First Aid, Chapter 8, Immunologic Disorders, Systemic Autoimmune Disease Flashcards
What are the clinical findings of Sjogren’s syndrome? Autoantibody’s? Treatment?
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
What are the clinical findings of Progressive systemic sclerosis or diffuse systemic sclerosis? Autoantibody’s? Treatment?
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
What are the clinical findings of Progressive systemic sclerosis; and limited (CREST syndrome)? Autoantibody’s? Treatment?
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
What are the clinical findings of Polymyositis? Autoantibody’s? Treatment?
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)
What are the clinical findings of Dermatomyositis? Autoantibody’s? Treatment?
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)
What autoantibody is associated with CREST syndrome?
Anticentomere antibody
What is Felty’s syndrome?
Triad of RA, neutropenia, and splenomegaly
What are the monoclonal ab used for RA?
TNFα blocker, α-IL-6R mAb (tocilizumab), CTLA-4-Ig (abatacept), antiCD20 mAb (rituximab)
What are the autoantibodies in RA?
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.
Which type of JIA has the highest risk for uveitis?
Pauciarticular JIA
What lab is associated with a good prognosis in scleroderma or progressive systemic sclerosis?
Anticentromere antibody (good prognosis if positive)
What are immunologic features of scleroderma or progressive systemic sclerosis? How is diagnosis made?
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.
What conditions can sjogren’s syndrome be associated with?
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.
What are the immunologic markers of sjogren’s syndrome?
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
What kind of infiltrate occurs in sjogren’s?
Characterized by a progressive mononuclear cell infiltration of exocrine glands, particularly the lacrimal and salivary glands (autoimmune exocrinopathy).
What are genetic dispositions for SLE?
Genetic factors include HLA-DR2, 3, early complement component deficiencies (C1, 2, 4) and FcγRII, III polymorphisms
What is the frequency of anti ds-DNA in SLE? Is it sensitive? Specific? What does it correlate with?
50–60%
Very specific but less sensitive
Correlates with active disease and lupus nephritis
Very uncommon in other diseases
What is the frequency of anti smith DNA in SLE? Is it sensitive? Specific? What does it correlate with?
30–40%
Very specific but less sensitive
Correlates with interstitial lung disease
Very uncommon in other diseases
What is the frequency of antihistone Ab in lupus? What kind of lupus?
50–70%
Drug-induced lupus
What is the frequency of Anti-Ro (SS-A) in SLE? What kind of SLE is it associated with?
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”)
What are the diagnostic criteria for SLE?
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
What is the female to male ratio in RA? What is the age of onset?
female: male
3:1
4th or 5th decade
What is the age of onset of JIA? How long are symptoms present prior to being able to diagnose?
6 weeks
What is the frequency of pauciarticular JIA, polyarticular JIA, juvenile spondylarthropathy, and systemic onset (Still’s disease)?
pauciarticular JIA
50–60%. Most common type.
polyarticular JIA
30–35%
juvenile spondylarthropathy
10–5%
Systemic onset (Still’s disease) 10-15%
What is the age of onset of pauciarticular JIA, polyarticular JIA, juvenile spondylarthropathy, and systemic onset (Still’s disease)?
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
What is the male:female ratio of pauciarticular JIA, polyarticular JIA, juvenile spondylarthropathy, and systemic onset (Still’s disease)?
pauciarticular JIA
1;5
polyarticular JIA
1:4
juvenile spondylarthropathy,
4:1
Systemic onset (Still's disease) 1:1
What is the arthritis
pattern in pauciarticular JIA, polyarticular JIA, juvenile spondylarthropathy, and systemic onset (Still’s disease)?
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
What are the extra articular patterns in pauciarticular JIA, polyarticular JIA, juvenile spondylarthropathy, and systemic onset (Still’s disease)?
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.
What are the relevant lab tests in pauciarticular JIA, polyarticular JIA, juvenile spondylarthropathy, and systemic onset (Still’s disease)?
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
What is the prognosis of pauciarticular JIA, polyarticular JIA, juvenile spondylarthropathy, and systemic onset (Still’s disease)?
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%
When should you suspect anti-phospholipid syndrome?
Antiphospholipid syndrome is commonly seen in patients with SLE, especially in setting of thromboembolic disease, spontaneous abortion, thrombocytopenia, and neuropsychiatric events. Treat with anticoagulants
What distinguishes myasthenia gravis from polymyositis/dermatomyositis?
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.
What is the treatment for renal crisis in scleroderma or progressive systemic sclerosis?
Renal crisis, especially in diffuse variant, which can lead to hypertension, microangiopathy, and renal insufficiency. Treatment of choice is ACE inhibitors
How is the inflammatory interstitial disease in scleroderma or progressive systemic sclerosis treated?
Inflammatory interstitial lung disease (ILD) is treated with cyclophosphamide.
How is Raynaud’s phenomenon treated?
CCB
What is the treatment for SLE?
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
What is the presentation of Sjogren’s syndrome?
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
What is the treatment of Sjogren’s?
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.
What is the treatment for RA?
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)
What are clinical features of RA?
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
What is the presentation of Polymyositis, Dermatomyositis, and Inclusion Body Myositis?
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
What are the immune markers in polymyositis and dermatomyositis?
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
What is the epidemiology of polymositis, dermatomyositis, and inclusion body myositis?
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
What is the pathophysiology of polymositis, dermatomyositis, and inclusion body myositis?
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
What is the presentation of polymositis, dermatomyositis, and inclusion body myositis?
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
How are polymositis, dermatomyositis, and inclusion body myositis diagnosed?
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
What is the treatment of polymositis, dermatomyositis, and inclusion body myositis?
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
What are some associations with polymositis, dermatomyositis, and inclusion body myositis?
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
What is the prognosis of polymositis, dermatomyositis, and inclusion body myositis?
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
What is deposited in skin and viscera in scleroderma or systemic sclerosis?
This systemic disorder is characterized by excess collagen deposition in skin and viscera. Vascular abnormalities are also present, including vasospasm and microvascular occlusion.
What are clinical features of scleroderma or progressive systemic sclerosis?
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)
What is the treatment of scleroderma or progressive systemic sclerosis?
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.
