What are the cutaneous manifestations associated with cardiac amyloidosis and how can I, as a dermatologist, contribute to a cardiologist's assessment and management of a patient with this condition?

Cutaneous Manifestations of Cardiac Amyloidosis and the Dermatologist's Role

Key Cutaneous Findings in AL Amyloidosis

As a dermatologist, you should immediately refer any patient with periorbital purpura or macroglossia for cardiac amyloidosis evaluation, as these are pathognomonic signs of AL amyloidosis that frequently precede cardiac diagnosis. 1

Pathognomonic Skin Findings (AL Amyloidosis Only)

• Periorbital purpura (periorbital ecchymoses) is the most characteristic dermatologic finding and should trigger immediate evaluation for AL amyloidosis 1, 2
• Pinch purpura occurs in skin folds and represents fragile blood vessels due to amyloid infiltration 3
• Macroglossia and submandibular gland enlargement from soft tissue amyloid infiltration are pathognomonic when present 1, 4
• Skin involvement is specifically listed as an extracardiac manifestation of AL (light-chain) amyloidosis but NOT of ATTR (transthyretin) amyloidosis 1

Additional Soft Tissue Manifestations

• Coagulopathy manifestations including easy bruising from acquired factor X deficiency 1
• Waxy, thickened skin may be present due to dermal amyloid deposits 2
• Inframammary erosions and ecchymoses in skin folds have been reported 3

Critical Distinction: AL vs ATTR Amyloidosis

The presence or absence of cutaneous findings helps distinguish between amyloid types, which is crucial because treatments are completely different. 1

AL Amyloidosis Cutaneous Pattern

• Periorbital purpura, macroglossia, and skin involvement are characteristic 1, 4
• Median survival is only 13 months (4 months with heart failure), making early recognition critical 1

ATTR Amyloidosis Pattern (No Skin Involvement)

• Musculoskeletal findings such as biceps tendon rupture and spinal stenosis are indicative of ATTR, not AL 1, 4, 2
• History of carpal tunnel syndrome is common in ATTR 1, 2
• No periorbital purpura or macroglossia 1, 4

Your Specific Contributions as a Dermatologist

1. Early Diagnostic Recognition

You can facilitate earlier diagnosis by recognizing subtle cutaneous signs before cardiac symptoms become severe. 5

• Identify periorbital purpura in patients who may attribute it to aging or minor trauma 2, 3
• Recognize macroglossia during oral examination 1, 6
• Document pinch purpura in skin folds during routine examination 3
• Note any unexplained easy bruising patterns 1

2. Facilitate Tissue Diagnosis

Skin biopsy can serve as a surrogate site for amyloid diagnosis, avoiding more invasive cardiac biopsy. 1, 6

• Abdominal fat pad aspiration has 84% sensitivity for AL cardiac amyloidosis 1
• Skin biopsy from affected areas (purpuric sites, macroglossia tissue) can demonstrate Congo red-positive amyloid deposits 6
• Critical caveat: If surrogate site biopsy is negative but clinical suspicion remains high, cardiac biopsy is still required 1
• Ensure tissue is sent for mass spectrometry (LC-MS/MS) typing, not just Congo red staining, as this is the gold standard with 88% sensitivity and 96% specificity 1, 7

3. Coordinate Comprehensive Workup

Initiate the diagnostic cascade by ordering or recommending specific tests. 1

• Order serum free light chain assay (sFLC), serum immunofixation electrophoresis (SIFE), and urine immunofixation electrophoresis (UIFE) simultaneously 1, 7
• Never rely on standard protein electrophoresis (SPEP/UPEP) alone as it has inadequate sensitivity 1, 7
• Refer to hematology for bone marrow biopsy to demonstrate clonal plasma cell proliferation 1, 7
• Coordinate with cardiology for echocardiography and cardiac biomarkers (NT-proBNP, troponin) 5, 6

4. Provide Prognostic Information

Inform the cardiologist that cutaneous findings indicate AL amyloidosis, which has dramatically worse prognosis than ATTR. 1

• AL amyloidosis with heart failure has median survival of only 4 months without treatment 1
• Cardiac involvement is the main driver of mortality in AL amyloidosis 7, 4
• Early recognition allows initiation of daratumumab-based chemotherapy regimens that can improve survival 7

5. Monitor for Treatment Complications

Collaborate in monitoring for dermatologic manifestations of chemotherapy toxicity. 7

• Daratumumab (anti-CD38 antibody) is first-line therapy for AL amyloidosis and can cause infusion reactions 7
• Corticosteroids (dexamethasone) require monitoring for skin changes, peripheral edema 7
• Proteasome inhibitors may cause skin reactions 7

Practical Clinical Algorithm for Dermatologists

When You See These Findings:

1. Periorbital purpura + any cardiac symptoms (dyspnea, fatigue, edema):

   • Order sFLC, SIFE, UIFE immediately 1, 7
   • Perform skin or fat pad biopsy with request for Congo red staining AND mass spectrometry 1, 6
   • Urgent cardiology referral 5

2. Macroglossia + unexplained weight loss or proteinuria:

   • Same workup as above 1
   • Consider nephrology referral 1, 4

3. Pinch purpura in skin folds + systemic symptoms:

   • Biopsy the purpuric area for amyloid typing 3
   • Complete monoclonal protein screening 1

Common Pitfalls to Avoid

• Do not dismiss periorbital purpura as cosmetic or age-related without excluding AL amyloidosis in patients over 50 years 2, 3
• Do not assume all cardiac amyloidosis has skin findings - ATTR amyloidosis (more common in elderly) has NO cutaneous manifestations 1, 4
• Do not accept negative SPEP/UPEP as ruling out AL amyloidosis - immunofixation and free light chains are mandatory 1, 7
• Do not delay referral waiting for "complete workup" - cardiac AL amyloidosis progresses rapidly and early treatment is life-saving 1, 5