Chronic Inflammatory Demyelinating Polyradiculoneuropathy

Practice Essentials

The term chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) has been used to identify patients with a chronically progressive or relapsing symmetric sensorimotor disorder with cytoalbuminologic dissociation and interstitial and perivascular endoneurial infiltration by lymphocytes and macrophages. It can be considered the chronic equivalent of acute inflammatory demyelinating polyradiculoneuropathy, the most common form of Guillain-Barré syndrome.

Signs and symptoms

CIDP typically starts insidiously and evolves slowly, in either a slowly progressive or a relapsing manner, with partial or complete recovery between recurrences; periods of worsening and improvement usually last weeks or months. Most experts consider the necessary duration of symptoms to be greater than 8 weeks for the diagnosis of CIDP to be made.

Symptoms reported include the following:

• Preceding infection (infrequent)
• Initial limb weakness, both proximal and distal
• Sensory symptoms (eg, tingling and numbness of hands and feet)
• Motor symptoms (usually predominant)
• In about 16% of patients, a relatively acute or subacute onset of symptoms
• In children, usually a more precipitous onset of symptoms
• Symptoms of autonomic system dysfunction (eg, orthostatic dizziness)

Pertinent physical findings are limited to the nervous system, except when the condition is associated with other diseases. Such findings may include the following.

• Signs of cranial nerve (CN) involvement (eg, facial muscle paralysis or diplopia)
• Gait abnormalities
• Motor deficits (eg, symmetric weakness of both proximal and distal muscles in upper and lower extremities)
• Diminished or absent deep tendon reflexes
• Sensory deficits (typically in stocking-glove distribution)
• Impaired coordination

See Clinical Presentation for more detail.

Diagnosis

Laboratory studies that may be helpful include the following:

• Cerebrospinal fluid analysis: Elevated protein levels are common (80% of patients); 10% of patients also have mild lymphocytic pleocytosis and increased gamma globulin
• Complete blood count (CBC), erythrocyte sedimentation rate (ESR), antinuclear antibody (ANA) level, biochemistry profile, and serum and urine immunoelectrophoresis (to exclude associated systemic disorders)
• In certain instances, genetic testing

Other tests and procedures that may be warranted are as follows:

• MRI of the spine with gadolinium enhancement
• Electromyography (EMG) is a critical test to determine whether the disorder is truly a peripheral neuropathy and whether the neuropathy is demyelinating
• Peripheral (sural) nerve biopsy (see the image below): This is considered when the diagnosis is not completely clear, when other causes cannot be excluded, or when profound axonal involvement is observed on EMG; biopsy was once commonly recommended for most patients before immunosuppressive therapy, but current guidelines no longer recommend it

  View Image

  Electron micrograph of the peripheral nerve of a patient with chronic inflammatory demyelinating polyradiculoneuropathy. Note "onion bulb" formation i....

   

  

   

See Workup for more detail.

Management

Principles of treatment are as follows:

• CIDP must be treated to prevent accumulating disability that necessitates physical and occupational therapy, orthotic devices, and long-term treatment
• Close follow-up care is necessary to adjust treatment
• Surgical and orthopedic consultation may be required for sural nerve biopsy or in severe disease with joint deformities
• Consultation with a neurologist is warranted
• Consultation with a physical medicine and rehabilitation specialist is appropriate for physical and occupational therapy and evaluation for orthotic devices
• Other consultations may be necessary if associated diseases are present
• Physical therapy and an active lifestyle should be encouraged

See Treatment and Medication for more detail.

• References

Background

Chronic inflammatory demyelinating polyradiculoneuropathy is presumed to occur because of immunologic antibody-mediated reaction along with interstitial and perivascular infiltration of the endoneurium with inflammatory T cells and macrophages. The consequence is a segmental demyelination of peripheral nerves.

Human leukocyte antigens Dw3, DRw3, A1, and B8 occur more frequently in patients with CIDP than in the healthy population.

Cytoalbuminologic dissociation is a characteristic finding in cerebrospinal fluid (CSF) pointing to nerve root involvement. Occasionally, CSF studies reveal mild lymphocytic pleocytosis and elevation of gamma globulin level, but this is observed most frequently in HIV-positive patients.

The term chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) has been used to identify patients with a chronically progressive or relapsing symmetric sensorimotor disorder with cytoalbuminologic dissociation and interstitial and perivascular endoneurial infiltration by lymphocytes and macrophages. In many ways, CIDP can be considered the chronic equivalent of acute inflammatory demyelinating polyradiculoneuropathy (AIDP), the most common form of Guillain-Barré syndrome (GBS).

A number of variants of CIDP have been described that have immune or inflammatory aspects and electrophysiologic and/or pathologic evidence of demyelination in common. No consensus exists on the best approach to the nomenclature of these disorders. CIDP is a major subset of chronic acquired demyelinating polyneuropathies (CADP). In this context, CIDP is considered when patients have a symmetric proximal and distal motor predominant disorder.

CIDP variants include patients with predominantly sensory symptoms, those with a distal symmetric disorder (DADS), those with multifocal sensorimotor neuropathy or sensorimotor mononeuropathy multiplex with prominent conduction block (also known as Lewis-Sumner neuropathy), and those with CIDP with associated CNS demyelination or with other systemic disorders.

The following disorders are considered distinct from CIDP because they have specific pathophysiologic features and respond to treatments differently than do patients with CIDP: Demyelinating neuropathies associated with immunoglobulin M (IgM) paraproteins, including those with anti–myelin-associated glycoprotein (MAG) antibodies; polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome; and multifocal motor neuropathy.

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Pathophysiology

Chronic inflammatory demyelinating polyradiculoneuropathy is presumed to occur because of immunologic antibody-mediated reaction along with interstitial and perivascular infiltration of the endoneurium with inflammatory T cells and macrophages. The consequence is a segmental demyelination of peripheral nerves.

Human leukocyte antigens Dw3, DRw3, A1, and B8 occur more frequently in patients with CIDP than in the healthy population.

Cytoalbuminologic dissociation is a characteristic finding in cerebrospinal fluid (CSF) pointing to nerve root involvement. Occasionally, CSF studies reveal mild lymphocytic pleocytosis and elevation of gamma globulin level, but this is observed most frequently in HIV-positive patients.

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Frequency

International

CIDP is uncommon. The estimated prevalence of CIDP in populations from the UK, Australia, Italy, Norway, and Japan is 0.8-7.7 per 100,000. A 2009 study showed that the incidence and prevalence is variable depending on diagnostic criteria. In Rutland, UK on May 1, 2008, the prevalence of CIDP was 4.77/100,000 if the EFNS/PNS criteria were used but only 1.97 per 100,000 if the AAN criteria were used. Similarly the annual incidence was 0.7 per 100,000 using the EFNS criteria and 0.35 using the AAN criteria.^[1]

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Mortality/Morbidity

Chronic inflammatory demyelinating polyradiculoneuropathy most commonly has an insidious onset and either chronic progressive or relapsing course. Occasionally, complete remissions occur. Quadriplegia, respiratory failure, and death have been described but are rare.

Race

No racial predilection has been identified.

Sex

Both sexes are affected. Of CADP variants, multifocal motor neuropathy has a male predominance of at least 2:1 based on a survey of the largest case series.

Age

Chronic inflammatory demyelinating polyradiculoneuropathy may occur at any age, but it is more common in the fifth and sixth decades. Relapsing course is associated with younger age of patients (third and fourth decades). CIDP has been described in childhood.

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History

Chronic inflammatory demyelinating polyradiculoneuropathy most frequently starts insidiously and evolves slowly, either in a slowly progressive (more than 60% of patients) or relapsing manner (approximately one third of patients), with partial or complete recovery between recurrences.

• Periods of worsening and improvement usually last weeks or months. Patients with a younger age of onset are said to have a higher frequency of relapsing course.
• Because of the insidious onset of CIDP, documenting precipitating illnesses or events is very difficult. However, preceding infection has been reported infrequently. Both respiratory and gastrointestinal infections have been cited, but no causative organism has been identified.
• Initial symptoms include weakness of the limbs, both proximal and distal, with proximal muscles affected at least as severely as distal.
• Sensory symptoms are common, such as tingling and numbness of hands and feet, but usually motor symptoms predominate.
• Only a small proportion of patients (approximately 16%) have a relatively acute or subacute onset of symptoms, with subsequent steadily progressive or fluctuating course.
• Children usually have a more precipitous onset of symptoms.
• Most experts consider the necessary duration of symptoms to be greater than 8 weeks for the diagnosis of CIDP to be made.
• Autonomic system dysfunction can occur; in such a case, the patient would complain of orthostatic dizziness, problems with bowel and bladder functions, and cardiac problems.

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Physical

Pertinent findings are limited to the nervous system, except for cases of CADP associated with other diseases, as already mentioned. Depending on the associated systemic disorder, abnormalities on physical examination may be found in multiple organ systems. Patients should be examined in detail for signs of autoimmune, inflammatory, and neoplastic conditions.

• Cranial nerves

  • Cranial nerves may be involved, particularly CN VII, with paralysis of both upper and lower facial muscles. Diplopia can occur with the involvement of CN III, IV, or VI. Rarely, bulbar muscles (eg, palate, tongue) can be affected.
  • Papilledema with pseudotumor cerebri syndrome (eg, headaches, transient visual obscurations, pulsatile tinnitus, visual field defects) are observed rarely in patients with CIDP and are due to a very high CSF protein level (usually >1000 mg/mL).

   

  

   
• Gait frequently is abnormal.
• Type of gait depends on location of weakness and degree of proprioceptive loss. With significant weakness in the lower extremities, patients may walk with steppage (ie, high elevation of both feet to compensate for weakness of foot dorsiflexors) or a slapping gait (ie, due to deficit of proprioception in the feet).
• Children are said to have more profound gait abnormalities than adults.
• Motor system

  • Usually relatively symmetric weakness of both proximal and distal muscles is present in upper and lower extremities.
  • Muscle tone can be normal or decreased. Hypotonia, atrophy, and fasciculations may be present.

   

  

   
• Deep tendon reflexes: Reflexes characteristically are diminished or absent even in regions with only mild weakness.
• Sensory system

  • Large-diameter, heavily myelinated fibers are affected most severely, leading to proprioceptive and vibratory deficits.
  • Loss or decrease of pain (ie, pinprick) and temperature sensations is less common.
  • Stocking-glove distribution of sensory deficits is typical.
  • Neuropathic pain in affected extremities may occur.

   

  

   
• Coordination: Patients may have sensory ataxia with positive Romberg sign due to damage to the large nerve fibers that convey proprioception.
• Pathological reflexes: Pathological reflexes (eg, Babinski, Chaddock, Oppenheim) usually are not observed in patients with CIDP.

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Causes

Chronic inflammatory demyelinating polyradiculoneuropathy is most frequently an idiopathic illness, but it has been known to occur with several conditions. In those cases, the associated condition is included in the main diagnosis (eg, CIDP with systemic lupus erythematosus, CIDP with HIV infection, CIDP associated with hepatitis B or C) to separate those cases from the idiopathic variety. Most reported conditions associated with CIDP are listed below.

• CIDP associated with other disorders cannot be distinguished clinically from isolated CIDP except where mentioned in this section. The disease mechanisms for all these disorders are not known. They appear to be immunologic; in some instances, antibody-mediated mechanisms have been shown to play a role.
• Vasculitis does not seem to be involved; physiologic and pathologic differences can distinguish the multifocal variants of CADP from vasculitic mononeuritis multiplex. Vasculitic neuropathies cause wallerian degeneration with minimal signs, if any, of segmental demyelination on biopsy and electromyographic studies (EMG). The multifocal variants of CADP have prominent conduction block and slowing—hallmarks of segmental demyelination.
• HIV infection: In these patients, mild lymphocytic pleocytosis and increased gamma globulin level in the CSF are seen frequently. CIDP has been observed with early disease and later on in the course of AIDS.
• Hodgkin lymphoma: Neuropathy associated with Hodgkin lymphoma is not caused by direct infiltration of the peripheral nerves but is a consequence of the autoimmune cascade that occurs with this disease; the mechanism is not completely clear.
• Paraproteinemias and/or plasma cell dyscrasias

  • CADP is seen with monoclonal gammopathies (eg, monoclonal gammopathy of unknown significance [MGUS]), most frequently gammopathy of IgM. Evidence exists to suggest that CADP with IgM MGUS has specific clinical and electrophysiologic characteristics. Patients usually have predominance of distal sensory symptoms that are greater than motor symptoms. Conduction slowing on nerve conduction testing is accentuated in distal nerve segments. Fifty percent of patients with IgM-associated neuropathies have antibodies directed against MAG, a protein found in noncompact myelin of peripheral nerves. Whether any clinical difference exists between patients with IgM gammopathy without anti-MAG antibodies and those with anti-MAG antibodies is not clear. In both cases, the response to immunosuppressive and/or immunomodulatory treatment is poor. However, a number of reports, including a double-blind controlled trial, describe a response to rituximab, a monoclonal antibody directed against B cells.
  • Some paraproteinemias occur as isolated phenomena and some are by-products of malignant cells, as in the cases of Waldenström macroglobulinemia and myeloma. In myeloma-associated neuropathy, the abnormal paraprotein usually consists mostly of lambda light chain component. Combination of osteosclerotic myeloma, organomegaly, endocrinopathy, M protein, sensorimotor neuropathy, and pigmentary skin changes is referred to as POEMS syndrome. In POEMS syndrome, the M protein is typically immunoglobulin G (IgG).
  • The association of CIDP with IgG or immunoglobulin A (IgA) gammopathy is less clear. IgG paraproteins can occur in 5% of the population and it is unclear that the incidence of IgG paraproteins is excessive in patients with demyelinating neuropathy. Patients with CIDP and IgG or IgA paraproteins have identical clinical and electrophysiologic features to patients with CIDP and no paraprotein. Response to treatment is also the same.

   

  

   
• Multiple sclerosis: Reports describe CNS white matter changes in patients with CIDP. Whether a true association exists between CIDP and multiple sclerosis remains unclear.
• Systemic lupus erythematosus
• Chronic active hepatitis (B or C): CIDP associated with hepatitis should be differentiated from cryoglobulinemic vasculitis. The latter causes either symmetric distal sensorimotor polyneuropathy or mononeuropathy multiplex but on pathologic examination shows wallerian degeneration and not the segmental demyelination seen in CIDP. Patients can respond to standard CIDP treatments, but in some patients, treatment of the hepatitis infection is associated with remission of the CIDP.
• Inflammatory bowel disease (IBD): CIDP has been described in association with Crohn disease and other inflammatory bowel conditions, although no direct correlation between the 2 afflictions is known. The mechanism of development of CIDP is presumed to be an autoimmune abnormality that is also causing the primary problem in inflammatory bowel disease, although the details are not known. The situation has become complicated with the recognition that TNF-alpha therapies used for IBD can cause CIDP.
• TNF-alpha blockers: CIDP, Lewis-Sumner syndrome, and multifocal motor neuropathy have been described in patients with rheumatoid arthritis and IBD who are treated with TNF-alpha blockers, particularly etanercept and infliximab. In some cases, discontinuation of the medication was associated with remission of the inflammatory neuropathy.
• Diabetes mellitus: Whether an increased incidence of CIDP occurs in patients with diabetes mellitus remains unclear. The most recent literature has not corroborated earlier reports of an association.
• Pregnancy: Pregnancy is known to exacerbate CIDP. Worsening usually occurs in the third trimester or in the postpartum period.

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Laboratory Studies

See the list below:

• Test CSF on patients in whom chronic inflammatory demyelinating polyradiculoneuropathy is suspected. Protein level is increased significantly in 80% of patients (usually between 50 and 200 mg/dL, but can be higher); 10% of patients also have mild lymphocytic pleocytosis (< 50 cells) and increased gamma globulin (usually associated with HIV infection).
• CBC count, sedimentation rate, antinuclear antibody, biochemistry profile, and serum and urine immunoelectrophoresis are necessary to exclude important associated systemic disorders.
• In certain instances, genetic testing may be helpful. Examples include patients with positive family history, very insidious symmetric course of the disease, or some atypical features, including lack of treatment effect. In such cases, genetic testing for Charcot-Marie-Tooth disease might be indicated. Hereditary neuropathy with predisposition to pressure palsies can be suspected and tested for in some patients. Charcot-Marie-Tooth disease type 1X and adult-onset Charcot-Marie-Tooth disease type 1B have been confused with CIDP.

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Imaging Studies

See the list below:

• Imaging studies can provide supportive evidence of CIDP.
• MRI of the spine with gadolinium enhancement may show enhancement of nerve roots.

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Other Tests

EMG is a critical test to determine whether the disorder is truly a peripheral neuropathy and whether the neuropathy is demyelinating. Findings of a demyelinating neuropathy are as follows:

• Multifocal conduction block or temporal dispersion of compound muscle action potential, as shown in the image below

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  Electromyography of a patient with chronic inflammatory demyelinating polyradiculoneuropathy illustrating conduction block, temporal dispersion of com....

   

  

   
• Prolonged distal latencies and dispersion of the distal compound motor action potential
• Variable conduction slowing to less than 70% of normal
• Absent or prolonged F wave latencies, as shown below

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  Prolonged F wave latencies (normal is < 31).

   

  

   

As the disease progresses, patients tend to develop secondary axonal degeneration.

Reports exist of a predominantly axonal neuropathy with clinical course and response to treatment similar to those of CIDP. Most cases of axonal neuropathy are not immune or inflammatory. However, some patients with an aggressive axonal neuropathy have been treated effectively with immunosuppressive and/or immunomodulatory therapy, raising the question of whether a chronic axonal inflammatory neuropathy, akin to the acute axonal variants of GBS, may be present. The relationship of these chronic axonal variants to CIDP is unclear.

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Procedures

Peripheral (sural) nerve biopsy is considered as supportive evidence of CIDP.

• Consider biopsy for those patients in whom the diagnosis is not completely clear, when other causes of neuropathy (eg, hereditary, vasculitic) cannot be excluded, or when profound axonal involvement is observed on EMG.
• Some experts recommend biopsy for most patients prior to initiating immunosuppressive therapy, but more recent guidelines no longer recommend biopsy.

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Histologic Findings

Tissue collected on biopsy of the sural nerve may demonstrate evidence of interstitial and perivascular infiltration of the endoneurium with inflammatory T cells and macrophages with local edema. Evidence exists of segmental demyelination and remyelination with occasional onion bulb formation, particularly in relapsing cases, like the one in the image below.

View Image

Electron micrograph of the peripheral nerve of a patient with chronic inflammatory demyelinating polyradiculoneuropathy. Note "onion bulb" formation i....

Some evidence of axonal damage also is observed, with loss of myelinated nerve fibers. The inflammatory infiltrate with neutrophil infiltration is observed in only a minority of patients.

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Medical Care

Untreated, chronic inflammatory demyelinating polyradiculoneuropathy is characterized by accumulating disability that requires physical and occupational therapy, orthotic devices, and long-term treatment. Close follow-up care with a physician knowledgeable in the field is necessary to adjust treatment.

Medications and plasma exchange may be utilized to avert disease progression.

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Surgical Care

Surgical and orthopedic consultation may be required for sural nerve biopsy or in severe disease with joint deformities that require corrective surgery.

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Consultations

Consult a neurologist for evaluation, diagnosis, and treatment of CIDP and possible associated diseases.

Consult a physical medicine and rehabilitation specialist for physical and occupational therapy and evaluation for orthotic devices.

Other consultations (eg, internist, hematologist, oncologist, rheumatologist) may be necessary if associated diseases are present. Some treatments may be best accomplished with the assistance of a hematologist or rheumatologist.

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Diet

No specific diet has been proven beneficial in CIDP.

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Activity

Activity generally depends on the level of disability. Encourage physical therapy and an active lifestyle.

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Medication Summary

If associated conditions are identified (HIV infection, lupus, paraproteinemia, lymphoma), treat them accordingly. The mainstay of treatment is immunosuppressive or immunomodulatory intervention.^{[2, 3]}

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Plasma Exchange

• Dosing, Interactions, etc.

Clinical Context:  Two controlled and blinded studies have confirmed benefit of plasma exchange. Proposed mechanism is removal of antibodies and complement components that are responsible for immune-mediated damage of peripheral nerves. Plasma removed from blood through method similar to dialysis. Requires 2 large-bore needles, one to remove whole blood and other to return blood cells with albumin and saline. Patients whose veins are not large enough for repeated needle insertions have double-lumen catheter placed, either Quinton catheter (can be kept in for few weeks) or Permacath (can remain inserted indefinitely). Has been shown to have similar efficacy as IVIg in treatment of CIDP.

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Immunoglobulin, intravenous (Gamunex, Privigen)

• Dosing, Interactions, etc.

Clinical Context:  Multiple clinical trials establish efficacy. Solution for IV infusion that is composed mostly of heterogenous human IgG but also small amounts of IgA and IgM. Its proposed mechanism of action based on thought that IVIg contains random set of antibodies that would neutralize immune factors, causing damage to peripheral nerve in CIDP. Used in infectious diseases to provide immediate passive immunity in situations in which time constraints do not allow development of active immunity via vaccination. Also used to treat multiple immune-mediated conditions, such as idiopathic thrombocytopenic purpura, GBS, and myasthenia gravis.

Activates complement cascade and provides multitude of antibodies capable of neutralization of many microorganisms, toxins, viruses, and presumably autoantibodies. Latter mechanism possibly underlies effect in CIDP. Several studies showed significant benefit in CIDP; this makes it useful alternative to plasmapheresis. On average, improvement seen by day 10 and continues through day 42.

Patients usually require repeated treatments every few weeks or months to maintain remission or treat recurrences.

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Immune globulin SC (Hizentra)

• Dosing, Interactions, etc.

Clinical Context:  SC immune globulin supplies a broad spectrum of opsonizing and neutralizing IgG antibodies against a wide variety of bacterial and viral agents. The mechanism of action has not been fully explained, but may include immunomodulatory effects. It is indicated as maintenance therapy for patients with CDIP to prevent relapse of neuromuscular disability and impairment. 

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Prednisone

• Dosing, Interactions, etc.

Clinical Context:  Oral corticosteroid that suppresses inflammation and immune responses by altering protein synthesis in cells. Naturally occurring hormone that crosses cell membranes to bind to cytoplasmic receptors. Some mechanisms of action in CIDP are altering mediator function at site of inflammation and suppressing immune response.

Studies have shown that 6 months of pulsed dexamethasone or 8 months of daily prednisone can achieve long-term remission in over 25% of patients.^[3]

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Azathioprine (Imuran)

• Dosing, Interactions, etc.

Clinical Context:  Purine analog that decreases metabolism of purines and also may inhibit DNA and RNA synthesis. Reduces disability and symptoms of CIDP by suppressing immune-mediated damage to nerves. A small trial did not show any beneficial effect but data are insufficient to draw conclusions.

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Mycophenolate (CellCept)

• Dosing, Interactions, etc.

Clinical Context:  Prodrug for immunosuppressive agent mycophenolic acid. Inhibits lymphocyte purine synthesis by inhibiting enzyme inosine monophosphate dehydrogenase. Reports of efficacy but no large controlled trials.

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Cyclosporine (Sandimmune, Neoral)

• Dosing, Interactions, etc.

Clinical Context:  Cyclic polypeptide consisting of 11 amino acids; effective in many autoimmune conditions. Inhibits first phase of T cell activation and does not affect humoral immunity. By suppressing T cells, may inhibit cell-mediated nerve damage at site of inflammatory/immune reaction. Small trial showed efficacy but data still insufficient to draw conclusions.

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Cyclophosphamide (Cytoxan)

• Dosing, Interactions, etc.

Clinical Context:  Cell-cycle phase-nonspecific antineoplastic agent and immunosuppressant that acts as alkylating agent.

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Class Summary

These agents include intravenous immunoglobulin (IVIg), plasma exchange (PE), prednisone, azathioprine, methotrexate, mycophenolate, cyclosporine, and cyclophosphamide. Their use is based on the proposed pathogenesis of CIDP as an immune-mediated condition.

The FDA approved IVIg product, Gamunex for chronic inflammatory demyelinating polyneuropathy (CIDP). Approval was based on a clinical trial^[4] that showed Gamunex effective at improving certain motor functions for up to 48 weeks after initial treatment compared with placebo. The Inflammatory Neuropathy Cause and Treatment scale (INCAT) was used to measure patients’ ability to perform tasks (eg, walking, motor hand tasks). Twenty-eight of 59 patients (47%) treated with Gamunex had significantly improved INCAT scores compared with 13 of 58 patients (22.4%) treated with placebo (25% difference; 95% CI 7-43%; p=0.006). Patients with improved INCAT scores participated in a follow-up trial for an additional 24 weeks; 86% who continued receiving Gamunex maintained their improved INCAT scores compared with 61% who received placebo during the follow-up trial.

In September 2017, the FDA approved Privigen (immune globulin intravenous [human] 10% liquid) for the treatment of adults with CIDP to improve neuromuscular disability. The approval was based on data from two Phase 3 studies, PATH and PRIMA. In PATH (n=207), 73% of patients were responsive to Privigen over 13 weeks, as measured by the adjusted score on the Inflammatory Neuropathy Cause and Treatment (INCAT) scale. In PRIMA (n=28), 61% of patients were responsive to Privigen over 25 weeks, as measured by their adjusted INCAT score.^{[39, 38]}

In March 2018, the FDA approved subcutaneous immune globulin (SCIg) (Hizentra) for treatment of CIDP. It is the first SCIg approved in the US for CIDP. Approval was based on data from the Polyneuropathy and Treatment with Hizentra (PATH) study. The PATH study demonstrated patients experiencing CIDP relapse or withdrawal for any other reason during SCIg treatment was significantly lower with Hizentra (38.6% on low-dose Hizentra [0.2 g/kg weekly]; 32.8% on high-dose Hizentra [0.4 g/kg weekly]) compared with placebo (63.2%).^[40]

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Gabapentin (Neurontin)

• Dosing, Interactions, etc.

Clinical Context:  Known to effect to GABA, but exact binding site unknown. Also has effects on calcium channels. Mostly used for treatment of epilepsy and neuropathic pain; 100-, 300-, and 400-mg cap and 600- and 800-mg film-coated tab are available.

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Carbamazepine (Tegretol)

• Dosing, Interactions, etc.

Clinical Context:  Blocks use-dependent sodium channels and inhibits sustained repetitive firing as well as reduces posttetanic potentiation of synaptic transmission in spinal cord. Potent enzyme inducer that can induce own metabolism. Used as anticonvulsant and for treatment of neuropathic pain.

Available in chewable 100-mg tab, in tab of 200 mg, XR tab of 100, 200, and 400 mg, and as susp of 100 mg/5 mL.

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Class Summary

In patients with CIDP, a variety of medications is used for treatment of neuropathic pain. Antiepileptic medications are quite effective. The 2 most frequently used medications, gabapentin and carbamazepine, are described.

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Amitriptyline

• Dosing, Interactions, etc.

Clinical Context:  Tertiary amine TCA known to decrease reuptake of serotonin and norepinephrine. Has been used more than other newer TCAs and has more proven benefits, although other TCAs, such as desipramine and nortriptyline, are also quite potent and have fewer adverse effects.

Tab available in 10, 25, 50, 75, 100, and 150 mg.

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Pregabalin

• Dosing, Interactions, etc.

Clinical Context:  Thought to have similar mode of action to gabapentin. Clinical trials have shown efficacy for diabetic neuropathy and shingles induced neuropathic pain.

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Duloxetine (Cymbalta)

• Dosing, Interactions, etc.

Clinical Context:  Duloxetine clinical trials have shown efficacy in diabetic neuropathy pain and for depression.

It is a selective serotonin and norepinephrine reuptake inhibitor.

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Class Summary

These medications are used frequently for the treatment of neuropathic pain. The most traditionally used medication, amitriptyline, is discussed.

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Further Outpatient Care

Outpatient care consists of visits to specialists such as neurologists and physiatrists and of treatment visits for IVIg infusions or to the plasma exchange unit.

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Further Inpatient Care

Most care is delivered on an outpatient basis, although patients may have to be admitted for a short stay for the initiation of plasma exchange or IVIg treatment, because of complications of chronic inflammatory demyelinating polyradiculoneuropathy or treatment, or for inpatient physical therapy.

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Inpatient & Outpatient Medications

Most medications are administered on an outpatient basis. IVIg can be administered as a home infusion or during an outpatient visit. An exception is plasma exchange, which requires visits to a specialized pheresis center.

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Complications

See the list below:

• If the disease becomes severe, swallowing and breathing functions can be affected. Aspiration pneumonia, atelectasis, and respiratory failure can occur.
• If autonomic function is involved, GI motility and bladder function can be abnormal. Orthostatic hypotension and cardiac conduction defects can occur.
• As already discussed, complications of treatment also must be considered.

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Prognosis

Some have suggested that patients with the relapsing disease have a better prognosis than patients with the chronic progressive course. Approximately 70% of patients are said to make relatively good recovery from their relapses, and close to 90% of patients respond to initial immunosuppressive therapy. Some patients do not respond to the usual treatments and accumulate significant disability. Some patients have only a short treatment effect and become treatment dependent. A useful way of understanding the clinical status of patients is to use the CIDP activity status (CDAS). This approach has been useful for both clinical research and for clinical practice.^[5]

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Patient Education

Refer to physical and occupational therapists and to a physiatrist for optimal outpatient therapy, orthotic devices, and adaptation at home.

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