Amyloid Light Chain Amyloidosis Involving the Heart and Temporal Arteries, Mimicking Giant Cell Arteritis

Abstract

Background

Amyloid light chain (AL) amyloidosis is an uncommon multisystem condition. We report a globally unique case of a patient with AL amyloidosis affecting the heart and temporal arteries.

Case Summary

A 74-year-old man presented with jaw claudication and temporal artery tenderness and was treated for giant cell arteritis. He was later admitted to the cardiology service with elevated cardiac biomarkers with echocardiographic features of an infiltrative cardiomyopathy. Cardiac magnetic resonance suggested amyloidosis, and diagnosis of AL amyloidosis was confirmed via temporal artery biopsy. Treatment with bortezomib, cyclophosphamide, and dexamethasone yielded an appropriate clinical response.

Discussion

Although AL amyloidosis is known to be associated with cardiac involvement with isolated cases of large vessel involvement, this is the first global case to our knowledge of AL amyloid affecting the temporal arteries and cardiac function simultaneously.

Take-Home Messages

AL amyloidosis is a multisystem disorder. Cardiac phenotyping should be mandatory.

Visual Summary

Visual Summary.

Timeline of Events

Timeline of events from first presentation with symptoms to current day follow-up. AL = amyloid light chain; CMR = cardiac magnetic resonance; PET = positron emission tomography; TTE = transthoracic echocardiogram.

History of Presentation

A 74-year-old man presented to his general practitioner with a 6-week history of jaw claudication, temporal arterial tenderness to touch, and visual disturbances. He was referred emergently for an ophthalmology and rheumatology review for a possible giant cell arteritis (GCA).

Ophthalmic and ocular examinations were normal. Palpable thickening with associated tenderness was noted within the left temporal artery. A left-sided carotid bruit was documented alongside bilateral upper limb stiffness.

Past Medical History

The patient’s past medical history included subarachnoid hemorrhage, ischemic heart disease with recent percutaneous coronary intervention to the right coronary artery with a single-drug eluting stent within the last 3 month, and long-standing monoclonal gammopathy of uncertain significance under hematologic surveillance. The patient was also under the care of a rheumatologist with a diagnosis of seronegative rheumatoid arthritis treated with methotrexate and was awaiting a start date to begin treatment with adalimumab.

Differential Diagnosis

At the time of presentation, the primary differential diagnosis was GCA with a high probability score of 19 (scores ≥10 suggest likely GCA) before ultrasound (US) scan. Amyloidosis was not considered at this time owing to the typicality of the presentation.

Investigations

Laboratory investigations revealed significantly elevated erythrocyte sedimentation rate (ESR) of 128 mm/h (normal range 2-30 mm/h) with mildly elevated C-reactive protein of 14 mg/L (normal range 0-7 mg/L). Normocytic anemia was also noted, with normal renal and liver function. A point-of-care US scan of the temporal artery showed diffuse temporal artery wall thickening (Figure 1) with a positive halo sign suggestive of GCA. A positron emission tomography (PET) scan was requested. Temporal artery biopsy was not performed as current guidelines in the United Kingdom state that a diagnosis of GCA can be made based on the presence of typical signs, symptoms, and US scan findings.¹

Figure 1.

Temporal Artery Ultrasound

Color Doppler ultrasound scan of the temporal artery showing narrowed lumen with thickened temporal artery wall consistent with giant cell arteritis.

Management

Given the clinical history, laboratory, and US scan findings, the patient was treated for GCA with oral prednisolone 40 mg daily and was started on tocilizumab (owing to its use in GCA and seronegative rheumatoid arthritis). There was rapid clinical and biochemical response (ESR decreased to 24 mm/h within 4 weeks), and PET scan did not show any evidence of active large-vessel vasculitis 3 days after corticosteroids were started. There was a gradual weaning of the oral corticosteroid dose; however, a recurrence of symptoms 8 months after the initial presentation precipitated an escalation of the oral corticosteroid dose by the rheumatology team.

One month after the escalation of corticosteroid treatment for GCA, the patient was admitted with significant progressive exertional breathlessness and peripheral edema. Electrocardiogram demonstrated sinus rhythm with low-voltage QRS complexes across all limb leads and no features of conduction disease (Figure 2). A computed tomography aortogram was performed to assess for the presence of a thoracic aortic outlet syndrome owing to the presence of marked peripheral venous dilatation and demonstrated evidence of subclavian artery mural thickening suggestive of a possible large vessel vasculitis. Cardiac biomarkers were measured and showed an elevated high-sensitivity troponin T without dynamic change on repeat testing and markedly elevated N-terminal pro–B-type natriuretic peptide (Table 1). A transthoracic echocardiogram (TTE) demonstrated increased left ventricular wall thickness with a normal ejection fraction of 64%, left atrial dilatation, and elevated filling pressures with some myocardial speckling noted (Figure 3, Video 1). The TTE findings along with the elevated cardiac biomarkers prompted referral for cardiac magnetic resonance (CMR). The patient was regularly reviewed by the rheumatology team and was treated for a suspected large vessel vasculitis with intravenous methylprednisolone 1 g daily for 3 days, while arranging a temporal artery biopsy.

Figure 2.

Admission Electrocardiogram

Standard 12-lead electrocardiogram taken at time of hospital admission showing sinus rhythm with low-voltage QRS complexes throughout the limb leads, especially when considering the left ventricular wall thickening seen on echocardiography and magnetic resonance imaging.

Table 1.

Admission Blood Test Results

Testa	Resultb	Reference Range
High-sensitivity TnT	52 ng/L	0-11 ng/L
NT-proBNP	3,871 pg/mL	0-400 pg/mL
Hemoglobin	121 g/L	130-170 g/L
MCV	102.5 fL	83-101 fL
Creatinine	67 μmol/L	59-104 μmol/L
Urea	6.4 mmol/L	2.5-7.8 mmol/L
Albumin	32 g/L	35-50 g/L
Total protein	60 g/L	60-80 g/L

MCV = mean corpuscular volume; NT-proBNP = N-terminal pro–B-type natriuretic peptide; TnT = troponin T.

^aTests include cardiac biomarkers, high-sensitivity TnT and NT-proBNP.

^bAbnormal results are in bold.

Figure 3.

Transthoracic Echocardiogram

Transthoracic echocardiogram apical 4-chamber view showing increased left ventricular wall thickness with endocardial speckling.

CMR demonstrated elevated longitudinal relaxation time (T1) mapping with extensive circumferential late gadolinium enhancement suggestive of cardiac amyloidosis (Figure 4). Serum and urine free light chains were measured, and serum electrophoresis was performed (Table 2). An urgent bone marrow biopsy was performed following hematology review.

Figure 4.

Cardiac Magnetic Resonance

Short axis section from cardiac magnetic resonance with arrow highlighting extensive circumferential subendocardial late gadolinium enhancement.

Table 2.

Amyloidosis Screening

Test	Resulta	Reference Range
Serum free kappa chains	6.71 mg/L	3.3-19.4 mg/L
Serum free lambda chains	116.27 mg/L	5.71-26.3 mg/L
Serum kappa/lambda ratio	0.06	0.26-1.65
Immunoglobulin G	<3.0 g/L	7.0-16.0 g/L
Immunoglobulin M	<0.25 g/L	0.4-2.3 g/L
Immunoglobulin A	Paraprotein present	—
Urine Bence-Jones protein	Negative	—

^aAbnormal results are in bold.

Temporal artery biopsy was reported to show unusual morphology of the media with large areas of amorphous eosinophilic material that appeared red and showed apple green birefringence on polarized light on Congo red staining, consistent with amyloid deposition. The bone marrow biopsy showed vessel thickening with 1 vessel demonstrating apple green birefringence on Congo red staining consistent with amyloidosis. A diagnosis of amyloid light chain (AL) amyloidosis affecting the heart and temporal artery was therefore made. The differential diagnosis of a large vessel vasculitis was excluded based on the lack of histopathologic evidence and poor clinical response to intravenous methylprednisolone, although biopsy of other possibly affected large vessels seen on computed tomography imaging was not performed, and PET was not performed during the acute hospital admission. The temporal artery biopsy specimen was sent to the UK National Amyloid Centre where immunohistochemical staining was performed and revealed amyloid staining to lambda immunoglobulin light chains. Laser capture mass spectrometry was not performed.

The patient was treated locally with 8 cycles of bortezomib, cyclophosphamide, and dexamethasone, and outpatient follow-up with the cardiology, rheumatology, and hematology teams was arranged, as well as clinical review at the National Amyloid Centre, Royal Free Hospital, London. Daratumumab was not used as it was not licensed for use in AL amyloidosis in the United Kingdom until March 2024.²

Outcome and Follow-Up

The patient had early post-discharge review in the National Amyloid Centre, and serum amyloid P component scintigraphy did not show any visceral amyloid deposits. Serum kappa/lambda ratio normalized within 2 weeks of starting treatment, and paraproteinemia subsequently also resolved. N-terminal pro–B-type natriuretic peptide has also improved and was most recently 438 ng/L (18 months after diagnosis). Serial echocardiography at the National Amyloid Centre has also shown stable appearances with no clinical or biochemical features of disease progression or relapse. The patient continues regular follow-up with the National Amyloid Centre and local hematology and rheumatology teams with a complete remission and no evidence of clinical instability.

Discussion

AL amyloidosis is a rare condition affecting 5.1 to 12.8 cases per 1 million person-years, although the incidence rates are increasing with improved awareness of the disease promoting suitable investigations.^3,4 It most commonly affects the cardiac (>75%), renal, and nervous systems, although other visceral organ involvement such as in the liver and gastrointestinal tract may also be observed.⁵ This potential multiorgan involvement means that patients can present with a wide variety of signs and symptoms that may lead to misdiagnosis as is exemplified by this case. AL amyloid deposits in the temporal arteries can mimic GCA symptoms and has been reported in the literature; however, the overall incidence rate is unknown.⁶ In this case, the diagnosis of AL amyloidosis was delayed because the patient presented with typical signs and symptoms of GCA with classic ultrasound scan appearances. Current UK guidance suggests early corticosteroid treatment for suspected GCA.¹ It was not until the development of cardiac symptoms prompting a TTE and subsequent CMR showing typical amyloidosis findings of concentric left ventricular wall thickening, markedly elevated T1 mapping, and extensive subendocardial late gadolinium enhancement that prompted the consideration of an alternative differential diagnosis. It is possible that the escalation of the corticosteroid dose precipitated the patient's rapid decline before the hospital admission owing to the propensity of corticosteroids to promote fluid retention in restrictive cardiomyopathies.

In AL amyloidosis, early treatment with bortezomib, cyclophosphamide, and dexamethasone (now in combination with daratumumab) is recommended when possible, as the condition can progress rapidly with poor survival outcomes if left untreated.^7,8 In this case, the initial response to corticosteroid treatment for suspected GCA with rapid improvement in ESR was falsely reassuring. The initial relapse of GCA symptoms was initially attributed to the tapering of steroids; however, the lack of clinical response to escalating corticosteroid doses prompted temporal artery biopsy, helping solidify the unifying diagnosis of AL amyloidosis, further strengthened by the lack of vasculitis symptoms following the initiation of treatment for AL amyloidosis.

Conclusions

This is a unique case of cardiac AL amyloidosis with large vessel amyloid deposits mimicking an acute vasculitis syndrome. There was a delay in diagnosis due to the emphasis on early corticosteroid treatment in patients presenting with typical symptoms of GCA. Amyloidosis should be considered in patients with atypical, multiorgan signs and symptoms. We recommend that physicians maintain a low threshold for pursuing further investigations when a unifying diagnosis is lacking. This approach may uncover uncommon disease, trigger swifter treatment, and inevitably promote better long-term patient health outcomes.

Funding Support and Author Disclosures

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Take-Home Messages

• •AL amyloidosis should be considered as a differential diagnosis in patients presenting with heart failure symptoms with associated noncardiac symptoms.
• •Early CMR should be considered in patients with unexplained elevated cardiac biomarkers.
• •Early treatment of AL amyloidosis is associated with better long-term clinical outcomes.

Appendix

Video 1

Transthoracic Echocardiogram Apical 4-Chamber View Showing Increased Left Ventricular Wall Thickness With Myocardial Speckling Consistent With Amyloid Light Chain Amyloidosis