Towards Early Diagnosis of Mixed Connective Tissue Disease: Updated Perspectives

Figures & data

Figure 1 Fibrotic Nonspecific Interstitial Pneumonia in a patient with a longstanding Mixed Connective Tissue Disease. The pattern is characterized by diffuse Ground Glass Opacities (yellow arrow), subpleural sparing (blue arrow), and presence of traction bronchiectasis (red arrow).

Table 1 Proposed Classification Criteria for Mixed Connective Tissue Disease

Sharp GC^Citation2	Khan MF et al^Citation5	Alarcon-Segovia and Villareal^Citation3	Kasukawa R et al^Citation4	Tanaka Y et al^Citation6
Major criteria ● Severe myositis ● Pulmonary involvement – DLCO <70% of the predicted – PAH – Proliferative vascular lesions at the biopsy ● RP or esophageal hypomotility ● Edema of the hands or sclerodactyly ● Anti-ENA antibodies ≥1:10,000 and anti-nRNP positive and anti-Sm Negative	Serological Anti-n-RNP antibodies titer >1:1.600	Serological Anti-n-RNP antibodies titer >1:1.600	Common symptoms RP Edema of the hands or fingers only Anti n-RNP antibodies positive	I. Common manifestations  1. RP  2. Puffy fingers and/or swollen hands II. Immunological manifestation  Positivity for anti-U1RNP III. Characteristic organ involvement  1. PAH  2. Aseptic meningitis  3. Trigeminal neuropathy IV. Overlapping manifestations A. SLE-like manifestations  1. Polyarthritis  2. Lymphadenopathy  3. Malar rash  4. Pericarditis or pleuritis  5.Leukopenia (4000/μL or less) or thrombocytopenia (100,000/μL or less) B. SSc-like manifestations  1. Sclerodactyly  2. Interstitial lung disease  3. Esophageal dysmotility or dilatation C.PM/DM-like manifestations  1. Muscle weakness  2. Elevated levels of myogenic enzymes  3. Myogenic abnormalities on EMG
Minor criteria ● Alopecia ● Leukopenia ● Anemia ● Pleurisy ● Pericarditis ● Arthritis ● Trigeminal neuropathy ● Malar rash ● Thrombocytopenia ● Moderate myositis ● Edema of the hands in the past	Clinical Swollen hands Synovitis Myositis RP	Clinical ● Edema of the hands ● Synovitis ● Myositis ● RP ● Acrosclerosis	Mixed symptoms ● SLE-like manifestations: – Polyarthritis – Lymphadenopathy – Erythema of the face – Pericarditis or pleuritis – Leukopenia or thrombocytopenia ● SSc-like events: – Sclerodactyly – Pulmonary fibrosis, changes restrictive or reduction of DLCO – Hypomotility or esophageal dilatation ● PM manifestations – Muscle fatigue – Elevated CPK levels – Myogenic pattern on EMG
For diagnosis: – 4 major criteria + anti-RNP titer >1:4000 (exclusion criterion: positivity for anti-Sm); – 2 among the first three major criteria + 2 minor criteria + anti-nRNP ≥1:1000	For diagnosis: Serological criterion + RP + ≥ 2 remaining clinical criteria	For diagnosis: Serological criteria + at least 3 clinical criteria	For diagnosis: At least 1 of the common symptoms + positivity for anti-nRNP + at least 1 mixed symptom of at least 2 or 3 categories of manifestation	For diagnosis: At least one common manifestation, immunological manifestation, and at least one characteristic organ involvement; or at least one common manifestation, immunological manifestation, and at least one feature each in 2 or more from items A, B, and C in overlapping manifestations.
Sensitivity 57.7%, specificity 90%^Citation34	Sensitivity 52.3%, specificity 99.4%^Citation34	Sensitivity 69.4%, specificity 99.4%^Citation34	Sensitivity 77.5%, specificity 92.2%^Citation34	Sensitivity 90.6%, specificity 98.4%^Citation6

Abbreviations: anti-Sm, Anti Smith antigen; anti-U1RNP, anti-U1 ribonucleoprotein antibody; CPK, Creatine Phosphokinase; DLCO, Diffusion Lung Capacity for Carbon Monoxide; DM, Dermatomyositis; EMG, Electromyography; ENA, Extractable Nuclear Antigen; PAH, Pulmonary Arterial Hypertension; PM, Polymyositis; RP, Raynaud’s Phenomenon; SLE, Systemic lupus erythematosus; SSc, Systemic Sclerosis.

Figure 2 Nailfold Videocapillaroscopy in a healthy subject (A) compared with a patient with Mixed Connective Tissue Disease (B–D). The pattern is characterized by the presence of multiple Giant Capillaries and neoangiogenesis.

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