Page 945 - Clinical Immunology_ Principles and Practice ( PDFDrive )

912 Part Seven Organ-Specific Inflammatory Disease

Patients with more severe cholinergic impairment have higher-titer
antibodies against ganglionic AChRs. Some of these symptoms
can be passively transferred to mice injected with the patient’s
IgG, suggesting that these antibodies may be pathogenic. Further,
rabbits immunized with a fragment of ganglionic AChR protein
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exhibit autonomic failure, similar to the human disease. Because
ganglionic AChRs have also been found in small cell lung car-
cinoma cell lines, cancer may be a potential initiator of ganglionic
AChR autoimmunity.

A
MONONEUROPATHY MULTIPLEX AND
LOCALIZED, ISOLATED VASCULITIS OF THE
PERIPHERAL NERVES

Polyneuropathy is a common manifestation of systemic vasculitis.
It occurs in patients with polyarteritis nodosa; connective tissue HLA-DR,
diseases, such as rheumatoid arthritis or Sjögren syndrome; Macrophages,
hypersensitivity vasculitis; Churg-Strauss syndrome; temporal CD8 T cells
arteritis; and viral infections, such as those with HIV, human
T-lymphocyte virus (HTLV)-1, and hepatitis B and C viruses.
It classically presents as mononeuritis multiplex affecting several
individual nerves with painful weakness and paresthesias caused B
by ischemia and infarcts caused by inflammation of endoneurial
blood vessels. There is, however, a distinct vasculitic entity local-
ized only to the peripheral nerve, known as isolated peripheral
nerve vasculitis (PNV). PNV involves the small and medium-sized
arteries of the epineurium and perineurium and causes ischemic
changes within the peripheral nerve. The presentation is similar
to the vasculitic neuropathy seen in systemic vasculitis—the only
difference is the lack of systemic organ involvement, slower onset
and progression, and negative serology. The diagnosis is confirmed
with nerve biopsy of the sural, superficial peroneal, or superficial
radial nerve. When nerve biopsy is combined with muscle biopsy, C
the diagnostic yield is higher. PNV has a better prognosis
compared with systemic vasculitides and is a treatable form of FIG 67.5 Serial sections of a nerve biopsy from a patient with
neuropathy. An evaluation for PNV should include all the tests human immunodeficiency virus (HIV)–chronic inflammatory
needed to exclude systemic vasculitis and cryoglobulinemia, as demyelinating polyneuropathy stained for (A) human leukocyte
well as hepatitis B and C infections, which can be associated antigen (HLA)-DR, (B) macrophages, and (C) CD8 T shows that
with PNV. the majority of the endoneurial cells are macrophages. Only rare
CD8 cells are noted.
NEUROPATHY WITH VIRUSES AND HUMAN
IMMUNODEFICIENCY VIRUS

Neuropathy can be seen in a setting of infectious, viral, or bacterial class II molecules on Schwann cells, endothelial cells, and/or
processes. In patients with Lyme disease, various neuropathies, macrophages, but sparse presence of CD8 and CD4 T cells, is
including GBS and mononeuritis (Bell palsy), have been noted. also noted (Fig. 67.5). It is possible that systemic viral infection
Other infections, such as CMV, hepatitis, herpes, leprosy, Chagas or rare HIV-infected endoneurial lymphoid cells may release
disease, and diphtheria, can affect the peripheral nerves, triggering cytokines that expose new nerve antigens against which there is
autoimmune peripheral neuropathy. no self-tolerance, generating a tissue-specific autoimmune attack.
Common neuropathies seen today in a setting of a viral A rare neuropathy seen in later-stage HIV infection is a
infection are those associated with HIV and include GBS, CIDP, lumbosacral polyradiculoneuropathy related to CMV infection
acute ganglioneuritis, or mononeuritis multiplex; they occur that affects roots and sensory ganglia. It presents with lower-
early in the infection, or they are the presenting manifestation extremity muscle weakness, sacral and distal paresthesias, areflexia,
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of unsuspected HIV infection. HIV has been cultured from the and atrophy, mostly of the legs, associated with sphincteric
peripheral nerves, and HIV viral RNA has been amplified from dysfunction resembling cauda equina syndrome. CMV inclusions
sural nerve biopsies of some patients in the author’s laboratory. can be found within Schwann cells or endothelial cells (Fig.
However, there is no convincing evidence that the neuropathy 67.6). Early recognition is important because anti-CMV therapy
results from direct infection of the peripheral nerves by the with ganciclovir or foscarnet can be helpful.
virus. Immunocytochemical studies have shown that HIV is At present, the most common neuropathy in patients with
present only in rare endoneurial macrophages, but not within acquired immunodeficiency syndrome (AIDS) is a painful sensory
Schwann cells or axons. A strong expression of HLA class I and axonal neuropathy that affects up to 70% of adults with AIDS and