Dear Editor, A 49-year-old white man was referred to the Manchester Psoriasis Service with a 21-year history of severe chronic plaque psoriasis refractory to therapy with topical agents, phototherapy (TL-01), systemic agents (methotrexate, ciclosporin and fumaderm) and the biologic agents adalimumab and ustekinumab, including with concurrent ciclosporin therapy. Relevant history included alcohol excess. There was no family history of demyelination. Following a flare of psoriasis in June 2011, treatment was changed from ustekinumab (90 mg dosing regimen) with ciclosporin 2 mg kg−1 daily, to infliximab intravenously (5 mg kg−1 at weeks 0, 2 and 6, and thereafter at 8-week intervals). On initiation of infliximab, ciclosporin was discontinued but reintroduced at 2 mg kg−1 daily due to a flare in December 2011. Two weeks later, the patient reported sudden onset of weakness of his right hand and numbness of the fingertips bilaterally. With no objective sensory disturbance and unilateral right upper limb weakness, urgent assessment by a neurologist led to a provisional diagnosis of brachial plexopathy secondary to ciclosporin, which was stopped. Due to the severity of the patient's psoriasis, infliximab therapy was continued. During January 2012 he reported worsening of sensory disturbance in the arms and new weakness in both legs. Neurological examination revealed reduced tone in the right upper limb, right forearm muscle wasting, right hand weakness in an ulnar and median nerve distribution. Reflexes were present in both arms with no sensory loss. The lower limbs had normal tone. Mild bilateral dorsiflexion weakness was noted. Sensation was normal; all reflexes were absent.

Urgent investigations included magnetic resonance imaging of the brain and cervical spine, which was normal. Nerve conduction studies revealed changes compatible with a primary demyelinating neuropathy and met diagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP). Cerebral spinal fluid findings demonstrated no pleocytosis or oligoclonal bands, protein and glucose were within normal parameters; nerve biopsy was not performed. With a working diagnosis of infliximab-associated CIDP, infliximab therapy was discontinued in February 2012 and ciclosporin reinstituted.

The patient's neurological condition deteriorated 3 months from onset of symptoms with marked global limb weakness with distal bias, sensory ataxia and severe neuropathic pain of the feet. Treatment with intravenous immunoglobulin (IVIg) was commenced [150 g over 5 days (0·4 mg kg−1)], with a second course a month later followed by concomitant oral prednisolone (40 mg daily) after 8 weeks, which resulted in a significant worsening of his condition. Clinical stabilization was achieved with a course of plasma exchange and continued monthly pulses of IVIg. One year after the initial onset of symptoms the patient's distal limb power has improved, he is able to mobilize with a stick but continues to be profoundly sensory ataxic and IVIg dependent. Following withdrawal of infliximab, the patient's psoriasis flared and now requires combination treatment with Fumaderm® (Almirall Hermal, Reinbek, Germany) 240 mg three times daily, acitretin 50 mg daily and ciclosporin 50 mg twice daily.

CIDP is an acquired demyelinating disease of the peripheral nervous system. It typically presents between the ages of 30 and 60 years and is characterized by progressive symmetrical proximal and distal muscle weakness, sensory dysfunction and impaired balance.[1] The course of the disease can be monophasic, relapsing and remitting or progressive.[1] Various diagnostic criteria exist, utilizing findings from clinical, electrophysiological and laboratory testing.[2] Because demyelination in CIDP is multifocal, clinical and pathological manifestations vary. The reported prevalence of 1–7·7 per 100 000 in Northern Europe[3] may be an underestimation due to difficulty in the identification of ‘atypical’ cases.[3]

The exact triggers for CIDP are unknown. A number of disorders are associated with CIDP including organ transplantation, inflammatory bowel disease, diabetes, and malignant melanoma where it has been hypothesized that carbohydrate epitopes shared by myelin sheath and melanoma act as target antigens. The usual therapeutic options for CIDP include oral corticosteroids, IVIg and plasma exchange. The prognosis is variable, some patients responding to cessation of the tumour necrosis factor (TNF) inhibitor, others requiring ongoing treatment with immunosuppressant therapy.

The development of CIDP has been described in 17 patients treated with all TNF inhibitors licensed for use in psoriasis: infliximab, nine;[4-7] etanercept, four;[5-7] and adalimumab, four,[7-10] one of whom received adalimumab for severe psoriasis.[8] Our case is consistent with previous reports (Table 1). There are several hypotheses as to how TNF inhibitors may be implicated in the pathogenesis of CIDP, including: TNF inhibitor therapy leading to autoantibody production via reduced regulatory T-cell activity[9]; or through the removal of the support to peripheral neurons played by constitutive TNF-α.[4] However, the mechanistic link is unclear, as TNF inhibitor therapy has not been discontinued[7, 10] in all such concomitant cases of CIDP, and paradoxically etanercept has been used successfully to treat the condition.

Table 1. Summary of chronic inflammatory demyelinating polyneuropathy (CIDP) cases reported during tumour necrosis factor inhibitor therapy
CaseAuthor and referenceCase age (years) and sexDiseaseTreatmentOnset of symptoms in relation to treatmentSymptomsElectrophysiologyAntibodyTreatmentFollow-up/outcome
Discontinuation of drugImmunosuppressant therapy
  1. RA, rheumatoid arthritis; AS, ankylosing spondylitis; IM, inflammatory myositis; N/A, not available; IVIg, intravenous immunoglobulin; EMG, electromyography; GBS, Guillain–Barré syndrome.

1Jarand et al.[4]50 FRAInfliximab (3 mg kg−1, total exposure 1000 mg)Following five doses of infliximabDiplopia, left hand weakness and numbnessDemyelinating polyneuropathy with conduction blockNot performedYIVIg monthly35 months; some improvement
2Richez et al.[5]73 FRAEtanercept17 monthsLower limb weakness, upper and lower limbsdysaesthesiaMild neurogenic patternsAntiganglioside GM1 (IgM) +veY6 months; neuropathy improved with improved EMG
347 MASInfliximab4 monthsLower limb weakness, distal upper limb dysaesthesiaMotor nerve conduction studies multifocal demyelinating neuropathy with partial conduction block in three nervesAntiganglioside GM2 (IgM) +veY6 months; mild paraesthesia and abnormal gait
4Solomon et al.[9]69 MRAAdalimumab2·5 yearsNumbness and weakness both handsSevere axonal sensorimotor polyneuropathyP/Q-type voltage-gated calcium channel antibody +veYIVIg then azathioprine and prednisolone18 months; partial improvement
5Lozeron et al.[10]50 MRAAdalimumab (total exposure 4000 mg)Unknown; worsening after 2 yearsTingling in both hands and feetDiagnostic of demyelinating polyneuropathyN/AReduced dosagePrednisolone2 years; remaining numbness in toes
6Alshekhlee et al.[6]45 FRAEtanercept1 weekLower limb weakness with bilateral foot drop, severe sensory ataxia, areflexiaEvidence of acquired demyelination including multiple conduction blocksAntiganglioside −veYIVIg after 2 months and prednisolone 1 mg kg−1; IVIg at 4-month intervals2 years; improvement in activities of daily living
749 MRAInfliximab1 yearNumbness in both hands after 1 year, progressing to proximal and distal muscle weakness and areflexia after a further yearEvidence of progressive acquired demyelinating sensory and motor peripheral polyneuropathyAntiganglioside −veYIVIg 2 g kg−1 daily for 5 days, then after 6 weeks, then 8 weeks, thereafter every 8 weeks2 years; some clinical improvement, walking unassisted
8Seror et al.[7]79 FRAInfliximab30 monthsAtaxia, foot drop, areflexiaNerve conduction study abnormalities showed typical features of CIDP in eight of nine cases. Nerve conduction abnormalities were conduction block or temporal dispersion in six, reduced motor nerve conduction velocity in six, prolonged F-wave latency in three and distal prolonged latency in threeAntiganglioside antibodies were tested in four patients and were found to be present in threeYIVIgPartial improvement, relapse with adalimumab
949 MASInfliximab16 monthsParaesthesia of all limbs, areflexiaYIVIgPartial improvement
1036 MASInfliximab6 weeksProximal and distal weakness all limbs with paraesthesiaYIVIgPartial improvement
1139 FRAAdalimumab8 monthsLower limb paraesthesia and ataxiaYIVIgComplete regression
1245 FRAEtanercept17 monthsMild distal weakness lower limbs, distal paraesthesia all limbsYNoneStabilization then delayed improvement
1347 MASInfliximab5 monthsWeakness lower limbs, paraesthesia distal upper limbs, diffuse areflexiaYNoneStabilization
1452 MASEtanercept31 monthsMild lower limb distal paraesthesiaNNoneStabilization
1555 FRAInfliximab32 monthsParaesthesia all limbs, diffuse areflexiaYIVIg and prednisoloneStabilization
1666 MIMInfliximab4·4 monthsDistal paraesthesia lower limbsYIVIgComplete regression, relapse
17Ahmed et al.[8]53 FPsoriasisAdalimumab10 monthsProximal and distal upper and lower limb weakness and areflexiaConsistent with severe demyelinating neuropathyN/AYIVIg and prednisoloneNB: History of GBS 29 years earlier. 12 months; recovery, treatment discontinued

The British Association of Dermatologists' 2009 guidelines for biologic interventions for psoriasis recommend that if symptoms suggestive of demyelination develop during therapy, treatment be withdrawn and specialist advice sought. Reporting of such events via patient registries such as the British Association of Dermatologists' Biologic Interventions Register is imperative to gain understanding of the role TNF inhibitors may play in the onset of peripheral demyelinating disease.


  1. Top of page
  2. Acknowledgments
  3. References

A.C.F. is an MRC Clinical Training Fellow supported by the North West England Medical Research Council Fellowship Scheme in Clinical Pharmacology and Therapeutics, which is funded by the Medical Research Council (grant no. G1000417/94909), ICON, GlaxoSmithKline, AstraZeneca and the Medical Evaluation Unit. R.B.W. is an NIHR Senior Clinical Lecturer; C.E.M.G. is an NIHR Senior Investigator.


  1. Top of page
  2. Acknowledgments
  3. References
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  • 2
    Joint Task Force of the EFNS and the PNS. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of paraproteinemic demyelinating neuropathies. Report of a Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society – first revision. J Peripher Nerv Syst 2010; 15:18595.
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    Vallat JM, Sommer C, Magy L. Chronic inflammatory demyelinating polyradiculoneuropathy: diagnostic and therapeutic challenges for a treatable condition. Lancet Neurol 2010; 9:40212.
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    Jarand J, Zochodne DW, Martin LO et al. Neurological complications of infliximab. J Rheumatol 2006; 33:101820.
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    Richez C, Blanco P, Lagueny A et al. Neuropathy resembling CIDP in patients receiving tumor necrosis factor-alpha blockers. Neurology 2005; 64:146870.
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    Alshekhlee A, Basiri K, Miles JD et al. Chronic inflammatory demyelinating polyneuropathy associated with tumor necrosis factor-alpha antagonists. Muscle Nerve 2010; 41:7237.
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    Seror R, Richez C, Sordet C et al. Pattern of demyelination occurring during anti-TNF-α therapy: a French national survey. Rheumatology (Oxford) 2013; 52:86874.
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    Lozeron P, Denier C, Lacroix C et al. Long-term course of demyelinating neuropathies occurring during tumor necrosis factor-alpha-blocker therapy. Arch Neurol 2009; 66:4907.