Other Rheumatic Conditions

Question 1

Sjogren syndrome - overview

Answer 1

*a systemic autoimmune disease characterized by destruction of exocrine glands (especially lacrimal and salivary) by lymphocytic infiltrates
*divided into 2 categories:
-primary: without other connective tissue disease
-secondary: secondary to another autoimmune disease (RA, SLE, systemic sclerosis)

Question 2

Sjogren syndrome - epidemiology

Answer 2

*predominantly affects females age 40-60 yo

Question 3

Sjogren syndrome - pathogenesis

Answer 3

*combination of many things (environmental trigger, genetic component/susceptibility, etc)
*results in autoantibody production → stimulation of inflammation response → lymphocytic infiltration in organs:
-predominantly CD4+ T cells
-primarily TH1 driven
-type IV hypersensitivity reaction

Question 4

Sjogren syndrome - clinical symptoms

Answer 4

1. exocrine gland dysfunction: oral dryness, eye dryness (SICCA symptoms)
2. extra-glandular dysfunction:
   -MSK, pulmonary, cardiac, GI, renal, hematologic, endocrine

Question 5

Sjogren syndrome - oral symptoms

Answer 5

*reduced salivary flow rate (xerostomia; oral sicca) → inability to speak continuously; gum disease; dental caries; halitosis; dysphagia
*mucosal atrophy
*salivary gland enlargement
*recurrent parotitis

Question 6

Sjogren syndrome - eye symptoms

Answer 6

*history: using tear substitutes > 3x daily, “sand or gravel feel” in eyes
*note that dry eyes does not necessarily mean Sjogren’s
*Sjogren’s dry eye diagnosed by ophthalmologist: “keratoconjunctivitis sicca”

Question 7

testing for keratoconjunctivitis sicca in Sjogren’s syndrome

Answer 7

1. Schrimer test:
   -objective measurement of tear production
   -sterile filter paper placed on margin of eye
   -measure wetting of paper after 5 min (<5mm is positive)
2. Rose Bengal dye:
   -stains devitalized areas of the eye
   -score based on what is involved
   -potentially toxic so not used often

Question 8

Sjogren’s syndrome - extraglandular involvement

Answer 8

*primary biliary cirrhosis
*Non-Hodgkin’s Lymphoma
*many others (MSK, cutaneous, pulmonary, cardiac, GI, renal, etc)

Question 9

Sjogren’s syndrome & increased risk of lymphoma

Answer 9

*risk of lymphoma increased 44x in pts with Sjogren’s syndrome
*clues for malignant transformation:
-loss of previously elevated rheumatoid factor (RF)
-monoclonal gammopathy
*poor prognostic factors for development of lymphoma: parotid enlargement, vasculitis, hypocomplementemia, cryoglobulinemia

Question 10

diagnosis of Sjogren’s syndrome

Answer 10

*multiple classification criteria, none very good at classifying the disease
*aspects involved in various criteria: subjective symptoms, objective clinical findings, abnormal serology, abnormal histology

Question 11

Sjogren’s syndrome - labs

Answer 11

*ANA + (most pts)
*anti-Ro (SSA) and anti-La (SSB) can be seen
*can be RF+
*negative anti-CCP
*elevated ESR/CRP (most pts)
*can also see:
-hypergammaglobulinemia
-monoclonal gammopathy
-hypocomplementemia

Question 12

Sjogren’s syndrome - minor salivary gland biopsy

Answer 12

*lymphocytic sialadenitis (focal lymphocytic infiltrates) with CD4+ T cells consistent with Sjogren’s syndrome
*seen on biopsy of lip
*there is a scoring system

Question 13

Sjogren’s syndrome - treatment

Answer 13

1. symptomatic treatment:
   -beware of drug side effects
   -artificial tears/nocturnal gels
   -cyclosporine eye drops
   -artificial saliva
   -skin moisturizers
2. stimulate glandular secretion (pilocarpine, cevimeline)
3. frequent follow up (dentist, ophthalmologist)
4. other options

Question 14

Sjogren’s syndrome - ddx

Answer 14

*infiltrative diseases (sarcoidosis, amyloidosis)
*IgG4-related disease
*graft vs. host disease
*diabetes mellitus
*hypertriglyceridemia
*chronic infection (HCV, HIV, HTLV-1)
*lymphoma: non-Hodgkin’s
*radiation therapy

Question 15

sarcoidosis - epidemiology

Answer 15

*more common in African Americans (caucasians tend to be more asymptomatic)
*genetic component

Question 16

sarcoidosis - clinical symptoms

Answer 16

*50% are found incidentally with CXR
*lungs most commonly involved site:
-cough, dyspnea on exertion, and chest pain
-hilar lymphadenopathy on CXR
*other systems involved:
-lymph nodes, skin rashes, arthritis, uveitis, etc

Question 17

sarcoidosis - diagnosis

Answer 17

*ALWAYS biopsy of involved tissue (unless it is Lofgren syndrome): non-caseating granulomas (TH1 CD4+ helper T cells, IL-2, and IFN gamma)
*gallium scan to look for uptake (Panda sign)
*labs: no reliable labs; hypercalcemia, elevated ACE levels

Question 18

Lofgren Syndrome - clinical presentation

Answer 18

*triad of symptoms:
1. erythema nodosum
2. hilar adenopathy
3. migratory polyarthralgia
*often young, predominantly female

note - this is the exception to the “always biopsy” rule of sarcoidosis

Question 19

Lofgren Syndrome - diagnosis, prognosis, treatment

Answer 19

*95% diagnostic specificity for sarcoidosis when all 3 triad symptoms are present; no need to biopsy
*treatment: NSAIDs alone
*good prognosis, likely to go into remission

Question 20

sarcoidosis - treatment

Answer 20

*steroids are mainstay
*may need steroid-sparing agents (methotrexate, azathioprine, TNF inhibitors)
*screen for eye disease and heart disease

Question 21

antiphospholipid antibody syndrome - epidemiology

Answer 21

*70-80% women
*more common in Caucasians
*can occur as a primary disease or in association with SLE

Question 22

antiphospholipid antibody syndrome - clinical presentations

Answer 22

1. APS with vascular events (venous or arterial clots)
2. APS with only pregnancy morbidity (recurrent miscarriages, pre-eclampsia, clotting of the cord)
3. catastrophic APS (3 organ systems within a week)

note: asymptomatic aPL positivity, incidentally found, is NOT antiphospholipid antibody syndrome (need symptoms to have disease)

Question 23

antiphospholipid antibody syndrome - Sapporo Criteria

Answer 23

1. clinical criteria: vascular thrombosis OR pregnancy morbidity (1+ unexplained death of normal fetus > 10 wks; 1+ premature births due to pre-eclampsia, eclampsia, or placental insufficiency; 3+ unexplained consecutive spontaneous abortions)
2. laboratory criteria (2 occasions, 12 weeks apart):
   *anti-cardiolipin antibody
   *lupus anticoagulant (DRVVT)
   *anti-beta 2 glycoprotein antibody

Question 24

antiphospholipid antibody syndrome - other manifestations

Answer 24

*Libman-Sacs Endocarditis: sterile platelet thrombi, mitral valve most commonly
*thrombocytopenia
*positive Coomb’s
*false positive VRDL
*seizures, TIA/CVA
*livedo reticularis
*clots in renal system

Question 25

catastrophic antiphospholipid antibody syndrome

Answer 25

*thrombosis at multiple organ sites (3 or more) occurring concurrently or over one week
*these people are very very sick
*high mortality

Question 26

antiphospholipid antibody syndrome - labs

Answer 26

*anti-cardiolipin antibody
*lupus anticoagulant (DRVVT)
*anti-beta 2 glycoprotein antibody

2 occasions, 12 weeks apart

Question 27

lupus anticoagulant testing

Answer 27

1. aPTT prolonged:
   -patient’s serum is tested
   -if not prolonged, test is negative
2. mixing study:
   -mix with normal plasma
   -if corrects, factor deficiency
   -if prolonged, inhibitor present
3. add phospholipids:
   -if corrects of improves, phospholipid dependent inhibitor

Question 28

antiphospholipid antibody syndrome - treatment

Answer 28

*long-term anticoagulation with warfarin (poor efficacy seen with newer anticoagulants)

*catastrophic APS: steroids, heparin, plasmapheresis, immunosuppression, antibiotics