Practical insights into chronic management of hepatic Wilson’s disease

Table 1 Clinical manifestations of Wilson’s disease, copper deficiency, and anti-copper drugs adverse events

Clinical manifestations
Wilson’s disease	Copper deficiency	Anticopper drugs adverse events
Cardiac disturbances	Cardiac disturbances	D-penicillamine (20%-30%)
Arrhythmia (atrial fibrillation)	Severe bradycardia	Alopecia
Autonomic disturbances	Cutaneous manifestations	Arthralgias/arthritis
Cardiomyopathy	Cutaneous defective keratinization	Degenerative dermatoses (cutis laxa, anetoderma caused with focal loss of elastic tissue, pseudoxanthoma elasticum, elastosis perforans serpiginosa)
Cutaneous and subcutaneous manifestations	Decubitus wounds	Chephalgia
Acantosis nigricans	Delayed wound healing	Eryhema
Anetoderma	Depigmentation of the skin and hair	Fatigue
Azure lunulae of the nails	Hematologic disturbances	Hematuria
Dermatomyositis	Anemia (microcytic, normocytic, or macrocytic)	Hirsutism
Hyperpigmentation of the legs	Leukopenia	Hypogeusia
Lipomas (multiple, mainly affecting trunk and extremities)	Pancytopenia	Increase of antinuclear antibodies
Xerosis	Thrombocytopenia (rare)	Leukopenia or bone marrow depression
Endocrine system manifestations	Neurologic involvement	Lupus erythematosus
Amenorrhea	Myelopathy or myeloneuropathy (spastic paraparesis or tetraparesis or spastic ataxic gait)	Myalgias
Growth disruption	Progressive optic neuropathy (unilateral or bilateral)	Nausea
Infertility		Paradoxical neurological worsening
Parathyroid failure		Proteinuria
Recurrent abortions		Pruritus
Hematologic disturbances		Sicca symptoms
Acute Coombs-negative hemolytic anemia		Trientine (5%-10%)
Leucopenia, anemia, and low platelet count		Arthralgias
Hepatic involvement		Eryhema
Acute liver failure		Hirsutism
Chronic hepatitis		Increase of antinuclear antibodies
Hepatocarcinoma		Leukopenia
Intrahepatic cholangiogellular carcinoma		Lupus erythematosus
Liver cirrhosis		Myalgia
Steatosis		Nausea and/or diarrhoea
Neurological manifestations		Paradoxical neurological worsening
Dysarthria		Pruritus
Dysphagia		Sideroblastic anemia
Dystonia		Zinc salts (3%-7%)
Gait disturbance		Gastritis
Risus sardonicus		Increase in amylase and/or lipase (with no clinical relevance)
Rigidity		Leukopenia and bone marrow suppression
Tremor
Less frequent manifestations: chorea, athetosis, seizures and pyramidal signs
Ophthalmologic signs
Degeneration of retina and optic nerve
Kayser-Fleischer corneal rings
Sunflower cataracts (rare, not associated with ipovisus)
Osteoarticular involvement
Arthropathy (affecting mainly knees and wrists)
Osteopenia and osteoporosis
Skeletal abnormalities
Renal involvement
Elevated levels of blood urea nitrogen, creatinine, and uric acid (not associated with renal impairment)
Urinary calculus

Table 2 Suggested clinical and biochemical chronic monitoring of patients with Wilson’s disease

Clinical and biochemical monitoring of Wilson’s disease
Clinical monitoring	Biochemical monitoring
Abdominal US (1/yr in non-cirrhotic, 1/6 mo in cirrhotic patients)	NCC = total serum copper concentration (in μg/dL; serum copper in μmol/dL × 63.5 = serum copper in μg/dL) - 3.15 × holo-ceruloplasmin in mg/dL
Neurological assessment (using the Unified Wilson’s Disease Rating Scale) at every follow-up visit	24-h urine copper excretion
Identification of possible side effects of anti-copper drugs	Liver enzymes and liver function tests (aspartate aminotransferase, alanine aminotransferase, γ-glutamyl-transferase, alkaline phosphatase, bilirubin, international normalized ratio, and albumin) creatinine, and complete blood count
Gastroscopy in cirrhotic patients, when appropriate	For patients treated with DPA and trientine: 24 h-urine protein test, anti-nuclear antibodies
Transient elastography (1/yr in non-cirrhotic patients)	For patients treated with zinc: 24-hour urine zinc excretion
Central bone density scan at diagnosis, then individualise follow-up
If non-compliance is suspected: Slit-lamp examination to search for Kayser-Fleischer rings, brain MRI
For patients treated with DPA: skin biopsy at 10 yr from treatment initiation

DPA: D-penicillamine; MRI: Magnetic resonance imaging; NCC: Non-ceruloplamin-bound copper; US: Ultrasound.