Efficacy of different modes of fractional CO2 laser in the treatment of primary cutaneous amyloidosis: A randomized clinical trial

Background

Primary cutaneous amyloidosis (PCA) comprises three main forms: macular, lichen, and nodular amyloidosis. The current available treatments are quite disappointing.

Objectives

Assess and compare the clinical and histological changes induced by different modes of Fractional CO₂ laser in treatment of PCA.

Patients and Methods

Twenty five patients with PCA (16 macular and 9 lichen amyloidosis) were treated by fractional CO₂ using; superficial ablation (area A ) and deep rejuvenation (area B ). Each patient received 4 sessions with 4 weeks intervals. Skin biopsies were obtained from all patients at baseline and one month after the last session. Patients were assessed clinically and histologically (Congo red staining, polarized light). Patients were followed‐up for 3 months after treatment.

Results

Both modes yielded significant reduction of pigmentation, thickness, itching, and amyloid deposits (P‐value < 0.001). However, the percentage of reduction of pigmentation was significantly higher in area A (P‐value = 0.003). Pain was significantly higher in area B. Significant reduction in dermal amyloid deposits denotes their trans‐epidermal elimination induced by fractional photothermolysis.

Conclusion

Both superficial and deep modes of fractional CO₂ laser showed comparable efficacy in treatment of PCA. Superficial mode being better tolerated by patients, is recommended as a valid therapeutic option. Lasers Surg. Med. 47:388–395, 2015. © 2015 Wiley Periodicals, Inc.     

原发性肝脏淀粉样变性7例报道及文献复习

目的 总结原发性肝脏淀粉样变性患者的临床特点,提高对本病的认识,减少误诊.方法 回顾性分析2007-2016年收治的7例原发性肝脏淀粉样变性患者的临床资料并复习相关文献.结果 7例患者临床表现主要为腹胀和食欲不振;肝功能检查γ-谷氨酰转肽酶(GGT)和碱性磷酸酶(ALP)升高明显;影像学提示肝脏均匀性增大.肝脏和胃部病理检查提示淀粉样物质沉积,刚果红染色阳性.1例患者肝脏穿刺后出血抢救无效死亡.4例未给予化疗,均因各种并发症死亡.1例给予马法兰联合泼尼松治疗,7个月后死亡.1例给予硼替佐米联合地塞米松治疗,治疗8个月病情稳定.结论 原发性肝脏淀粉样变性临床少见,肝脏均匀性增大,肝功能以GGT和ALP升高为主,病理检查是金标准.一般预后差,如果早期发现,可尝试给予新型蛋白酶体抑制剂化疗.     

Primary localized cutaneous nodular amyloidosis successfully treated with cyclophosphamide

Primary localized cutaneous nodular amyloidosis (PLCNA) is a rare subtype of localized cutaneous amyloidosis and can be associated with various connective tissue disorders. It can be difficult to treat and past therapies include surgical excision, dermabrasion, electrodessication and curettage, cryotherapy and laser therapy. We present a case of a middle‐aged woman with PLCNA associated with CREST (calcinosis, Raynaud phenomenon, oesophageal motility disorders, sclerodactyly and telangiectasia) syndrome and Sjögren's syndrome responding to cyclophosphamide with no new amyloid deposits and resolution of skin ulceration after many years of resistance to drug therapy. It is important to monitor these patients for progression into systemic amyloidosis.     

Amyloidosis of the tongue with kappa light chain disease

A 70-year-old woman presented with a painful, red tongue with papules associated with xerostomia and systemic symptoms including weight loss, difficulty in swallowing and breathing, haemochezia and leg swelling. Biopsy from the tongue demonstrated amyloid deposits and, on further investigation, kappa chain disease was diagnosed. Primary systemic amyloidosis was diagnosed and the patient died within weeks of presentation.     

原发性干燥综合征继发肺淀粉样变性影像学表现以及文献复习

目的 结合回顾文献分析原发性干燥综合征（pSS）继发肺淀粉样变性（PA）的CT及¹⁸F-FDG PET/CT表现。方法 回顾性收集4例经病理证实的pSS继发PA患者,均接受胸部CT检查,其中1例接受全身¹⁸F-FDG PET/CT检查;结合文献分析pSS继发PA的CT及¹⁸F-FDG PET/CT表现。结果 4例胸部CT均表现为双肺多发结节或团块,病灶最大径3~36 mm、中位最大径13 mm,CT值15~410 HU、中位CT值65 HU,部分伴钙化（3/4）;并均见肺囊腔样病变（4/4）。¹⁸F-FDG PET/CT示部分结节¹⁸F-FDG摄取轻度升高。结论 pSS继发PA的CT表现具有一定特征性;结合¹⁸F-FDG PET/CT有助于与肿瘤性病变相鉴别。     

Cytokeratins in primary cutaneous amyloidosis

The expression of keratins was investigated immunohistochemically on formalin-fixed and snap-frozen primary cutaneous amyloidosis tissue with a panel of monospecific and polyspecific antikeratin antibodies which recognized keratins K1, K5, K6, K7, K8, K10, K14, K16, K17, K18, and K19. Amyloid deposits in frozen section of seven cases of macular amyloidosis and lichen amyloidosus always reacted with antibodies LP34 (labeling K5, K6 and K18) MNF (labeling K5, K6, K8, K10, K17 and K18) and RCK 102 (labeling K5 and K8); frozen section in one case each of the seven cases also reacted with antibodies LL001 (labeling K14), Lp1K (labeling K7 and K17), and LP2K (labeling K19), LP1K (labelling K7 and K17), and LP2K (labelling K19), In formalin fixed section of 13 cases of macular amyloidosis and lichen amyloidosus amyloid deposits were labeled with LP34 in three section LL020 ()labelling keratins K5 and K6) in one section and LP2K in two section. In nodular primary cutaneous amyloidosis amyloid deposits were not labeled with any antikeratin antibodies. These data confirm that amyloid in macular amyloidosis and lichen amyloidosus contains keratin epitopes, and suggests derivation of the fibrillar component from keratin intermediate filaments Several different keratins appear to undergo conversion to amyloid, LP34, MNF 116 and RCK 102 antibodies, which have in common the labelling of keratin K5, may be useful in the diagnosis of macular and popular amyloidosis with frozen tissue section.     

Monoclonal gammopathy of undetermined significance in systemic transthyretin amyloidosis (ATTR)

Objective: To identify the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in patients with transthyretin (ATTR) amyloidosis.

Patients and methods: We performed a retrospective analysis of patients with biopsy-proven ATTRwt (wild-type transthyretin amyloid protein) and genopositive ATTR V122I (valine-to-isoleucine substitution at position 122 of the TTR gene) amyloidosis evaluated at the Amyloidosis Center at Boston University and Boston Medical Center between 1 January 2003 and 31 December 2016.

Results: There were a total of 226 patients with ATTRwt and ATTR V122I amyloidosis evaluated during the specified time frame with 155 and 71 patients in each cohort, respectively. Those with complete medical records, 140 patients with ATTRwt and 57 V1221 ATTRm subjects, were included in the analyses. Fifty-five patients (39%) in the ATTRwt cohort and 28 patients (49%) in the ATTR V122I cohort had an MGUS, as indicated by an abnormality in the serum-free light-chain ratio and/or serum immunofixation electrophoresis.

Conclusion: These data confirm the high prevalence of coexistent MGUS with ATTR amyloidosis in this patient population, with an MGUS rate that is higher than the general population. These findings also highlight the importance of a thorough diagnostic evaluation in patients with amyloidosis to determine the precursor protein, as the clinical course and treatment of AL (light-chain amyloid protein) and ATTR amyloidosis are distinct.     

Clinical Importance of Left Atrial Infiltration in Cardiac Transthyretin Amyloidosis

ObjectivesThe aim of this study was to characterize left atrial (LA) pathology in explanted hearts with transthyretin amyloid cardiomyopathy (ATTR-CM); LA mechanics using echocardiographic speckle-tracking in a large cohort of patients with ATTR-CM; and to study the association with mortality.BackgroundThe clinical significance of LA involvement in ATTR-CM is of great clinical interest.MethodsCongo red staining and immunohistochemistry was performed to assess the presence, type, and extent of amyloid and associated changes in 5 explanted ATTR-CM atria. Echo speckle tracking was used to assess LA reservoir, conduit, contractile function, and stiffness in 906 patients with ATTR-CM (551 wild-type (wt)-ATTR-CM; 93 T60A-ATTR-CM; 241 V122I-ATTR-CM; 21 other).ResultsThere was extensive ATTR amyloid infiltration in the 5 atria, with loss of normal architecture, vessels remodeling, capillary disruption, and subendocardial fibrosis. Echo speckle tracking in 906 patients with ATTR-CM demonstrated increased atrial stiffness (median [25th-75th quartile] 1.83 [1.15-2.92]) that remained independently associated with prognosis after adjusting for known predictors (lnLA stiff: HR: 1.23; 95% CI: 1.03-1.49; P = 0.029). There was substantial impairment of the 3 phasic functional atrial components (reservoir 8.86% [5.94%-12.97%]; conduit 6.5% [4.53%-9.28%]; contraction function 4.0% [2.29%-6.56%]). Atrial contraction was absent in 22.1% of patients whose electrocardiograms showed sinus rhythm (SR) “atrial electromechanical dissociation” (AEMD). AEMD was associated with poorer prognosis compared with patients with SR and effective mechanical contraction (P = 0.0018). AEMD conferred a similar prognosis to patients in atrial fibrillation.ConclusionsThe phenotype of ATTR-CM includes significant infiltration of the atrial walls, with progressive loss of atrial function and increased stiffness, which is a strong independent predictor of mortality. AEMD emerged as a distinctive phenotype identifying patients in SR with poor prognosis.     

How to diagnose amyloidosis

Amyloidosis is a rare but devastating condition caused by deposition of misfolded proteins as aggregates in the extracellular tissues of the body, leading to impairment of organ function. High clinical suspicion is required to facilitate early diagnosis. Correct identification of the causal amyloid protein is absolutely crucial for clinical management in order to avoid misdiagnosis and inappropriate, potentially harmful treatment, to assess prognosis, and to offer genetic counselling if relevant. This review summarises the current evidence on which the diagnosis and subtyping of amyloidosis is based, outlines the limitations of various diagnostic techniques, particularly in an Australian and New Zealand context, and discusses optimal strategies for the diagnostic approach to these patients. Recommendations are provided for when particularly to suspect amyloidosis, what investigations are required, as well as an approach to accurate subtyping of amyloidosis.