Mixed Connective Tissue Disease

InCheat Sheets / Rheumatology

Mixed connective tissue disease combines clinical features of systemic sclerosis, SLE, and polymyositis. It is associated with high titres of anti-U1-RNP antibodies.

It is more common in women and peaks between 30 and 40 years of age.

Systemic features

System	Clinical features
Dermatological	Photosensitive rash, scleroderma-like changes, alopecia
Gastrointestinal	Oesophageal dysfunction
Respiratory	Pericarditis, pericardial effusion, and coronary artery disease
Haematological	Pleuritis, pulmonary hypertension, interstitial lung disease
Cardiac	Pleuritis, pulmonary hypertension, and interstitial lung disease
Renal	Glomerulonephritis
Neuropsychiatric	Seizures, mood disturbance

Risk factors
- Female gender
- HLA-DR4 and HLA-DR2
- Autoimmunity
- Infectious triggers, e.g., EBV, CMV, and retroviruses
- Hormonal influence
- Exposure to environmental factors, e.g., ultraviolet radiation, silica dust, and certain drugs
Pathophysiology
- Genetic predisposition and environmental triggers → production of autoantibodies against U1 ribonucleoprotein (U1RNP) → immune complex formation and deposition
Signs and symptoms
- Raynaud’s phenomenon (90%)
  - Precedes other symptoms
- Polyarthralgia and polyarthritis
- Myalgia
- Dactylitis
Differentials
- SLE
- Systemic sclerosis
- Polymyositis
Investigations
- Anti-U1 RNP (an extractable nuclear antigen) positive
- ANA positive
- anti-dsDNA and anti-Scl70 negative
Treatment
- NSAIDs for arthralgia or myalgia
- Calcium channel blockers for Raynaud’s phenomenon
- Corticosteroids (first-line) for acute flares and severe organ-threatening disease
- Hydroxychloroquine for mild cases or as a steroid-sparing agent
- Antimetabolites (methotrexate, azathioprine, and mycophenolate) for refractory cases
Complications
- Pulmonary hypertension
- Interstitial lung disease
- Myocardial infarction
- Rheumatoid arthritis
- Gastroesophageal reflux disease
- Malabsorption
- Glomerulonephritis
- Anaemia
- Stroke
- Peripheral neuropathy

Dr Jeffrey Kalei

Author and illustrator for Hyperexcision. Interested in emergency room medicine. I have a passion for medical education and drawing.

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Biochemistry

Adrenocorticotrophic hormone	P: <80 ng/L
Alanine aminotransferase (ALT)	P: 5–35 U/L
Albumin	P: 35–50 g/L
Aldosterone	P: 100–500 pmol/L
Alkaline phosphatase	P: 30–130 U/L (adults)
α-Amylase	P: 0–180 IU/dL
α-Fetoprotein	S: <10 kU/L
Angiotensin II	P: 5–35 pmol/L
Antidiuretic hormone (ADH)	P: 0.9–4.6 pmol/L
Aspartate transaminase	P: 5–35 U/L
Bicarbonate	P: 24–30 mmol/L
Bilirubin	P: 3–17 μmol/L
BNP	P: <50 ng/L
C-reactive protein	P: <10 mg/L
Calcitonin	P: <0.1 mcg/L
Calcium (ionized)	P: 1.0–1.25 mmol/L
Calcium (total)	P: 2.12–2.60 mmol/L
Chloride	P: 95–105 mmol/L
Cholesterol	P: <5.0 mmol/L
VLDL	P: 0.128–0.645 mmol/L
LDL	P: <2.0 mmol/L
HDL	P: 0.9–1.93 mmol/L
Cortisol	P: AM 450–700 nmol/L, Midnight 80–280 nmol/L
Creatine kinase (CK)	P: ♂ 25–195 U/L, ♀ 25–170 U/L
Creatinine	P: 70–100 μmol/L
Ferritin	P: 12–200 mcg/L
Folate	S: 2.1 mcg/L
FSH	P/S: 2–8 U/L ♂ (luteal); >25 U/L menopause
Gamma-glutamyl transpeptidase	P: ♂ 11–51 U/L, ♀ 7–33 U/L
Glucose (fasting)	P: 3.5–5.5 mmol/L
Growth hormone	P: <20 mu/L
HbA1C (DCCT)	B: 4–6%
HbA1C (IFCC)	B: 20–42 mmol/mol
Iron	S: ♂ 14–31 μmol/L, ♀ 11–30 μmol/L
Lactate	P: Venous 0.6–2.4 mmol/L, Arterial 0.6–1.8 mmol/L
Lactate dehydrogenase (LDH)	P: 70–250 U/L
Lead	B: <1.8 mmol/L
LH	P: 3–16 U/L (luteal)
Magnesium	P: 0.75–1.05 mmol/L
Osmolality	P: 278–305 mosmol/kg
Parathyroid hormone (PTH)	P: 0.8–8.5 pmol/L
Potassium	P: 3.5–5.3 mmol/L
Prolactin	P: ♂ <450 U/L, ♀ <600 U/L
PSA	P: 0–4 mcg/mL
Protein (total)	P: 60–80 g/L
Red cell folate	B: 0.36–1.44 μmol/L
Renin	P: Erect 2.8–4.5, Recumbent 1.1–2.7 pmol/mL/h
Sodium	P: 135–145 mmol/L
TBG	P: 7–17 mg/L
TSH	P: 0.5–4.2 mU/L
Thyroxine (T4)	P: 70–140 nmol/L
Free T4	P: 9–22 pmol/L
Total iron-binding capacity	S: 54–75 μmol/L
Triglycerides (fasting)	P: 0.50–2.3 mmol/L
Triiodothyronine (T3)	P: 1.2–3.0 nmol/L
Troponin T	P: <0.1 mcg/L
Urate	P: ♂ 210–480 μmol/L, ♀ 150–390 μmol/L
Urea	P: 2.5–6.7 mmol/L
Vitamin B12	S: 0.13–0.68 nmol/L
Vitamin D	S: 50 nmol/L

Arterial Blood Gases

pH	7.35–7.45
PaCO₂	4.7–6.0 kPa
PaO₂	>10.6 kPa
Base excess	±2 mmol/L

Urine

Cortisol (free)	<280 nmol/24h
Hydroxyindole acetic acid	16–73 μmol/24h
Hydroxymethylmandelic acid	16–48 μmol/24h
Metanephrines	0.03–0.69 μmol/mmol creatinine
Osmolality	350–1000 mosmol/kg
17-Oxogenic steroids	♂ 28–30 μmol/24h, ♀ 21–66 μmol/24h
17-Oxosteroids (neutral)	♂ 17–76 μmol/24h, ♀ 14–59 μmol/24h
Phosphate (inorganic)	15–50 mmol/24h
Potassium	14–120 mmol/24h
Protein	<150 mg/24h
Protein/creatinine ratio	<3 mg/mmol
Sodium	100–250 mmol/24h

Haematology

WCC	4.0–11.0 ×10⁹/L
Red cell count	♂ 4.5–6.5 ×10¹²/L, ♀ 3.9–5.6 ×10¹²/L
Haemoglobin	♂ 130–180 g/L, ♀ 115–160 g/L
PCV / Haematocrit	♂ 0.4–0.54 L/L, ♀ 0.37–0.47 L/L
MCV	76–96 fL
MCH	27–32 pg
MCHC	300–360 g/L
RDW	11.6–14.6%
Neutrophils	2.0–7.5 ×10⁹/L (40–75%)
Lymphocytes	1.0–4.5 ×10⁹/L (20–45%)
Eosinophils	0.04–0.44 ×10⁹/L (1–6%)
Basophils	0–0.10 ×10⁹/L (0–1%)
Monocytes	0.2–0.8 ×10⁹/L (2–10%)
Platelet count	150–400 ×10⁹/L
Reticulocyte count	0.8–2.0% / 25–100 ×10⁹/L
ESR	Depends on age
Prothrombin time	10–14 s
APTT	35–45 s

Paediatric

Pulse Rate (beats per minute)
Neonate (<1 month)	140–160
Infant (<1 year)	120–140
1–5 years	110–130
5–12 years	80–120
>12 years	70–100
Temperature
Normal range	36.6–37.2 °C
38.0 °C	Fever (infant)
38.5 °C	Fever (>3 months)
Respiratory Rate (tachypnoea)
Neonate (0–2 months)	≥60 breaths/min
2–12 months	≥50 breaths/min
1–5 years	≥40 breaths/min
>5 years	≥30 breaths/min
Blood Pressure (mmHg)
Term	65/45
1 year	75/50
4 years	85/60
8 years	95/65
10 years	100/70
Head Circumference
Term	35 cm ± 2
1 year	+1 cm/month
2–3 years	+2 cm/year
4–5 years	+1 cm/year
5 years	~53 cm
10 years	56–57 cm
Height
Term	52–55 cm
1 year	75 cm
2–12 years	6a + 77 cm
Weight Formulas
3–12 months	(a + 9)/2 kg
1–6 years	2a + 8 kg
>6 years	(7a − 5)/2 kg
Developmental Milestones
Social smile	1.5 months
Head control	4 months
Sits unsupported	7 months
Crawls	10 months
Stands unsupported	10–12 months
Walks	12–13 months
Talks	18 months
MUAC (6 months–5 years)
Obese	>17.5 cm
Normal	13.5–17.4 cm
At risk	12.5–13.4 cm
Moderate malnutrition	11.5–12.4 cm
Severe malnutrition	<11.5 cm
Blood Transfusion
Whole blood	20 mL/kg
pRBC	10 mL/kg
Formula	6 × (weight in kg) × Hb deficit
Normal Paediatric Lab Values
Haemoglobin (g/dL)	Hematocrit (%)
Term newborn: 13–20	40–58
1 month: 11–18	32–54
2 months: 10–15	28–44
1–2 years: 10–13	32–40
>2 years: 11–14	33–42
CSF WBC (/mm³)
Term newborn	0–25
>2 weeks	0–5

Dr Jeffrey Kalei

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