Approach to Skin Rash
Anderson–Fabry Disease • Lysosomal Storage Disorder • MRCP (UK) PACES
A structured approach to a patient presenting with a skin rash caused by Anderson–Fabry disease. Learn how to recognise angiokeratomas, identify multisystem involvement, perform a focused assessment and explain the diagnosis, investigations and treatment with confidence.
At a Glance
Red Flags
PACES Approach
Organ Involvement Snapshot
LVH
Arrhythmias
Valve disease
TIA
Stroke
Neuropathic pain
Cornea verticillata
Retinal vessel tortuosity
Proteinuria
CKD
Renal failure
Acroparesthesia
Burning pain
Hypohidrosis
Angiokeratomas
Heat intolerance
Overview
Anderson–Fabry disease is a rare X-linked lysosomal storage disorder caused by deficiency of α-galactosidase A, leading to progressive accumulation of glycosphingolipids in blood vessels and multiple organs. Patients may initially present with angiokeratomas, burning neuropathic pain, renal impairment, cardiac disease or early cerebrovascular events. In MRCP (UK) PACES, recognising the characteristic skin lesions together with the multisystem manifestations is the key to making the diagnosis and explaining modern treatment options, including enzyme replacement therapy.
Structured History
- Onset, distribution and progression of the skin rash
- Burning pain in the hands and feet (acroparesthesia)
- Heat intolerance or reduced sweating (hypohidrosis)
- Exercise-induced pain or worsening symptoms with fever
- Foamy urine, haematuria or declining renal function
- Palpitations, chest pain or exertional breathlessness
- History of TIA, stroke or dizziness
- Visual symptoms or previous ophthalmology review
- Gastrointestinal symptoms (abdominal pain or diarrhoea)
- Family history of kidney disease, cardiomyopathy or early stroke
Examination
- Inspect for angiokeratomas (trunk, groin and upper thighs)
- Assess distribution and extent of skin lesions
- Look for cornea verticillata if slit-lamp findings are available
- Cardiovascular examination for LVH or murmurs
- Blood pressure measurement
- Neurological examination including peripheral sensation
- Assess gait and proprioception
- Examine for peripheral oedema
- Look for evidence of chronic kidney disease
- General examination for multisystem involvement
Differential Diagnosis
Investigations
- α-Galactosidase A enzyme assay
- GLA gene mutation analysis
- Urinalysis and urine protein quantification
- Renal profile (U&E, eGFR)
- ECG and Echocardiography
- Cardiac MRI if cardiomyopathy is suspected
- MRI brain if cerebrovascular involvement is suspected
- Ophthalmology assessment for cornea verticillata
- Audiology assessment if hearing symptoms are present
- Family screening and genetic counselling
Diagnosis
Anderson–Fabry Disease
The diagnosis is suggested by angiokeratomas together with burning neuropathic pain, renal impairment and cardiac involvement. Confirmation is by demonstrating reduced α-galactosidase A activity and identifying a pathogenic mutation in the GLA gene.
Management
Explaining to the Patient
"The skin changes, together with your other symptoms, suggest a rare inherited condition called Anderson–Fabry disease. It can affect several organs including the kidneys, heart and nervous system. Further blood tests and genetic testing will confirm the diagnosis. Effective treatments are available to slow disease progression, and your care will involve a team of specialists."
Examiner's Corner
What is Anderson–Fabry disease?
Anderson–Fabry disease is a rare X-linked lysosomal storage disorder caused by deficiency of the enzyme α-galactosidase A. This leads to accumulation of globotriaosylceramide (Gb3) within blood vessels and multiple organs, producing progressive renal, cardiac, neurological and cutaneous disease.
What are the classical clinical features?
Common Viva Questions
- What is the inheritance pattern?
- Which enzyme is deficient?
- How is the diagnosis confirmed?
- What organs are commonly affected?
- What treatments are available?
- Which family members should be screened?
- What is the prognosis?
Disease-specific Treatment
- Enzyme replacement therapy (Agalsidase alfa or beta)
- Pharmacological chaperone therapy (selected mutations)
- Neuropathic pain management
- ACE inhibitor or ARB for proteinuria
- Management of cardiac and cerebrovascular complications
- Regular multidisciplinary follow-up
Pathfinder Pearls
Common Pitfalls
- Assuming the rash is an isolated dermatological condition.
- Failing to ask about burning neuropathic pain.
- Ignoring renal involvement and proteinuria.
- Not screening for cardiac disease or arrhythmias.
- Overlooking cornea verticillata.
- Forgetting the X-linked inheritance pattern.
- Missing the opportunity for family screening and genetic counselling.
Master MRCP (UK) PACES with PACES Pathfinders
Develop a structured approach to presenting complaints, communication stations and short cases through interactive online teaching, mock stations, examiner-focused discussions and comprehensive recorded revision resources.