Overlap CTD

Question 1

🧩 Core concept

Answer 1

Overlap CTD = coexistence of two autoimmune CTDs (e.g., SSc + Myositis). MCTD = single U1-RNP entity. UCTD = ANA+ but no specific antibody.

Question 2

🌉 Prototype

Answer 2

Scleromyositis = Systemic Sclerosis + Myositis overlap.

Question 3

🎯 Autoantigen

Answer 3

PM-Scl 75/100 targets fibroblast + myocyte autoantigens.

Question 4

🧬 Genetics

Answer 4

HLA-DRB10301 / DQA10501; cytokines IL-6↑, IFN-γ↑, TGF-β↑.

Question 5

🔬 Defining antibody

Answer 5

Anti-PM-Scl 75/100; ANA nucleolar pattern.

Question 6

⚖️ PM-Scl 75 vs 100

Answer 6

PM-Scl 75 → ILD-dominant; PM-Scl 100 → skin-fibrosis-dominant.

Question 7

🧠 Other antibodies

Answer 7

Ku (arthralgia + ILD); U1-RNP (MCTD); U3-RNP (diffuse SSc).

Question 8

👩‍⚕️ Epidemiology

Answer 8

10% of SSc; 5% of IIM; F:M 3:1; onset 40–60 years.

Question 9

🩺 Skin

Answer 9

Sclerodactyly, telangiectasia, late Raynaud, calcinosis.

Question 10

💪 Muscle

Answer 10

Proximal weakness, CK 1000–5000 U/L, DM-like biopsy.

Question 11

🦴 Joints

Answer 11

Arthralgia > arthritis; non-erosive.

Question 12

🌫️ Lungs

Answer 12

ILD (NSIP>OP>UIP) ~50–60%; PH 10–15%.

Question 13

❤️ Heart

Answer 13

Myocarditis or right heart failure due to PH.

Question 14

🧃 Renal

Answer 14

Mild proteinuria; renal crisis rare.

Question 15

🍽️ GI

Answer 15

Oesophageal hypomotility and reflux.

Question 16

🔎 Lab hallmark

Answer 16

ANA nucleolar; Anti-PM-Scl positive; CK↑; complements normal.

Question 17

🚫 Negative antibodies

Answer 17

U1-RNP, dsDNA, Scl-70, Jo-1 all negative.

Question 18

🩻 MRI

Answer 18

Patchy proximal T2 hyperintensity (‘cotton-wool signal’).

Question 19

🔬 Muscle biopsy

Answer 19

Perifascicular atrophy, perivascular lymphocytes, C5b-9 deposition.

Question 20

🧴 Skin biopsy

Answer 20

Intimal thickening + perivascular lymphocytes.

Question 21

🌫️ HRCT

Answer 21

Basal NSIP > OP > UIP (‘foggy bases’).

Question 22

💓 Screening

Answer 22

Echo + DLCO baseline, repeat every 6–12 months.

Question 23

🫀 Confirm PH

Answer 23

Right-heart cath if PAP >25 mmHg.

Question 24

💊 First-line therapy

Answer 24

Pred 0.5–1 mg/kg/day → taper 6–8 wks + MMF or AZA.

Question 25

🚑 Rapid ILD

Answer 25

Cyclophosphamide; Rituximab if refractory; IVIG for dysphagia.

Question 26

❄️ Raynaud

Answer 26

CCB → PDE-5 inhibitor → IV Iloprost; Bosentan prevents ulcers.

Question 27

🧴 Fibrosis

Answer 27

MMF slows fibrosis; Nintedanib ↓ FVC decline ~40 mL/yr (Lancet 2023).

Question 28

💨 PH therapy

Answer 28

PDE-5 i ± ERA ± prostacyclin (JAMA 2023).

Question 29

⚠️ Steroid nuance

Answer 29

Short-term safe; avoid chronic >15 mg/day if vasculopathy dominant.

Question 30

📈 Prognosis

Answer 30

5-yr 95%, 10-yr 85–90%; ILD 50–60%, PH 10–15%.

Question 31

✅ Good prognosis

Answer 31

PM-Scl+, limited skin, early MMF therapy.

Question 32

🚫 Poor prognosis

Answer 32

Ku+, severe ILD/PH, older age, delayed therapy.

Question 33

⚰️ Mortality

Answer 33

ILD > PH ≫ cardiac or renal.

Question 34

🔵 MCTD

Answer 34

U1-RNP + Puffy fingers + Raynaud + PH ± Myositis.

Question 35

🟣 PM-Scl overlap

Answer 35

SSc skin + Myositis + Nucleolar ANA.

Question 36

🟠 Ku overlap

Answer 36

Mild skin + arthralgia ± ILD.

Question 37

🔴 Sclerolupus

Answer 37

SLE + SSc (dsDNA + Scl-70).

Question 38

🟢 Rhupus

Answer 38

RA + SLE (RF + dsDNA, erosive arthritis).

Question 39

⭐ Exam pearl 1

Answer 39

ANA nucleolar = PM-Scl or Fibrillarin.

Question 40

⭐ Exam pearl 2

Answer 40

CK↑ + SSc skin = Scleromyositis until proven otherwise.

Question 41

⭐ Exam pearl 3

Answer 41

PH follows ILD (unlike MCTD).

Question 42

⭐ Exam pearl 4

Answer 42

Raynaud appears later than MCTD.

Question 43

⭐ Exam pearl 5

Answer 43

SRC rare → steroids safe short-term.

Question 44

⭐ Exam pearl 6

Answer 44

MTX contraindicated if ILD.

Question 45

⭐ Exam pearl 7

Answer 45

Malignancy risk low → age-based screening only.

Question 46

💡 Mnemonic 1

Answer 46

PM-Scl = Puffy Muscle + Scleroderma Link.

Question 47

💡 Mnemonic 2

Answer 47

Overlap ≠ Mix-up → identify dominant antibody and organ.

Question 48

💡 Mnemonic 3

Answer 48

CK↑ + Nucleolar ANA = Scleromyositis.

Question 49

💡 Mnemonic 4

Answer 49

NSIP before PH → lungs lead the story.

Question 50

📚 NEJM 2022

Answer 50

Dalakas MC – immune pathogenesis of overlap myositis.

Question 51

📚 Lancet 2021

Answer 51

Lundberg IE – IIM classification includes overlaps.

Question 52

📚 EULAR 2023

Answer 52

Overlap CTD = classification descriptor, not distinct entity.

Question 53

📚 Lancet Resp Med 2023

Answer 53

MMF + Nintedanib efficacy in fibrosing CTD-ILD.

Question 54

📚 Ann Rheum Dis 2024

Answer 54

PM-Scl+ overlap → best survival vs SSc/DM alone.

Question 55

📚 JAMA 2023

Answer 55

PH therapy meta-analysis in CTD.