Patisiran Treatment in Patients with Transthyretin Cardiac Amyloidosis.

BACKGROUND: Transthyretin amyloidosis, also called ATTR amyloidosis, is associated with accumulation of ATTR amyloid deposits in the heart and commonly manifests as progressive cardiomyopathy. Patisiran, an RNA interference therapeutic agent, inhibits the production of hepatic transthyretin. METHODS: In this phase 3, double-blind, randomized trial, we assigned patients with hereditary, also known as variant, or wild-type ATTR cardiac amyloidosis, in a 1:1 ratio, to receive patisiran (0.3 mg per kilogram of body weight) or placebo once every 3 weeks for 12 months. A hierarchical procedure was used to test the primary and three secondary end points. The primary end point was the change from baseline in the distance covered on the 6-minute walk test at 12 months. The first secondary end point was the change from baseline to month 12 in the Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) score (with higher scores indicating better health status). The second secondary end point was a composite of death from any cause, cardiovascular events, and change from baseline in the 6-minute walk test distance over 12 months. The third secondary end point was a composite of death from any cause, hospitalizations for any cause, and urgent heart failure visits over 12 months. RESULTS: A total of 360 patients were randomly assigned to receive patisiran (181 patients) or placebo (179 patients). At month 12, the decline in the 6-minute walk distance was lower in the patisiran group than in the placebo group (Hodges-Lehmann estimate of median difference, 14.69 m; 95% confidence interval [CI], 0.69 to 28.69; P = 0.02); the KCCQ-OS score increased in the patisiran group and declined in the placebo group (least-squares mean difference, 3.7 points; 95% CI, 0.2 to 7.2; P = 0.04). Significant benefits were not observed for the second secondary end point. Infusion-related reactions, arthralgia, and muscle spasms occurred more often among patients in the patisiran group than among those in the placebo group. CONCLUSIONS: In this trial, administration of patisiran over a period of 12 months resulted in preserved functional capacity in patients with ATTR cardiac amyloidosis. (Funded by Alnylam Pharmaceuticals; APOLLO-B ClinicalTrials.gov number, NCT03997383.).

A unique case of concurrent cutaneous lichen amyloidosis and myxedema.

Lichen amyloidosis is believed to be caused by damage to keratinocytes, often by chronic scratching. It has also been associated with autoimmune conditions, including thyroid disease. Dermatologic manifestations of poorly controlled thyroid disease are well described within the medical literature, within both hypothyroid and hyperthyroid states. Myxedema is a rare complication of Graves disease. We report a unique case of concurrent myxedema and lichen amyloidosis in a 63-year-old patient with uncontrolled hypothyroidism in the setting of post-ablative Graves disease.

Primary Localized Cutaneous Amyloidosis Secondary to Sand Rubbing in a Wrestler.

A 40-year-old male, wrestler since 15 years of age presented with asymptomatic hyperpigmentation over both his both upper extremities for 10 years. There was no history of preceding itching or redness; of using a nylon brush, scrubbers, or sponges during bathing; or of excessive towel rubbing after bathing and applying cosmetics; however, he had been rubbing sand over both arms for 15 years. He had no personal or family history of atopy, diabetes, or thyroid disease. Cutaneous examination revealed the presence of symmetrical sharply defined reticulate brownish hyperpigmentation over both arms and favoring the left (Figure 1). Dermatoscopy revealed multiple uniform small brown fine streaks radiating from the center becoming reticulated (Figure 2). Hematologic and biochemical studies, in particular thyroid studies, were normal. Histopathologic examination revealed an amorphous eosinophilic deposit in the papillary dermis suggestive of macular amyloidosis (MA) (Figure 3). Methyl violet stain revealed amyloid positive areas (Figure 4), and a diagnosis of MA was made. With the cessation of the sand rubbing and the application of tacrolimus ointment (0.1%), the lesions slowly diminished. (SKINmed. 2022;20:141-143).

AL Lambda Amyloidosis Activates Acute Liver Failure in the Absence of Plasma Cell Dyscrasia.

A patient with systemic amyloidosis developed portal hypertension, acute liver failure and multiorgan dysfunction. Extensive testing was unrevealing for paraproteinemia, plasma cell dyscrasia, infectious, or inflammatory conditions. He was transferred to our institution for orthotopic liver transplant evaluation but was ultimately declined given clinical instability and dysautonomia. Post-mortem evaluation revealed extensive amyloid deposition in multiple organs determined to be AL-lambda amyloidosis.

Combined Heart-Liver and Domino Liver Transplantation in Familial Amyloidosis.

BACKGROUND: Combined heart-liver transplantation (CHLT) is the only curative option for patients with concomitant pathology affecting the heart and liver. In some cases, the native livers of familial amyloidosis (FA) patients may be suitable for domino transplantation into other recipients. METHODS: Retrospective analysis (2013 to 2019) of all CHLT at our center was performed. Continuous data were presented as mean with standard deviation and discrete variables as percentages. RESULTS: Familial amyloidosis was the indication for CHLT in 5 out of 6 patients. The mean recipient age was 55 ± 5.62 years. Two patients were bridged with total artificial heart. The mean model for end-stage liver disease score at transplant was 17.17 ± 3.7. Two explanted livers were used for transplantation in a domino fashion. The median intensive care and hospital stays were 5.5 and 19 days, respectively. Complications included renal failure (1), groin abscess (1), pulmonary embolism (1), and cardiac rejection (1). Patient and graft survival for both organs was 100% at a median follow-up of 59 (range 20-76) months. DISCUSSION: Combined heart-liver transplantation for FA achieves excellent outcomes. The possible use of livers explanted from patients with FA for domino liver transplantation can contribute to the liver donor pool.

Nodular Pulmonary Amyloidosis Associated with Sjögren's Syndrome.

Amyloidosis is a rare disease characterized by the deposition of abnormal proteins in extracellular tissues. We herein report a case with instructive radiologic features of nodular pulmonary amyloidosis associated with Sjögren's syndrome. A 67-year-old woman was referred to our department because of an abnormal chest radiograph. Chest computed tomography revealed multiple round cysts accompanied by calcified nodules. The patient was clinically diagnosed with primary Sjögren's syndrome and pathologically diagnosed with nodular pulmonary amyloidosis (light chain, kappa). Although multiple lung cysts have many etiologies, the presence of calcified nodules associated with multiple lung cysts is useful for narrowing down the differential diagnosis.

Soluble TREM-1 Levels in Familial Mediterranean Fever Related AA-Amyloidosis.

Objectives: Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) is a monocyte and neutrophil receptor functioning in innate immunity. TREM-1 activity has been studied in various autoimmune diseases such as RA and SLE but there is no data in autoinflammatory pathologies. We studied soluble TREM-1 (sTREM-1) activity in Familial Mediterranean Fever (FMF) cases to evaluate the clinical role of TREM-1 in amyloidosis. Methods: The study includes 62 patients with FMF (42 with amyloidosis) who are regular attendees of a tertiary center for autoinflammatory diseases. For control purposes, 5 patients with AA amyloidosis secondary to other inflammatory diseases, and 20 healthy individuals were also included. Soluble TREM-1 levels were measured using enzyme-linked immunosorbent assay (ELISA). All FMF patients were in an attack-free period during the collection of the blood samples.Results: Soluble TREM-1 levels were found to be significantly higher in the FMF amyloidosis group compared to FMF without amyloidosis group and healthy controls (p = .001 and 0.002). Nevertheless, this difference between sTREM-1 levels was not found among FMF amyloidosis and other AA amyloidosis groups (p = .447) as well as between only FMF patients and healthy controls (p = .532). Soluble TREM-1 levels were found in correlation with creatinine and CRP in the FMF patient group regardless of their amyloidosis diagnosis (r = 0.314, p = .013; r = 0.846, p < .001).Conclusion: TREM-1 seems to be related to renal function rather than disease activity in FMF. Its role as an early diagnostic marker of amyloidosis in FMF complicated with AA amyloidosis should be tested in larger patient groups.

Diagnostic challenges in systemic amyloidosis: a case report with clinical and laboratorial pitfalls

Currently, there is growing evidence in the literature warning of misdiagnosis involving amyloidosis and chronic inflammatory demyelinating polyneuropathy (CIDP). Although inducing clinical manifestations outside the peripheral nervous system, light chain and transthyretin amyloidosis may initially present with peripheral neuropathy, which can be indistinguishable from CIDP, leading to a delay in the correct diagnosis. Besides, the precise identification of the amyloid subtype is often challenging. This case report exemplifies clinical and laboratory pitfalls in diagnosing amyloidosis and subtyping amyloid, exposing the patient to potentially harmful procedures.

A comparative study of the efficacy of fractional neodymium-doped yttrium aluminum garnet (Nd:YAG) laser therapy alone and in combination with erbium:YAG laser therapy: tracing and objective measurement of melanin index in macular amyloidosis.

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.

Brownish macules on the right temple.

A 28-year-old male presented with multiple pigmented macules on his right temple over two years. Physical examination showed multiple, discrete, brownish macules on his right temple. These lesions coalesced into reticular shape. Histology of the lesion demonstrated a deposit of eosinophilic acellular material in the dermal papillae. These features were consistent with macular amyloidosis (MA). Macular amyloidosis typically presented over the legs, the arms, and the upper back. We present this patient of MA involving the temple areas, which, to the best of our knowledge, has not previously been reported to occur in this region.

Clinical resolution of generalized lichen amyloidosis with dupilumab: a new alternative therapy.

Lichen amyloidosis is a subtype of primary localized cutaneous amyloidosis characterized by deposition of amyloid protein in the skin without visceral involvement. Although it is usually limited to localized areas of the body, it rarely can present in a generalized fashion and is severely pruritic. The limited form is treated with skin directed therapies such as topical or intralesional corticosteroids or topical tacrolimus but the generalized type is more difficult to treat. We present a patient with generalized primary cutaneous lichen amyloidosis successfully treated with dupilumab.