Diffuse hyperpigmented macules in a 48-year-old woman

Mireia Seguí, Pedro Rodríguez-Jiménez, Aurora Fernández-Galván, Javier Fraga, Pablo Chicharro
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On dermoscopic examination, brownish areas with globular and dotted pigmentation alternating with round hypopigmented spots were observed (Figure 2). Laboratory investigations including a blood cell count, serum electrolytes and renal and liver function testing as well as protein serum electrophoresis revealed no abnormalities. Two skin biopsies were taken from the back of the patient (Figure 3).</p><p>Amyloidosis cutis dyschromica (ACD).</p><p>Two skin biopsies from the back showed deposition of amyloid in the papillary dermis confirmed by positive Congo red staining and immunohistochemical studies revealed that the amyloid expressed cytokeratins CK 5/6. There was also a mild inflammatory infiltrate, mostly composed of lymphocytes (Figure 3a,b). Based on the clinical and histopathological findings, the patient was diagnosed with ACD and due to the absence of symptoms scheduled for periodic follow-up.</p><p>ACD is a rare form of primary cutaneous amyloidosis, first described by Morishima in 1970.<span><sup>1</sup></span> ACD is characterized by (i) dotted, reticular hyperpigmentation with hypopigmented macules distributed over nearly all of the body, (ii) no or little itch, (iii) usual onset before puberty and (iv) focal amyloid deposition under the epidermis.<span><sup>1, 2</sup></span> Since this first description, both familiar and sporadic cases have been reported and most of the documented cases are from Asia. We herein present a sporadic case of a woman from Spain showing a late-onset of ACD.</p><p>Primary cutaneous amyloidosis is associated with the deposition of amyloid in the skin but not in internal organs. The most common variants of primary cutaneous amyloidosis include macular and lichen amyloidosis. 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引用次数: 0

Abstract

A 48-year-old woman presented with a 4-year history of diffuse hyperpigmented papules beginning on the cleavage and progressing over the rest of the trunk and extremities. The lesions were mild pruritic. There were no family members with similar symptoms and both she and her family were from Spain and Caucasian. Her only significant past medical history was a papillary thyroid carcinoma that required total thyroidectomy. Clinical examination revealed generalized mottled hyper and hypopigmented macules on the trunk and extremities. Diffuse hyperpigmented small papules were also noted (Figure 1a−c). On dermoscopic examination, brownish areas with globular and dotted pigmentation alternating with round hypopigmented spots were observed (Figure 2). Laboratory investigations including a blood cell count, serum electrolytes and renal and liver function testing as well as protein serum electrophoresis revealed no abnormalities. Two skin biopsies were taken from the back of the patient (Figure 3).

Amyloidosis cutis dyschromica (ACD).

Two skin biopsies from the back showed deposition of amyloid in the papillary dermis confirmed by positive Congo red staining and immunohistochemical studies revealed that the amyloid expressed cytokeratins CK 5/6. There was also a mild inflammatory infiltrate, mostly composed of lymphocytes (Figure 3a,b). Based on the clinical and histopathological findings, the patient was diagnosed with ACD and due to the absence of symptoms scheduled for periodic follow-up.

ACD is a rare form of primary cutaneous amyloidosis, first described by Morishima in 1970.1 ACD is characterized by (i) dotted, reticular hyperpigmentation with hypopigmented macules distributed over nearly all of the body, (ii) no or little itch, (iii) usual onset before puberty and (iv) focal amyloid deposition under the epidermis.1, 2 Since this first description, both familiar and sporadic cases have been reported and most of the documented cases are from Asia. We herein present a sporadic case of a woman from Spain showing a late-onset of ACD.

Primary cutaneous amyloidosis is associated with the deposition of amyloid in the skin but not in internal organs. The most common variants of primary cutaneous amyloidosis include macular and lichen amyloidosis. ACD is a rare variant of primary cutaneous amyloidosis, characterized by reticular areas of hyperpigmentation with overlying hypopigmented macules and localized keratinocyte derived amyloid deposition within the papillary dermis. ACD has been most commonly reported in South and East Asian ethnic groups, having only few cases been reported in Caucasian ethnicity.2

Although most of the reported cases are familiar, sporadic cases have also been reported. Recent studies point out that most cases of ACD result from autosomal recessive mutations in GPNMB, encoding glycoprotein nonmetastatic gene B.3, 4 GPNMB has been found to have critical roles in melanosome formation, autophagy, phagocytosis, tissue repair and downregulation of inflammation. Nevertheless, the mechanism by which loss of function of GPNMB induces the pigment dyschromia and amyloidosis in ACD is not yet clear.

The onset of ACD is typically in early childhood or at a prepubertal age.2 Our patient refers starting with the lesions at her forties, showing an unusual presentation of ACD. There are few cases of ACD with postpuberal onset reported in the literature.5 The distinguishing features of the clinical presentation include generalized mottled hyper and hypopigmented macules. In addition, diffuse hyperpigmented small papules have also been documented. The size of the macules and papules range from 2 to 10 mm. The lesions are more pronounced on the trunk and the limbs with relative sparing of the face, hands, feet and neck. The extent of the dyspigmentation in ACD progresses very gradually over years, becoming more extensive through adulthood. Although the lesions of ACD are generally asymptomatic in opposition to the other subtypes of primary cutaneous amyloidosis, pruritus is reported in 19% of cases.2

Histopathological findings include amyloid deposition in the papillary dermis confirmed by positive Congo red staining. A mild inflammatory infiltrate, mostly composed of lymphocytes and sparse melanophages, can also be found in the dermis. Positive staining for the cytokeratins CK34βE12 and CK5/6 in ACD suggests that the amyloid is derived from keratinocytes.6 In our case, immunohistochemical studies were performed for cytokeratins CK 5/6, with positive staining.

The differential diagnosis of ACD includes dyschromatosis universalis hereditaria, xeroderma pigmentosum, poikiloderma-like amyloidosis, idiopathic guttate hypomelanosis and progressive macular hypomelanosis.

Treatment of ACD is not well documented, although acitretin has been reported to improve the dyschromia in some cases.

All authors discussed the results and contributed to the final manuscript.

The authors declare no conflict of interest.

The patient in this manuscript has given written informed consent for the use of her deidentified, anonymized, aggregated data and her case details (including photographs) for publication. Ethical approval: not applicable.

Abstract Image

一名 48 岁女性身上的弥漫性色素沉着斑
一名 48 岁的妇女因弥漫性色素沉着性丘疹就诊 4 年,丘疹从乳沟开始,逐渐扩展到躯干和四肢的其他部位。皮损有轻度瘙痒。她和家人都来自西班牙,是白种人。她唯一重要的既往病史是甲状腺乳头状癌,需要进行甲状腺全切除术。临床检查发现,她的躯干和四肢出现全身斑驳的色素沉着过多和过少斑块。此外,还发现弥漫性色素沉着小丘疹(图 1a-c)。皮肤镜检查发现,棕色区域有球状和点状色素沉着,与圆形色素减退斑交替出现(图 2)。实验室检查包括血细胞计数、血清电解质、肝肾功能检测以及蛋白血清电泳,均未发现异常。从患者背部取下的两块皮肤活检组织(图 3)显示,淀粉样变性皮肤色素沉着症(ACD)的真皮乳头处有淀粉样蛋白沉积,刚果红染色阳性,免疫组化研究显示,淀粉样蛋白表达细胞角蛋白 CK 5/6。此外,还有轻度炎症浸润,主要由淋巴细胞组成(图 3a、b)。ACD 是一种罕见的原发性皮肤淀粉样变性,由森岛于 1970 年首次描述。1 ACD 的特点是:(i) 点状、网状色素沉着,几乎全身都有色素减退斑;(ii) 无痒或少痒;(iii) 通常在青春期前发病;(iv) 表皮下有局灶性淀粉样沉积、2 自首次描述以来,熟悉的病例和散发性病例均有报道,大多数记录在案的病例来自亚洲。原发性皮肤淀粉样变性与淀粉样蛋白沉积于皮肤而非内脏有关。最常见的原发性皮肤淀粉样变性包括斑状淀粉样变性和苔藓样淀粉样变性。ACD是原发性皮肤淀粉样变性病的一种罕见变异型,其特征是网状色素沉着区,上覆色素减退斑,局部角质细胞衍生的淀粉样蛋白沉积在乳头状真皮层内。ACD 最常见于南亚和东亚人种,高加索人种中仅有少数病例报道2 。最近的研究指出,大多数 ACD 病例是由于编码糖蛋白非转移基因 B 的 GPNMB 发生常染色体隐性突变所致。然而,GPNMB 功能缺失诱发 ACD 中色素失调和淀粉样变性的机制尚不清楚。文献中关于青春期后发病的 ACD 病例报道很少。5 临床表现的显著特征包括全身斑驳的色素沉着过多和过少斑块。此外,还有弥漫性色素沉着小丘疹的记录。黄斑和丘疹的大小从 2 毫米到 10 毫米不等。躯干和四肢的皮损更为明显,面部、手部、足部和颈部相对较少。ACD 患者色素沉着的程度会随着年龄的增长而逐渐加重,到成年后会变得更加广泛。虽然与其他亚型的原发性皮肤淀粉样变性不同,ACD 的病变一般没有症状,但有报告称 19% 的病例会出现瘙痒。真皮中还可发现轻度炎症浸润,主要由淋巴细胞和稀疏的嗜黑素细胞组成。ACD 中细胞角蛋白 CK34βE12 和 CK5/6 染色阳性,表明淀粉样蛋白来自角质细胞。在我们的病例中,对细胞角蛋白 CK 5/6 进行了免疫组化研究,结果显示染色阳性。ACD 的鉴别诊断包括遗传性色素沉着病(dyschromatosis universalis hereditaria)、色素性红斑(xeroderma pigmentosum)、痘样淀粉样变性(poikiloderma-like amyloidosis)、特发性灰质色素沉着病(idiopathic guttate hypomelanosis)和进行性黄斑色素沉着病(progressive macular hypomelanosis)。尽管有报道称阿西曲汀可改善某些病例的色素沉着症,但ACD的治疗方法尚无明确记载。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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