What findings are typically seen in a patient with amyloidosis?

Amyloidosis is a rare but serious disease characterized by the buildup of abnormal proteins, called amyloid fibrils, in organs and tissues. The clinical picture is broad and depends heavily on which organs are affected, meaning a variety of findings are typically seen in a patient with amyloidosis. This buildup can ultimately lead to organ dysfunction and, if left untreated, failure.

Quick Summary

A patient with amyloidosis may present with widespread, non-specific findings such as profound fatigue and swelling, alongside more specific organ-based signs like foamy urine, irregular heartbeat, carpal tunnel syndrome, and an enlarged tongue. The constellation of symptoms depends on the affected organs and the specific type of amyloid protein involved.

Key Points

• Multiorgan Symptoms: Findings in amyloidosis are determined by which organs are infiltrated, leading to a wide array of symptoms including fatigue, swelling, and organ dysfunction.

• Red Flags: Certain signs are considered 'red flags' for amyloidosis, such as unexplained bilateral carpal tunnel syndrome, macroglossia (enlarged tongue), and periorbital purpura (raccoon eyes).

• Cardiac Features: Cardiac involvement, a serious complication, presents with restrictive heart muscle thickening, often with low voltage on ECG and heart failure symptoms like shortness of breath.

• Renal Findings: Kidney involvement frequently manifests as proteinuria, which can cause foamy urine and significant edema in the extremities.

• Nervous System Effects: Peripheral and autonomic neuropathies can cause numbness, pain, tingling, and dizziness when standing, depending on which nerves are affected.

• Biopsy is Definitive: While various tests can point to amyloidosis, a tissue biopsy stained with Congo red remains the gold standard for confirmation.

Understanding the Systemic Nature of Amyloidosis

Amyloidosis is not a single disease but a group of conditions that share a common pathology: the extracellular deposition of abnormal protein aggregates. The systemic forms of the disease, such as AL and ATTR amyloidosis, can affect multiple organs simultaneously, leading to a complex and often non-specific initial presentation. This overlap of symptoms is why early diagnosis can be challenging and often requires a high index of clinical suspicion. Common early findings that may prompt further investigation include unexplained weight loss, persistent and profound fatigue, and generalized weakness.

Cardiovascular Findings in Cardiac Amyloidosis

Cardiac involvement is a particularly critical manifestation of amyloidosis, with deposits infiltrating the heart muscle and impacting its function. Findings on physical examination and diagnostic imaging are key indicators:

• Symptoms: Patients often report shortness of breath, swelling (edema) in the legs and ankles, and an irregular heartbeat (arrhythmia). In advanced stages, this can progress to heart failure.
• Echocardiogram: A classic finding is thickened myocardial walls, often with a granular or sparkling appearance. This occurs while the ventricular size is preserved or even reduced, and diastolic dysfunction is a universal observation. Reduced global longitudinal strain with apical sparing is a pathognomonic sign in many cases.
• Electrocardiogram (ECG): Low voltage in the limb leads is a common but non-specific finding, contrasting with the often-present left ventricular hypertrophy. Conduction blocks and atrial fibrillation are also frequently observed.
• Cardiac MRI: Diffuse, subendocardial late gadolinium enhancement is highly suggestive of cardiac amyloidosis.

Renal and Gastrointestinal Involvement

The kidneys are another common target for amyloid deposits, particularly in AL and AA amyloidosis.

• Kidney Findings: Renal involvement often leads to significant proteinuria, sometimes presenting as nephrotic syndrome. This can manifest as foamy urine or swelling in the legs, arms, and face due to fluid retention. Over time, this damage can lead to chronic kidney disease and eventually kidney failure, potentially requiring dialysis.
• Gastrointestinal (GI) Findings: GI tract involvement can cause alternating diarrhea and constipation, nausea, unexplained weight loss, and a feeling of fullness after eating small amounts. An enlarged tongue, known as macroglossia, is a distinctive sign often seen in AL amyloidosis.

Neurological and Skin Manifestations

Amyloid deposits can also affect the nervous system and skin, leading to a variety of findings.

• Peripheral Neuropathy: Damage to the peripheral nerves can cause pain, numbness, tingling, and weakness, particularly in the hands and feet. Carpal tunnel syndrome, often bilateral, is a common neurological finding and can precede the diagnosis by many years, especially in ATTR amyloidosis.
• Autonomic Neuropathy: Dysfunction of the autonomic nervous system can cause dizziness upon standing (orthostatic hypotension), gastrointestinal motility issues, and other involuntary function problems.
• Skin Findings: Cutaneous manifestations can include easy bruising, purplish patches around the eyes (periorbital purpura), and skin thickening. Periorbital purpura is highly suggestive of systemic AL amyloidosis.

Diagnostic Findings

Ultimately, a definitive diagnosis of amyloidosis and its specific type is essential for proper treatment and relies on a combination of tests.

1. Biopsy: Tissue biopsy remains the gold standard. A biopsy of the abdominal fat pad is a common initial approach, though a bone marrow or affected organ biopsy may be necessary if that is negative. The tissue sample is stained with Congo red dye, which shows characteristic apple-green birefringence under polarized light, confirming the presence of amyloid.
2. Laboratory Tests: Blood and urine tests, including serum and urine immunofixation electrophoresis and serum free light chain assays, can help detect the abnormal proteins associated with AL amyloidosis. Other tests, such as NT-proBNP and troponin, can indicate cardiac involvement.
3. Nuclear Scintigraphy: For suspected ATTR cardiac amyloidosis, a bone tracer scan (e.g., DPD or PYP) can often confirm the diagnosis without the need for an invasive biopsy.
4. Mass Spectrometry: This is the gold standard for accurately typing the specific protein involved, which is crucial for determining the correct course of treatment.

Comparison of AL and ATTR Amyloidosis Findings

Feature	AL Amyloidosis (Light Chain)	ATTR Amyloidosis (Transthyretin)
Primary Cause	Abnormal light chains from bone marrow plasma cells.	Misfolding of transthyretin protein from the liver.
Hereditary	Acquired, not inherited.	Can be inherited (hATTR) or wild-type (wtATTR), which is age-related.
Common Organ Involvement	Heart, kidneys, nerves, liver, GI tract, skin.	Heart, nerves, GI tract.
Specific Signs	Macroglossia, periorbital purpura.	Bilateral carpal tunnel syndrome, lumbar spinal stenosis, history of ruptured biceps tendon.
Diagnostic Scan	Typically negative or mild uptake on bone tracer scintigraphy.	Strong cardiac uptake on bone tracer scintigraphy (Perugini Grade 2/3).
Protein Identification	Requires evaluation for monoclonal gammopathy via blood and urine tests.	Identified by genetic testing (hATTR) or ruled out through lab tests (wtATTR).

Conclusion

What findings are typically seen in a patient with amyloidosis are diverse and depend on the specific type of amyloidosis and which organs are affected. From non-specific fatigue and weight loss to highly specific signs like macroglossia or periorbital purpura, recognizing these clinical clues is the first step towards a diagnosis. Since early and accurate diagnosis is critical for guiding effective treatment and improving patient outcomes, a high degree of clinical suspicion is essential. For more detailed information on specific diagnostic approaches, further reading from authoritative sources is recommended, such as the Amyloidosis Foundation.

Frequently Asked Questions

What is the most definitive test to find amyloidosis?

The most definitive test is a tissue biopsy, where a sample is taken from an affected organ or a site like the abdominal fat pad. When stained with Congo red, amyloid deposits show a characteristic apple-green birefringence under a polarized microscope.

Can blood tests alone confirm amyloidosis?

No, while blood tests can suggest the presence of abnormal proteins often associated with amyloidosis (such as free light chains), a biopsy is required to confirm the diagnosis by visually identifying the protein deposits in tissue.

Are there specific findings that point to a particular type of amyloidosis?

Yes. For example, macroglossia and periorbital purpura are highly suggestive of AL amyloidosis, while a history of bilateral carpal tunnel syndrome and lumbar spinal stenosis can be red flags for ATTR amyloidosis.

What does cardiac amyloidosis look like on an echocardiogram?

On an echocardiogram, cardiac amyloidosis can present with thickened heart muscle walls, a granular or sparkling texture, and reduced global longitudinal strain, often with relative sparing of the apex.

Why is it important to determine the specific type of amyloidosis?

Typing the specific amyloid protein is crucial because treatment strategies vary significantly depending on the protein involved. For instance, treatments for AL amyloidosis focus on the plasma cells, whereas treatments for ATTR focus on stabilizing the transthyretin protein or suppressing its production.

Can a patient have amyloidosis and not show symptoms?

Yes, it is possible for some individuals to have amyloidosis without experiencing noticeable symptoms, particularly in the early stages. The disease's wide range of presentation is one reason it can be challenging to diagnose.

What are the first signs of amyloidosis affecting the kidneys?

The earliest signs of kidney involvement often include proteinuria, which can cause the urine to appear foamy, and unexplained swelling (edema) in the legs, feet, and ankles.