Abstract
Corresponding Author(s)
Lisa Beck, DO, 300 Schuylkill Road, Phoenix- ville, PA 19460.
E-mail address: lnb114@gmail.com.
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Case presentation
A 10-year-old Caucasian patient presented to the emergency department with severe headaches, facial edema, and nausea that had been worsening over the past two weeks. The headache distribution was right sided and was temporarily relieved with ibuprofen. The patient also noted a sore throat and low-grade fever three weeks prior, which lasted several days. Caregivers observed an increasing frequency in the patient’s urinary habits during the past three weeks as well. The patient denied dysuria or hematuria and there were no changes in the patient’s dietary habits.
On presentation, blood pressure was 163/111 mm Hg and the patient was afebrile and of normal stature for age. Physical examination showed a young patient in mild dis- tress with headache, bilateral trace ankle edema, and peri- orbital edema. Cardiac auscultation and pulses were normal and neurologic functioning was intact. Laboratory studies and imaging were performed. Computed tomography of the head was normal. Urine analysis showed 2+ protein, mi- croscopic hematuria, and red blood cell casts. Hemoglobin and hematocrit were 9.8 gm/dL and 29.3%, respectively. Electrolytes, liver function tests, and kidney function studies were normal. The complement level of C3 was found to be abnormally low at 17 mg/dL (normal >85 mg/dL) and a pharyngeal culture for group A Streptococcus (GAS) was positive. An antistreptolysin O (ASO) titer was elevated at 860 IU (normal 12–166 IU). A diagnosis of postinfectious glomerulonephritis (PIGN) was made based on the history, physical examination, and laboratory data.
Topic review
PIGN is an acute self-limiting process causing nephropathy after infection with certain strains of GAS. It is the leading cause of acute nephritic syndrome in children. Cases of poststreptococcal illnesses including PIGN and rheumatic fever are most prevalent in ages three through ten.1 There appears to be no racial preference associated with PIGN, but it is found predominately more in males than females.
GAS infections have many manifestations in the pediat- ric population. Pharyngitis, scarlet fever, glomerulonephri- tis, and rheumatic fever can all be seen after a GAS insult. Psychiatric manifestations can also be seen as a result of GAS infections in children. Pediatric autoimmune neuro- psychiatric disorders associated with streptococcal infec- tions (PANDAS) are conditions in which children with a tic disorder and/or obsessive-compulsive disorder note wors- ening of their disorder after a streptococcal infection.2,3
Damage to the kidneys in PIGN is initiated by outside bacterial insult, usually as a result of GAS. Other forms of acute glomerulonephritis can be caused by internally pro- duced antigens, such as lupus. In PIGN, the antigenicity of certain nephritogenic strains of beta-hemolytic GAS— namely 1, 4, and 12—are ultimately responsible for glomer- ular damage. These damaging strains of GAS initiate a harmful cascade by which antigen-antibody complexes de- velop and cause proliferation, inflammation, and ultimately damage the glomerular cells of the basement membrane.4 However, the exact mechanism of damage from immune complexes is unknown. The molecular size of immune complexes and the size of pores in the basement membrane offer an explanation of why children are much more af- fected with PIGN than adults. The basement membrane pores are much smaller in children; therefore, large immune complexes are more easily trapped in the pores, causing basement membrane damage.5 The time period in which glomerular damage occurs is approximately 10 days after GAS pharyngitis or two weeks after impetigo caused by GAS.1
PIGN presentation is variable but usually includes oli- guric acute renal failure, headaches, and hematuria. The hematuria produced will often be described as smoke- or tea-colored. Edema can be present caused by loss of protein in the urine from nephritis. Back pain may also be present because of edema of the renal capsule. Laboratory data reveals an increased ASO titer and decreased complement levels, specifically C3.6 Renal biopsies in patients with PIGN show inflammatory infiltrates, whereas urinary sedi- ment demonstrates red blood cell casts and protein.
A diagnosis of PIGN requires clinical suspicion, appro- priate laboratory testing, and a thorough history and phys- ical examination. In addition to blood urea nitrogen and creatinine levels, ASO titers, complement levels, urine stud- ies, and a pharyngeal culture should be obtained to support the diagnosis of PIGN. Acute phase reactants such as eryth- rocyte sedimentation rate will initially be elevated in PIGN because of glomerular inflammation. An increased ASO titer develops over two weeks and represents a GAS infec- tion in the previous one to two months. These values decline over four to six months after the infection. However, ASO values can be normal in a small percentage of people with PIGN. The more expensive anti-DNAse-B assay can be performed if clinical suspicion is high but an ASO titer is normal. Anti-DNAse-B assay can also be helpful in a de- layed diagnosis of PIGN because it is detectable longer than ASO titers.7 The streptozyme test, which is a combination of ASO, anti-DNAse-B, streptokinase, Ahase, and anti- NAD, appears to be more sensitive for recent GAS infection than ASO alone. This may be useful in a difficult clinical scenario, with borderline elevations in ASO titers.8 How- ever, the streptozyme test is somewhat less sensitive in infants and the elderly. In these age groups, ASO titer levels can often be near or below the level of sensitivity of the streptozyme test because streptococcal infections are less common in these categories. For this reason, interpretation of the results should be done cautiously in these popula- tions.9
Treatment of PIGN consists of supportive care, such as blood pressure control and fluid volume maintenance, as well as elimination of the initial infection source. Hyper- tension and increased extracellular volume can be treated with antihypertensive agents and diuretics.5 Although there is no preferred antihypertensive medication, beta blockers and calcium channel blockers are chosen most often by clinicians. Antibiotic treatment for GAS pharyngitis is aimed at preventing rheumatic heart disease. Recent data suggests that, to prevent complications, a course of four to five days of a cephalosporin has superior bacterial cure rates than the same duration of penicillin when treating culture- positive GAS.10 However, it is unclear whether antibiotics also prevent PIGN by avoiding an antibody response by the glomeruli. A recent Cochrane review showed that antibiot- ics may have some protective qualities in preventing PIGN, but more cases need to be examined.11 After resolution of the streptococcal infection, 95% of children with PIGN will completely recover within three to four weeks. The symp- toms of hypertension and hypocomplementemia usually re- solve within eight weeks after the initial insult. Proteinuria may last up to six months. Subsequent bouts with PIGN are rare because of the immunity imposed from the initial strep- tococcal surface proteins. Mortality rates in PIGN are ex- tremely low in children. Progression to end-stage renal disease is also uncommon in this age group. The most common sequelae of persistent hematuria and albuminuria can be seen in up to 20% of patients when followed up 15 years later.12 Renal failure, hematuria, proteinuria, and decreased glomerular filtration rate are more common sequelae in those with PIGN during adulthood. These potentially severe se- quelae demand a rapid diagnosis, adequate management, and follow-up in children and adults with PIGN.
Patient outcome
After the diagnosis of PIGN was made, the patient was admitted to the hospital for blood pressure stabilization. During the short hospital stay, the patient’s blood pressures normalized with oral antihypertensives, and a 10-day course of oral azithromycin was started for GAS pharyngitis. Azithromycin was chosen because of the patient’s allergy to penicillin, which would have resulted in diffuse urticaria. Upon discharge, the patient was instructed to keep a headache diary and a daily blood pressure record. He continued taking labetalol and nifedipine for blood pressure management until outpatient follow-up four weeks later. At this follow-up visit, the patient was found to be normotensive and symptom-free, so oral antihypertensives were discontinued. There was no edema on physical examination and urinalysis showed trace protein but no red blood cells or casts.
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