Multisystem Flashcards
Natural Hx of SLE
Chronic inflammatory mulitsystem AI disease which releases and remits. Natural progression of the disease and its treatment leads to comorbidites.
Increased rate of atherosclerosis, malignancy and infections
Epidemiology of SLE
10:1 women:men, 20/100000
Increased incidence in afrocarribeans 16-40 y/o
HLADR2 and 3
Aetiology of SLE
Homozygous deficiencies of C1q, C2 or C4 confer a high risk but are very rare
24% risk in monozygotic twins
Seen in premenopausal women more
Viruses and UV can both trigger flares
Pathogenesis of SLE
Cell death is triggered via viral illness, UV light, smoking and occurs via apoptosis leads to DNA and histone presentation on the cell surface. These are interpreted as foreign antigens and phagocytosed . In SLE this process is inefficient leading to APC presenting the cell fragments to T cells which intern activate B cells to produce antinuclear antibodies. These form circulating complexes or deposit in tissues leading to complement activation and influx of neutrophils. This perpetuates the response
PC SLE - Bones and non specific
Most patients suffer non specific fatigue, fever, symmetrical small join arthralgia with pain but structurally normal joints +/- some swelling
Discoid lupus
Confined to the skin, rash appears on the face as a well defined erythematous plaque that progresses to a plaque and pigmentation
SLE and the skin
Photosensitive rash with a butterfly distribution over the bridge of the nose.
Vasculitic lesions on the finger tips, purpura and urticaria
Livedo reticularis
Scarring alopecia can = irreversible bald patches
Raynauds - 20%
Oral and mucosal ulcers
Jaccouds arthritis
Deforming non erosive arthropathy characterised by ulnar deviation of the second to 5th fingers with MCP subluxation.
SLICC Critera for SLE
Need > 4 criteria (1 clinical and 1 lab)
or
biopsy proven lupus nephritis with +ve ANA or antidsDNA stain
Lung and Heart SLE
Pleurisy and recurrent exudative pleural effusions. These can lead to restrictive lung disease
Pericarditis and pericardial effusions (25%). Increased risk of IHD and strokes due to HTN, hypercholestrolemia and chronic inflammation
Very rarely there may be myocarditis - arrhythmias, aortic valve lesions and a non infective endocarditis (Libman-Sachs syndrome)
Renal and SLE
Risk of lupus nephritis a RPGN which can lead to end stage renal failure. Screening with urine dipstick for proteinuria and haematuria is crucial
Nervous system and SLE
60% of cases may be mild depression but occasionally more severe psychotic features
Epilepsy, seizures, migraine, ataxia, aseptic meningitis etc
Raynaud’s disease
Peripheral digital schema often precipitated by cold or emotion.
PC = digit pain can be very severe
white to blue to red
In severe cases can = digital infarction and self amputation
Aetiology of raynauds
1 - Raynauds phenomenen
2 - SLE, RA, Sjogrens, systemic sclerosis, polymyositis
Obstructive causes - Buegers, takayasu’s atherosclerosis
B-blockers, occupational drugs involving vibration
Mx Raynauds
Look for a diagnosis! Gloves stop outdoor work, CCB’s - DHP i.e. nifedipine or ACEi
O/E SLE
Hands - raynauds, thickening of the flexor tendons
Lymphadenopathy
Diffuse scarring alopecia, discoid or photosensitive rash
Oral or mucosal ulcers
BP and urine dip to check for lupus nephritis
Investigations SLE
High ESR,
Leucopenia, lymphopenia +/- thrombocytopenia
Normocytic anaemia of chronic disease or AIHA
Low C3 and C4 complement in acute disease
Biopsy = deposition of IgG and complement
Autoantibodies in SLE
95% ANA +ve but poor sensitivity seen in old age and increased in many other AI conditions
anti-dsDNA high specificity - homologous pattern of staining
Anti smith - increase prevalence in black african populations
SLE and Sjogrens
Anti Ro70 and Ro52 showing a speckled ANA pattern and Anti Ui RNP showing nuclear ANA pattern are linked to an increased risk of Sjogrens and high risk of Ab crossing the placenta and causing congenital heart block and rash in foetus
Drug induced SLE
Sulphasalazine, procaimide, antieplieptics all anti-histone +ve
Anti-TNF = anti dsDNA +ve
Mx of SLE
Immunosuppression - hyrdroxychoroquine and NSAIDs
IV steroids for acute flares (prednisolone and cyclophosphamide)
Monitor anti ds-DNA and C3/C4 levels - sensitive for relapse
Check urine for evidence of lupus nephritis
Reduce risk of IHD and osteoporosis
Lofgrens syndrome
Subtype of sarcoidosis. Arthralgia, bilateral hilarlympadenopathy and erythema nodosum
Antiphospholipid syndrome PC
Thrombosis
Recurrent miscarriage
Livedo reticularis
Thrombocytopenia, high APT, +ve Coombs test
20% of pt suffer ischemic strokes, 40% DVTs. 27% of women who have 2+ spontaneous miscarriage = anti phospholipid syndrome
SLE and preganacys
Hydroxycholoquine and azathioprine, low dose steriods are safe. Beware those with anti-Ro and La. 2% risk of fatal heart block
Aetiology of antiphospholipid
70% = idiopathic 30% = SLE
Autoantibodies in APS
Anti-cardiolipin - Detects antibodies that bind to the negatively charged phospholipid cardiolipin
Lupus anticoagulant - Caused by anti phospholipid antibodies causes increased APTT (opposite effect to within the body)
Anti B2 glycoprotein
Mx APS
Aspirin
If recurrent thrombosis = anticoagulation with warfarin INR 3.5
Vasculitis
Inflammation of the blood vessels often characterised by multi-system involvement, fatigue, wt loss. Classified by size of vessels effected and the presence of ANCA
Large cell vasculitis
GCA and takayasu’s
Giant cell arteritis
Inflammatory granulomatous arteritis of the large cerebral arteries. Seen above the age of 50, 2:1 female:male, highest incidence in northern europe.
PC GCA
Often debilitating bitemporal headache - not improved by analgesia, lasts the whole day
Ocular symptoms
Scalp tenderness, neck ache, jaw claudication
Systemically - wt loss, fever, limb claudication due to subclavian stenosis, abdo pain SMA stenosis, HTN
Ocular symptoms in GCA
Amaurosis fungax - temporary blindness , reduced visual acuity, RAPD, reduced colour vision and visual field defects
O/E - diffuse pale optic disc swelling, cotton wool spots - nerve ischemia
60% due to arctentic anterior ischemic optic neuropathy this occludes the posterior ciliary vessels leading to infarction of the optic nerve head
Complications of GCA
Increased risk of thoracic aneurysms
Stenosis of cerebral and subclavian arteries
Ischemic consequences of coronary and mesenteric arteries
Investigations into GCA
ESR >50
Normocytic anaemia, thrombocytopenia
Deranged LFTs - high ALP
USS doppler - Black halo sign shows vessel ischemia, , loss of radio-echo signal = infiltrate and oedema
Biopsy in GCA
From affected side. Inflammatory infiltrate from T cell, B lymphocytes and giant cell. Can be -ve biopsy due to skip lesions
Central retinal artery occlusion
Rapid visual loss, reducing acuity and RAPD.
O/E = cherry red spot @ fovea due to alternate blood supply
Diagnostic criteria of GCA
Age >50, new headache, temporal artery abnormality, ESR >60, +ve biopsy
Mx GCA no visual symptoms
60mg prednisolone
Mx GCA + visual symptoms
3 days methyprednisolone 0.5-1g stat
Steroids in GCA
Reduced the dose by 5mg every 2weeks, as the dose gets lower the dosing interval should shrink to 1mg
SE = wt gain, infection, cataracts, skin fragility and purpura, mood changes, proximal weakness, Cushings, osteoporosis
Polymyalgia rheumatica PC
Sudden onset severe pain and stiffness in the muscles of the shoulders and the neck. Often symmetrical crucially with no muscle weakness. Worse in morning lasting from 30 mins to several hours.
1/3rd of its have wt loss, fever, lethargy and depression
Invx in to PMR
high ESR, ALP
normal CK
possibly a normocytic anaemia
Diagnostic criteria of PMR
Morning stiffness > 45mins = 2 Rh or anti-CCP -ve = 2 Pelvic girdle pain = 1 No other painful joints = 1 USS changes @ shoulders = 1
Takayau’s arteritis PC
Isolated aortitis with granulomatous nodules. Young japanese females
Pre vasculitis stage of fever, fatigue, wt loss
PC - vascular bruits @ carotids and abdo vessels
renal artery stenosis = HTN
diminished or absent pulses in arms due to complete stenosis
upper limb claudication with BP difference >20mmHg
symptoms of visual loss and dizziness if involving the carotids
coronary artery involvement = HF and aortic root dilation
Mx Takayasu’s
CT PET to show areas of inflammation
Immunsupression with methotrexate
Medium vessel vasculitis
Polyarteritis nodosa
Polyarteritis nodosa (PAN)
Seen in middle aged men, no ANCA association; 30% of cases are linked to hep B
PC PAN
Constitutional symptoms of fever, malaise, wt loss and myalgia
Acute features
Neuro - mononeuritis multiplex due to arteritis of the vasa nervorum
Skin - subcutaneous haemorrghe and gangrene. In chronic cases persistent livedo reticularis
Cardiac - can = MI, pericarditis and HF
Abdo - most common 1/3rd can mimic pancreatitis, appendicitis. GI haemorrhage due to mucosal ulceration
Invx and Mx PAN
Anaemia, leucocytosis and a raised ESR
Mx = corticosteriods
Kawasaki’s PC
Acute systemic vasculitis.
fever lasting >5 days, bilateral conjunctival congestion, dryness and redness of the lips and oral cavity
cervical lymphadenopathy
Polymorphic rash
Redness and oedema of the palms and soles 2-5 days after onset
Mx = single stat dose of immunoglobulin 2g/kg
Small vessel vasculitis
ANCA associated = GPA, eGPA, MPA
Immune complex associated (ANCA -ve)
= SLE, anti-GBM, HSP, cryoglobulinemia
Pulmonary renal syndromes
SLE, Goodpastures, GPA, MPA
Vasculitic signs and symptoms
Non specific - wt loss, fever, night sweats
Skin - purpuric rash - painful and non-blanching
digital infarction - terminal capillary
livedo reticularis
oral and nasal ulcers and polyps
ENT - Epistaxis, crusting, sinusitis, hoarse voice, can get a saddle shaped nose deformity due to loss of nasal cartilage
Eyes - Episcleritis - red eye ball, pain and photophobia, tis is also seen in RA, IBD and systemic vasculitis. Can lead to scleromalacia where the pigment of the underlying choroid can be seen
MSK - arthralgia, myalgia and muscle wasting
Abdo - Iron deficiency anaemia from GI blood loss, abdo pain, diarrhoea and intestinal obstruction
Cardio and resp - Pain, SOB, haemoptysis - pul haemorrhage
Neuro - transverse myelitis, peripheral neuropathy, mononeuritis multiplex
Mono-neuritis multiplex
Simultaneous involvement of individual nerve trunks evolving over days to years. Acute/subacute sensory and motor loss of individual neurones
Causes = DM, vasculitis, SLE, sarcoid
Granulomatosis with polyangitis (GPA) PC
Upper airway disease - recurrent sinusitis and epistaxis, can lead to destruction of the nasal cartilage = saddle shaped nose deformity. Bronchial/tracheal stenosis
Pulmonary parenchymal disease - granuloma formation leads to cough, SOB and pleuritic chest pain - can lead to pulmonary haemorrhage
- CXR multiple nodules, consolidation and ground glass
Renal - RPGN
Eyes - scleritis and conjunctivitis
Invx GPA
PR3 +ve in 90%, biopsy - granulomatosis inflammation in vessel walls,
Microscopic polyangitis (MPA) PC
Never URTI involvement. Usually presents with RPGN and skin involvement - maculopapular purpura. Has a higher incidence of neurological involvement.=
Low incidence of pulmonary parenchymal disease but high risk of pulmonary haemorrhage.
Inv MPA
Mixed picture MPO (p-anca) +ve in 90%, can have +ve c-anca PR3 in 20% of cases
Crucially on biopsy = no granulomas
Eosinophilic granulomatosis with polyangitis PC
Early adulthood onset allergic rhinitis and asthma like symptoms. Features of a systemic vasculitis often appear later.
Skin - tender subcutaneous nodules, petichae and purpura
Neuro (80%) - mononeuritis multiplex
Very rare = alveolar haemorrhage.
EGPA Inv
MPO, panca +ve
Biopsy = eosinophils, no granulomas
Mx of all small vessel vasculitis
Induced remission with high dose of steroids
Maintenance with methotrexate and azithprione
Henoch-Scholein purpura PC
Most common childhood vasculitis 3-8y/o post URTI
Triad of colicky abdo pain, palpable purpuric rash over buttocks and thighs. Haematuria and proteinuria leading to nephrotic syndrome
+/- arthralgia, GI haemorrhage or intusseception
HSP Inv and Mx
High IgA, CRP, high platelets - not ITP
May need steroids, most return to baseline with no renal impairment. Much higher incidence of ESRF in adults
Cryoglobulinemia
Simple - Monoclonal IgM due to myeloma / CLL / Waldenstroms
PC = Hyperviscosity Visual disturbance Bleeding from mucus mems Thrombosis Headache, seizures
Mixed (80%)
Polyclonal IgM secondary to SLE, Sjog, HCV, Mycoplasma
PC = Immune complex disease GN Palpable purpura Arthralgia Peripheral neuropathy
SLE auto antibodies
Anti-dsDNA = specific for SLE and TNFa induced SLE
Anti histone = drug induced - isoanzid, methotrexate, hydralazine, procainmide
Both show homogenous patterns of staining
Anti-smith = speckled staining
Sjogrens auto antibodies
Anti Ro and anti La speckled pattern
Systemic sclerosis
Diffuse - Scl70 antitopisomerase
Limited - anti-centromere
PC Raynauds
Classically white - blue - red. Worse at times of stress and cold. In severe can lead to digital ulceration and gangrene
Inv Raynauds
Rule out a secondary cause. Nail fold cappilaroscopy
Causes of Raynauds
1 - idiopathic
2 - B blockers, systemic sclerosis, SLE, RA, Sjorgens, Vasculitis, polycythemia
Pathogenesis of systemic sclerosis
Widespread vascular damage involving small arteries, arterioles and capillaries. There is initial endothelial cell damage this perpetuates with cytokine involvement leading to fibroblast activation. Increased levels of type I and III collagen in lower layer of dermis and internal organs
Limited systemic sclerosis PC
Calcinosis - fingers
Raynauds - 100% often begins 15yrs before skin changes
Eosophegal dysmotility
Sclerodactyl - shortened fat fingers + microstomia
Telengectasia (facial blanching on pressure)
Crucially skin involvement is limited to the hands, face, feet and forearms. No chest or neck involvement
15% cases = pul HTN
Investigations limited systemic sclerosis
Anti-centromere Abx
Dilated nail fold capillary loops
Barium swallow shows duck neck.
Diffuse systemic sclerosis PC
Usually begins with oedema and Raynauds and progresses rapidly. More severe involving multiple organs systems. Skin involvement above the elbows on the neck and trunk
Lung = 40% develop ILD - restrictive lung disease with basal reticular nodular shadowing on X-ray
20 % also develop pulmonary HTN
Cardiac = rare involvement - conduction defects
GI = Very common to have oesophageal dysmotility - dysphagia, reflux, heartburn, occasionally anal incontinence. Atony of small bowel, GAVE, malabsorption due to bacterial overgrowth.
Renal - acute hypertensive crisis
Inv for diffuse systemic sclerosis
Antitopisomerase - scl70
RNA polymerase III - increased risk of renal involvement
Enlarged capillary loops with significant loss
Systemic sclerosis renal crisis
PC malignant HTN, high renin, microangiopathic haemolytic anaemia. Protein and haematuria
Affects 10% with dSS. Can be precipitated by steriods
Mx = aggressive ACEi. Prognosis linked to level of skin involvement, RNA III polymerase levels and tendon friction rub
MAHA (microangiopathic haemolytic anaemia)
red cells are ripped apart by physical trauma. Often in the small vessels. SLE and SS are also includes. Crucially schisocytes on blood film
- Disseminated intravascular coagulation (DIC) – a nasty condition in which there is bleeding and clotting at the same time in the patient. Lots of things can cause DIC (like malignancy, obstetric complications, trauma, and sepsis) – and it’s complicated enough that we’ll get into it in a future post.
- Thrombotic thrombocytopenic purpura (TTP) – a syndrome in which the patient gets little thrombi within the microvasculature anywhere in the body, but especially the CNS and kidneys. We’ve talked a little about TTP before.
- Hemolytic-uremic syndrome (HUS) – a disorder often related to ingestion of food (especially raw hamburger, but also spinach, other vegetables, you name it) containing E. coli 0157:H7. The bug makes a toxin that damages endothelial cells, and for some reason, the kidneys are hit the hardest.
GI complications of SS
GORD - Barretts oesophegus (squamous - glandular)
Duodenum - dilation can lead to atony
GAVE - gastric central vascular ectasia 25% of pt with high RNA polyermase III. Dilated submucosal vessels on antrum may precipitate GI bleed.
Investigations in systemic sclerosis
FBC - normocytic anaemia
Urine dip - proteinuria, A:CR
Serial PFT’s, echo and BNP to monitor
Barium swallow may show beak shaped deformity
ILD usually manifests with reticulonodular shadowing @ the bases. However can develop apical if due to recurrent aspiration. HRCT to diagnose
Mx of SS
Avoid the cold, wear gloves
Rarely any management options for oesophageal problems - PPI if symptomatic
Malabsorption - Abx for bacterial overgrowth, nutritional substitutes
Monitor for renal involvement - ACEi stat!
Pulmonary fibrosis = aggressive steroid therapy IV cyclophosphamide and azathioprine
Localised scleroderma
Morphea - localised subcutaneous confined to the skin in young adults and children.Seen in bluish patches on the trunk can progress to central white atrophy.
Sjogrens syndrome PC
SICCA symptoms = dryness of eyes, mouth, vaginal, larynx. These can = nutritional defects, tooth decay, dyspareunia, salivary gland enlargement and chronic eye infections - dry gritty eyes
Fatigue
Systemic signs of Sjogrens
Arthralgia - non progressive polyarthritis
Raynauds
TIN leading to renal tubular acidosis
20x increase of MALT - non hodgkin B cell lymphoma
Rare - oesophageal dysmotility, pulmonary fibrosis
Primary Sjogrens
9:1 Female:males
Onset 40-50y/o
Absence of RA, SLE,
Secondary Sjogrens
Linked to HLA DR3 - AIH, PBC, RA, SLE, SS, MCTD, thyroid disease
Investigations into Sjogrens
100 % for ANA and RF
- Specific = antiRo and La
High ESR, low C3, hypergabbaglobulinemia
Labial and parotid biopsy shows focal infiltration of B cells and lymphocytes.
Crucial to palpate for lymphadenopathy
Schirmer test
Tests for tear production strip of filter paper placed on inside of lower eyelid for 5 minutes
>15mm = normal <5mm = Sjogrens
Mx Sjogrens
Artifical tears and saliva replacements
NSAIDS and hydroxchloroquine for arthralgia
Immunosuppres for systemic disease
Check for lymphoma!!!
Myalgia vs myositis
Myalgia - common feature of many AI, no weakness normal muscle enzymes
Myositis - Inflammatory myopathies characterised by proximal > distal weakness often symmetrical in pt 50+
Polymyositis
Idiopathic inflammation of striated muscle, 3x more common in female
PC polymyositis
Progressive symmetrical proximal weakness often affecting the shoulders and the pelvic girdle. Spares distal and ocular muscles.
Systemic features of wt loss, fever, anorexia
Can lead to dysphonia, dysphagia and involvement of laryngeal muscles
Invx of polymyositis
Biopsy - cytotoxic CD8 T cells in endomysium.
High CK and LDH (1000s in active disease)
Crucial to take trop T for baseline
Anti-Jo
Livedo reticularis
Anti phospholipid, RA, TB, SLE, RCC, dermatomyositis
Polyarteritis nodosa, cryoglobulinemia, myeloma
Bechets
Oral and genital ulceration, anterior and posterior uveitis, arthralgia
Dermatomyositis
Polymyositis + skin involvement
- Heliotrope rash on eyelids +/- oedema
- Gottrans papules lichenoid changes over knuckles
- Macular rash (Shawls sign) photosensitive over back and shoulders
- Mechanics hands painful rough cracked skin without vesicles
Always hunt for Cancer approx 40% linked to.
Inv dermatomyositis
High CK, LDH, ALT
Raised ESR and CRP
Anti Mi 2
EMG = triad of spontaneous fibrillation @ rest, polyphasic potentials on voluntary contraction, repetitive potentials on mechanical stimulation
Biopsy - CD4 infiltrate, lowest possible steroid dose, screen for malignancy
Cancer linked to dermatomyositis
Ovary, lung, Non-hodgkin lymphoma, pancreatic and stomach
Complication of inflammatory myopathies
High incidence of ILD and oesophageal dysmotility
Anti Jo +ve (anti trna synthase)
Mechanics hands are highly suggestive, increased risk of ILD and raynauds
Anti Mi
Better prognosis. low incidence of ILD, more cutaneous signs
MCTD
PC = ILD, Raynauds, skin and muscle involvement, fatigue and arthritis
Anti U1 RNP
Antiphospholipid syndrome diagnosis
1 x clinical = vascular thrombosis (FHx),
pregnancy >3 unexplained miscarriages >1 late abortion
1 x lab = Lupus anticoagulant (2 x 12 weeks apart)
anticardiolipin / anti B2 glycoprotein
DMARDs in pregnancy
Safe = azathioprine and hydroxychlorquine
Stop known teratogens i.e. MMF, methotrexate and cyclophosphamide. Rituxamib linked to 2nd/3rd trimester B cell depletion.
Pre-pregnancy counselling
Achieve disease quiscense 6 months prior to conception.
Measure C3, dsDNA, BP and urine @ baseline
Maternal Ro/La = 2% risk of fetal HB at birth, Low dose aspirin for all with SLE,
Manage flares with lowest dose possible methylpred. Pregnancy makes rheumatic conditions much worse! High dose folic acid. Consultant led care
