What is Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)?

What is Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)?

CIDP is an acquired autoimmune disorder causing progressive or relapsing weakness and sensory dysfunction through immune-mediated demyelination of peripheral nerves, distinguished from acute conditions like Guillain-Barré syndrome by its progression over more than 2 months. 1, 2

Core Disease Characteristics

CIDP is fundamentally an autoimmune polyneuropathy where both cellular and humoral immune processes attack peripheral nerve myelin, leading to inflammatory demyelination. 2, 3 The condition typically affects older individuals with male predominance, unlike many other autoimmune diseases. 2

Temporal Pattern and Course

• The hallmark distinguishing feature is progression over more than 2 months, which separates CIDP from Guillain-Barré syndrome that progresses over days to weeks. 1
• The onset is generally insidious, taking up to 8 weeks or longer, with either a chronic progressive pattern or a relapsing-recovery pattern. 2
• The disease causes variable but often severe chronic disability that can last months to years. 3

Clinical Presentation

Motor and Sensory Features

• Progressive weakness affects both distal and proximal muscles of upper and lower limbs, distinguishing it from typical length-dependent polyneuropathies. 2, 4
• Sensory dysfunction includes numbness, tingling, and paresthesias affecting both distal and proximal distributions. 2, 4
• Reduced or absent tendon reflexes are characteristic findings on examination. 2, 4
• Loss of balance and loss of coordination are frequently reported manifestations. 4

Additional Manifestations

• Neuropathic pain occurs in a subset of patients. 2
• Cranial nerve involvement can occur, causing focal deficits. 2
• Autonomic symptoms may be present in some cases. 2
• Ataxia can develop as part of the clinical picture. 2

Most Bothersome Symptoms

• Patients identify fatigue as the most bothersome symptom, with weakness and fatigue considered the most important symptoms to treat. 4
• Weakness, fatigue, loss of balance, tingling, numbness, pain, and loss of coordination are the most frequently reported and salient symptoms. 4

Diagnostic Approach

Electrodiagnostic Studies

• Electrophysiological studies show evidence of demyelination and help distinguish CIDP from other neuropathies. 1
• CIDP can present with features of axonal neuropathy on nerve conduction studies, particularly in atypical forms showing significant axonal involvement. 5
• The varied electrodiagnostic patterns make diagnosis challenging in non-classic presentations. 5

Cerebrospinal Fluid Analysis

• CSF typically shows cytoalbuminologic dissociation (elevated protein with normal cell count). 1

Imaging and Biopsy

• MRI of the brachial or lumbosacral plexus can identify focal or diffuse peripheral nerve abnormalities. 1
• Nerve biopsy is generally accepted as useful in evaluating atypical forms of CIDP, particularly when the presentation is non-classic or when vasculitis is suspected. 6, 5

CIDP Variants

Multifocal Acquired Demyelinating Sensory and Motor Neuropathy (MADSAM)

• Also known as Lewis-Sumner Syndrome, this variant is characterized by asymmetric involvement with preserved reflexes in areas not affected by weakness. 1

Chronic Neurovisceral Variants

• These variants may present with slower progression of neurological symptoms compared to typical CIDP. 1

Impact on Quality of Life

Physical Functioning

• Difficulty walking and climbing stairs are prominent functional limitations. 4
• Reduced manual dexterity affects hand function and fine motor tasks. 4
• Activities of daily living become impaired, including difficulty with personal care. 4

Broader Life Impact

• Work capacity is affected, with some patients unable to work. 4
• Emotional wellbeing suffers, including development of depression. 4
• Social wellbeing is impacted through reduced participation in social and leisure activities. 4
• Sleep disturbances occur, including difficulty falling asleep. 4
• Cognitive symptoms such as "brain fog" are reported. 4

Pathophysiology and Etiology

Immune Mechanisms

• Both cellular and humoral immune processes drive the inflammatory demyelination. 2, 3
• Possible antigenic targets include myelin protein 0, myelin protein 2, peripheral myelin protein 22, Connexin 32, and myelin basic protein. 2
• Antibodies targeting Ranvier node proteins (contactin-1, contactin-associated protein 1, and neurofascin 155) have been described. 2

Triggering Factors

• Case reports have found associations with multiple pathogenic organisms including Hepatitis B and C viruses, Bartonella henselae, Mycoplasma pneumoniae, HIV, Cytomegalovirus, and Epstein-Barr virus. 2
• Like all autoimmune diseases, the etiology is multifactorial with both genetic and environmental factors contributing. 2

Treatment Principles

First-Line Therapies

• For severe or progressing symptoms, pulse corticosteroids (methylprednisolone 1g IV daily for 3-5 days) plus IVIG 2g/kg over 5 days are recommended. 1
• Corticosteroids, intravenous or subcutaneous immunoglobulin, and plasma exchange are established first-line therapies. 7, 2
• IVIg is considered the preferred first treatment despite high cost due to its favorable safety profile. 3

Second-Line and Refractory Cases

• Plasmapheresis may be used in severe cases not responding to other therapies. 1
• Rituximab may be considered in consultation for cases with limited improvement. 1
• Immunosuppressive agents (methotrexate, cyclophosphamide, mycophenolate mofetil) are widely used in clinical practice despite limited evidence. 2, 8

Treatment Challenges

• Patients report that current CIDP treatments lack effectiveness in treating specific symptoms, cause unwanted side effects, and impact independence. 4
• There is no reliable disease activity biomarker to guide treatment, making optimization challenging. 8
• Serial clinical assessments are key to understanding the value of continued immunotherapy. 8