PRIMARY AMYLOIDOSIS INVOLVONG THE HEART: CLINICAL OBSERVATION

Primary amyloidosis is a disease with a complex and not fully understood pathogenesis, which is characterized by a wide range of clinical manifestations. Light chain amyloidosis is the most common form of systemic amyloidosis. At this, the heart is the dominant target organ in systemic amyloidosis. Cardiac amyloidosis (amyloid cardiomyopathy) is most often manifested by diastolic heart failure resulting from restrictive cardiomyopathy. Therapy of amyloid cardiopathy includes optimal treatment of heart failure and chemotherapy. To reduce the symptoms of heart failure, diuretics are the main means, since other pathogenetic agents cannot be used due to hypotension and a possible decrease in cardiac output. With the introduction of new medicinal products into clinical practice, such as the proteosome inhibitor Bortezomib, the prognosis for patients has improved. However, amyloidosis remains a difficult disease to diagnose and treat.

Anaesthetic challenges in the spine surgery of a young Asian man with lumbar amyloidosis

Primary amyloidosis is a rare systemic disorder often associated with multiple organ dysfunction. The most common form, light chain amyloidosis, has an estimated age-adjusted incidence of 5.1–12.8 cases per million person-years. Spine involvement is extremely uncommon. We present the case of a young Asian man with newly diagnosed amyloidosis involving the lumbar spine among multiple organs with a pathological vertebral fracture that required urgent spine surgery. We believe this is the first reported case to discuss the perianaesthetic challenges in the management of lumbar spine amyloidosis.

The Influence of Deterioration of Kidney Function on the Diagnostic Power of Laboratory Parameters Used in the Prognostic Classification of AL Amyloidosis

There is a possibility that renal dysfunction may potentially reduce the diagnostic power of the laboratory parameters Tn, NT-proBNP and sFLC levels, used in the current prognostic classification of AL amyloidosis and the diagnosis of heart involvement by amyloid. In this study, the impact of lowering the eGFR value on the usefulness of these parameters in the prognosis and diagnosis of the presence of amyloid in the myocardium was assessed in a group of 71 patients with newly diagnosed primary amyloidosis. The assessment of diagnostic power of laboratory parameters was performed on the entire study group, and in the ranges of eGFR ≥ 60 and < 60 mL/min/1.73 m2. It has been proven that, with a decrease in the eGFR value, the concentrations of NT-proBNP and the κ uninvolved light chains increase significantly (p < 0.001). To assess the diagnostic power of laboratory parameters used in the diagnosis of myocardial involvement in patients with AL amyloidosis, an ROC analysis was performed. The highest values of AUC were obtained for the NT-proBNP concentration (AUC = 0.906). The lowest values of the AUC and Youden’s index were obtained for the dFLC values (AUC = 0.723), and involved κ FLC concentration (AUC = 0.613). For all compared parameters, the smallest values of the AUC were obtained for eGFR (<60 mL/min/1.73 m2). It seems that the most suitable cardiac parameter used in the prognostic classification of AL amyloidosis, independent of renal function, is TnI. It should be noted that a concentration of involved λ chains hada higher diagnostic power to assess the heart involvement, compared to the routinely used “cardiac parameters”, TnI and NT-proBNP. It can therefore be an additional parameter used to assess the presence of amyloid in the myocardium. A decrease in eGFR value influenced the change in the diagnostic cut-off points of the most analyzed laboratory parameters. Finally, it is concluded that lowering the eGFR value reduces the utility of laboratory parameters used in the prognostic classification of AL amyloidosis.

Rare presentation of kappa light chain proximal tubulopathy with fibrillar aggregates

Introduction/Objective Patients with dysproteinemias may show a spectrum of renal alterations due to organized deposits of excess immunoglobulins, including primary amyloidosis, myeloma cast nephropathy, monoclonal immunoglobulin deposition disease, and light chain proximal tubulopathy (LCPT). Among the least common is LCPT, which shows ultrastructural cytoplasmic light chain inclusions with crystalline morphology or rarely fibrillar aggregates. We present the case of a patient with LCPT with fibrillar aggregates that is the only such case registered in our large academic surgical pathology electronic database. Our aim is to increase understanding and recognition of this rare variant. Methods/Case Report A 73-year-old man presented with 540 mg/day proteinuria, serum creatinine 5.73 mg/dL, platelets 178,000/cc, and 20% plasma cells in his bone marrow biopsy specimen. Kidney needle biopsy cores examined by light, fluorescent and transmission electron microscopy (EM) showed kappa light chain cast nephropathy and kappa LCPT with fibrillary aggregates, the latter requiring unmasking of kappa epitopes using pronase-treated paraffin sections. Congo red stain was negative. By EM, proximal tubules contained intracellular bundles of tightly aggregated fibrils with mean fibril diameter of 7.7 +/- 1.6 nm. Individual bundles were variably shaped as round, oval, spicular or irregular blobs. Fibrils were not seen in glomeruli. Results (if a Case Study enter NA) NA Conclusion This rare presentation of LCPT with fibrillar aggregates reinforces the utility of renal biopsy diagnosis that includes careful ultrastructural examination of renal tubules. In the absence of EM, the unique fibrillar organization of these cytoplasmic light chain aggregates would otherwise go unrecognized.

AB0855 FIBROUS ARTHROPATHY AS THE KEY FEATURE OF JUVENILE SCLERODERMA - CASE REPORT

Background:Systemic sclerosis (SSc) is an autoimmune disease characterized by endothelial dysfunction, immunological disorders, and excessive synthesis of collagen and its deposition in various tissues and organs. The juvenile onset SSc before the age of 16 is very rare, with annual incidence of 0.27-0.5 cases per million children according to English and Finnish authors [1,2].Objectives:To present a clinical case of juvenile onset SSc, manifesting from the childhood predominantly with fibrous contractures.Methods:Patient K., 30 yo. Clinical presentation on admission to the Institute of Rheumatology in September 2020: thickening of the trunk and limbs skin (mRSS 10 scores), pronounced induration of subcutaneous tissues and muscles; contractures of the elbow, shoulder, hip and knee joints, short stature (height 142 cm) with proportional shortening of the limbs. ANA (HEp-2) 1/320, a-Scl-70, a-RNP-70 and ACA tests were negative. Ultrasonography revealed left-sided coxitis, esophagogastroduodenoscopy - Barrett’s esophagus. Chest CT, echocardiography, electrocardiography and capillaroscopy yielded no specific findings.The patient has been ill since the age of 3, when SSc manifested with skin thickening, “dry” arthritis and rapid development of contractures of the large joints. Thorough diagnostic elaboration ruled out such potential causes as phenylketonuria, glycogenosis, mucopolysaccharidoses, primary amyloidosis, and porphyria. Histological findings (2007) of a biopsied skin specimen containing subcutaneous fat and muscle tissue included focal vacuolization of keratinocytes, poor perivascular lymphocytic and histiocytic infiltration, fibrosis and hyalinosis of collagen fibers of varying intensity in the in mid- and deep dermis, infiltration of collagen fibers by fibroblasts, skin appendages atrophy – all of them representing a pattern of morphological changes characteristic of SSc. Therapeutic regimens including prednisone at 5-15 mg/day and D-penicillamine were ineffective.Results:In this case, in view of fibrotic arthropathy, a differential diagnosis was made with deep morphea and stiff skin syndrome. Visceral involvement, immunological disorders and biopsy findings substantiated a diagnosis of juvenile onset SSc. Oral MTX was initiated at 15 mg to target skin lesion and osteoarticular symptoms.Conclusion:Predominance of fibrotic arthropathy in presented case caused difficulties in establishing SSc diagnosis, as this patient did not have such inherent features as the Raynaud’s phenomenon, interstitial lung disease or pulmonary hypertension. Juvenile onset SSc manifesting before the age of 16 has its own clinical features, usually persisting through the adulthood, and therefore, such one-of-a-kind appearances of juvenile onset SSc should not be missed or misinterpreted.References:[1]Herrick AL, Ennis H, Bhushan M et al. Incidence of childhood linear scleroderma and systemic sclerosis in the UK and Ireland. Arthritis Care Res. 2010 Feb;62(2):213-8. doi: 10.1002/acr.20070.[2]Pelkonen PM, Jalanko HJ, Lantto RK et al. Incidence of systemic connective tissue diseases in children: a nationwide prospective study in Finland. J Rheumatol. 1994 Nov;21(11):2143-6Disclosure of Interests:None declared

Nephrotic Syndrome Following Resection of an Adrenal Incidentaloma:A Case Report

A 69 year old man had a 5 cm right adrenal lesion discovered incidentally while being investigated for a deterioration in previously well-controlled hypertension. Routine investigations including serum albumin were normal. Further investigation confirmed a non-functioning adrenal lesion. MRI revealed a ‘non-fat-containing T1 hyperintense indeterminate adrenal lesion with speckling of T2 hyperintensity, not typical for adenoma, hyperplasia, myelolipoma, haemangioma or pheochromocytoma’. An uncomplicated laparoscopic adrenalectomy was performed. Histology revealed a 118 g adrenal neoplasm, modified Weiss score 0, with abundant hyaline deposits.3 months later the patient complained of peripheral oedema. Investigations revealed a serum albumin of 24 g/L and 14 g of proteinuria in 24 hours. Serum protein electrophoresis revealed a monoclonal IgA type lambda band. Renal biopsy revealed amorphous material displaying apple green birefringence on staining with Congo Red, which stained with antibodies to lambda light chains, confirming AL amyloid. Therefore the patient’s resected adrenal specimen was retrieved and stained with Congo Red, revealing apple green birefringence in the walls of the blood vessels, confirming the presence of amyloidosis. Although adrenal gland involvement in secondary amyloidosis is common, adrenal involvement in primary amyloidosis is less well described. This case illustrates the indolent nature of primary amyloidosis, prior to the development of often catastrophic symptoms. Consideration should be given to Congo Red staining of resected pathologic specimens containing hyaline deposition, to potentially allow for earlier recognition of this devastating disease. A pathophysiologic link between the patient’s incidentaloma, adrenalectomy, and onset of nephrotic syndrome remains a matter for conjecture.