Dermatology Online Journal

Systemic amyloidosis with an exceptional cutaneous presentation
Juan Barja¹ MD, Francisca Piñeyro¹ MD, Manuel Almagro¹ MD, Felipe Sacristán² MD, Romina Rodríguez-Lojo¹ MD, Beatriz Fernández-Jorge¹ MD, Sonia Ruanova³ MD, Jesus García-Silva¹ MD
Dermatology Online Journal 19 (1): 11

1. Department of Dermatology
2. Department of Pathology
3. Department of Internal Medicine
Complejo Hospitalario Universitario de A Coruña, Spain

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Abstract

Alopecia and nail distrophy are rare signs of systemic amyloidosis. We present a case with both manifestations and give a brief review of the cutaneous signs of this disease. A biopsy of affected or unaffected skin may provide the diagnosis.

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Case report

Figure 1
Figure 1. 1A. Diffuse alopecia, with thin hair, lacked of scalp infiltration, and positive hair pull test. 1B. Dystrophic finger nails with longitudinal ridging, brittleness, and distal onychoschizia.

A 73-year-old woman presented with a 1-year history of dyspnea, weakness, dysphagia, dry eye and mouth, and pain in her legs. Physical examination revealed paleness, submandibular swelling, macroglossia, right basal hypophonesis on chest auscultation, and peripheral edema. There was a diffuse alopecia with thin hair and positive hair pull test without infiltration of the scalp (Figure 1A). Eyebrows and eyelashes were affected and axillary and genital hair was absent. Fingernails were thin and brittle, with longitudinal ridging and distal onychoschizia (Figure 1B). These nail changes had started two years before and they were initially attributed to propanolol therapy for hypertension.

Blood analysis showed mild anemia. A chest X-Ray showed right pleural effusion. A computed tomography showed an infiltration in the gastric wall. Protein electrophoresis was normal, but IgG 526, IgA 48, and IgM 16 were low. Immunofixation revealed monoclonal production of the immunoglobulin light chain lambda, which also appeared in a 24-hour urine sample. Electromyography proved sensitive and detected motor axonal polyneuropathy. A gastroscopy showed a thick and micronodular mucous membrane.

Figure 2
Figure 2. 2A. H&E stain and Congo red. Scalp biopsy showed an amorphous material deposited around and inside follicular units and vessels. Rounded storage of this material is present in the dermis. 2B. Immunohistochemistry: Diffuse staining with P-sustance and lambda light chain.

A scalp biopsy showed loss of follicular units related to the infiltration of an amorphous, eosinophilic material which was deposited around the hair follicles and vessels, and in some areas, inside the follicles. The material was stained with Congo red (Figure 2A) and did not vanish with potassium permanganate.

Immunohistochemistry was positive for P-substance and AL (Figure 2B).

A gastric biopsy showed amyloid infiltration of the mucous membrane.

A bone marrow aspiration and biopsy revealed 8 to 14 percent of atypical plasma cells. Serial X-Ray of the bones was normal and a diagnosis of systemic primary amyloidosis, without apparent myeloma, was made. Treatment with melphalan and prednisone was started, but the patient died four months later.

Discussion

Systemic amyloidosis (SA) is caused by extracellular tissue deposition of circulating immunoglobulin monoclonal light chains, which are produced by clonal proliferation of plasma cells [1]. Resulting from the amyloid infiltration of the involved organs, SA has multiple clinical manifestations, which may make it a diagnostic challenge. Clinical skin involvement occurs in 20 to 40 percent of the cases [2] and may be the first and only manifestation of the disease. A biopsy of affected or unaffected skin may provide the diagnosis [3].

Classical cutaneous signs are purpuric lesions and waxy, smooth, shiny, non tender, non pruritic papules, nodules or plaques, often with purpuric appearance, located on flexural areas, eyelids, anogenital region, and mouth [4]. Less common features are infiltrative lesions [4, 5], blisters [5], chronic paronychia [2], and Sjögren-like syndrome [3].

Alopecia has been reported in only a few cases. It is generally diffuse, with thin hair, without scarring and with positive hair pull test. It may affect all the hair-bearing areas of the body [6, 7]. Histopathologically there is perifollicular amyloid deposition. Hunt et al suggested that the amyloid infiltration could affect perifollicular blood vessels and lead to a failure in anagen restoration [7]. In our case with end-stage disease the amyloid also infiltrated the hair follicles and destroyed them.

Nail dystrophy is another uncommon presentation of SA. The changes are similar to those caused by lichen planus: brittleness, crumbling, longitudinal ridging, onychoschizia, subungual thickening, onycholisis and anonychia [5, 8, 9]. Histopathology reveals dermal amyloid deposition of matrix and nail bed [8, 9].

In conclusion, dermatologists must know this life-threatening systemic disease and keep it in mind when facing atypical cases of alopecia, nail dystrophy, paronychia, sicca syndrome or diffuse skin infiltration. Biopsies of any suspicious lesions and serum protein electrophoresis testing should reveal the plasma cell dyscrasia.

References

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10. Mancuso G, Fanti PA, Berdondini RM. Nail changes as the only skin abnormality in myeloma-associated systemic amyloidosis. Br J Dermatol. 1997; 137(3):471-2. [PubMed]

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