Cutaneous Amyloid Elastosis Revealing Multiple Myeloma with Systemic Amyloidosis

Abstract

Cutaneous amyloid elastosis is a rare presentation of amyloidosis. Only 5 cases have been reported since 1985; 4 in the setting of various presentations of systemic amyloidosis and 1 primary cutaneous localized amyloid elastosis. We report here an additional case, initially misdiagnosed as pseudoxanthoma elasticum (PXE). CASE REPORTA 69-year-old woman was referred for fatigue, dyspnoea on exertion and skin changes. Five years earlier, papules on several aspects of the neck had appeared suddenly (over a single night according to the patient), and had quickly extended following oedematous episodes. The patient's medical history included myocardial infarction, hypertension and concentric hypertrophic cardiomyopathy, osteoporosis, hypothyroidism and depression. Dermatological examination revealed diffuse but subtle, whitish or skin-coloured papules, located mainly in cervical, flexural, periumbilical, abdominal and lumbar areas, but also on the gingiva and the inner aspect of the lower lip. Debilitating pruritus was present, as well as hand paraesthesia and vague aches. There was no macroglossia. Cardiac auscultation revealed a systolic murmur (3/6) related to aortic valve stenosis. On echocardiography, septal hypertrophy with a small pericardial effusion was present. Laboratory findings showed normochromic, normocytic, aregenerative anaemia (haemoglobin 10.9 g/dl), but no leucopaenia or thrombopaenia. Renal and hepatic functions and serum calcium level were normal. There was moderate inflammatory syndrome. The beta-2-microglobulin level was high (5.25 g/l). Massive nonselective proteinuria (6-8 g/24 h) was also present. Serum protein electrophoresis revealed a high peak in gammaglobulins (15.7 g/l) with monoclonal immunoglobulin (Ig)G-λ gammopathy. Residual IgA, IgM and albumin levels were decreased. Free λ light chains were present in the urine. Brain natriuretic peptide was high (971 pg/ml -n < 100). The diagnosis of multiple myeloma was established after demonstration of 20% bone marrow infiltration with plasma cells displaying a hyperdiploid karyotype. There were no lytic bone lesions.A skin biopsy was performed, and haematoxylin and eosin (H&E) and orcein staining revealed an accumulation of dystrophic basophilic elastic fibres in the dermis. Some elastic fibres were fragmented, showing a striking "fishbone" appearance at high magnification (Fig. 1). Congo red staining was negative. Electron microscopy of a skin sample revealed an abundant microfibrillar material highly suggestive of amyloid fibrils that coated the oxytalan and elaunin fibres in the papillar dermis and the mature elastic fibres in the mid-dermis (Fig. 2). Renal biopsy demonstrated amyloidosis with amorphous deposits within tubules and arterioles. Congo red staining was positive in the kidney. The patient was treated with melphalan, dexamethasone and bortezomib. After the third injection of bortezomib, the patient developed left-side heart failure, presumably due to cardiac amyloidosis. Treatment was suspended until the heart function improved ...

Cutaneous Nodules and Violaceous Patches on the Legs: Answer

“…Although amyloid elastosis is very rare, its accurate diagnosis is clinically relevant because it may be the first clue to an undiagnosed systemic amyloidosis, for example, in the context of a clonal B-cell dyscrasia, such as monoclonal gammopathy 2 or multiple myeloma. 3 The diagnosis of amyloid elastosis depends on the dermatopathologist because clinical suspicion of a rare disease with no specific clinical features is unlikely (Fig. 1).…”

“…Amyloid elastosis manifests clinically as symmetrically distributed discrete, rubbery, yellow-brown patches, papules, and nodules [1][2][3][4]10 ; itch may be severe. 3 Amyloid elastosisrelated skin changes may be diffused and are frequently located on the body folds, especially the neck, but also in the extremities, trunk, and mucosal sites. 4,10 When the vasculature is prominently affected, there can be sclerodermoid and poikilodermatous changes, cordlike thickening of superficial blood vessels, Raynaud phenomenon, livedo reticularis, and even thrombosis.…”

Primary Systemic (Amyloid Light-Chain) Amyloidosis Masquerading as Pseudoxanthoma Elasticum

“…Review of the English-language literature on MEDLINE demonstrated 3 cases that mentioned PXE-like appearance as part of a constellation of cutaneous findings found in amyloid elastosis. 1-3 A total of 5 cases of this entity have been reported [1][2][3][4][5] ; the other 2 cases featured other distinct cutaneous findings but an absence of cutaneous PXE-like plaques. 4,5 Winkelman et al 5 first defined this entity in 1985 based on the finding of striking, disseminated amyloid-coated elastic fibers in visceral, vascular, and subcutaneous sites.…”

“…Disseminated accumulation of amyloid around elastic fibers has sometimes accompanied an aggressive course of amyloidosis, as evidenced by 3 reports of lethal outcome. 2,3,5 Further study is required to determine if any prognostic significance is associated with the differentiation of PXElike plaques with normal elastic fibers from amyloid elastosis. Recognition of this unique cutaneous presentation of AL amyloidosis could be instrumental in the early detection and rapid treatment of this severe multisystem disease.…”

“…1-3 A total of 5 cases of this entity have been reported [1][2][3][4][5] ; the other 2 cases featured other distinct cutaneous findings but an absence of cutaneous PXE-like plaques. 4,5 Winkelman et al 5 first defined this entity in 1985 based on the finding of striking, disseminated amyloid-coated elastic fibers in visceral, vascular, and subcutaneous sites.…”