Page 937 - Clinical Immunology_ Principles and Practice ( PDFDrive )

904 Part Seven Organ-Specific Inflammatory Disease

TABLE 67.1 Common autoimmune of muscles, such as hypokalemia, inflammatory myopathy
neuropathies (especially the necrotizing autoimmune subtype), acute rhab-
domyolysis, or periodic paralysis; and other rare causes of acute
• Guillain-Barré syndrome(s) (GBS) neuropathy, such as porphyria, toxins, vasculitis, or critical illness
• Chronic inflammatory demyelinating polyneuropathy (CIDP) and its polyneuropathy.
variants
• Polyneuropathy associated with paraproteinemias Antecedent Illnesses or Events
• Immunoglobulin M (IgM) monoclonal gammopathies
• IgG and IgA monoclonal gammopathy Two-thirds of patients with GBS give a history of a flu-like illness
• Polyneuropathy, organomegaly, endocrinopathy, myeloma, and skin or acute dysenteric episodes that precede the development of
changes (POEMS) syndrome GBS by 1–3 weeks. Among the implicated viruses are CMV,
1-5
• Cryoglobulinemic polyneuropathy EBV, herpesvirus, hepatitis A, HIV, and now Zika virus. Among
• Multifocal motor neuropathy with conduction block
• Paraneoplastic neuropathies associated with anti-Hu antibodies bacteria, infection with Mycoplasma pneumoniae and, most
• Autoimmune autonomic neuropathies importantly, C. jejuni may be present in >25% of the patients
1-5
• Vasculitic neuropathies and in some parts of the world up to 50%. Campylobacter
• Infectious neuropathies (human immunodeficiency virus [HIV], is of special interest because it contains glycoconjugates that
cytomegalovirus [CMV], Epstein-Barr virus [EBV], and herpes virus share epitopes with the peripheral myelin, as discussed later. Two
infections; Lyme disease; leprosy; Chagas disease; diphtheria; vaccines—one against rabies and the other against the swine flu
others)
A/New Jersey influenza strain that caused an outbreak of GBS in
1-5
1976 —have been convincingly associated with development
of GBS. Administration of rabies vaccine that contains brain
material is followed by GBS in about 1 in 1000 cases. Apart
• Sensory ataxic GBS results from the involvement of roots and from these vaccines, however, despite anecdotal reports, there is
ganglionic neurons. Some of these patients have antibodies no convincing evidence that the incidence of GBS is increased
to GD1b ganglioside, probably forming a continuum with in association with other vaccines. Presently there is concern
MFS because they share autoantibodies with the same sialic that Zika virus, an arbovirus in the family of Flaviviridae, is
groups. 1-7 emerging in several countries and territories of South America
• Acute pandysautonomic neuropathy, where the target antigen as a cause of microcephaly and GBS. Although the information
is seemingly in the ganglionic neurons, although never identi- is still evolving, compelling data from French Polynesia provide
fied. Autonomic symptoms, however, can coexist in all forms evidence that Zika is associated with GBS in the form of AMAN
of GBS during the acute, stable, or even the recovery phase. 1-5 with rapid disease evolution—within 4–6 days—and antiglycolipid
8
antibodies in 31% of the patients. On the basis of the total
Diagnosis number of 42 reported cases from October 2013 to March 3014,
The diagnosis is often suspected on clinical grounds, but it is the risk of GBS was estimated to be 0.24 per 1000 Zika virus
8
confirmed with elevated levels of cerebrospinal fluid (CSF) protein infections. Although this is clearly alarming, considering that
and abnormal results of electrophysiological studies consistent Zika is a mosquito-borne virus, more data are needed. Surgery
1-4
with active demyelination or nerve inexcitability. can precede the development of GBS in some patients ; surgical
CSF protein may be normal in the early phase of the disease, stress, the release of nerve autoantigens, and infections have been
but it can be as high as 1000 mg/dL by the sixth week. The eleva- proposed as possible explanations for this association. Three
tion of CSF protein levels may result from the involvement of drugs—gold, perhexiline, and suramin at high doses—have been
the roots related to inflammation, but, as the blood–nerve barrier causally associated with acute demyelinating neuropathy. GBS
becomes impaired, serum albumin and IgG may enter freely has occurred in patients who suffer from neoplasms, especially
1-4
into CSF, contributing further to protein elevation. CSF cell count lymphoma, melanoma, and Hodgkin disease. Interestingly,
is normal (or slightly increased <50 cells per microliter); there GBS is rarely seen as part of another connective tissue disorder.
is, however, lymphocytosis when GBS occurs in conjunction
with viral infections, such as human immunodeficiency virus Immunopathology of Guillain-Barré Syndrome
(HIV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), or GBS is an inflammatory demyelinating polyneuropathy in which
Lyme disease. When CSF protein is very high, papilledema can the peripheral myelin, the axon, the node of Ranvier, or the
develop because of impaired reabsorption of CSF and raised Schwann cell are the putative target antigens of an immune
intracranial pressure. Oligoclonal IgG bands can be also seen. attack, possibly triggered by various antecedent events. Both the
Results of nerve conduction studies can be normal early in the cellular and the humoral components of the immune system
disease; they are, however, often helpful to distinguish AIDP have been implicated. 1-5
from AMAN or AMSAN, although sometimes serial studies are
needed in the ensuing weeks. Nerve conduction studies may also Cellular Factors
have prognostic value because features of demyelination suggest Two histopathological features are prominent in typical GBS:
higher chances of needing mechanical ventilation, whereas the perivascular and endoneurial inflammatory infiltrates throughout
1-4
presence of low compound muscle axon potentials from the the nerves, roots, or plexuses and segmental demyelination
4,5
outset (indicative of axonal loss) predicts poor outcome. Dif- in areas associated with the lymphoid infiltrates, especially
ferential diagnosis of GBS should include other forms of acute macrophages. Macrophages, which are the most prominent
flaccid paralysis, such as brainstem stroke; brainstem encephalitis; cells in contact with nerve fibers, break through the basement
acute motor neuron involvement caused by poliomyelitis or West membrane of healthy Schwann cells and make direct contact
Nile virus infection; acute myelopathy; disorders of neuromuscular with the outermost myelin lamellae, leading finally to lysis of the
transmissions, such as myasthenia gravis or botulism; disorders superficial myelin sheath (macrophage-mediated demyelination).