Case Of Primary Cutaneous Amyloidosis Research Articles

Dermoscopy aids in differentiating primary cutaneous amyloidosis and post-inflammatory hyperpigmentation: A clinico-dermoscopic-histopathaological study.

Primary cutaneous amyloidosis (PCA) and post-inflammatory hyperpigmentation (PIH) are common causes of cutaneous hyperpigmentation that are usually diagnosed clinically. However, their presentations are sometimes atypical, and their differentiation is difficult. Dermoscopy is a valuable diagnostic tool for pigmented diseases that might aid in their diagnosis. To describe the characteristic dermoscopic features of PCA and PIH together with histopathological correlation, and to differentiate between these conditions in a non-invasive way. Fifty-two patients with PCA (n=26) and PIH (n=26) were enrolled. A detailed history, skin examination, dermoscopic examination using handheld and video dermoscopy, and histopathological evaluation were performed. A statistically significant difference could be detected between PCA and PIH in terms of the duration of the disease (p=0.027), symmetry (p=0.044), rippling (p < 0.001), and back affection (p=0.048). On dermoscopic examination, central hubs were seen more in the PCA group (p < 0.001) with different patterns of peripheral pigmentation. Histopathologically, the number of melanophages per high-power field was significantly higher in the PCA group (p=0.013). The results of this study shed the light on the potential of dermoscopy as a non-invasive diagnostic tool in differentiating between doubtful cases of PCA and PIH.

Primary cutaneous amyloidosis: A clinicopathological, histochemical, and immunohistochemical study.

Primary cutaneous amyloidosis (PCA) comprises several forms of localized cutaneous amyloidosis characterized by amyloid deposits occurring at or near dermal-epidermal junctions. Immunohistochemical studies have shown the expression of cytokeratin (CK) suggesting that it has an epidermal origin. To study the clinicopathological features of PCA and expression of CK5/6 and correlate it with Congo red stain. A total of 30 histologically proven cases of PCA were studied. Congo red staining and immunohistochemical expression of CK5/6 were analyzed. : The qualitative data has been expressed as proportions and the quantitative data has been expressed as mean ± SD. All data was analyzed using the Statistical Package for Social Sciences (SPSS) software version 22. Deposits of amyloid in papillary dermis were seen in all 30 cases. Mild focal basal cell vacuolar degeneration and apoptotic bodies in epidermis were seen in six cases. The presence of pigment cells in dermis were seen in 26 cases. CK5/6 showed weak/mild immunopositivity in nine cases, moderate in 20 cases, and strong in one case. The presence of dermal melanophages interspersed within eosinophilic deposits gives a clue to the diagnosis. Congo red stain highlights the deposits and visualization under polarized light gives apple green birefringence which is diagnostic of amyloid. Staining of amyloid deposits by CK5/6 proves that the amyloid is of keratinocyte origin. There was 100% sensitivity with Congo red and CK5/6. Thus, CK5/6 can be used as an adjunct tool to Congo red stain in the diagnosis of primary cutaneous amyloidosis.

A clinicopathological study of primary cutaneous amyloidosis

Background: Primary localized cutaneous amyloidosis (PCA) is a common problem encountered in dermatology outpatient characterized by deposition of amyloid in dermis without any systemic involvement. Three subtypes have been recognized namely Macular, Papular (Lichen) and Nodular forms. Histopathological examination of the lesions reveals amorphous eosinophilic deposits in papillary dermis which stain positively with congo red. Aim: To study and correlate the clinical and histological profile of all three forms of primary cutaneous amyloidosis. Materials and Methods: A total number of 85 cases of primary cutaneous amyloidosis were included in the study. After a detailed history and complete examination, the patient was subjected to skin biopsy from the affected area. The clinical and histopathological findings obtained were analyzed and results correlated. Results: Of the 85 cases of Primary localized cutaneous amyloidosis, 43 cases (50.6%) were of Lichen amyloidosis and 36 cases (42.35%) were Macular amyloidosis. 6 cases (7%) were biphasic amyloidosis. Most of patients were in the age group of 21-50 years with slight female predominance 1:1.3. Majority of the cases of Lichen amyloidosis involved the pretibial area where as Macular amyloidosis affected the upper back and extensor aspect of arms. Histopathologically, the epidermis showed hyperkeratosis and irregular acanthosis which was more prominent finding in Lichen amyloidosis than the macular form. In both these variants there was expansion of dermal papillae by amyloid deposits showing positive congo red staining. Conclusions: Similar demographic profile and histopathological characteristics between Lichen and Macular amyloidosis suggests that these two forms are closely related variants of a single disease.

An unusual presentation of primary cutaneous amyloidosis

Primary localized cutaneous amyloidosis refers to a group of disorders characterized by deposition of amyloid in the dermis without any systemic involvement. It comprises the following clinical types: macular, lichenoid, nodular, and biphasic. There are also rare variants such as amyloidosis cutis dyscromica and poikiloderma-like cutaneous amyloidosis. We report a case of primary cutaneous amyloidosis in a 17-year-old boy with unusual pigmentation of various patterns (reticulate and diffuse pigmentation with mottling and rippling at places) and hypopigmented atrophic macules. Our patient also had nail, oral, and mucosal pigmentation that have not been described. Amyloid deposits were shown histopathologically in both hyperpigmented and hypopigmented macules.

Thalidomide improves clinical symptoms of primary cutaneous amyloidosis: report of familiar and sporadic cases

Primary cutaneous amyloidosis (PCA), either familial or sporadic, poses a therapeutic challenge. We conducted an open trial using thalidomide to treat three cases of familial and three cases of sporadic PCA, at initial dose of 100 mg/day. Dosage adjustment was made according to improvement of symptoms or patient's own choice. All except one sporadic case experienced moderate to significant relief on the symptoms of itching, over an observational period of 8 weeks by visual analog score (from 8.08 ± 0.88 to 1.60 ± 0.68, on average) as well as clinical amelioration of symptoms. Side effects included fatigue, drowsiness, numbness, and facial and leg edema in some of the patients. From the present observation, it seems that thalidomide is a promising drug to treat PCA.

Role of oligomers in the amyloidogenesis of primary cutaneous amyloidosis

Primary cutaneous amyloidosis (PCA) describes a heterogeneous group of cutaneous diseases characterized by amyloid deposition; this may manifest as macules, papules, or nodules, depending on the subtype involved. To date, relatively little is known about the process of amyloidogenesis in the skin; however, investigators recently have identified small amyloid species, known as oligomers, which give rise to large amyloid fibrillar aggregates. The purpose of the current study was to identify small oligomers in patients with PCA using novel immunohistochemical techniques and to examine our findings in light of previous hypotheses of amyloid formation in these diseases. Six cases of PCA were analyzed using Congo red, thioflavin S, and hematoxylin-eosin. We also analyzed these samples with the novel oligomer-specific conformational antibody I-11 to detect the small, misfolded protein oligomers. Semiquantitative analysis was performed on these samples to grade the amount of amyloid aggregates and oligomers detected in the skin samples with light and polarized microscopy. In the cases examined, we detected intracellular oligomers in the basal cell layer of the epidermis and the surrounding cells in the dermis. We also were able to detect large aggregates of amyloid in our samples and to correlate the relationship of oligomers to amyloid aggregates in accordance with previous studies on cutaneous amyloidosis and other amyloid-related diseases. Small sample size is a limitation. PCA is an amyloid-related disease that likely follows a similar mechanism as other more intensively studied amyloid diseases.

Novel IL31RA gene mutation and ancestral OSMR mutant allele in familial primary cutaneous amyloidosis

Primary cutaneous amyloidosis (PCA) is an itchy skin disorder associated with amyloid deposits in the superficial dermis. The disease is relatively common in Southeast Asia and South America. Autosomal dominant PCA has been mapped earlier to 5p13.1-q11.2 and two pathogenic missense mutations in the OSMR gene, which encodes the interleukin-6 family cytokine receptor oncostatin M receptor beta (OSMRbeta), were reported. Here, we investigated 29 Taiwanese pedigrees with PCA and found that 10 had heterozygous missense mutations in OSMR: p.D647V (one family), p.P694L (six families), and p.K697T (three families). The mutation p.P694L was associated with the same haplotype in five of six families and also detected in two sporadic cases of PCA. Of the other 19 pedigrees that lacked OSMR pathology, 8 mapped to the same locus on chromosome 5, which also contains the genes for 3 other interleukin-6 family cytokine receptors, including interleukin-31 receptor A (IL31RA), which can form a heterodimeric receptor with OSMRbeta through interleukin-31 signaling. In one family, we identified a point mutation in the IL31RA gene, c.1562C>T that results in a missense mutation, p.S521F, which is also sited within a fibronectin type III-like repeat domain as observed in the OSMR mutations. PCA is a genetically heterogeneous disorder but our study shows that it can be caused by mutations in two biologically associated cytokine receptor genes located on chromosome 5. The identification of OSMR and IL31RA gene pathology provides an explanation of the high prevalence of PCA in Taiwan as well as new insight into disease pathophysiology.

Hypopigmented macular amyloidosis with or without hyperpigmentation

Primary cutaneous amyloidosis (PCA) is a chronic pruritic skin disorder with characteristic amyloid deposits in the papillary dermis. We report three cases of PCA, which shared common features of hypopigmentation as a predominant feature with or without reticular hyperpigmentation, no itching, adult onset and dermal papillary amyloid deposition. These cases did not conform to the usual features of PCA.

Genome-wide scan identifies a susceptibility locus for familial primary cutaneous amyloidosis on chromosome 5p13.1-q11.2

Primary cutaneous amyloidosis (PCA) is a relatively common skin disorder in South America and Southeast Asia. Most cases of PCA are sporadic but familial aggregation has been reported from South America and Taiwan. The different susceptibility among ethnic groups suggests that genetic factors may play an important role in its pathogenesis. We aimed to perform a genome-wide scan by linkage analysis across 15 families with familial primary cutaneous amyloidosis (FPCA) to map the disease gene(s) for FPCA. A total of 15 FPCA families including 50 individuals affected with PCA were recruited. Throughout the 22 autosomes, 369 polymorphic microsatellite markers were used initially. Regions showing a LOD score > 1 identified in the initial scan were further analysed with additional markers. Two-point and multipoint linkage analysis were performed by using the LINKAGE program. Nonparametric linkage (NPL) analysis and reconstruction of haplotypes were performed with the GENEHUNTER program. A maximum two-point LOD score of 4.76 for the marker D5S1490 (theta = 0.10, alpha = 0.60) and a multipoint LOD score of 4.50 between D5S822 and D5S623 (alpha = 0.60) were obtained under the assumption of heterogeneity. A peak NPL score of 5.23 (P value = 0.000007) was found from D5S1490 to D5S2076. Further analysis focusing on two major families identifies a common haplotype shared by all affected individuals between D5S1490 and D5S623. To our knowledge, this is the first report of genome-wide analysis of a large number of FPCA pedigrees. Our study provides evidence for significant linkage to chromosome 5p13.1-q11.2 in a subset of FPCA families.

Detection of Epstein-Barr virus in primary cutaneous amyloidosis

To determine the association of Epstein-Barr virus (EBV) with primary cutaneous amyloidosis (PCA), a retrospective study was conducted on skin tissue from 27 Chinese patients with lichen amyloidosus and macular amyloidosis. In situ hybridization with oligonucleotide probes was used to detect the expression of EBV-encoded RNAs (EBERs). Eleven of 27 cases (40.7%) were found to contain the EBV genome. No EBV genome was detected in the skin of the control groups, including three cases of secondary cutaneous amyloidosis, two cases of primary systemic amyloidosis, and four cases of lichen simplex chronicus. Our study showed no correlation between the presence of EBV in PCA patients and the patients' age, sex, clinical type or severity of the skin lesions. Although our results suggest that EBV may be associated with some cases of PCA, the true aetiological role of EBV in PCA remains unknown.

Evaluation of cutaneous amyloid employing anti-keratin antibodies and the immunoperoxidase technique (PAP method)

Thirty-one cases of primary cutaneous amyloidosis were studied by the immunoperoxidase technique (PAP method) employing anti-keratin antibodies. All specimens were examined using consecutive paraffin sections to confirm the correspondence between amyloid existing area and reactive sites. All of the sections examined were non-reactive in amyloid deposited sites whereas the epidermis always showed strong reaction with anti-keratin antibodies.

Primary cutaneous amyloidosis: clinical, laboratorial and histopathological study of 25 cases. Identification of gammaglobulins and C3 in the lesions by immunofluorescence.

25 cases of primary cutaneous amyloidosis are studied. 16 patients had macular amyloidosis (MPA) and 9 lichen amyloidosus (LPA). gamma-Globulins were increased in 50% of the patients. IgG and IgA were increased in the serum of 5 and 3 patients with MPA and 4 and 2 patients with LPA, respectively. Volume of amyloid deposits was similar in both forms. By direct immunofluorescence we demonstrated IgG in the amyloid deposits of 21 of the 25 cases and C3 in 13; IgM was present in 9 cases of MPA and in 3 cases of LPA. MPA was more frequent than LPA; histologically, it was impossible to distinguish MPA from LPA; correlation between serum levels of gamma-globulins and their presence in amyloid deposits was weak; MPA and LPA seem to be distinct clinical manifestations of the same disease and itching does not cause transformation of MPA in LPA.