AMYLOIDOSIS
The term amyloidosis refers to a heterogeneous group of diseases. Systemic and cutaneous forms of amyloidosis can occur and are caused by the deposition of one of many different amyloid proteins. The primary cutaneous forms are more frequently seen. They include nodular, lichen, and macular amyloidosis (also referred to as lichen or macular amyloidosis). The systemic form is a multisystem, life-threatening disorder that requires systemic therapy. Most systemic disease is caused by an abnormality in plasma cells; myeloma-associated amyloid is a distant second in incidence. In addition to amyloidosis of the skin, the central nervous system may be involved with amyloidosis, as it is in Alzheimer’s disease.
Clinical
Findings: Systemic amyloidosis is caused by abnormal production of amyloid AL
protein (immuno-globulin light chains) and its deposition in various organ
systems. These effects can be seen in patients with plasma cell dyscrasia or
myeloma. Mucocutaneous findings are often part of systemic amyloidosis, and on
occasion they are the initial presentation of the disease. The hallmark cutaneous
finding is translucent papules and plaques with varying degrees of hemorrhage.
These papules are composed of the abnormal AL protein. Soft, rubbery papules
may also occur within the oral mucous membranes. Pinch purpura of the skin is
almost universal and results from weakening of the superficial cutaneous
vessels by deposition of the AL protein. Peri-orbital ecchymoses may
circumferentially surround the eye, which has led to the term “raccoon eyes.”
The ecchymoses may be induced by coughing or by super-ficial trauma. The palms
and soles may have a waxy appearance. The tongue is often strikingly enlarged
due to amyloid deposits.
Deposition
of the AL protein in close approximation to the dermal elastic fibers produces
a rare finding termed amyloid elastosis. Clinically, this may mimic cutis laxa;
the skin is easily distensible and lacks elastic recoil.
Deposition
of amyloid in the renal glomeruli, liver, or heart muscle can cause significant
end-organ damage. Renal insufficiency leading to renal failure is a major cause
of morbidity and mortality. Hepatomegaly, leading to fibrosis and liver
failure, may occur. Amyloid protein that is deposited in the muscle of the
heart may lead to arrhythmias and congestive heart failure.
The primary
cutaneous diseases known as lichen amyloidosis and macular amyloidosis are
localized to the leg and the back, respectively. Most cases are believed to be
directly caused by keratinocyte-derived amyloid protein. There are no systemic
symptoms. Patients present with pruritic hyperpigmented macules and papules
that may coalesce into plaques. Nodular primary cutaneous amyloidosis is caused
by the local production of AL protein by plasma cells in the skin. This
condition is extremely rare and may progress to systemic amyloidosis.
Pathogenesis:
Systemic
AL amyloidosis results from plasma cell dyscrasia or from myeloma-associated
disease. It is directly caused by a proliferation of abnormal plasma cells. The
plasma cells produce excessive amounts of immunoglobulin light chains, predominantly
λ chains. The excessive amounts of AL protein are
deposited within the walls of the cutaneous vasculature; this leads to
weakening of the walls and is responsible for their easy rupture. The AL
protein is deposited in many organ systems. Rarely, the plasma cells produce
immunoglobulin heavy chains; this is termed AH protein.
Histology:
Amyloidosis
is a disease caused by the abnormal deposition of amorphous AL protein in the
dermis and subcutaneous tissue. Biopsies of involved skin show eosinophilic
deposits on routine staining. The amyloid protein is accentuated with special
staining methods such as the Congo red stain. It shows an apple-green
birefringence under polarized light microscopy and appears reddish under
routine microscopy.
Treatment:
Systemic
amyloidosis is best treated with combination chemotherapy. Traditionally,
prednisone and melphalan were the
agents of choice. Newer proteosome inhibitors are currently used. Bone marrow
transplantation is performed in certain cases.
Therapy for primary cutaneous amyloidosis is directed at symptomatic control. Topical corticosteroids and oral antihistamines are used to control itching. Varying results have been reported with ultraviolet phototherapy. No randomized, prospective studies of the treatment of primary cutaneous amyloid have been published.
