What is the treatment approach for amyloidosis (a condition characterized by the deposition of amyloid proteins) of the skin?

Treatment of Cutaneous Amyloidosis

Primary Localized Cutaneous Amyloidosis (PLCA)

For primary localized cutaneous amyloidosis, the most effective treatment is combination therapy with UVA1 phototherapy plus high-potency topical corticosteroids, which achieved complete symptom clearance in the highest proportion of patients. 1

Classification and Diagnosis

PLCA is defined by amyloid protein deposition in the skin without systemic involvement and includes three main subtypes: 1, 2

• Lichen amyloidosis (LA) - most common subtype (56.8% of cases) 1
• Macular amyloidosis (MA) - second most common (28% of cases) 1
• Biphasic amyloidosis (BA) - less common (16.2% of cases) 1
• Nodular amyloidosis (NA) - rare subtype 2

Diagnosis requires histopathologic confirmation with Congo red staining showing characteristic apple-green birefringence under polarized light. 3, 4

Treatment Algorithm for PLCA

First-line therapy:

• UVA1 phototherapy combined with high-potency topical corticosteroids - this combination showed complete clearance in 10.8% of patients and represents the most effective treatment option 1

Second-line options (showing substantial improvement in 12.7% of patients): 1

• High-potency topical corticosteroids alone
• High-potency topical corticosteroids plus bath PUVA
• UVA1 phototherapy monotherapy
• Capsaicin 0.075% cream

Less effective options to avoid:

• Low- or medium-potency topical corticosteroids (alone or with UVBnb phototherapy) showed lower efficacy 1

Additional Treatment Modalities

While evidence is limited to case reports and small series, other reported options include: 2

• Retinoids
• Cyclophosphamide
• Cyclosporine
• Amitriptyline
• Colchicine
• Tacrolimus
• Dimethyl sulfoxide
• Vitamin D3 analogs
• Menthol
• Hydrocolloid dressings
• Surgical modalities
• Laser treatment

Critical caveat: No randomized controlled trials exist for PLCA treatment, and most evidence comes from case reports, making definitive treatment recommendations challenging. 2

Systemic Amyloidosis with Cutaneous Involvement

Diagnostic Approach

When systemic amyloidosis is suspected, skin biopsy has exceptionally high diagnostic yield (97% positive rate in one series), making it a valuable diagnostic tool. 5 Amyloid deposits can be found in: 5

• Papillary dermis
• Reticular dermis
• Subcutis
• Around appendages
• In or around blood vessels

Essential next steps after confirming amyloid on skin biopsy: 3, 4

1. Type the amyloid protein using mass spectrometry (gold standard), immunohistochemistry, or immunofluorescence 4
2. Perform monoclonal protein screening with serum free light chain assay, serum immunofixation electrophoresis, and urine immunofixation electrophoresis (do NOT use standard protein electrophoresis alone due to lower sensitivity) 4
3. Obtain bone marrow biopsy to demonstrate clonal plasma cell proliferation 4

Treatment of Systemic AL Amyloidosis

The treatment of systemic AL amyloidosis targets the underlying plasma cell disorder, NOT the skin manifestations directly. 3, 4

First-line treatment for most patients:

• Daratumumab plus cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) - FDA-approved and demonstrated very good partial responses or better in 78.5% of patients versus 49.2% with CyBorD alone 6, 4

For transplant-eligible patients (approximately 25% of newly diagnosed cases): 6

• Consider high-dose melphalan followed by autologous stem cell transplantation (HDM/SCT)
• Eligibility criteria: ejection fraction >40%, ability to tolerate fluid shifts and infections, limited organ involvement 6
• Treatment-related mortality is approximately 3% in experienced centers 3, 6
• Prior to transplant, give 2-4 cycles of bortezomib-based induction if bone marrow plasma cells >10% 6

Critical Monitoring Considerations

Cardiac toxicities of treatments: 3, 6, 4

• Daratumumab: cardiac failure (12%), cardiac arrhythmia (8%), atrial fibrillation (6%)
• Bortezomib: grade 3 heart failure (6.4%), >10% decrease in LVEF (23%)
• Corticosteroids: peripheral edema, pulmonary edema, fluid overload

Response assessment timeline: 6

• Hematologic response typically occurs within 3-6 months
• Organ-specific response (including skin) generally occurs 6-12 months after hematologic response

Common Pitfalls

• Do NOT treat systemic amyloidosis skin lesions with topical therapies alone - this misses the underlying life-threatening plasma cell disorder 3, 4
• Do NOT use standard protein electrophoresis (SPEP/UPEP) alone for diagnosis due to lower sensitivity 4
• Do NOT delay referral to hematology - cardiac involvement is the main driver of mortality and early treatment improves survival 6, 4
• Differentiate between AL and ATTR amyloidosis - management differs significantly, with ATTR requiring different targeted therapies 6, 4