CASE REPOR T
JEADV (2005) 19, 481– 483 DOI: 10.1111/j.1468-3083.2004.01182.x
Extensive nodular cutaneous amyloidosis: an unusual presentation Blackwell Publishing, Ltd.
PR Criado,*†‡ CS Silva,† C Vasconcellos,†‡ NYS Valente,† JB Maito† †Dermatology Unit, Hospital do Servidor Público Estadual de São Paulo, Brazil, ‡Laboratório de Investigação Médica 53 (LM53), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, *Corresponding author, Rua Xingu 245/182, Bairro Valparaíso, Santo André, Brazil, 09060050, tel./fax +55 11 50888293; E-mail:
[email protected]
ABSTRAC T Amyloidosis is characterized by the deposition of a group of unrelated proteins leading to changes in tissue architecture and function. The nodular variant is the rarest form of the cutaneous amyloidoses. We report a patient with localized nodular amyloidosis without systemic amyloid involvement or paraproteinaemia after 6 years of follow-up. The unusual aspects of our case were a plaque presentation rather than nodular, and the disseminated pattern observed. Key words: amyloid, nodular amyloidosis, primary cutaneous nodular amyloidosis Received: 15 March 2004, accepted 5 July 2004
Introduction Amyloidosis results from the deposition of insoluble, fibrous amyloid proteins, mainly in the extracellular spaces of organs and tissues.1–3 Depending upon the biochemical nature of the amyloid precursor protein, amyloid fibrils can be locally deposited or may affect virtually every organ of the body.3 Amyloidosis is divided into two groups: systemic and localized.4 Primary cutaneous amyloidosis is a form of localized amyloidosis and consists of three subtypes: nodular, macular and lichenoid.1 We report a case of nodular primary localized cutaneous amyloidosis (NPLCA) that presented as plaques on the face, trunk and upper limbs of a middle-aged man. There was no evidence of underlying disease that could be responsible for a secondary amyloidosis after 6 years of follow-up.
Case report A 59-year-old man had noticed asymptomatic papules and plaques on his face for the last 6 years, with new lesions erupting all over this time, affecting the trunk and upper limbs. Cutaneous examination revealed brownish to yellow plaques ranging from approximately 1– 6 cm in diameter on the trunk, upper limbs and face (fig. 1). Purpura was observed in several lesions. © 2004 European Academy of Dermatology and Venereology
Abnormal physical findings included lethargy, pallor, and hepatosplenomegaly and pan focal systolic murmur. Significant history included chronic alcohol consumption and megaloblastic anaemia, managed with oral folic acid and vitamin B1. The patient reported a history of pleural tuberculosis 2 years after the beginning of the cutaneous eruption. He was then treated with rifampin, isoniazid and pyrazinamide with resolution of the symptoms and no evidence of active disease. In the 4-year period after tuberculosis diagnosis, the patient underwent multiple examinations, including pleural and hepatic biopsy that showed fibrosis and alcoholic hepatitis, respectively, without amyloid deposits. Sternal marrow biopsy showed no increase in plasma cells. Chest radiographs were normal. Thoracic and abdominal computerized tomography showed no significant abnormalities. Determination of serum electrolytes, serum immunoglobulins and proteins electrophoresis, antinuclear antibody, blood glucose level, assay for Bence-Jones protein, serology for syphilis, hepatitis B and C, renal and hepatic functions showed no abnormalities. Abnormal tests results included an elevated lactic dehydrogenase level of 1560 UI/mL, erythrocyte sedimentation rate of 60 mm/h and haemoglobin level of 6.4 g /dL. Biopsy specimens revealed an atrophic epidermis overlying a large, amorphous clefted mass of hyalinized eosinophilic material throughout the dermis (fig. 2). Deposits were found around adnexal structures and blood vessels. The dermal deposits 481
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fig. 3 Ultrastructural examination of amyloid deposits shows randomly masses orientated extracellular around the dermal vessels (electron transmission microscopy, original magnification × 1800).
Discussion
fig. 1 Multiple brownish to erythematous papules and plaques on the face.
fig. 2 Large masses of amyloid deposits through the dermis (haematoxylin and eosin, original magnification × 40).
demonstrated apple-green birefringence with Congo red stain when examined under polarized light. Ultrastructural examination revealed randomly orientated extracellular cylindrical masses consistent with amyloid substance (fig. 3). Over the 6 years since his condition started, there has been no evidence of primary systemic amyloidosis or any underlying disease that might be responsible for a secondary amyloidosis.
Amyloidosis refers to the extracellular deposition of any unrelated proteins leading to changes in tissue architecture and function.1 Nodular amyloidosis is the rarest cutaneous presentation of amyloidosis.2 Women are affected twice as men, usually in the sixth and seventh decades of life.5 There is a variable progression of nodular localized lesions to systemic amyloidosis (7–50% of cases).5–7 Nodular amyloidosis is characterized by single or multiple, firm, brown to erythematous nodules involving the legs, head, trunk, arms and genitalia in decreasing order of frequency.2 There are exceptional cases of plaques rather than nodules,8–11 as occurred in our patient. Moreover, cutaneous lesions in nodular amyloidosis can appear atrophic, anetodermic or bullous, possibly from dermal destruction of elastic and collagen fibres.11,12 The key of histological diagnosis of nodular cutaneous amyloidosis is the presence of hyaline, eosinophilic masses filling the entire dermis, in contrast to lichenoid and macular amyloidosis, in which they are limited to the papillary dermis.5 These amyloid deposits are indistinguishable from those of primary systemic amyloidosis.4 Cutaneous nodular primary amyloidosis can be distinguished from certain types of systemic amyloidosis only after a careful physical examination and laboratory evaluation to rule out extracutaneous amyloid deposits.12 In our patient, pleural, hepatic, bone marrow biopsies, chest and skull X-ray and computerized tomography of thorax and abdomen showed no evidence of extracutaneous amyloid deposits or an underlying myeloma. Tuberculosis is a cause of secondary amyloidosis1 but, in our patient, the cutaneous lesions appeared 2 years before the diagnosis of pleural tuberculosis and continued to appear for 4 years after the cure of tuberculosis was achieved, indicating a casual association.
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The serum amyloid P (SAP) scintigraphy scanning is a sensitive, specific, quantitative method for imaging amyloid deposits in vivo using radioiodinated SAP component as a diagnostic tracer.6 All amyloid deposits show SAP due its calcium-dependent binding affinity for all types of amyloid fibril.6 The scan reveals the distribution of amyloid within organs and is diagnostically extremely sensitive.6 This scintigraphic method can provide useful information regarding systemic involvement in patients with NLPCA.6 The point estimate by Woollons and Black6 for progression to systemic amyloidosis is 7% (only one of 15 patients), which is lower than the point estimate for 50% progression in Brownstein and Helwig’s series of 10 patients reported in 1970.13 Even though this is the largest study of this type of amyloid to date, the sample size is small and with such samples confidence intervals are always wide.14 Woollons and Black14 state that, owing to the small sample size, higher rates of progression to systemic amyloidosis may be possible. A larger prospective study would produce a more precise estimate of progression to systemic amyloidosis.14 We agree with Borrowman et al.15 that suggest long-term monitoring for all patients with NPLCA, even though the exact risk of systemic amyloidosis occurring at a later date is still unknown. We believe that the diagnostic best considered in our case is of NPLCA. The unusual aspects of our case were a plaque presentation rather than nodules and the cutaneous disseminated pattern observed. We are convinced that periodic clinical and laboratory observation in these cases is strongly recommended for paraproteinaemia early diagnosis.
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© 2004 European Academy of Dermatology and Venereology JEADV (2005) 19, 481– 483
