Primary Localized Cutaneous Nodular Amyloidosis Following Local Trauma

Primary localized cutaneous nodular amyloidosis (nodular amyloidosis) is a rare and distinct type of amyloidosis, in which amyloid L deposition is limited to the skin and typically manifested as a tumefactive nodule on the acral sites. However, the definite cause of nodular amyloidosis is still unknown. Although it is relatively well known that the amyloid deposits in nodular amyloidosis originate from immunoglobulin light chains secreted by local plasma cells, traumatic injury to the skin has rarely been recognized as a triggering factor of nodular amyloidosis. Herein, we present a case of a 50-year-old male patient with primary localized cutaneous nodular amyloidosis, which occurred after local trauma, and discuss the relationship between traumatic damage and dermal amyloid L deposition.     

Unusual primary cutaneous localized amyloidosis

The case of a 41-year-old female patient with an unusual type of primary localized cutaneous amyloidosis is reported. Clinical examination revealed lesions typical for macular cutaneous amyloidosis, while histology and histochemistry, in contrast, revealed the presence of nodular amyloidosis of the skin with deposition of lambda light chain amyloid.     

Ultrastructural localization of amyloid P component in primary localized cutaneous amyloidosis

Amyloid P component (AP) was specifically localized to dermal amyloid deposits in the papular and nodular variants of primary localized cutaneous amyloidosis by an immunoperoxidase technique using an antibody to serum amyloid P component (SAP). Specific staining with anti-SAP of elastic fibre microfibrils which has previously been observed in normal skin, was also present and was noted in close proximity 10 deposits of amyloid material. AP associated with normal elastic fibre microfibrils may be involved in the deposition of amyloid fibrils in vivo.     

Disseminated Superficial Porokeratosis with Amyloid Deposition

Two patients with disseminated superficial porokeratosis (DSP) with amyloid deposition are reported. The skin lesions were distributed over both sun-exposed areas and sun-protected areas. No exacerbation by sun exposure was noted. Abundant amyloid substances were deposited at the papillary dermis, not only beneath the cornoid lamellae but also within the annular margin. The skin lesions and amyloid deposition regressed with topical application of dimethyl sulfoxide in one patient, suggesting that DSP is one of the clinical phenotypes of primary localized cutaneous amyloidosis. Another possibility is that amyloid substances are produced by poorly differentiated keratinocytes in DSP.     

Amyloid in localized cutaneous amyloidosis: immunofluorescence studies with anti-keratin antiserum especially concerning the difference between systemic and localized cutaneous amyloidosis

Amyloid of localized cutaneous amyloidosis and systemic amyloidosis were subjected to study with an indirect immunofluorescence technique using anti-keratin antiserum. Anti-keratin antiserum was prepared ad modum Sun & Green. Amyloid of localized cutaneous amyloidosis was positively stained for the antiserum, whereas amyloid of systemic amyloidosis (primary and multiple myeloma-associated) was negative. There was no difference between primary localized cutaneous amyloidosis (lichen amyloidosus and macular amyloidosis) and secondary localized cutaneous amyloidosis (amyloidosis associated with skin tumor). These results indicate that amyloid of localized cutaneous amyloidosis contains components derived from epidermal fibrous protein, probably tonofilaments of keratinocytes.     

Secondary localized cutaneous amyloidosis in solar elastosis

A case of secondary localized cutaneous amyloidosis in solar elastosis was studied by light and electron microscopy. Amyloid deposition was restricted to areas with elastotic changes, and in some areas both changes were intermingled with each other. The amyloid was permanganate-sensitive, and proved to be protein AA. Ultrastructurally it was composed of fine tubular filaments. It is suggested that the amyloid deposition in this case was related to sunlight damage of the skin.     

Advanced glycation end product-modified beta2-microglobulin is a component of amyloid fibrils of primary localized cutaneous nodular amyloidosis

Primary localized cutaneous nodular amyloidosis is a rare form of cutaneous amyloidosis. Amyloid fibrils in primary localized cutaneous nodular amyloidosis have been reported to be originated from immunoglobulin light chains. Immunohistochemical studies on the lesional skins of four patients with primary localized cutaneous nodular amyloidosis demonstrated that amyloid deposits of all cases showed a positive reaction with the antibodies for beta2-microglobulin and advanced glycation end products as well as immunoglobulin light chain (kappa or lambda). No beta2-microglobulin and advanced glycation end product immunoreactivity was found in the amyloid deposits of other primary localized cutaneous amyloidosis (lichen amyloidosis and macular amyloidosis). Double immunofluorescence study of the lesional skin of primary localized cutaneous nodular amyloidosis showed that anti-kappa light chain, anti-beta2-microglobulin and anti-advanced glycation end product antibodies mostly reacted with the same area of amyloid deposit. Amyloid proteins were sequentially extracted with distilled water from one case of primary localized cutaneous nodular amyloidosis and recovered in the five water-soluble fractions (fractions I-V). Immunoblot assay of amyloid fibril proteins demonstrated that immunoreactive polypeptides with anti-kappa light chain antibody (29 kDa) and with anti-beta2-microglobulin antibody (12 kDa) were detected in fractions I-V, whereas immunoreactive polypeptide with anti-advanced glycation end product antibody (12 kDa) was detected exclusively in fractions III-V but not in fractions I and II. Two-dimensional polyacrylamide gel electrophoresis revealed that 12 kDa polypeptide in fractions I and II was electrophoretically identical with authentic beta2-microglobulin and that beta2-microglobulin in fractions III-V was advanced glycation end product-modified beta2-microglobulin with more acidic pI value. These results indicate that beta2-microglobulin is another major component of amyloid fibrils in primary localized cutaneous nodular amyloidosis and that beta2-microglobulin in primary localized cutaneous nodular amyloidosis is partly subjected to the modification of advanced glycation end product.     

Successful treatment of lichen amyloidosus associated with atopic dermatitis using a combination of narrowband ultraviolet B phototherapy,topical corticosteroids and an antihistamine

Lichen amyloidosus (LA) is a type of primary localized cutaneous amyloidosis characterized by multiple pruritic discrete hyperkeratotic papules with amyloid deposition in the papillary dermis. Clinical regression is usually difficult to achieve, even after treatment. In this study, we report a case of an adult man with LA associated with atopic dermatitis (AD) which was successfully treated with narrowband ultraviolet B (NB‐UVB) phototherapy, topical corticosteroids and an oral antihistamine. This case suggests that NB‐UVB phototherapy may be a useful adjuvant for LA associated with AD.     

Localized primary cutaneous nodular amyloidosis: case report

Amyloidosis results from deposition of fibrous and insoluble amyloid protein in extracellular spaces of organs and tissues. Amyloid deposition can be localized or systemic and either primary or secondary. We report a case of localized primary cutaneous nodular amyloidosis manifested by papular-nodular, reddish-brown lesions affecting the nasal area, without evidence of systemic involvement. Immunohistochemistry showed the presence of immunoglobulin kappa light chain.     

Amyloid P components in normal human skin and skin with lesions

Amyloid P component (AP) is a glycoprotein which is found in tissue deposits of all types of amyloid and is identical to and derived from serum amyloid P component (SAP). SAP binds in a calcium-dependent fashion to various ligands, such as agarose, desoxyribonucleic acid, fibronectin, C4-binding protein, glycosaminoglycans and isolated amyloid fibrils. Tissue AP (TAP) is also a constituent of the normal human renal glomerular basement membrane and is, in adult humans, invariably associated with elastic fiber microfibrils in connective tissue throughout the body, including that of blood vessels. In normal human skin anti-AP antibody binding was localized to the microfibrils of oxytalan fibers in the papillary dermis and to the peripheral microfibrillar mantle of elaunin and mature elastic fibers in the reticular dermis. Since SAP binds to fibronectin and glycosaminoglycans, which in turn bind to collagen fibers, TAP on elastic fiber microfibrils may play an important role in the maintenance of the normal dermal architecture and in dermo-epidermal adhesion. Under pathological conditions, AP is found in all forms of cutaneous amyloidosis, including primary localized cutaneous amyloid (PLCA); it is also detectable on keratin bodies, which represent precursor structures for PLCA. The association of AP with elastic fiber microfibrils and amyloid fibrils and their close anatomical relationship in vivo may reflect the significance of AP in the deposition of cutaneous amyloid.     

Discoid lupus erythematosus with secondary amyloidosis

BACKGROUND: Secondary localized cutaneous amyloidosis is a clinically unapparent phenomenon associated with various cutaneous pathologies, usually tumours of epidermal origin. The amyloid is thought to be derived from keratinocytes. OBJECTIVES: To characterize the amyloid deposition observed incidentally within lesional biopsies from three patients with discoid lupus erythematosus (DLE), and retrospectively to study the phenomenon within DLE skin samples. METHODS: Localized amyloid deposition was observed in three cases of DLE by immunofluorescence studies, and these cases were further studied by histology and immunohistochemistry using a monoclonal anticytokeratin antibody. Retrospective histological review of DLE tissue specimens archived over 12 months was performed to look for evidence of previously undetected amyloid. RESULTS: Amyloid deposition was confirmed histologically in the three index cases by staining with Congo red and thioflavin T. Positive staining with an anticytokeratin antibody demonstrated the epidermal origin of the amyloid protein. Of the 18 archived cases reviewed amyloid was retrospectively detected in one sample. CONCLUSIONS: Secondary cutaneous amyloidosis of keratinocyte origin can be seen in DLE lesions. It may be a not infrequent occurrence and may remain under-reported. We discuss the possible role of disease chronicity and colloid body degradation in the pathogenesis of amyloidosis.     

Nodular localized primary cutaneous amyloidosis: a bullous variant

Primary cutaneous amyloidosis describes a group of disorders in which amyloid is deposited in the skin without evidence of systemic involvement. Nodular localized primary cutaneous amyloidosis (NLPCA) is a rare form of these skin‐restricted amyloidoses. We present an unusual case of NLPCA in a 51‐year‐old man, who had clinical and histopathological evidence of subepidermal bullous formation, a unique feature in NLPCA. The possible pathogenesis of this change is discussed.     

Lichen amyloidosis,ankylosing spondylitis and autoimmune thyroiditis: coincidence or association?

Primary localized cutaneous amyloidosis (PLCA) is characterized by the deposition of amyloid in a previously apparently normal skin with the absence of other systemic or cutaneous disorder. Although ankylosing spondylitis may be associated with secondary systemic amyloidosis, no reports have been found showing the association of this disease with PLCA. In addition, the association of PLCA with autoimmune thyroiditis has not been previously reported. We report a concomitant occurrence of lichen amyloidosis, ankylosing spondylitis and autoimmune thyroiditis in a caucasian woman.     

Epidermal origin of the amyloid in localized cutaneous amyloidosis

A case of localized cutaneous amyloidosis which developed after a lichen planus-like skin reaction is reported. The amyloid consisted of amyloid fibrils enveloped by heparan sulphate granules. These amyloid fibrils reacted to anti-human keratin antibody, indicating an epidermal origin for the fibrils.     

Primary localized cutaneous nodular amyloidosis successfully treated with cyclophosphamide

Primary localized cutaneous nodular amyloidosis (PLCNA) is a rare subtype of localized cutaneous amyloidosis and can be associated with various connective tissue disorders. It can be difficult to treat and past therapies include surgical excision, dermabrasion, electrodessication and curettage, cryotherapy and laser therapy. We present a case of a middle‐aged woman with PLCNA associated with CREST (calcinosis, Raynaud phenomenon, oesophageal motility disorders, sclerodactyly and telangiectasia) syndrome and Sjögren's syndrome responding to cyclophosphamide with no new amyloid deposits and resolution of skin ulceration after many years of resistance to drug therapy. It is important to monitor these patients for progression into systemic amyloidosis.     

Amyloid elastosis: analysis of the role of amyloid P component.

We report the second case of amyloid elastosis. Our patient had an underlying primary systemic amyloidosis with lambda light chain paraproteinemia. Salient clinical features included a sclerodermatous facial appearance, cordlike thickening of superficial blood vessels, neck skin resembling that in pseudoxanthoma elasticum, livedo reticularis-like changes on the trunk, Raynaud's phenomenon, arterial and venous thromboses, and the nephrotic syndrome. Amyloid deposits were present in the dermis, around appendages, in blood vessel walls, and in a striking distribution surrounding individual elastic fibers, that appeared shortened and fragmented. Immunofluorescence, electron microscopic, and immunoultrastructural studies with antibodies to lambda light chain, localized the amyloid deposits to the region of the elastic fiber microfibrils, with which amyloid P component (AP) is invariably associated in normal tissues. Because AP binds amyloid fibrils, codistribution of amyloid deposits and AP in amyloid elastosis strongly supports the theory that elastic fiber-associated AP may act as a nidus for amyloid deposition.     

AL amyloidosis is not present as an incidental finding in cutaneous biopsies of patients with multiple myeloma

Multiple myeloma (MM) is a monoclonal B-cell neoplasm characterized by autonomous proliferation of immunoglobulin-secreting plasma cells that are capable of synthesizing amyloidogenic light chains resulting in AL amyloidosis. Clinically occult AL amyloid deposition may occur in up to 31% of patients with MM. The prognosis of combined amyloidosis and MM is improving with new therapeutic options. Thus it is imperative that patients with MM be screened for amyloidosis. Sixty-six consecutive skin biopsies from patients with MM and the diagnosis of graft vs. host disease (GVHD) were stained with Congo red and assessed for the presence of amyloid deposition. Twelve cases that had amyloid deposition in other tissue and had a cutaneous biopsy were also stained with Congo red and assessed for the presence of amyloid deposition. None of the 66 biopsies of GVHD, and none of the 12 cases that had documented amyloid deposition in other tissue showed evidence of amyloid deposition in the cutaneous biopsies. In the absence of specific cutaneous manifestations of amyloidosis, it is unlikely that amyloidogenic light chain deposition in the skin would be found. Type I collagen may appear similar to amyloid, both by light microscopy and fluorescence, after staining with Congo red. Thus care must be taken not to confuse type I collagen autofluorescence with positivity for amyloid when assessing skin biopsies stained with Congo red.     

Primary localized cutaneous nodular amyloidosis: case report and biochemical analysis of amyloid.

We report a patient with scalp lesions of primary localized cutaneous nodular amyloidosis. The extensive examination revealed no systemic involvement. Analysis of glycosaminoglycans (GAGs) in amyloid deposits showed a twofold increase as compared with normal skin, which was due to the increase in dermatan sulfate. Local disorders of GAG metabolism may be related to the amyloid fibril formation. Amyloid fibrils were purified and identified electron-microscopically, which consisted of two major 12,000- and 13,000-dalton and minor 29,000- and 48,000-dalton peptides. Western blotting analysis showed a minor 29,000-dalton peptide reactive with antibodies against both kappa and lambda light chains of immunoglobulin. There is a possibility that some components of amyloid in some cases of primary localized cutaneous nodular amyloidosis may consist of both kappa and lambda immunoglobulin light chains.     

Primary systemic amyloidosis presenting as extensive cutaneous ulceration

BACKGROUND: We report a case of primary systemic amyloidosis in a 78-year-old Caucasian woman presented as a nonhealing ulcer on the right thigh for 3 months. Histopathology of the skin revealed widely thickened walls of middermal and subcutaneous vessels from deposition of amorphous eosinophilic material that stained positively with Congo red and crystal violet. OBJECTIVE: This case represents a very unusual presentation of primary systemic amyloidosis, one in which the cutaneous manifestations provided the first signs of a devastatingly widespread multiorgan infiltration of amyloid protein. CONCLUSION: This presentation of the disease may signify an advanced stage with a grave prognosis as our patient passed away 3 months after development of the cutaneous ulceration.     

Nodular amyloidosis in a patient with liver cirrhosis

A 43-year-old Japanese man with alcoholic liver cirrhosis developed a nodule on the face 1 year prior to presentation. Histopathological examination showed amyloid deposition in the entire dermis, with numerous plasma cells. Nodular primary localized cutaneous amyloidosis is a rare form of amyloidosis, which needs long-term follow-up because of the possibility of the development of systemic amyloidosis. Also, this type of cutaneous amyloidosis may have other complications.