Connective tissue disorders Flashcards
SLE, Sjogren's Syndrome, Systemic Sclerosis, Mixed Connective Tissue Disease, Anti-Phospholipid Syndrome
What are the key factors in SLE aetiology? → Systemic Lupus Erythematosus
(1) Autoimmune, genetic predisposition (HLA genes)
(2) Hormonal (↑ oestrogen)
(3) Environmental
(UV light, infections, medications)
Who is most at risk for SLE?
(1) Women aged 20-40
(2) Especially of Afro-Caribbean, Hispanic, Asian, or Chinese descent
(3) Smokers
What is the key immune mechanism in SLE pathophysiology?
The immune system attacks cells, forming immune complexes (Type III hypersensitivity) causing inflammation and tissue damage
What are the three levels of SLE severity?
Mild (cutaneous)
Moderate (arthritis, effusions) Severe (organ-threatening disease)
What are some non-specific symptoms of SLE?
Fever, fatigue, weight loss
What is a key cutaneous feature of SLE?
Photosensitive malar rash, usually on the face
What is the difference between SLE arthritis and RA?
SLE arthritis is non-erosive, with no damage to joints. Deformities are reversible
What are common haematological findings in SLE?
(1) Leukopenia
(2) Thrombocytopenia
(3) Haemolytic anaemia
(4) Lymphadenopathy
What is required to diagnose SLE according to the EULAR/ACR criteria?
(1) ≥11 criteria
(2) With at least 1 clinical and 1 lab finding, or biopsy-proven lupus nephritis
(3) with positive ANA or anti-dsDNA
What is the significance of ANA in SLE diagnosis?
High sensitivity; a negative ANA test makes SLE unlikely
Which autoantibody is most specific for SLE?
Anti-Smith (Anti-Sm)
What does a positive urine dipstick indicate in suspected SLE patients?
Proteinuria >0.5g/24 hours suggests lupus nephritis; biopsy confirms
What is the 1st line treatment for mild-moderate SLE? (technically 2nd)
Hydroxychloroquine + NSAIDs
= for short-term symptom control
What is the first-line treatment of SLE?
- Sun management
- Minimize steroid use
What do you stop if the patient has lupus nephritis?
NSAID
What is the 3rd line treatment for moderate-severe SLE?
(1) Hydroxychloroquine
(2) Acute flareups: azathioprine (immunosuppressant) + oral steroids (short periods)
What is the 4th line treatment for severe SLE?
Hydroxychloroquine + prednisolone + warfarin + mycophenolate mofetil
Example of severe SLE
lupus nephritis or CNS lupus
What complication is associated with steroid use in SLE?
Avascular necrosis, especially of the femoral head
What are key factors monitored in SLE management?
Anti-dsDNA,
Complement levels
Urinalysis
What heart-related complication can occur in babies born to SLE mothers?
Congenital heart block
What is the basic definition of Sjögren’s syndrome?
An autoimmune condition that destroys exocrine glands, causing dryness
What is the primary demographic affected by Sjögren’s syndrome?
Middle-aged females (9:1 ratio)
What glands are primarily affected in Sjögren’s syndrome?
Lacrimal (tear) and salivary glands
What are the main symptoms of Sjögren’s syndrome?
(1) Dry eyes
(2) Dry mouth
(3) Dry throat
(4) Vaginal dryness
(5) Joint pain
(6) Fatigue
What is a key eye symptom of Sjögren’s syndrome?
Gritty feeling in the eyes
What is the most specific antibody for diagnosing Sjögren’s syndrome?
Anti-Ro and Anti-La antibodies
What are common blood markers seen in Sjögren’s syndrome?
- Positive ANA, anti-Ro, anti-La, 2. 2. Raised IgG
- High ESR/plasma viscosity
What test may be done if antibodies are negative in suspected Sjögren’s syndrome?
Salivary gland ultrasound and biopsy
What medication can help with Sjögren’s syndrome sicca (dryness) symptoms?
Pilocarpine
Which drug can sometimes help with arthralgia and fatigue in Sjögren’s syndrome?
Hydroxychloroquine
What type of arthritis is associated with Sjögren’s syndrome as a complication?
Psoriatic arthritis
What is the primary management strategy for Sjögren’s syndrome?
Symptom control with tear and salivary replacements
What is systemic sclerosis?
Autoimmune inflammation and skin thickening (Scleroderma) due to increased collagen deposition
What are the peak incidence years for Scleroderma?
30-50 years
What are the two types of systemic sclerosis?
Limited systemic sclerosis (lSSc) and diffuse systemic sclerosis (dSSc)
What is the triad of symptoms in Scleroderma?
(1) Vascular changes
(2) Fibrosis
(3) Activation of the immune system
What is the primary manifestation of limited systemic sclerosis (lSSc)?
Skin involvement is usually confined to the face, hands, forearms, and feet
What is the association of antibodies with limited systemic sclerosis?
Anti-centromere antibody (ACA)
What is the association of antibodies with diffuse systemic sclerosis?
Anti-SCL-50 antibody and anti-RNA polymerase III association
Describe the difference between dSCC with ISCC
(1) Skin changes develop more rapidly
(2) Can involve the trunk
(3) Early significant organ involvement
(4) The Raynaud phenomenon often coincides with or follows the onset of other symptoms whereas in ISCC, the Raynaud phenomenon precedes the onset of other symptoms.
What is the difference between ISCC and dSCC?
Diffuse - above and below elbows and knees + face and trunk
Limited - only below elbows and knees + face
Symptoms of systemic sclerosis
(1) Thickening and hardening of the skin
(2) Sclerodactyly - thickening of the skin of the fingers and hands which can cause loss of dexterity of hands
What condition is characterized by vascular spasms that reduce blood supply to the fingers, especially in cold conditions?
Raynaud’s phenomenon
What colour changes occur in the fingers during a Raynaud’s episode?
- White (blanching)
- Blue (acrocyanosis)
- Red (reactive hyperaemia)
What are some common symptoms associated with Raynaud’s phenomenon?
(1) Multiple painful ulcers
(2) Fatigue
(3) Weakness
(4) Joint stiffness/ pain
What is the primary treatment recommendation for Raynaud’s phenomenon?
Keep the hands warm
Who is most commonly affected by primary Raynaud’s phenomenon?
(1) Teenagers with no underlying autoimmune disease - typically benign
How often should systemic sclerosis patients be screened for pulmonary complications?
yearly
What screening test is used to monitor for pulmonary arterial hypertension in SSc patients?
Echocardiogram
What medication is commonly used to treat Raynaud’s phenomenon in systemic sclerosis?
Nifedipine → calcium channel blocker
What uncommon, specifically defined condition features and symptoms also seen in other connective tissue diseases?
Mixed Connective Tissue Disease
What is a common vascular symptom in Mixed Connective Tissue Disease?
Raynaud’s phenomenon
What are the common joint symptoms associated with Mixed Connective Tissue Disease?
Arthralgia (joint pain) and arthritis
Which muscle-related condition can present in patients with Mixed Connective Tissue Disease?
Myositis (muscle inflammation)
What skin condition is commonly seen in patients with Mixed Connective Tissue Disease?
Sclerodactyly
= thickening and tightening of the skin on the fingers
What antibody is strongly associated with Mixed Connective Tissue Disease?
Anti-RNP antibodies
What medication may help treat Raynaud’s phenomenon in Mixed Connective Tissue Disease?
Calcium Channel Blockers
What regular monitoring should be done for patients with Mixed Connective Tissue Disease (MCTD) for pulmonary complications?
Annual echocardiograms for pulmonary hypertension and Pulmonary Function Tests (PFTs) for ILD
What autoimmune disorder is characterized by recurrent venous or arterial thrombosis and/or fetal loss?
Antiphospholipid Syndrome (APS)
What class of medication may be used in the management of Mixed Connective Tissue Disease (MCTD) to reduce inflammation?
Corticosteroids
What genetic factor is associated with Antiphospholipid Syndrome (APS)?
HLA-DR7 genetic predisposition
What is the difference between primary and secondary Antiphospholipid Syndrome?
Primary APS is more common in young females, while secondary APS occurs in association with systemic lupus erythematosus (SLE) or another autoimmune disorder
What are the common venous complications associated with Antiphospholipid Syndrome (APS)?
DVT and PE
What skin condition is associated with APS, presenting as a purplish, net-like discolouration?
Livedo reticularis
What type of pregnancy complications are common in Antiphospholipid Syndrome?
(1) Recurrent miscarriages, including late spontaneous fetal loss and recurrent early fetal loss
What neurological symptom is often experienced by patients with Antiphospholipid Syndrome (APS)?
Migraine
What is the first-line treatment for Antiphospholipid Syndrome (APS) involving thrombosis?
(1) Acute low molecular weight heparin (LMWH)
(2) Warfarin
(3) Aspirin prophylaxis
What is the management strategy for pregnant women with Antiphospholipid Syndrome (APS)?
LMWH and aspirin
What complication involving pregnancy is commonly associated with Antiphospholipid Syndrome (APS)?
Recurrent miscarriage
Which of the most specific antibodies for SLE?
Anti-double stranded DNA antibody
What does Lymphopenia mean and what is it associated with?
Low lymphocyte count
= SLE
What medication is always apart of the treatment for SLE?
Hydroxychloroquine
A 32-year-old woman is seen by her GP. She describes a rash on her face which she first noticed two years ago. The rash is intermittent and usually lasts for several weeks at a time. It is worse in the summer months. She denies any weight loss, fatigue, fevers or aches and pains of any sort. On examination there is a red scaly rash on her face, sparing the nasolabial folds.
What is the most appropriate treatment for this condition?
Hydroxychloroquine
When would a medication such as mycophenolate mofetil be used in regards to treating SLE?
Severe SLE
(eg) lupus nephritis
A 23-year-old woman recently diagnosed with antiphospholipid syndrome presents to the GP. She has just been discharged from the hospital with warfarin following a pulmonary embolism (PE) and would like some advice on how to prevent recurrence in the future.
She reports taking the combined oral contraceptive pill since she was 17 and smoking 10 cigarettes a day.
The GP advises her to switch to an alternative method of contraception. Explain why?
The combined oral contraceptive pill contains oestrogen, which is contraindicated in patients with antiphospholipid syndrome and a history of clots
What is the laboratory criteria to confirm the diagnosis of Antiphospholipid syndrome?
On at least 2 occasions at least 12 weeks apart, any of the following are positive:
(1) Anticardiolipin antibodies
(2) Anti-beta2-glycoprotein I antibodies
(3) Lupus anticoagulant
A 40-year-old woman visits her doctor complaining of pain and swelling in her right lower limb, which has worsened over the past week. On examination, her right calf is erythematous, warm and 5cm in diameter more swollen than the left calf. The patient has a past medical history of systemic lupus erythematosus (SLE) and two previous miscarriages.
What blood test is the most useful in determining the underlying cause of this patient’s deep vein thrombosis?
Anticardiolipin antibody
A 42-year-old female is referred to a rheumatology clinic by her GP as she has been complaining of dry eyes and dry mouth. This means it can be difficult to swallow food sometimes, and she has also required courses of nystatin in the past.
What test may be used to help confirm the likely underlying cause?
Schirmer’s test
A 32-year-old female attends her GP as she has developed a rash on her face on both cheeks which is worse after sun exposure. She is also complaining of non-specific joint pains. She has no other past medical or drug history. On examination, the GP notes mucosal ulcers.
Which antibody is most likely poistive and why
Anti-nuclear antibody (ANA)
=
Anti-nuclear antibodies are positive in over 95% of SLE patients.
Anti-double-stranded DNA (dsDNA) autoantibodies are a subgroup of ANA.
dsDNA is more specific but only positive in around 60% of SLE patients
A 41-year-old female with a history of antiphospholipid syndrome (APS) is seen by her rheumatologist post-hospital discharge. She was admitted to hospital for 6 days after suffering from a deep vein thrombosis, likely related to her APS.
Which is the most appropriate anticoagulation management?
Warfarin, INR 3-4
A 34-year-old female with long-standing systemic lupus erythematosus (SLE) presents to A&E with a red, swollen, painful left leg. On examination, her observations are normal and her legs have a lacy, mottled appearance. A FBC shows thrombocytopenia.
What investigation findings is consistent with the most likely diagnosis?
Positive anti-cardiolipin antibody
A 35 year old Afro-Caribbean woman with known Systemic Lupus Erythematosus (SLE) attends the Rheumatology clinic for her regular review. She had initially presented with a photosensitive malar rash which spared the nasolabial folds. She denies any joint pain. She was anaemic and her dsDNA antibody titres were markedly raised.
What bedside test needs to be done for her in the clinic?
Urine dipstick test
A 42-year-old woman presents to rheumatology following 18 months of fatigue and pain in multiple joints. She presents today as she developed a facial rash after returning from a holiday in Spain. On examination, she has an erythematous well-demarcated rash with scales on her face and neck. She has no proximal muscle weakness.
Given the most likely diagnosis, what is the next best investigation?
Urinalysis
If the urinalysis screen is abnormal and you suspect the patient has SLE. What is the next step?
24h urine collection
What is the most commonest pattern of psoriatic arthritis?
Asymmetrical oligoarthritis - 60%
A 41-year-old female with a background of systemic lupus erythematosus is seen by her rheumatologist because she has started noticing colour changes and numbness in her hands when she is exposed to the cold. Her doctor suspects that she has developed Raynaud’s phenomenon.
What is the first-line treatment for Raynaud’s phenomenon?
Calcium Channel Blockers
= Nifedipine
An anti-histone antibody was found positive. What could this potentially mean?
Drug-induced lupus
A 40-year-old male presents with pain and swelling in his right leg. His swelling started a month ago and had gradually become worse, followed by pain and black discolouration. He denies any history of recent surgery, prolonged immobilisation or long-haul flights. He has no comorbidities except for one episode of transient ischaemic attack 2 months ago and a history of hospitalisation a year ago due to DVT on the same leg. He was commenced on Aspirin but he was not compliant.
As part of his investigations, his clinician orders serum lupus coagulant, anti-cardiolipin antibody and anti–β2-glycoprotein 1 antibodies.
What additional test should be requested to exclude a false positive result? and why?
Treponemal serology
= Syphilis can cause false-positive results for antiphospholipid antibodies such as lupus coagulant, anti-cardiolipin antibody, and anti–β2-glycoprotein 1 antibodies
What disease is the anti-Scl-70 antibody highly specific for?
Scleroderma
A 34 year old man comes to the GP in winter, because his fingers get painful in the cold. He also describes paraesthesia in his fingertips. On examination in the consultation room, you notice dilated capillaries at the nailbeds. There is no colour change at the fingertips but he describes a demarcated line beyond which his fingertips turn pale in cold weather. He has attended the GP 3 times in the last month with cramping pain in the sole of his feet. His history is significant for smoking (60 pack years). On examination the pedal pulses are absent.
What is the most likely diagnosis?
Beurgers disease
= secondary to Raynaud’s phenomenon
Which marker is not used to monitor disease activity in patients with SLE?
ENA antibody
A 34-year-old woman presents with painful hands, especially during the winter. She describes her fingers changing colours from white to blue to red.
What medication should she avoid?
Propanolol
A 24-year-old college student presents to the hospital with generalised body swelling, symmetrical joint pain, colour changes of the fingers and facial rash. She has elevated blood pressure of 170/90 mmHg.
What is the most suitable medication to control her hypertension?
ACE or ARB
A 50-year-old woman complains of dry mouth and a gritty sensation in her eyes. She also noticed intermittent joint pain in her fingers.
Which would be the most definitive test to confirm her diagnosis?
Salivary labial gland biopsy
Explain what is lupus nephritis
Lupus nephritis is a kidney inflammation caused by systemic lupus erythematosus (SLE), an autoimmune disease. The immune system attacks the kidneys, leading to symptoms like swelling, high blood pressure, and protein in the urine
A 52-year-old male presents to his GP with a 4-week history of tiredness, generalised muscle aches, and pain in his hands and feet. He is not taking any medications. On examination, there is slight swelling and tenderness in his MCP’s and PIP’s. There is also a slight symmetrical red rash over his cheeks. His observations are: T 37.7, BP 130/90, HR 80, RR 16, O2 99% on air.
Given the most likely diagnosis, which autoantibody is most likely going to be positive and why
Anti-dsDNA
= Anti-dsDNA is specific to SLE. This patient likely has SLE due to the characteristic malar (butterfly) rash over his cheeks in combination with systemic illness and a mild arthritis/arthralgia
A 50-year-old female presents to her General Practitioner with a 6-month history of bloating, watery stools and generalised abdominal discomfort.
Abdominal examination reveals no abnormalities. However, she has a bluish discolouration of her peripheries.
What is the next best investigation to evaluate the underlying diagnosis? and why have you chosen that answer?
Anti-centromere antibodies
= This patient has CREST syndrome features, including calcinosis, secondary Raynaud’s phenomenon, gastrointestinal dysmotility, sclerodactyly and telangiectasia. Her symptoms of malabsorption are likely due to small bowel bacterial overgrowth due to intestinal hypomotility
pulmonary arterial hypertension but its a connective tissue disorder
systemic sclerosis
antiphospholipid syndrome commonly occurs secondary to what?
SLE
A 30-year-old woman presents to her GP with a four-week history of worsening pain and stiffness in her hands.
Her past medical history includes a five-year history of Raynaud’s phenomenon which she manages conservatively with gloves and hot water bottles in cold weather. She also was recently started on omeprazole for difficult-to-manage gastroesophageal reflux.
On examination, you note sclerodactyly bilaterally with a small ulcer on the tip of the fourth finger on the right. On the face, there are diffuse telangiectasia and microstomia. She is otherwise systemically well.
Why is the correct diagnosis for this condition limited cutaneous systemic sclerosis and not diffuse cutaneous systemic sclerosis?
Patients with diffuse cutaneous systemic sclerosis tend to present more acutely with widespread skin and organ involvement
The combination of a relatively indolent history of skin tightening limited to the hands and face, along with GORD is more suggestive of limited cutaneous versus diffuse cutaneous disease
Pulmonary hypertension is a well known complication for which connective tissue disorder?
Systemic sclerosis, especially the limited cutaneous (also known as CREST syndrome) subtype
Diffuse cutaneous SSc tends to cause pulmonary fibrosis instead
A 45-year-old woman presents with Raynaud’s phenomenon, skin thickening on her hands and face, and dysphagia. She is otherwise well, and her past medical history includes raised cholesterol and hypertension. There is a family history of psoriatic arthritis and vitiligo.
What investigation finding is most specific for the likely diagnosis?
Anti-Scl-70 antibodies
A 58-year-old female with longstanding diffuse cutaneous systemic sclerosis (SSc) presents to A&E with a severe headache. On examination, her observations are: T 37.6, BP 200/120, HR 89, RR 17, SaO2 98% on air. U&E’s show Urea 9.1, Creatinine 201.
Given the most likely diagnosis, what is the most appropriate initial management?
ACE inhibitor - pril
What is Hypromellose?
acts as artificial tears and are applied as eye drops to soothe eyes
INR of 3-4 is a target for what?
recurrent thrombosis
A patient has SLE symptoms and has just experienced pulmonary TB. What autoantibody would this patient most likely have present in their bloods?
Anti histone
A ‘full house’ pattern refers to glomerular deposits that stain dominantly for IgG, IgA, IgM, C3 and C1q- five major stains on a renal biopsy are all positive
What does this describe
lupus nephritis
A patient presents with unexplained thrombosis and recurrent pregnancy loss; given the most likely diagnosis, which clotting test may be prolonged?
Activated partial thromboplastin time (aPTT)
