A 57-year-old landscape architect presents with four months of worsening generalized itching. It is most troublesome at night and now interrupts her sleep. She has also noticed gradually enlarging, painless yellow patches on both palms.

She has primary biliary cholangitis, diagnosed six years earlier after persistent alkaline phosphatase elevation, positive antimitochondrial antibodies, and imaging that excluded biliary obstruction.

She weighs 68 kg and takes ursodeoxycholic acid 500 mg twice daily. She reports consistent adherence. Her alkaline phosphatase has remained between 300 and 450 U/L during the preceding 18 months.

She has no diabetes, hypertension, known cardiovascular disease, or history of smoking. There is no family history of premature cardiovascular disease. A lipid panel obtained before her PBC diagnosis showed total cholesterol of 184 mg/dL and LDL-C of 108 mg/dL.

She denies fever, abdominal pain, gastrointestinal bleeding, abdominal swelling, or confusion. She has not started any new medications or supplements.

Her blood pressure is 118/72 mmHg, pulse 74/min, and temperature 36.8°C.

Examination reveals yellow orange plaques along the flexion creases of the palms and fingers. Excoriations are present on her trunk. There is no ascites, peripheral edema, or asterixis.

See image below.

Image: Maldonado Carrasco CL, Garcés JC, Silva ML, Loayza E. “Xantoma estriado palmar.” Rev. Med. UCSG. 2025;25(1):31–36, Figure 1. © The authors, 2025. Reproduced under CC BY 4.0. Original source.

Her fasting lipid panel shows:

An abdominal ultrasound shows no bile-duct dilation, focal liver lesion, or ascites.

Which diagnosis best explains the skin lesions and lipid findings?

A. Cholestasis-associated xanthomas with lipoprotein X accumulation
B. Familial hypercholesterolemia
C. Familial dysbetalipoproteinemia
D. Palmoplantar psoriasis
E. Allergic contact dermatitis

Choose your answer before reading on.

The yellow palmar plaques are consistent with xanthomas. The key biochemical clue is the enormous discrepancy between the reported LDL-C and apoB.

In cholestasis, lipoprotein X, an abnormal particle rich in unesterified cholesterol and phospholipids, can accumulate in plasma. Unlike ordinary LDL, it lacks apoB. Routine lipid testing may therefore report a striking cholesterol elevation without a corresponding increase in apoB-containing particles.

Here, the calculated LDL-C is mathematically consistent with the lipid panel, but it should not be interpreted as 689 mg/dL of ordinary LDL cholesterol. The combination of cholestasis, xanthomas, and relatively modest apoB strongly suggests a substantial Lp-X contribution. Specialized testing can confirm it.

Lipoprotein electrophoresis performed by a reference laboratory identifies Lp-X.

Familial hypercholesterolemia can produce very high LDL-C and xanthomas, often with normal triglycerides. Therefore, the triglyceride value does not exclude it.

However, this patient’s previously unremarkable untreated lipid profile, absence of a suggestive family history, and marked cholesterol–apoB discrepancy make familial hypercholesterolemia a much weaker explanation. A coexisting inherited disorder would merit reassessment if atherogenic lipid abnormalities persisted after improvement in cholestasis.

This is a meaningful alternative because palmar-crease xanthomas are a classic clue. However, dysbetalipoproteinemia typically produces a mixed elevation of cholesterol and triglycerides from remnant accumulation.

The modest triglyceride elevation, established cholestasis, and subsequent identification of Lp-X favor answer A. ApoB discordance alone would not reliably distinguish these conditions.

Psoriasis can affect the palms. It generally produces sharply demarcated, thickened, scaly lesions, often with painful fissures.

The smooth yellow plaques without scaling or fissuring are much more consistent with xanthomas. Psoriasis also does not explain the cholesterol–apoB discrepancy.

Contact dermatitis usually produces an itchy eczematous eruption with erythema, scaling, fissuring, and sometimes vesicles. An exposure history may support the diagnosis.

Here, the plaques have the appearance of lipid deposits, and the itching is generalized rather than confined to an eczematous eruption. Contact dermatitis does not explain the lipid findings.

Lp-X-associated cholesterol does not carry the same established atherosclerotic risk as ordinary LDL. Statins do not adequately treat Lp-X itself, although patients with PBC may still need statins for a separate cardiovascular indication.

The priorities are to assess the underlying cholestasis and determine the true atherogenic particle burden.

Normal or mildly elevated triglycerides alone cannot make that distinction.

This patient has persistent biochemical disease activity despite an appropriate prescribed UDCA dose, worsening pruritus, and newly increased bilirubin.

I would contact her hepatologist that week. I would review laboratory trends, adherence, medication interactions, and previous fibrosis assessments; repeat liver chemistries and bilirubin fractions; and arrange updated fibrosis assessment.

The ultrasound reduces concern for major obstruction, but worsening results or new symptoms could justify further biliary imaging. Normal albumin, INR, and platelets are reassuring without excluding significant fibrosis.

Her presentation supports expedited outpatient assessment. Fever with abdominal pain, rapidly worsening jaundice, confusion, bleeding, or new ascites would change the urgency.

I would review cardiovascular history and risk factors. I would not start a high-intensity statin solely because the calculated LDL-C is 689 mg/dL.

ApoB of 79 mg/dL does not establish zero cardiovascular risk or a universal treatment target. A separate indication for lipid-lowering treatment would still deserve treatment.

Her UDCA dose is 1,000 mg/day, approximately 14.7 mg/kg/day, within the recommended 13–15 mg/kg/day range. I would continue it.

Persistent ALP elevation after prolonged adequate treatment warrants discussion of an additional agent.

For this patient, seladelpar 10 mg orally once daily is a reasonable option to discuss with hepatology, particularly because itching is prominent. Its trial demonstrated improvement in biochemical response and pruritus.

Before prescribing, I would confirm the absence of decompensated cirrhosis or complete biliary obstruction, review interactions, and document baseline liver tests and bone health. I would monitor liver tests during treatment.

Seladelpar’s approval is based on biochemical improvement; improved survival and prevention of decompensation have not yet been demonstrated. This is a treatment choice for an eligible patient, not an automatic prescription for every patient with PBC and itching.

I would record a baseline itch score from 0–10 and its effect on sleep. I would recommend moisturizers, cool showers, and avoiding excessive heat.

First step: Start cholestyramine 4 g once daily, titrating according to benefit and tolerability, up to 16 g/day. Constipation and medication-binding interactions often limit treatment.

Other oral medicines should generally be taken at least 1 hour before or 4–6 hours after cholestyramine. Seladelpar specifically requires at least 4 hours of separation on either side. I would provide a written medication schedule.

If itching remains disruptive: Reassess within two to four weeks and discuss linerixibat, now FDA-approved for cholestatic pruritus in adults with PBC.

The labeled dose is 40 mg twice daily, at least 30 minutes before food or beverages other than water. Separate it from bile acid-binding resins by at least four hours.

Before treatment, obtain liver tests, vitamins A, D and E, and INR; monitor during treatment. Discuss diarrhea, dehydration, vitamin deficiency, and bone health. Avoid it in patients with current or previous hepatic decompensation. It treats itching and does not replace disease-directed PBC therapy.

If these options are unsuitable or unavailable, hepatology can consider established alternatives such as rifampin, naltrexone, or sertraline. Rifampin requires liver monitoring and should be avoided when bilirubin is ≥2.5 mg/dL. These options require individualized assessment rather than automatic escalation through a fixed list.

I would review:

• Bone health: Prior fractures, DEXA results, vitamin D, and calcium intake; arrange DEXA if overdue.
• Vitamin deficiency: Assess for malabsorption and deficiencies with worsening cholestasis; obtain the additional baseline tests required if starting linerixibat.
• Thyroid disease: Continue annual TSH assessment.
• Cirrhosis-related surveillance: If staging identifies cirrhosis, initiate appropriate liver-cancer surveillance and portal-hypertension assessment.

I would review itching and treatment tolerability within two to four weeks, repeat liver tests approximately four weeks after a treatment change, and reassess the lipid panel and apoB in roughly eight to twelve weeks, adjusting these intervals to the clinical course.

Those intervals are my proposed monitoring plan for this constructed case, not universal label-mandated schedules.

I would document the skin lesions so that later improvement can be assessed. There is no current indication for plasma exchange in this stable patient; that is a specialist option for severe symptomatic Lp-X complications, including hyperviscosity.

Transplant evaluation becomes relevant with advanced or decompensated disease, substantially rising bilirubin, or truly refractory pruritus. The cholesterol number alone does not establish that need.

Patient details and clinical findings are simulated; the photograph is a representative image from a separate published source.