical presentation, the laboratory data, and results of skin biopsy, a diagnosis of acute infectious purpura fulminans (PF) following sepsis due to S pneumoniae pneumonia was made. Meanwhile, the skin lesions were protected with loose gauze, lamb’s wool boots, and petroleum jelly.

On day 11, the patient became hypotensive with an acute drop in hemoglobin to 4 g/dL. An abdominal CT scan showed a rectus sheath hematoma, a right psoas hematoma, and left lower lung lobe necrosis. The patient received transfusion with packed red blood cells, platelets, and fresh frozen plasma. Anticoagulation was withheld.

The patient was reintubated on day 12 for respiratory distress secondary to fluid overload and was extubated on day 15. Transthoracic echocardiography findings showed global hypokinesia and a left ventricular ejection fraction of 10%. Hemodialysis was initiated on day 17 with completion of CRRT. At that time, the patient was transferred to the medical floor with no respiratory distress and a stable hemoglobin level. The patient completed a course of moxifloxacin for S pneumoniae and bacteremia. She remained stable hemodynamically. Liver function test results, complete blood cell count findings, and renal function test results also improved.

Over the following weeks, the patient continued to receive hemodialysis and began working with physical therapy as she prepared to undergo further rehabilitation at a long-term acute-care facility.

The patient was readmitted 6 weeks later to the vascular surgery service for wound debridement, followed by bilateral above-the-knee amputation and right hand amputation.

Discussion

PF is a potentially disabling and life-threatening disorder caused by microvascular occlusion followed by hemorrhagic infarction of the dermis resulting in large purpura and bullae. Three distinct categories of PF can be identified: inherited or acquired abnormalities of protein C or other coagulation systems, acute infectious PF, and idiopathic PF.^1,2 Most cases of acute infectious PF are associated with meningococcal sepsis.¹ Approximately 60% to 70% of cases of acute PF have been reported among children younger than 2 years,^1,3 whereas our patient was 60 years old.

The lesions of PF have a characteristic appearance, which distinguishes them from other purpuric lesions.^2,4 Erythema is rapidly followed by irregular central areas of blue-black hemorrhagic necrosis with a surrounding erythematous border.⁵ Late findings are the formation of vesicles and bullae, which mark the development of hemorrhagic necrosis, and finally firm eschar, which ultimately sloughs. The distal extremities are often most severely involved.¹

The majority of cases of pneumococcus-related PF occur in asplenic patients, since the spleen is crucial in clearing encapsulated organisms.⁶ Our patient had no history of splenic trauma, sickle cell disease, prior splenectomy, or other known hyposplenism, and her spleen was morphologically normal on abdominal CT scan.

The pathogenesis is described as a “Schwartzman-like” reaction, which is a necrotizing inflammatory lesion provoked by endotoxin from gram-negative bacteria.⁴ Management must be tailored to the individual patient and involves supportive therapy and replacement of blood products and clotting factors as appropriate.⁴

In acute infectious PF, aggressive resuscitation, antibiotics, and volume expansion are important for good outcome. Correction of acid-base and electrolyte abnormalities and early use of oxygen and mechanical ventilation are helpful.⁴ Fresh frozen plasma and platelets are used only for significant bleeding. Heparin is used to inhibit the intravascular coagulation process. Other experimental modalities such as the administration of protein C concentrate, antithrombin III concentrate, hyperbaric oxygen, and plasmapheresis have been tried.⁷ Early evaluation by vascular surgery is important for wound debridement, fasciotomies, and amputations.

This patient’s case highlights the need for a high index of suspicion for this life-threatening complication associated with sepsis and to differentiate it from conditions such as TTP, collagen vascular diseases, and other conditions associated with peripheral gangrene.

Pinky Jha, MD, MPH, is an assistant professor in the Division of General Internal Medicine at the Medical College of Wisconsin in Milwaukee.

Sierra Jin, BS, is a third-year medical student at the Medical College of Wisconsin in Milwaukee.

References:

1. Kalra OP, Agarwal S, Khaira A. Acute infectious purpura fulminans due to Klebsiella pneumoniae: A case report. J Indian Acad Clin Med. 2003;4(2):​156-158.
2. Adcock DM, Brozna J, Marlar RA. Proposed classification and pathologic mechanisms of purpura fulminans and skin necrosis. Semin Thromb Hemost. 1990;16(4):333-340.
3. Cnota JF, Barton LL, Rhee KH. Purpura fulminans associated with Streptococcus pneumoniae infection in a child. Pediatr Emerg Care. 1999;15(3):​187-188.
4. Nolan J, Sinclair R. Review of management of purpura fulminans and two case reports. Br J Anaesth. 2001;86(4):581-586.
5. Adcock DM, Hicks MJ. Dermatopathology of skin necrosis associated with purpura fulminans. Semin Thromb Hemost. 1990;16(4):283-292.
6. Saraceni C, Schwed-Lustgarten D. Pneumococcal sepsis-induced purpura fulminans in an asplenic adult patient without disseminated intravascular coagulation. Am J Med Sci. 2013;346(6):514-516.
7. Darmstadt GL. Acute infectious purpura fulminans: pathogenesis and medical management. Pediatr Dermatol. 1998;15(3):169-183.