What diagnosis and management should be considered for a 16‑year‑old obese girl with flank pain, joint pain, irregular menses, elevated erythrocyte sedimentation rate, hepatomegaly, low‑level pyuria, and a reactive antistreptolysin O titer?

Diagnosis: Post-Streptococcal Glomerulonephritis (PSGN) with Hepatomegaly

This 16-year-old obese girl most likely has acute post-streptococcal glomerulonephritis (PSGN) presenting with nephritic syndrome, and the hepatomegaly requires evaluation for metabolic storage disorders or non-alcoholic fatty liver disease (NAFLD). 1, 2

Primary Diagnosis: Post-Streptococcal Glomerulonephritis

Key Diagnostic Features Present

• Reactive ASO titer confirms recent streptococcal infection, which is the hallmark trigger for PSGN 1, 3
• Elevated ESR indicates active inflammation, consistent with immune-complex mediated glomerular injury 2, 1
• Flank pain suggests renal involvement, typical of nephritic syndrome presentation 4, 1
• Joint pains can occur with PSGN as part of the systemic inflammatory response 1, 3
• Stab cells (band forms) at 4% indicate left shift, reflecting acute inflammatory response to glomerulonephritis 2

Immediate Laboratory Workup Required

• Measure serum C3 and C4 complement levels immediately—low C3 occurs in >90% of PSGN cases and appears earlier than ASO titer elevation 1, 5
• Obtain urinalysis with microscopy looking for RBC casts, which are pathognomonic for nephritic syndrome and distinguish this from nephrotic syndrome 4, 1
• Check serum creatinine and BUN to assess for acute kidney injury, which peaks in the first 7-10 days of PSGN 1, 5
• Measure blood pressure as hypertension is a cardinal feature of nephritic syndrome and requires aggressive management 4, 1
• Quantify proteinuria with spot urine protein-to-creatinine ratio—nephritic syndrome typically shows <3.5 g/day, unlike nephrotic syndrome 4

Critical Timing Considerations

• The latency period between streptococcal infection and nephritis is 1-2 weeks for pharyngitis or 2-6 weeks for skin infections 1, 5
• Concurrent infection and nephritis symptoms should raise suspicion for alternative diagnoses such as IgA nephropathy or infection-related glomerulonephritis from other organisms 1, 6
• The first 7-10 days require maximum vigilance for hypertensive emergencies, pulmonary edema, and severe acute kidney injury 1, 5

Secondary Concern: Hepatomegaly Evaluation

Differential Diagnosis for 17.8 cm Hepatomegaly

• NAFLD is the most likely cause in an obese adolescent with irregular menses suggesting possible polycystic ovary syndrome 2
• Metabolic storage disorders must be excluded, particularly lysosomal storage diseases like acid sphingomyelinase deficiency (ASMD) which presents with massive hepatosplenomegaly, dyslipidemia, and elevated transaminases 2, 7
• Hepatic congestion from PSGN-related fluid overload can transiently enlarge the liver 1, 5

Hepatomegaly Workup Algorithm

• Obtain complete metabolic panel including liver transaminases (AST, ALT), alkaline phosphatase, and GGT—elevated transaminases occur early in NAFLD and storage disorders 2, 7
• Check fasting lipid profile—mixed dyslipidemia with low HDL and high triglycerides suggests NAFLD or storage disorders 2, 7
• Measure fasting glucose and insulin to assess for insulin resistance and type 2 diabetes, which are obesity-related complications 2
• Perform abdominal ultrasound to assess liver echogenicity (fatty infiltration), spleen size, and rule out focal lesions 2, 7
• Refer to pediatric gastroenterology/hepatology as the liver is the primary affected organ requiring specialist evaluation 7

Storage Disorder Red Flags

• If splenomegaly is also present on ultrasound, consider enzymatic testing for ASMD or lysosomal acid lipase deficiency (LALD) 2, 7
• Massive splenomegaly (>10x normal) with hepatomegaly strongly suggests ASMD 2, 7
• Very young age or lack of obesity would mandate testing for monogenic causes including fatty acid oxidation defects and peroxisomal disorders 2

Management of PSGN

Acute Phase Treatment (First 7-10 Days)

• Initiate loop diuretics (furosemide) as first-line therapy for hypertension, edema, and hyperkalemia—this is the most effective treatment for PSGN complications 1, 5
• Add thiazide diuretics if loop diuretics are insufficient for blood pressure and volume control 1
• Restrict sodium intake to <2 g/day and fluid restriction to 400 mL plus urine output to manage volume overload 5
• Avoid ACE inhibitors or ARBs initially as they carry risk of hyperkalemia and may temporarily impair renal function recovery 1

Antibiotic Therapy

• Administer penicillin or amoxicillin for 10 days to eradicate residual streptococcal infection and prevent transmission, even though antibiotics do not alter PSGN course 3, 5
• Use azithromycin for 5 days if penicillin-allergic 5

Monitoring Protocol

• Check blood pressure, weight, and urine output daily during the acute phase 5
• Repeat serum creatinine every 2-3 days until stable or improving 5
• Monitor serum potassium closely especially if using diuretics or if oliguria is present 1, 5
• Recheck C3 level at 8 weeks—persistent hypocomplementemia beyond 8-12 weeks suggests alternative diagnosis like membranoproliferative glomerulonephritis 1, 5

Indications for Kidney Biopsy

• Perform kidney biopsy if diagnostic uncertainty exists, particularly if concurrent infection and nephritis symptoms suggest alternative diagnosis 1, 6
• Biopsy is indicated for rapidly progressive glomerulonephritis with rapidly rising creatinine or oliguria/anuria 5
• Persistent hypocomplementemia beyond 8-12 weeks mandates biopsy to exclude other glomerulonephritides 1, 5
• Atypical features such as nephrotic-range proteinuria (>3.5 g/day) or age >12 years warrant biopsy consideration 4, 5

Management of Obesity-Related Complications

Irregular Menses Evaluation

• Screen for polycystic ovary syndrome (PCOS) with history of oligomenorrhea, hirsutism, and acanthosis nigricans 2
• Check for acanthosis nigricans on physical exam, which is associated with insulin resistance and type 2 diabetes 2
• Assess for signs of Cushing's syndrome including striae, which would require further endocrine evaluation 2

Cardiovascular Risk Assessment

• Measure blood pressure at every visit using age-appropriate percentile charts—obesity increases CVD risk 2
• Calculate BMI and plot on CDC growth curves—BMI >95th percentile warrants comprehensive metabolic evaluation 2
• Screen for depression and eating disorders as these require psychiatric evaluation and affect treatment adherence 2

Prognosis and Long-Term Follow-Up

Expected PSGN Outcomes

• The prognosis for PSGN is excellent with >95% complete recovery in children, even with severe initial presentation 1, 8, 5
• Persistent microscopic hematuria and proteinuria may occur in <10% of patients but rarely progresses to chronic kidney disease 1, 5
• Complete resolution of hypertension and edema typically occurs within 2-4 weeks 5
• Serum creatinine normalizes within 3-4 weeks in most cases 5

Long-Term Monitoring Schedule

• Recheck urinalysis and blood pressure at 2 weeks, 4 weeks, 3 months, 6 months, and 12 months after diagnosis 5
• Annual follow-up for 5 years is recommended to monitor for late development of hypertension or proteinuria 8, 5
• Patients with persistent abnormalities beyond 1 year require nephrology referral for possible kidney biopsy 5

Critical Pitfalls to Avoid

• Do not delay diuretic therapy while awaiting biopsy results—hypertensive emergencies and pulmonary edema require immediate treatment 1, 5
• Do not assume hepatomegaly is solely from PSGN-related congestion—obesity mandates NAFLD evaluation and storage disorders must be excluded 2, 7
• Do not dismiss the diagnosis based on normal serum albumin—nephritic syndrome does not cause hypoalbuminemia unlike nephrotic syndrome 4
• Do not overlook thrombocytopenia or leukopenia—these may indicate storage disorders rather than simple PSGN 2
• Do not use ACE inhibitors as first-line antihypertensives in acute PSGN—loop diuretics are superior and ACE inhibitors risk hyperkalemia 1