Rheumatology Flashcards
ANCA-associated vasculitis
GPA, MPA, EPA Three systemic autoimmune small vessel vasculitis syndromes are associated with antineutrophil cytoplasmic autoantibodies (ANCAs): 1. Microscopic polyangiitis (MPA) 2. Granulomatosis with polyangiitis (GPA), formerly known as Wegener’s granulomatosis 3. Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome
Differentiate Churg-Strauss (EPA) from Wegener’s (GPA)
EPA: eosinophilia + long history of asthma
Difference between anti-GBM disease presentation and other GPA?
anti-GBM GPA Upper airway involvement: - +
Types of ANCA
P3-ANCA MPO-ANCA ANCAs causing a cytoplasmic immunofluorescence pattern (C-ANCAs) on neutrophils that react with proteinase 3 (PR3-ANCAs) ANCAs causing a perinuclear immunofluorescence pattern (P-ANCAs) on neutrophils that react with myeloperoxidase (MPO-ANCAs) PR3-ANCAs occur in the vast majority of patients with GPA, while MPO-ANCAs occur far less frequently. In contrast, MPO-ANCAs are the predominant type of ANCAs in patients with both MPA and EGPA.
Limited systemic sclerosis + pulmonary hypertension: Rx
Sildenafil
In SLE, commonest cardiac involvement:
pericarditis
Unilateral, warm, swollen foot in DM2 with neuropathy, normal ESR
Diabetic neuropathic arthropathy
- Variable presentation
- Classical: sudden onset of unilateral warmth, redness, and edema over the foot or ankle, often with a history of minor trauma.
- The affected foot several degrees (centigrade) warmer than the contralateral foot.
- Alternatively: slowly over months or years, and occasional acute attacks.
- Most Frequently: tarsus and tarsometatarsal joints, followed by the MTP joints and the ankle.
Pes anserinus
“Pes anserinus” refers to the insertion of the conjoined tendons of sartorius, gracilis, and semitendinosus, which is said to resemble the footprint of a goose.
ACL tear: tests
- Anterior drawer
- Lachman
- Pivot shift test
CREST antibodies
Anti-centromere
Antinuclear antibody (ANA). 95% sensitivity for SSc
Antitopoisomerase I (anti-Scl-70) antibody: diffuse cutaneous SSc (dcSSc) and a higher risk of severe interstitial lung disease [2,3].
Anticentromere antibody (ACA). The presence of ACA is usually associated with limited cutaneous SSc (lcSSc); only 5 percent of patients with dcSSc have ACA.
Anti-RNA polymerase III antibody. Antibodies to RNA polymerase III are found in patients with dcSSc and are associated with rapidly progressive skin involvement as well as an increased risk for scleroderma renal crisis [4,5]. These patients may also be at increased risk for concomitant cancer [6,7].
The antitopoisomerase I (anti-Scl-70), ACA, and anti-RNA polymerase III tests are highly specific (>99.5 percent in some studies) for SSc but are only moderately sensitive (20 to 50 percent) [2,8,9]. The autoantibodies are almost always mutually exclusive. Among those with RP but without definite SSc or a related autoimmune rheumatic disease, the presence of these antibodies predicts an increased risk of progression to SSc, particularly in combination with abnormal nailfold capillaroscopy [10]. (See “Clinical manifestations and diagnosis of the Raynaud phenomenon”.)
To help in the differential diagnosis of SSc, we also may order the following when appropriate:
●Rheumatoid factor
●Antibodies to citrullinated peptides (anti-CCP)
●Lupus-associated antibodies (eg, anti-double-stranded DNA and/or anti-Smith)
●Antibodies associated with overlap connective tissue diseases (eg, RNP antibodies)
Since these antibodies are uncommon in patients with SSc, their presence points toward overlap syndromes with other systemic rheumatic diseases. These syndromes are characterized by a more prominent arthritis than seen in SSc [11]. (See “Undifferentiated systemic rheumatic (connective tissue) diseases and overlap syndromes”.)
CREST
Limited cutaneous form of systemic sclerosis (lcSSc) is a multisystem connective tissue disorder.
- Calcinosis
- Raynaud’s phenomenon
- esophageal dysmotility
- sclerodactyly
- telangiectasia.
Serology: anti-centromeres (a component of the cell nucleus)
Spares the kidneys (a feature more common in the related condition systemic scleroderma). If the lungs are involved: pulmonary hypertension.
Anti-smooth muscle
Autoimmune hepatitis
Antibodies specific to SLE
anti-dsDNA
Exact mechanism: still unknown, it is likely extracellular DNA is one cause of an immune response against dsDNA. There is a great deal of evidence that dead or dying cells are one major source of this extracellular DNA.
Defective Apoptosis in SLE and other autoimmune disorders, causing either an increase in cell death and/or a decrease in the rate of dead cell clearance.
Scleroderma.classification
he scleroderma disorders comprise a heterogeneous group of conditions linked by the presence of thickened, sclerotic skin lesions.
-
localized
- Linear (in kids, dermatomal)
- Morpheaeform
-
systemic forms of the disease.
- Diffuse cutaneous SSc (dcSSc)
- Limited cutaneous SSc (lcSSc)
- SSc sine scleroderma, in which patients have only internal organ involvement
- Environmentally-induced scleroderma
- Overlap syndromes
The term systemic sclerosis (SSc) is more appropriate for the latter forms; it emphasizes that frequent involvement of internal organs.
●Localized scleroderma can be divided into linear scleroderma (“en coup de sabre”), which most commonly occurs in childhood and follows a dermatomal distribution on one side of the body, and localized and generalized morpheae, which are characterized by patches of sclerotic skin that develop on the trunk and limbs at sites of previously normal texture .
Unlike SSc, generalized morphea typically spares the hands and face and is not associated with major vascular symptoms or with visceral disease. (See ‘Localized scleroderma’ above.)
●The extent of skin involvement and the accompanying pattern of internal organ involvement form the basis for the classification of SSc (table 2). The principal subsets of SSc are (see ‘Systemic sclerosis’ above):
- Diffuse cutaneous SSc (dcSSc) (see ‘Limited and diffuse cutaneous SSc’ above)
- Limited cutaneous SSc (lcSSc) (see ‘Limited and diffuse cutaneous SSc’ above)
- SSc sine scleroderma, in which patients have only internal organ involvement (see ‘SSc sine scleroderma’ above)
- Environmentally-induced scleroderma (see ‘Environmentally induced scleroderma’ above)
- Overlap syndromes, in which features of SSc coexist with elements of other rheumatic disorders (see ‘Overlap syndromes’ above)
Sjogren syndrome.antibodies
anti-Ro/SSA and anti-La/SSB antibodies
The combination of anti-Ro and anti-La antibodies is relatively specific for the diagnoses of SLE and Sjögren’s syndrome.
- Ro/SSA autoantigens may recognize one or both of two cellular proteins with molecular weights of ~ 52 and 60 kD; the autoantigens are referred to as “Ro52” and “Ro60,” respectively. Ro60 : nucleus and nucleolus, and Ro52 : cytoplasm.
- La/SSB autoantigen (La) interact with a 47-kD protein, redominantly: nucleus.
●Solid phase assays, including enzyme-linked immunosorbent assays (ELISA) and flow cytometry-based assays, with either native or recombinant protein as substrate, are generally used to detect antibodies directed against the Ro and La antigens. Anti-Ro antibodies may not be detected by indirect immunofluorescence using a traditional human epithelial cell line-2 (HEp-2) cell substrate
●Anti-Ro antibodies are not specific for Sjögren’s syndrome and systemic lupus erythematosus (SLE) and may also be present in patients with a range of autoimmune disorders, dermatomyositis, polymyositis, systemic sclerosis, mixed connective tissue disease (MCTD), and primary biliary cholangitis (PBC; previously referred to as primary biliary cirrhosis). Women with anti-Ro (with or without co-occurring anti-La) autoantibodies are at increased risk for having a child with neonatal lupus syndrome. Anti-Ro antibodies may be the only autoantibodies present in more than half of the patients with “antinuclear antibody (ANA)-negative” SLE. The combination of anti-Ro and anti-La antibodies is relatively specific for the diagnoses of SLE and Sjögren’s syndrome.
●Patients for whom testing for anti-Ro and anti-La antibodies is indicated include (see ‘Indications for anti-Ro and anti-La testing’ above):
- Patients with findings that suggest Sjögren’s syndrome
- Women with SLE or Sjögren’s syndrome who wish to become pregnant
- Women with a history of giving birth to a child with congenital heart block
- Women planning to become pregnant who are known to be ANA-positive, although the cost-effectiveness of such testing has not been studied
- Patients with symptoms and findings that suggest the diagnosis of SLE in whom the indirect immunofluorescence test for ANA is negative
