Shock, Sepsis & Multisystem · Topic 13 of 14

Sarcoidosis & Amyloidosis

Multisystem · infiltrative disease

Sarcoidosis & Amyloidosis

Granulomas or amyloid fibrils infiltrate heart, lungs and kidneys. Prove it on tissue, and think of the heart: block, arrhythmia, stiff ventricle.

Key numbers

Heart block under 60: suspect sarcoidage < 60

Cardiac sarcoid needing pacing gets an ICDICD if LVEF ≤ 35%

01 · Defined bySarcoid: noncaseating granulomas, mimics excluded

Sarcoidosis is diagnosed by a compatible picture (classically bilateral hilar adenopathy), noncaseating granulomas on biopsy, and exclusion of other granulomatous causes — stain tissue for mycobacteria and fungi and ask about beryllium.

02 · FirstHeart block under 60: suspect sarcoid

Suspect cardiac sarcoidosis in known sarcoidosis or in a patient younger than 60 with unexplained AV block, ventricular tachycardia or cardiomyopathy; order cardiac MRI and FDG-PET and look for extracardiac disease to biopsy.

03 · Defined byCongo red apple-green birefringence

Amyloidosis is proven on tissue: Congo red stain shows apple-green birefringence under polarized light. Abdominal fat aspirate finds AL in about 80% (ATTR < 25%); if negative, biopsy an involved organ.

What it is

Core idea

Granulomas make calcitriol: hypercalcemia, hypercalciuriaSarcoid macrophages convert vitamin D to 1,25-dihydroxyvitamin D, causing hypercalcemia and, more often, hypercalciuria — even with normal serum calcium — which leads to nephrolithiasis.

Presentation

What you'll see

Löfgren: erythema nodosum, arthritis, hilar adenopathyLöfgren syndrome — erythema nodosum, acute polyarthritis and bilateral hilar adenopathy — is self-limited, treated with NSAIDs, and usually needs no biopsy when tuberculosis risk factors are absent.

Macroglossia and periorbital purpura suggest ALClues to AL amyloidosis: macroglossia, periorbital bruising after minor strain ('raccoon eyes'), nephrotic syndrome, peripheral neuropathy with paresthesias, autonomic orthostatic hypotension and massive painless hepatomegaly.

Management

Orders

Cardiac sarcoid needing pacing gets an ICD must knowIn cardiac sarcoidosis, choose an ICD rather than a plain pacemaker when pacing is indicated; an ICD is recommended after sustained VT or cardiac arrest, or for LVEF ≤ 35% despite therapy, alongside glucocorticoids.

Exclude AL first with free light chains must knowIn suspected amyloidosis, order serum free light chains and serum and urine immunofixation first: AL amyloidosis needs chemotherapy (ATTR does not), and AL with severe cardiomyopathy has median survival under 1 year.

Prednisone 20–40 mg daily for organ-threatening sarcoidTreat sarcoidosis that threatens organs — heart, nervous system, eyes, moderate-severe hypercalcemia, worsening lung function — with prednisone 20–40 mg daily; abnormal imaging without symptoms or decline is not an indication.

Methotrexate is the steroid-sparing agentAdd methotrexate 10–15 mg weekly (with folic acid; screen hepatitis B and C) when prednisone cannot be tapered below 10–15 mg; infliximab is for refractory disease after TB screening.

AL amyloid: daratumumab plus CyBorDFirst-line AL treatment is daratumumab with cyclophosphamide, bortezomib and dexamethasone (Dara-CyBorD); high-dose melphalan with autologous stem cell transplant suits selected patients.

ATTR cardiomyopathy: tafamidis or acoramidisWild-type ATTR cardiomyopathy affects older adults with HFpEF or aortic stenosis; once AL is excluded a technetium pyrophosphate scan diagnoses it, and tafamidis or acoramidis lowers mortality and admissions.

EBUS-guided node biopsy diagnoses thoracic sarcoidEndobronchial ultrasound-guided transbronchial needle aspiration of mediastinal nodes (about 90% yield) is the diagnostic procedure of choice for intrathoracic sarcoidosis.

Red flags & don'ts

Avoid harm

Renal sarcoid: hypercalciuria, interstitial nephritis, stones complicationSarcoidosis reaches the kidney through hypercalciuria (most common), granulomatous interstitial nephritis, and nephrolithiasis or nephrocalcinosis that can progress to CKD needing dialysis.

Renal amyloid presents as nephrotic syndrome complicationGlomerular amyloid causes proteinuria progressing to nephrotic syndrome or ESKD; treat edema with salt restriction and loop diuretics, without protein restriction.

Amyloid heart: avoid digoxin, CCBs, beta-blockers avoidAmyloid cardiomyopathy (thick ventricle, low QRS voltage, heart block) is managed with salt restriction and loop diuretics; digoxin, calcium channel blockers, beta-blockers and ACE inhibitors or ARBs are poorly tolerated.

Sarcoidosis or amyloidosis?

Commonly confused

Tissue diagnosis	Noncaseating granulomas
Heart	AV block, VT, sudden death (often < 60 y)
Kidney	Hypercalciuria, stones, interstitial nephritis
Key lab	Hypercalcemia (granuloma calcitriol)
Treatment	Glucocorticoids, then methotrexate

More detail

Reference

Show 9 reference facts

Cardiac sarcoidosis causes AV block in about 35–50% of cases, and sudden cardiac death accounts for many sarcoid deaths, sometimes as the first sign of heart involvement.

In cardiac sarcoidosis, avoid class I antiarrhythmics; a pacemaker (preferably an ICD) is reasonable for qualifying AV block even if the block reverses.

Neurosarcoidosis most often causes facial nerve palsy; Heerfordt syndrome combines uveitis, parotid swelling, facial palsy and fever.

Chest radiograph stages: I hilar adenopathy alone (60–80% remit), II adenopathy plus infiltrates (50–65%), III infiltrates alone (< 30%), IV fibrosis; stage does not predict extrapulmonary severity.

Serum ACE level is not diagnostic of sarcoidosis; when elevated it can help monitor adherence because it falls even on low-dose corticosteroids.

Mild sarcoid hypercalcemia is managed with a low-calcium diet, hydration and less sunlight; hydroxychloroquine also helps hypercalcemia, skin and joint disease.

AA amyloidosis follows chronic inflammation or infection and favors the kidneys, liver and spleen; treat the underlying disease (colchicine for familial Mediterranean fever).

The V122I transthyretin variant, present in about 4% of Black Americans, causes hereditary ATTR cardiomyopathy; carpal tunnel syndrome often precedes wild-type ATTR heart disease.

Amyloid autonomic neuropathy causes orthostatic hypotension, which often improves with high-dose midodrine; cerebral amyloid angiopathy most often causes spontaneous intracerebral hemorrhage.

Pearl

Young patient, unexplained heart block: think sarcoid. Thick heart, low voltage: think amyloid.

Sources · Merck Manual Professional — Sarcoidosis (updated Feb 2025) · Merck Manual Professional — Cardiac Sarcoidosis · Merck Manual Professional — Amyloidosis · Starter sheet built from the verified AGACNP fact map (facts reviewed 2026-10-15).