Cholestasis-Edema Syndrome (Cholestasis-Lymphedema Syndrome)

Types
Causes
Symptoms
Diagnostic tests
Non-pharmacological treatments (therapies & others)
Drug treatments
Dietary “molecular” supplements
Regenerative / stem-cell” drugs
Surgeries
Preventions (practical risk-reduction tips)
When to see doctors urgently
Foods to favor and to limit/avoid
Frequently Asked Questions

Cholestasis-edema syndrome is a rare, inherited condition in which bile cannot flow out of the liver normally (cholestasis) and lasting swelling (lymphedema) develops—usually in the legs. Babies commonly show jaundice, pale stools, dark urine and poor weight gain from neonatal cholestasis. The swelling of the legs tends to appear later in childhood or adolescence and can slowly progress. Many children improve from repeated cholestasis episodes as they grow, but a minority can develop scarring (cirrhosis) of the liver and may ultimately need a liver transplant. The syndrome is also called Aagenaes syndrome or cholestasis-lymphedema syndrome (LCS1). OrphaNCBImalacards.org

Cholestasis” means bile is not flowing out of the liver the way it should. Bile builds up in the liver and in the blood. This hurts liver cells and affects many body functions. “Edema” means swelling caused by extra fluid in body tissues. When cholestasis is long-lasting or severe, people can hold on to salt and water. Protein in the blood may go down. Pressure in the belly veins can rise. These changes make fluid leak into the legs, feet, and belly (ascites). So, “cholestasis-edema syndrome” describes a state where a person has both bile-flow problems and swelling.

In 2023 researchers showed that most patients share a “founder” change (c.–98G>T) in the UNC45A gene (a myosin chaperone) that lowers UNC45A protein levels and mislocates key bile-export pumps (BSEP and MRP2) in liver cells. This explains the cholestasis and probably links to a developmental lymphatic defect, which causes lymphedema. research-repository.st-andrews.ac.uk

Key features you might see:

Recurrent or intermittent jaundice in infancy/early childhood, often improving with age
Fat malabsorption → poor growth, vitamin A/D/E/K deficiency (bleeding, rickets, neuropathy)
Progressive lymphedema of lower limbs (sometimes upper limbs/chest)
Risk (about 1 in 4) of cirrhosis later in childhood/adulthood in historical series malacards.org

Because this is rare, care is best coordinated by a pediatric or adult hepatology team and a lymphedema clinic.

There is also a rare genetic condition where cholestasis happens together with true lymphedema (swelling from lymph vessel problems). It is called cholestasis-lymphedema syndrome or Aagenaes syndrome. Babies have neonatal cholestasis, and over time they develop chronic lymphedema, usually in the legs. This is a recognized disorder in medical genetics. OrphaNCBIGenetic Diseases Info Center

Two ideas are important:

Many people with liver or bile-duct disease develop edema and/or ascites from salt and water retention, low albumin, and high portal vein pressure. NCBI+1
A small group have the specific genetic cholestasis-lymphedema (Aagenaes) syndrome where faulty lymphatics cause lymphedema along with cholestasis. OrphaGenetic Diseases Info Center

Other names you may see

Cholestasis with edema
Cholestatic liver disease with fluid retention
Ascites due to cholestasis or cirrhosis
Cholestasis-lymphedema syndrome (CLS, LCS1) — the formal name for Aagenaes syndrome (rare genetic form; sometimes called “Norwegian type”). OrphaWikipedia

Cholestasis-edema syndrome is a practical, umbrella term for a patient who has bile-flow blockage or bile-flow failure (cholestasis) and shows tissue swelling (edema) or belly fluid (ascites). The swelling may come from low blood protein, kidney salt and water retention, and high pressure in the liver’s portal vein system. In the rare cholestasis-lymphedema (Aagenaes) syndrome, swelling comes mainly from poor lymph drainage and starts in infancy. NCBI+1Orpha

Why edema happens in cholestasis

Bile backs up. When bile cannot exit, detergents in bile injure liver cell membranes and slow normal transport. NCBI
The liver makes less albumin. Albumin is a blood protein that holds water inside blood vessels. Low albumin lets water leak into tissues and the belly. ScienceDirect
Portal pressure rises. Scarring and blockage raise pressure in the portal vein. Water then moves into the abdomen and causes ascites. NCBI
The kidneys retain salt and water. Hormones respond to low blood volume and high pressure by saving salt and water, which adds to swelling and ascites. NCBI
In some patients, lymph vessels are abnormal. In Aagenaes syndrome, lymph drainage is poor, so protein-rich fluid stays in the legs and other tissues. Orpha
Skin and tissue molecules may trap water. In obstructive cholestasis, changes in glycosaminoglycans like hyaluronan can attract water and add to edema. BioMed Central

Types

Genetic cholestasis with lymphedema (Aagenaes/CLS). Starts in infancy. Cholestasis can improve with age, but leg lymphedema is chronic. Some develop cirrhosis later. Orpha
Obstructive (extrahepatic) cholestasis with edema/ascites. A stone, stricture, tumor, or inflammation blocks the bile duct; long disease leads to fluid retention. NCBIExploration Publishing
Intrahepatic cholestasis with edema/ascites. The bile pumps inside the liver fail from drugs, pregnancy, infections, sepsis, TPN, autoimmune disease, or genetic transporter defects; over time, fluid builds up. NCBIPMC
Neonatal cholestasis with edema/ascites. Many neonatal liver disorders present with cholestatic jaundice; the abdomen may swell from ascites. PMCNational Organization for Rare Disorders

Causes

Gallstones in the common bile duct (choledocholithiasis). A stone blocks bile flow and causes cholestatic jaundice. Wikipedia
Benign bile-duct stricture. Narrowing after surgery or pancreatitis slows bile and leads to cholestasis. Exploration Publishing
Malignant obstruction. Cancer of the pancreas, ampulla, or bile ducts can block flow. Exploration Publishing
Primary sclerosing cholangitis (PSC). Inflammation and scarring of bile ducts inside and outside the liver. Exploration Publishing
Primary biliary cholangitis (PBC). Autoimmune injury to small intrahepatic ducts; leads to cholestasis and pruritus. NCBI
Drug-induced cholestasis. Anabolic steroids, estrogens, some antibiotics, and others can block transporter function. Wikipedia
Intrahepatic cholestasis of pregnancy. Itching and high bile acids in late pregnancy; sometimes mild jaundice. AAP Publications
Sepsis-related cholestasis. Severe infection can cause intrahepatic cholestasis. PMC
Total parenteral nutrition (TPN) cholestasis. Long-term IV feeding can impair bile flow. PMC
Viral hepatitis leading to cholestatic pattern. HBV/HCV and others may present with cholestasis, especially if chronic disease progresses. NCBI
Alcohol-associated liver disease with cholestasis. Inflammation and fibrosis may produce a mixed or cholestatic pattern.
Non-alcoholic fatty liver disease with cholestasis features. Advanced disease can show cholestatic labs and fluid retention.
Biliary atresia (infants). Extrahepatic bile ducts fail to develop or become blocked. PMC
Choledochal cysts. Congenital bile-duct dilations can cause obstruction and recurrent cholestasis. Exploration Publishing
Ascending cholangitis. Infection of the bile ducts with obstruction causes jaundice and sepsis. Exploration Publishing
Autoimmune cholangiopathies (IgG4-related). Swelling of ducts from IgG4 disease can obstruct bile flow. NCBI
Budd–Chiari syndrome (hepatic vein blockage). Venous outflow block increases liver pressure and can lead to ascites.
Right-sided heart failure / constrictive pericarditis. Congestive hepatopathy mimics cholestasis and causes edema and ascites. NCBI
Parasitic or helminth infections with biliary involvement. Can inflame or block ducts. Exploration Publishing
Genetic transporter defects (PFIC variants) and Aagenaes (CLS). Inherited problems in bile-salt transport or lymphatics cause cholestasis and swelling. Orpha

Symptoms

Yellow skin and eyes (jaundice). Bile pigments build up in blood. NCBI
Itchy skin (pruritus). Bile constituents and signaling molecules trigger itch, often early. FrontiersNCBI
Dark urine. Conjugated bilirubin spills into urine.
Pale or clay-colored stool. Little bile reaches the gut.
Right upper belly discomfort. The liver and ducts are irritated.
Fatigue and poor appetite. Common in liver disease.
Swollen legs and feet (edema). Fluid leaks from vessels into tissues.
Swollen abdomen (ascites). Fluid collects in the peritoneal cavity. Cleveland ClinicNCBI
Easy bruising or bleeding. Vitamin K and clotting factors are low.
Greasy stools (steatorrhea). Poor bile flow reduces fat absorption.
Weight loss or failure to thrive (infants). Fat and vitamins are not absorbed well. PMC
Bone pain or soft bones. Vitamin D deficiency from fat malabsorption.
Night blindness or dry eyes. Vitamin A deficiency from cholestasis.
Numbness or unsteady walking. Vitamin E deficiency can cause neuropathy.
Fevers and chills. Possible with cholangitis or infection of fluid collections.

Diagnostic tests

(Grouped as Physical Exam, Manual tests, Lab/Pathology, Electrodiagnostic, Imaging. Each item says what it looks for and why it helps.)

A) Physical exam

General inspection for jaundice and scratch marks. Yellow skin and excoriations suggest cholestasis with itching. This supports a cholestatic process. NCBI
Scleral icterus check. Yellow eyes are a sensitive sign of bilirubin buildup.
Liver and spleen size assessment. An enlarged, tender liver or a big spleen suggests ongoing cholestasis or portal hypertension.
Stigmata of chronic liver disease. Spider veins on the chest, palmar redness, muscle loss, and testicular atrophy point to long-standing liver injury.

B) Manual bedside tests

Pitting-edema pressure test. Gentle thumb pressure on the shin leaves a pit if fluid is in the tissues; shows severity of edema.
Stemmer sign for lymphedema. Trying to pinch the skin at the base of the second toe; if you cannot lift it, lymphedema is likely — useful when Aagenaes/CLS is suspected. Orpha
Shifting dullness. Percussion before and after turning on the side; a change suggests free fluid (ascites). NCBI
Fluid-wave test. A palpable wave across the belly supports moderate to large ascites. NCBI

C) Laboratory and pathology tests

Liver enzyme pattern (ALT, AST, ALP, GGT). A high ALP and GGT with lesser ALT/AST increase suggests a cholestatic pattern. This guides the search toward bile-flow problems. NCBI
Total and direct bilirubin. A high direct (conjugated) bilirubin supports cholestasis or obstruction. NCBI
Serum bile acids. High levels fit intrahepatic cholestasis (e.g., pregnancy) and help track itch severity. AAP PublicationsFrontiers
Serum albumin and total protein. Low albumin explains leg edema and ascites and shows poor liver synthesis or protein loss. ScienceDirect
Coagulation tests (PT/INR, platelet count). A long PT/INR suggests poor clotting factor production or vitamin K deficiency; low platelets can reflect portal hypertension.
Viral hepatitis tests (HBsAg, anti-HCV, others). Rule in or rule out viral causes that can lead to cholestatic or advanced liver disease. NCBI
Autoimmune panels (AMA, ANA, ASMA, IgG4). Help diagnose PBC, autoimmune hepatitis overlap, or IgG4-related cholangitis. NCBI
Liver biopsy (when needed). Shows bile plugs, duct injury, inflammation, fibrosis, or cirrhosis; in CLS, may show giant-cell change or nonspecific features. Lippincott Journals

(Optional in specific cases: genetic testing for PFIC genes or for CLS locus; fat-soluble vitamin levels to guide replacement.) Genetic Diseases Info Center

D) Electrodiagnostic tests

Electrocardiogram (ECG). Looks for right-heart strain or rhythm issues if edema might be partly cardiac (congestive hepatopathy).
Nerve conduction studies (if neuropathy). Vitamin E deficiency from chronic cholestasis can cause neuropathy; testing documents nerve damage.

E) Imaging tests

Abdominal ultrasound with Doppler. First-line test. It looks for dilated bile ducts, gallstones, liver texture, spleen size, and ascites; Doppler checks portal and hepatic vein flow. NCBI
MRCP (magnetic resonance cholangiopancreatography). Non-invasive map of bile ducts to find strictures, stones, or PSC changes. ERCP is diagnostic and therapeutic when intervention is needed. NCBI

Non-pharmacological treatments (therapies & others)

Goals: keep bile flowing and skin comfortable during cholestasis; control swelling; protect skin; maintain nutrition; prevent complications.

Complete Decongestive Therapy (CDT) – the cornerstone for lymphedema
What it is: A program combining compression, manual techniques, exercise, skin care, patient education and self-management (often delivered by certified lymphedema therapists).
Purpose: reduce limb volume, improve symptoms and function.
Mechanism: external pressure and muscle pumping shift lymph fluid from congested tissues; meticulous skin care cuts infection risk. PubMed+1
Graduated Compression Garments
Purpose: maintain size after decongestion; reduce daily swelling.
Mechanism: sustained external pressure counteracts fluid leakage and supports lymph flow. Use as prescribed (daytime wear; special nighttime garments). PubMed
Multilayer Short-Stretch Bandaging (intensive phase)
Purpose: faster limb volume reduction before switching to garments.
Mechanism: low resting/high working pressure bandages enhance the “muscle pump.” PubMed
Manual Lymphatic Drainage (MLD)
Purpose: soft, directed massage to move lymph toward healthy basins.
Mechanism: gentle skin-stretching sequences stimulate superficial lymphatics and rerouting. Works best as part of CDT. PubMed
Pneumatic Compression Pump (home adjunct)
Purpose: periodic sessions to maintain volume control when clinic access is limited.
Mechanism: sequential inflation sleeves push fluid proximally; use under therapist guidance. PubMed
Targeted Exercise & Walking Program
Purpose: amplify the calf/forearm “muscle pump”; improve fitness and mood.
Mechanism: rhythmic muscle contractions propel lymph; combine with compression for best effect. PubMed
Meticulous Skin & Nail Care
Purpose: prevent cellulitis and fungal infection (which worsen swelling).
Mechanism: daily emollients, prompt wound care, antifungals when needed; protect from trauma. PubMed
Weight Management & Healthy BMI
Purpose: extra body weight increases limb load and inflammation, worsening lymphedema.
Mechanism: gradual weight loss lowers tissue pressure and improves mobility. PubMed
Elevation and Positioning
Purpose: short-term swelling relief.
Mechanism: gravity assists venous/lymphatic return; avoid prolonged dependent sitting. PubMed
Sun/Heat & Itch Avoidance Strategies
Purpose: minimize triggers of cholestatic itch (heat, wool, stress).
Mechanism: cool baths, breathable fabrics, nails short to protect skin. PMC
Structured Nutrition Plan
Purpose: overcome fat malabsorption; prevent vitamin deficiencies; support growth.
Mechanism: energy-dense meals, medium-chain triglycerides (MCT), fat-soluble vitamins A/D/E/K; specialist dietetic input. NCBI
Pruritus Self-care (non-drug)
Purpose: reduce skin irritation and sleep disruption.
Mechanism: menthol moisturizers, oatmeal baths, cooling packs; sleep hygiene routines. PMC
Itch-focused Cognitive-Behavioral Coping
Purpose: break the itch-scratch cycle; manage stress that worsens itch perception.
Mechanism: CBT and relaxation reduce central amplification of itch. PMC
Infection Action Plan
Purpose: rapid treatment of cellulitis (red, hot, painful limb ± fever).
Mechanism: early antibiotics as directed by clinicians; carry an emergency letter if recurrent. PubMed
School/Workplace Adaptations
Purpose: reduce limb dependency and skin trauma; allow therapy time.
Mechanism: breaks for elevation, compression tolerance, climate control.
Vaccination & Bleeding-Risk Safety
Purpose: protect from infections; minimize bleeding due to vitamin K deficiency.
Mechanism: stay current with vaccines; care teams monitor INR and give vitamin K when appropriate. NCBI
Sunlight/Jaundice Monitoring
Purpose: recognize cholestasis flares early.
Mechanism: track stool/urine color, pruritus, scleral icterus; notify hepatology team. Orpha
Bone-Health Program
Purpose: prevent rickets/osteopenia with chronic cholestasis.
Mechanism: vitamin D repletion, calcium intake, weight-bearing activity as advised. malacards.org
Specialist Lymphedema Footwear & Orthotics
Purpose: reduce friction/pressure; improve gait with swelling.
Patient Community & Psychosocial Support
Purpose: improve quality of life; share practical strategies.
Mechanism: rare-disease groups and counseling improve coping and adherence. PMC

Drug treatments

Medication choices must be individualized by your liver/lymphedema specialists—especially in children. Pediatric dosing is often weight-based.

Ursodeoxycholic acid (UDCA)
Purpose: improve bile flow in cholestasis episodes (used off-label here).
Dose/Time: adults often 13–15 mg/kg/day in divided doses; pediatric dosing per specialist.
Mechanism: hydrophilic bile acid that protects cholangiocytes and enhances bile secretion.
Side effects: GI upset; rare liver test changes. (General cholestasis practice.)
Cholestyramine (or Colestipol/Colesevelam) – first-line for cholestatic itch
Dose/Time: 4 g 1–4×/day (separate from other meds—esp. UDCA—by 4–6 h).
Mechanism: binds bile acids in the gut so less recirculates → less itch.
Side effects: bloating, constipation; drug–drug interactions. PMC
Rifampin (rifampicin) – for moderate–severe itch not controlled by resins
Dose/Time: 150–300 mg twice daily (adult typical); careful liver monitoring.
Mechanism: activates PXR, alters pruritogenic pathways (e.g., autotaxin).
Side effects: hepatotoxicity, orange discoloration of fluids, drug interactions. AASLDPMC
Naltrexone (opioid antagonist) – third-line for refractory itch
Dose/Time: adults often 25–50 mg daily; pediatric dosing is weight-based and specialist-guided.
Mechanism: resets opioid tone involved in cholestatic pruritus.
Side effects: withdrawal-like symptoms in opioid users, nausea, fatigue. PMC
Sertraline (SSRI) – option when others fail or as add-on
Dose/Time: 50–100 mg daily (adult typical).
Mechanism: central modulation of itch perception and mood.
Side effects: GI upset, sleep changes, sexual dysfunction. AASLD
Antihistamines (e.g., Hydroxyzine at night)
Purpose: help sleep and provide mild itch relief (histamine is not the main driver).
Mechanism: sedation and some antipruritic effect.
Side effects: drowsiness, anticholinergic effects. PMC
IBAT inhibitors (Maralixibat, Odevixibat) – specialist use in pediatric cholestatic diseases
Purpose: reduce pruritus by blocking bile-acid reuptake in the ileum.
Mechanism: less enterohepatic recycling → lower serum bile acids → less itch.
Regulatory status: Maralixibat approved for Alagille syndrome; Odevixibat for PFIC. Use in LCS1 is off-label and specialist-only.
Key points: weight-based dosing; possible diarrhea, abdominal pain; monitor fat-soluble vitamins. FDA Access Data+1PMC
Vitamin K
Purpose: correct bleeding tendency from malabsorption.
Mechanism: restores clotting-factor gamma-carboxylation.
Side effects: rare hypersensitivity with IV forms; oral usually well tolerated. NCBI
Vitamin D (± Calcium), Vitamin A, Vitamin E supplementation
Purpose: prevent rickets, neuropathy, vision and neurologic complications.
Mechanism: repletion of fat-soluble vitamins affected by cholestasis.
Side effects: hypervitaminosis if overdosed → monitor levels. NCBI
Medium-Chain Triglyceride (MCT) formulas (medical nutrition)
Purpose: improve energy intake when long-chain fat absorption is poor.
Mechanism: MCTs absorb directly via portal vein, bypassing bile-dependent micelles.
Side effects: GI upset if excessive. NCBI
Ursodiol + Resin spacing strategy
Purpose: practical regimen to keep both therapies effective.
Mechanism: take UDCA well apart from cholestyramine (≥4–6 h) to avoid binding. PMC
Antibiotics for cellulitis (if lymphedema-related skin infections occur)
Purpose: treat/manage acute infections that flare edema.
Mechanism: pathogen-directed therapy per local protocols; sometimes prophylaxis if recurrent. PubMed
Bile-acid lowering combinations
Purpose: add-on sequences (resin → rifampin → naltrexone/sertraline) for stubborn itch under supervision.
Mechanism: stepwise, additive regimen per liver guidelines. AASLD
Topical therapies for itch (menthol/calamine/Pramoxine lotions)
Purpose: symptomatic relief to reduce scratching.
Mechanism: counter-irritation or local anesthetic effect. PMC
Diuretics (limited role; for non-lymphatic edema/ascites only)
Purpose: manage fluid overload from other causes; do not treat true lymphedema.
Mechanism: renal sodium/water excretion.
Caution: not helpful for lymphedema; avoid dehydration. PubMed

Dietary “molecular” supplements

Always coordinate with your hepatology dietitian; absorption can be variable in cholestasis.

Vitamin K – dose per labs/clinic protocol
Function: clotting; prevents bleeding.
Mechanism: cofactor for clotting-factor activation. NCBI
Vitamin D3 – dose to target normal 25-OH-D
Function: bone health; prevents rickets/osteopenia.
Mechanism: calcium/phosphate metabolism. malacards.org
Vitamin A – dose per level; avoid megadoses
Function: vision/immune function; prevents night blindness.
Mechanism: retinoid signaling. malacards.org
Vitamin E (natural d-alpha-tocopherol or water-miscible mixed tocopherols)
Function: neurologic protection; antioxidant.
Mechanism: membrane stabilization; free-radical scavenging. malacards.org
MCT oil / MCT-based formulas – start small (e.g., 5–10 mL with meals)
Function: calorie support when fat absorption is poor.
Mechanism: bile-independent absorption to portal vein. NCBI
Omega-3 (EPA/DHA) – typical adult 1–2 g/day (ask your team)
Function: anti-inflammatory; may help fatty-acid balance in cholestasis.
Mechanism: eicosanoid modulation.
Taurine – specialist-guided
Function: bile-acid conjugation support (theoretical benefit).
Mechanism: facilitates bile salt formation.
Zinc – dose per deficiency
Function: growth, wound healing; taste.
Mechanism: cofactor for many enzymes.
S-adenosyl-L-methionine (SAMe) – specialist-guided, adult use
Function: methyl donor; studied in intrahepatic cholestasis for fatigue/itch in adults.
Mechanism: influences bile flow and detox pathways.
Probiotics (selected strains)
Function: gut barrier/microbiome support during fat malabsorption.
Mechanism: bile salt deconjugation and anti-inflammatory effects (evidence evolving).

(Items 6–10 have emerging or condition-specific evidence; your team will individualize.)

Regenerative / stem-cell” drugs

There are no approved stem-cell or “regenerative” drugs for cholestasis-edema (Aagenaes) syndrome. The items below are investigational or apply to other cholestatic/lymphatic disorders and should not be used outside clinical trials.

VEGF-C Gene Therapy (e.g., Lymfactin®) – experimental
Function/mechanism: delivers VEGF-C to stimulate lymphangiogenesis, sometimes combined with lymph node transfer. Early human studies show feasibility; larger trials are ongoing. ScienceDirectClinicalTrials.govPubMed
Mesenchymal Stromal/Stem Cells (MSCs) – experimental
Function/mechanism: proposed to modulate inflammation and promote lymphatic repair in secondary lymphedema; small trials/series only. PMC
Lymphatic Vessel/Node Tissue Engineering (scaffolds + stem cells) – preclinical/early clinical
Function/mechanism: decellularized scaffolds seeded with stem cells to rebuild lymphatic structures. Nature
Hepatocyte Transplantation – experimental/selected pediatric cholestatic diseases
Function/mechanism: donor liver cells infused to bridge or partially correct metabolic cholestasis; mixed, disease-specific results. Not standard for LCS1. Gastro Journal
Apelin + VEGF-C mRNA Combinations – preclinical
Function/mechanism: synergistic restoration of lymphatic function in models. EMBO Press
Growth-factor/MSC sheet therapies for lymphatic regeneration – preclinical/early clinical concepts
Function/mechanism: engineered cell sheets to promote lymphatic network regrowth. ScienceDirect

Surgeries

Surgery is not first-line. It is considered for refractory lymphedema or advanced liver disease after conservative measures and drug regimens.

Lymphaticovenous Bypass / Lymphovenous Anastomosis (LVA/LVB)
What: super-microsurgery connecting tiny lymphatics to venules to bypass blockages.
Why: reduce limb volume and infections in early-stage lymphedema when functioning lymphatics remain. Evidence shows volume reduction and quality-of-life benefits in selected patients. Lymphoedema Education Solutions
Vascularized Lymph Node Transfer (VLNT)
What: move a packet of healthy lymph nodes with their blood supply to the affected area.
Why: create a new drainage “hub” for chronic lymphedema when LVA is not sufficient; studies show meaningful volume and QoL improvements. JVS Venous+1
Liposuction (Suction-Assisted Lipectomy) for Lymphedema
What: removes fibrofatty tissue in late-stage, non-pitting limbs.
Why: reduces limb size when fluid-shifting surgeries are unlikely to work; requires lifelong compression afterward. PubMed
Biliary Diversion Procedures (select pediatric cholestatic disorders)
What: partial external biliary diversion or related operations to reduce enterohepatic bile acid load.
Why: in intractable cholestatic pruritus of select diseases to delay/avoid transplant; role in LCS1 is specialist-judged and uncommon in modern practice. FDA Access Data
Liver Transplantation
What: replace diseased liver.
Why: end-stage liver disease or unmanageable complications; standard of care across pediatric cholestatic conditions when criteria are met. ScienceDirectClinMed Journals

Preventions (practical risk-reduction tips)

Early recognition of cholestasis flares (jaundice, pale stools, dark urine, rising itch) and prompt labs. Orpha
Adherence to compression/CDT to prevent progression of lymphedema. PubMed
Daily skin care + foot protection to prevent cellulitis. PubMed
Vaccinations up to date; protect against infections that can worsen liver status. Orpha
Vitamin monitoring and repletion (A, D, E, K) to avoid bone/neurologic issues. malacards.org
Nutrition plans with MCT and adequate calories for growth/maintenance. NCBI
Avoid overheating and scratch triggers; keep nails short; cotton/soft fabrics. PMC
Weight management and regular activity within tolerance. PubMed
Medication timing (space cholestyramine from other meds). PMC
Regular specialist follow-up (hepatology + lymphedema clinic) with tailored care plans. PubMed

When to see doctors urgently

Fever, red/hot/painful swollen limb, or rapidly worsening swelling → possible cellulitis. PubMed
Worsening jaundice, pale/gray stools, very dark urine, or severe itch disrupting sleep despite treatment. AASLD
Bleeding/bruising, especially with known vitamin K issues. NCBI
Poor growth/weight loss (children) or fatigue and muscle wasting (adults). malacards.org
Signs of decompensated liver disease: ascites, confusion, GI bleeding—seek emergency care. (General hepatology standards.)

Foods to favor and to limit/avoid

Eat more of (as tolerated with your team’s advice):

Energy-dense meals using MCT oil for cooking or add-ins. NCBI
Lean proteins (fish, poultry, legumes) for growth/repair.
Calcium-rich options (dairy or fortified alternatives) with vitamin D plan. malacards.org
Colorful fruits/vegetables for micronutrients and fiber.
Whole grains as tolerated for energy and bowel health.
Bananas/avocado/yogurt (gentle, calorie-dense snacks).
Nut butters (portion-controlled for calories/protein).
Hydration: water; oral rehydration when unwell.
Omega-3 sources (fatty fish; consider supplements per clinic).
Small, frequent meals to meet energy needs.

Limit/avoid:

Very fatty, fried foods if they worsen steatorrhea (greasy stools).
Alcohol (adults) due to liver strain.
Highly salted foods if fluid retention is an issue.
Unpasteurized foods/undercooked meats (infection risk).
Herbal/botanical “liver cleanses” (possible hepatotoxicity).
Mega-doses of fat-soluble vitamins without supervision. malacards.org
Energy drinks and excess caffeine (sleep disruption/itch).
Wool/irritating fabric contact with skin (not a food, but an itch trigger to remember). PMC
High-sugar ultra-processed snacks (weight gain/inflammation).
Grapefruit if on interacting meds (ask pharmacist/hepatology).

Frequently Asked Questions

Is cholestasis-edema syndrome the same as Aagenaes syndrome?
Yes. It’s also called cholestasis-lymphedema syndrome (LCS1), a rare inherited condition first described in Norway. Orpha
What gene is involved?
Most patients carry a UNC45A 5’-UTR variant (c.–98G>T) that lowers UNC45A and mislocalizes bile transporters; inheritance is autosomal recessive. research-repository.st-andrews.ac.uk
Do all children “outgrow” cholestasis?
Many experience fewer and milder episodes with age, but some develop liver scarring; ongoing follow-up is essential. malacards.org
Why does my child need vitamins even if they eat well?
Fat-soluble vitamins (A, D, E, K) are poorly absorbed when bile flow is low, so supplements prevent bone, bleeding and nerve problems. malacards.org
What actually causes the terrible itch?
Multiple signals—including bile acids and enzymes like autotaxin/LPA—sensitize nerves. That’s why therapies target bile acids, nuclear receptors, opioid pathways, and serotonin. PMC
Which medicine is first for itch?
Cholestyramine (a bile-acid resin) is the recommended first step, followed by rifampin, naltrexone, or sertraline if needed—under clinician oversight. AASLDPMC
Are new medicines available for pediatric cholestatic itch?
Yes—IBAT inhibitors (maralixibat for Alagille syndrome, odevixibat for PFIC) reduce pruritus by cutting bile-acid recycling. Use for LCS1 would be off-label and specialist-guided. FDA Access DataPMC
Do diuretics help the leg swelling?
Not for true lymphedema. They can help other kinds of fluid overload but don’t fix lymphatic congestion. CDT and compression are key. PubMed
Will surgery cure lymphedema?
No guaranteed cure, but LVA/LVB or VLNT can reduce volume and infections in selected patients, especially when paired with lifelong compression. Lymphoedema Education SolutionsJVS Venous
When is liver transplant considered?
With end-stage liver disease or complications not controlled by medical care. It’s standard across pediatric cholestatic diseases when criteria are met. ScienceDirect
How common is this syndrome?
Exceptionally rare—~100 reported worldwide, highest prevalence in Norway. PMC
Can adults be diagnosed?
Yes; some are recognized later, especially if childhood jaundice was intermittent but lymphedema progressed. Genetic testing can confirm. research-repository.st-andrews.ac.uk
Is pregnancy safe for women with past cholestasis episodes?
Individual risk varies; plan with hepatology/obstetrics because pregnancy can affect bile flow and itch.
Are “stem-cell therapies” available?
Not as approved treatments for this syndrome. Gene/stem-cell/VEGF-C approaches are experimental and should be limited to clinical trials. PMCScienceDirect
What matters most day-to-day?
Consistent compression & skin care, nutrition and vitamins, timely itch management, and regular specialist follow-up. These steps protect your liver, skin and quality of life. PubMedAASL

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