Sign Of Systemic Amyloidosis Research Articles

Diagnosing Systemic Amyloidosis Presenting as Carpal Tunnel Syndrome: A Risk Nomogram to Guide Biopsy at Time of Carpal Tunnel Release.

As carpal tunnel syndrome often precedes other signs of systemic amyloidosis, tenosynovial biopsy at the time of carpal tunnel release may facilitate early diagnosis and treatment. However, evidence-based guidelines for amyloidosis screening during carpal tunnel release have not been established. We sought to develop a predictive model for amyloidosis after carpal tunnel release to inform screening efforts. We performed a retrospective cohort study of adults without known amyloidosis undergoing at least 1 carpal tunnel release from 2000 to 2019 with use of the national Veterans Health Administration database. After estimating the cumulative incidence of amyloidosis after carpal tunnel release, we identified risk factors, constructed a predictive nomogram based on a multivariable subdistribution-hazard competing-risks model, and performed cross-validation. Among 89,981 patients undergoing at least 1 carpal tunnel release, 310 were subsequently diagnosed with amyloidosis at a median interval of 4.5 years, corresponding to a cumulative incidence of 0.55% (95% confidence interval [CI]: 0.47% to 0.63%) at 10 years. Amyloidosis diagnosis following carpal tunnel release was associated with an increased hazard of heart failure (hazard ratio [HR], 4.68; 95% CI: 4.26 to 5.55) and death (HR, 1.27; 95% CI: 1.07 to 1.51) after adjustment for potential confounders. Age, male sex, Black race, monoclonal gammopathy of undetermined significance or multiple myeloma, rheumatoid arthritis, atrial fibrillation, spinal stenosis, and bilateral carpal tunnel syndrome were independently associated with increased risk of amyloidosis diagnosis and were included in the risk nomogram. Amyloidosis diagnosis after carpal tunnel release is rare but is associated with poor outcomes. We present an amyloidosis-risk nomogram to help guide tenosynovial biopsy at time of carpal tunnel release. Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Myeloma cast nephropathy with diffuse amyloid casts without systemic amyloidosis: two cases report

BackgroundMultiple myeloma (MM) is a plasma-cell derived hematologic malignant disease. The malignant proliferating plasma cells secrete massive monoclonal immunoglobulins which lead to various pathologic types of renal injury. Myeloma cast nephropathy (MCN) is the most common histopathologic lesion with the worst renal prognosis. Rarely, the free light chains in the protein casts can form amyloid fibrils. Here, we reported two rare cases of MCN with diffuse amyloid casts.Case presentationCase 1: A 54-year-old Chinese man presented with a 4-year history of multiple myeloma, proteinuria and hematuria. He had monoclonal IgAλ plus free λ spike in both serum and urine. He had been on chemotherapy for 4 years and maintained normal serum creatinine until 11 months ago. Then, his renal function deteriorated and he went on hemodialysis 4 months before admission. Renal biopsy showed diffuse amyloid casts in the tubular lumens, without any obvious amyloid deposits in other kidney compartments or signs of extra-renal amyloidosis. The amyloid fibrils formed around mononuclear cells which were CD68 negative. According to the morphology and location, these mononuclear cells were considered as tubular epithelial cells. The patient was maintained on chemotherapy and hemodialysis. He died 8 months after renal biopsy.Case 2: A 58-year-old Chinese man presented with a one-and-a-half-year history of proteinuria and slowly rising serum creatinine. He had monoclonal IgDλ spike in both serum and urine. Amyloid casts were observed in the tubular lumens and mononuclear cells could be identified in the center of some casts. There were no amyloid deposits in other kidney compartments and no sign of systemic amyloidosis. The patient also had fine granular deposits along the tubular basement membrane with λ linear staining along tubular basement membrane suggesting light chain deposition disease. He was treated with bortezomib-based chemotherapy followed by lenalidomide-based chemotherapy and achieved very good partial remission (VGPR). After 27 months of follow-up, the patient still showed no signs of systemic amyloidosis.ConclusionsThese 2 cases of MCN with diffuse amyloid casts have different histopathologic characteristics from the usual myeloma casts and tubular epithelial cells might play important roles in the pathogenesis.

Hereditary cardiac amyloidosis associated with Pro24Ser transthyretin mutation: a case report

BackgroundTransthyretin amyloidosis is a systemic disorder caused by extracellular deposition of insoluble amyloid fibrils in peripheral and autonomic nerves, heart, kidney, gastrointestinal tract, and other organs. Hereditary transthyretin amyloidosis is an autosomal dominant disease. More than 120 mutations have been reported in the transthyretin gene with considerable phenotypic heterogeneity and geographic diversity. Among them, a sporadic case of hereditary transthyretin amyloidosis with cardiac-predominant phenotype is very rare, progressive, and potentially fatal if left undiagnosed. However, a clinical diagnosis of cardiac amyloidosis still remains challenging due to non-specific symptoms, and less sensitivity and specificity of medical examinations.Case presentationA 60-year-old Japanese man with a history of embolic stroke and hypertrophic cardiomyopathy visited our department for heart failure. The present case exhibited only cardiomyopathy without any clinical signs of systemic amyloidosis manifested as carpal tunnel syndrome, polyneuropathy, or autonomic dysfunction. An echocardiogram revealed severe asymmetric left ventricular hypertrophy, biatrial dilatation, pericardial effusion, and preserved left ventricular ejection fraction of 50% with severe diastolic dysfunction. Technetium pyrophosphate scintigraphy indicated marked diffuse myocardial uptake of technetium pyrophosphate, strongly suggesting transthyretin cardiac amyloidosis, which was firmly confirmed by a left ventricular endomyocardial biopsy. Genetic analysis demonstrated a transthyretin C70T (Pro24Ser) heterozygous mutation. Tafamidis, a transthyretin stabilizer, was started. His cardiac symptoms remained unchanged for 12 months.ConclusionsHere we report the case of a patient with hereditary cardiac amyloidosis associated with a Pro24Ser mutation in transthyretin, which is the first case reported in Japan. Technetium pyrophosphate scintigraphy was extremely useful for definitive diagnosis. Thus, we propose that the nuclear imaging technique should be taken into account even for an exploratory diagnosis of transthyretin cardiac amyloidosis.

Nail Biopsy in the Diagnosis of Systemic Amyloidosis

A 60-year-old woman with a 13-year history of monoclonal gammopathy of unknown significance (MGUS) presented with worsening nail dystrophy. Prior workup for systemic amyloidosis had been unrevealing, and no other signs of cutaneous disease were present. Nail biopsy was consistent with amyloid deposition, and the patient subsequently underwent autologous hematopoietic stem cell transplantation for AL amyloidosis. In light of the growing literature regarding nail changes as a presenting sign of systemic amyloidosis and the promising utility of nail biopsy, we suggest a low threshold for biopsy in appropriate patients when nail changes characteristic of amyloidosis are refractory to conventional treatment.

Diagnosis of Cardiac Amyloidosis by Skin Lesions

In June 2011, a 74-year-old man was admitted for recurrent heart failure. He had hypertension, diabetes mellitus, renal failure due to nephrosclerosis and diabetic nephropathy, prostate cancer, tuberculosis, and gouty arthritis, and had received a parathyroidectomy. In 2009, he had received a mechanical prosthesis to treat aortic stenosis. Cardiac auscultation was rhythmic, with no murmurs, and with normal prosthetic sounds. The patient presented petechiae, purpura, papules, and spontaneous ecchymosis at the eyelids, groin, neck, and axillas (Figure 1), with onset after initiation of acenocoumarol in 2009. The electrocardiogram demonstrated sinus rhythm with a long P-R interval, right bundle branch block with left anterior hemiblock, and low voltage, consistent with infiltrative cardiomyopathy (Figure 2). The echocardiogram demonstrated left ventricular hypertrophy with increased echogenicity (Figures 3A and B), ejection fraction of 45%, and a restrictive pattern on pulsed Doppler (Figure 3C: increased E/A ratio) and tissue Doppler (Figure 3D: decreased E’ and A’ peaks). Examination of skin biopsy specimens with Congo red stain showed amyloidosis secondary to monoclonal gammopathy, with positive immunohistochemistry for lambda light chains. He was treated with melphalan and dexamethasone, which were discontinued because of a favorable hematological response, with normalization of serum free light chain concentrations. Thereafter, he was hospitalized several times for heart failure and ultimately died of this cause in 2013. The purpura, petechiae, and ecchymosis were due to intracutaneous bleeding, resulting from a fragile vascular status secondary to amyloid infiltration. This is sometimes the first and only sign of systemic amyloidosis. Although these features are not specific to this disease, they may be an aid to its diagnosis and prompt treatment in the appropriate clinical context. Figure 3. Figure 1. I

Intraocular ALλ amyloidoma with plasma cell neoplasia in a cat

An 11-year-old, neutered male domestic short-hair cat was presented with buphthalmos of the right eye and diagnosed with advanced glaucoma. Sonographic examination revealed an iridial thickening. Neoplasia was suspected and an enucleation was performed. Histopathology of the enucleated eye revealed abundant amyloid deposition predominantly in the anterior uveal tract accompanied by few to moderate numbers of well-differentiated plasma cells. The amyloid deposits were identified by staining with Congo red and showing green birefringence under polarized light. Immunohistochemically, amyloid and plasma cells stained intensely only with anti-ALλ antibody, supporting the amyloid tumor being an immunoglobulin-λ-light chain origin. Additional abnormalities included narrowing of the filtration angle and collapse of the ciliary cleft, and trabecular meshwork. One year post-enucleation, the cat was still healthy without signs of systemic amyloidosis or apparent metastatic disease. This is the first report of a cat with noncutaneous extramedullary plasmacytoma originating in the anterior uveal tract with resulting local amyloid.

Amyloidoma Involving the Orbit, Meckel's Cave and Infratemporal Fossa: 3T MRI Findings

Amyloidoma is a rare lesion characterized by tissue deposition of an abnormal fibrillary protein (amyloid). It is the focal and localized counterpart of systemic amyloidosis, where the deposition of amyloid diffusely involves several organs. The few literature reports of intracranial amyloidomas include lesions involving the pituitary gland, orbit, cerebral hemispheres, temporal bone, cerebellopontine angle and jugular foramen. We describe the case of a 27-year-old woman presenting with painless slowly progressive proptosis of the right eye. The patient underwent a contrast-enhanced CT study of the head, followed by 3T MRI which disclosed a homogeneous mass in the right Meckel's cave and cavernous sinus, extending through an enlarged foramen ovale to the infratemporal fossa. The right optic nerve and ocular muscles were enlarged and infiltrated along with the retrobulbar fat by contrast-enhancing tissue. Thin contrast-enhanced MRI scans through the area of interest showed the mass to extend posterior to the gasserian ganglion, involving the cerebellopontine angle cistern, where the intracisternal parts of the III, V, and VI nerves bilaterally appeared enlarged and showed perineural enhancement. The lesion closely mimicked a malignant tumor with perineural tumor infiltration, so we performed fine needle biopsy of the portion of the lesion near the right foramen ovale under fluoroscopic guidance. Histopathology revealed that the lesion was an amyloidoma. Further clinical and blood examinations, serum chemistry, followed by biopsy of the periumbilical fat showed no signs of systemic amyloidosis or an underlying inflammatory or neoplastic disorder. No further treatment was instituted, follow-up MRI six months later showed no enlargement of the mass.

Splenic hypoperfusion as a sign of systemic amyloidosis

The spleen is frequently involved in systemic amyloidosis; however, the computed tomographic (CT) or magnetic resonance (MR) pattern of splenic amyloidosis is not sufficiently described in the literature. This study evaluated the contrast-enhanced CT and MR findings of the spleen in patients with systemic amyloidosis. Data were extracted by reviewing pathology and radiology department records of the teaching hospital of Naples over 10 years, from 1 January 1993 to 31 December 2002. Thirty-three patients with amyloidosis were identified, 10 of whom had a CT scan and two of whom had an MR study. The population-based study was composed of 12 patients with histologically proved amyloidosis who underwent contrast-enhanced CT or MR scan of the abdomen. The spleen and liver were evaluated for organ size and perfusion. The spleen was hypoperfused in nine of 12 patients. Mild splenomegaly was present in only one case. Hepatomegaly was associated with markedly acute left lobe margin in nine patients and with rounded anterior profile of segments 3 and 4 in four patients. Moreover, a large area of low attenuation with indefinite geographic margins involving the right hepatic lobe was observed in three patients. The finding of splenic hypoperfusion may be a marker of systemic amyloidosis, which represents a useful clue when clinical findings fail to suggest the proper diagnosis.

Lipoid proteinosis: report of a possible localized form on both hands and wrists

A 28-year-old woman was seen for pruritic lesions on both hands and wrists which had been present since the age of 10 years. Both palms showed symmetric, diffuse hyperkeratosis extending over both wrists and the dorsal aspects of both hands with well-demarcated, erythematous, lichenified plaques (Figs 1 and 2). The borders of the plaques were pigmented and studded with papules (Fig. 2). The skin lesions were not related to sun exposure. No similar lesions were found elsewhere on the body. The hair, nails, and dental development were normal. A skin biopsy was taken for histopathologic and ultrastructural studies under the clinical impression of pityriasis rubra pilaris. Microscopically, homogeneous perivascular deposits of hyaline-like material were seen in the papillary and reticular dermis, accompanied by mononuclear cells (Figs 3 and 4). The overlying epidermis was acanthotic with hyperkeratosis (Fig. 3). The hyaline deposits were positive for periodic acid-Schiff (PAS) and oil-red O stains (Figs 5 and 6). Congo red stain was negative. Electron microscopic examination showed abundant amorphous material intermingled with short collagen fibrils in the dermis and around the blood vessels (Figs 7 and 8). Further examination revealed that the patient could protrude her tongue freely. The oral mucosa and vocal cords were smooth. There was no sign of systemic amyloidosis. The patient's complete blood cell count, biochemical tests, and protein electrophoresis were all within normal limits. Antinuclear antibody was negative. Results of porphyrin screening tests were negative for uroporphyrins and coproporphyrins in the urine and feces. The possibility of porphyria was therefore excluded. Both neurologic and ophthalmic examinations were negative. No intracranial calcification was found on a skull X-ray examination. The patient was treated with topical steroid and urea. She was lost to follow-up.

Amyloid goiter as the first clinical sign of systemic amyloidosis in a patient with adult-onset Still’s disease

We present a patient with amyloid goiter due to secondary amyloidosis which resulted from adult-onset Still’s disease. Amyloid goiter occurs as one of the rare manifestations of systemic amyloidosis. In our case the initial manifestation of amyloidosis was a fast growing goiter without other clinical abnormalities, which is unusual in the context of previously reported cases.

Plasmacytoma of the nasal cavity with lambda III amyloid deposition

A patient presented with a large nasal plasmacytoma that involved the palate, ethmoid and maxillary sinuses and contained deposits of amyloid. Immunoglobulin (AL) amyloid was found in the tumor. Amyloid fibrils extracted from the resected tumor were found to contain lambda light chain protein. Complete sequence analysis identified the protein as lambda III immunoglobulin light chain. Evaluation of the patient failed to reveal any sign of systemic amyloidosis and three years of follow-up has shown no evidence of recurrence.

Speech disorders in systemic amyloidosis

The purpose of this study was to define more completely the speech disorders that can occur in systemic amyloidosis. Fifty-nine patients with histologically established primary systemic amyloidosis were studied. Of this group, 81% had abnormal voice quality, 43% had abnormal pitch, 7% had abnormal resonation and 15% had abnormal articulation. Twenty-two patients also had abnormal findings at laryngeal examination, consisting of bowing, oedema, thickening, dry irritation and polypoid changes of the vocal folds. Macroglossia was found in 17% of the patients and submandibular swelling in 10%. These results support previous studies which showed that abnormal phonation is a sign of systemic amyloidosis and that abnormal voice is by far the most common abnormal speech sign. The relationship between amyloid deposit and dysphonia was not clear. In 23 patients who had laryngeal examinations, no evidence of actual amyloid deposits was documented.