What are the symptoms and treatment options for systemic sarcoidosis?

Symptoms and Treatment of Systemic Sarcoidosis

Systemic sarcoidosis presents with diverse manifestations affecting multiple organ systems, with lungs and intrathoracic lymph nodes involved in over 90% of cases, while treatment decisions should be based on risk of mortality, permanent disability, and quality of life impact. 1, 2

Clinical Presentation

General Symptoms

• Fatigue, night sweats, weight loss, and fever are common constitutional symptoms 3
• Arthralgia and myalgia may occur as part of systemic manifestations 3
• Less than half of patients initially present with respiratory symptoms 2

Organ-Specific Manifestations

Pulmonary (Most Common)

• Cough (typically dry) and dyspnea are the primary respiratory symptoms 3, 4
• Disease often detected as incidental finding of lymphadenopathy on chest x-ray 2
• Bilateral hilar adenopathy is the most common radiographic finding 5

Cardiac

• Arrhythmias and heart failure may develop 3
• Cardiac involvement can lead to significant mortality 1
• New-onset third-degree AV block in young or middle-aged adults is highly suggestive 1

Neurologic

• Headache and cranial nerve palsies, particularly seventh cranial nerve paralysis 1, 3
• Small-fiber neuropathy causing neuropathic pain and autonomic dysfunction 1
• Central nervous system involvement can cause significant morbidity 1

Ocular

• Uveitis, optic neuritis, scleritis, and retinitis 1
• Lacrimal gland swelling may occur 1
• Eye involvement is a common extrapulmonary manifestation 1

Cutaneous

• Various skin lesions including lupus pernio (violaceous lesions on nose, cheeks) 1
• Erythema nodosum, especially in acute presentations 1, 3
• Maculopapular, erythematous, or violaceous skin lesions 1

Other Manifestations

• Hypercalcemia or hypercalciuria with abnormal vitamin D metabolism 1
• Hepatosplenomegaly 1
• Renal involvement with potential for treatment-responsive renal failure 1

Diagnostic Syndromes

• Löfgren's syndrome: bilateral hilar adenopathy with erythema nodosum and/or periarticular arthritis (highly diagnostic) 1, 3
• Heerfordt syndrome: fever, parotid enlargement, uveitis, and facial nerve palsy 2
• Lupus pernio: chronic violaceous lesions on face, particularly nose 2

Treatment Approach

Treatment Indications

• Treatment is indicated for risk of death/permanent disability or to improve quality of life 1
• Many patients have good outcomes and never require treatment 1
• Less than 10% of patients die from sarcoidosis, mostly from advanced lung disease 1

First-Line Treatment

• Glucocorticoids (prednisone) remain first-line therapy for symptomatic disease 6, 4
• Indicated for symptomatic pulmonary disease, cardiac involvement, neurosarcoidosis, and other serious extrapulmonary manifestations 2, 7
• Recurrence of disease is common if treatment is withdrawn too soon 1
• At least 25% of patients require treatment for more than 2 years 1

Second-Line and Alternative Treatments

• Methotrexate or hydroxychloroquine for steroid-sparing effect or if steroids are ineffective 2
• TNF inhibitors (infliximab, adalimumab) for refractory cases, particularly for small-fiber neuropathy 1
• Intravenous immunoglobulin (IVIg) may be considered for persistent small-fiber neuropathy symptoms 1

Treatment for Small-Fiber Neuropathy

• For mild/non-disabling symptoms: consider topiramate, tramadol, α-lipoic acid, or topical therapies (lidocaine, capsaicin) 1
• For severe/disabling symptoms: GABA analogues or antidepressants 1
• For persistent symptoms despite first-line treatment: consider IVIg or TNF inhibitors 1

Treatment Duration and Monitoring

• Relapse rates of 20-80% have been reported upon glucocorticoid withdrawal after 2 years 1
• Withdrawal of methotrexate after 2 additional years was associated with 80% re-institution of systemic therapy 1
• Discontinuation of infliximab after 6-12 months was associated with relapse in more than half of cases 1

Special Considerations

• Treatment decisions should be individualized based on organ involvement, disease severity, and impact on quality of life 1
• Refractory or complex cases should be co-managed with a sarcoidosis subspecialist 2
• End-stage disease may require organ transplantation for eligible patients 7, 4
• Careful assessment of all potential organ involvement is essential as sarcoidosis can affect multiple systems simultaneously 1