1. Immunomodulatory or immunosuppressive-induced neuropathies
Bill O*, Tsouni P*, Benninger D, Truffert A, Ochsner F, Renard D, Buclin T, Kuntzer T
*: co-first authors; to:
Background and Objective
Anti-TNF alpha medications are increasingly used for auto-immune conditions, such as inflammatory bowel disease, multiple sclerosis, inflammatory myopathies and peripheral neuropathies, and arthritis.
The long term tolerability and safety of these immunosuppressive therapies in the routine clinical practice remains unclear.
The purpose of this work is to show that immune-induced neuropathies (I-induced NP) occur during initial or maintenance treatment.
Results
Patient #1
# 2
# 3
# 4 #5
Age (y.o.) & Gender 45 f 32 m 52 59 25
Treated disorder
Crohn's disease (CD) CD
ulcerative colitis
kidney recipient
spondyl-arthropathy
Treatment
adalimumab
infliximab
tacrolimus
etanercept
Duration of
treatment
4 y
6 m
10 m
10 y
6 m after switch
Clinical Manifestations
Small fiber PN
and erythromelalgia
Left femoral PN
Lewis-Sumner syndrome
Late-onset CIDP
S1 right radiculomyelitis
Nerve conduction studies
Prolonged median nerve DML
 CMAP amplitude of the left femoral nerve +
Proximal conduction block
Multifocal sensorymotor
conduction blocks
Absent SNAPs
prolonged DML in 6 nerves
Absent
right H-reflex
Effective
Capsaicin
(0.025%)
Ineffective prednisone acetyl salicylic acid
pregabalin
surgical decompression
1X IVIG
(2g/kg)
4X IVIG
1 PLEX
Ineffective
Prednisone
(worsening of muscle weakness)
golimumab
High-dose dexamethasone
Outcome
Pain reduction
Recovery
(with persistant quadriceps muscle wasting)
Improvement
Switch to adalimumab after 3 months
Almost full recovery
Switch to sirolimus
Partial recovery S F C MF G A
= sensitive
= motor
Onset type :
Acute , Subacute, Chronic onset
Methods and Patients
During the last 5 years – and among a population of 8,500 patients seen in our neuromuscular outpatient clinic – we have encountered 5 such patients. A 6th patient was excluded by the discovery of a familial basis of the neuropathy.
Pattern :
Focal, MultiFocal, Generalised
Conclusions
Our I-induced PNs were surprisingly heterogeneous in their clinical manifestations (onset, pattern, type) and were seen during initial or maintenance therapy periods.
No true peripheral nerve toxicity (i.e., dependent on cumulative dose) was identified.
Recognition of the I-induced neuropathies has management (targeted immunotherapy) and prognostic (mostly favorable) implications.
References
Yang et al. Clin rheumatol 2012; Alshekhlee A et al. Muscle Nerve 2010; Richez C et al. Neuroloy 2005; Bouchra et al. Clin Rheumatol 2009; Stubgen et al. J Neurol Sci, 2011; Tristano et al. J Neurol, 2010