Epidemiology
- Defined by presence of features of SLE, polydermatomyositis, and Scleroderma (and occasionally Sjogren’s Syndrome)
- MCTD may differentiate into other rheumatologic diseases: differentiation appears to be genetically determined
- Incidence: 1 in 10k persons
- Sex: F:M is 9:1
- Peak Age: 30’s
Physiology
- Vasculitis of Small Arterioles and Large Arteries (Pulmonary, Coronary, Renal)
Diagnosis
Serology
- Anti-U1-RNP (targets small nuclear proteins): usually positive at >1:1600 (at >1:10,000 titer, this is almost diagnostic of MCTD), but not in all cases
- May be positive in scleroderma and SLE also
- Anti-U2-RNP: may be positive in myositis-overlap syndromes
- Anti-GBM: negative
Other
- Erythocyte Sedimentation Rate (ESR): usually elevated
Clinical Manifestations
Dermatologic Manifestations
- General Comments: almost always involved
- Alopecia
- Cutaneous Lupus
- Dyspigmentation
- Periungual Telanigectasia
- Photosensitivity
- Sclerodactyly
Gastrointestinal Manifestations
- Esophageal Dysfunction: dysmotility occurs in 80% of cases
Hematologic Manifestations
Neurologic Manifestations
- Central Nervous System Involvement
- Fatigue (see Fatigue, [[Fatigue]])
Pulmonary Manifestations
General Comments
Interstitial Lung Disease (see Interstitial Lung Disease-Etiology, [[Interstitial Lung Disease-Etiology]])
- Epidemiology
- Interstitial lung disease is the most common pulmonary manifestation
- Sex: F: M ratio is 8:1
- Race: no race predilection
- Diagnosis
- CXR Pattern
- Interstitial Infiltrates (lower-lobe predominance): seen with chronic disease or recurrent DAH
- May mimic the appearance of IPF
- Chest CT Pattern
- Ground-glass infiltrates
- Subpleural micronodules
- Non-septal linear opacities
- Honeycombing: small cystic changes (seen best in lower fields) seen late in course
- PFT’s: restriction with decreased DLCO
- Lung Biopsy
- Proliferative vasculopathy (prominent): medial hypertrophy with intimal thickening of pulmonary arteries and arterioles or plexogenic angiopathy
- Interstitial fibrosis
- Clinical
- Presents with dyspnea, pleuritic chest pain, cough, bibasilar rales, increased P2, absence of clubbing
- 33% of cases are asymptomatic: 75% of these cases have CXR or PFT abnormalities and resting hypoxemia
- Interstitial lung disease is often subclinical (usually detected only by CXR or PFT’s)
- Treatment: corticosteroids + cytotoxic (cyclophosphamide or azathioprine)
Acute Lung Injury-ARDS (see Acute Lung Injury-ARDS, [[Acute Lung Injury-ARDS]])
- Pathology: diffuse alveolar damage
- Diagnosis: HRCT -> diffuse ground-glass infiltrates and/or consolidation, reticular infiltrates, honeycombing (mimics accelerated idiopathic pulmonary fibrosis)
- Clinical: acute respiratory deterioration
- May occur as the initial presentation of the disease (without pre-existing lung manifestations)
- Treatment and Prognosis: most cases die within months, despite steroid therapy
- Case reports describe the use of cyclosporin A + either prednisolone or cyclophosphamide
Pleurisy/Pleural Effusion (see Pleural Effusion-Exudate, [[Pleural Effusion-Exudate]])
- Epidemiology
- Occurs in 35-40% of cases
- May be the first manifestation of MCTD
- Diagnosis
- Pleural Fluid: exudate
- CXR/Chest CT
- Pleural effusion: seen in some cases
- Pleural thickening is seen in only 3% of cases
- Clinical
- Pleural effusion
- Pleurisy/pleuritic chest pain
- Treatment
- Usually small and resolve spontaneously
- Occasionally require corticosteroids
Pulmonary Hypertension (see Pulmonary Hypertension, [[Pulmonary Hypertension]])
- Physiologic Mechanisms
- Vasoconstriction: due to hyperreactive pulmonary vasculature)
- Proliferative Vasculopathy: vascular medial hypertrophy with intimal fibrosis (not a true pulmonary vasculitis though)
- Plexogenic Angiopathy
- CTEPH:
- Advanced ILD:
- Clinical: usually insidious onset
- Prognosis: may be fatal in some cases
Chronic Aspiration Pneumonia (see Aspiration Pneumonia, [[Aspiration Pneumonia]])
- Epidemiology: common
- Physiology: may be due to esophageal dysmotility
Diffuse Alveolar Hemorrhage (DAH) (see Diffuse Alveolar Hemorrhage, [[Diffuse Alveolar Hemorrhage]])
- Epidemiology: uncommonly complicates MCTD
- Most cases are associated with co-existing systemic vasculitis
- One case reported with isolated lung vasculitis [Chest 1998; 113: 1609-1615]
- Most cases of alveolar hemorrhage occur after the primary diagnosis of MCTD
- Diagnosis
- CXR/Chest CT: diffuse or patchy alveolar infiltrates
- PFT’s: increased DLCO during alveolar hemorrhage
- Lung Biopsy: pulmonary capillaritis
Respiratory Muscle Weakness with Acute/Chronic Hypoventilation (see Acute Hypoventilation, [[Acute Hypoventilation]] and Chronic Hypoventilation, [[Chronic Hypoventilation]])
- Physiology: myopathy
- Clinical
- Atelectasis with small lung volumes may occur
Renal Manifestations
Rheumatologic Manifestations
- Arthralgias/Arthritis (see Arthritis, [[Arthritis]]): most cases
- Myalgias/Myositis (see Myositis, [[Myositis]])
- Raynaud’s Phenomenon (see Raynaud’s Phenomenon, [[Raynauds Phenomenon]])
- Swollen Hands
- Vasculitis (see Vasculitis, [[Vasculitis]])
Treatment
- Steroids/Immunosuppressives: indicated early for ILD (although no studies show prevention of progression to fibrosis)
Treatment of Pulmonary Hypertension
- Usually difficult to treat
Prognosis
- Disease course seems to follow that connetcive tissue disease that MCTD most resembles
- Survival is better if anti-U1-RNP is present
References
- Long-term outcome in mixed connective tissue disease: longitudinal clinical and serologic findings. Arthritis Rheum 1999; 42:899-909
- Diffuse Alveolar Damage: Uncommon Manifestation of Pulmonary Involvement in Patients With Connective Tissue Diseases. Chest 2006; 130:553–558
- Immunosuppressive therapy in lupus- and mixed connective tissue disease-associated pulmonary arterial hypertension: a retrospective analysis of twenty-three cases. Arthritis Rheum 2008;58:521-31