Connective tissue diseases Flashcards
(107 cards)
What is the prevalence of common CTD worldwide?
RA
- 16% in women
- 44% in men
Global2
0.24% (of 291 conditions studied, RA was ranked as the 42nd highest contributor to global disability, just below malaria and just above iodine deficiency)
Total (direct, indirect, and intangible) annual societal costs
>39 billion USD
SLE
Malaysia
43/100,000 overall
uk
28 per 100,000
estimated patient group of 10500 in England and Wales
Racial/gender differences
Afro-Caribbean women 206 per 100,000
SLE is 8 to 10 times more common in women than in men
globally
40-100 per 100,000
global burden
Total 12-month direct costs for all patients withSLEamount to more than US$207 million ($13,305 per patient)
Primary Sjogrens 250 per 100,000(commonest)
Systemic sclerosis 20 per million
Polymyositis/Dermatomyositis 5 per 100,000
MCTDincidence 2 persons per 100,000 person-years
What are the impact and outcomes of RA?
Physical and work disability
Almost 40 percent of patients with RA will have work disability within 10 years of diagnosis
Reduced quality of life
Joint replacement surgery
Up to 25% of patients with RA will have a joint replacement in the 20 years after disease onset
Development of other chronic diseases
Cardiovascular disease, lung diseases, psychiatric disorders, osteoporosis and fractures, and some malignancies (eg lymphoma, lung and non-melanotic skin cancers)
Premature mortality compared with the general population
cardiovascular disease, respiratory disease, and cancer leading causes of death in RA
What are the issues with epidemiological data for CTD(especially RA)
Data (US centric)
Recognition
Impact in developing countries
Impact of new therapies
What is mixed connective tissue disease?
Mixture of RA, SLE, Myositis, Scleroderma
Raynauds, digital ulcers Puffy hands Fatigue Muscle Involvement Skin Arthritis ILD-interstital lung PAH
What Investigations are done for mixed connective tissue disease?
It does have its own antibody…………………. RNP Anti-U1 RNP Higher incidence If RNP antibody positive checg for EROSIVE ARTHRITIS PAH -CXR for ILD
How does Antiphospholipid syndrome manifest and what are the complications?
Antiphospholipid syndrome (APS)
Pathophysiology
Antibodies to cell membrane phospholipids.
Presentation
CLOT:
Arterial (cerebral, renal) and venous (PE)CLOTs. Recurrent PEs may lead to pulmonary hypertension.
Coagulation defects.
Livedo reticularis.
Obstetric problems: recurrent miscarriage.
Thrombocytopenia
In most cases it is a standalone condition, but it affects 25% of SLE patients.
Hypercoagulability and recurrent thrombosis can affect virtually any organ system, including the following:
Peripheral venous system (DVT)
CNS (stroke, sinus thrombosis, seizures, chorea, reversible cerebral vasoconstriction syndrome)
Obstetric (pregnancy loss, eclampsia)
Pulmonary (PE, PH)
Dermatologic (livedo reticularis, purpura, infarcts/ulceration)
Cardiac (Libman-Sacks valvulopathy, MI, diastolic dysfunction)
Ocular (amaurosis, retinal thrombosis)
Adrenal (infarction/hemorrhage)
MSK (AVN of bone)
Renal
(thrombotic microangiopathy)
What is the diagnostic criteria for antiphospholipid syndrome?
At least one clinical and one lab criteria
Clinical
Vascular thrombosis
Pregnancy morbidity
≥1 late-term spontaneous abortions
≥1 premature births of a morphologically healthy neonate at or before 34 weeks’ gestation because of severe preeclampsia or eclampsia or severe placental insufficiency
≥3 unexplained, consecutive, spontaneous abortions (<10 weeks’ gestation)
Lab criteria
Elevated levels of immunoglobulin G (IgG) or immunoglobulin M (IgM) anticardiolipin (aCL) Anti–beta-2 glycoprotein I
Lupus anticoagulant
On at least two occasions at least 12 weeks apart
What DMARDS are safe to use in pregnancy?
Hydroxychloroquine in all SLE pregnancies
Azathioprine is safe in pregnancy
In severe refractory maternal disease consider pulsed iv methylprednisolone, IVIG or 2nd or 3rd
trimester cyclophosphamide
Withdraw known teratogens
Mycophenolate, methotrexate and cyclophosphamide
What maternal antibodies need to checked in pregnancy and why?
Maternal Ro/La should be checked due to the 1-2% risk of foetal congenital heart block. If positive, a foetal cardiac scan should be performed at 16-20 and 28 weeks gestation.
How can Antiphospholipid syndrome be investigated & managed?
Investigations
Coagulation:
Paradoxical ↑aPTT: proteins are anticoagulant in vitro, but pro-thrombotic in vivo. Normal PT. Same pattern seen in heparin use and clotting factor deficiencies.
Follow with mixing study. In a factor deficiency, clotting will be normalised, but in APS it will remain abnormal.
Antibodies:
Anti-cardiolipin IgG/M.
Lupus anticoagulant test: looks for clotting pattern characteristic of presence of lupus anticoagulant IgG/M. ‘Anticoagulant’ refers to in vitro property, as in vivo it’s pro-thrombotic.
Anti β2-glycoprotein IgG/M.
Diagnosis
{Clotsormiscarriage >10 weeks} plus {Ab +ve (any antibody) on 2 occasions}.
Management
Manage vascular risk factors: smoking cessation, weight loss, exercise, blood pressure and lipid control.
Aspirin for primary prevention of arterial thrombosis and obstetric complications, though evidence of benefit is mixed.
If thrombosis occurs, give LMWH followed by long-term warfarin. Prednisolone, IVIG, or rituximab can be used if anticoagulation is insufficient.
During pregnancy: aspirin once pregnancy confirmed and LMWH once fetal heart visualised.
What Conditions give the following patterns on immunofluorescence
1) Homogenous
2) Speckled
3) Nucleolar
4) Centromere
1)Homogenous
DsDNA-SLE
Histones-DLE,Autoimmune hep
2)Speckled
RNA polymerase-Diffuse SS Scl-70-Diffuse SS Anti sm-SLE,drug induced SLE RO-Sjogens LA-Sjogrens 3)Nucleolar-SS and polymyositis 4)Centromere-Limited ss
What is Sjorgen’s Syndrome
Sjogren’s syndrome
Background
Pathophysiology
Autoimmune disease characterised by lymphocytic infiltration of exocrine glands, especially salivary and lacrimal.
Extraglandular manifestations also occur, due to vasculitis and lymphocytic infiltration of other organs.
Classification
Primary Sjögren’s syndrome: standalone condition.
Secondary Sjögren’s syndrome: SS in the presence of another (usually autoimmune) disease, most commonly RA (30% of RA patients), SLE (20%), systemic sclerosis (50%), or primary biliary cirrhosis (10%).
Epidemiology
Affect 0.1-4%
Like many autoimmune conditions, it is commoner in women (x10) and middle age
What are the clinicals manifestations of Sjorgens and what are they at risk of?
Presentation
Sicca symptoms (Latinsiccus= dry) are the commonest manifestation:
Dry eyes (‘keratoconjunctivitis sicca’ or ‘xerophthalmia’), often described as ‘gritty’.
Dry mouth (‘xerostomia’). Can lead to eating difficulty, salivary stones, dental caries, and candidiasis.
Other features:
Parotid enlargement.
Dryness of other mucous membranes: respiratory tract (→cough), GI tract (→dysphagia), vagina (→dyspareunia).
Extraglandular presentations: arthralgia, fatigue, lymphadenopathy, interstitial lung disease, polyneuropathy, renal tubular acidosis, thyroid disease, pancreatitis.
Fatigue
Skin features: dryness (‘xerosis’), purpuric rash, Raynaud’s, annular erythema.
Non-Hodgkin’s lymphoma: >18.9x commoner than general population
20 fold increase in lymphoma
What are the differentials for wlSicca syndrome?
DDx: Sicca symptoms
Age-related gland atrophy. Commonest cause.
Drugs: anticholinergics, antihistamines, sympathomimetics, benzodiazepines, antidepressants, opioids.
Sjogren’s syndrome.
Parotid infiltration: sarcoidosis, lymphoma/leukaemia.
Infection: hepatitis C, HIV.
What Investigations and management are done for Sjorgen’s
Diagnosis and investigation
Diagnosis requires all 3 of:
Subjective dry eyes and/or mouth.
Objective evidence of dry eyes and/or mouth. Tests of dry eyes include Schirmer’s test of tear function (filter strip under eyes), or ocular surface staining (Rose Bengal, lissamine green, or fluorescein). Tests of ↓salivary production include whole sialometry (spit into test tube), parotid sialography, or salivary scintigraphy.
Serological or histopathological evidence of SS. Diagnostic autoantibodies are anti-Ro/SS-A (50%) and anti-La/SS-B (35%). Biopsy of minor salivary glands may show focal lymphocytic sialoadenitis.
Other investigations:
Basic bloods: ↓Hb (20%), ↑ESR/CRP (30%).
Non-diagnostic autoantibodies: ANA (70%), RF (50%).
Others immunological features:screen development of lymphoma ↑gammaglobulins, ↑cryoglobulins, ↓complement.
Management
Lifestyle and preventative:
Regular fluid sips and chewing gum.
Good oral hygiene.
Avoid exacerbating drugs, including smoking and alcohol.
Medical:
ACR/EULAR criteria for diagnosis- BSR management guidelines
Sicca symptoms-
Dry eye- tears/stimulants
Dry mouth- sugar free pastilles, artificial saliva, oral hygiene
Dry skin- moisture
Dry vagina- vaginal creams
Lung involvement- Prednisolone/DMARDs/Cyclophosphomide/ Rituximab
Neurologic involvement- conservative management and systemic treatments
Cytopenias- Cyclosporine/ Systemic
What are the risk factors for Raynaud’s ?
6 -10%population
F > M
Raynaud phenomenon manifests as recurrent vasospasm of the fingers and toes and usually occurs in response to stress or cold exposure
In individuals with Raynaud phenomenon, one or more body parts experience intense vasospasm with associated color change and subsequent hyperemia. Patients often describe 3 phases of change with intial white (vasoconstriction), followed by blue (cyanosis), and then red (rapid blood reflow). The affected body parts are usually those most susceptible to cold injury. A clear line of demarcation exists between the ischemic and unaffected areas (see the image below).
Progressive systemic sclerosis including the diffuse and limited
SLE
Mixed connective tissue disease
DM and PM
RA
Sjögren syndrome
Vasculitis
Primary pulmonary hypertension
Episodic vasospasm of extremities triggered by:
COLD
Emotional Stress
Primary - common
Secondary - multiple causes
Caused by reversible constriction of small arteries, capillaries arterioles and venules.
Associated with many Connective Tissue Diseases
What are the 2 main types of systemic sclerosis and how they present?
Limited cutaneous systemic sclerosis (lcSSc): skin fibrosis restricted to hands, distal arms, face, and neck.
Diffuse cutaneous systemic sclerosis (dcSSc): skin fibrosis includes chest, abdomen, and upper arms. Internal organ disease more common.
Epidemiology
1/10,000 UK prevalence.
5x commoner in women.
Peak onset in 40s.
Diffuse
Scl-70, RNA polymerase III
Raynauds Digital ulceration Diffuse skin thickening ILD GI Renal(RNA polymerase III associated with scleroderma renal crisis) Cardiac
Limited
Anti centromere
Calcinosis Raynauds oEsophageal (GI general) Sclerodactly Telangiectasia Scleroderma of neck and face PH Fibrotic lung disease Mild GI disease
How does systemic sclerosis present?
Presentation
Thickened, firm, tight skin (scleroderma):
Commonly affects the fingers, ‘sclerodactyly’. May lead to finger flexion contractures. Other finger changes in SSc include abnormal nailfold capillaries, fingertip pitting scars or ulcers, and puffiness. Similar changes seen in toes.
In the face, it can lead to microstomia (small mouth).
May be pruritic.
Often has a shiny appearance, and skin may become hyper/hypopigmented.
In addition to the GI tract, almost any internal organ can be affected, including:
Lungs: interstitial lung disease (SOB, cough, crackles), pulmonary hypertension.
Kidneys: scleroderma renal crisis, presenting with AKI, hypertension, and microangiopathic haemolysis or thrombocytopaenia.
Heart: heart failure (esp. RHF due to pulmonary HTN), pericardial disease, myocardial fibrosis, arrhythmias.
Connective tissue disease:
Tendon or bursal friction rubs.
Arthritis
Sicca symptoms: dry mouth, dry eyes.
Carpal tunnel syndrome.
Muscular pain/cramps. May be due to inflammatory myositis.
Non-specific symptoms, including fatigue, weakness, and sleeping difficulties, are also common.
What investigations are done for Systemic sclerosis?
Investigations
Diagnosis
Diagnosis requires presence of bilateral finger skin thickening, or a combination of other clinical features and auto-antibodies. Skin thickening which spares the fingers is unlikely to be SSc.
90% are anti-nuclear Ab +ve, including the following sub-types:
Anti-centromere Ab (50%). Associated with lcSSc.
Anti-Scl-70, aka anti-topoisomerase I (30%). Associated with dcSSc.
Anti-RNA polymerase III (20%).
Capillaroscopy – magnified nailfold visualisation to look for abnormal capillaries – can aid diagnosis.
Assessing disease extent
Basics bloods:
FBC: Hb may be low due to GI bleeding.
↑ESR/CRP suggests ongoing inflammation.
Organ involvement:
Kidneys: U&E, urinalysis.
Heart: ECG, echo.
Lungs: PFTs, CXR, CT chest.
GI tract: barium swallow, endoscopy.
How is systemic sclerosis managed?
Management
Skin and connective tissue disease:
Skin thickening: cyclophosphamide, methotrexate, or mycophenolate mofetil. Emollients or antihistamines for itch.
Raynaud’s: 1st line calcium channel blockers (e.g. amlodipine), 2nd line add/switch to PDE-5 inhibitors (e.g. sildenafil, tadalafil).
Calcinosis: consider surgical resection if severe.
Internal organ disease:
Oesophageal dysmotility: PPIs, prokinetic agent (e.g. metoclopromide, erythromycin).
Scleroderma renal crisis: ACEi, renal replacement therapy if severe.
ILD: cyclophosphamide, transplantation if severe.
Pulmonary HTN: PDE-5 inhibitor,endothelin receptorantagonist (bosentan, ambrisentan, macitentan).
Ongoing inflammation (synovitis, myositis, arthritis): low dose steroids.
Prognosis
dcSSc: 30% 10 year mortality, usually due to internal organ involvement, especially the lungs.
lcSSc: better prognosis, but requires monitoring for progression to diffuse disease.
What are the causes of secondary vasculitis?
Rheumatological
SLE
Rheumatoid arthritis
Sjogren’s syndrome
Malignancy
Haematological
Para-neoplastic
Drugs hydralazine propylthiouracil allopurinol sulfasalazine penicillamine
Infection (Direct damage to vessel wall) Steptococcus Staphylococcus Syphilis Rickettsia
Infection (immune complex) HIV Hepatitis B Hepatitis C!
What are eye symptoms of vasculitis?
Episcleritis is present in the superficial layers of the nasal portion of the eye, causing tenderness and discomfort. The patient has rheumatoid arthritis, but this reaction is nonspecific and occurs in other disorders.
Anterior uveitis is present. Although blindness can arise from anterior uveitis, this complication is much more common in posterior uveitis, which affects the vitreous body and retina.
The dark area in the sclera is typical of the scleromalacia. This darkening results from thinning of the sclera, which allows the pigment of the underlying choroid to be seen. Inflammatory manifestations such as episcleritis, scleritis, conjunctivitis, and iritis may precede scleromalacia.
Other disease with uveitis= Ankylosing spondylitis: iridocyclitis with synechiae
Ciliary injection and irregularity of the pupil are present. Adhesions between the iris and lens (synechiae) appear at the 1-o’clock and 4-o’clock positions. Synechiae are caused by repeated episodes of iritis and may eventually lead to glaucoma and blindness. The pupil is dilated from medication. The medial aspect of the sclera has been blanched by topical medication.
What are specific features of a vasculitic rash
Vasculitic ulcers can have quite specific features–deep,punched out appearance,painful,purpura associated,edges are bluish or redish
What are the red flags of mimics of vasculitis
Presence of a heart murmur Necrosis of lower extremity digits Splinter haemorrhages Prominent liver dysfunction History of recreational drug use History of high-risk sexual activity Prior diagnosis of neoplastic disease Unusually high fevers
mimics
Multiple myeloma Antiphospholipid Infective endocarditis Paraneoplastic syndromes Athermoatous vascular disease Cocaine and amphetamine use atheroembolic disease Hypersensitivity reactions Genetic(Marfans)
