What are the clinical features of sarcoidosis?

Clinical Features of Sarcoidosis

Sarcoidosis presents with a highly variable multisystem pattern, but certain clinical features are so specific they are considered diagnostic without biopsy, particularly Löfgren's syndrome, lupus pernio, and Heerfordt's syndrome. 1

Highly Specific Diagnostic Features (No Biopsy Required)

These presentations are pathognomonic and allow diagnosis without histologic confirmation:

• Löfgren's syndrome: The triad of bilateral hilar adenopathy with erythema nodosum and/or periarticular arthritis is so specific it establishes the diagnosis 1, 2, 3
• Lupus pernio: Chronic violaceous skin lesions on the nose, cheeks, and ears that indicate severe, chronic disease requiring aggressive systemic therapy 1, 2, 4, 3
• Heerfordt's syndrome: Parotid enlargement, uveitis, facial nerve palsy, and fever 1

Pulmonary Manifestations (Present in >90% of Cases)

The lungs are involved in at least 90% of sarcoidosis patients, though many remain asymptomatic 5:

• Bilateral hilar adenopathy: The hallmark finding, present in approximately 90% of cases, appearing symmetrical on imaging 1, 2, 3
• Perilymphatic nodules: Characteristic distribution on chest CT following lymphatic pathways 1, 2
• Upper lobe predominant infiltrates: Diffuse or upper lobe distribution with symmetrical pattern 1, 4, 3
• Peribronchial thickening: Visible on CT imaging 1
• Persistent dry cough, dyspnea, and chest pain as presenting symptoms 6, 7

Cutaneous Manifestations (10-30% Clinical Involvement)

Skin involvement frequency ranges from 10-30% when clinically apparent 5:

• Erythema nodosum: Tender raised nodules on the shins, often part of Löfgren's syndrome 1, 3
• Maculopapular, erythematous, or violaceous lesions: Common on the back and trunk 1, 4, 3
• Subcutaneous nodules: Palpable nodules beneath the skin 1, 4, 3

Ocular Manifestations (10-30% Clinical Involvement)

Eye involvement requires screening in all patients as asymptomatic disease can cause permanent vision loss 5:

• Uveitis: The most common extrapulmonary manifestation, often bilateral 1, 3
• Optic neuritis: Inflammation of the optic nerve 1, 3
• Scleritis and retinitis: Additional ocular inflammatory findings 1, 3
• Lacrimal gland swelling: Causes dry eyes and visible enlargement 1, 3

Cardiac Manifestations (25% Pathologic, 5% Clinical)

Cardiac involvement is present in 25% of all sarcoidosis cases but only causes clinical problems in 5%, yet it may be suddenly fatal and requires screening in all patients 5:

• New-onset third-degree AV block: Critical finding in young or middle-aged adults without other risk factors 1, 4, 3
• Ventricular tachycardia: Spontaneous or inducible VT without traditional cardiac risk factors 1, 3
• Cardiomyopathy: Treatment-responsive CM or reduced LVEF without other explanations 1, 3
• Conduction abnormalities: AV node block that responds to treatment 1, 3
• Increased inflammatory activity visible on cardiac MRI, PET, or gallium scanning 1

Neurologic Manifestations (5-15% of Cases)

Neurosarcoidosis affects 5-15% of patients and requires aggressive treatment 4, 3:

• Seventh cranial nerve paralysis: Facial nerve palsy, often unilateral 1, 3
• Seizures: Result from parenchymal brain involvement 3
• Gadolinium enhancement on brain MRI: Indicates CNS inflammation 1

Head and Neck Manifestations

• Symmetrical parotid gland enlargement: Bilateral swelling of parotid glands 1, 3
• Parotid uptake on gallium or PET scanning: Functional imaging finding 1
• Granulomatous lesions on laryngoscopy: Direct visualization of airway involvement 1, 3

Hepatic and Splenic Manifestations (10-30% Clinical Involvement)

• Hepatomegaly and/or splenomegaly: Palpable organ enlargement 1, 3
• Alkaline phosphatase elevation: Greater than three times the upper limit of normal 1
• Nodules or enlargement on imaging: Visible on CT, PET, or MRI 1, 3

Renal Manifestations

• Hypercalcemia or hypercalciuria: Due to abnormal vitamin D metabolism (normal-to-low PTH, normal-to-elevated 1,25-dihydroxyvitamin D, normal-to-low 25-hydroxyvitamin D) 1
• Nephrolithiasis: Calcium stones from hypercalciuria 1, 3
• Treatment-responsive renal failure: Kidney dysfunction that improves with immunosuppression 1, 3

Musculoskeletal and Bone Manifestations

• Periarticular arthritis: Often part of Löfgren's syndrome 1
• Osteolysis, cysts, or punched-out lesions: Characteristic bone involvement on X-ray, CT, or MRI 1
• Trabecular pattern in bone: Visible on imaging 1
• Inflammatory bone lesions: Detected on gallium, PET, or MRI 1, 3

Lymphatic Manifestations

• Two or more enlarged extrathoracic lymph nodes: Visible on CT, MRI, or PET 1

Laboratory Findings

• Elevated ACE level: Greater than 50% above the upper limit of normal (not specific but supportive) 1, 2, 3
• BAL lymphocytosis with elevated CD4:CD8 ratio: Bronchoalveolar lavage finding that supports diagnosis 1, 2, 3

Constitutional Symptoms

Nonspecific systemic features include:

• Fatigue (extremely common and may persist despite treatment) 6, 5, 7
• Fever and night sweats 6, 8, 7
• Weight loss 6, 7

Critical Clinical Pitfalls

Failure to screen for cardiac involvement is the most dangerous oversight, as cardiac sarcoidosis carries significant mortality risk from sudden death due to arrhythmias or heart failure, and may present subtly with only conduction abnormalities before progressing to life-threatening complications 4, 3, 5. All patients require cardiac screening regardless of symptoms 5.

Inadequate screening for ocular involvement leads to preventable vision loss, as asymptomatic patients may have progressive eye disease 5. All patients require ophthalmologic evaluation even without symptoms 5.

Insufficient exclusion of infections, particularly tuberculosis and fungal diseases, is the most common cause of misdiagnosis, as these granulomatous infections mimic sarcoidosis exactly 3. Negative microorganism stains and cultures are essential before confirming sarcoidosis 2, 3.