Baylor University Medical Center Proceedings April 2014, Volume 27, Number 2 | Page 40

Table. Laboratory test results
Laboratory test

Result

Sodium (mEq/L)

135

Potassium (mEq/L)

4.1

Blood urea nitrogen (mg/dL)
Serum creatinine (mg/dL)

9
0.45

CO2 (mEq/L)

29

Alanine aminotransferase (U/L)

23

Aspartate aminotransferase (U/L)

25

Albumin (g/dL)

3.9

Bilirubin (mg/dL)

0.4

Erythrocyte sedimentation rate (mm/hr)

76

C-reactive protein (mg/L)

11.6

Rheumatoid factor (IU/mL)

7

Creatine kinase (ng/mL)

20

Antinuclear antibodies

Negative

Heavy metal screen

Negative

Cyclic citrullinated peptide antibodies

Negative

Acetylcholine receptor antibodies

Negative

Anti–muscle-specific tyrosine kinase antibodies

Negative

HIV 1, 2 antibodies

Nonreactive

Hepatitis panel

Nonreactive

Immunoglobulin A (mg/dL)

164

DISCUSSION
Demyelinating neuropathies have been reported as rare adverse events with anti–TNF-α therapy. The reported culprit has
more often been infliximab than etanercept or adalimumab.
Acute or chronic demyelinating neuropathies may occur a few
months after the institution of TNF-α treatment, very often
associated with conduction blocks on nerve conduction studies.
However, discontinuation of the offending drug and treatment
for demyelinating neuropathies have been associated with improvement in the neuropathy (3–5).
The proposed pathogeneses of TNF-α-blocker–associated
neuropathies include both a T-cell and humoral immune attack
against peripheral nerve myelin and inhibition of vital axonal
signaling functions. Vasculitis-induced nerve ischemia, either
from the underlying condition or enhanced by the drugs, remains
a possibility in some cases. Neuromuscular biopsies in several
patients, especially with mononeuritis simplex or multiplex, have
revealed necrotizing vasculitis (6). The temporal relationship between initiation of TNF-α antagonist therapy and the onset or
progression of vasculitis suggests that TNF-α inhibition triggers
or exacerbates vessel inflammation (6). Proposed mechanisms
whereby TNF-α inhibitors promote vasculitis include 1) development of antidrug or autoantibodies during TNF-α blockade
that form immune complexes that deposit in the walls of small
blood vessels to activate complement and trigger a type III hy114

persensitivity reaction; 2) changes in T-cell cytokine production;
3) elevation of nuclear antigen levels in the blood because of
increased apoptosis of cells targeted by TNF-α inhibitors; and 4)
an increase in the immunogenic load related to downregulation
of C-reactive protein by TNF-α inhibitors (7, 8).
Adalimumab (Humira; Abbott, Abbott Park, IL) is a recombinant human IgG1 monoclonal antibody specific for human
TNF-α. The drug was developed using phage display technology resulting in an antibody with human -derived heavy- and
light-chain variable regions and human IgG-1 constant regions.
Adalimumab binds specifically with TNF-α, blocking its interaction with the p55 and p75 cell surface TNF receptors and thereby
modulating TNF-induced or -modulated biological responses.
Neurologic deficits seen in patients who are receiving adalimumab include Guillain-Barré syndrome (9), wrist drop (10),
progressive sensory demyelinating polyneuropathy (11), and
optic neuropathy (12–14). Alexopoulou et al reported the other
case of acute bilateral phrenic neuropathy following treatment
with adalimumab (15). This patient was treated with adalimumab for psoriasis and developed acute bilateral phrenic neuropathy after the fourth dose. She was treated with oxygen, and
her symptoms resolved 4 weeks following the discontinuation of
adalimumab. This is the second reported case of diaphragmatic
paralysis in association with adalimumab use. In this case, the
temporal association of the phrenic nerve paralysis with the
administration of adalimumab and the absence of any other
known trigger suggest adalimumab to be the culprit agent for
this condition. The patient had no evidence of other causes
of mononeuropathies, including diabetes mellitus, amyloidosis, infections (e.g., HIV), malignancy, myasthenia gravis, and
amyotrophic lateral sclerosis. Although monofocal motor neuropathy with conduction block and electrophysiological evidence of demyelinating neuropathy might be a rare side effect of
adalimumab and other TNF-α blockers, these agents should be
considered in the differential diagnoses of these neuropathies.
1.
2.

3.

4.

5.

6.

7.

8.

Stübgen JP. Tumor necrosis factor-alpha antagonists and neuropathy.
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Richette P, Dieudé P, Damiano J, Lioté F, Orcel P, Bardin T. Sensory
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Baylor University Medical Center Proceedings

Volume 27, Number 2