Signs and symptoms due to the cryoglobulins of type I disease reflect the hyperviscosity and deposition of cryoglobulins within the blood vessels which reduce or stop blood perfusion to tissues. These events occur particularly in cases where blood cryoglobulin levels of monoclonal IgM are high in patients with IgM MGUS, smoldering Waldenström's macroglobulinemia, or Waldenström's macroglobulinemia and in uncommon cases where the levels of monoclonal IgA, IgG, free κ light chains, or free λ light chains are extremely high in patients with non-IgM MGUS, non-IgM smoldering multiple myeloma, or multiple myeloma. The interruption of blood flow to neurological tissues can cause symptoms of confusion, headache, hearing loss, and peripheral neuropathy. Interruption of blood flow to other tissues in type I disease can cause cutaneous manifestations of purpura, acrocyanosis, necrosis, ulcers, and livedo reticularis; spontaneous nose bleeds, joint pain, membranoproliferative glomerulonephritis; and cardiovascular disturbances such as shortness of breath, hypoxemia, and congestive heart failure.

Types II and III (or mixed or variant) cryoglobulinemic disease may also present with symptoms and signs of blood hyperviscosity and intravascular cryoglobulin deposition but also include those attributable to cryoglobulinemic vasculitis. "Meltzer's triad" of palpable purpura, joint pain, and generalized weakness occurs in ~33% of patients presenting with type II or type III disease. One or more skin lesions including palpable purpura, ulcers, digital gangrene, and areas of necrosis occur in 69-89% of these mixed disease cases (see attached photograph); less common findings include painful peripheral neuropathy (19-44% of cases), kidney disease (primarily membranoproliferative glomerulonephritis (30%), joint pain (28%), and, less commonly, dry eye syndrome, Raynaud phenomenon (i.e. episodic painful reductions in blood flow to the fingers and toes). While the glomerulonephritis occurring in mixed disease appears to be due to inflammatory vasculitis, the glomerulonephritis occurring in type I disease appears due to the interruption of blood flow. The hematological, infectious, and autoimmune diseases underlying type II cryoglobulinemic disease and the infectious and autoimmune diseases underlying type III cryoglobulinemic disease are also critical parts of the disease's clinical findings.

Hypersensitivity vasculitis (allergic vasculitis). Usually due to a hypersensitivity reaction to a known drug. Drugs most commonly implicated are penicillin, sulphonamides and thiazide diuretics. There is presence of skin vaculitis with palpable petechiae or purpura. Biopsy of these lesions reveal inflammation of the small vessels, termed leukocytoclastic vasculitis, which is most prominent in postcapillary venules. At least 3 out of 5 criteria yields sensitivity and specificity of 71 and 84%:

- age > 16

- use of possible triggering drug in relation to symptoms

- palpable purpura

- maculopapular rash

- skin biopsy showing neutrophils around vessel

IgA vasculitis (IgAV; formerly known as Henoch-Schonlein purpura). Systemic vasculitis due to tissue deposition of IgA-containing immune complexes. Biopsy of lesions shows inflammation of small vessels. It is considered a form of hypersensitivity vasculitis but is distinguished by prominent deposits of IgA. This is the most common vasculitis in children. Presence of 3 or more criteria yielded sensitivity of 87% while less than 2 criteria yielded hypersensitivity vasculitis in 74%:

- palpable purpura (usually of buttocks & legs)

- bowel angina

- GI bleed

- hematuria

- onset < 20 years

- no new medications

Essential cryoglobulinemic vasculitis. Most often due to hepatitis C infection, immune complexes of cryoglobulins --- proteins that consists of immunoglobulins and complement and precipitate in the cold while dissolving upon rewarming --- are deposited in walls of capillaries, venules, or arterioles. Therefore, complement will be low with histology showing vessel inflammation with immune deposits.

Patients usually present with systemic symptoms with single or multiorgan dysfunction. Common (and nonspecific) complaints include fatigue, weakness, fever, arthralgias, abdominal pain, hypertension, renal insufficiency, and neurologic dysfunction. The following symptoms should raise a strong suspicion of a vasculitis:

- Mononeuritis multiplex. Also known as asymmetric polyneuropathy, in a non-diabetic this is suggestive of vasculitis.

- Palpable purpura. If patients have this in isolation, it is most likely due to cutaneous leukocytoclastic vasculitis. If the purpura is in combination with systemic organ involvement, it is most likely to be Henoch-Schonlein purpura or microscopic polyarteritis.

- Pulmonary-renal syndrome. Individuals who are coughing up blood and have kidney involvement are likely to have granulomatosis with polyangiitis, microscopic polyangiitis, or anti-GBM disease (Goodpasture's syndrome).

MCTD combines features of scleroderma, myositis, systemic lupus erythematosus, and rheumatoid arthritis (with some sources adding polymyositis, dermatomyositis, and inclusion body myositis) and is thus considered an overlap syndrome.

MCTD commonly causes:

- joint pain/swelling,

- malaise,

- Raynaud phenomenon,

- muscle inflammation, and

- sclerodactyly (thickening of the skin of the pads of the fingers)

Distinguishing laboratory characteristics are a positive, speckled anti-nuclear antibody and an anti-U1-RNP antibody.

A broad range of autoimmune diseases have been reported to be associated with cryofibrinogenemia. These diseases include systemic lupus erythematosis, Sjorgren's syndrome, rheumatoid arthritis, mixed connective tissue disease, polymyositis, dermatomyositis, systemic sclerosis, antiphospholipid antibody syndrome, Hashimoto disease, Graves disease, sarcoidosis, pyoderma gangrenosum, spondyloarthropathy, Crohn disease, and ulcerative colitis.

Cryofibrinogenmic disease commonly begins in adults aged 40–50 years old with symptoms of the diseases occurring in the almost always affected organ, skin. Cutaneous symptoms include on or more of the following: cold contact-induced urticarial (which may be the first sign of the disease); painful episodes of finger and/or toe arterial spasms termed Ranaud phenomena; cyanosis, s palpable purpura termed Cryofibrinogenemic purpura), and a lace-like purplish discoloration termed livedo reticularis all of which occur primarily in the lower extremities but some of which may occur in the nose, ears, and buttocks; non-healing painful ulcerations and gangrene of the areas impacted by the cited symptoms. Patients also have a history of cold sensitivity (~25% of cases), arthralgia (14-58%), neuritis (7-19%), myalgia (0-14%); and overt thrombosis of arteries and veins (25-40%) which may on rare occasions involve major arteries such of those of the brain and kidney. Signs of renal involvement (proteinuria, hematuria, decreased glomerular filtration rate, and/or, rarely, renal failure) occur in 4-25% of cases. Compared to secondary cryofibrinogemia, primary crygofibrinogenemia has a higher incidence of cutaneous lesions, arthralgia, and cold sensitivity while having a far lower incidence of renal involvement. Patients with secondary cryofibrinogenemia also exhibit signs and symptoms specific to the infectious, malignant, premalignant vasculitis, and autoimmune disorders associated with their disease. While rare, individuals with cryofibrinogemic disease may experience pathological bleeding due to the consumption of blood clotting factors consequential to the formation of cryofibrinogen precipitates.

The condition can cause pain within the affected extremities, discoloration (paleness), and sensations of cold and/or numbness. This can often be distressing to those who are undiagnosed, and sometimes it can be obstructive. If someone with Raynaud's is placed into a cold climate, it could potentially become dangerous.

1. When exposed to cold temperatures, the blood supply to the fingers or toes, and in some cases the nose or earlobes, is markedly reduced; the skin turns pale or white (called pallor) and becomes cold and numb.

2. When the oxygen supply is depleted, the skin color turns blue (called cyanosis).

3. These events are episodic, and when the episode subsides or the area is warmed, the blood flow returns, and the skin color first turns red (rubor), and then back to normal, often accompanied by swelling, tingling, and a painful "pins and needles" sensation.

All three color changes are observed in classic Raynaud's. However, not all patients see all of the aforementioned color changes in all episodes, especially in milder cases of the condition. Symptoms are thought to be due to reactive hyperemias of the areas deprived of blood flow.

In pregnancy, this sign normally disappears owing to increased surface blood flow. Raynaud's has also occurred in breastfeeding mothers, causing nipples to turn white and become extremely painful. Nifedipine, a calcium channel blocker and vasodilator, was recommended to increase blood flow to the extremities and noticeably relieved pain in the breast in an extremely small study group.

Paraproteinemias may be categorized according to the type of monoclonal protein found in blood:

- Light chains only (or Bence Jones protein). This may be associated with multiple myeloma or AL amyloidosis.

- Heavy chains only (also known as "heavy chain disease");

- Whole immunoglobulins. In this case, the paraprotein goes under the name of "M-protein" ("M" for monoclonal). If immunoglobulins tend to precipitate within blood vessels with cold, that phenomenon takes the name of cryoglobulinaemia.

The three types of paraproteins may occur alone or in combination in a given individual. Note that while most heavy chains or whole immunoglobulins remain within blood vessels, light chains frequently escape and are excreted by the kidneys into urine, where they take the name of Bence Jones protein.

It is also possible for paraproteins (usually whole immunoglobulins) to form polymers by aggregating with each other; this takes the name of macroglobulinemia and may lead to further complications. For example, certain macroglobulins tend to precipitate within blood vessel with cold, a phenomenon known as cryoglobulinemia. Others may make blood too viscous to flow smoothly (usually with IgM pentamer macroglobulins), a phenomenon known as Waldenström macroglobulinemia.

Causes of paraproteinemia include the following:

- Leukemias and lymphomas of various types, but usually B-cell Non-Hodgkin lymphomas with a plasma cell component.

- Myeloma

- Plasmacytoma

- Lymphoplasmacytic lymphoma

- Idiopathic (no discernible cause): some of these will be revealed as leukemias or lymphomas over the years.

- Monoclonal gammopathy of undetermined significance

- Primary AL amyloidosis (light chains only)

Raynaud syndrome, also known as Raynaud's phenomenon, is a medical condition in which spasm of arteries cause episodes of reduced blood flow. Typically the fingers, and less commonly the toes, are involved. Rarely, the nose, ears, or lips are affected. The episodes result in the affected part turning white and then blue. Often, there is numbness or pain. As blood flow returns, the area turns red and burns. The episodes typically last minutes, but can last up to several hours.

Episodes are often triggered by cold or emotional stress. There are two main types: primary Raynaud's, when the cause is unknown, and secondary Raynaud's, which occurs as a result of another condition. Secondary Raynaud's can occur due to a connective tissue disorder, such as scleroderma or lupus, injuries to the hands, smoking, thyroid problems, and certain medications, such as birth control pills. Diagnosis is typically based on the symptoms.

The primary treatment is avoiding the cold. Other measures include the discontinuation of nicotine or stimulants use. Medications for treatment of cases that do not improve include calcium channel blockers and iloprost. Little evidence supports alternative medicine. Severe disease may rarely be complicated by skin sores or gangrene.

About 4% of people have the condition. Onset of the primary form is typically between ages 15 and 30 and occurs more frequently in females. The secondary form usually affects older people. Both forms are more common in cold climates. It is named after the French physician Maurice Raynaud, who described the condition in 1862.

PAPA syndrome usually begins with arthritis at a young age, with the skin changes more prominent from the time of puberty.

The arthritis is the predominant feature, noted by its juvenile onset and destructive course. Individuals often recall episodes of arthritis precipitated by a traumatic event. With repeated episodes the joints become damaged with multiple joint replacements required. Hopefully, with improved treatment options, the damage will be limited in new cases.

Pyoderma gangrenosum is variably expressed, which means that it is not always present in all individuals with the disease. It presents as poorly healing ulcers with undermined edges. Pathergy is an important feature (this term refers to the tendency of ulcers to arise at points of injury). There are reports of lesions developing at the site of a joint replacement wound, central venous line and intravenous drip insertion.

Acne affects most individuals with PAPA syndrome but to a variable degree. It is usually of a severe nodulocystic type which if untreated results in scarring.

Hematopoietic ulcers are those occurring with sickle cell anemia, congenital hemolytic anemia, polycythemia vera, thrombocytopenic purpura, macroglobulinemia, and cryoglobulinemia.

The following symptoms (signs) are consistent with complement deficiency in general:

Acquired hypocomplementemia may occur in the setting of bone infections (osteomyelitis), infection of the lining of the heart (endocarditis), and cryoglobulinemia. Systemic lupus erythematosus is associated with low C3 and C4 Membranoproliferative glomerulonephritis usually has low C3.

PAPA syndrome is an acronym for pyogenic arthritis, pyoderma gangrenosum and acne. It is a rare genetic disorder characterised by its effects on skin and joints.

The life span in patients with Schnitzler syndrome has not been shown to differ much from the general population. Careful follow-up is advised, however. A significant proportion of patients develops a lymphoproliferative disorder as a complication, most commonly Waldenström's macroglobulinemia. This may lead to symptoms of hyperviscosity syndrome. AA amyloidosis has also been reported in people with Schnitzler syndrome.

Blood tests show a high concentration of specific gamma-globulins (monoclonal gammopathy) of the IgM type. It almost always has light chains of the κ-type. A variant in which IgG is raised has been described, which appears to be ten times as rare. The immunoglobulins may show up in the urine as Bence Jones proteins. Signs of inflammation are often present: these include an increased white blood cell count (leukocytosis) and a raised erythrocyte sedimentation rate and C-reactive protein. There can be anemia of chronic disease. Bone abnormalities can be seen on radiological imaging (often increased density or osteosclerosis) or biopsy.

Because it is such a rare condition (as of September 2014, only 281 cases have been reported), it is important to rule out other conditions which can cause periodic fevers, paraproteins or chronic hives. These include (and are not limited to) autoimmune or autoinflammatory disorders such as adult-onset Still's disease, angioedema, hematological disorders such as lymphoma or monoclonal gammopathy of undetermined significance, other causes of hives, cryoglobulinemia, mastocytosis, chronic neonatal onset multisystem inflammatory disease or Muckle–Wells syndrome.

It is however possible to have more than one rare condition as seen by a patient with Schnitzler's syndrome and cold induced urticaria.

A meeting of experts, including Dr Liliane Schnitzler (then retired) took place in Strasbourg in May 2012 and drew up diagnostic criteria known as the "Strasbourg Criteria". These included two obligate criteria (chronic urticarial rash and monoclonal IgM or IgG) and several minor criteria; a definite diagnosis requires the two obligate criteria and two minor criteria if IgM, three if IgG; a probable diagnosis requires the two obligate criteria and one (IgM) or two (IgG) minor criteria.

The familial amyloid neuropathies (or familial amyloidotic neuropathies, neuropathic heredofamilial amyloidosis, familial amyloid polyneuropathy) are a rare group of autosomal dominant diseases wherein the autonomic nervous system and/or other nerves are compromised by protein aggregation and/or amyloid fibril formation.

The aggregation of one precursor protein leads to peripheral neuropathy and/or autonomic nervous system dysfunction. These proteins include: transthyretin (ATTR, the most commonly implicated protein), apolipoprotein A1, and gelsolin.

Due to the rareness of the other types of familial neuropathies, transthyretin amyloidogenesis-associated polyneuropathy should probably be considered first.

"FAP-I" and "FAP-II" are associated with transthyretin. (Senile systemic amyloidosis [abbreviated "SSA"] is also associated with transthyretin aggregation.)

"FAP-III" is also known as "Iowa-type", and involves apolipoprotein A1.

"FAP-IV" is also known as "Finnish-type", and involves gelsolin.

Fibrinogen, apolipoprotein A1, and lysozyme are associated with a closely related condition, familial visceral amyloidosis.

Signs and symptoms of WM include weakness, fatigue, weight loss, and chronic oozing of blood from the nose and gums. Peripheral neuropathy occurs in 10% of patients. Enlargement of the lymph nodes, spleen, and/or liver are present in 30–40% of cases. Other possible signs and symptoms include blurring or loss of vision, headache, and (rarely) stroke or coma.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired immune-mediated inflammatory disorder of the peripheral nervous system. The disorder is sometimes called chronic relapsing polyneuropathy (CRP) or chronic inflammatory demyelinating polyradiculoneuropathy (because it involves the nerve roots). CIDP is closely related to Guillain–Barré syndrome and it is considered the chronic counterpart of that acute disease. Its symptoms are also similar to progressive inflammatory neuropathy. An asymmetrical variant of CIDP is known as Lewis-Sumner Syndrome.

Vascular-related cutaneous conditions result from dysfunction of the blood or blood vessels in the dermis, or lymphatics in the subcutaneous tissues.

- Aagenaes syndrome

- Acroangiodermatitis (acroangiodermatitis of Mali, Mali acroangiodermatitis, Pseudo-Kaposi's sarcoma)

- Acute hemorrhagic edema of infancy (acute hemorrhagic edema of childhood, Finkelstein's disease, infantile postinfectious iris-like purpura and edema, medallion-like purpura, purpura en cocarde avec oedema, Seidlmayer syndrome)

- Arterial insufficiency ulcer (ischemic ulcer)

- Arteriosclerosis obliterans

- Bier spots

- Blueberry muffin baby

- Bonnet–Dechaume–Blanc syndrome (Wyburn–Mason syndrome)

- Bullous lymphedema

- Bullous small vessel vasculitis (bullous variant of small vessel vasculitis)

- Calciphylaxis

- Caput succedaneum

- Cholesterol embolus (warfarin blue toe syndrome)

- Cobb syndrome

- Corona phlebectatica

- Cryofibrinogenemic purpura

- Cryoglobulinemic purpura

- Cryoglobulinemic vasculitis

- Cutaneous small-vessel vasculitis (cutaneous leukocytoclastic angiitis, cutaneous leukocytoclastic vasculitis, cutaneous necrotizing venulitis, hypersensitivity angiitis)

- Deep venous thrombosis

- Disseminated intravascular coagulation

- Doucas and Kapetanakis pigmented purpura

- Drug-induced purpura

- Drug-induced thrombocytopenic purpura

- Eczematid-like purpura of Doucas and Kapetanakis

- Epidemic dropsy

- Erythema elevatum diutinum

- Erythromelalgia (acromelalgia, erythermalgia)

- Factitial lymphedema (hysterical edema)

- Fibrinolysis syndrome (defibrinating syndrome, hypofibrinogenemia)

- Food-induced purpura

- Generalized essential telangiectasia (general essential telangiectasia)

- Giant-cell arteritis

- Gougerot–Blum syndrome (pigmented purpuric lichenoid dermatitis, pigmented purpuric lichenoid dermatitis of Gougerot and Blum)

- Harlequin color change

- Hematopoietic ulcer

- Hennekam syndrome (Hennekam lymphangiectasia-lymphedema syndrome, intestinal lymphagiectasia-lymphedema-mental retardation syndrome)

- Henoch–Schönlein purpura (anaphylactoid purpura, purpura rheumatica, Schönlein–Henoch purpura)

- Hereditary hemorrhagic telangiectasia (Osler's disease, Osler–Weber–Rendu disease)

- Idiopathic thrombocytopenic purpura (autoimmune thrombocytopenic purpura, Werlhof's disease)

- IgA vasculitis

- Kawasaki's disease (mucocutaneous lymph node syndrome)

- Levamisole-induced vasculitis

- Lichen aureus (lichen purpuricus)

- Livedo racemosa

- Livedo reticularis

- Livedoid dermatitis (embolia cutis medicamentosa, Nicolau syndrome)

- Livedoid vasculopathy (atrophie blanche, livedo reticularis with summer ulceration, livedoid vasculitis, PURPLE syndrome, segmental hyalinizing vasculitis)

- Lymphedema praecox

- Lymphedema–distichiasis syndrome

- Maffucci syndrome

- Majocchi's disease (purpura annularis telangiectodes, purpura annularis telangiectodes of Majocchi)

- Malignant atrophic papulosis (Degos' disease)

- Marshall–White syndrome

- Meige lymphedema

- Microscopic polyangiitis (microscopic polyarteritis, microscopic polyarteritis nodosa)

- Mondor's disease (Mondor's syndrome of superficial thrombophlebitis)

- Neuropathic ulcer (mal perforans)

- Njolstad syndrome

- Nonne–Milroy–Meige syndrome (hereditary lymphedema, Milroy disease)

- Obstructive purpura

- Orthostatic purpura (stasis purpura)

- Painful bruising syndrome (autoerythrocyte sensitization, Gardner–Diamond syndrome, psychogenic purpura)

- Parkes Weber syndrome

- Paroxysmal hand hematoma (Achenbach syndrome)

- Paroxysmal nocturnal hemoglobinuria

- Polyarteritis nodosa (panarteritis nodosa, periarteritis nodosa)

- Postcardiotomy syndrome

- Perinatal gangrene of the buttock

- Pigmentary purpuric eruptions (progressive pigmentary dermatosis, progressive pigmenting purpura, purpura pigmentosa chronica)

- Postinflammatory lymphedema

- Postmastectomy lymphangiosarcoma (Stewart–Treves syndrome)

- Purpura fulminans (purpura gangrenosa)

- Purpura secondary to clotting disorders

- Purpuric agave dermatitis

- Raynaud phenomenon

- Raynaud's disease (primary Raynaud's phenomenon)

- Reactive angioendotheliomatosis

- Schamberg's disease (progressive pigmentary dermatosis of Schamberg, purpura pigmentosa progressiva, Schamberg's purpura)

- Secondary lymphedema

- Septic thrombophlebitis

- Sinusoidal hemangioma

- Sneddon's syndrome (idiopathic livedo reticularis with cerebrovascular accidents)

- Solar purpura (actinic purpura, senile purpura)

- Stasis dermatitis (congestion eczema, gravitational dermatitis, gravitational eczema, stasis eczema, varicose eczema)

- Superficial thrombophlebitis

- Takayasu arteritis (aortic arch syndrome, pulseless disease)

- Temporal arteritis (cranial arteritis, Horton's disease)

- Thromboangiitis obliterans (Buerger's disease)

- Thrombotic thrombocytopenic purpura (Moschcowitz syndrome)

- Traumatic purpura

- Trousseau's syndrome

- Unilateral nevoid telangiectasia (nevoid telangiectasia)

- Urticarial vasculitis (chronic urticaria as a manifestation of venulitis, hypocomplementemic urticarial vasculitis syndrome, hypocomplementemic vasculitis, unusual lupus-like syndrome)

- Venous insufficiency ulceration

- Waldenström hyperglobulinemic purpura (purpura hyperglobulinemica)

- Waldenström macroglobulinemia

- Wegener granulomatosis

- Yellow nail syndrome (primary lymphedema associated with yellow nails and pleural effusion)

There are several types of immune-mediated neuropathies recognised. These include

- Chronic inflammatory demyelinating polyneuropathy (CIPD) with subtypes:

- Classical CIDP

- CIDP with diabetes

- CIDP/monoclonal gammopathy of undetermined significance

- Sensory CIDP

- Multifocal motor neuropathy

- Multifocal acquired demyelinating sensory and motor neuropathy (Lewis-Sumner syndrome)

- Multifocal acquired sensory and motor neuropathy

- Distal acquired demyelinating sensory neuropathy

- Guillain-Barre syndrome with subtypes:

- Acute inflammatory demyelinating polyradiculoneuropathy

- Acute motor axonal neuropathy

- Acute motor and sensory axonal neuropathy

- Acute pandysautonomia

- Miller Fisher syndrome

- IgM monoclonal gammopathies with subtypes:

- Waldenstrom's macroglobulinemia

- Mixed cryoglobulinemia, gait ataxia, late-onset polyneuropathy syndrome

- Myelin-associated glycoprotein-associated gammopathy, polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes syndrome (POEMS)

For this reason a diagnosis of chronic inflammatory demyelinating polyneuropathy needs further investigations.

The diagnosis is usually provisionally made through a clinical neurological examination. Patients usually present with a history of weakness, numbness, tingling, pain and difficulty in walking. They may additionally present with fainting spells while standing up or burning pain in extremities. Some patients may have sudden onset of back pain or neck pain radiating down the extremities, usually diagnosed as radicular pain. These symptoms are usually progressive and may be intermittent.

Autonomic system dysfunction can occur; in such a case, the patient would complain of orthostatic dizziness, problems breathing, eye, bowel, bladder and cardiac problems. The patient may also present with a single cranial nerve or peripheral nerve dysfunction.

On examination the patients may have weakness, and loss of deep tendon reflexes (rarely increased or normal). There may be atrophy (shrinkage) of muscles, fasciculations (twitching) and loss of sensation. Patients may have multi-focal motor neuropathy, as they have no sensory loss.

Most experts consider the necessary duration of symptoms to be greater than 8 weeks for the diagnosis of CIDP to be made.

Typical diagnostic tests include:

- Electrodiagnostics – electromyography (EMG) and nerve conduction study (NCS). In usual CIDP, the nerve conduction studies show demyelination. These findings include:

1. a reduction in nerve conduction velocities;

2. the presence of conduction block or abnormal temporal dispersion in at least one motor nerve;

3. prolonged distal latencies in at least two nerves;

4. absent F waves or prolonged minimum F wave latencies in at least two motor nerves. (In some case EMG/NCV can be normal).

- Serum test to exclude other autoimmune diseases.

- Lumbar puncture and serum test for anti-ganglioside antibodies. These antibodies are present in the branch of CIDP diseases comprised by anti-GM1, anti-GD1a, and anti-GQ1b.

- Sural nerve biopsy; biopsy is considered for those patients in whom the diagnosis is not completely clear, when other causes of neuropathy (e.g., hereditary, vasculitic) cannot be excluded, or when profound axonal involvement is observed on EMG.

- Ultrasound of the periferal nerves may show swelling of the affected nerves

- MRI can also be used in the diagnosic workup

In some cases electrophysiological studies fail to show any evidence of demyelination. Though conventional electrophysiological diagnostic criteria are not met, the patient may still respond to immunomodulatory treatments. In such cases, presence of clinical characteristics suggestive of CIDP are critical, justifying full investigations, including sural nerve biopsy.