Ch. 44-Sjogrens, Still's, Relapsing polychondritis Flashcards
(138 cards)
1
Q
What features are required for a diagnosis of systemic onset JIA
A
- High episodic fevers daily for 2 weeks
- Atleast one of: evanescent rash, splenomegaly, hepatomegaly, serositis, general LAD
- Symmetric poly arthritis > oligo arthritis (erosive in 20%) –> onset may be delayed months to years
2
Q
Name 6 lab abnormalities in juvenile stills
A
Elevated ferritin Elevated ESR/CRP Anemia Leukocytosis with neutrophilic Thrombocytosis *RF and ANA neg Polyclonal gammopathy
3
Q
What type of immune system activation is seen in juvenile Still’s
A
Innate immune with Il-1, TNF alpha and IL-6 production
4
Q
Name 6 signs and symptoms Still’s
A
- Daily spiking fevers >38.9 often in evening
- Arthralgia, often coincide with fevers
- Arthritis-often polyarticular and symmetric, can come at same time rash onset or months to years later, often knees, ankles, hips, small hand joints
- Transient evanescent rash
- lymphadenopathy
- hepatosmplemegaly
5
Q
Describe 4 cutaneous characteristics of juvenile stills
A
- transient, evanescent pink salmon coloured rash often coincides with fevers
- predilection to axillae, waist, linear lesions/flagellate erythema
- periorbital edema/erythema
- may get RA nodules
- persistent plaques, which also may be linear
6
Q
Name 2 path findings show of juvenile Stills
A
-perivascular and interstitial neutrophil-dominant mixed infiltrate –> “neutrophilic urticarial dermatosis”
A variable number of dyskeratotic keratinocytes, located primarily in the upper epidermal layers, is also a typical finding.
7
Q
what % sJIA have persistent arthritis
A
In ~40–50% of patients, the arthritis resolves completely.
50% of the children may have a chronic course that includes persistent arthritis
8
Q
Name 6 treatment options sJIA
A
NSAIDS for mild articular disease Steroids +- MTX Leflunomide Aza Abatacept Anti-tnf (less for systemic JIA >JIA) Anti-IL-1 (anakinra) Anti IL-6 (toci) Stem cell transplant
9
Q
Average age onset AOSD?
A
Before age 30 in majority, usually young adults
10
Q
What type of immune response is seen in stills, name 5 cytokines elevated?
A
Th1 response
TNFalpha IFN gamma IL-2 IL-6 IL-18
11
Q
Name 6 non skin manifestations AOSD
A
- Fever-often 39+, daily in evening
- Sore throat
- Constitutional sx
- Hepatomegaly > splenomegaly
- Arthritis- symetric, knees wrists ankles, present in 65-100%, joint pain often with fever spike,
- carpal ankylosis-minimal pain but difficulty moving carpal bones, can also occur DIP, PIP and C-spein but sparing MCPS
- Other organists can occur but rare (pull fibrosis, pleuritic, pericarditis, myocarditis, nephritis
12
Q
Name 5 lab findings in AOSD
A
elevated ESR/CRP Elevated ferritin thrombocytosis Leukocytosis Anemia
13
Q
Describe the skin rash in AOSD
A
Salmon-pink Asymptomatic Transient, occurs with fever spikes Macular Points of pressure--> most often on trunk but can be extremities Koebner and flagellate erythema (rare) Eyelid edema (rare)
Violaceous to reddish brown, scaly, persistent papules and plaques can also occur
14
Q
Pathology findings AOSD
A
Same as sJIA
mixed perivascular and interstitial infiltrate composed of neutrophils and lymphocytes–> “neutrophilic urticarial dermatosis”
dyskeratotic keratinocytes
15
Q
Manistay treatment of stills? Name 4 other options
A
Prednisone first line MTX second line Toci (Îl-1) or anti IL-6 Ritux Anti-tnf
16
Q
Relapsing polychondritis: For a diagnosis you need bx proven chondrites in 2/3 sites. What 3 sites?
A
Auricular
Nasal
Laryngotracheal
17
Q
If only 1 bx site proven chondrites, you need what other criteria to make diagnosis?
A
At least 2 of the following: ocular inflammation vestibular dysfunction hearing loss seronegative inflammatory arthritis
18
Q
Average age onset polychondritis?
A
20-60
19
Q
Race most commonly affected polychondritis?
A
Caucasian
20
Q
Proposed antigen being attacked in relapsing polychondritis?
A
Type 2 collagen
21
Q
What % patients with relapsing polychondritis have autoantibodies ?
A
50% against type II collagen
22
Q
Describe the cutaneous clinical features auricular chondrites
A
Erythema, swelling and pain of cartilaginous portion auricle, can last days to weeks, compromise hearing, eventually develop scarring and destruction of cartilage, sparing the earlobe
23
Q
What are the most common sites of chondritis
A
Ear/auricle
Nose
Costochondral joints
Larynx, trachea, bronchi (respiratory tract)
24
Q
Describe 10 manifestations of relapsing polyhchondritis
A
- Auricular chondritis
- Nasal chondritis and saddle nose deformity (pain, stuffiness, crusting, rhinorrhea, epistaxis and compromise of olfaction can occur)
- Chostochondral chondritis
- Respiratory tract chondritis with cough, hoarseness, choking, dyspnea, wheezing, or tenderness to palpation of the anterior neck in sites overlying the larynx or trachea –> airway obstruction or collapse, flail chest, and secondary pulmonary infections.
- Arthritis-asymetric, migrating, oligo
- Ocular inflammation
- Cutaneous lesions
- Renal- GN, AIN
- cardiovascular-aortitis, peri and myocarditis, conduction defects
- neurologic - cranial nerve palsies, vasculitis peripheral nerves
25
Name 7 non-cartilage cutaneous lesions in relapsing polychondritis
```
Apthae
SVV
annular urticarial lesions
lived reticularis
sweets
EED
Erythema nodosum
```
26
What is MAGIC syndrome
Mouth and genital ulcers and inflamed cartilage
-relapsing polychondritis and beeches overlap
27
Name 2 diseases associated with relapsing polychondritis
Myelodysplastic syndrome
| Other autoimmune disorders
28
What features increase risk MDS in relapsing polychondritis
Apthous ulcers
| Small vessel vasculitis
29
Pathology of relapsing polychondritis?
Neutrophilic infiltrates early--> lymphoplasmacytic later--> eventual fibrosis and granulation tissue
30
Name 10 things on ddx for nasal deformity or destruction
Infectious--> Bacterial, leprosy, tb/lupus vulgarisms, rhinoscleroma, dimorphic fungi (parcocci), syphillis (tertiary), mycobacterial, aspergillosis, leish
Inflammatory--> GPA, sarcoid, SAVI, PLAID,
Neoplastic--> Nasal NK T cell lymphoma (anglocentric T cell lymphoma), SCC, BCC, sarcomas
Cocaine use
Factitious/trauma
31
Most common causes of death in relapsing polychondritis
pneumonia, systemic vasculitis, airway collapse and renal failure
32
List 6 treatments for relapsing polychondritis
```
Prednisone mainstay
NSAIDs and colchicine
HCQ
Other immune suppresants--> MTX. AZA, cyclosporine, MMF, cyclophosphamide)
Anakinra
Toci
```
33
4 factors associated with poor prognosis in SJogrens
vasculitis
hypocomplementemia
cryoglobulinemia
parotid enlargement
34
What are the ACR criteria for Sjogrens?
Score 4+
Must meet inclusion criteria and exclusion criteria
1. SSA/RO + = +3
2. Labial salivary gland with focal lymphocytic sialadenitis and focus score of ≥ 1 foci/4 mm = +3
3. Ocular staining score 5+ in one eye
4. Schirmer test less than or equal to 5mm in one eye/5 min
5. Whole salivary flow rate less or equal to 0.1 ml/min
35
What are the inclusion criteria for Sjogrens ACR criteria
Must be yes to at least one:
(1) Have you had daily, persistent, troublesome dry eyes for more than 3 months?
(2) Do you have a recurrent sensation of sand or gravel in the eyes? (3) Do you use tear substitutes more than 3 times a day?
(4) Have you had a daily feeling of dry mouth for more than 3 months?
(5) Do you frequently drink liquids to aid in swallowing dry food
36
What are 7 exclusion criteria of Sjogrens (can't have these)
1. AIDS
2. Sarcoid
3. Amyloid
4. H/N radiation
5. Active Hep C
6. GVHD
7. IgG4-related disease
37
What medications should be stopped before evaluating for SJogrens
Anticholingergics
38
Prevalence of Sjogrens in population? M:F ratio? Average age onset?
F:M 9:1
0.3-0.6% pop'n
4th/5th decade in onset
39
3 most common disease associations in Sjogrens (Secondary sjogrens)
rheumatoid arthritis
systemic lupus erythematosus (LE)
scleroderma
40
What is the disease with 20x increased risk in Sjogrens
Lymphoma
| *These B-cell lymphomas are often extranodal and can originate in salivary as well as lacrimal glands
41
Major defining features of Sjogrens
Xeropthalmia--> can lead to e keratitis, corneal thinning and ulceration, and recurrent infections
Xerostomia--> can lead to dental caries, salivary gland infections, GERD, thrush,
Vaginal dryness--> candida
42
How to test for xeropthalmia
Sschirmer test
or
Corneal evaluation by optho--> fluorescein
43
How to test for xerostomia
Salivary gland scintigraphy
Sialometry
Parotid gland sialography
*Salivary gland biopsy most commonly done
44
Most common cutaneous manifestation Sjogrens
Xerosis with pruritus
45
Name 7 cutaneous manifestations Sjogrens other than xerosis
```
*Purpura palpable and non palpable, petchiae--> lots of reasons
Cutaneous SVV
Hypergammaglobulinemic purpura of waldenstrom--> capillarities or petechiae
Urticarial vasculitis
Annular erythema
Erythema nodosum
Nodular amyloidosis
Sweets syndrome
Cryoglobulinemia
Raynauds
```
46
Name 3 RF for developing B cell lymphomas and increased mortality
vasculitis
cryoglobulinemia
hypocomplementemia
47
Extraglandular sjogrens organ involvement, name 5
Lungs-interstitial pneumonitis
Renal -interstital nephritis
Bone marrow
Neuro--> peripheral neuropathy, short term memory loss, depression, hearing loss
Arthritis*--> polyarticular, non-erosive, chronic and progressive, and it can be asymmetric, knees and ankles
48
What type of lymphoma are Sjogren's patients at risk of developing
B-cell lymphomas, often extranodal in origin (e.g. salivary glands, lacrimal glands) and usually marginal zone lymphomas of the MALT origin
49
Name 5 lab findings in Sjogrens
```
SSA- 60-80%
SSB-40-60
ESR
RF
Hypergammaglobulinemia
```
50
Treatment xerophthalmia
- artificial tears
- punctal plugs
- topical cyclosporine
- home humidifiers
51
Treatment xerostomia
Lifestyles: stop smoking, reduce salty/spicy/acidic foods and drinks, lower sugars/carbs (dental caries), avoid anti-histaminesand anticholinergics, use sodium bicarb rinses, humidifiers, DENTAL CARE
Saliva substituteS: Biotene spray or gel, lozenges
Saliva stimulants:
- local--> xylitol containing gums/lozenges
- systemics: Pilocarpine, cimevuline
52
When to consider systemic treatment in sjogrens
Cutaneous vasculitis or internal organ involvement
53
Name 4 systemic treatments for Sjogrens
Prednisone
MTX
MMF
AZA
54
What antibody associated with MTCD
U1RNP
55
Major cause of death in MCTD
pulmonary hypertension
56
MCTD encompasses which AI diseases?
SLE-less likely renal
Systemic sclerosis-often pHTN
Myositis/polymyositis (rare to see DM findings)
RA-arhtirits ranges from mild to erosive
57
Name 6 core features of MCTD
1. high-titer IgG anti-U1 ribonuclear protein (U1RNP) antibodies,
2. Raynaud phenomenon-ulcers can occur
3. swollen hands or sclerodactyly
4. myositis-inflammatory, no DM usually
5. esophageal dysmotility and GERD
6. arthritis-mild to erosive
7. pHTN in 25%
8. Pleurisy and pericarditis
58
Name 8 cutaneous findings in MCTD
1. Raynauds with ice pick digital infarcts, often nail fold capillaries show dropout
2. Scleredema and sclerodatyly
3. Poikilodermatous lesions on upper trunk and extremity
4. ACLE or SCLE lesions
5. Livedoid vasculopathy
6. cSVV
7. Calcinosis cutis
8. cutaneous mucinosis
9. RA nodules
10. Oral mucosal lesions--> ulcers, septal perforation
59
2 lab findings suggestive pHTN in MCTD
APLS labs +
| NtPROBNP
60
3 labs tests to help distinguish MCTD from SLE
Lack of:
- hypocomplementemia
- anti-dsDNA
- anti-Sm antibodie
61
How to distinguish MCTD vs. SSc
Severity arthritis and myositis
62
Name 10 cutaneous manifestations in or seen in RA
Palisading granulomas
- RA nodules
- Palisaded neutrophilic and granulomatous dermatitis (PNGD) and interstitial granulomous dermatitis (IGD)
Neutrophilic
- Pyoderma gangrenosum
- Sweets
- Neutrophilic lobular panniculitis
- rheumatoid neutrophilic dermatitis
Vascular
- Bywaters lesions
- small and medium vasculitis
- feltys
- EED
- Intravascular/intralymphatic histiocytosis
- Superficial ulcerating rheumatoid necrobiosis.
* drug cutaneous manifestations related separately
63
What % patients with RA get nodules
20%
64
What is a RF for rheumatoid nodules?
RF+ moderate to high titres
65
Where do rheumatoid nodules occur? What do they look like
Extensor surfaces and pressures points
Periarticular
*Forearms extensor, around elbow, around MCPS, PIPs and DIPS
Firm/Semi-mobile papulonodules often asymptomatic, skin coloured
66
What 2 medications are though maybe to stimulate nodulous?
MTX
TNF's
*Also associated usually with steroid tapers tho so hard to know
67
What drug can cause a papular eruption whose histologic features overlap with those of interstitial granuloma annulare and interstitial granulomatous dermatitis
MTX
68
Pathology for RA nodules
Acute or early lesions may show leukocytoclastic vasculitis and/or an interstitial neutrophilic infiltrate.
central zone of eosinophilic fibrin surrounded by palisaded histiocytes, deep dermis or subcutis
69
DDX RA nodules
Subcutaneous granuloma annulare
gouty tophi
Synovial hyperplasia/cysts (softer, painful)
70
3 RF for RA vasculitis
high titre RF
severe erosive arthritis
RA nodules
71
When does RA vasculitis typically appear
Late stage
72
What % RA patients get vasculitis
2-5%, but up to 1/3 autopsies
73
How does RA vasculitis present on the skin
with palpable and non-palpable purpura in small vessel disease
nodules, ulcerations, necrotizing livedo reticularis, and/or digital infarcts in medium-sized vessel disease
74
Name 7 extra cutaneous manifestations RA vasculitis
```
neuropathies
cerebral infarction
scleritis
alveolitis
carditis
intestinal ulcers
renal involvement with proteinuria.
```
75
Most common non cutaneous manfiestiaon RA vasculitis
Neuropathy-mononeuritis multiplex
76
If suspect RA vasculitis but can't get cutaneous biopsy, next step?
Nerve conduction studies follower by sural nerve bx or muscle bx
77
Mortality rate RA vasculitis
AS high as 40%
78
What are by waters lesions
Purpuric papules distal digits like pulp or nail fold thromboses
Path shows LCV
Not associated systemic vascular
79
What is Felty's syndrome
Seropostiive RA
Splenomegaly
Neutropenia
Leg ulcers-often treatment resistant, pretibial
79
What is Felty's syndrome
```
Seropostiive RA
Splenomegaly
Neutropenia-increase infix risk
Leg ulcers-often treatment resistant, pretibial
Increased risk lymphoma and leukaemia
```
80
Causes felty syndrome ulcers
```
Multifactorial, could be:
PG
Vasculitis
Ulcerative PNGD
venous HTN
Neuropathy
```
81
What does Rheumatoid neutrophilic dermatitis resemble?
Clincally/histopathologically resembles Sweet's
Often in seropositive RA
-erythematous urticarial papules and plaques that are persistent and asymptomatic, but occasionally ulcerate. Lesions are symmetrically distributed, most commonly on the extensor forearms and hands, but they can occur elsewhere.
82
How to tell PAN from RA vasculitis on path
Direct immunofluorescence in rheumatoid vasculitis shows prominent deposition of IgM as well as C3 in small and medium-sized vessels,
in polyarteritis nodosa the IgM and C3 vascular deposits are weaker and sparse and limited to medium-sized vessels.
83
Main ddx based on lab markers for RA vasculitis
Cryoglobulinemia due to + RF, vasculitis and low complements
*Cryo typically low C4 tho, lower titre RF
84
Ddx ulcers in RA
```
PG
Vasculitis
Infection from immunosuppresion
Ulcerative PNGD
Secondary APLS
Angiocentric lymphomas
Thromboembolic
Suprecifical ulcerating necrobiosis
```
85
Ddx palisaded necrotizing granuloma
```
EGPA
GPA
Rheumatic fever nodule
Palisaded neutrophilic granulamtous dermatitis - in association with AI-CTD (RA, vasculitis)
Rheumatoid nodule
```
86
PAlisaded necrotizing granuloma with basophilic collagen degeneration, neutrophil dominant, C-ANCA +?
Most likely GPA
87
Palisaded necrotizing granuloma with basophilic degeneration or eosinophilic degeneration, eos dominant?
EGPA
88
Palisaded necrotizing granuloma, basophilic collagen degeneration, netrophil dominant and P-ANCA + or ANCA neg?
AI-CTD like RA or vasculitis
89
Palisaded necrotizing granuloma eosinohpilc degeneration that is neutrophil dominant? NExt step and ddx
RF+ —> Rheumtoid nodu;e
| RF- —> Rheumatic fever nodule
90
Name 2 treatments RA nodules
Excision-but often recurs
| ILK- often not complete resolution
91
Name 3 treatment options rheumatoid neutrophilic vasculitis
Steroids
DApsone
Colchicine
92
Name 2 treatments Feltys
G-CSF and/or splenectomy
93
Main tx for aggressvie RA vasculitis
Pulse IV pred + cyclo and plex
94
Name 3 tx options SVV in RA
MMF or AZA
*MTX often doesnt work
TNF’s
Ritux
95
Name 2 tx options RA PG
Steroids +Cyclosporine
| TNFs
96
What is PAPA syndrome? What is the gene mutation?
Pyogenic sterile arthritis
Pyoderma gangrenosum
Acne
Mutation in PSTPIP1
Protein: CD2 binding protein 1
97
What is mode inheritance PAPA
AD
98
What is PASH?
Pyoderma gangrenosum, acne, suppurative hidradenitis
99
What is PAPASH
Pyogenic arthritis, pyoderma gangrenosum, acne, supparative hidradentitis
100
Name 6 hereditary periodic fever syndromes
Familial Mediterranean Fever (FMF)
TNF receptor associated periodic fever (TRAPS)
Hyperimmunoglobulinemia D with periodic fever syndrome (HIDS)
CAPS-Cryoporin associated periodic syndromes
1. NOMID- Neonatal onset multisystem inflammatory disease
2. Muckle Wells
3. FCAS
101
What is mode of inheritance FMF
AR
102
What ethnicity does FMF affect
```
Turkish
Sephardic jewwish (spain and portugal)
Italian
Armenian
Arab
```
103
What gene is mutated in FMF? What protein?
Gene: MEFV
Protein: Pyrin
104
Average attack length in FMF
1-3 days
105
What are the cutaneous findings of FMF
Erysipeloid erythema and edema
Favors lower leg and foot
LCV/IgA vasculitis in 5-10%
106
Name 5 non cutaneous findings in FMF
```
Peritonitis > pleuritis >pericarditis
Monoarthritis > exercised induced myalgia
Rarely aseptic meningitis
Acute scrotal swelling
Splenomegaly
```
107
Name 1 laboratory finding in FMF
Low C5a inhibitor in serosal fluids
108
Treatment FMF-Name 3
1. Colchicine ppx
2. NSAIDS
3. TNF inhibitors
4. Thalidomide
5. Herbal remedies?
109
Mode of inheritance HIDS
AR
110
Gene mutated in HIDS? Protein?
MVK
Protein: Mevalonate kinase
Key enzyme cholesterol pathway
111
Lengthj of attack in HIDS
3-7 days
112
Cutaneous lesions in HIDS
Erythematous macules and edematous papules which may become purpuric
Occasional vaginal and oral ulcers
Widepspread on face , trunk and extremities
Common to get HSP/LCV
113
Average onset of HIDS
6 months
114
Typical flare signs/symptoms HIDS
```
Fever
Skin
Cervical LAD
Hepatosplenomegaly
Abdominal pain, rarely serositis
Arthralgias
HEADACHE
```
115
What lab value is elevated in HIDS
High serum IgD (>100)
| High IgA1 mevalonate in urine
116
Mode inheritance of HIDS
AR
117
Name 4 treatment options HIDS
Steroids acute attacks
Anakinra
TNF inhibitors
Simvastatin
118
Mode inheritance of TRAPS
AD
119
Gene and protein mutated in TRAPS
Gene: TNFRSF1A
| ProteinL TNF receptor 1A
120
Length of attacks in TRAPS
Often over 1 week
121
Cutaneous features of TRAPS
Erythematous patches and edematous plaques often with annular or serpiginous
LAter ecchymotic
Rarely oral ulcers
Migrate distally on an extremity with underlying myalgia, may be more widespread
122
Flare symptoms of TRAPS
Skin
Peritonitis>Pleuritis and pericarditis
Migratory myalgia>Arthralgia >monoarthritis
Periorbital edema, conjuctivitis, rarely uveitis
Headache
Scrotal pain, splenomegaly, occasional LAN
123
Name 2 tx options TRAPS
Steroids
| TNF inhibitor
124
Lab marker TRAPS
Low serum soluble TNF receptor-1 between attacks
125
What gene is mutated in the cryoporin associated periodic syndromes
NLRP3
| Protein: Cryoporin
126
Mode inheritance of CAPS
AD for all of them
127
What chromosome is NLRP3 on?
1q44
128
What ethnic group typically sffected by CAPS
Any ethnic group
129
How does MWS present?
- flare length
- cutaneous findings
- extra cutaneous findings
1-2 days
Urticarial papules and plaques-widesapread on face, trunk, extremities
Non skin:
-abdo pain but rarely serositis
-Myalgias with lancinating limb pain
-arthralgias, sometimes large joint oligoarticular arthritis
-conjuctivitis, episcleritis, optic disc edema
-sensorienrural hearing loss
-headache
130
What % MWS develop amyloidosis
25%
131
Name 4 tx options MWS
Steroids
| IL-1 antagonists : Rilonacept, canakinumab, Anakinra
132
Attack length in FCAS
Minutes-3 days
133
Cutaneous findings in FCAS
Cold induced urticarial papules and plaques
| Extremities >trunk and face
134
Non cutaneous flare signs and symptoms in FCAS
Arthralgia>myalgias
Conjuctivitis
HEadache
135
Treatments FCAS: NAme 1
IL-1/IL-1R antagonists
136
Describe 8 features of NOMID
1. Skin-urticarial papules and plauqes, occasionally ulcers on face, trunk extremities
2. Often continuous disease, flares in between
3. MSK: Epiphyseal and patellar overgrowth, arthritis, deforming arhtropathy
4. Eyes: Conjuctivitis, uveitis, optic disc edema, blindness
5. Neuro: sensorineural hearing loss, aseptic meningitis, seizures
6. Lymph: LAN, HSM
7. Dysmorphic facies, frontal bossing, protruding eyes
137
Treatment NOMID
Il-1/IL-1R antagonists
