Cutaneous amyloidosis includes various disorders characterized by the deposition of amyloid in the dermis.
Amyloidosis is a rare condition characterized by the extracellular deposition of an abnormal protein called amyloid in various organs. Cutaneous amyloidosis may be both primary and secondary, systemic and localized. Skin lesions in amyloidosis appear as purpura, macules and papules that may affect various parts of the body. Nails and hair may also be affected.
Causes and risk factors
Localized amyloidosis occurs when only the skin is affected and systemic amyloidosis develops as a part of systemic amyloidosis. Multiple myeloma and other malignant lymphomas are associated with systemic amyloidosis. Localized amyloidosis may be idiopathic or secondary due to skin neoplasms. Systemic secondary amyloidosis with skin manifestation develops in case of chronic inflammatory conditions (osteomyelitis, rheumatoid arthritis) or chronic infections (tuberculosis).
It is suggested that amyloid consists of immunoglobulin protein AL (light chain amyloid) in primary and myeloma-associated amyloidosis whereas in secondary amyloidosis amyloid is composed of non-immunoglobulin
protein (amyloid AA). However, in primary cutaneous amyloidosis the fibrils are built up of cytokeratine derivative.
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Primary cutaneous amyloidosis
Primary cutaneous amyloidosis includes several forms:
- Lichen amyloidosis initially presents as multiple discrete, firm, scaly, hyperkeratotic raised spots called papules, red-brown in color. Commonly the lesions appear on the shins and other extensor sides of the thighs, feet or forearms. The face, chest and abdomen are involved rarely. Later the papules coalesce forming thickened plaques with rippled pattern. Initially, only one side is affected and then gradually distribute symmetrically. Usually the affected person experiences extreme pruritus.
- Macular amyloidosis is characterized by the small brown or gray macules appear symmetrically on the upper back (especially interscapular area) and (less frequently) the extensor surface of the arms, in some cases chest and thighs may also be involved. A reticulated/rippled pattern is characteristic for these macules. Progressively macules interlock forming patches of darkened skin. The rash may be pruritic or asymptomatic.
- Nodular amyloidosis is a rare form of primary cutaneous amyloidosis caused, unlike the other forms of primary cutaneous amyloidosis, by the deposition of AL amyloid in the skin. Nodular amyloidosis is characterized by the red-brown nodules with central atrophy or ulceration.
- The combination of lichen and macular amyloidosis in one patient at the same time is called biphasic amyloidosis.
Secondary cutaneous amyloidosis
Localized amyloidosis of the skin is associated with epithelial tumors such as basal cell carcinoma, squamos cell carcinoma, seborrheic keratosis, actinic keratosus. Amyloid may be stored along the elastic fibers and develop in association with actinic elastosis or PUVA therapy.
Skin manifestation of primary systemic amyloidosis
Primary systemic amyloidosis is caused by the proliferation monoclonal light-chains. This condition is associated with various B cell disorders such as Waldenström macroglobulinemia, Bence-Jones plasmocytoma, etc. From 10% and up to 20% of those who suffer from multiple myeloma develop primary systemic amyloidosis with AL-type amyloid.
Typical lesions seen in systemic amyloidosis are purpura, petechiae, and
ecchymoses. The vessels become fragile due to the deposition of amyloid and therefore may be damaged even by a minor trauma. This results in characteristic purpura. Eyelid purpura is common as well. In the periorbital area (around the eyelids) may be detected xanthomatous plaques and waxy yellowish hemorrhagic lesions.
The tongue and the mucous membranes of the mouth may also be involved. Macroglossia (pathologically big tongue) is typical. Nails appear thin, whiten and fragile. Sometimes develops anonychia (complete absence of the nail). Hair may also be affected and even fall out causing alopecia.
Skin lesions in secondary amyloidosis
Secondary amyloidosis develops due to various chronic infections/inflammatory diseases such as tuberculosis, rheumatoid arthritis, inflammatory bowel disease, osteomyelitis. It is suggested that intense scratching is involved in the accumulation of amyloid in the skin.
Long-term haemodialysis is known to cause dialysis-related amyloidosis that may also lead to the skin involvement. In this case β2-microglobulin amyloid deposits in the skin appear as cutaneous or subcutaneous nodules.
The diagnosis is confirmed by performing a skin biopsy and blind aspiration biopsy. Later the samples are painted with the Congo red stain. To verify the systemic amyloidosis and underlying conditions other tests should be performed.
There is no treatment for cutaneous amyloidosis. However, some measures may reduce the symptoms and lessen the affected area of the skin.
General recommendations for treating skin lesions include avoiding irritation of the skin and cease the scratching. Sedating antihistamines (Chlorpheniramine, Diphenhydramine) and topical menthol cream are used to reduce the pruritus.
Treatment of primary cutaneous amyloidosis includes both conservative and surgical measures.
Ultraviolet B (UV-B) light (narrow band and broadband) and PUVA (psoralen with UVA) phototherapy may be performed at least for 8 weeks as a symptomatic treatment.
If the previous treatment wasn’t effective dermabrasion, CO2 laser, and laser vaporisation are used as an alternative measure. Lesion excision or electrodedesiccation was suggested as an aggressive surgical treatment.
It is essential to identify and treat the underlying condition in case of systemic amyloidosis.
Medicines administered in the treatment of primary cutaneous amyloidosis include the following:
- Topical corticosteroids (0,1% Betamethasone 17-valerate ointment);
- Topical anti-inflammatory agents such as Dimethyl sulfoxide (10-100%);
- Topical calcineurin inhibitors (0.1% Tacrolimus oinment);
- Intralesional corticosteroids (Triamcinolone);
- Systemic retinoids (Acitretin, etretinate, topical tocoretinate);
- Systemic cyclophosphamide 50 mg per day;
- Cyclosporine 4mg/kg per day for at least 12 months;