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Report of a Case
A 60-year-old man presented with a 2-year history of nail dystrophy, alopecia, and blisters and milia on his hands. Review of systems revealed weight loss, hoarseness, and dyspnea on exertion. Medical history included cardiac dysfunction, gastroesophageal reflux disease, and bilateral carpal-tunnel syndrome. Physical examination demonstrated atrophic scars with erosions and milia on the dorsal hands and diffuse alopecia of the scalp and eyebrows. Onychodystrophy of all 20 nails with longitudinal ridging and onychorrhexis, mimicking lichen planus, was also observed (Figure 1A and B).
A and B, Longitudinal ridging and onychorrhexis of the fingernails and toenails. C, Resolution of the nail changes after bone-marrow transplantation and chemotherapy.
Skin biopsies from lesions on the hand and scalp demonstrated amyloid deposition. A longitudinal nail biopsy demonstrated amorphous pink deposits in the nail bed and nail matrix dermis and vessels; polarizing light examination revealed apple-green birefringence with Congo red staining, confirming amyloid deposition (Figure 2). The most prominent amyloid deposition was observed in the proximal nail matrix, which was associated with nail plate atrophy.
Striking amorphous pink deposits (black arrowheads) in the nail matrix, dermis, and vessels and substantial nail plate (NP) atrophy (white arrowhead) are demonstrated over the proximal nail matrix, corresponding with the most severe amyloid deposition (arrowheads) (hematoxylin-eosin, original magnification ×40). MP indicates proximal nail matrix; MD, distal nail matrix. The inset shows Congo red stain under polarizing light examination with apple green birefringence, confirming amyloid deposition.
Hematology was consulted, and a bone-marrow biopsy revealed multiple myeloma. The patient underwent 4 rounds of chemotherapy with cyclophosphamide-bortezomib-dexamethasone before undergoing an autologous stem-cell transplant, followed by maintenance bortezomib therapy. Remarkably, his nail changes resolved 1 year after treatment (Figure 1C). To our knowledge, this is the first reported case of resolution of nail findings of amyloidosis with treatment.
Primary systemic amyloidosis, or amyloid light-chain (AL) amyloidosis, can present with a myriad of cutaneous manifestations. An underlying plasma cell dyscrasia causes abnormal deposition of light chain fibrils. The patient’s constellation of symptoms, in addition to his skin findings, clued the astute physician to recognize the unifying theme of amyloid deposition. This unique case highlights that cutaneous signs of amyloidosis can resolve after treatment, and may suggest that systemic deposition of amyloidosis is, to a certain degree, reversible as well.
Cutaneous lesions of systemic amyloidosis are demonstrated in approximately 20% to 40% of patients.1 Characteristic lesions include waxy papules, “pinch purpura” of the periorbital area, macroglossia, and hemorrhagic bullae. Ecchymoses and purpura are caused by amyloid infiltration in the blood vessels making the skin susceptible to trauma. The presentation of milia on the hands is a recently recognized manifestation of amyloidosis; minor trauma is implicated in the formation of these lesions.1
Nail findings of amyloidosis were first confirmed in 1979 by a longitudinal nail biopsy and may mimic lichen planus and graft-vs-host disease.2,3 In a review of 20 cases of systemic amyloidosis, five patients had nail dystrophy as the sole cutaneous indicator of systemic amyloidosis.3 Amyloid infiltration of the nail matrix is thought to be the cause of brittleness, longitudinal ridging and crumbling; patients may complain of having soft or thin nails.1-4
Characteristic findings on the scalp can further serve as a clue of underlying disease. Infiltration of hair follicles by amyloid protein results in diffuse nonscarring alopecia.5 Amyloid deposition is appreciated in a perifollicular distribution in scalp biopsies and is hypothesized to cause vascular impairment, resulting in inhibition of anagen reconstitution.6 The affected hair demonstrates thinning, broken hairs, black dots, and salmon-colored halos surrounding the follicular ostia.5
In summary, the cutaneous manifestations of systemic amyloidosis can present with nail and skin findings, and should be recognized timely for the most efficacious management. As demonstrated in this case, nail changes are not only diagnostic of the disease and may mimic lichen planus clinically, but can serve as an indicator for treatment response. Future research should be explored to see if cutaneous resolution helps predict regression of systemic amyloidosis and a more favorable prognosis in patients with underlying plasma cell dyscrasias.
Corresponding Author: Kate E. Oberlin, MD, Department of Dermatology and Cutaneous Surgery, Jackson Memorial Hospital, University of Miami School of Medicine, 1600 NW 10th Ave, RMSB 2023A, Miami, FL 33136 (firstname.lastname@example.org).
Published Online: September 28, 2016. doi:10.1001/jamadermatol.2016.3178
Conflict of Interest Disclosures: None reported.
Additional Contributions: We thank the patient for granting permission to publish this information.
Oberlin KE, Wei EX, Cho-Vega JH, Tosti A. Nail Changes of Systemic Amyloidosis After Bone-Marrow Transplantation in a Patient With Multiple Myeloma. JAMA Dermatol. 2016;152(12):1395–1396. doi:10.1001/jamadermatol.2016.3178
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