Systemic Conditions Associated with Angioid Streaks
Patients with angioid streaks should be evaluated primarily for pseudoxanthoma elasticum (PXE), Paget's disease of bone, and sickle cell hemoglobinopathies, as these three conditions account for the majority of systemic associations. 1, 2
Primary Systemic Associations
Pseudoxanthoma Elasticum (Most Common)
- PXE is the most frequently associated systemic condition with angioid streaks, characterized by autosomal recessive inheritance causing elastin calcification in multiple organ systems 3, 4
- Look for characteristic skin findings: yellowish papules and redundant, lax skin in flexural areas (neck, axillae, antecubital and popliteal fossae) 3
- Cardiovascular manifestations include premature atherosclerosis, claudication, and increased risk of myocardial infarction and stroke requiring cardiology evaluation 3
- Confirm diagnosis with skin biopsy showing fragmented and calcified elastic fibers 3
Paget's Disease of Bone
- This metabolic bone disorder causes abnormal bone remodeling and is the second most common association 1, 2
- Screen with serum alkaline phosphatase levels and bone-specific markers 4
- Look for bone pain, skeletal deformities, and increased skull size 2
Sickle Cell Hemoglobinopathies
- Includes sickle cell disease and sickle cell trait as important associations 1, 2
- Order hemoglobin electrophoresis for definitive diagnosis 4
- These patients have additional retinal vascular complications beyond angioid streaks 2
Secondary Systemic Associations
Connective Tissue Disorders
- Ehlers-Danlos syndrome presents with joint hypermobility, skin hyperextensibility, and tissue fragility 2, 5
- Marfan syndrome shows tall stature, arachnodactyly, and cardiovascular abnormalities 2
Diagnostic Workup Algorithm
When angioid streaks are identified, implement this systematic evaluation:
Dermatologic examination for PXE skin lesions (flexural areas, neck) with dermatology referral if suspicious findings present 3
Laboratory testing including:
Cardiovascular assessment with cardiology referral, particularly if PXE suspected, given risk of premature atherosclerosis and vascular complications 3
Skin biopsy if clinical findings suggest PXE, looking for fragmented and calcified elastic fibers 3
Prevalence and Clinical Context
- Up to 50% of patients with angioid streaks have an identifiable systemic disease association 4
- The remaining cases may be idiopathic, though thorough systemic evaluation should still be performed 4
- Angioid streaks represent irregular, linear breaks in Bruch's membrane that appear as pigmented lines radiating from the optic disc 4, 5
Critical Management Considerations
The brittle nature of Bruch's membrane in these patients creates vulnerability to subretinal hemorrhage even from minor trauma, necessitating patient counseling about avoiding contact sports and head trauma 4
Choroidal neovascular membrane development represents the major vision-threatening complication, requiring close monitoring with optical coherence tomography and prompt treatment with intravitreal anti-VEGF agents when detected 4, 5
A multidisciplinary team approach is essential involving ophthalmology, dermatology, cardiology, and hematology depending on the underlying systemic condition identified 3
Common Pitfalls to Avoid
- Do not assume angioid streaks are idiopathic without completing comprehensive systemic evaluation, as missing PXE can result in life-threatening cardiovascular complications 3
- Do not overlook subtle skin changes of PXE, which may require careful examination of flexural areas under good lighting 3
- Do not delay cardiovascular evaluation in confirmed or suspected PXE cases, as these patients face significantly increased risk of premature atherosclerotic disease 3