8.13 Disorders with primary and secondary deposition in the skin

Amyloidosis, Mucinosis, Myxoedema, Hyalinosis, Xanthoma/Xanthelasma, Gout/Hyperuricaemia, Calciphylaxis, localized hypergammaglobulinemia deposition, Tattoo.

Disorders with primary and secondary deposition in the skin are a heterogenous group of diseases, characterized by the pathological accumulation of materials in the extracellular matrix of the dermis or subcutis. Primary cutaneous deposition disorders are limited to the skin, while secondary deposition disorders are the consequence of systemic diseases. These disorders can generally be diagnosed by histology. Systemic diseases associated with depositional disorders include myeloma, plasmacytoma or other lymphoma (amyloidosis), lymphoma (mucinosis, gammaglobulins), hyperuricaemia or leukaemia (gout), hypercalcaemia or renal failure (calciphylaxis), metabolic disorders (xanthoma/xanthelesma).

Primary localized cutaneous amyloidosis can be caused by mutations in the OSMR or IL31RA gene. In primary localized cutaneous amyloidosis (lichen and macular amyloidosis), scratching the itchy skin is believed to induce keratinocyte necrosis, releasing proteins that abnormally clump together and form amyloids.

Secondary (AL) amyloidosis is a consequence of light chain deposits that are produced by malignant plasma cells.

Mucinosis may be triggered by thyreotic disorders (myxoedema), lymphomas, be associated with inflammatory skin diseases (such as lupus erythematosus) or be idiopathic.

Uric acid deposits (gout) may be idiopathic or linked to an excessive alcohol and/or food (especially red meat) intake (majority of cases), be genetic (rare) or linked to drugs (diuretics), haematological disorders or chronic kidney disease.

Calciphylaxis is caused by chronic, terminal renal failure.

Skin calcinosis may also be associated with connective tissue diseases (systemic sclerosis, lupus erythematosus, dermatomyositis).

Tattoo is a consequence of trauma, or may be a voluntary intradermal pigment injection or a deposition of dust and burnt substances after an explosion in the immediate proximity.

• Primary localized cutaneous amyloidosis may be characterized by severely itchy patches of thickened, scaly and reddish-brown skin with multiple small bumps (lichen amyloidosis) or flat and dark brown patches (macular amyloidosis).

• Secondary (AL) amyloidosis is characterized by vessel fragility with pinch purpura and periorbital purpura, unexplained bleeding or macroglossia.

• Mucinosis presents as flat, shiny erythematous plaques.

• Progressive lipo-lymphedema associated with monoclonal gammopathy with diffuse plaque-like infiltrates

• Myxoedema presents with skin-coloured flexible plaques, “orange peel” surface often on pretibial areas. These lesions may rarely be kyperkeratotic.

• Xanthoma/xanthelasma is characterized by small yellowish, grouped soft nodules.

• Connective tissue disorders-associated calcinosis is defined by rock hard subcutaneous nodules that may fistulate.

• Calciphylaxis presents with skin necrosis with accompanying erythematous network like maculae (livedo), these are extremely painful.

• Pathological tattoo is characterized by localized black, grey or brown macules of millimetric size.

For secondary amyloidosis, blood count, serum electrophoresis and immunofixation, kappa/lambda light chain measurement in blood, eventually bone marrow aspiration are useful to diagnose multiple myeloma. Gammopathy by peripheral gammaglobulins to check.

Myxoedema should lead to measure thyroid hormones.

Xanthoma/xanthelasma should lead to measure serum lipids (triglycerides and cholesterol).

For calciphylaxis, serum calcium, phosphore, albumin, and renal function must be investigated.

Dermatopathology is essential in the diagnosis of most depositional disorders. In amyloidosis congo red stain shows a green birefringence, frequently located in the vessel walls. Immunohistochemistry for discrimination of cutaneous and systemic amyloidosis. In gout aspirates from the tophus or histology may show cristal depositions. In xanthoma and xanthelasma lipid deposits are visible. In mucinosis and myxoedema mucopolysacharids can be found.