What is the possibility of a 16-year-old patient with anasarca, deep vein thrombosis (DVT), negative D-dimer, mild computed tomography pulmonary angiography (CTPA) without embolism, contrast-enhanced computed tomography (CECT) showing vein dilation, elevated creatine phosphokinase (CPK), elevated serum immunoglobulin E (S-IgE), pulmonary hypertension with all chamber dilation and tricuspid regurgitation (TR) on echocardiogram, and negative pro-brain natriuretic peptide (pro-BNP)?

Diagnostic Considerations for a 16-Year-Old with Pulmonary Hypertension and Multi-System Involvement

This clinical presentation most likely represents pulmonary arterial hypertension (PAH) with possible underlying connective tissue disease or hereditary PAH, given the young age, elevated IgE, elevated CPK, and absence of thromboembolic disease on imaging.

Critical Diagnostic Framework

Pulmonary Hypertension Classification

The patient has confirmed pulmonary hypertension with all-chamber dilation and tricuspid regurgitation on echo, but the negative CTPA and absence of thromboembolic disease effectively rules out chronic thromboembolic pulmonary hypertension (CTEPH) 1. The negative D-dimer further supports the absence of acute or chronic thromboembolic disease 1, 2.

Key diagnostic distinction: The presence of all-chamber dilation (not just right-sided chambers) raises concern for either:

• Group 1 PAH (pulmonary arterial hypertension) - most likely given the age and clinical picture 1
• Group 2 PH (left heart disease) - must be excluded given the chamber dilation 3

Paradoxical BNP Finding

The "negative" pro-BNP at 5000 pg/mL is actually markedly elevated and indicates severe cardiac dysfunction 1. Normal BNP is <100 pg/mL, and values >300 pg/mL indicate cardiac origin of symptoms 4. This patient's BNP of 5000 pg/mL confirms severe right ventricular strain and poor prognosis 1.

Elevated IgE and CPK Significance

• Elevated IgE suggests possible underlying connective tissue disease, particularly systemic sclerosis or other autoimmune conditions that can cause PAH 5
• Elevated CPK may indicate myositis or inflammatory myopathy, which can be associated with connective tissue disease-related PAH 1
• The combination of these findings in a 16-year-old warrants investigation for hereditary PAH with BMPR2 mutation, which can present in childhood (documented cases as young as 10 years) 1

Immediate Diagnostic Requirements

Right Heart Catheterization is Mandatory

Right heart catheterization must be performed immediately to:

• Confirm pulmonary hypertension diagnosis (mean PA pressure ≥25 mmHg) 1
• Measure pulmonary capillary wedge pressure (Ppcw) to differentiate pre-capillary PAH (Ppcw ≤15 mmHg) from post-capillary PH due to left heart disease (Ppcw >15 mmHg) 1, 3
• Calculate pulmonary vascular resistance (PVR ≥3 Wood units confirms PAH) 1
• Perform acute vasoreactivity testing with inhaled nitric oxide to identify vasoreactive patients who may respond to calcium channel blockers 1

Essential Additional Workup

Connective tissue disease screening:

• Antinuclear antibody (ANA), anti-Scl-70, anti-centromere antibodies 1
• Complete rheumatologic panel given elevated IgE 5
• Skin examination for telangiectasia, sclerodactyly, digital ulceration 5

Genetic testing:

• BMPR2 mutation testing given young age (PAH can present at age 10 with genetic anticipation) 1
• Family history assessment for pulmonary vascular disease 1

Exclude other causes:

• HIV testing 1
• Liver function tests and abdominal ultrasound to exclude portopulmonary hypertension 1
• High-resolution CT chest to exclude interstitial lung disease 1

Anasarca and Vein Dilation Interpretation

The anasarca (generalized edema) with CECT showing vein dilation represents severe right ventricular failure with:

• Elevated right atrial pressure causing systemic venous congestion 1, 5
• Hepatic congestion (likely pulsatile hepatomegaly on exam) 5, 6
• Peripheral edema and ascites from fluid retention 5, 6

These findings indicate advanced disease with poor prognosis 1, 6.

Prognostic Assessment

This patient has multiple poor prognostic indicators:

• BNP 5000 pg/mL (extremely elevated, normal <100 pg/mL) 1, 4
• All-chamber dilation suggesting biventricular involvement 1
• Anasarca indicating severe right heart failure 6
• Young age with severe presentation 1

The combination of these factors places this patient at high risk for mortality without aggressive treatment 1, 6.

Treatment Implications Based on Diagnosis

If Pre-Capillary PAH (Group 1) is Confirmed:

Immediate referral to pulmonary hypertension expert center is mandatory 1. Given the severity (likely WHO functional class III-IV based on anasarca), treatment options include:

• Combination therapy with endothelin receptor antagonist plus phosphodiesterase-5 inhibitor 1
• Consider prostacyclin therapy (intravenous) given severe presentation 1
• Oral anticoagulation with warfarin (target INR 2.0-3.0) is recommended for idiopathic PAH 1, 7
• Diuretics for volume overload management 3

If Post-Capillary PH (Group 2) is Confirmed:

PAH-specific therapies are contraindicated and may cause harm 3. Treatment focuses on:

• Optimal management of underlying left heart disease 3
• Diuretics (loop diuretics like furosemide) to reduce pulmonary venous congestion 3

Critical Pitfalls to Avoid

• Do not assume negative D-dimer excludes all pathology - it correctly excludes acute PE but does not rule out PAH 1, 2
• Do not misinterpret BNP 5000 as "negative" - this is severely elevated and indicates poor prognosis 1, 4
• Do not start PAH-specific therapy before confirming diagnosis with right heart catheterization - if this is Group 2 PH, PAH medications are harmful 3
• Do not delay genetic testing in young patients - hereditary PAH requires family screening 1
• Do not overlook connective tissue disease - elevated IgE and CPK warrant thorough autoimmune workup 5

1, 3, 5, 6, 7, 2, 4