Hospital Paediatrics

Rheumatology
Various conditions

• Impossible to cover
(some if not all)
them in details
 To recognize the condition
• History
– Pay attention to and verify relevant symptoms
– Beware of “red flags”
• Physical examination
– Know what is normal
• Recognize the pattern and investigate accordingly
• Revisit the diagnosis
 History
• Common themes:
– Fever: pyrexia of unknown origin
– Constitutional: fatigue, anorexia, weight loss
– Rash
esp wf morning stiffness

– Musculoskeletal: joint pain, swelling, limping

– Multisystem involvement
Arthritis
Rash: Sites, colour, border, raised, ulcer……
 Red Flags and mimics
• Constitutional symptoms: common, overlapping with other conditions
– Systemically unwell
• High spiking fever, night sweating, weight loss
• Nature of painful joint
– Extremely painful joint/limb
symmetrical

– Non-articular pain esp those BM inflitrating cancer

• Important differentials – life threatening

– Malignancy
• Leukaemia, lymphoma, bone tumor, neuroblastoma
– Unusual infection
• Osteomyelitis, septic arthritis
– Non accidental injury
 Differential diagnosis
• Joint pain with no swelling • Joint pain with swelling

• Hypermobility • Trauma
• Idiopathic pain syndrome • Haemophlia
– Fibromyalgia • Infection
• Orthopedics condition – e.g. reactive arthritis, parvovirus and etc
• Perthes disease • Other connective tissue diseases
– SLE, MCTD and etc
• Other conditions with arthritis
– IBD, Down’s syndrome
• Other inflammatory conditions
– Autoinflammatory diseases
 Others
• Social history
– Possible stressors
– Impact of the chronic +/- life threatening condition

• Family history
 Physical examination
• Growth, puberty
• Skin, nails, nail folds, hairs
• Eyes
• Ears (hearing, skin changes)
• Mucous membrane (hard palate ulcer)
• Teeth (caries, TMJ condition)
• Lymph node enlargement
• Edema, pulses (vasculitis)
• CVS/Resp/Abdo/CNS/joints
Gait

Modica RF et al Pediatric Annals 41:11 (Nov 2012)

Arm
Leg
Spine
Case illustration
 Wong CY
• F/ 13 years old
• 2 months’ history of
– Rash over lower limbs
– Joint pain affecting wrists, fingers, neck, hips, ankles
– Morning stiffness for about 15 mins
• In the past 2 weeks
– Fever
– Facial puffiness
– Feeling tired, poor appetite, weight loss 3 kg
 Physical exam
• Febrile temperature 38 degrees
• BP 119/89, normal pulse and respiratory rate
• Facial rash
 Investigation
• Hb 13.9, wcc 6.2, lymphocyte 0.6, platelet 95
• Urea 7.6 (ref range 2.6-6.6) kidney problem

• Creatinine 98 (ref range 49-83)

• Albumin 26 (ref range 35-52)
• ALT 103 (ref range <55)

• Urine multistix RBC 2+, protein 4+

• 24 hour urine total protein 8.1g/day (ref range <0.1)
• CrCl 62min/ml/m2
 Clinical Impression
• Chinese adolescent girl
• Malar rash, rash over limbs, arthritis, systemic upset
• Thrombocytopenia, lymphopenia, renal insufficiency, heavy
proteinuria with hypoalbuminaemia, hepatitis

• Systemic Lupus Erythematosus

 Systemic Lupus Erythematosus
• Multisystem, autoimmune and markedly
heterogeneous

• Epidemiology:
– Annual incidence: varies, 0.36 to 0.8/100,000 in <18 yo
– Prevalence: 10-20/100,000

• More in girls after puberty (F vs M from 5:1 to 8-10:1)

• Higher incidence and more severe in Asian, African and
Hispanic children
 Juvenile-onset SLE
• 15-20% of all SLE are childhood onset

• Comparing to adult-onset disease

– More acute and severe at onset
– More aggressive course and more organ damage
– More hematological, renal and neurological manifestations
– More use of steroid and immunosuppressants
• And hence more side effects
– Higher mortality
Brunner HI et al. Arthritis Rheum 2008 Feb;58(2):556-562
Mina R, Brunner HI. Rheuma Disc Clin North Am. 2010 Feb;36(1):53-80
Constitutional Fever, malaise, weight loss

Cutaneous Butterfly rash, discoid lupus, periungual erythema,

photosensitivity, mucocutaneous ulcerations, alopecia
Musculoskeletal Polyarthritis and arthralgia, tenosynovitis, myopathy,
aseptic necrosis
Vascular Lupus crisis, Raynaud’s phenomenon, thrombophlebitis, livedo
reticularis, lupus profundus

Cardiovascular Pericarditis and effusion, myocarditis, Libman-Sacks endocarditis

Pulmonary Pleuritis, basilar pneumonitis, atelectasis, hemorrhage

Gastrointestinal Abdominal crisis, esophageal motor dysfunction, colitis, pancreatitis

Liver, spleen, Hepatomegaly, splenomegaly, hepatitis, lymphadenopathy

and nodes

Neurologic Organic brain syndrome, convulsions, psychosis, chorea,

cerebrovascular accident, polyneuritis and peripheral neuropathy,
cranial nerve palsies, pseudotumor cerebri

Ocular Cotton-wool spots, papilledema, retinopathy

Renal Glomerulonephritis, nephrotic syndrome, uremia, hypertension

Malar
rash
Rash Vasculitic rash
Discoid rash with scar

Only in hand; similar appearance diff distribution as in hand foot mouth dx

Retinitis
pleuritis
 Lupus Nephritis
• Major determinant of long term outcome
• 60-80% JSLE
• Presentation: variable
– Microscopic (rarely macroscopic) haematuria
– Proteinuria: mild to heavy, can up be nephrotic range
– Impaired renal function
– Acute renal failure: olioguria, hypertension, metabolic acidosis
– Can present as isolated lupus nephritis (positive ANA +/- anti dsDNA)
or in the presence of generalized activity
Treatment of lupus nephritis
is guided by renal biopsy
• Aggressive treatment with
immunosuppressant:
– Active Class III (Class IIIA)
• IIIA/C + V
– Class IVA
• IVA/C + V
– Class VA
• Protineuria >1g/day despite anti-
proteinuric drugs (renin-angiotensin-
aldosterone system blocker)
• Biopsy if any sign of renal
involvement
– Proteinuria >0.5g/day (repeated)
• Esp with glomerular haematuria/case
 Central nervous system

Commonly in the presence of generalized disease activity

 Suspect SLE in patients with unexplained
multistystems involvement
• Active disease profiles: • Autoantibodies
– Raised ESR, normal CRP – ANA: sensitive, but common in healthy
– except in arthritis/serositis/infection population
– Low complements (C3, C4) especially – Anti dsDNA (specific), Extractable
in active lupus nephritis nuclear antigen (anti Smith: ”anti Sm”)
– Cytopenia: anaemia, leucopenia, – Antiphospholipis antibodies
lymphopenia, thrombocytopenia • Anticardiolipin, Lupus anticoagulant, anti
beta 2 glycoprotein
– Abnormal urinalysis

• Biopsy if any sign of renal • Organ specific investigation

involvement – LP, EEG, MRI brain and etc
– Proteinuria >0.5g/day (repeated)
• Esp with glomerular haematuria/case
ACR revised criteria (1997)
for classification of SLE 4 of 11 criteria

Criteria Definition
Malar rash Fixed erythema, flat or raised, over malar emiences, tending to spare nasonabial folds

Discoid lupus Erythematous raised patches of adherent keratotic scaling and follicular plugging. Atrophic
scarring may be seen in older lesions
Photosensitivity Skin rash as a result of unusual reaction to sunlight

Oral or nasal Usually painless, observed by a physician

ulceration
Non-erosive Involving > 2 peripheral joints, tenderness, swelling or effusion
arthritis
Serositis Pleuritis: pleuretic pain, rub or effusion or Pericarditis: ECG, rub or effusion

Nephritis Proteinuria >0.5g/day or >3+ or Cellular cast (RBC, Hb, granular, tubular or mixed)

Neurological Seizure or Psychosis

Haematological Hemolytic anaemia with reticulocytosis or leucopenia <4 (>2 occ)or lymphopenia <1.5 (>
2 occ) or Thrombocytopenia <100
Immunological Anti dsDNA Ab or Anti Sm Ab or Anti-phospholipid Ab (anticariolipin IgM or IgG, lupus
anticoagulant, false positive VDRL)
ANA Exclude drug effect
 SLICC classification criteria for SLE
1) Biopsy-proven lupus nephritis with ANA or anti-dsDNA OR joint S/S not mandatory
2) 4 of the criteria, including at least 1 clinical and 1 immunologic criterion

Clinical Criteria Immunologic Criteria

1. Acute or subacute cutaneous lupus 1. ANA above laboratory reference range
2. Chronic cutaneous lupus 2. Anti-dsDNA above laboratory reference range
3. Oral/Nasal ulcers (except ELISA: twice above laboratory reference range)
4. Nonscarring alopecia 3. Anti-Sm
5. Inflammatory synovitis: physician-observed 4. Antiphospholipid antibody:
swelling of two or more joints OR tender joints lupus anticoagulant
with morning stiffness
6. Serositis false-positive test for syphilis
7. Renal: Urine protein/creatinine (or 24 hr urine anticardiolipin–at least twice normal or
protein) representing at least 500 mg of protein medium-high titer
in 24 hr or red blood cell casts anti-b2 glycoprotein 1
8. Neurologic: seizures, psychosis, mononeuritis 5. Low complement
multiplex, myelitis, peripheral or cranial low C3
neuropathy, cerebritis (acute confusional state)
9. Hemolytic anemia low C4
10. Leukopenia (<4000/mm3 at least once) OR low CH50
Lymphopenia (<1000/mm3 at least once) 6. Direct Coombs test in the absence of hemolytic
11. Thrombocytopenia (<100,000/mm3) at least anemia
once
 Medication in paediatric SLE: the reality

• No drug is approved specifically

for paediatric SLE patient

• Off label use

Brunner HI et al. Nat. Rev. Rheumatol.7,225-233(2011)

 Treatment
• General but important
– Counseling, education, compliance, risk behaviour
– Adequate rest, use of sunscreens
– Management of infection, Immunizations
– Pregnancy issues

• Hydroxychloroquine
– Cutaneous, articular symptoms
– Overall better disease control, better lupus nephritis control
– Improve lipid profile, decrease thrombotic/artherogenic risk and etc

• Nonsteroidal anti-inflammatory drugs

– Arthritis, arthralgia, mild serositis
 Systemic glucocorticoid
• Rapid control acute disease activities even life threatening
manifestations
– Prednisolone: up to 2mg/kg/day, 60-80mg/day in divided doses
– Methylprednisolone iv pulse: 10-30mg/kg/dose (max 1g/dose), 3 to 5
consecutive days, can be repeated
• NPSLE, nephritis, hematological, GI failure

• Taper to lowest dose whenever possible

• Low dose is commonly needed for maintenance

Side effects
both acute & long term
• Change in body habitus
– Buffalo hump, central obesity, striae
• Infection
• Growth retardation
• Impaired bone health
– Osteopenia, Osteonecrosis, fracture
• Eye
– Cataract, increase intraocular pressure
• Cardiovascular and Metabolic
– Hypertension, hyperglycaemia, premature artherosclerosis
• Psychiatric
– Psychosis
 Immunosuppressant
• Cyclophosphamide • Mycophenolate mofetil
– Intravenous pulses (oral) – Lupus nephritis, CNS,
– Remission induction or hematological, skin
maintenance – Side effects:
– Major organ involvement: NPSLE, • Immunosuppression, cytopenia, GI
nephritis and etc upset, variation in individual
pharmacokinetics
– Side effects
• Haemorrhagic cystitis, SIADH,
neutropenia
• Gonadal failure (accumulative dose),
immunosuppression
• Infection
– Pneumocytic carinii prophylaxis
• Azathioprine • Lupus nephritis
– Lupus nephritis (maintanence), – Corticosteroid
skin, haematological, liver – Immunosuppressants
• Cyclosporin • Class IIIA, IVA (or mix): iv CYC, MMF
– Lupus nephritis • Class VA: MMF, CSA
• Maintanence: MMF, AZA
• Methotrexate – Anti proteinuric (ACEI, ARB)
– Arthritis
• CNS
• IVIg: – Steroid, iv CYC, IVIg, Plasmapheresis
– NPSLE, in setting of infection – Maintanence: AZA, MMF
• Skin:
– Steroid, HCQ, MMF, AZA
 Biologics in SLE
• Rituximab
– Anti B cell (CD20) antibodies
– Rescue in refractory severe or life threatening manifestation
– Failed RCTs

• Belimumab
– BLyS monoclonal antibody
– FDA Approved biologics in SLE
• For >18 years old
• Improved overall disease activities in moderate SLE, arthritis, cutaneous
Juvenile Idiopathic Arthritis
 Juvenile Idiopathic Arthritis

• The commonest inflammatory • Subtypes:

joint disease in children – Oligoarticular JIA
• Persistent
• Extended
• Age of onset
– Polyarticular JIA, RF –ve
– Less than 16 years old
– Polyarticular JIA, RF +ve
• Duration of arthritis – Enthesitis related arthritis
– At least 6 weeks – Psoriatic arthritis
– Systemic onset JIA
• Absence of infection or other – Other/undifferentiate
defined cause
 Case 1: Deng SN
• F/ 2 years old
• 4 months’ history of:
– Bilateral knee pain
– Unable to walk in the morning, grumpy
– Limping gait
Physical examination
 Investigation
• ANA+, Rheumatoid Factor –ve, HLA B27 –ve
• Other blood tests normal

• She developed asymptomatic uveitis, detected by slit lamp

examination
 Case 2: Chan CT
• F/ 14 years old
• 3 months’ history of multiple joints pain
• Joints involved:
– Most of the PIPs, both wrists, both elbows, both shoulders, both
knees, both ankles

• Physical examination: active arthritis of the above named

joints
Her R hand and R ankle
 Investigation
• Hb 9.9 (ref range 11.7-14.8), wcc 6.4, platelet 410 (ref rang
170-380), ESR 120 (<20), CRP 8.45 (<0.76)
• Rheumatoid Factor +ve, ANA +ve
• Anti CCP >250 (<20), HLA B27 -ve
 Case 3: Cheung HY
• F/ 12 years old
• Presented to us in 5/2009
– R TMJ pain since 5/2008
– R wrist pain and swelling since 8/2008
• From 3/ 2009 she developed widespread join pain:
– Decrease mouth opening, decreased neck ROM, R wrist, L elbow, both
ankles, both knees
– P/E: active arthritis and decrease ROM of the above joints

• i.e. <5 joints in first 6 months, extended to more than 5

afterwards
 Investigation
• Hb 12.6 (ref range 11.7-14.8), wcc 7.4, platelet 342 (ref rang
170-380), ESR 57 (<20), CRP 41 (<0.6),
• Rheumatoid Factor -ve, ANA +ve, HLA B27 -ve
 Case 4: Choi E
• M/ 13 years old
• 3 months history of joint pain iliac joint
enthesistis? atella tendon? achillel tendon???

– Bilateral knees, R shoulder, R buttock

• Also pain over inferior pole of both patella (places of enthesis)

• Physical examination:
– Arthritis of knees
– Tenderness of inferior border of both patella
• Site of patellar tendon insertion
– R SIJ tenderness: Patrick’s test +ve
– Modified Schober test: 15cm to 21cm
 Investigation
• Hb 13.7, wcc 8.4, platelet 526 (high), ESR 60
(<20), CRP 43 (<9.9)
• Rheumatoid Factor -ve, ANA-ve, HLA B27 +ve
 Investigation
• Exclude other causes (infections, malignancies)

• Blood: not diagnostic

– Inflammatory markers e.g. CRP, ESR: can be normal
– Autoantibodies: ANA, Rheumatoid factor, anti CCP
– HLA B27 antigen

• Imaging: assess synovitis/enthesitis/tenosynovitis, damage, other pathologies

(e.g. fasciitis, myositis)
– X Ray
– USG
– MRI
 Oligoarticular JIA
• F>M (4:1), peak incidence 2 -4 years old

• Definition
– <4 joints in first 6 months (<5 joints)
• Extended: more than 4 joints are involved after first 6 months
• Persistent: remains < 4 joints
• Exclusion
– Psoriasis, first degree relatives with history of psoriasis, Reiter, Ankylosing sppondylitis,
acute uveitis, sacroiliitis in IBD, ERA, RF positive, SIA, HLA B27+ve in boy with onset >6
years old
 Features
• 50 – 60% JIA • Asymmetrical large joint
• F>M (4:1) involvement
• Peak incidence 2 -4 years old
• Morning stiffness, swelling,
• ANA +ve in 80% limping gait, refuse to bear
weight
– RF negative, HLA B27 negative

• Normal inflammatory markers

 Oligoarticular JIA
• Mostly large joints e.g. knee, ankle

• Risk: joint destruction, leg length

discrepancy

• Remission: 50-60%

• Worse in
– Extended subtype
– Uveitis
 Extra-articular manifestation – uveitis
• Chronic anterior uveitis:
– Up to 20-30%
• Asymptomatic (neither red or photophobic)
– Regular slit lamp examination

• Higher risk: F, younger, ANA+ve

– May be independent to the arthritis course
– Can manifest prior to onset of arthritis

• Untreated: cataract, band keratopathy, secondary glaucoma

 Polyarticular JIA, RF -ve
• Definition
– > 5 joints involvement
– RF -ve

– Exclusion
• Psoriasis, first degree relatives with history of psoriasis, Reiter,
Ankylosing spondylitis, acute uveitis, sacroiliitis in IBD, ERA, RF
positive, SJIA, HLA B27+ve in boy with onset > 6 years old
 Polyarticular JIA, RF +ve
• Definition:
– >5 joints involvement
– RF +ve for 2 occ, at least 3 months apart

– Exclusion
• Psoriasis, first degree relatives with history of psoriasis, Reiter,
Ankylosing spondylitis, acute uveitis, sacroiliitis in IBD, ERA, SJIA, HLA
B27+ve in boy with onset > 6 years old
 Features
Poly RF +ve Poly RF –ve
• 5-10% JIA • 20-30% JIA
• F>M • F>M
• Usually >10 years old • Peaks 2-4 and 7-12 yo
• RF positive • RF negative
– ANA positive in 50% – ANA positive in 60-80%
– HLA B27 negative – HLA B27 negative

• Prolong erosive arthritis especially • Heterogeneous

those Anti CCP +ve • Some with fewer joints involvement
• Symmetrical multiple small and large behave like oligoarticular JIA with
joints, ESR and CRP raised iridocyclitis
• Continuous activity into adulthood • Remission ~20-50%
 Enthesitis related arthritis - ERA
• Definition
– Enthesitis and arthritis, or arthritis with at least 2 of the followings
• Male with age onset > 6 years old
• HLA B27 positive
• SacroiIiac joint tenderness and/or inflammatory lumbrosacral pain
• Acute anterior uveitis
• HLA B27 disease in first degree relative(IBD, Uveitis, AS, Sacroiliitis, Reiter
syndrome)
– Exclusion: SJIA, Psoriasis in patient or in first degree relatives, RF positive
• 15% of all JIA • Asymmetrical large joints
• M>F, onset after 6 years old involvement
• HLA B27 +ve in 80% – Peripheral arthritis
– Axial involvement (sacroiliitis,
• ANA-ve, RF –ve spondylitiis) as presentation:
uncommon
• Inflammatory markers normal or
• Evolving to AS
elevated – May develop axial disease
– Sacroiliitis and spinal inflammation
– Especially in HLA B27 positive individual

• Acute uveitis
 Psoriatic arthritis
• Definition:
– Arthritis and psoriasis, or arthritis and at least 2 of the following:
• Dactylitis
• Nail abnormalities (2 or more nail pits, onycholysis)
• Family history of psoriasis in a first degree relatives

• Possible uveitis

• HLA B27 individuals could develop axial disease

Arthritis in Children and Adolescents. Juvenile
Idiopathic Arthritis. Szer LS, Kimura Y, Malleson PE.
Southwood TR. Oxford University Press 2006
Treatment options
• NSAIDs

• Intra-articular steroid injection

• Synthetic DMARDs

• Biological DMARDs

• Others: physiotherapy, occupational therapy

Intra-articular steroid injection
• Stops inflammation and therefore rapid pain relief
• Repeated as needed (once in 4 months)

.
Synthetic Disease Modifying Anti-Rheumatic Drugs
• Methotrexate
– Potent competitive inhibitor of several enzymes in the folate pathway
– PJIA, PsA, SJIA (arthritic symptoms), +/-ERA, JIA associated uveitis

• Leflunomide
– Inhibits de novo pyrimidine synthesis
– PJIA

• Sulfasalazine
– Analog of 5-aminosalicyclic acid linked to sulfapyridine
– ERA
 Biological DMARDs
• Selectively target specific cytokine • Anti TNF inhibitors
known to be instrumental in the
• Etanercept, adalimumab
pathophysiology of inflammatory
arthritis • T cell co-stimulation inhibitor
• Abatacept
• Anti interleukins
• Anti IL 1: Canakinumab
• Anti IL 6: Tocilizumab

• Others
• Anti CD 20 antibody: Rituximab,
• JAK inhibitor: Tofacitinib
 Indication
• Highly effective, especially in DMARDs refractory cases
– Provided much needed symptomatic relief
• Generally well tolerated and safe

• Indication:
– Anti TNF (Etanercept & Adalimumab) PJIA, Extended oligoJIA, ERA, PsA
• Adalimumab: JIA associated uveitis
– Anti IL 6 (Tocilizumab): PJIA
– T cell costimulatory inhibitor (Abatacept): PJIA refractory to anti TNF
– Side effects
• Local injection reaction, sting, infusion reaction, infection (TB)
 Treatment – oligoarticular JIA
• Mild: NSAIDs

• Intra-articular steroid injection

– Repeat if flares, up to 3 times in 12 months

• Established/extended disease/uveitis:
– Disease Modifying Anti-Rheumatic Drug(DMARD):
• Methotrexate: oral or subcutaneous injection
– Biologics
• Anti TNF inhibitors: Etanercept, Adalimumab
 Treatment- polyarticular course JIA
• PJIA(RF positive and negative), Extended OligoJIA, PsA
– Early aggressive treatment

• DMARDs
– Methotrexate
– Leflunomide
– (ERA: sulphasalazine)

• Biologics
– Anti TNF inhibitor
• Etanercept, Adalimumab
– Anti IL-6 antibody
• Tocilizumab - PJIA
– T cell costimulation inhibitor
• Abatacept - PJIA
 Treatment - ERA
• Mild disease or enthesitis: NSAID

• DMARDs
– Sulphasalazine for peripheral arthritis

• Biologics
– Anti TNF inhibitor
• Etanercept
• Adalimumab
 Systemic onset JIA
• M and F ratio similar, peak 4-7 years old, ~10% of JIA

• Definition:
– Arthritis and Fever >39 degrees for >2 weeks and at least one of the following
• Evanescent rash
• Lymphadenopathy (generalised)
• Serositis (pericarditis)
• Hepatomegaly +/- splenomegaly
– Exclusion
• Psoriasis, first degree relatives with history of psoriasis, Reiter, Ankylosing spondylitis, acute
uveitis, sacroiliitis in IBD, ERA, RF positive, HLA B27+ve in boy with onset >=6 years old

• Distinct immune pathogenesis when compared with other JIA “subtypes”

Quotidian fever pattern

At least a single
spike of fever
per day
Evanescent Rash
 Laboratory features
• Very high inflammatory markers
– Increased ESR, CRP, immunoglobulins (polyclonal), complements, ferritin
– Complete blood picture:
• Leucocytosis (neutrophilia), thrombocytosis, anaemia

• Autoantibodies: generally not present

• Need to exclude other possibilities

– Malignancies (leukaemia, neuroblastoma), unusual infection,
Kawasaki disease, vasculitides (cutaneous polyarteritis), other
autoinflammatory conditions
 Macrophage Activation Syndrome
• Clinical features
– Unremitting high fever
– Hepatosplenomegaly
– Renal involvement
– CNS dysfunction
• Irritability, disorientation, headache, seizures, coma
– Coagulopathy: purpura, haemorrhage
– Paradoxical drop in cell counts and inflammatory markers

• Life threatening condition

– Mortality up to 20 to 30%
– Prompt recognition & Rx (Dexamethazone, Cyclosporin, Etoposide)
 Treatment
• Moderate to severe disease:
– Systemic steroid:
• High dose oral Prednisolone or iv Methylprednisolone pulses
– DMARDs
• Methotrexate (for arthritis)
– Immunosuppressive
• Cyclosporin (for systemic symptoms)
– Biologics
• Anti IL-1 inhibitor (Canakinumab)
• Anti IL-6 inhibitor (Tocilizumab)
(Mild case: NSAID e.g. Indomethacin)
It may not always be that straightforward……

SLE

Cause of
vasculitis
was not
identified
Fever, rash, LN enlargement

T cell
lymphoma
 To recognize the condition
• History
– Pay attention to relevant symptoms
– Look for red flags
• Infection, malignancy and non-accidental injury
• Physical examination
– Know what is normal
• Recognize the pattern and investigate accordingly
• Revisit the diagnosis
Go to ward
See patients, listen to them
Learn from them