Comprehensive Wellness Guide to Understanding and Managing Sarcoidosis

200,000 US cases—60% pulmonary, 30% extrapulmonary. Löfgren syndrome: 90% spontaneous remission. This 2025 expert-reviewed guide covers phenotypes (Löfgren, Heerfordt), Scadding stages, serum ACE (sens 60%), biopsy (non-caseating granuloma), prednisone 20 mg taper, methotrexate/infliximab, cardiac MRI/PET, hypercalcemia protocol, fatigue CBT, and AI CT granuloma scoring. Includes organ-specific protocols, monitoring, and lifestyle.

Definition and Epidemiology

• Definition: Multisystem granulomatous disease of unknown etiology
• Incidence: 5–40/100,000 (highest in African Americans, Scandinavians)
• Age: 20–50 years; second peak >60 in women
• Risk: HLA-DRB1*03, BTNL2 gene, occupational (firefighters, WTC)

Pathophysiology: The Granuloma Cascade

Antigen → CD4+ Th1 response → macrophage aggregation → non-caseating granuloma

• Triggers: Unknown (mycobacteria?, propionibacterium?, inorganic)
• Cytokines: TNF-α, IL-2, IFN-γ
• Fibrosis: Chronic → TGF-β → scarring
• Hypercalcemia: 1α-hydroxylase in macrophages → ↑ 1,25-(OH)₂-D

Clinical Phenotypes

Syndrome	Features	Prognosis
Löfgren	BHA, erythema nodosum, arthritis, fever	90% remit in 2 yrs
Heerfordt-Waldenström	Uveitis, parotid swelling, facial palsy, fever	Good
Chronic Fibrotic	Stage IV, dyspnea, fatigue	Poor

Pulmonary Involvement: Scadding Stages

Stage	CXR	FVC %	Spont. Remission
0	Normal	—	—
I	BHA only	Normal	60–80%
II	BHA + reticulonodular	80–100%	50%
III	Reticulonodular, no BHA	60–80%	30%
IV	Fibrosis, bullae	<50%	0%

Diagnostic Workup

1. Clinical + CXR/HRCT (perilymphatic nodules)
2. Biopsy: Non-caseating granuloma (EBUS-TBNA, skin, lymph node)
3. Serum ACE: ↑ in 60% (not specific)
4. Hypercalcemia/Hypercalciuria: 10–15%
5. PFTs: Restrictive (↓FVC, normal FEV1/FVC), ↓DLCO
6. Organ-specific: Cardiac MRI, PET, ophthalmology, neuro

Treatment Algorithm (2020 ATS/ERS)

Indications for Therapy

• Dangerous organ involvement (cardiac, neuro, eye, hypercalcemia)
• Symptomatic pulmonary (dyspnea, cough)
• Stage II–III with FVC <70% or decline >10%

First-Line: Corticosteroids

• Prednisone: 20 mg/day × 4–6 weeks → taper over 6–12 months
• Response: 60–70% improve
• Relapse: 30–50% on taper

Second-Line: Immunosuppressants

Agent	Dose	Indication	Monitoring
Methotrexate	10–15 mg/week	Steroid-sparing	LFT, CBC q1–3mo
Azathioprine	50–150 mg/day	Alternative	TPMT, CBC
Mycophenolate	1–2 g/day	Skin, neuro	CBC

Third-Line: Biologics

• Infliximab: 5 mg/kg IV at 0, 2, 6 weeks → q4–8 weeks
• Response: 70–80% in refractory
• Adalimumab: Alternative if anti-drug antibodies

Organ-Specific Management

Cardiac Sarcoidosis (10–25% autopsy)

• Screen: ECG, echo, Holter
• Confirm: Cardiac MRI (LGE) or FDG-PET
• Treat: Prednisone + ICD if VT or EF <35%

Ocular (Uveitis 30–60%)

• Topical steroids (anterior)
• Systemic if posterior/panuveitis

Neurosarcoidosis (5–15%)

• Cranial neuropathy (VII), meningitis, seizures
• MRI + CSF (↑ protein, lymphocytosis)
• High-dose steroids ± infliximab

Cutaneous (25%)

• Lupus pernio, EN
• Topical steroids, hydroxychloroquine

Fatigue Management (60–80% of patients)

• Screen: FAS (Fatigue Assessment Scale) >22
• CBT: 12 sessions → 30% reduction
• Exercise: Graded aerobic 3×/week
• Sleep hygiene
• Armodafinil: 150–250 mg (modest benefit)

Monitoring Protocol

Parameter	Frequency
PFTs (FVC, DLCO)	q3–6mo on Rx
Symptoms (dyspnea, fatigue)	Every visit
Calcium, ACE	q3mo initially
Ophthalmology	Yearly if uveitis risk
ECG/Holter	Yearly

Lifestyle and Supportive Care

• Vitamin D: Avoid supplements if hypercalcemia
• Smoking cessation: Worsens lung function
• Pulmonary rehab: Stage II–III
• Support groups: FSR, WASOG
• Diet: Anti-inflammatory (Mediterranean)

Emerging Therapies (2025)

• AI HRCT Analysis: Granuloma burden scoring (Sens 94%)
• Repository Corticotropin Injection (RCI): ACTH analog
• JAK Inhibitors: Tofacitinib in refractory
• Anti-GM-CSF: Phase II

Red Flags: Urgent Evaluation

• Syncope, VT, heart block (cardiac)
• Vision loss, red eye (uveitis)
• Seizures, cranial neuropathy (neuro)
• Serum Ca >11 mg/dL or renal stones

Conclusion

Sarcoidosis is heterogeneous but manageable. Diagnose early, treat only if needed, spare steroids, monitor organs. With AI imaging, biologics, and fatigue protocols, 70% achieve good QoL. Partner with your sarcoid team—you are more than your granulomas.