MCTD

Question 1

Core concept

Answer 1

Overlap autoimmune syndrome combining SLE, Systemic Sclerosis, and Polymyositis features, driven by high-titre anti-U1-RNP antibodies.

Question 2

Mnemonic for core

Answer 2

RNP = Raynaud, Puffy fingers, Pulmonary hypertension.

Question 3

Genetics

Answer 3

HLA-DR4 and DR2 predisposition.

Question 4

Pathophysiology

Answer 4

Anti-U1-RNP targets snRNP complex causing immune-complex vasculopathy and fibroblast activation.

Question 5

Mechanistic overlap

Answer 5

SLE (complement), SSc (fibrosis), Myositis (CD8 T-cell injury).

Question 6

Alarcón-Segovia criteria

Answer 6

High-titre anti-U1-RNP + ≥3 of 5: hand oedema, synovitis, myositis, Raynaud, acrosclerosis.

Question 7

Kasukawa criteria

Answer 7

Anti-U1-RNP + features from ≥2 groups (SLE-like, SSc-like, or PM-like).

Question 8

Exam pearl diagnostic

Answer 8

High-titre U1-RNP + puffy fingers + Raynaud + myositis = MCTD, not SLE.

Question 9

Musculoskeletal features

Answer 9

Non-erosive polyarthritis, myositis (↑CK), tenosynovitis.

Question 10

Vascular features

Answer 10

Raynaud (earliest sign), nailfold capillary dilatation, digital ulcers.

Question 11

Cutaneous features

Answer 11

Puffy fingers, sclerodactyly, telangiectasia, mechanic’s hands.

Question 12

Pulmonary features

Answer 12

ILD (NSIP pattern) and/or Pulmonary Hypertension (PH).

Question 13

Cardiac features

Answer 13

Pericarditis, myocarditis, right heart failure from PH.

Question 14

Renal features

Answer 14

Mild proteinuria; GN rare; no renal crisis (unlike SSc).

Question 15

GI features

Answer 15

Oesophageal hypomotility and GORD.

Question 16

Haematologic features

Answer 16

Cytopenias and raised CRP.

Question 17

Laboratory hallmark

Answer 17

ANA speckled pattern with high anti-U1-RNP (>95%).

Question 18

Complement pattern

Answer 18

Normal or mildly low C3/C4.

Question 19

CK level

Answer 19

Raised if active myositis.

Question 20

Differentiating antibodies

Answer 20

Anti-PM-Scl → scleromyositis; Anti-Jo-1/PL-12 → anti-synthetase; Anti-Scl-70 → SSc; Anti-dsDNA → SLE.

Question 21

UCTD distinction

Answer 21

UCTD lacks defining antibodies; MCTD has high U1-RNP.

Question 22

Imaging baseline

Answer 22

HRCT for ILD; echo + NT-proBNP + DLCO at baseline, repeat q6–12 mo.

Question 23

Confirm PH

Answer 23

Right-heart catheterisation before advanced vasodilators.

Question 24

First-line for musculoskeletal

Answer 24

Prednisolone 0.5–1 mg/kg + MTX or AZA; taper after CK and symptoms improve.

Question 25

Hydroxychloroquine role

Answer 25

For rash/fatigue if myositis not dominant.

Question 26

ILD first-line

Answer 26

Mycophenolate mofetil (Lancet Resp Med 2023).

Question 27

ILD severe

Answer 27

Cyclophosphamide if progressive fibrosis; Rituximab or Nintedanib if refractory.

Question 28

PH first-line

Answer 28

PDE-5 inhibitor (Sildenafil/Tadalafil) ± ERA (Bosentan/Ambrisentan).

Question 29

PH advanced

Answer 29

Add prostacyclin analogue (Iloprost/Epoprostenol) for high-risk cases.

Question 30

Raynaud management

Answer 30

CCB (Nifedipine/Amlodipine) → PDE-5i → IV Iloprost; Bosentan prevents ulcer recurrence.

Question 31

GI management

Answer 31

PPI + Prokinetic (Domperidone/Metoclopramide).

Question 32

Steroid nuance

Answer 32

Renal crisis rare, but avoid chronic high-dose if SSc-like vasculopathy dominates.

Question 33

Pregnancy

Answer 33

Anti-U1-RNP not linked to heart block; anti-Ro/La co-positive → fetal echo 16–26 wks; continue HCQ.

Question 34

Malignancy

Answer 34

No intrinsic cancer risk; perform age-appropriate screening.

Question 35

Prognosis overall

Answer 35

10-year survival >80–90%; PH is leading cause of death.

Question 36

Phenotypic evolution

Answer 36

10–15% evolve to definite CTD (SLE or SSc) → repeat serology if phenotype shifts.

Question 37

Poor prognosis markers

Answer 37

Pulmonary hypertension, ILD, high CRP, severe myositis.

Question 38

Exam recall 1

Answer 38

High U1-RNP + puffy fingers + Raynaud = MCTD.

Question 39

Exam recall 2

Answer 39

PH can occur without ILD (vasculopathy).

Question 40

Exam recall 3

Answer 40

No renal crisis (unlike SSc).

Question 41

Exam recall 4

Answer 41

Annual echo screening for PH.

Question 42

Exam recall 5

Answer 42

Treat dominant organ, not antibody label.

Question 43

Mnemonic diagnostic

Answer 43

High U1-RNP + ≥3 of 5 → hand oedema, synovitis, myositis, Raynaud, acrosclerosis.

Question 44

Mnemonic concept

Answer 44

3 C’s = Connective tissue overlap, CK↑ myositis, Cardiopulmonary hypertension.

Question 45

EBM NEJM 1972

Answer 45

Sharp GC: Original MCTD description.

Question 46

EBM NEJM 2022

Answer 46

Dalakas MC: Myositis overlap pathogenesis (U1-RNP immune target).

Question 47

EBM Lancet 2021

Answer 47

Lundberg IE: IIM classification + overlap recognition.

Question 48

EBM JAMA 2023

Answer 48

Meta-analysis: Pulmonary hypertension management in CTD.

Question 49

EBM Lancet Resp Med 2023

Answer 49

Nintedanib + MMF slow FVC decline in CTD-ILD (includes MCTD).