Can Systemic Amyloidosis Cause Itching?
Systemic amyloidosis itself does not directly cause pruritus as a disease manifestation, but itching can occur as a medication side effect when treating autonomic complications of the disease, specifically from midodrine used for orthostatic hypotension.
Direct Disease-Related Pruritus
Systemic amyloidosis (both AL and ATTR types) does not typically present with pruritus as a primary symptom. The 2023 American College of Cardiology comprehensive guidelines on cardiac amyloidosis do not list itching among the clinical manifestations of either AL or ATTR systemic amyloidosis 1.
The key organ systems affected by systemic amyloidosis include:
- Heart (restrictive cardiomyopathy) 1
- Kidneys (proteinuria, nephrotic syndrome) 1
- Gastrointestinal tract (malabsorption, dysmotility, bleeding) 1
- Peripheral and autonomic nervous systems (neuropathy, orthostatic hypotension) 1
- Soft tissues in AL amyloidosis (macroglossia, periorbital purpura) 1
Treatment-Related Pruritus
The most clinically relevant connection between systemic amyloidosis and itching is as an adverse effect of midodrine, a sympathomimetic agent used to treat orthostatic hypotension in amyloidosis patients. According to the American College of Cardiology, midodrine causes "supine hypertension; itching (especially scalp itching) due to pilomotor activation; urinary retention; and headaches" 1, 2, 3.
Midodrine dosing and monitoring considerations:
- Starting dose: 2.5 mg three times daily 2
- Maximum dose: 10 mg three times daily 2
- Titrate based on symptoms and blood pressure 1
- May be poorly tolerated in heart failure patients 1, 2, 3
Important Distinction: Localized vs. Systemic Amyloidosis
A critical pitfall is confusing systemic amyloidosis with primary localized cutaneous amyloidosis (PLCA), which includes lichen amyloidosis and macular amyloidosis. These are entirely different entities where pruritus is a cardinal feature 4, 5, 6. In PLCA, chronic scratching leads to keratinocyte necrosis and amyloid deposition in the papillary dermis 5. This is NOT systemic amyloidosis and does not involve internal organs 6.
Cutaneous Manifestations of Systemic AL Amyloidosis
When skin involvement does occur in systemic AL amyloidosis, the typical presentations are:
- Periorbital purpura 1
- Petechiae and ecchymoses from vascular wall infiltration 7
- Papular lesions (uncommon) 7
- Nail abnormalities 8
Notably, these cutaneous manifestations of systemic AL amyloidosis are typically described as non-pruritic 7.
Clinical Algorithm
When evaluating a patient with systemic amyloidosis and itching:
First, review medications - Is the patient taking midodrine for orthostatic hypotension? If yes, this is the likely cause 1, 2, 3
Consider alternative causes of pruritus - Systemic amyloidosis can cause renal involvement with uremia, which itself can cause pruritus 1
Rule out unrelated dermatologic conditions - The presence of systemic amyloidosis does not preclude other causes of itching 1
Do not confuse with localized cutaneous amyloidosis - If skin lesions with pruritus preceded systemic symptoms, consider that these may be separate conditions 5, 6
Management Considerations
If midodrine-induced pruritus is problematic, alternative agents for orthostatic hypotension include:
- Droxidopa (100-600 mg three times daily) - causes supine hypertension, headaches, dizziness, and nausea but NOT specifically itching 1
- Pyridostigmine (30-60 mg 2-3 times daily) - less likely to cause supine hypertension 1
Severe autonomic dysfunction requiring midodrine or droxidopa that cannot be weaned is considered a contraindication to heart transplantation in cardiac amyloidosis patients 1, 2, 3.