Mixed Connective Tissue Disease (MCTD)
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
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