Group B Streptococcal Cellulitis In A Child With Steroid-Responsive Nephrotic Syndrome

Although infectious complications of nephrotic syndrome are common, group B Streptococcus is a rare pathogen in these patients. We present a 4-year-old child with nephrotic syndrome who developed group B streptococcal cellulitis and bacteremia, an association not previously discussed in the literature, and review the factors that predispose patients with nephrotic syndrome to infection. Group B Streptococcu s (GBS), or Streptococcus agalactiae, is well-known as a pathogen in neonates and pregnant women. It also is a potential pathogen in adults and children with other immunocompromising conditions. The association of nephrotic syndrome with invasive GBS infection has, to our knowledge, been described only twice, and both patients had GBS peritonitis. 1, 2 We present a child with nephrotic syndrome who developed GBS bacteremia and cellulitis and review the factors that may have predisposed him to developing this infection. This presentation is a reminder that GBS should be considered a potential pathogen in patients of any age in whom there is an alteration of humoral immunity. Case report. A 4-year-old Caucasian boy with a history of multiple congenital anomalies of unknown etiology, including absence of the arms, severe scoliosis and bowel malrotation, was admitted to Texas Children’s Hospital with a 2-week history of a 10-pound weight gain and development of periorbital, abdominal and lower extremity edema. Otherwise previously healthy, the patient’s only prior hospitalization had been for surgical correction of the bowel malrotation. At admission the patient was afebrile and had normal vital signs. The initial physical examination was notable for dysmorphic facial features, absence of the arms at the shoulders and moderate anasarca with abdominal ascites and pitting edema of the trunk and extremities. Except for edema the skin evaluation was unremarkable. A urine specimen was slightly cloudy and had a specific gravity of >1.035, pH 6.0, 4+ protein, 1+ bilirubin, 2+ blood, 5 to 20 granular casts/high power field (hpf), 0 to 4 red blood cells/hpf and 0 to 4 white blood cells/hpf. The serum sodium was 136 mmol/l, potassium 5.1 mmol/l, chloride 109 mmol/l, bicarbonate 27 mmol/l, blood urea nitrogen 13 mg/dl, creatinine 0.2 mg/dl, glucose 70 mg/dl, protein 4.3 g/dl, albumin 1.6 g/dl, triglyceride 110 mg/dl and cholesterol 456 mg/dl (normal range, 135 to 200). The C3 was 142 (normal range, 89 to 170), C4 was 24 (normal range, 14 to 36), and a fluorescent antinuclear antibody screening test was nonspecific with a 1:40 speckled pattern. A 24-h urine collection measured 914 mg of protein (55 mg/m 2 /h). A diagnosis of nephrotic syndrome was made, and therapy was initiated with a regimen of intravenous methylprednisolone (2 mg/kg/day), furosemide and albumin infusions along with sodium and water restriction. On the third hospital day he developed a fever to 104.4°F and an area of dark violaceous discoloration measuring 4 by 6 cm over the left lower quadrant of his abdomen bordering the left groin. The area was indurated, warm and tender. It was surrounded by a faint erythema that extended over the left flank. Bowel sounds were active, and the remainder of the abdomen was nontender without guarding or rebound. The patient’s blood pressure remained stable, and mental status was unaltered. The white blood cell count was 30 100/mm 3 (42% neutrophils, 22% band forms, 25% lymphocytes, 10% monocytes and 1% eosinophils), hemoglobin 10.3 g/dl, hematocrit 30.6% and platelet count 533 000/mm 3. Blood and urine cultures were obtained, and vancomycin, amikacin and ceftazidime therapy was initiated. The blood culture grew GBS that later was characterized as a serotype V strain, and the urine culture was sterile. When the organism was identified, the antimicrobial regimen was changed to ampicillin (200 mg/kg/day) alone. (Ampicillin was used rather than penicillin G because of a temporary shortage of penicillin.) Within 3 days antibiotics commencement, the abdominal wall erythema and tenderness resolved. The patient completed a 10-day course of intravenous ampicillin, along with the steroid and diuretic regimen for the nephrotic syndrome. At discharge the patient’s edema was resolved, and the urinalysis was negative for protein. Prednisone, administered orally, was continued at the time of hospital discharge, and the patient was scheduled for follow-up in the renal clinic. Discussion. Nephrotic syndrome, defined as edema with hypoalbuminemia (<2.5 g/dl) and proteinuria (>40 mg/m 2 /h), is most commonly associated with minimal change disease in children. Before the advent of antibiotic and steroid use for this condition, the mortality rate was >40% with one-half of the deaths secondary to infectious complications. 3 This mortality rate has now decreased to ∼4%, but infections remain a significant cause of morbidity and occasionally mortality in nephrotic patients. 4 Immune system function in nephrotic syndrome has been studied extensively to identify factors predisposing patients to infection. Almost every aspect of the immune system is affected in the syndrome. First, serum IgG and IgA are low in nephrotic patients, and IgM is high, likely secondary both to urinary loss and defective immunoglobulin class-switching. 5 Second, the plasma of patients with nephrotic syndrome impairs lymphocyte function, perhaps because of a circulating suppressor lymphokine. 6 Third, several components of the complement cascade, including proteins of the alternative pathway, are low in the serum of nephrotics. 7 Finally, splenic hypofunction has been demonstrated in nephrotic syndrome patients. 8 Each of these factors, coupled with the immunosuppressive therapy for nephrotic syndrome, may contribute to enhancing susceptibility to infection. Encapsulated organisms, such as Streptococcus pneumoniae or GBS, likely have an advantage in nephrotic patients because of impairment of the alternative complement cascade and splenic function, key components in their removal in the immunocompetent patient. The classic infection in children with nephrotic syndrome is S. pneumoniae peritonitis. 1 Gram-negative rods, including Escherichia coli, also are major pathogens in this patient group. In addition to peritonitis, cellulitis and bacteremia without a focus are common infectious complications of nephrotic syndrome. 4 GBS is a known cause of infection in neonates and elderly adults, and it occasionally manifests as cellulitis. 9, 10 Although renal failure is a known predisposing factor to GBS infection, 9 only two patients with GBS infection complicating nephrotic syndrome have been reported. 1, 2 These were a 4-year-old and a 12-year-old, each receiving steroid treatment for known nephrotic syndrome; both developed GBS peritonitis. To our knowledge this is the first report of a patient with GBS cellulitis and nephrotic syndrome. The GBS serotype isolated from this patient was type V. Serotype V isolates have caused an increasing proportion of invasive disease since their emergence in the mid-1980s. According to prospective population-based surveillance data, serotype V now accounts for a substantial proportion of GBS disease in neonates, pregnant women and nonpregnant adults, causing ∼11, 25 and 31%, respectively, of the invasive GBS infections in these groups. 11 The reason for this rise in prevalence is unknown, but it has important implications for GBS vaccine development. GBS has remained penicillin-susceptible, and penicillin G is the drug of choice once the organism has been identified. Empiric broad spectrum antibiotic therapy for Gram-positive and Gram-negative organisms is prudent while awaiting culture results in patients with nephrotic syndrome and suspected serious infection. This presentation is a reminder of the importance of GBS as a pathogen in individuals with conditions compromising their immune function, including nephrotic syndrome. Susan J. Sickler, M.D. Morven S. Edwards, M.D. Section of Infectious Diseases, Department of Pediartics, Baylor College of Medicine, Houston, TX