Transcript By the pricking of my thumbs… - The Australian Rheumatology

AUSTRALIAN RHEUMATOLOGY ASSOCIATION
NEW SOUTH WALES BRANCH
Presented by
Prince of Wales Hospital
Venue: Concord Hospital
Main Lecture Theatre
Clinical Science Building
Thursday, 27th April 2012
6.15 pm Dinner for 7.00pm Meeting
***************
Programme:
1 “By the pricking of my thumbs…”
2 “…something wicked this way comes”
3 “ Double, double toil and trouble”
Presenters: Dr Ted Tsai and Dr Fred Joshua
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CATERING AND VIDEO-CONFERENCING SPONOSRED BY
“By the pricking of my thumbs,
something wicked this way comes...”
2 PORTENTOUS TALES IN
RHEUMATOLOGY
ted tsai
Fred Joshua
Prince of Wales Hospital
By the pricking of my thumbs...
Mr CD
73y/o previously healthy panel beater
 Etoh ½ bottle spirits/day
 no known CLD
 stapedectomy/bilat hearing loss/aids since age 18
 Dec 11 - elective admission under Plastics ?R hand cellulitis
 2wks ago thorn injury into R thumb pad
 progressive R thenar and thumb pain, erythema and swelling
 4 wks later, spread to 2nd MCP and tip of thumb
 1yr of Dupuytren’s contracture R 5th finger
Dec 11 admission
 well except for constant dull hand pain
 responsive to NSAIDS
 no fevers, night sweats, chills/rigors
 ESR 2, CRP 5
 FBC/EUC/LFT/CMP/glucose: unremarkable
 TSH/HBV/HCV: unremarkable
 ANA 1:320, ENA neg
 CCP/RF/ACE: neg
 HLA B27: neg
 Urate 0.30
 Xray R hand (Nov): no FB/#s, chondrocalcinosis of
triangular cartilage. Degenerative changes.
 R hand US: hypoechoic nodules palmar fascia at the 2nd
(25mm x 18mm) to 5th fingers (8 x 7mm), most likely palmar
fibromas ddx tendon sheath giant cell tumour
Progress
 ID R/V: exclude norcardia on bx; declined by derm
 Rheum RV: ?PsA ?gout ?other
 Empiric IV cephazolin and Flagyl x3/7, then PO fluclox
500mg qid x 5/7
 Colchicine 0.5mg bd x 1wk; PRN indocid
 Hand splinted in elevation sling
 D/C with outpt MRI R thumb
 Plastics/rheum F/U ?Dupuytren’s release
Rheum clinic F/U Feb
 Pain worsened
 Swelling and erythema now entire hand
 Spreading to L hand
 Subjective swelling feet/toe-pulps
 10mg predisone 3wk weaning course private rheumatologist
since D/C – little response
 Unable to hold objects/perform ADLs due to swelling and pain
 Poor oral intake
 5kg wt loss over 3mnths
Feb 12
MRI R thumb
with gadolinium
T2
Jan
R thenar eminence T2
MRI R thumb
with gadolinium
Jan
Small erosions at the radial margin of the first metacarpal head and base of
proximal phalanx at the first MCP joint with associated enhancement.
No other erosions identified. No significant effusion in the first MCP joint
but there is diffuse synovial enhancement consistent with synovitis.
Impression
Appearances would be consistent with an early inflammatory
arthropathy such as psoriatic arthropathy.
Gout is also a possibility.
Ix Feb 12
 Rpt bloods unchanged; neg inflam markers
 CT R hand: normal study
MRI R wrist/hand
Feb
MRI R wrist/hand
Feb
Impression
Nonspecific, diffuse distribution of abnormality.
Mild inflammatory changes of:
 subcutaneous and deep extra-articular soft tissue planes,
 tenosynovial compartments of flexor and extensor tendons,
 and joint spaces.
Mx
 Commenced on prednisone 25mg wean with





good response
Naproxen 500mg bd PRN
Nexium 40mg
Thiamine 100mg daily
Panadol osteo 2 tds
R Hand splint for analgesia
DIAGNOSTIC INVESTIGATION...
Ix
 CT C/A/P
multiple enlarged upper para-aortic and paracaval lymph
nodes. Largest 18 mm diameter in left para-aortic lymph node , and a 17
mm left para-aortic lymph node just below the level of the left renal
artery. There are also a few small retrocrural lymph nodes. No pelvic
lymphadenopathy.
Impression
There is bulky para-aortic and paracaval lymphadenopathy in the upper
abdomen and several small retrocrural lymph nodes. No primary tumour
site is identified. Lymphoma should be considered.
 LDH 328 (ULN 250)
 Beta2 microglobulin 3.9 (ULN 1.8)
 PSA neg
 clinically no easily accessible nodes for bx
PET report
diffuse intense uptake in
retrocrural and intra-ab para-aortic LNs
c/w high grade lymphoma
CT guided LN core bx
Cytology: features consistent with metastatic large cell
carcinoma.
Histopath: features c/w met adenocarcinoma from
upper GI, or biliary tract, or pancreas.
Endoscopies:
EUS:
unremarkable
2.8cm heterogeneous mass in inferior
uncinate process c/w pancreatic ca with lymph
node metastases
summary
 73y/o healthy man
 3mnths progressive hand/feet inflammation
and contractures
 assoc 5kg wt loss
 ab lymphadenopathy on CT C/A/P and PET
 pancreatic ca dx on EUS
Diagnoses
Met pancreatic adenoca
Paraneoplastic palmar fasciitis and polyarthritis
Palmar Fasciitis +/- Polyarthritis
Palmar fasciitis
 rare (~40 cases in literature) paraneoplastic condition, commonly
described with ovarian cancer.
 Malignancies: breast, cervical, bladder, endometrial, gastric,
hepatocellular, lung.
Clinical Presentation
 progressive fibrosis of the hands, resulting in flexion contractures.
Usually bilateral and rapidly progressive.
 woody skin texture suggestive of scleroderma or RSD.
 +/- coincident carpal tunnel syndrome.
 polyarticular arthralgias and joint tenderness mimicking inflammatory
arthritis.
Mx
 usually refractory to therapy but occasional response to steroids
 successful treatment of the underlying malignancy may improve or halt
progression.
something wicked this way comes...
Mrs VC
 58y/o north coast ex-RN T/F Dr Hanish Bagga
B/G
1. Right NOF#
2. Hyperlipidaemia
3. HT
4. Depression
 Ex-smoker
 EtOH++
p/w
2wks facial swelling, prox LL weakness and rash
 acute onset rash
 quadriceps weakness R>L;
difficulty with stairs
 no bladder/bowel disturbance
 no wt loss/fevers
 O/E
 3+ neck flexors
 4/5 shoulder and hip flexion
 Cardio/resp/ab exams
unremarkable
Ix
 ESR 25 / CRP 34
 CK 952
 ANA 1:320 h
 ENA / Mi2
 ds DNA /C3/4/ RF / CCP
 Cryoglobs / LAC
 EMG [deltoid/vastus lateralis]: small polyphasic motor units,
reduced interference patterns, no spontaneous activity.
 MRI thighs: diffuse T2 hyperintensity and mild atrophy all
thigh muscle groups.
 Skin biopsies: mild interface dermatitis.
 Muscle Bx [vastus lateralis]: atrophic myofibres, increased
MHC1 and MAC staining c/w autoimmune myositis.
Malignancy Screen
 CA 19.9 135 (<40)
 AFP/CA125/CEA




CXR
CT brain + C/A/P
Bone scan
Mammogram




GI endoscopies
PAP smear
Pelvic U/S
CT neck
PET Scan: markedly glucose avid lesion left
level 2 cervical lymph node
 Level 2 neck LN bx: poorly differentiated metastatic
squamous cell carcinoma.
 Nasal endoscopy bx (multiple sites):
L base of tongue SCC
Mx
 Prednisone 75mg daily
 IVIG 33g x 5/7
 Radiation Tx
summary
 58y/o ex-smoker/etoh dependence
 classic DM presentation with extensive skin dz
 neg extensive conventional malignancy screen
 met base of tongue SCC found only via PET and
subsequent blind nasal endoscopy bxs
paraneoplastic rheumatisms
Dermatoses
Myositis
Synovitis
Bone
Vasculitis
paraneoplastic rheumatisms
 Pathogenesis




Immune eg. DM
Hormonal eg. FGF-23 osteomalacia
Cytotoxic tumor factors eg. myopathy
Cytokines eg. myalgia
paraneoplastic rheumatisms
 Rheumatic symptoms may manifest before, during, or
after malignancy dx
 Course parallels activity of malignancy
 Treatment of underlying malignancy may be curative
 Respond poorly to conventional rheumatic treatments
 Steroids helpful in inflammatory paraneoplasms and
lymphoproliferative dz
 Immunosuppression in immune-mediated
paraneoplasms
paraneoplastic rheumatisms
Dermatoses
Myositis
Synovitis
Bone
Vasculitis
Paraneoplastic dermatoses
 Eosinophilic Fasciitis-Panniculitis syndrome
 prox limb +/- trnk
 haem ca.
 poor steroid response
 PPP = panniculitis, polyarthritis, and pancreatic disease
?periarticular fat necrosis from pancreatic enzymes
 Schmids triad: pancreatic tumour, eosinophilia, polyarthritis
Ashouri and Daikh. Rheumatic Manifestations of Cancer.
Rheum Dis Clin N Am 37 (2011) 489–505.
Bazex syndrome
(acrokeratosis paraneoplastica)
Paraneoplastic dermatoses
Bazex syndrome (acrokeratosis paraneoplastica)
 mimicks SLE, seborrhoeic dermatitis, psoriasis
 symmetric psoriasiform plaques
 Nose, helices, earlobes, distal extremities
 nail dystrophy
 palmarplantar keratoderma
 men >40y/o, smokers/etoh +, HLA A2/B8
 upper aerodigestive SCC (64%)
 met nodal disease 50%
Paraneoplastic dermatoses
 Scleroderma


+ve RNA III polymerase autoab subgrp (?)
breast ca, lung, ovarian, GI ca
Shah & Rosen.
Cancer and systemic sclerosis:
novel insights into pathogenesis and clinical implications.
Current Opinion in Rheumatology 2011, 23:530–535.
Multicentric Reticulohistiocytosis
Wright GD, Doherty M.
Unusual but memorable. Multicentric reticulohistiocytosis.
Ann Rheum Dis. 1997 Feb;56(2):134.
Paraneoplastic dermatoses
Multicentric reticulohistiocytosis
 Caucasian women fourth decade
 15-30% underlying ca: lung, breast, gastric, cervical
 characteristic dermatosis with destructive polyarthritis
 firm brown papules and nodules over ears, hands, head
and skin over jt-lines
 coral bead sign: aligned periungual papules
 symmetric erosive arthritis, progressing to arthritis
mutilans
Wright GD, Doherty M.
Unusual but memorable. Multicentric reticulohistiocytosis.
Ann Rheum Dis. 1997 Feb;56(2):134.
 ?histiocytes differentiating into osteoclastlike
multinucleated giant cells in the skin
 Bisphosphonates
 Mtx and TNFi
paraneoplastic rheumatisms
Dermatoses
Myositis
Synovitis
Bone
Vasculitis
Paraneoplastic myopathies
 DM >> PM, (IBM)
 ?immune cancer control
 20-30% malignancy association with DM dx
 DM: SIR 6.5 [CI 3.9–10], PM: SIR 2.0 [CI, 1.4–2.7]
 Ca. risk highest 1yr of DM dx, extending to 5yrs
 Adenocas: lung, ovary, cervical, stomach,
pancreas, colorectal and lymphoma (esp PM)
Predictors for underlying ca.
age>52
male
skin manifestations
(necrosis, periungual erythema, V or shawl sign)
dysphagia
 severe, refractory or recurrent muscle weakness
Protective factors
arthritis, Raynauds, ILD, Jo-1 abs
neg anti-p155 ab (TGFb signalling, NPV 93-97%)
Selva-O’Callaghan A, Trallero-Araguas E, Grau-Junyent JM, et al.
Malignancy and myositis: novel autoantibodies and new insights.
Curr Opin Rheumatol 2010;22(6):627–32.
Selva-O’Callaghan A, Grau JM, Gamez-Cenzano C, et al.
Conventional cancer screening versus PET/CT in
dermatomyositis/polymyositis. Am J Med 2010; 123(6):558–62.
 prospective 3-year multicenter study
 55 consecutive DM/PM patients
 Conventional screening
•complete physical examination, routine pathology
•CT chest/ab
•tumor markers (CEA, CA-125**, CA-19-9, PSA)
•gynecologic examination incl US and mammography
vs PET/CT
9/55 pts with malignancy
PET/CT = good single test
 RESULTS: similar predictive value of 93% and equivalent
sensitivity, specificity, PPV, and NPV for excluding occult
malignancy.
 CONCLUSION: PET/CT is comparable to broad and
extensive cancer screening in terms of accuracy, and
advantage of being one single, convenient test
Proposed yearly PET/CT scans in anti-p155 positive pts,
single PET/CT scan at diagnosis in anti-p155 negative pts
Paraneoplastic myopathies
atypical PMR
 Haematologic malignancies
 Age <50
 ESR<40 or >100mm/h
 Asymmetric dz
 Poor response to low dose steroids
 Prolonged symptoms
 GCA case reports: lung, breast, cervical ca, MM, CML
paraneoplastic rheumatisms
Dermatoses
Myositis
Synovitis
Bone
Vasculitis
Carcinoma Polyarthritis
 men, >60y/o
 lung, breast, colon, ovarian, lymphoproliferative ca
 asymmetric, migratory or additive oligoarticular dz
 lower limb large jts, spares hands
 subset mimicks late-onset RA, prominent constitutional sxs
 high inflammatory markers
 RF+ 46%, CCP <1%
 no erosions
 ?immune complex deposition in synovium
RS3PE
Revue du Rhumatisme 71 (2004) 484-488
Le syndrome RS3PE existe-t-il ?
Thierry Schaeverbeke, Christophe Richez, Joel Dehais
RS3PE
remitting Seronegative Symmetric
Synovitis with pitting edema
 ?late-onset RA subset
 idiopathic vs paraneoplastic variant
 systemic signs/symptoms and poor steroid
response in paraneoplastic variant
 prostate, colon, gastric, ovarian, endometrial ca
 CLL, lymphoma and MDS
 ?immunogenic T cell inflammatory response
RS3PE
 wrists, carpus, small hand jts,
flexor sheaths, ankles
 prominent pitting limb oedema , ‘boxing-glove’
 non-erosive
 excellent steroid response and prognosis unless
paraneoplastic (>10mg/d)
Amyloid Arthritis
 monoclonal light chain deposition in synovium
 ?5% MM pts
 mimicks RA
 non-inflammatory synovial fluid, amyloid bodies
in sediment (synovial villi with amyloid deposits)
 poor prognosis
paraneoplastic rheumatisms
Dermatoses
Myositis
Synovitis
Bone
Vasculitis
HPOA
 NSCLCa, mesothelioma, GI and nasopharyngeal ca
 periostitis at ends of long bones, large appendicular
joints, (MCP/MTPs)
 occasional frank synovitis and soft tissue
inflammation
 ?activation of pulmonary factor in R-L shunting
?VEGF release ?PDGF
 Xray: periosteal lucency, bone scan more sensitive
 COX-2 inhibition helpful ?PGE-2 pathology
Osteogenic Osteomalacia
 = tumour-induced osteomalacia
 ectopic FGF23 secretion -> hypoPO4
 small mesenchymal ca requiring PET/octreotide scan
 neurofibromatosis, polyostotic fibrous dysplasia,
prostate ca, oat cell ca, haematologic ca
 generalised weakness, multiple #s, bone pain
and radiologic osteomalacia
paraneoplastic rheumatisms
Dermatoses
Myositis
Synovitis
Bone
Vasculitis
paraneoplastic vasculitis
 2-5% of all vasculitides
 prevalence 1: 1800 haem ca, 1: 80,800 solid
tumours
 commonest: leukocytoclastic vasculitis (LCV)
with haematologic ca
 no ca-vasculopathy correlation except PAN and
hairy-cell leukaemia, leukaemia and Sweet’s
syndrome
paraneoplastic vasculitis
 ANCA vasculitides (MPA, GPA, CSS)
 <5%, but RR 6 [3.7-9.7] concurrent ca dx
 PAN
 15% of all paraneoplastic vasculitides
 hairy-cell leukaemia, bladder, GI, lung, liver, MDS, CML
 Immune-complex
 LCV: commonest, haem ca
 Cryo: type I, hyperviscosity
 HSP: elderly men with renal involvement
Case 1: by the pricking of my thumbs
Case 2: something wicked this way comes
paraneoplastic rheumatisms
Dermatoses
Myositis
Synovitis
Bone
Vasculitis
acknowledgments
 Dr Michael Tjeuw
 Dr David Veitch
 Dr Penny Clohessy