Amyloidosis Cutis Dyschromica Research Articles

Amyloidosis Cutis Dyschromica: A Rare Subtype of Primary Cutaneous Amyloidosis with Dermoscopy.

Amyloidosis Cutis Dyschromica: A Rare Subtype of Primary Cutaneous Amyloidosis with Dermoscopy.

Amyloidosis Cutis Dyschromica in a 16-Year-Old Filipino Girl: A Case Report

Amyloidosis cutis dyschromica is a rare variant of primary cutaneous amyloidosis characterized by hyper- and hypopigmented macules. In this paper, we reported a case of a 16-year-old Filipino girl with hyper- and hypopigmented to depigmented macules on the upper and lower extremities, which started when she was 9 years of age.

Amyloidosis cutis dyschromica cases caused by GPNMB mutations with different inheritance patterns

BackgroundAmyloidosis cutis dyschromica (ACD) is a rare form of primary cutaneous amyloidosis featured by reticulate dotted hypo- and hyperpigmentation. Recently, loss-of-function mutations in GPNMB, encoding glycoprotein (transmembrane) nonmetastatic melanoma protein B, were found in autosomal-recessive or semi-dominant ACD. ObjectiveThis study aims to detect the genetic defect underlying ACD in nine separate cases and to investigate the functional consequences of the mutants. MethodsNine ACD cases were collected including eight with autosomal-recessive pattern and one with autosomal-dominant pattern. Whole-exome sequencing or Sanger sequencing of the GPNMB gene was performed to detect the pathogenic mutations. Haplotype analysis was employed to determine the origin of mutation c.565C > T using adjacent highly polymorphic SNPs. Immunoblotting and subcellular localization assessments were performed to evaluate the expression of the mutants using HEK293 cells transfected with the GPNMB constructs. ResultsWe detected four recurrent mutations (c.393 T > G, p.Y131*; c.565C > T, p.R189*; c.1056delT, p.P353Lfs*20; c.1238 G > C, p.C413S) and two novel mutations (c.935delA, p.N312Tfs*4; c.969 T > A, p.C323*) in GPNMB. Mutation c.565C > T found in six separate ACD cases shared a common haplotype. The two novel mutations caused a decreased abundance of truncated proteins. The c.1238 G > C mutation, which was detected in the autosomal-dominant case, caused abnormal reticular subcellular localization of the protein. A major percentage of wildtype changed its expression pattern when co-expressed with this mutant. ConclusionsOur findings proved that the recurrent mutation c.565C > T originated from a founder effect. The autosomal-dominant ACD associated mutation p.C413S played its pathogenic role through a dominant-negative effect on wild-type GPNMB. This study expands the genotype and inherited modes of ACD and improves our understanding of the pathogenesis of this disorder.

Sequence analysis of GPNMB in 9 patients with amyloidosis cutis dyschromica

Sequence analysis of GPNMB in 9 patients with amyloidosis cutis dyschromica

Amyloidosis cutis dyschromica due to homozygous variants of the GPNMB gene in a Chinese pedigree

To explore the genetic basis for a Chinese pedigree affected with amyloidosis cutis dyschromica. High-throughput sequencing was carried out for the proband. Bioinformatic analysis was used to identify the pathogenic variants. The result was verified by Sanger sequencing. A homozygous nonsense variant c.565C>T (p.Arg189X) of the GPNMB gene was identified in the proband, his elder brother and younger sister, which resulted a truncated protein with loss of function. The father of the proband was a heterozygous carrier for the variant. The genotype of his mother was unknown since she had passed away. Based on the American College of Medical Genetics and Genomics standards and guidelines, the c.565C>T variant was predicted to be likely pathogenic (PS3+ PM2+ PP1+PP3). The novel homozygous GPNMB variant probably underlay the amyloidosis cutis dyschromica in this pedigree. Above finding has expanded the spectrum of GPNMB gene variants.

Amyloidosis Cutis Dyschromica, A Rare Subtype of Primary Cutaneous Amyloidosis: Case Report and Literature Review.

Amyloidosis Cutis Dyschromica, A Rare Subtype of Primary Cutaneous Amyloidosis: Case Report and Literature Review.

Molecular basis and inheritance patterns of amyloidosis cutis dyschromica.

Molecular basis and inheritance patterns of amyloidosis cutis dyschromica.

Late-onset amyloidosis cutis dyschromica: an unusual case

Amyloidosis cutis dyschromica (ACD) is a rare form of primary cutaneous amyloidosis. ACD, first described by Morishima in 1970 is characterized by (i) macular, speckled, reticular hyperpigmentation with hypopigmented spots distributed extensively over the body; (ii) little or no pruritus; (iii) prepubertal onset; and (iv) focal subepidermal amyloid deposition. A 49-year-old woman presented with a 20-year history of progressive, asymptomatic, generalized mottled hyper- and hypopigmented macules all over the body. Histopathological examination of a punch biopsy specimen showed deposition of homogeneous, eosinophilic material in the papillary dermis. This amorphous, eosinophilic material was stained metachromatically with crystal violet stain and found to be compatible with amyloid. Based on the clinical and histopathological findings, the patient was diagnosed as having ACD. Amyloidosis cutis dyschromica must be considered in the differential diagnosis of patients with diffuse dyschromatosis including both hyperpigmented and hypopigmented lesions and histopathological confirmation is necessary in order to reach a correct diagnosis.

Amyloidosis cutis dyschromica: report of 3 cases

Amyloidosis cutis dyschromica (ACD) is a rare pigmentary disorder with about 50 cases having been reported in the English literature. Only one case of ACD has been reported from Iran. We present three patients who presented with generalized hyper- and hypopigmented patches, sparing face, hands, and feet in all three cases. The presence of amorphous eosinophilic deposits in the papillary dermis confirmed the diagnosis of ACD; the deposits were stained by crystal violet in the histopathological examination of the lesions. In all three cases, similar lesions were present in some of the family members. ACD should be considered in the differential diagnosis of diffuse hyperpigmentation studded with hypopigmentation, especially when beginning in childhood.

Amyloidosis cutis dyschromica: A rare dyschromic pigmentary disorder

Primary cutaneous amyloidosis (PCA) is the deposition of amyloid proteins in the skin without systemic involvement. Amyloidosis cutis dyschromica (ACD) is a rare variant of PCA with onset typically in early childhood or at a prepubertal age. It is more common in the Asian and Southeast Asian people. Clinically it manifests as asymptomatic diffuse hyperpigmentation interspersed with hypopigmented spots without papulation. Histologically, small foci of amyloid closely under the epidermis are seen. There are only few case reports in the literature of this rarer variant. We report a case of a 32-year-old male presenting as dyschromatosis with a prepubertal onset and histopathological evidence of intradermal deposits in the upper dermis which was confirmed on Congo red staining and hence was diagnosed as a case of ACD.

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

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.

Amyloidosis cutis dyschromica: A rare dyschromic subtype of primary cutaneous amyloidosis

Amyloidosis cutis dyschromica (ACD) is a very rare and distinctive variant of primary cutaneous amyloidosis, clinically characterized by the appearance of hyperpigmented and hypopigmented or depigmented macules on normal looking skin before puberty in generalized distribution. We herein report a 30-year-old male with ACD involving whole body except hands, feet, palm, soles, genitalia, and mucosa since 10 years of age and positive family history. His 25-year-old younger sister also had the similar mottled pigmentary lesions since 8 years of age. On histopathological examination (HPE) of the hyperpigmented macules, increased melanin in the basal layer, pigmentary incontinence, and amorphous eosinophilic deposits were seen in the papillary dermis. HPE of depigmented lesions demonstrated a significant decrease in the number of melanocytes and melanin in the basal layer along with deposition of eosinophilic amyloids in papillary dermis. Based on these HP findings, diagnosis of ACD was made.

Amyloidosis Cutis Dyschromica: A Rare Reticulate Pigmentary Dermatosis.

We are reporting a rare case of amyloidosis cutis dyschromica in a 41-year-old man. This is a rare form of primary cutaneous amyloidosis characterized by reticulate pigmentation with hypopigmented and hyperpigmented macules, onset in childhood, familial tendency in some, occasional mild itching and deposition of amyloid in the papillary dermis. Our case also had multiple bilaterally symmetrical hyperpigmented keratotic papules abutting the axillary vault resembling those seen in Dowling–Deogs disease. The other unusual feature in this patient was the strong family history of vitiligo, which we are unable to explain. We have also tried to explain the mechanism leading to the hyperpigmentation and hypopigmentation in amyloidosis cutis dyschromica.

Amyloidosis cutis dyschromica

Amyloidosis cutis dyschromica is a very rare form of primary cutaneous amyloidosis characterized by prepubertal onset of hyper and hypopigmented spots and amyloid deposits in the papillary dermis. We report a case of a 26 year old female with amyloidosis cutis dyschromica who presented with dyschromic skin since birth.

Amyloidosis cutis dyschromica

BackgroundAmyloidosis cutis dyschromica is a rarely documented variant of cutaneous amyloidosis. To date, only 26 cases have been reported.ObjectiveThe purpose of this study was to improve the clinical and histopathological data for this variant of amyloidosis and to highlight the immunohistochemical features of the disease. The published cases were also reviewed.MethodsWe performed a retrospective review of patients with amyloidosis cutis dyschromica in a single centre. The clinical, histopathological and immunohistochemical features were documented and analysed.ObservationsWe described 10 cases of amyloidosis cutis dyschromica. Six of them were female. Five patients were from the same family, and the other 5 were sporadic. The distinguishing features of the clinical presentation included generalised mottled hyper- and hypopigmented macules, which were asymptomatic or mild pruritic. The typical onset of the lesions occurred in childhood (n = 7) and occasionally after puberty (n = 3). No evidence of systemic amyloidosis deposition was observed in these cases of amyloidosis cutis dyschromica. Amyloid deposits were observed in the papillary dermis and were positive for the Congo red stain. An immunohistochemical study showed that the amyloid expresses cytokeratins CK34βE12 and CK5/6.ConclusionsWe described the largest series of amyloidosis cutis dyschromica to date and reviewed the published patients. This rare disease is featured by generalised mottled hyper- and hypopigmented lesions, and it is a rare variant of primary cutaneous amyloidosis without evidence of systemic amyloid deposition. Positive staining for the cytokeratins CK34βE12 and CK5/6 in amyloidosis cutis dyschromica suggests that the amyloid is derived from keratinocytes.

Amyloidosis cutis dyschromica associated with atypical Parkinsonism, spasticity and motor weakness in a Pakistani female

Amyloidosis cutis dyschromica is a rare form of cutaneous amyloidosis in which there is deposition of keratinocyte-derived amyloid with involvement of almost the entire integument, leading to diffuse dyschromia without associated systemic abnormalities. We report the case of a 40-year-old female who presented with the onset of diffuse hyperpigmentation shortly after birth, which was followed by the widespread development of numerous 2-5 mm hypopigmented macules. Biopsy of the one of these macules revealed eosinophilic globular material in the papillary dermis with Congo red birefringence which also stained positively for high-molecular weight cytokeratin. Electron microscopy confirmed the presence of 11 nm hollow fibrils, consistent with amyloid. Similar clinical changes were noted in a younger male sibling. Both patients also suffered from an unexplained neurological disorder characterized by atypical Parkinsonism, spasticity and motor weakness. This association has not been shown before and may represent a heretofore unreported contiguous gene syndrome.

Amyloidosis cutis dyschromica: a rare pigmentary disorder

Amyloidosis cutis dyschromica represents a rare type of primary cutaneous amyloidosis with few reported cases worldwide. It is characterized by asymptomatic, generalized hyperpigmentation with intermingled hypopigmented macules without atrophy or telangiectasia. We report herein a 19-year-old female who developed this pigmentary abnormality at 4 years of age. Her aunt and great grandfather also had similar skin pigmentation. An unusual finding in our patient was the presence of papules in addition to characteristic macules. Amyloid deposits were shown histopathologically in both dyschromic macules and papules.

Amyloidosis cutis dyschromica in two female siblings: cases report

BackgroundCutaneous amyloidosis has been classified into primary cutaneous amyloidosis (PCA, OMIM #105250), secondary cutaneous amyloidosis and systemic cutaneous amyloidosis. PCA is the deposition of amyloid in previously apparent normal skin without systemic involvement. Amyloidosis cutis dyschromica (ACD) is a rare distinct type of PCA. Here, the unique clinical and histological findings of two Chinese female siblings with ACD were described.Cases presentationsPatient 1 was a 34-year-old female, presented with mildly pruritic, diffuse mottled hyperpigmentation and hypopigmentation. The lesions involved all over the body since she was 10 years old. There were a few itchy blisters appearing on her arms, lower legs and truck, especially on the sun-exposed areas in summer. Some hypopigmented macules presented with slight atrophy. Patient 2 was 39-year-old, the elder sister of patient 1. She had similar skin lesions since the same age as the former. The atrophy and blisters on the skin of the patient with amyloidosis cutis dyschromica have not been described in previous literature. Histological examinations of the skin biopsies taken from both patients revealed amyloid deposits in the whole papillary dermis. Depending on the histological assessment, the two cases were diagnosed as amyloidosis cutis dyschromica.ConclusionThe two cases suggest that the atrophy and blisters may be the uncommon manifestations of amyloidosis cutis dyschromica. It alerts clinicians to consider the possibility of ACD when meeting patients with cutaneous dyschromia. Skin biopsy is essential and family consultation of genetic investigation is very important in such cases.

Familial amyloidosis cutis dyschromica

Primary cutaneous amyloidosis is a rare progressive disease that is characterized with the deposition of amyloid under the skin instead of internal organs. Major types are the macular, papular, nodular types. Amyloidosis cutis dyschromica is a very rare specific type of vitiliginous amyloidosis. A 16 year-old female patient and 22 year-old male patient, siblings, referred to the hospital with the complaint of non-pruritic diffuse hyperpigmentation beginning from trunk and spreading to all body. The histopathologic findings and crystal violet stain were consistent with amyloidosis cutis dyschromica. All other investigations were normal. There are few reported cases related with this amyloidosis type and it was seldom reported as familial. This case is the first familial case from Turkey.

Amyloidosis cutis dyschromica: four cases from two families

International Journal of DermatologyVolume 48, Issue 5 p. 518-521 Amyloidosis cutis dyschromica: four cases from two families Wei-Hsuan Huang MD, Wei-Hsuan Huang MD From the Department of Dermatology and Pathology, Tri-Service General Hospital, Taipei, TaiwanSearch for more papers by this authorChou-Yueh Wu MD, Chou-Yueh Wu MD From the Department of Dermatology and Pathology, Tri-Service General Hospital, Taipei, TaiwanSearch for more papers by this authorCheng-Ping Yu MD, Cheng-Ping Yu MD From the Department of Dermatology and Pathology, Tri-Service General Hospital, Taipei, TaiwanSearch for more papers by this authorChien-Ping Chiang MD, Chien-Ping Chiang MD From the Department of Dermatology and Pathology, Tri-Service General Hospital, Taipei, TaiwanSearch for more papers by this author Wei-Hsuan Huang MD, Wei-Hsuan Huang MD From the Department of Dermatology and Pathology, Tri-Service General Hospital, Taipei, TaiwanSearch for more papers by this authorChou-Yueh Wu MD, Chou-Yueh Wu MD From the Department of Dermatology and Pathology, Tri-Service General Hospital, Taipei, TaiwanSearch for more papers by this authorCheng-Ping Yu MD, Cheng-Ping Yu MD From the Department of Dermatology and Pathology, Tri-Service General Hospital, Taipei, TaiwanSearch for more papers by this authorChien-Ping Chiang MD, Chien-Ping Chiang MD From the Department of Dermatology and Pathology, Tri-Service General Hospital, Taipei, TaiwanSearch for more papers by this author First published: 09 April 2009 https://doi.org/10.1111/j.1365-4632.2009.03844.xCitations: 16 Chien-Ping Chiang, md Department of Dermatology Tri-Service General Hospital National Defense Medical Center No. 325, Cheng-Kung Road Sec. 2, Neihu District 114 Taipei, TaiwanE-mail: chiang@ndmctsgh.edu.tw Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume48, Issue5May 2009Pages 518-521 RelatedInformation