Patients undergoing dialysis are unable to properly eliminate β2-microglobulin, a component of major histocompatibility complex, type 1, which is catabolized in the kidney. Accumulation of β2-microglobulin favors the formation of amyloid, the deposition of which causes dialysis-related amyloidosis (DRA). Symptoms are initially osteoarticular, but progression of the disease involves systemic manifestations including cutaneous ones.
A woman in her 50s presented with a history of subcutaneous masses on her back that she had noticed 8 years previously and that were producing postural discomfort. History included hepatitis C infection 23 years earlier and bilateral nephrectomy requiring treatment with dialysis for the last 31 years. After 20 years of hemodialysis, she developed bilateral carpal tunnel syndrome and flexion contractures on her fingers; hence, she was diagnosed with DRA.
On physical examination, she was found to have 3 massive nodules projecting from her back, each with an elongated shape (Figure 1). The largest (measuring about 31.0 × 5.5 × 4.5 cm) was located over her spine, and the others (each measuring about 27.0 × 2.5 × 1.0 cm) were located symmetrically on either side of the spine. These masses had firm consistency and were covered by normal skin. Computed tomography revealed infiltration of subcutaneous fat without evidence of calcification. Examination also revealed macroglossia and some yellowish nodules (about 2-4 mm each) on the sides of her tongue.
Figure 1. Clinical Appearance of the Back of the Patient
Three massive, elongated, parallel, skin-colored subcutaneous masses.
Skin biopsy of the central mass of her back was performed demonstrating subcutaneous deposition of amorphous eosinophilic material (Figure 2A). The deposits stained positive with Congo red, showing apple-green birefringence under polarization. Immunostaining of the amorphous material was positive for β2-microglobulin amyloid (Figure 2B).
Figure 2. Histologic Features Related to β2-Microglobulin Amyloidosis
A, Eosinophilic amorphous material deposited in the subcutaneous tissue (hematoxylin-eosin, original magnification ×20). B, Immunohistochemical staining for β2-microglobulin (β2-microglobulin antibody; Dako, Denmark; 1/20.000 concentration) (original magnification ×100).
Up to 65% of patients undergoing dialysis for more than 10 years develop DRA, and the prevalence increases over the years.1 Unlike other types of systemic amyloidosis, amyloid deposition in the skin or subcutaneous fat is extremely rare.2,3 However, 3 types of cutaneous manifestations related to β2-microglobulin amyloid deposition have been described: lichenoid plaque, hyperpigmentation, and subcutaneous masses.2-4 Lingual involvement includes yellowish nodules and macroglossia4; our patient had both lingual signs.
To our knowledge only 10 cases of subcutaneous nodules related to DRA have been reported.2,3,5,6 Most previous reports describe masses located on the buttocks; only in 2 cases did the nodules occur in other sites (popliteal and shoulder area).2,6 The explanation for the preferred location of the masses on the buttocks is that the chronic pressure or trauma favors the deposit of β2-microglobulin amyloid.2 The masses in the present case also presented in an area of increased pressure; the patient has severe kyphosis, and the deposit locations match the points of greatest pressure on her back.
These massive nodules grow slowly and asymptomatically over the years, and so they are often reported only when the patient complains of discomfort caused by their large size.2,3,5 Because of the particular location of the deposits and the lack of symptoms until they become massive, this could be an underreported entity.
In 9 of 10 cases, and in the present case, there are previous osteoarticular symptoms of DRA such as carpal tunnel syndrome, bone cysts, or amyloid arthropathy from years ago.2,3,5 Since the masses appear at a late stage of the disease, their presence could reveal progression from the initial osteoarticular form to a systemic one,1 pointing out the need for adjustment in the dialysis therapy to decrease the accumulation of β2-microglobulin. This is achieved by switching from lower-flux to higher-flux biocompatible dialysis membranes and using convective therapies as online hemodiafiltration. Renal transplantation, if possible, would be a definitive solution. Patients with a history of long-term hemodialysis and symptoms of DRA involving the musculoskeletal system should undergo dermatologic examination focusing on the tongue and pressure points to identify any possible cutaneous involvement.
Corresponding Author: Vanessa Gargallo, MD, Department of Dermatology, 12 de Octubre University Hospital, Avda de Cordoba s/n, Madrid 28232 Spain (firstname.lastname@example.org).
Published Online: January 21, 2015. doi:10.1001/jamadermatol.2014.5022.
Conflict of Interest Disclosures: None reported.
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