Secondary amyloidosis, as opposed to primary amyloidosis, is a complication of an already existing infection or inflammatory chronic disease. The localization of protein deposits varies and may assume a regional or systemic pattern.

The predominant symptoms caused by secondary amyloidosis pertain to renal dysfunction [1]. Proteinuria, gradually developing organ insufficiency, peripheral edema, fatigue, weight loss and nephrotic syndrome are direct results of renal involvement [2] [3]. Hypertension is another symptom that often perplexes the clinical picture, and it is yet to be confirmed if it is a type of renal hypertension or if a different pathophysiological mechanism underlies its onset.

Cardiac function may also be compromised due to secondary amyloidosis, although it is not a common sign; congestive heart failure may develop [4]. Other organs targeted by the disease are the thyroid gland, viscera, and blood vessels. A clinical picture resembling bowel obstruction and malabsorption may be extremely uncommon but are yet possible. Peritonitis is a potential complication of protein deposits on bowel walls and gastrointestinal bleeding can be caused by vascular amyloid presence [5]. Thyroid gland involvement leads to the development of goiter; some other patients may present with hepatosplenomegaly. Peripheral neuropathy is another possible manifestation of secondary amyloidosis.

The clinical picture is completed by the symptoms manifested due to the underlying disease itself, such as deformed extremities due to rheumatic arthritis and a variety of other symptoms not related directly to amyloidosis.

• Anemia

  Laboratory examination revealed normocytic anemia, renal dysfunction, and proteinurea. He had been suffering from arthralgia and joint deformity, for 8 years. [ci.nii.ac.jp]

  Laboratory tests showed an increase of inflammatory reactants, anemia, hypocalcemia, and severe hypoalbuminemia and hypoproteinemia. [ncbi.nlm.nih.gov]

  P74 ) Endocrine, nutritional and metabolic diseases E70-E88 2019 ICD-10-CM Range E70-E88 Metabolic disorders Type 1 Excludes androgen insensitivity syndrome ( E34.5- ) congenital adrenal hyperplasia ( E25.0 ) Ehlers-Danlos syndrome ( Q79.6 ) hemolytic anemias [icd10data.com]

  Biochemical analysis showed mild anemia (124 g/L) and leukocytosis (12.7 x 10 9 /L) with lymphocytosis (5.75 x 10 9 /L). C-reactive protein was elevated at 71 mg/L. [acgcasereports.gi.org]

  Patients with 10% clonal plasma cells should be tested to see if they meet criteria for multiple myeloma, including screening for lytic bone lesions, anemia, renal insufficiency, and hypercalcemia. [msdmanuals.com]

• Fever of Unknown Origin

  Giant cell (temporal) arteritis (GCA) may be a cause of fever of unknown origin (FUO) in elderly patients. The development of secondary (reactive) amyloidosis is an unusual complication of the disease. [ncbi.nlm.nih.gov]

• Splenomegaly

  Hepatomegaly, splenomegaly, and autonomic neuropathy frequently occur as the disease progresses; cardiomyopathy occurs rarely. [bu.edu]

  Oedema accompanied by proteinuria was present in 88% of the cases, hepatomegaly in 17%, and splenomegaly in 11%. The mean systolic and diastolic blood pressures were 115 /-26 and 73 /-15 mmHg respectively. [ncbi.nlm.nih.gov]

  The appearance of hepatosplenomegaly in a patient with ongoing inflammation should prompt investigation for amyloidosis, although some patients with severe RA develop splenomegaly with subsequent Felty syndrome (splenomegaly and neutropenia or pancytopenia [emedicine.medscape.com]

  Others may include splenomegaly, pleuritis, pericarditis, and hepatic abnormalities 1 ). [kjim.org]

  Hepatomegaly occurs in 25% of patients, whereas splenomegaly is present in less than 5% and macroglossia in only 10%. Anemia is infrequent unless multiple myeloma, renal insufficiency, or gastrointestinal bleeding occurs. [circ.ahajournals.org]

• Recurrent Diarrhea

  In this report, we discuss the association of CVID and tuberculosis to secondary amyloidosis and recurrent diarrhea. [ncbi.nlm.nih.gov]

• Periodontitis

  Periodontal health and disease were evaluated using gingival index (GI), papillary bleeding index (PBI), plaque index (PI), and periodontal disease index (PDI). [ncbi.nlm.nih.gov]

• Hypertension

  Rarely, primary amyloidosis may present with evidence of portal hypertension or hepatic failure. [ncbi.nlm.nih.gov]

  Physical Examination Patients with amyloid renal disease are commonly hypertensive, although whether the hypertension is associated with the renal amyloidosis or is a coincidental finding is not always clear. [emedicine.medscape.com]

  Patients with AA-amyloidosis presented with progressive renal disease and nephrotic-range proteinuria but most patients had no peripheral edema or systemic hypertension. [doi.org]

• Hepatomegaly

  Hepatomegaly, splenomegaly, and autonomic neuropathy frequently occur as the disease progresses; cardiomyopathy occurs rarely. [bu.edu]

  Oedema accompanied by proteinuria was present in 88% of the cases, hepatomegaly in 17%, and splenomegaly in 11%. The mean systolic and diastolic blood pressures were 115 /-26 and 73 /-15 mmHg respectively. [ncbi.nlm.nih.gov]

  Rarely, a more specific symptom, such as abdominal fullness or right upper quadrant discomfort (reflecting hepatomegaly), might bring the patient to the physician. [emedicine.medscape.com]

  Hepatomegaly (enlarged liver). Systemic amyloidosis Lichen amyloidosis Also called papular amyloidosis Lichen amyloidosis is the most common form of primary localised cutaneous amyloidosis. [dermnetnz.org]

  Systemic Amyloidosis Symptoms of nephrotic-range proteinuria (nondiabetic), cardiomyopathy (no ischemic history), hepatomegaly (no contrast dye filling defect by imaging) and/or peripheral neuropathy (nondiabetic) should prompt an investigation for extraocular [eyewiki.aao.org]

• Hepatosplenomegaly

  Thyroid gland involvement leads to the development of goiter; some other patients may present with hepatosplenomegaly. Peripheral neuropathy is another possible manifestation of secondary amyloidosis. [symptoma.com]

  The appearance of hepatosplenomegaly in a patient with ongoing inflammation should prompt investigation for amyloidosis, although some patients with severe RA develop splenomegaly with subsequent Felty syndrome (splenomegaly and neutropenia or pancytopenia [emedicine.medscape.com]

  These symptoms depend on the organ involved, and include nephrotic syndrome, hepatosplenomegaly, congestive heart failure, carpal tunnel syndrome, gastrointestinal (GI) symptoms and macroglossia [ 2 ]. [intechopen.com]

• Facial Swelling

  She later presented to our tertiary care centre with facial swelling, flushing and bilateral pedal swelling for 3 months. Along with generalized body swelling she had frothy urine. [ncbi.nlm.nih.gov]

• Quadriplegia

  There have been few reported cases of progression to frank quadriplegia. Secondary amyloidosis refers to the deposition of amyloid in various tissues due to an underlying chronic inflammatory state. [ncbi.nlm.nih.gov]

Secondary amyloidosis constitutes a diagnostic challenge, mainly because it always appears as a complication of an underlying pathology and no specific laboratory finding can ascertain the diagnosis; its initial inclusion in the differential diagnosis is, in itself, a challenge as well.

Since the primary finding is related to renal function, urinalysis is expected to show elevated protein. Serum creatinine is usually elevated, exceeding 2 mg/dL. The presence of an acidic blood pH after blood gas analysis and hypo- or hyperkalemia is indicative of renal tubular acidosis early in the course of renal dysfunction. Another pathological laboratory finding may be diminished serum albumin, less than 2.5 mg/dL. In general, the presence of proteinuria and signs of renal decompensation in a patient suffering from a known inflammatory disease, such as Chron's disease or rheumatic disorders should raise suspicion of secondary amyloidosis.

Other pathological blood parameters include polyclonal hypergammaglobulinemia, which is attributed to the underlying inflammatory process, and increased serum amyloid A precursor, which is unfortunately not pathognomonic of secondary amyloidosis in these cases.

Iodine-123–labeled serum amyloid P (SAP) component scintigraphy is a promising imaging modality which can illustrate the primary regions where amyloid deposits are organized; it is, however, not widely available [6]. Cardiac involvement can be evaluated with the use of echocardiography, electrocardiography, and catheterization [7].

A definitive diagnosis still requires deep organ biopsy for a 100% accurate result. However, since the late 20th century, subcutaneous fat tissue aspiration is opted for as the initial, noninvasive method to obtain biopsy samples in many institutions [8]. It has shown a specificity of up to 100% and sensitivity ranging between 50-80%, while the rectal mucosa biopsy, also used as a successful noninvasive technique, exhibits a similar sensitivity [9] [10]. Finally, a minor salivary gland biopsy maintains an up to 100% sensitivity in the detection of amyloid buildup [11] [12].

The major therapy in AA amyloidosis is treatment of the underlying inflammatory or infectious disease. Treatment which suppresses or eliminates the inflammation or infection also decreases the serum amyloid A (SAA) protein. [bu.edu]

Both the numbers increased from 1988 to 1996, patients under treatment from 201 to 550 and visits from 1091 to 2198, respectively. [ncbi.nlm.nih.gov]

All treatment options should be based upon a greater control of the underlying disease, adequate organ support, and treatment of symptoms. [doi.org]

Hepatic amyloidosis with cholestasis may be a predictor of involvement of other organs and thus of poor prognosis. We report a case of a 67 year old man with renal failure and prominent cholestasis due to AA amyloid deposition in the liver. [ncbi.nlm.nih.gov]

It can successfully identify anatomical patterns of amyloid deposition throughout the body and enables not only an initial estimation of prognosis, but also the monitoring of the course of the disease and the response to treatment. [doi.org]

One year after diagnosis, she developed nephrotic syndrome, the etiology of which was found to be secondary amyloidosis based on renal biopsy. As the patient rejected therapy, she was discharged after only symptomatic treatment. [ncbi.nlm.nih.gov]

Given the etiologic diversity of AA amyloidosis, common therapeutic strategies are scarce. All treatment options should be based upon a greater control of the underlying disease, adequate organ support, and treatment of symptoms. [doi.org]

Etiology Both infectious and noninfectious diseases have been associated with AA amyloidosis. [emedicine.com]

Keywords: amyloidosis, epidemiology, nephrotic syndrome, rheumatoid arthritis, Congo red, eprodisate This work is published and licensed by Dove Medical Press Limited. [doi.org]

Recent epidemiological data is discussed that suggests geographical location and the subcutaneous (SC) route of drug administration are both contributing factors to the development of AA amyloidosis and not chronic infection with HIV, HBV or HCV. [ncbi.nlm.nih.gov]

The pathophysiological steps in progressing a patient from FMF to amyloidosis are not definitely known. [ncbi.nlm.nih.gov]

Hypertension is another symptom that often perplexes the clinical picture, and it is yet to be confirmed if it is a type of renal hypertension or if a different pathophysiological mechanism underlies its onset. [symptoma.com]

Pathophysiology Although the precursor protein and cellular source of amyloid fibrils is different for each disease, a common pathophysiology underlies all of these diseases, as well as Alzheimer’s and other neurodegenerative diseases. [clinicaladvisor.com]

Pathophysiology Chronic or acute, recurrent, substantial elevations of SAA are necessary but not sufficient for the development of amyloidosis. [emedicine.com]

New frontiers and insights in pathophysiology, diagnosis, and management". Texas Heart Institute Journal. 32 (2): 178–184. PMC 1163465. PMID 16107109. Mead, Simon; Gandhi, Sonia; et al. (2013). [en.wikipedia.org]

Thus, preventing or treating periodontitis might prevent or at least alleviate the progression of amyloidosis. Periodontal evaluation should be performed as part of a medical assessment and considered as an etiologic factor for secondary amyloidosis. [ncbi.nlm.nih.gov]

FibrillexTM has been designed to interfere with the interaction of AA amyloid protein with glycosaminoglycans in tissues and thus prevent fibril formation and deposition. [bu.edu]

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