What is the differential diagnosis for a patient with portal hypertension and a crusted scaly skin lesion?

Differential Diagnosis: Portal Hypertension with Crusted Scaly Skin Lesions

Primary Consideration: Chronic Arsenicosis

The most critical diagnosis to consider in a patient with portal hypertension and crusted scaly skin lesions is chronic arsenicosis, particularly in patients with a history of indigenous or traditional medication use. 1

Key Diagnostic Features of Arsenicosis:

• Skin manifestations: Diffuse hyperpigmented papules and nodules distributed across the body, with characteristic palmoplantar thickening and hyperkeratosis presenting as crusted, scaly lesions (often described as "raindrop" pigmentation) 1
• Portal hypertension pattern: Non-cirrhotic portal fibrosis (NCPF) with normal liver function tests, normal liver size on imaging, and dilated portal/splenic veins with splenomegaly 1
• Critical history: Exposure to oral indigenous medications or contaminated water sources, especially in endemic areas 1

This diagnosis is particularly important because it represents a presinusoidal cause of non-cirrhotic portal hypertension where liver synthetic function remains preserved despite significant portal hypertension 2.

Differential Diagnosis Framework

Non-Cirrhotic Portal Hypertension with Dermatologic Manifestations:

1. Idiopathic Non-Cirrhotic Portal Hypertension (INCPH)

• Presents with splenomegaly, esophageal varices, and preserved liver function 2
• Associated conditions include thrombophilia (40% prevalence in Western patients), immunological disorders, and specific medications (azathioprine, didanosine) 2
• HIV infection is a recognized cause that may present with cutaneous manifestations 2
• Liver biopsy shows phlebosclerosis, nodular regeneration, and perisinusoidal fibrosis without cirrhosis 2

2. Hereditary Hemorrhagic Telangiectasia (HHT)

• Portal hypertension results from hepatic arteriovenous malformations causing nodular regenerative hyperplasia 2
• Skin findings: Cutaneous and mucosal telangiectases (not typically crusted/scaly, but important vascular skin lesions) 2
• Additional features: Epistaxis, family history, enlarged hepatic artery on imaging 2
• Liver appears nodular and may be misinterpreted as cirrhosis 2

3. Myeloproliferative Disorders

• Can cause portal vein thrombosis leading to extrahepatic portal hypertension 2
• May present with various cutaneous manifestations related to the underlying hematologic disorder 2
• Screening for EHPVO should be considered in patients with known myeloproliferative disease 2

Cirrhotic Portal Hypertension with Skin Manifestations:

4. Primary Biliary Cholangitis (PBC)

• Causes sinusoidal portal hypertension with cholestatic features 3
• Skin manifestations include pruritus with secondary excoriations and lichenification (crusted, scaly appearance from chronic scratching)
• Elevated alkaline phosphatase and gamma-glutamyl-transpeptidase 2

5. Schistosomiasis

• Presinusoidal cause of portal hypertension 3
• Endemic exposure history is critical
• May have associated dermatologic findings from cercarial penetration or chronic disease

Diagnostic Approach

Essential Initial Workup:

1. Detailed exposure history: Indigenous medications, arsenic-contaminated water, occupational exposures, travel to endemic areas 1
2. Liver function assessment: Normal synthetic function suggests non-cirrhotic causes 2, 4
3. Doppler ultrasound: First-line investigation for portal vein patency and liver morphology 2, 5
4. Skin biopsy: From representative crusted/scaly lesions to evaluate for arsenical keratosis or other specific dermatoses 1

Advanced Investigations:

• Liver biopsy: Essential to exclude cirrhosis and identify specific histologic patterns (phlebosclerosis, nodular regenerative hyperplasia) 2
• Transient elastography: Low liver stiffness (<12 kPa) suggests INCPH rather than cirrhosis 2
• Thrombophilia screening: If INCPH suspected 2
• Arsenic levels: Urine or tissue arsenic if arsenicosis suspected 1
• CT/MRI with contrast: For diagnostic confirmation and assessment of vascular anatomy 2, 5

Critical Clinical Pitfalls

Common misdiagnosis: Patients with NCPH are frequently misclassified as cirrhotic on imaging due to liver surface nodularity and portal vein wall thickening 2. However, preserved liver synthetic function and normal platelet counts should raise suspicion for non-cirrhotic causes 2, 4.

Geographic considerations: In developing countries, particularly Asia, non-cirrhotic causes are more common than cirrhosis as the etiology of portal hypertension 4. Indigenous medication use is particularly relevant in the Indian subcontinent 1.

Prognostic implications: Mortality from variceal hemorrhage in NCPH is significantly lower than in cirrhotic patients due to preserved liver function 2, making accurate diagnosis crucial for appropriate counseling and management planning.