01OverviewDefinition, clinical context and the essential points that orientate the chapter.
CIDP is an acquired immune-mediated neuropathy affecting myelin, nodes and sometimes axons. Typical disease develops over more than 8 weeks with symmetric weakness involving shoulder or hip as well as distal muscles, sensory impairment in more than one limb and generalized hyporeflexia or areflexia. Difficulty rising, climbing, lifting and using hands occurs alongside numbness and sensory ataxia. Variants include distal, multifocal or Lewis-Sumner, focal, motor and sensory-predominant syndromes, but diagnostic certainty is lower and mimics more numerous. Cranial involvement can occur; prominent sphincter dysfunction, a sensory level, severe pain or major autonomic failure should prompt alternative localisation.
Electrodiagnosis anchors the label. Multiple motor nerves must show acquired demyelinating abnormalities meeting EAN/PNS or locally adopted criteria, with temperature, entrapment and axonal loss interpreted carefully. Diabetes can cause modest slowing but rarely the convincing multifocal conduction block of acquired demyelination. CSF protein elevation with low cells supports proximal root involvement, yet high protein alone is a common source of overdiagnosis. MRI or ultrasound nerve enlargement, sensory studies, treatment response and, in selected cases, nodal antibodies provide supportive evidence. Screen blood count, glucose, renal, liver, thyroid, B12, immunoglobulins and electrophoresis or immunofixation and history-led infection, autoimmune, amyloid and genetic causes. Nerve biopsy is rarely needed.
IVIg, corticosteroids and plasma exchange are evidence-based initial therapies selected around phenotype, speed, comorbidity, access and preference. A common IVIg induction is total 2 g/kg over 2–5 days, followed by maintenance tailored to objective wear-off and function. Plasma exchange acts quickly but requires vascular access and ongoing sessions. Corticosteroid regimens may be daily oral or pulsed through specialist practice, but diabetes, osteoporosis, infection, psychiatric effects and motor-CIDP deterioration influence choice. Subcutaneous immunoglobulin is an option for maintenance after IVIg response, not a rapid induction for major deterioration. If first-line treatments fail despite secure diagnosis, specialist immunosuppressive options may be considered with limited evidence. Rehabilitation, falls management and pain care continue while immune treatment prevents further injury; longstanding axonal loss may cap recovery.
Key points
- Typical CIDP causes progressive or relapsing symmetrical proximal and distal weakness, sensory loss and reduced or absent reflexes over at least 8 weeks.
- The time course distinguishes it from monophasic GBS, although acute-onset CIDP can initially reach severe weakness quickly and declare itself through later progression or relapses.
- Nerve-conduction evidence of acquired demyelination across multiple nerves is central: conduction block, temporal dispersion, prolonged distal latencies and slowed velocities must meet validated criteria.
- Raised CSF protein with few cells supports CIDP but is neither required nor specific, especially with older age, diabetes or spinal disease.
- Exclude paraproteinaemic, hereditary, toxic, diabetic, amyloid, POEMS, anti-MAG and nodal or paranodal antibody disorders because treatment response and prognosis differ.
- First-line disease-modifying options are IV immunoglobulin, corticosteroids or plasma exchange; IVIg is generally preferred initially for motor CIDP because steroids can worsen some cases.
- After response, individualise IVIg or subcutaneous immunoglobulin maintenance interval and dose; end-of-dose symptoms alone should be confirmed with objective measures.
- Use grip strength, MRC sum score, INCAT or another disability scale and timed function before and after therapy to prevent placebo-driven diagnosis and overtreatment.
- Failure to improve should trigger re-evaluation of diagnosis, dose and irreversible axonal loss rather than indefinite escalation of expensive and risky immunotherapy.
02AetiologyUnderlying causes, associations and risk factors, with why each one matters.
Idiopathic autoimmune neuropathy
Most CIDP reflects acquired immune attack on peripheral myelin or nodal structures without a single identified trigger, producing chronic or relapsing sensorimotor dysfunction.
Paraprotein and nodal subgroups
Monoclonal proteins and antibodies to nodal or paranodal targets define clinically important subgroups with different phenotypes, treatment responses and associated disease.
Systemic associations
Diabetes, immune disease, infection and malignancy may coexist or occasionally contribute, but their presence does not replace the need for electroclinical evidence of acquired demyelination.
03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.
- 1Immune myelin injury
Antibodies, macrophages and lymphocytes damage Schwann-cell myelin and nodal organisation across multiple peripheral nerves and roots.
- 2Conduction slowing and block
Demyelinated segments conduct slowly or fail, causing temporal dispersion, weakness, sensory loss and reduced reflexes across proximal and distal muscles.
- 3Secondary axonal degeneration
Repeated inflammatory attacks and prolonged conduction failure injure axons, converting treatable dysfunction into fixed weakness, wasting and sensory disability.
04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.
More than 8 weeks of symmetric proximal and distal weakness, sensory loss and generalized areflexia is the core clinical phenotype.
Objective deterioration and improvement separated over months can occur, but day-to-day fatigue or pain fluctuation should not be labelled immune relapse without examination.
An apparent GBS episode that continues progressing beyond 8 weeks or has repeated treatment-related deteriorations may evolve into a chronic immune neuropathy.
Asymmetric sensory and motor deficits in individual nerve distributions with demyelinating physiology suggests multifocal acquired demyelinating sensory and motor neuropathy.
Weakness with little sensory loss can represent motor CIDP, but motor neurone disease and multifocal motor neuropathy require careful exclusion.
05InvestigationsWhat to request, why it matters and how to interpret it.
Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.
- 01
Nerve-conduction studies and EMGFirst step - Why
- Demonstrate acquired demyelination across sufficient nerves and quantify secondary axonal loss.
- Interpretation and limitations
- Apply validated criteria and limb temperature control; isolated slowing at entrapment sites or low-amplitude-dependent slowing is not enough.
- 02
Lumbar puncture - Why
- Seek supportive raised protein with low cell count and investigate alternative inflammatory or infectious polyradiculopathy.
- Interpretation and limitations
- Protein rises with age, diabetes and spinal stenosis; pleocytosis should prompt HIV, Lyme, malignancy, sarcoid or another diagnosis.
- 03
Paraprotein and baseline blood screen - Why
- Find monoclonal gammopathy and common metabolic or nutritional neuropathy contributors.
- Interpretation and limitations
- Immunofixation, immunoglobulins and free light-chain pathways may be needed; IgM anti-MAG and POEMS phenotypes require specialist haematological interpretation.
- 04
Nerve ultrasound or MRI - Why
- Provide supportive evidence of root, plexus or nerve enlargement and exclude structural disease in selected cases.
- Interpretation and limitations
- Enlargement is not specific and cannot rescue absent electroclinical criteria; enhancement or focal mass may redirect investigation.
- 05
Nodal or paranodal antibodies - Why
- Classify selected severe, tremor, ataxia or treatment-resistant phenotypes through a specialist laboratory.
- Interpretation and limitations
- NF155, CNTN1, Caspr1 and related antibodies can define autoimmune nodopathy with different IVIg response; testing is not a blanket screen.
- 06
Objective disability and strength baseline - Why
- Create a reproducible measure before immunotherapy for diagnostic support, dosing and commissioning review.
- Interpretation and limitations
- Use grip dynamometry, MRC, INCAT, timed walk or patient-specific function; subjective energy alone is insufficient proof of immune response.
06Differential diagnosisRealistic alternatives and the features that help distinguish them.
Guillain–Barré syndrome
A monophasic illness reaching its worst within weeks favours GBS; progression or relapse beyond the expected acute course raises CIDP or acute-onset CIDP.
Charcot–Marie–Tooth disease
Uniform slowing, longstanding cavus feet and a family history favour inherited neuropathy, while conduction block and relapsing proximal weakness support CIDP.
Diabetic, amyloid or paraprotein neuropathy
Predominantly axonal length-dependent loss, prominent autonomic features or a specific protein pattern may indicate another neuropathy that will not respond like CIDP.
Motor neurone or spinal disease
Upper motor-neurone signs, a sensory level or preserved sensory studies should redirect localisation away from a diffuse demyelinating sensorimotor neuropathy.
Additional chapter-specific clues
Monoclonal protein, severe pain, weight loss, autonomic failure, family foot deformity or poor objective treatment response raises amyloid, POEMS, anti-MAG, hereditary or other disease.
07ManagementImmediate care, first-line treatment, alternatives and escalation.
01ConfirmRequire electroclinical concordanceFirst stepChronic or relapsing areflexic weakness raises possible CIDP.+
- 1AlternativeDocument more-than-8-week tempo, proximal and distal power, sensory modalities, reflexes, gait and alternative central or motor-neurone signs.
- 2Obtain expert nerve conduction using validated demyelination criteria and repeat or expand testing when the first study is technically limited.
- 3Screen paraprotein, diabetes, B12, thyroid, renal, liver, infection, hereditary and amyloid clues, using CSF and imaging only as supportive evidence.
- 4Record objective strength and disability before treatment so a response cannot retroactively become the only diagnostic criterion.
02InduceSelect first-line immune treatmentFirst lineProbable or definite CIDP causes meaningful progression or disability.+
- 1Choose IVIg, corticosteroid or plasma exchange with specialist advice based on motor phenotype, speed, diabetes, thrombotic or renal risk, access and preference.
- 2Use IVIg preferentially for pure motor disease and for rapid practical response where appropriate, following NHS commissioned dosing governance.
- 3Measure strength and disability at a predefined interval and classify improvement, stability or failure against the documented baseline.
- 4AlternativeIf no objective response occurs, reassess diagnosis, irreversible axonal loss and alternative treatment before repeating indefinitely.
03MaintainFind the minimum effective exposureAn objective response to induction is established and ongoing treatment is required.+
- 1Individualise IVIg dose and interval or consider subcutaneous immunoglobulin, recording function across the cycle and true end-of-dose deterioration.
- 2Periodically reduce dose or extend interval under specialist supervision to test continuing need while avoiding preventable relapse.
- 3Monitor immunoglobulin, steroid or exchange toxicity and add bone, infection, thrombosis and vascular-access prevention as relevant.
- 4Combine rehabilitation, orthoses, falls and pain care with disease control and revisit diagnosis when progression continues despite adequate therapy.
Key medicines and prescribing safety3 treatments · regimens, roles and cautions+
Intravenous human immunoglobulin
A common induction totals 2 g/kg over 2–5 days; maintenance dose and interval are individualised under NHS England commissioning and objective response criteria.Thrombosis, renal injury, haemolysis, aseptic meningitis, headache, fluid load and reaction risk require product-specific monitoring and periodic need review.
Corticosteroid therapy
Use a specialist daily oral or pulsed regimen with planned taper, response measurement and bone, gastric and infection protection appropriate to exposure.Diabetes, hypertension, osteoporosis, infection, mood, eye and adrenal effects are substantial; pure motor CIDP can deteriorate and generally starts with IVIg.
Subcutaneous immunoglobulin
Convert an IVIg-responsive patient to the commissioned product-specific weekly dose, then adjust against objective strength and disability across treatment cycles.Local reactions are common; systemic reactions and thrombosis remain possible, training is required and it is not the usual rescue for acute major decline.
08ComplicationsImportant consequences, why they occur and why they matter clinically.
Progressive weakness and falls
Proximal and distal motor failure impairs rising, stairs, grip and foot clearance, causing falls and loss of independence.
Sensory ataxia and pain
Large-fibre loss destabilises gait and removes protective sensation, while neuropathic pain and tremor may persist despite improved strength.
Irreversible axonal disability
Delayed recognition or repeated relapse causes axonal loss that limits recovery even when inflammation is later suppressed.
Long-term treatment harm
Immunoglobulin, corticosteroids and plasma exchange carry thrombotic, metabolic, infective, vascular-access and resource burdens, making objective response monitoring essential.
09Monitoring and follow-upTreatment response, safety checks and longer-term review.
- Repeat the same MRC sum score, grip strength, INCAT or functional tests at treatment trough and comparable timepoints to document meaningful response.
- Track sensory ataxia, falls, walking aid, hand function, pain and employment separately because strength scales alone miss important disability.
- During immunoglobulin monitor thrombosis symptoms, renal function, haemolysis, headache, infusion reaction and dose per commissioned weight method.
- During corticosteroids monitor glucose, blood pressure, weight, mood, infection, eyes and bone protection and plan adrenal-safe tapering.
- Perform supervised dose reduction or interval extension periodically in stable disease to find the minimum effective treatment and test ongoing dependency.
- Reconsider paraprotein, amyloid, inherited and nodal disease if objective progression continues or repeated adequate first-line therapies fail.
10Special situationsVariants, exceptions and circumstances that change the usual approach.
Protein is supportive, not sovereign
Mild CSF protein elevation is frequent in older adults, diabetes and spinal stenosis and cannot replace acquired demyelination on expert neurophysiology.
Response needs an instrument
Feeling energised after an infusion is real but non-specific; strength, walking and disability measures determine whether immune nerve function changed.
Axons set the recovery ceiling
Stopping immune demyelination may stabilise disease without restoring longstanding denervated muscle, so incomplete recovery is not always treatment failure.
Motor CIDP behaves differently
Corticosteroids can worsen motor-predominant disease, making accurate sensory history and electrophysiological classification important before first-line selection.
Wear-off can be tested
Repeated matched measurements before and after infusions distinguish biological end-of-dose weakness from pain, fatigue or expectation and guide interval adjustment.
11Common pitfallsFrequent interpretation and management errors.
- 01
Diagnosing CIDP from raised CSF protein and diabetic neuropathy without neurophysiological evidence meeting acquired demyelination criteria.
- 02
Calling mild slowing in cold limbs or across common entrapment sites diffuse inflammatory demyelination.
- 03
Using subjective fatigue improvement as the sole reason for lifelong immunoglobulin without objective baseline and withdrawal testing.
- 04
Starting corticosteroids reflexively in pure motor CIDP despite potential deterioration and the preference for IVIg.
- 05
Missing paraprotein, amyloid, POEMS or hereditary neuropathy when systemic features and poor treatment response contradict typical CIDP.
- 06
Escalating immune therapy indefinitely when severe secondary axonal loss, not ongoing demyelination, limits functional recovery.