RHEUMATOLOGY

RHEUMATOID ARTHRITIS

Boutounniere Deformity
Peri - Articular / Juxta - Articular osteopenia
•• Seropositive chronic inflammatory, symmetric
•• Narrowing of joint space can occur in any
polyarthritis (> 5joints)
arthritis/ arthropathy ,only exception can be
•• Common in females, 30-60 yrs age, females gout & acromegaly related arthropathy.
develop more severe symptoms
•• Extra articular manifestation-
•• Genetic association - HLA DR4
Q

1. Lymphadenopathy (MC)
•• Environmental association – smoking
2. MC malignancy associated with RA- NHL
•• Seropositive - RF +, ACPA +, anti CCP + Ab, anti (DLBCL)
Q

MCV + Ab.
3. MC cardiac manifestation- pericarditis , RCM
•• When ↑↑ titres, severity ↑, ↑risk of extra-
articular involvement. 4. MC pulmonary manifestation is pleuritic, with
exudative pleural effusion with low glucose.
•• Acute - <6 weeks, chronic - >6 weeks
5. MC skin manifestation- subcutaneous nodules,
•• Inflammatory - ↑CRP / ↑ESR
mobile, on extensors, painless
•• Any inflammatory arthritis: Early morning
stiffness for >1 hour, pain ↓ with exercise / 6. MC ocular manifestation- keratoconjunctivits
movement, ↑with rest. sicca/dry eyes → MCC of 2° Sjogren’s
syndrome.
•• It is an Additive arthritis - more & more joints
will keep on adding 7. Late kidney involvement seen in amyloidosis
•• MC joint – MCP joint > PIP joint &wrist joint. (AA type) {early kidney involvement is seen
in SLE} MGN also seen.
•• MC large joint involved – knee joint
8. Pulmonary – RA nodules in upper limb,
•• Spared joint - DIP > thoracolumbar spine associated with pneumoconiosis like silicosis
(RA+pneumoconiosis- Caplan syndrome)
Q
•• Can develop erosions, erosive arthritis.
•• Deformities - Boutounniere, swan neck (hyper 9. MC ILD seen in RA- UIP (all other CTD have
flexion at DIP, hyper - extension at PIP), Z – NSIP as MC ILD)
deformity of thumb
Q

10. Hematological – Anemia (AOCD)

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11. Felty syndrome- late erosive RA with •• TOC in acute flare - corticosteroids, <2 joints
extremely high titres + massive splenomegaly - intraarticular corticosteroids, >3 joints -
+ neutropenia
systemic corticosteroids. (before starting tx,
–– D/D of felty syndrome - T-cell LGL (CD16+, always r/o joint infection)
Q

CD57+)
–– In case of large joint, do joint aspiration
12. MCC death - CV risk
before starting steroids.
13. Pregnant female- good prognosis

•• Triple Therapy c. Other anti-TNF – used upto 3rd trimester

Conventional synthetics- BIO-DMARDS
d. Azathioprine – not much used as it is less
sulfasalazine + HCQ
effective in RA, but used in pregnancy
1ST choice- anti TNF Target synthetics-
DMARDs because it is safe. Give extra folate as there
DMARDS- methotrexate, alternate- Leflunomide is ↑risk of NTD.
–– Before starting anti – TNF, r/o latent TB
e. NSAIDs- SOS. Avoid in >30 weeks.
{Mantoux test, IGRA}
f. Low dose corticosteroids can be continued.
–– s/e of anti TNF- drug induced LE. It can
result in HBV reactivation as well. Rituximab
has highest risk of HBV reactivation.

•• Treatment in Pregnancy–

a. HCQ / Sulfasalazine – safe

b. Anti-TNF – Certolizumab is safest

Q

* For Making Notes

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Seronegative Spondyloarthropathies
•• Common features - RF-, ACPA-, ANA -. Peripheral arthritis. Variable association with HLA-B27.
•• Inflammatory back pain, early morning stiffness >1hr that improves with exercise. NSAIDS very useful. Most commonly involved
is thoracolumbar spine (only exception is psoriatic arthopathy). Sacroilitis present. Peripheral arthritis - oligoarticular &
asymmetric, LL > UL. Achilles enthesities. Dactylitis. Sausage shaped digits. MC extra - articular manifestation - Ant. uveitis.
Distinguishing features
Disorder AS PsA ReA EA
Axial 1° peripheral arthritis +/- axial
Disease type Oligoarticular /asymmetric
Sometimes, PsA can mimic RA by involving small joints of upper limb
Males / <40yrs Males =females Males /<40yrs Males =females
Gender/ Mean age (yrs)
>40yrs /<40yrs
Axial involvement, Correlates 100% 20-40% 40-60% 5-20%
with HLAB27
Sacroilitis – 1st Ix to be done Symmetric Asymmetric symmetric
when Sacroilitis is suspected is
XRAY - ankyloses/fusion.
MRI – gold standard. BM
edema.
Peripheral distribution UL>LL UL>LL LL>UL UL>LL
Enthesitis ++ ++ ++ Rare
Dactylitis Rare ++ ++ Rare
Q Q
Ocular Ant uveitis Episcleritis +/-ant uveitis conjunctivitis Rare
Rare Psoriatic skin & nail changes Circinate balanitis, Erythema
(80%) keratoderma nodosum,
Skin
blenorrhagicum Pyoderma
gangrenosum
Q
Shiny corner sign / Pencil in cup DIP deformity Asymmetric No specific
bamboo spine/ dagger syndesmophytes
Imaging
sign/symmetric
syndersmophytes
Q
UL fibrosis Types: •• Arthritis (sterile) h/o IBD
MC valvular disease- 1. asymmetric oligoarticular + conjunctivitis 2 Types
AR 2. symmetric polyarticular (sterile) + urethritis Type 1 –
3. isolated DIP (sterile/non sterile) oligoarticular /
4.psoriatic spondylitis asymmetric
•• Reactive arthritis correlates with
Other features 5.athritis mutilans
occurs as a reaction IBD activity.
to infections -
GIT - shigella /
GU - chlamydia (l2b
serovar)
Treatment: DMARDS -
1. Pain- NSAIDs •• Conventional- no efficacy on axial disease
2. Control- DMARDS •• Target synthetic- can be used for both axial &peripheral if disease is refractory to conventional
3. Apremilast – PDE4i – PsA DMARDs & anti TNF.
Q
4. Antibiotics – doxycycline in •• Biological DMARD - best .
PsA
- Anti-TNFα- infliximab /adalimumab
- Anti IL-17 inhibitor- Secukinumab / Ixekizumab – approved for AS/ PsA
- Anti IL-12/23 inhibitor- Ustekinumab
* For Making Notes
- Anti IL-23 inhibitor- GuselkUmab
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B/L Symmetric Ankylosis - AS

Pencil in Cup Deformity, Classic of PsA.

CRYSTAL ARTHROPATHIES &

AOSD
Dactylitis- Reiter Syndrome & PsA Gout (d/t deposition Pseudogout (d/t
Features of monosodium urate deposition of calcium
crystals) pyrophosphate crystals)

Sudden onset, severe

nocturnal pain, MC •• Monoarticular
joint involved is 1st / asymmetric
metatarsal jt (k/a
oligoarticular
Psoriatic Nail Changes Acute PODAGRA), initial
•• MC joint involved is
attack is monoarticular
→ later polyarticular Knee / MCP , Wrist
attacks. Can have joint
associated cellulitis.

•• Tophi deposition
seen in Joints (toe
•• Pseudo RA- Early
jt/ finger jt/wrist
morning stiffness
Chronic jt/knee jt.)
•• Pseudo OA- non
Enthesitis - seen in all arthropathies except enteropathic •• Soft Tissue (pinna
inflammatory
arthritis / olecranon bursa/
Achilles)
3H-
Associated Metabolic syndrome / hyperparathyroidism
conditions CKD/HF Hypomanesemia
hemochromatosis

* For Making Notes

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Gout (d/t deposition Pseudogout (d/t HIGH YIELD POINTS

Features of monosodium urate deposition of calcium
crystals) pyrophosphate crystals) •• Rasburicase – approved and used only for tumor
•• MSU
lysis syndrome not chronic gout
•• IOC- joint
•• IOC- joint
aspiration .
•• Pegloticase – can be used for chronic gout, not
aspiration approved for tumor lysis syndrome.
Crystals •• Rhomboid shape,
•• Negatively
birefringent, needle
weakly positive •• C/I of Pegloticase & Rasburicase – G6PD
Q birefringence deficiency
shaped
•• Acute – non specific
•• Chondrocalcinosis
Q •• Uricosurics- Probenecid –organic anion
•• Chronic – Martel transport inhibitor
Imaging •• MC seen in knee
G sign, MSK USG - Benzbromarone - selective uric
joint, wrist joint
double contour seen transporter Selective urate
inhibitor
Lesinurad

Treatment
Acute Gout & Acute Pseudogout:
•• 1st line - NSAIDs +/- Colchicine (for 3-6 Martel G Sign /Ratbite Erosions
months) → ↓recurrence
•• Alternate – corticosteroid / ACTH /anti-IL-1 –
Anakinra < Canakimumab (preferred)
•• s/e of colchicine-
–– GI disturbances, diarrhea mostly
–– Agranulocytosis (dangerous s/e)

Chronic Gout
Double Contour Sign
•• Indications for uric acid lowering therapy: >
2attacks / year / Tophi / EGFR <60 / urolithiasis
•• Allopurinol – purine based XO inhibitor →
allopurinol hypersensitivity syndrome mainly in
HLA B 5801.
•• Febuxostat – non purine XO inhibitor
•• Both Allopurinol , Febuxostat → avoided with
Azathioprine / 6-MP (↑BM suppression)
Q
Chondrocalcinosis (Pseudogout)

* For Making Notes

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•• Plasma cell / dendritic cell type – linked to

ADULT ONSET STILL DISEASE pathogenesis of SLE
•• Auto inflammatory (innate immunity is •• Signature cytokine- IFN-α
affected) disease affecting those in 16-35 yrs
•• Constitutional symptom- fatigue (MC) / fever/
of age. {In autoimmune conditions, acquired
malaise/weight loss
immunity is affected}
•• MC system involved in body- MSK (>90-95%) –
•• Presents like PUO, arthritis, salmon rash, ↑↑ arthralgia / arthritis (non erosive )
TLC, hepatosplenomegaly, ↑ inflammatory
markers like ↑CRP / ↑ESR / ↑↑↑Ferritin, •• 25% deformity →Jaccoud’s arthropathy
Q

serology negative – RF- / ACPA - / ANA-

•• Mucocutaneous –
•• r/o other disorders
a. Oral /nasal (painless) ulcers
•• It is diagnosis of exclusion.
b. Alopecia ( non scarring)
•• Yamaguchi criteria
c. Skin-
•• Tx: DMARDs , anti IL-1 therapy .
ƒƒ ACLE- malar rash , mainly face
JIA
ƒƒ SCLE- anti Ro antibody, spare face
•• <16 yrs of age
ƒƒ CCLE- DLE , MC face>scalp , scarring type,
•• 3 Types- over time ↑risk of squamous cell cancer
–– Oligoarticular / asymmetric
–– All SLE related skin lesions are
–– Polyarticular / symmetric photosensitive.
–– Systemic JIA – still’s disease •• Serositis can result in pleuritic (associated with
•• +/- Growth affected small pleural effusions ) / pericarditis
•• +/- anterior uveitis •• Major organ development- MCC of death in SLE
is CV risk
•• Serology negative – RF-/ACPA-/ANA-
Hematological Kidney Neuropsychiatric Lungs
•• TOC- DMARDs
Q

1. Anemia (anti 1. Lupus 1. MC- ↓cognition 1. <5% - ILD

SLE erythrocyte Ab)– nephritis (associated (MC- NSIP)
AOCD / warm (anti ds with anti NMDA 2.
type AIHA(IgG) DNA Ab/ receptor Ab/anti endocarditis
– DCT+ anti smith glutamate Ab) – libman
2. Leukopenia / Ab) – MC 2. Headache sach’s
lymphopenia (anti & most 3. Seizures endocarditis
lymphocyte Ab) / severe –sterile
4.Psychosis (anti
thrombocytopenia form is vegetations
ribosomal P ab /
(20 ITP)
Q class IV. 3. RCM – HF
APLA ab)
Wire loop d/t diastolic
5. Vascular
lesions are failure.
complications-
seen in
•• Middle age female in reproductive age group stroke (APLA Ab)
this.
•• Genetic association- early classic complement
pathway deficiency (C1q/ C4/C2). SLE - Antibodies
•• C1q- severe disease, TREX gene associated •• C3/C4 can be used as marker of disease activity.
•• Environmental → EBV / hormonal → estrogen /
•• If low C3/C4- active disease
Q

drugs → procainamide, hydralazine

* For Making Notes

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•• CRP can be normal in active disease, if ↑↑- Anti histone Ab- drug induced SLE. Drugs causing this –
suspect infection in SLE. MD - SHIP

•• ESR – normal M - Minocycline , Methyldopa

Ab Significance D - D- penicillamine
Most sensitive, >98-99%, poor S - sulfonamides
ANA
specificity , >1:80 titres H - hydralazine
Specificity >95%, poor
I - isoniazid, interferons, infliximab
Anti ds DNA sensitivity - 50-70%, correlate
P - Procainamide
to lupus nephritis /vasculitis
Anti histone SLE → mild arthritis / serositis Lupus Nephritis
•• Specific for sjogren
syndrome. Class I – Minimal mesangial Asymptomatic →
•• Seen in SLE-Sjogren Class II- mesangial proliferative
Q
Tx: observe &ACEi
overlap

Anti Ro/La (SSA/ •• SCLE, Photsensitivity, Class III- focal

myocarditis, myositis, Nephritic →hematuria ,
SSB) Class IV- diffuse
shrinking lung syndrome, rbc cast +/- proteinuria
proliferative
neuromyelitis optica +/-AKI/HTN
immunosuppression
spectrum disorder,
neonatal lupus → CHB (need
Class V- membranous → Nephrotic → proteinuria/
permanent pacemaker)
edema
Anti U1 RNP MCTD
Class VI- advanced sclerosing → ESRD → standard
Anti Ribosomal P Specific for SLE (Pschiatric?) ESRD Tx.

Anti cardiolipin Ab /lupus SLE – management

anticoagulant Ab/ anti β2
glycoprotein Ab
C - Clotting, venous >arterial
APLAs
L - livedo reticularis
O - obstetrics complication
(recurrent pregnancy loss)
T - thrombocytopenia
Anti smith – 30% sensitive< 99-
Others
100% specific

•• SLEDAI – SLE disease activity index

–– When SLEDAI = 0 + Patient is not on
glucocorticoids → REMISSION
•• HCQ reduces flare.

* For Making Notes

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SYSTEMIC SCLEROSIS •• 1° vascular disease, skin thickening is a reaction

to underlying vascular damage and resultant
hypoxia.

•• Every patient has 2° raynaud’s phenomenon

abnormal nail fold capillaroscopy.

•• Female, middle age group

Limited Scleroderma Diffuse Scleroderma

Constitutional symptoms more common
General
. fever/fatigue/arthalgia
Skin (LEROY CLASSIFICATION)
Face &neck involvement common in Distal to knees/elbows Distal & proximal
both. + +
Raynaud’s phenomenon
Type 1 PAH >ILD ILD(MC is NSIP) > PAH
Pulmonary
PAH is the MCc of death ILD is the MCc of death
Esophageal dismotility → severe GERD ↓ intestinal motility
GI
1° biliary cirrhosis Constipation
SRC common (early )
Renal Scleroderma renal crisis rare (late) High dose corticosteroids ↑risk of
SRC, therefore avoided.
Cardiac rare RCM, conduction block common
Others Crest syndrome Raynaud’s
Anti Th/To Ab
ANA+ (>90-95%), RF+( 30%)
Anti topo I(anti SCL-70 Ab)→↑risk of
Ab Anti centromere Ab (40-50%)→↑risk
Q ILD & ↑SRC (anti RNA poly III)
of PAH Q
Anti U3 RNP
Prognosis Decent. >70% in 10years Poor prognosis, 40-50% in 10 yrs

–– H/o diffuse cutaneous systemic sclerosis

Treatment +MAHA (hemolysis / schistocytes) +
•• Skin thickening - Mtx /MMF ↓Platelet + severe AKI + ↑BP
•• ILD – MMF /Tocilizumab /Nintedanib •• PAH (Type 1) - Ambrisentan + Tadalafil +/-
Prostanoids
Q

•• Scleroderma renal crisis – ACEi only

* For Making Notes

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SJOGREN SYNDROME GLANDULAR EXTRAGLANDULAR

•• MC , develop early •• constitutional symptoms
•• Dry eyes →↓quality of •• MSK – Arthralgias /arthritis
life (abnormal sensation) •• ILD- MC NSIP
→ corneal ulceration •• RCM , Conduction block
•• Dry mouth → bad •• Distal RTA
odour/dental caries/
•• Hemat- MC is anemia (AOCD)
dysphagia/taste
•• Monoclonal gammopathy
•• Dyspareunia
-20%→↑risk of lymphomas
•• Dry skin- xerosis
•• MC cancer- NHL (Maltoma)
•• b/l parotid enlargement
•• Peripheral neuropathy (small
(symmetric & painless)
fibre) → Ix with skin biopsy

Ix: Triad
1.Serology –
1° Sjogren syndrome-
•• Idiopathic •• Anti Ro (SSA) - specific
Q

•• Female, 40-50 yrs of age

•• MC ANA + (>95%) non specific
•• Extraglandular manifestation - CD4 T cell
infilteration 2.Dry mouth- sialometry
•• Dry eyes - schirmer test
2° Sjogren syndrome-
3. Labial biopsy – focus score >1/4mm2
•• Some associated disease.
•• Treatment – Conservative &supportive
•• MCc- RA
•• Dry eyes- CMC ,cyclosporine eye drops
•• Dry mouth - pilocarpine

INFLAMMATORY MYOSITIS
Features DM PM sIBM NAM
Females>males, 30-40yrs age , Female>males, 30-40 Female>males, Any age
Epidemiology Males, >50 yrs
Can affect children also yrs age
Skin +/- proximal weakness Both proximal(MC
•• if only skin is involved – affected – quadriceps)
k/a Amyopathic DM (anti Proximal muscle +distal (long finger
Clinical Proximal muscle weakness
CADM 140/MDA5 Ab) weaknesss flexors) muscle
•• abnormal nail fold weakness + associated
capillaroscopy neuropathy

CPK ↑↑(>50X) ↑↑ (>50X) Normal/mild↑(<10X) Mildly ↑(<10X)

•• Anti SRP Ab (NAM
+cardiac involvement)
Anti NXP2 Ab •• Anti mup44 Ab, •• Anti HMG CoA
Q
Ab Anti TIF18(P155/140)Ab Anti Jo-1 Ab •• Anti 5’cytonucleotide reductase Ab
Q
Anti mi2 Ab Ab •• Anti 200/100 AG Ab
•• Both are associated
with statin exposure

* For Making Notes Inflammation less, No inflammation.

Peri-fascicular/peri fascial Endomysial inflammation
Biopsy inclusion body seen → β Necrosis , macrophage
inflammation(CD4) (CD8)
amyloid infiltration
Response to CS yes yes No yes
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•• Anti amino acyl tRNAsynthetase Ab

–– Histidyl = anti Jo-1 (MC synthetase antibody)
Q

SYNTHETASE SYNDROME
1. Fever
2. Raynaud’s
3. Myositis (polymyositis)
Holster Sign
4. ILD
5. Mechanic’s hands
•• Malignancy + myositis → can be associated with
polymyositis or dermatomyositis. Anti TIF-1ϒ
(p155/140)

V Sign

Heliotrope Rash

Mechanic’s Hands

RAYNAUD’S PHENOMENON

Shawl Sign

Triphasic Response. Pallor-Cyanosis-Reperfusion

Gottron Rash

* For Making Notes

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1° Raynaud - MC (>70—80%) 2° Raynaud (<10-20%)

Vessel wall Functionally abnormal Structurally abnormal
•• CTD (SLE/RA)
•• PAD(Buerger’s)
Etiologies idiopathic
•• Hematological
•• Drugs- ergot compound/cocaine
Epidemiology Females, 20-40 yrs of age Females, >30yrs age
Clinical Mildly symmetric, no tissue injured Severely asymmetric, thumb
Auto Ab No present (CTD related)
Nailfold Normal Abnormal (dilation & tortuosity seen)
Mild- moderate- CCB like nitrates
Moderate- severe- PDE5-
Treatment
Digit threatening- prostanoids
Recurrent /refractory – digital sympathectomy

VASCULITIS
Large Vessels Medium Vessels Small Vessels
Feature
TAKAYASU GCA PAN AAV IC
Female ,<40yrs Females , >50yrs, Variable, middle aged HSP, males, <20 yrs, Cryoglobulinemia-
Epidemiology Caucasians Variable variable
Asians 5-10% are HBV+
•• Microaneurysms
•• Infarcts to
Renal artery kidney.
stenosis / •• ++GN → Hematuria, RBC casts/ HTN/AKI
Renal renovasular rare •• HTN,↑S.
•• RPGN
hypertension Creatinine
•• Hematuria,
•• No RBC casts
Pulmonary rare - rare common Cryo >HSP (rare)
PN Rare/uncommon + + +
+
GI rare + + ( HSP> CRYO)
microneursym
+→palpable
purpura
Skin Rare none + + Raynauds
phenomenon,
PLT count
normal
Granulomas Yes no Yes, except MPA No
TRIAD-
MC artery involved
Wegener’s granulomas- Skin - palpable
is superficial
ENT involvement, pulmonary purpura –
temporal artery,
renal syndrome (MCc of death). common in LL/
temporal Q
MC artery C-ANCA + butts
Headache (MC), jaw
involved is Churg strauss syndrome +
claudication (2nd Q
subclavian HBS Ag+ , Testicular (EGPA) - bronchial asthma. MCC GI – abdominal
Others MC)
artery, arm pain, involvement of death is cardiac involvement. pain, +/-
ESR↑↑
pulseless radial P-ANCA + bleeding
Q Ophthalmic artery-
artery MPA - present with pulmonary +
artery AION , * For Making Notes immune syndrome, no ENT / Arthralgia
Blindness
no eosinophilia/ no bronchial +/- renal- IgA
IOC- Temporal Q
asthma. P-ANCA+ mesangial
artery bx
deposits
TOC-
Treatment HSP- NSAID’S
corticosteroids
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BEHCET’S DISEASE KAWASAKI DISEASE

•• HLA B51 •• Medium vessel vasculitis
Q

•• Recurrent oral apthous ulcers •• Coronary artery aneurysm

Q

•• Recurrent genital apthous ulcers- male : scrotum •• Children <5yrs, males, Asians
> shaft of penis
•• Gold standard Ix - Coronary angiography
•• Females: labia
•• Monitor disease - ECHO
•• Skin – erythema nodosum
•• Tx: IV Ig + aspirin
Q

•• Eyes- posterior uveitis >anterior uveitis,

F - fever, > 5days
hypopyon formation
E - enathems
•• Pathergy positivity
B - bulbar conjunctivitis (sterile)
•• Superficial thrombophlebitis +DVT
R - rash- groin /perianal
•• Arthritis /fever
I - internal organ involvement : coronary artery
•• CNS – brainstem involvement
involvement → aneurysm → AF/MI → death
L - Lymphadenopathy
E - extremity changes

* For Making Notes