Connective tissue disease-associated interstitial lung disease

Interstitial lung disease (ILD), also called diffuse parenchymal lung disease, is a diverse group of nonmalignant disorders causing inflammation and scarring of the alveolar interstitium, presenting as subacute to chronic exertional dyspnea and nonproductive cough. Diagnosis rests on pulmonary function testing plus high-resolution CT pattern recognition; management is exposure removal, glucocorticoids for inflammatory disease, antifibrotic therapy for progressive fibrotic disease, oxygen for hypoxemia, and early transplant referral.

Systemic sclerosis is a multiorgan disease of vascular injury and progressive fibrosis in which diffuse cutaneous disease extends skin thickening proximal to the elbows and knees and drives early visceral fibrosis. Diagnosis rests on the 2013 ACR/EULAR classification criteria and an antibody split (anti-Scl-70, anticentromere, anti-RNA polymerase III), and treatment is organ-specific: mycophenolate or nintedanib for interstitial lung disease, calcium channel blockers for Raynaud phenomenon, and captopril for scleroderma renal crisis.

Rheumatoid arthritis is a chronic systemic autoimmune disease causing symmetric small-joint polyarthritis of the hands and feet that spares the distal interphalangeal joints, with morning stiffness over an hour. Diagnosis combines the ACR/EULAR classification criteria with rheumatoid factor, anti-CCP antibody, and radiographs. Treat-to-target management anchors on methotrexate, escalating to a biologic or targeted synthetic disease-modifying antirheumatic drug when remission is not reached.

Dermatomyositis is a complement-mediated inflammatory myopathy causing symmetric proximal weakness with pathognomonic skin findings, heliotrope rash and Gottron papules, that separate it from polymyositis. It carries a 3- to 12-fold increased malignancy risk and a distinct interstitial lung disease burden that drive workup and therapy. First-line treatment is high-dose prednisone with an early steroid-sparing agent.

Polymyositis is an idiopathic inflammatory myopathy causing symmetric, subacute proximal muscle weakness with no rash, driven by endomysial CD8-positive T-cell invasion of non-necrotic, MHC class I-expressing muscle fibers. It is a diagnosis of exclusion confirmed by muscle biopsy, and first-line treatment is high-dose prednisone with a steroid-sparing agent such as methotrexate or azathioprine started concurrently.

Sjogren syndrome is a systemic autoimmune exocrinopathy in which lymphocytic infiltration of the lacrimal and salivary glands causes keratoconjunctivitis sicca and xerostomia, occurring alone (primary) or alongside another rheumatologic disease such as rheumatoid arthritis or lupus (secondary). Diagnosis combines the anti-Ro (SSA) and anti-La (SSB) antibody panel, objective dryness testing, and labial salivary gland biopsy under the 2016 ACR/EULAR classification criteria. Management centers on sicca-directed therapy, pilocarpine or cevimeline for xerostomia and topical cyclosporine for keratoconjunctivitis, with hydroxychloroquine or immunosuppression for extraglandular disease.

Mixed connective tissue disease is an overlap syndrome defined by a high-titer anti-U1-ribonucleoprotein antibody together with clinical features of systemic lupus erythematosus, systemic sclerosis, and inflammatory myositis, with Raynaud phenomenon and puffy fingers as near-universal early findings. Treatment is organ-directed, built on hydroxychloroquine and glucocorticoids with methotrexate, azathioprine, or mycophenolate mofetil escalation guided by the dominant manifestation.

Undifferentiated connective tissue disease is a diagnosis of exclusion: autoimmune features, most often Raynaud phenomenon, inflammatory arthralgia, rash, sicca, cytopenias, or serositis, plus a positive antinuclear antibody usually at 1:80 or higher, without meeting classification criteria for any specific connective tissue disease. There is no dedicated regimen; treatment is manifestation-directed, for example a calcium channel blocker for Raynaud phenomenon or hydroxychloroquine and an NSAID for arthritis. A minority evolve to a defined disease, most often systemic lupus erythematosus, usually within 2 to 5 years.

Systemic lupus erythematosus is a chronic multisystem autoimmune disease in which antinuclear and other autoantibodies drive immune-complex deposition and organ injury across skin, joints, kidneys, blood, serosa, and the nervous system. Diagnosis rests on a positive antinuclear antibody plus weighted 2019 EULAR/ACR criteria totaling 10 or more points. Hydroxychloroquine is lifelong first-line therapy for nearly every patient, with glucocorticoids and steroid-sparing immunosuppression added for moderate to severe or organ-threatening disease.