UNASSIGNED: Genetic mutations or inflammatory, degenerative, or neoplastic conditions can trigger amyloidosis. Hereditary gelsolin amyloidosis is a genetic disorder primarily marked by amyloid fibrils composed of misfolded gelsolin fragments.
UNASSIGNED: We present three sisters with AGel amyloidosis, illustrating its clinical diversity. Patient 1, a 51-year-old, had bilateral ptosis, ocular discomfort, and dry eye syndrome due to cranial nerve involvement. Patient 2, a 53-year-old, experienced progressive bilateral visual impairment. Patient 3, a 50-year-old, exhibited right eye ectropion. Genetic analysis, with the identical mutation, heterozygous c.640G > A (p.Asp214Asn) mutation, confirmed AGel amyloidosis diagnoses, with common findings including lattice corneal amyloidosis, reduced corneal sensitivity, and recurrent corneal erosions. Neurological manifestations included ataxia and peripheral neuropathy, with skin abnormalities observed in patient 1. Ocular involvement severity and distribution varied among patients.
UNASSIGNED: Common ocular and neurological manifestations validated AGel amyloidosis diagnoses, reinforcing its hereditary basis. Neurological symptoms highlighted the disorder\'s impact on various organ systems, while skin abnormalities contributed to ocular discomfort. Variable ocular involvement emphasized the disorder\'s heterogeneity. These patients emphasize hereditary gelsolin amyloidosis\'s clinical diversity and suggest potential environmental influences on disease expression. Genetic confirmation and confocal microscopy findings reaffirm the genetic basis while raising questions about assessing systemic disease severity, necessitating further investigation in larger cohorts. Ophthalmologists\' specialized care is crucial for managing ocular symptoms, given the absence of a universal cure.

BACKGROUND: Primary cutaneous macular amyloidosis (PCMA) is a chronic pruritic cutaneous disease characterized by heterogeneous extracellular deposition of amyloid protein in the skin.
OBJECTIVE: This study aimed to evaluate the efficacy of topical 6% gabapentin cream for the treatment of patients with PCMA.
METHODS: In this triple-blind clinical trial, a total of 34 patients, who were diagnosed with PCMA, treated using two different strategies of topical gabapentin as the active group and vehicle cream as the control group.
RESULTS: Pruritus score reduction in both groups was statistically significant compared with the baseline value (p < 0.001). There was a significant pigmentation score reduction in intervention group compared with control group after 1 month of the study (p < 0.001). The differences of pigmentation score changes between the groups were not significant at month 2 (p = 0.52) and month 3 (p = 0.22).
CONCLUSIONS: The results of this study suggest that topical gabapentin cream may be effective as a topical agent in the treatment of pruritus associated with PCMA without any significant adverse effects. It is recommended to perform similar studies with a larger sample size and longer duration in both sexes.

暂无摘要。

Hereditary transthyretin amyloidosis is the most common form of hereditary amyloidosis, with an autosomal dominant inheritance and a variable penetrance. ATTRv amyloidosis can present as a progressive, axonal sensory autonomic and motor neuropathy or as an infiltrative cardiomyopathy. The definition of biomarkers for the early diagnosis of ATTRv is particularly important in the current era of emerging treatments. In this sense, metabolomics could be an instrument able to provide metabolic profiles with their related metabolic pathways, and we would propose them as possible fluid biomarkers. The aim of this study is to identify altered metabolites (free fatty acids and amino acids) in subjects with a confirmed pathogenic TTR variant. Out of the studied total free fatty acids and amino acids, the serum values of palmitic acid are significantly lower in the ATTRv patients compared to the recruited healthy subjects. The metabolic remodeling identified in this neurogenetic disorder could be the manifestation of pathophysiological processes of the disease, such as mitochondrial dysfunction and neuroinflammation, and contribute to explaining some of its clinical manifestations.

UNASSIGNED: 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.
UNASSIGNED: To study the clinicopathological features of PCA and expression of CK5/6 and correlate it with Congo red stain.
UNASSIGNED: A total of 30 histologically proven cases of PCA were studied. Congo red staining and immunohistochemical expression of CK5/6 were analyzed.
UNASSIGNED: : 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

Primary cutaneous amyloidosis (PCA) is a pruritic disease characterized by amyloid deposition in the skin. Interleukin-31 (IL-31) is a pruritus-mediating cytokine. Fractional carbon dioxide (CO2 ) laser has shown efficacy in the treatment of PCA regarding the clinical appearance, histological pattern, and pruritus. The aim of this study is to assess the effect of fractional CO2 laser on pruritus associated with PCA, and analyze whether this effect is related to IL-31 and IL-31 receptor (R) expression.
The study included 24 patients with PCA and 24 healthy controls. Each patient received four fractional CO2 laser sessions, 4 weeks apart, using the superficial ablative mode. Skin biopsies were taken from patients before and after treatment, as well as controls, for assessment of IL-31 and IL-31R by real-time polymerase chain reaction.
Treatment resulted in significant improvement of all clinical parameters, including pruritus (P < 0.001). Patients before treatment had significantly higher IL-31 and IL-31R than controls (P = 0.000 for both). In addition, there was a statistically significant decrease in IL-31 and IL-31R after treatment than their values before treatment (P = 0.000 for both).
This study confirms the therapeutic efficacy of fractional CO2 laser in treatment of PCA. Reduction of IL-31 and its receptor seems to be one of the involved mechanisms; however, its relation to improvement of pruritus is still not clear. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Primary localized cutaneous amyloidosis (PLCA) is a recalcitrant sporadic dermatological condition and most treatments have failed so far. We studied the efficacy of topical dimethyl sulfoxide (DMSO) 50% solution in comparison with tretinoin 0.5% cream in treatment of macular amyloidosis. In this split-side within-person single-blinded randomized clinical trial, 18 patients with bilateral macular amyloidosis received topical DMSO 50% solution and tretinoin 0.5% cream either on their right or the left side. The colorimetry, pruritus scoring, and photography were done. A significant pigmentation decline per each follow-up was observed in DMSO group compared to the tretinoin group (tretinoin: -1.31 vs DMSO: -7.34; difference in slopes: -6.03 [95% confidence interval: -12.06 to -0.01], PInteraction = .049). An insignificant diminution trend in pigmentation was observed for both treatments (Ptretinoin = .672, PDMSO = .092). Also, both treatments relived itchiness, but DMSO completely dispatched itchiness from the first follow-up (P = .003 for tretinoin and <.0001 for DMSO). In conclusion, our results showed DMSO and tretinoin cream have the positive effect on the both pigmentation and itchiness in PLCA. DMSO may be more beneficial than tretinoin, since DMSO was significantly better in reducing itchiness. More investigations are warranted to provide sufficient evidence.

Hereditary gelsolin (AGel) amyloidosis is an autosomal dominantly inherited systemic amyloidosis that manifests with the characteristic triad of progressive ophthalmological, neurological and dermatological signs and symptoms. The National Finnish Gelsolin Amyloidosis Registry (FIN-GAR) was founded in 2013 to collect clinical data on patients with AGel amyloidosis, including altogether approximately one third of the Finnish patients. We aim to deepen knowledge on the disease burden and life span of the patients using data from the updated FIN-GAR registry. We sent an updated questionnaire concerning the symptoms and signs, symptomatic treatments and subjective perception on disease progression to 240 members of the Finnish Amyloidosis Association (SAMY). We analyzed the lifespan of 478 patients using the relative survival (RS) framework.
The updated FIN-GAR registry includes 261 patients. Symptoms and signs corresponding to the classical triad of ophthalmological (dry eyes in 93%; corneal lattice amyloidosis in 89%), neurological (numbness, tingling and other paresthesias in 75%; facial paresis in 67%), and dermatological (drooping eyelids in 86%; cutis laxa in 84%) manifestations were highly prevalent. Cardiac arrhythmias were reported by 15% of the patients and 5% had a cardiac pacemaker installed. Proteinuria was reported by 13% and renal failure by 5% of the patients. A total of 65% of the patients had undergone a skin or soft tissue surgery, 26% carpal tunnel surgery and 24% at least unilateral cataract surgery. As regards life span, relative survival estimates exceeded 1 for males and females until the age group of 70-74 years, for which it was 0.96.
AGel amyloidosis causes a wide variety of ophthalmological, neurological, cutaneous, and oral symptoms that together with repeated surgeries cause a clinically significant disease burden. Severe renal and cardiac manifestations are rare as compared to other systemic amyloidoses, explaining in part the finding that AGel amyloidosis does not shorten the life span of the patients at least for the first 75 years.

Macular amyloidosis (MA) is a common form of primary localized cutaneous amyloidosis, characterized by the eruption of brown pigments of the skin with a rippled pattern. MA can be of cosmetic concern for patients, and its treatment is challenging. In this study, we aimed to find new effective approaches for MA treatment. A total of 39 patients with the clinical diagnosis of MA were treated with two types of laser therapy, and the effectiveness of each approach was examined. Fractional Q-switched 10.64 nm neodymium-doped yttrium aluminum garnet (Nd:YAG) laser therapy was compared with a combination of fractional Q-switched 10.64 nm Nd:YAG laser and long-pulsed fractional erbium:YAG laser therapy. Melanin biometric measurements were performed using a Mexameter, objective image-based evaluation was carried out, and the itching score and patient satisfaction were examined. Mexameter-based analysis showed that both types of laser therapy were effective in the treatment of MA, causing a significant decrease in the amount of melanin in the treated areas (P < 0.05). Also, combination of two types of laser therapy was significantly more effective than one type alone (P < 0.05). The itching score significantly decreased in patients undergoing a combination of laser therapies. Also, a positive correlation was observed between the amount of melanin and degree of itching in the treated areas. Moreover, analysis of patient satisfaction showed that more than 90% of patients had excellent satisfaction with combination laser therapy. The results confirmed the significant positive effects of both fractional Nd:YAG laser alone and in combination with fractional erbium:YAG laser therapy considering the reduction in melanin content; however, combination of two types of laser therapy was more effective than one type alone. Trial registration: IRCT20080901001159N23.

UNASSIGNED: This aim of this study was to determine the effect of 1540-nm nonablative fractional erbium on macular amyloidosis.
UNASSIGNED: This phase-II clinical trial study has been performed with parallel group with blinding of the evaluator. The skin lesions of the patients (15 patients and 30 lesions) with cutaneous macular amyloidosis were randomly assigned into laser and no-treatment groups. In the laser group, treatment was performed by 1540-nm nonablative fractional erbium laser. Thereafter, the patients\' lesions were compared in terms of pigmentation, rippling, thickness, and subjective response.
UNASSIGNED: The lesions of the intervention group significantly improved in the three-month follow-up compared to the control group (in the control and intervention group, improved pigmentation was observed in 20 and 53.3% with p = .02, improved rippling in 6.7 and 60% with p = .007, diminished lichenification in 0 and 53.1% with p = .007, and overall lesion improvement in 20 and 60% with p = .03, respectively). In investigating the subjective response through patient global assessment, the patients in the intervention group had a greater satisfaction (p = .01). There was a considerable improvement of pruritus in the intervention group (p = .001).
UNASSIGNED: Use of 1540-nm nonablative fractional erbium laser offered a suitable efficacy to treat macular amyloidosis without significant complications.