First Aid, Chapter 8, Immunologic Disorders, Systemic Autoimmune Disease

Question 1

What are the clinical findings of Sjogren’s syndrome? Autoantibody’s? Treatment?

Answer 1

Xerophthalmia, xerostomia (sicca symptoms), arthritis, interstitial nephritis, renal tubular acidosis, and pulmonary involvement

ANA, SS-A, SS-B, and RF

Symptomatic (muscarinic agonists, cyclosporine ophthalmic drops, and artificial tears); and immunosuppressives for severe extraglandular features

Question 2

What are the clinical findings of Progressive systemic sclerosis or diffuse systemic sclerosis? Autoantibody’s? Treatment?

Answer 2

Fibrosis of skin, vasculopathy, hypertensive renal disease, interstitial lung disease, and CREST symptoms

ANA and Scl-70

Symptomatic: ACE inhibitor for renal crisis; various immune suppressive therapies with varying response

Question 3

What are the clinical findings of Progressive systemic sclerosis; and limited (CREST syndrome)? Autoantibody’s? Treatment?

Answer 3

Calcinosis, Raynaud’s, esophageal motility, sclerodactyly, telangiectasia, and PAH (pulmonary arterial hypertension)

Anticentromere Ab

Symptomatic (Ca channel blockers, PPI, metoclopramide); and PAH = oral anticoagulation, Ca channel blockers, endothelin receptor antagonist, prostanoids, and epoprostenol in refractory cases

Question 4

What are the clinical findings of Polymyositis? Autoantibody’s? Treatment?

Answer 4

Idiopathic myositis, weakness of proximal skeletal muscle, increased CPK, and aldolase

ANA, Anti-Jo-1, anti SRP, and anti-PL-7 (antithreonyl-tRNA synthetase)

Corticosteroids and immunosuppressives (azathioprine and MTX)

Question 5

What are the clinical findings of Dermatomyositis? Autoantibody’s? Treatment?

Answer 5

Similar to polymyositis but also with dermatologic features; Gottron’s papules, heliotrope rash, “mechanic hands”, and association with malignancy

ANA, Anti-Jo-1, and Anti-PL-7, (antithreonyl tRNA synthetase); andAnti-Mi2 Ab (helicase)

Corticosteroids and immunosuppressives (azathioprine, and MTX)

Question 6

What autoantibody is associated with CREST syndrome?

Answer 6

Anticentomere antibody

Question 7

What is Felty’s syndrome?

Answer 7

Triad of RA, neutropenia, and splenomegaly

Question 8

What are the monoclonal ab used for RA?

Answer 8

TNFα blocker, α-IL-6R mAb (tocilizumab), CTLA-4-Ig (abatacept), antiCD20 mAb (rituximab)

Question 9

What are the autoantibodies in RA?

Answer 9

RF in 80% of patients, RF is the Ig that binds IgG Fc, usually IgM isotype, higher = worse prognosis

Anti-cyclic citrullinated peptide (CCP) or ACPA: As sensitive as RF, but more specific:
o May precede onset of symptoms and is associated with worsening prognosis.

Question 10

Which type of JIA has the highest risk for uveitis?

Answer 10

Pauciarticular JIA

Question 11

What lab is associated with a good prognosis in scleroderma or progressive systemic sclerosis?

Answer 11

Anticentromere antibody (good prognosis if positive)

Question 12

What are immunologic features of scleroderma or progressive systemic sclerosis? How is diagnosis made?

Answer 12

Polyclonal hypergammaglobulinemia common, plus presence of ANA and antiendothelial Abs

ANA: 80% of patients have ANA in centromere or nucleolar pattern

Antiendothelial Ab

Anticentromere antibody (good prognosis if positive)

Antiscleroderma-70 antibody more common with diffuse disease

Diagnosis—Anticardiolipin antibody or antiscleroderma-70 antibody Ab testing may be used to confirm the clinical suspicion. Skin biopsy is rarely needed.

Question 13

What conditions can sjogren’s syndrome be associated with?

Answer 13

SS is also associated with primary biliary cirrhosis, HIV I, and hepatitis C.

Secondary Sjogren’s: Complication of connective tissue disorder include RA, SLE, polymyositis (PM), or scleroderma.

Question 14

What are the immunologic markers of sjogren’s syndrome?

Answer 14

Ro/SS-A and La/SS-B: Most clinically significant in primary SS

Anti-Ro: 60–75%; Anti-La: 40% in primary SS

ANA + / RF + = 60–80% patients with primary SS

Question 15

What kind of infiltrate occurs in sjogren’s?

Answer 15

Characterized by a progressive mononuclear cell infiltration of exocrine glands, particularly the lacrimal and salivary glands (autoimmune exocrinopathy).

Question 16

What are genetic dispositions for SLE?

Answer 16

Genetic factors include HLA-DR2, 3, early complement component deficiencies (C1, 2, 4) and FcγRII, III polymorphisms

Question 17

What is the frequency of anti ds-DNA in SLE? Is it sensitive? Specific? What does it correlate with?

Answer 17

50–60%

Very specific but less sensitive

Correlates with active disease and lupus nephritis

Very uncommon in other diseases

Question 18

What is the frequency of anti smith DNA in SLE? Is it sensitive? Specific? What does it correlate with?

Answer 18

30–40%

Very specific but less sensitive

Correlates with interstitial lung disease

Very uncommon in other diseases

Question 19

What is the frequency of antihistone Ab in lupus? What kind of lupus?

Answer 19

50–70%

Drug-induced lupus

Question 20

What is the frequency of Anti-Ro (SS-A) in SLE? What kind of SLE is it associated with?

Answer 20

25–30%
But see in 60–75% of Sjögren’s syndrome

Seen in subacute cutaneous lupus, neonatal lupus syndrome (congenital heart block, thrombocytopenia, and annular rash; “Anti-Ro makes baby’s heart GO”)

Question 21

What are the diagnostic criteria for SLE?

Answer 21

Four or more criteria are needed to make the diagnosis of SLE.
Malar rash = fixed malar erythema, flat or raised (Figure 8-6)

Discoid rash = erythematous raised patches, with keratotic scaling and follicular plugging

Photosensitivity = skin rash as an unusual reaction to sunlight

Oral or nasopharyngeal ulcers

Arthritis = nonerosive

Serositis = pleuritis or pericarditis

Renal disorder (nephritis): Proteinuria ≥0.5 g or 3+; and cellular casts

Neurologic disorder: Seizures, and psychosis

Hematologic disorder: Hemolytic anemia, leukopenia

Question 22

What is the female to male ratio in RA? What is the age of onset?

Answer 22

female: male
3:1
4th or 5th decade

Question 23

What is the age of onset of JIA? How long are symptoms present prior to being able to diagnose?

Answer 23

6 weeks

Question 24

What is the frequency of pauciarticular JIA, polyarticular JIA, juvenile spondylarthropathy, and systemic onset (Still’s disease)?

Answer 24

pauciarticular JIA
50–60%. Most common type.

polyarticular JIA
30–35%

juvenile spondylarthropathy
10–5%

Systemic onset (Still’s disease) 10-15%

Question 25

What is the age of onset of pauciarticular JIA, polyarticular JIA, juvenile spondylarthropathy, and systemic onset (Still’s disease)?

Answer 25

pauciarticular JIA
18-36 months

polyarticular JIA
18-36 months

juvenile spondylarthropathy:
Late childhood/adolescent (range 2.8–17.6 years)

Systemic onset (Still’s disease): no definite peak age of onset

Question 26

What is the male:female ratio of pauciarticular JIA, polyarticular JIA, juvenile spondylarthropathy, and systemic onset (Still’s disease)?

Answer 26

pauciarticular JIA
1;5

polyarticular JIA
1:4

juvenile spondylarthropathy,
4:1

Systemic onset (Still's disease)
1:1

Question 27

What is the arthritis

pattern in pauciarticular JIA, polyarticular JIA, juvenile spondylarthropathy, and systemic onset (Still’s disease)?

Answer 27

pauciarticular JIA
Mono- or oligoarticular and usually involves larger joints

polyarticular JIA
Symmetrical polyarticular. ≥5 cumulative joints

juvenile spondylarthropathy,
Axial arthritis, sacroiliitis, can be oligoarthritis or polyarthritis

Systemic onset (Still's disease)
polyarticular

Question 28

What are the extra articular patterns in pauciarticular JIA, polyarticular JIA, juvenile spondylarthropathy, and systemic onset (Still’s disease)?

Answer 28

pauciarticular JIA
Systemic features are often minimal; Highest uveitis risk (20% patients)

polyarticular JIA
Intermediate risk for uveitis

juvenile spondylarthropathy,
Enthesopathy, uveitis (20% in adult, less common in children), aortic insufficiency

Systemic onset (Still's disease)
Fever, rash, serositis, lymphadenopathy, myopericarditis, and Köbner’s phenomenon (h (i.e., faint, evanescent, salmon-colored eruption that occurs with fever) can be triggered by stroking the skin.

Question 29

What are the relevant lab tests in pauciarticular JIA, polyarticular JIA, juvenile spondylarthropathy, and systemic onset (Still’s disease)?

Answer 29

pauciarticular JIA
RF almost always negative 65–85% ANA

polyarticular JIA
15% RF+ 80% ANA+ in RF+ patients, 57% ANA+ in RF-negative patients

juvenile spondylarthropathy,
90% HLA B27+ (children) RF— absent

Systemic onset (Still's disease)
Polyclonal elevation of immunoglobulin levels RF, ANA are uncommon and not useful for diagnosis. Increased LFTs, ESR/CRP and ferritin

Question 30

What is the prognosis of pauciarticular JIA, polyarticular JIA, juvenile spondylarthropathy, and systemic onset (Still’s disease)?

Answer 30

pauciarticular JIA
variable

polyarticular JIA
variable, RF+ -> more disability

juvenile spondylarthropathy,
usually chronic

Systemic onset (Still's disease):
Chronic arthritis in 50%, remission ~1/3 and severe in 20%

Question 31

When should you suspect anti-phospholipid syndrome?

Answer 31

Antiphospholipid syndrome is commonly seen in patients with SLE, especially in setting of thromboembolic disease, spontaneous abortion, thrombocytopenia, and neuropsychiatric events. Treat with anticoagulants

Question 32

What distinguishes myasthenia gravis from polymyositis/dermatomyositis?

Answer 32

Classic clinical manifestations for polymyositis/dermatomy ositis is a difficulty getting up from a chair, climbing stairs, reaching above the head, or the combing hair. Distal muscle and ocular involvement are uncommon (distinguished from myasthenia gravis). Sensation and reflexes are preserved.

Question 33

What is the treatment for renal crisis in scleroderma or progressive systemic sclerosis?

Answer 33

Renal crisis, especially in diffuse variant, which can lead to hypertension, microangiopathy, and renal insufficiency. Treatment of choice is ACE inhibitors

Question 34

How is the inflammatory interstitial disease in scleroderma or progressive systemic sclerosis treated?

Answer 34

Inflammatory interstitial lung disease (ILD) is treated with cyclophosphamide.

Question 35

How is Raynaud’s phenomenon treated?

Answer 35

CCB

Question 36

What is the treatment for SLE?

Answer 36

Corticosteroids are generally used to treat SLE, but milder forms of the disease can be treated with less potent medications such as NSAIDS. Rash can be treated with topical steroids. Hydroxychloroquine can be used for control of skin disease and arthritis.

For kidney disease that threatens kidney function, treatment should involve:

• High-dose corticosteroids
• IV cyclophosphamide
• Mycophenolate mofetil
• Azathioprine
• Methotrexate
• Type I interferons

Question 37

What is the presentation of Sjogren’s syndrome?

Answer 37

Presentation—The most common symptoms of SS are related to xerostomia and xerophthalmia (keratitis sicca). Swelling of parotid gland can be unilateral or symmetrical, and recurrent.

Physical findings include:

• Dry skin
• Palpable purpura
• Urticaria
• Arthralgias without arthritis -Frequent sinus infections
• Obstructive airway disease
• Interstitial pneumonitis (may progress to pulmonary fibrosis)
• Dysphagia
• CNS involvement, including immune-mediated hearing loss, vasculitis, neuropsychiatric manifestations, and mononeuritis multiplex, especially in association with cutaneous vasculitis

Question 38

What is the treatment of Sjogren’s?

Answer 38

Treatment—In cases of SS, treatment with artificial tears and pilocarpine can improve dryness. Cholinergic agents should be administered for dry mouth. Encourage patients to practice good dental hygiene to prevent dental caries.

Question 39

What is the treatment for RA?

Answer 39

NSAIDS

Steroids

Intrasynovial joint injections

Disease-modifying antirheumatic drugs (DMARDs) and

TNFα blocker, α-IL-6R mAb (tocilizumab), CTLA-4-Ig (abatacept), antiCD20 mAb (rituximab)

Question 40

What are clinical features of RA?

Answer 40

Common prodrome of weakness and fatigue

Initial presentation with multiple symmetrical joints usually involved, most often hands and feet (i.e., metacarpophalangeal [MCP], metatarsophalangeal [MTP], and proximal interphalangeal [PIP] joints). Joint effusions and restricted motion usually present early

Eventual joint deformities due to chronic inflammation

Other findings include rheumatoid nodules over bony prominences, splenomegaly, pericarditis, vasculitis, eye disease, and renal amyloidosis

Question 41

What is the presentation of Polymyositis, Dermatomyositis, and Inclusion Body Myositis?

Answer 41

Presentation—Cutaneous signs:

Heliotrope rash on the upper eyelids (Figure 8-7A)

Erythematous rash on the face

May also involve the back and shoulders (shawl sign), neck and chest (Vshape), and knees and elbows

Gottron’s papules (i.e., violaceous papules overlying dorsal interphalangeal or metacarpophalangeal areas, elbow, or knee joints) (Figure 8-7B)

Photosensitivity

Nail cracking, thickening, and irregularity with periungual telangiectasia

Mechanic’s hand: Fissured, hyperpigmented, scaly, and hyperkeratotic; also associated with increased risk of interstitial lung disease

Question 42

What are the immune markers in polymyositis and dermatomyositis?

Answer 42

Polymyositis: Anti-Jo-1 associated with interstitial lung disease Anti-SRP associated with acute onset, refractory to treatment

Dermatomyositis: Anti-Jo-1 Anti-Mi-2 associated with rash, good outcome. Antibodies rare in children

Question 43

What is the epidemiology of polymositis, dermatomyositis, and inclusion body myositis?

Answer 43

polymositis
Females > Males 18 years of age and older

dermatomyositis
Females > Males Children & adults

inclusion body myositis
Males > Females 50 years of age and older

Question 44

What is the pathophysiology of polymositis, dermatomyositis, and inclusion body myositis?

Answer 44

polymositis
Cell-mediated endomysial inflammatory infiltrate with primarily CD8 T cells. Not Ab-mediated

dermatomyositis
Perifascicular atrophy due to microvascular damage. Ab mediated complement attack

inclusion body myositis
CD8 T cells

Question 45

What is the presentation of polymositis, dermatomyositis, and inclusion body myositis?

Answer 45

polymositis
Subacute onset of proximal muscle weakness; systemic autoimmune disease occurs more commonly; and respiratory problems

dermatomyositis
Subacute onset of proximal muscle weakness; esophageal dysmotility often seen; ECG changes; skin findings (see below); and respiratory problems

inclusion body myositis
Proximal muscle weakness and atrophy that may involve distal spread; progresses over months to years; and dysphagia

Question 46

How are polymositis, dermatomyositis, and inclusion body myositis diagnosed?

Answer 46

polymositis, dermatomyositis
Biopsy, CPK, and EMG and nerve conduction studies

inclusion body myositis
Biopsy may reveal basophilic-rimmed vacuoles as well as characteristic filamentous inclusions and vacuoles (i.e., ragged red fibers on EM); muscle enzymes normal-tomildly elevated; and no assoc. with ANA

Question 47

What is the treatment of polymositis, dermatomyositis, and inclusion body myositis?

Answer 47

polymositis, dermatomyositis,
Steroids; consider IVIG and cyclophosphamide Hydroxychloroquine for skin lesions of DM

inclusion body myositis
Resistant to therapy; but, consider steroids, IVIG, and immune suppression

Question 48

What are some associations with polymositis, dermatomyositis, and inclusion body myositis?

Answer 48

polymositis:
May be seen in patients with scleroderma, SLE, and MCTD

dermatomyositis:
Associated with cancer in patients older than 50 years of age

inclusion body myositis
Possible association with viral etiology

Question 49

What is the prognosis of polymositis, dermatomyositis, and inclusion body myositis?

Answer 49

polymositis, dermatomyositis:
50% of patients will go into remission and stop therapy within 5 years. Poor prognostic indicators include delay in diagnosis, older age, recalcitrant disease, malignancy, interstitial pulmonary fibrosis, dysphagia, leukocytosis, fever, and anorexia

inclusion body myositis:
The older the age at onset of the disease, the more rapid is the loss of strength and function

Question 50

What is deposited in skin and viscera in scleroderma or systemic sclerosis?

Answer 50

This systemic disorder is characterized by excess collagen deposition in skin and viscera. Vascular abnormalities are also present, including vasospasm and microvascular occlusion.

Question 51

What are clinical features of scleroderma or progressive systemic sclerosis?

Answer 51

Thickening of skin

Calcinosis and telangiectasias occur later in disease

Raynaud’s phenomenon: Universal among patients with systemic sclerosis

Esophageal dysmotility: Most common GI manifestation and may be accompanied by dysphagia, reflux, and strictures. Decreased motility results in bacterial overgrowth, diarrhea, and malabsorption

Pulmonary parenchymal fibrosis common but often asymptomatic

Cardiac involvement

Renal crisis, especially in diffuse variant, which can lead to hypertension, microangiopathy, and renal insufficiency. Treatment of choice is ACE inhibitors

CREST syndrome:  
o Calcinosis 
o Raynaud's syndrome 
o Esophageal dysmotility 
o Sclerodactyly 
o Telangiectasias (in CREST scleroderma, is limited to distal extremities)

Question 52

What is the treatment of scleroderma or progressive systemic sclerosis?

Answer 52

Treatment—Symptomatic and problem-oriented. Raynaud’s phenomenon may respond to a calcium channel blocker. Corticosteroids are reserved for resistant symptoms. Esophageal symptoms are useful for protein pump inhibitors, H2 blockers, and promotility agents. Inflammatory interstitial lung disease (ILD) is treated with cyclophosphamide.