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CHAPTER 126: Rheumatology in the ICU 1249

Antineutrophil Cytoplasmic Autoantibodies: The detection of antibod- can present with gastrointestinal tract involvement and hemorrhage,
ies directed against neutrophil cytoplasmic components offers a useful compromised renal function or progressive peripheral neuropathy, and
serologic tool for the diagnosis and management of a group of disorders skin ulceration.
characterized by systemic necrotizing vasculitis and glomerulonephri- ■
tis. 59,60 These disorders include GPA, microscopic polyangiitis, Churg- ANTIBODIES TO CYCLIC CITRULLINATED PEPTIDE
Strauss syndrome, and idiopathic crescentic glomerulonephritis. The Antibodies directed against cyclic citrullinated peptide (CCP) have
renal lesions in these disorders have in common necrotizing vascular been associated with rheumatoid arthritis and are currently used (along
injury and a paucity of immune deposits. Antineutrophil cytoplasmic with RF) in the diagnosis of this disease. Antibodies to CCP have been
autoantibodies (ANCA) are found in 90% of patients with active, shown to have higher specificity (95%) for rheumatoid arthritis than
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generalized GPA and 60% to 70% of those with limited disease. The RF (85%), although the sensitivity appears to be similar in both tests
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titer often parallels disease activity and may be helpful in distinguish- (67% for CCP and 69% for RF). The high specificity of antibodies to
ing a disease flare from intercurrent infection or other morbidity in CCP has been reevaluated in the light of finding antibodies to CCP in
patients with GPA. ANCA can be found in 80% of patients with active SLE ; however, the authors note that CCP prevalence in other systemic
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pauci-immune necrotizing and crescentic glomerulonephritis, which autoimmune diseases is low. The percent of the general population with
is one of the major causes of rapidly progressing glomerulonephritis. positive CCP antibodies but no clinical RA is unclear. Some believe that
Specific patterns of ANCA have been identified and are referred to as immune interaction with citrulline has a pathogenic role in the develop-
cytoplasmic ANCA (C-ANCA: caused by antibodies to proteinase-3) and ment of rheumatoid arthritis and antibodies to CCP have been shown
perinuclear ANCA (P-ANCA: caused by antibodies to myeloperoxidase). to be present before the development of clinical rheumatoid arthritis.
In general, patients with GPA have demonstrated C-ANCA, whereas
those with idiopathic crescentic glomerulonephritis have demonstrated ■ COMPLEMENT LEVELS
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P-ANCA. P-ANCA has been reported with other forms of systemic
vasculitis, including microscopic polyangiitis and Churg-Strauss vas- SLE is the prototypical disease that involves the complement cascade.
culitis. Atypical perinuclear ANCA (now called UC-ANCA) has also During active disease, antigen-antibody immune complexes fix comple-
been observed in patients with inflammatory bowel disease. The clinical ment leading to depletion of complement factor 3 (C3) and complement
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scenarios that warrant measurement of ANCA are patients with known factor 4 (C4). Decreased levels of C3 and C4 can be a marker of disease
or suspected GPA or other small-vessel vasculitis and patients with rap- activity in some but not all SLE patients. However, caution is advised;
idly progressing glomerulonephritis. These antibodies have also been C3 synthesis is increased by acute inflammation of any cause, serving as
uncommonly identified in Takayasu disease, SLE, relapsing polychon- an acute-phase reactant. For instance, a patient with SLE being treated
dritis, and Behcet disease. with corticosteroids may have increased consumption of C3 secondary
to immune complex formation. Such a patient may develop a secondary
Antibodies in Polymyositis/Dermatomyositis: In general, serologic testing bacterial infection, which stimulates the production of C3 in its role as
has been of little practical value in the diagnosis and management of an acute-phase reactant. The end result could be a normal serum level
patients with polymyositis or dermatomyositis. Recently, the emergence of C3, which may engender a false sense of security with regard to SLE
of a family of autoantibodies that are found nearly exclusively in patients disease activity. Conversely, the significantly reduced synthesis of C3
with myositis, known as myositis-specific autoantibodies or MSA, has in many hepatic diseases is reflected in low plasma levels that can be
focused interest on the role of humoral immunity in this disease. MSA misinterpreted. Patients with SLE or overlap variants may have hetero-
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are usually directed against intracellular, intracytoplasmic antigens zygous or homozygous defects in C4 production. These patients will
involved in protein synthesis. The exact role of these antibodies in the always have low C4 levels, regardless of disease activity. ICU patients
management of patients is unclear, but identification of these antibod- admitted with either meningococcemia or gonococcemia provide one of
ies may be useful in patients who represent a diagnostic dilemma. Jo-1 the reasons for the determination of total hemolytic complement level
antibody is the most common of the MSA and belongs to a family of (CH50 or CH100). This assay serves as a screening test that depends on
autoantibodies known as antisynthetases. It can be found in 15% to 40% the functional presence of all individual complement components. A
of patients with polymyositis, and less commonly in dermatomyositis. significant decrease in hemolytic activity may identify patients with a
The presence of the antibody highly correlates with associated intersti- terminal complement component deficiency at high risk for recurrent
tial lung disease. MSA titers have not proved useful in monitoring the bacteremia.
course of patients with polymyositis or dermatomyositis. Specific MSA
may prove to define unique clinical and immunogenetic groups that ■ CRYOGLOBULINS
represent separate but related diseases. Antibody to PM-1 or PM-Scl Cryoglobulins are immunoglobulins with a propensity for precipita-
defines a small subset of polymyositis patients (10%), half of whom will tion at temperatures below normal body temperature and subsequent
have accompanying features of scleroderma. resolubilization with warming. They can be monoclonal, oligoclonal,
■ RHEUMATOID FACTOR or polyclonal and often are associated with hepatitis C infection, but
can be found in association with other systemic autoimmune diseases,
Rheumatoid factors (RF) are autoantibodies, predominantly IgM iso- malignancy, and bacterial or viral infections. Cryoglobulins are frequently
type, that are directed against multispecies antigenic determinants on reported as a cryocrit—the percent volume of the precipitant. Cryocrits
the heavy chain of IgG and are associated with rheumatoid arthritis. It are convenient ways to present the amount of cryoglobulin but can
is generally accepted that RF is found in approximately 70% to 90% of be somewhat unreliable. Cryoglobulin-mediated vasculitis should be
patients with rheumatoid arthritis; however, RF can be found in 5% of followed in terms of its clinical activity; clinicians should not rely on
normal individuals (perhaps as frequent as 30% in some populations). cryocrit decreases during therapy. Pseudoleukocytosis can occur when
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Rheumatoid factors can arise during acute illness or chronic antigenic automated cell-counting procedures count crystallized cryoproteins as
stimulation of almost any cause. They are present, sometimes in signifi- white blood cells. Pseudohypogammaglobulinemia and pseudothrom-
cant titer, in bacterial endocarditis, granulomatous diseases, and most bocytosis have also been reported.
in tandem with significant decreases of serum complement components ■ ANTICARDIOLIPIN ANTIBODIES
rheumatic diseases at some point in time. The presence of RF, occurring
C3 and C4, may provide a diagnostic clue in rarely encountered clinical The anticardiolipin (ACL) antibodies belong to a family of antiphos-
syndromes such as rheumatoid vasculitis with cryoglobulins or hepatitis pholipid antibodies (APLA), including those responsible for the
C–associated mixed cryoglobulinemia and vasculitis. These syndromes lupus anticoagulant (LA), the false-positive test for syphilis, and

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