Cutaneous Amyloidosis

Mereuta, Oana Madalina; Doğan, Ahmet

doi:10.1007/978-3-319-19294-9_34

Cited by 5 publications

(5 citation statements)

References 92 publications

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“…The major subtypes include the more common macular and lichen amyloidosis and the rare nodular amyloidosis. 1 Most cases are sporadic. Autosomal-dominant PLCA results from heterozygous missense mutations in OSMR (encoding oncostatin M receptor-beta [OSMRb] [MIM: 105250]) and IL31RA (encoding interleukin [IL]-31 receptor-alpha [MIM: 613955]), both of which belong to the IL-6 cytokine family.…”

Section: Introductionmentioning

confidence: 99%

Loss of GPNMB Causes Autosomal-Recessive Amyloidosis Cutis Dyschromica in Humans

Yang

Lin

Chiang

et al. 2018

The American Journal of Human Genetics

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Amyloidosis cutis dyschromica (ACD) is a distinct form of primary cutaneous amyloidosis characterized by generalized hyperpigmentation mottled with small hypopigmented macules on the trunks and limbs. Affected families and sporadic case subjects have been reported predominantly in East and Southeast Asian ethnicities; however, the genetic cause has not been elucidated. We report here that the compound heterozygosity or homozygosity of GPNMB truncating alleles is the cause of autosomal-recessive ACD. Six nonsense or frameshift mutations were identified in nine individuals diagnosed with ACD. Immunofluorescence analysis of skin biopsies showed that GPNMB is expressed in all epidermal cells, with the highest staining observed in melanocytes. GPNMB staining is significantly reduced in the lesional skin of affected individuals. Hyperpigmented lesions exhibited significantly increased amounts of DNA/keratin-positive amyloid deposits in the papillary dermis and infiltrating macrophages compared with hypo- or depigmented macules. Depigmentation of the lesions was attributable to loss of melanocytes. Intracytoplasmic fibrillary aggregates were observed in keratinocytes scattered in the lesional epidermis. Thus, our analysis indicates that loss of GPNMB, which has been implicated in melanosome formation, autophagy, phagocytosis, tissue repair, and negative regulation of inflammation, underlies autosomal-recessive ACD and provides insights into the etiology of amyloidosis and pigment dyschromia.

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Section: Introductionmentioning

confidence: 99%

Loss of GPNMB Causes Autosomal-Recessive Amyloidosis Cutis Dyschromica in Humans

Yang

Lin

Chiang

et al. 2018

The American Journal of Human Genetics

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“…Nodular CA is usually related to AL-type amyloidosis, preceding by a different physiopathology. 14 In some entities such as lichenoid dermatitis, erythropoietic protoporphyria, and lipoid proteinosis, it can be seen as amorphous eosinophilic material which requires differential diagnosis with amyloidosis.…”

Section: Introductionmentioning

confidence: 99%

C4d as a Practical Marker for Cutaneous Amyloidosis

Yaman

Kumbaraci

González

et al. 2021

The American Journal of Dermatopathology

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Cutaneous amyloidosis (CA) is defined by the accumulation of amyloid in the dermis; it might be primary or secondary. The diagnosis is based on histopathological findings with the demonstration of amyloid deposits, confirmed by Congo red stain under the polarized light. Studies on other diagnostic markers are ongoing in the literature. The aim of this study was to demonstrate the utility of C4d staining in the recognition of amyloid in CA and using it as an alternative or substitute marker for the diagnosis. In this retrospective study, 199 skin biopsies with a clinical provisional diagnosis of CA were analyzed, the Congo red stain was performed, and, in a subgroup (n = 97) with histopathological findings probably for CA, C4d immunohistochemistry was assessed. Forty-eight cases of CA were detected. Congo red birefringence was positive in all cases, whereas in 14 cases, it was faded. In these 14 cases, the diagnosis of CA was made by means of Congo red fluorescence and Thioflavin T because the histopathological findings were highly suggestive for CA. All CA cases were positive with C4d, and in 12 of the 49 inflammatory dermatoses, C4d was positive. The interpretation of C4d immunohistochemistry can be performed more easily and rapidly than Congo red evaluation. The sensitivity and specificity of C4d were 100% and 75.5%, respectively. In our experience, C4d staining was a useful method for detecting amyloid deposits in CA. Although Congo red staining is the gold standard for amyloid detection, we propose C4d immunohistochemistry as a routine screening method or hybrid transition while further investigations are completed.

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“…9,21,24 The kPLCAs occur independently or secondary to underlying diseases, such as basal cell tumors, nevus, seborrheic keratosis, and actinic keratosis. 22 In basal cell carcinomas, which is one of the most common cancers in humans, 3 amyloid deposits are observed at an incidence ranging from 11% to 75%. 7 Cytokeratins (CKs) are suspected as possible amyloid precursor proteins, 1,13 and especially CK5 has been detected in amyloid deposits of the skin.…”

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confidence: 99%

“…22 PLCA is further divided into keratinic PLCA (kPLCA) and nodular PLCA based on pathological features. 22 Lichen amyloidosis and macular amyloidosis are kPLCAs commonly detected in Asians and South Americans. 21,24 In this disease, amyloid deposits accumulate under the basal layer of the epidermis, resulting in the deterioration of the patient's quality of life owing to severe pruritus, pigmentation, and lichenification.…”

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Keratinic amyloid deposition in canine hair follicle tumors

et al. 2022

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Keratinic primary localized cutaneous amyloidosis is a disease in humans; however, no similar condition has been reported in animals. This study aimed to investigate cutaneous keratinic amyloid deposition in dogs and elucidate its etiology. Canine hair follicle tumor tissues were histopathologically analyzed. Immunohistochemistry and mass spectrometry–based proteomic analyses were performed to identify precursor protein candidates. Structural prediction and in vitro fibrillization analyses were conducted to determine the amyloidogenic region and gene sequencing analysis was performed to assess mutations. Of the 266 samples, 16 had amyloid deposition. Amyloid deposits were found in the stroma of tumors and in the margins of keratin debris and around normal hair follicles. Cytokeratin 5 (CK5) was identified as a precursor protein candidate. C-terminal truncation of CK5 was observed in amyloid deposits, and the truncation sites varied depending on the deposition pattern. There was a significantly higher incidence of amyloid deposition in Shiba dogs, and CK5 amino acid polymorphisms were identified in these dogs. A part of the C-terminal region of both canine and human CK5 exhibited highly amyloidogenic properties in vitro. This study revealed the existence of cutaneous keratinic amyloid deposition in animals and identified CK5 as an amyloid precursor protein, providing novel insights into understanding the etiology of cutaneous amyloidosis.

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Cutaneous Amyloidosis

Cited by 5 publications

References 92 publications

Loss of GPNMB Causes Autosomal-Recessive Amyloidosis Cutis Dyschromica in Humans

Loss of GPNMB Causes Autosomal-Recessive Amyloidosis Cutis Dyschromica in Humans

C4d as a Practical Marker for Cutaneous Amyloidosis

Keratinic amyloid deposition in canine hair follicle tumors

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