Paraneoplastic syndrome

Last updated

Paraneoplastic syndrome
Specialty Oncology
FrequencyRare [1]

A paraneoplastic syndrome is a syndrome (a set of signs and symptoms) that is the consequence of a tumor in the body (usually a cancerous one). [1] It is specifically due to the production of chemical signaling molecules (such as hormones or cytokines) by tumor cells or by an immune response against the tumor. [2] Unlike a mass effect, it is not due to the local presence of cancer cells. [3]

Contents

Paraneoplastic syndromes are typical among middle-aged to older people, and they most commonly occur with cancers of the lung, breast, ovaries or lymphatic system (a lymphoma). [4] Sometimes, the symptoms of paraneoplastic syndromes show before the diagnosis of a malignancy, which has been hypothesized to relate to the disease pathogenesis. In this paradigm, tumor cells express tissue-restricted antigens (e.g., neuronal proteins), triggering an anti-tumor immune response which may be partially or, rarely, completely effective [5] in suppressing tumor growth and symptoms. [6] [7] Patients then come to clinical attention when this tumor immune response breaks immune tolerance and begins to attack the normal tissue expressing that (e.g., neuronal) protein.

The abbreviation PNS is sometimes used for paraneoplastic syndrome, although it is used more often to refer to the peripheral nervous system.

Signs and symptoms

Symptomatic features of paraneoplastic syndrome cultivate in four ways: endocrine, neurological, mucocutaneous, and hematological. The most common presentation is a fever (release of endogenous pyrogens often related to lymphokines or tissue pyrogens), but the overall picture will often include several clinical cases observed which may specifically simulate more common benign conditions. [8]

Endocrine

The following diseases manifest by means of endocrine dysfunction: Cushing syndrome, syndrome of inappropriate antidiuretic hormone, hypercalcemia, hypoglycemia, carcinoid syndrome, and hyperaldosteronism. [8]

Neurological

The following diseases manifest by means of neurological dysfunction: Lambert–Eaton myasthenic syndrome, paraneoplastic cerebellar degeneration, encephalomyelitis, limbic encephalitis, brainstem encephalitis, opsoclonus myoclonus ataxia syndrome, anti-NMDA receptor encephalitis, and polymyositis. [8]

Mucocutaneous

The following diseases manifest by means of mucocutaneous dysfunction: acanthosis nigricans, dermatomyositis, Leser-Trélat sign, necrolytic migratory erythema, Sweet's syndrome, Florid cutaneous papillomatosis, pyoderma gangrenosum, and acquired generalized hypertrichosis. Mucocutaneous dysfunctions of paraneoplastic syndromes can be seen in cases of itching (hypereosinophilia), immune system depression (latent varicella-zoster virus in sensory ganglia), pancreatic tumors (leading to adipose nodular necrosis of subcutaneous tissues), flushes (prostaglandin secretions), and even dermic melanosis (cannot be eliminated via urine and results in grey to black-blueish skin tones). [8]

Hematological

The following diseases manifest by means of hematological dysfunction: granulocytosis, polycythemia, Trousseau sign, nonbacterial thrombotic endocarditis, and anemia. Hematological dysfunction of paraneoplastic syndromes can be seen from an increase of erythropoietin (EPO), which may occur in response to hypoxia or ectopic EPO production/altered catabolism. Erythrocytosis is common in regions of the liver, kidney, adrenal glands, lung, thymus, and central nervous system (as well as gynecological tumors and myosarcomas). [8]

Other

The following diseases manifest by means of physiological dysfunction besides the categories above: membranous glomerulonephritis, tumor-induced osteomalacia, Stauffer syndrome, Neoplastic fever, and thymoma-associated multiorgan autoimmunity. Rheumatologic (hypertrophic osteoarthropathy), renal (secondary kidney amyloidosis and sedimentation of the immunocomplexes in nephrons), and gastrointestinal (production of molecules that affect the motility and secretory activity of the digestive tract) dysfunctions, for example, may relate to paraneoplastic syndromes. [8]

Mechanism

The mechanism for a paraneoplastic syndrome varies from case to case. However, pathophysiological outcomes usually arise when a tumor does. Paraneoplastic syndrome often occurs alongside associated cancers as a result of an activated immune system. In this scenario, the body may produce antibodies to fight off the tumor by directly binding and destroying the tumor cell. Paraneoplastic disorders may arise in that antibodies would cross-react with normal tissues and destroy them. [9]

Diagnosis

Diagnostic testing in a possible paraneoplastic syndrome depends on the symptoms and the suspected underlying cancer.[ citation needed ]

Diagnosis may be difficult in patients in whom paraneoplastic antibodies cannot be detected. In the absence of these antibodies, other tests that may be helpful include MRI, PET, lumbar puncture and electrophysiology. [10]

Types

Syndrome classSyndromeMain causal cancersCausal mechanism
Endocrine [11]
Cushing syndrome Ectopic ACTH and ACTH-like substance
Syndrome of inappropriate antidiuretic hormone Antidiuretic hormone [12]
Hypercalcemia PTHrP (Parathyroid hormone-related protein), TGF-α, TNF, IL-1 [12]
Hypoglycemia Insulin or insulin-like substance [12] or "big" IGF-II
Carcinoid syndrome Serotonin, bradykinin [12]
Hyperaldosteronism Aldosterone [14]
Neurological [15] Lambert–Eaton myasthenic syndrome
  • Small-cell lung cancer
Immunologic
Paraneoplastic cerebellar degeneration
Encephalomyelitis Inflammation of the brain and spinal cord
Limbic encephalitis
  • Small-cell lung carcinoma
Brainstem encephalitis
  • Lung cancer
  • Testicular cancer
Antineuronal antibodies (anti-Hu, anti-Ri, and anti-Ma2). Some forms are amenable to immunotherapy while others are not. [16]
Opsoclonus myoclonus ataxia syndrome
  • Breast carcinoma
  • Ovarian carcinoma
  • Small-cell lung carcinoma
  • Neuroblastoma (in children)
Autoimmune reaction against the RNA-binding protein Nova-1 [17]
Anti-NMDA receptor encephalitis Autoimmune reaction against NMDA-receptor subunits
Polymyositis
Mucocutaneous [19] Acanthosis nigricans
Dermatomyositis Immunologic [12]
Leser-Trélat sign
Necrolytic migratory erythema Glucagonoma
Sweet's syndrome
Florid cutaneous papillomatosis
Pyoderma gangrenosum
Acquired generalized hypertrichosis
Hematological [21] Granulocytosis G-CSF
Polycythemia Erythropoietin [12]
Trousseau sign Mucins that activate clotting, [12] others
Nonbacterial thrombotic endocarditis
  • Advanced cancers [12]
Hypercoagulability [12]
Anemia Unknown [12]
Others Membranous glomerulonephritis
Tumor-induced osteomalacia
Stauffer syndrome
Neoplastic fever [23]
Thymoma-associated multiorgan autoimmunity

A specifically devastating form of (neurological) paraneoplastic syndromes is a group of disorders classified as paraneoplastic neurological disorders (PNDs). [24] These PNDs affect the central or peripheral nervous system; some are degenerative, [25] though others (such as LEMS) may improve with treatment of the condition or the tumor. Symptoms of PNDs may include difficulty with walking and balance, dizziness, rapid uncontrolled eye movements, difficulty swallowing, loss of muscle tone, loss of fine motor coordination, slurred speech, memory loss, vision problems, sleep disturbances, dementia, seizures, and sensory loss in the limbs.[ citation needed ]

The most common cancers associated with PNDs are breast, ovarian, and lung cancers, but many other cancers can produce paraneoplastic symptoms, as well.[ citation needed ]

The root cause is extremely difficult to identify for paraneoplastic syndrome, as there are so many ways the disease can manifest (which may eventually lead to cancer)[ citation needed ]. Ideas may relate to age-related diseases (unable to handle environmental or physical stress in combination with genetic pre-dispositions), accumulation of damaged biomolecules (damages signaling pathways in various regions of the body), increased oxygen free radicals in the body (alters metabolic processes in various regions of the body), etc. [ citation needed ].

However, prophylactic efforts include routine checks with physicians (particularly those that specialize in neurology and oncology) especially when a patient notices subtle changes in his or her own body.[ citation needed ]

Treatment

Treatment options include:[ citation needed ]

  1. Therapies to eliminate the underlying cancer, such as chemotherapy, radiation and surgery.
  2. Therapies to reduce or slow neurological degeneration. In this scenario, rapid diagnosis and treatment are critical for the patient to have the best chance of recovery. Since these disorders are relatively rare, few doctors have seen or treated paraneoplastic neurological disorders (PNDs). Therefore, PND patients should consult with a specialist with experience in diagnosing and treating paraneoplastic neurological disorders.

A specific prognosis for those with paraneoplastic syndromes links to each unique case presented. Thus, prognosis for paraneoplastic syndromes may vary greatly. For example, paraneoplastic pemphigus often included infection as a major cause of death. [26] Paraneoplastic pemphigus is one of the three major subtypes that affects IgG autoantibodies that are characteristically raised against desmoglein 1 and desmoglein 3 (which are cell-cell adhesion molecules found in desmosomes). [27] Underlying cancer or irreversible system impairment, seen in acute heart failure or kidney failure, may result in death as well.[ citation needed ]

Research directions

Prostate cancer is the second most common urological malignancy to be associated with paraneoplastic syndromes after renal cell carcinoma. Paraneoplastic syndromes of this nature tend to occur in the setting of late stage and aggressive tumors with poor overall outcomes (endocrine manifestations, neurological entities, dermatological conditions, and other syndromes). A vast majority of prostate cancer cases (over 70%) document paraneoplastic syndrome as a major clinical manifestation of prostate cancer; and (under 20%), the syndrome as an initial sign of disease progression to the castrate-resistant state. [28] Urologist researchers identify serum markers that are associated with the syndrome in order to specific what type of therapies may work most effectively.[ citation needed ]

Paraneoplastic neurological syndromes may be related immune checkpoint inhibitors (ICIs), one of the underlying causes in inflammatory central nervous system diseases (CNS). The central idea around such research pinpoints treatment strategies to combat cancer related outcomes in the clinical arena, specifically ICIs. Research suggests that patients who are treated with ICIs are more susceptible to CNS disease (since the mechanism of ICIs induces adverse effects on the CNS due to augmented immune responses and neurotoxicity). [29] The purpose of this exploration was to shed light on immunotherapies and distinguishing between neurotoxicity and brain metastasis in the early stages of treatment. In other research, scientists have found that paraneoplastic peripheral nerve disorders (autoantibodies linked to multifocal motor neuropathy) may provide important clinical manifestations. [30] This is especially important for patients who experience inflammatory neuropathies since solid tumors are often associated with peripheral nerve disorders. CV2 autoantibodies, which target dihydropyriminase-related protein 5 (DRP5, or CRMP5) are also associated with a variety of paraneoplastic neurological syndromes, including sensorimotor polyneuropathies. [31] [32] Patients undergoing immune therapies or tumor removal respond very well to antibodies that target CASPR2 (to treat nerve hyperexcitability and neuromyotonia). [33] [34]

Related Research Articles

Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements, that indicates dysfunction of parts of the nervous system that coordinate movement, such as the cerebellum.

Neuromyotonia (NMT) is a form of peripheral nerve hyperexcitability that causes spontaneous muscular activity resulting from repetitive motor unit action potentials of peripheral origin. NMT along with Morvan's syndrome are the most severe types in the Peripheral Nerve Hyperexciteability spectrum. Example of two more common and less severe syndromes in the spectrum are cramp fasciculation syndrome and benign fasciculation syndrome. NMT can have both hereditary and acquired (non-inherited) forms. The prevalence of NMT is unknown.

Morvan's syndrome is a rare, life-threatening autoimmune disease named after the nineteenth century French physician Augustin Marie Morvan. "La chorée fibrillaire" was first coined by Morvan in 1890 when describing patients with multiple, irregular contractions of the long muscles, cramping, weakness, pruritus, hyperhidrosis, insomnia and delirium. It normally presents with a slow insidious onset over months to years. Approximately 90% of cases spontaneously go into remission, while the other 10% of cases lead to death.

Myelitis is inflammation of the spinal cord which can disrupt the normal responses from the brain to the rest of the body, and from the rest of the body to the brain. Inflammation in the spinal cord can cause the myelin and axon to be damaged resulting in symptoms such as paralysis and sensory loss. Myelitis is classified to several categories depending on the area or the cause of the lesion; however, any inflammatory attack on the spinal cord is often referred to as transverse myelitis.

Opsoclonus myoclonus syndrome (OMS), also known as opsoclonus-myoclonus-ataxia (OMA), is a rare neurological disorder of unknown cause which appears to be the result of an autoimmune process involving the nervous system. It is an extremely rare condition, affecting as few as 1 in 10,000,000 people per year. It affects 2 to 3% of children with neuroblastoma and has been reported to occur with celiac disease and diseases of neurologic and autonomic dysfunction.

<span class="mw-page-title-main">Pemphigus</span> Blistering autoimmune diseases

Pemphigus is a rare group of blistering autoimmune diseases that affect the skin and mucous membranes. The name is derived from the Greek root pemphix, meaning "blister".

Neuromyelitis optica spectrum disorders (NMOSD) are a spectrum of autoimmune diseases characterized by acute inflammation of the optic nerve and the spinal cord (myelitis). Episodes of ON and myelitis can be simultaneous or successive. A relapsing disease course is common, especially in untreated patients.

An autoantibody is an antibody produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases are associated with such antibodies.

<span class="mw-page-title-main">Stiff-person syndrome</span> Human medical condition

Stiff-person syndrome (SPS), also known as stiff-man syndrome, is a rare neurologic disorder of unclear cause characterized by progressive muscular rigidity and stiffness. The stiffness primarily affects the truncal muscles and is characterised by spasms, resulting in postural deformities. Chronic pain, impaired mobility, and lumbar hyperlordosis are common symptoms.

<span class="mw-page-title-main">Neuritis</span> Inflammation of a nerve or generally any part of the nervous system

Neuritis, from the Greek νεῦρον), is inflammation of a nerve or the general inflammation of the peripheral nervous system. Inflammation, and frequently concomitant demyelination, cause impaired transmission of neural signals and leads to aberrant nerve function. Neuritis is often conflated with neuropathy, a broad term describing any disease process which affects the peripheral nervous system. However, neuropathies may be due to either inflammatory or non-inflammatory causes, and the term encompasses any form of damage, degeneration, or dysfunction, while neuritis refers specifically to the inflammatory process.

Paraneoplastic cerebellar degeneration (PCD) is a paraneoplastic syndrome associated with a broad variety of tumors including lung cancer, ovarian cancer, breast cancer, Hodgkin’s lymphoma and others. PCD is a rare condition that occurs in less than 1% of cancer patients.

<span class="mw-page-title-main">Limbic encephalitis</span> Inflammation involving the limbic system in the brain

Limbic encephalitis is a form of encephalitis, a disease characterized by inflammation of the brain. Limbic encephalitis is caused by autoimmunity: an abnormal state where the body produces antibodies against itself. Some cases are associated with cancer and some are not. Although the disease is known as "limbic" encephalitis, it is seldom limited to the limbic system and post-mortem studies usually show involvement of other parts of the brain. The disease was first described by Brierley and others in 1960 as a series of three cases. The link to cancer was first noted in 1968 and confirmed by later investigators.

<span class="mw-page-title-main">Robert B. Darnell</span> American biochemist (born 1957)

Robert Bernard Darnell is an American neurooncologist and neuroscientist, founding director and former CEO of the New York Genome Center, the Robert and Harriet Heilbrunn Professor of Cancer Biology at The Rockefeller University, and an Investigator of the Howard Hughes Medical Institute. His research into rare autoimmune brain diseases led to the invention of the HITS-CLIP method to study RNA regulation, and he is developing ways to explore the regulatory portions—known as the "dark matter"—of the human genome.

Paraneoplastic pemphigus (PNP) is an autoimmune disorder stemming from an underlying tumor. It is hypothesized that antigens associated with the tumor trigger an immune response resulting in blistering of the skin and mucous membranes.

<span class="mw-page-title-main">Anti-NMDA receptor encephalitis</span> Rare disease which results in brain inflammation

Anti-NMDA receptor encephalitis is a type of brain inflammation caused by antibodies. Early symptoms may include fever, headache, and feeling tired. This is then typically followed by psychosis which presents with false beliefs (delusions) and seeing or hearing things that others do not see or hear (hallucinations). People are also often agitated or confused. Over time, seizures, decreased breathing, and blood pressure and heart rate variability typically occur. In some cases, patients may develop catatonia.

<span class="mw-page-title-main">Autoimmune encephalitis</span> Type of encephalitis

Autoimmune encephalitis (AIE) is a type of encephalitis, and one of the most common causes of noninfectious encephalitis. It can be triggered by tumors, infections, or it may be cryptogenic. The neurological manifestations can be either acute or subacute and usually develop within six weeks. The clinical manifestations include behavioral and psychiatric symptoms, autonomic disturbances, movement disorders, and seizures.

<span class="mw-page-title-main">Autoimmune autonomic ganglionopathy</span> Medical condition

Autoimmune autonomic ganglionopathy is a type of immune-mediated autonomic failure that is associated with antibodies against the ganglionic nicotinic acetylcholine receptor present in sympathetic, parasympathetic, and enteric ganglia. Typical symptoms include gastrointestinal dysmotility, orthostatic hypotension, and tonic pupils. Many cases have a sudden onset, but others worsen over time, resembling degenerative forms of autonomic dysfunction. For milder cases, supportive treatment is used to manage symptoms. Plasma exchange, intravenous immunoglobulin, corticosteroids, or immunosuppression have been used successfully to treat more severe cases.

Anti-VGKC-complex encephalitis are caused by antibodies against the voltage gated potassium channel-complex (VGKC-complex) and are implicated in several autoimmune conditions including limbic encephalitis, epilepsy and neuromyotonia.

Anti-Hu associated encephalitis, also known as Anti-ANNA1 associated encephalitis, is an uncommon form of brain inflammation that is associated with an underlying cancer. It can cause psychiatric symptoms such as depression, anxiety, and hallucinations. It can also produce neurological symptoms such as confusion, memory loss, weakness, sensory loss, pain, seizures, and problems coordinating the movement of the body.

Anti-IgLON5 disease is an uncommon neurological autoimmune condition linked to autoantibodies directed against the IgLON5 protein. Sleep disturbance, bulbar symptoms, and abnormal gait make up the majority of the clinical presentation, which is then followed by cognitive dysfunction. The diagnosis of anti-IgLON5 disease is primarily based on clinical signs and the identification of IgLON5 antibodies in patient serum and/or cerebrospinal fluid.

References

  1. 1 2 "Paraneoplastic Syndromes". National Institute of Neurological Disorders and Stroke. Retrieved 5 September 2023.
  2. ↑ Sardiña González, Cristina; Martínez Vivero, Clara; López Castro, José (June 2022). "Paraneoplastic syndromes review: The great forgotten ones" . Critical Reviews in Oncology/Hematology. 174: 103676. doi:10.1016/j.critrevonc.2022.103676. ISSN   1879-0461. PMID   35378267. S2CID   247934655.
  3. ↑ Paraneoplastic Syndromes, 2011, Darnell & Posner
  4. ↑ NINDS Paraneoplastic Syndromes Information Page Archived 2015-01-04 at the Wayback Machine National Institute of Neurological Disorders and Stroke
  5. ↑ Darnell RB, DeAngelis LM (January 1993). "Regression of small-cell lung carcinoma in patients with paraneoplastic neuronal antibodies". Lancet. 341 (8836): 21–22. doi: 10.1016/0140-6736(93)92485-c . PMID   8093269. S2CID   205040647.
  6. ↑ Roberts WK, Darnell RB (October 2004). "Neuroimmunology of the paraneoplastic neurological degenerations". Current Opinion in Immunology. 16 (5): 616–622. doi:10.1016/j.coi.2004.07.009. PMID   15342008.
  7. ↑ Albert ML, Darnell RB (January 2004). "Paraneoplastic neurological degenerations: keys to tumour immunity". Nature Reviews. Cancer. 4 (1): 36–44. doi:10.1038/nrc1255. PMID   14708025. S2CID   7319871.
  8. 1 2 3 4 5 6 Santacroce L, Diomede L, Balducci L (3 February 2019). Talavera F, Movsas B (eds.). "Background of Paraneoplastic Syndromes". Medscape. WebMD LLC.
  9. ↑ Pittock SJ, Kryzer TJ, Lennon VA (November 2004). "Paraneoplastic antibodies coexist and predict cancer, not neurological syndrome". Annals of Neurology. 56 (5): 715–719. doi:10.1002/ana.20269. PMID   15468074. S2CID   31651589.
  10. ↑ Dalmau J, Rosenfield MR (6 December 2016). "Overview of paraneoplastic syndromes of the nervous system" . UpToDate. Retrieved 23 December 2017.
  11. ↑ Paraneoplastic+endocrine+syndromes at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
  12. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 Table 6-5 in: Mitchell RS, Kumar V, Abbas AK, Fausto N (2007). Robbins Basic Pathology. Philadelphia: Saunders. ISBN   978-1-4160-2973-1. 8th edition.
  13. 1 2 Goldner W (May 2016). "Cancer-Related Hypercalcemia". Journal of Oncology Practice. 12 (5): 426–432. doi: 10.1200/JOP.2016.011155 . PMID   27170690.
  14. ↑ Mulatero P, Rabbia F, Veglio F (May 2001). "Paraneoplastic hyperaldosteronism associated with non-Hodgkin's lymphoma". The New England Journal of Medicine. 344 (20): 1558–1559. doi: 10.1056/NEJM200105173442017 . PMID   11368052.
  15. ↑ Nervous+system+paraneoplastic+syndromes at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
  16. ↑ Blaes F (April 2013). "Paraneoplastic brain stem encephalitis". Current Treatment Options in Neurology. 15 (2): 201–209. doi:10.1007/s11940-013-0221-1. PMID   23378230. S2CID   21581917.
  17. ↑ Buckanovich RJ, Posner JB, Darnell RB (October 1993). "Nova, the paraneoplastic Ri antigen, is homologous to an RNA-binding protein and is specifically expressed in the developing motor system". Neuron. 11 (4): 657–672. doi:10.1016/0896-6273(93)90077-5. PMID   8398153. S2CID   22554933.
  18. ↑ Dalmau J, Tüzün E, Wu HY, Masjuan J, Rossi JE, Voloschin A, et al. (January 2007). "Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma". Annals of Neurology. 61 (1): 25–36. doi:10.1002/ana.21050. PMC   2430743 . PMID   17262855.
  19. ↑ Cohen PR, Kurzrock R (June 1997). "Mucocutaneous paraneoplastic syndromes". Seminars in Oncology. 24 (3): 334–359. PMID   9208889.
  20. ↑ Hill CL, Zhang Y, Sigurgeirsson B, Pukkala E, Mellemkjaer L, Airio A, et al. (January 2001). "Frequency of specific cancer types in dermatomyositis and polymyositis: a population-based study". Lancet. 357 (9250): 96–100. doi:10.1016/S0140-6736(00)03540-6. PMID   11197446. S2CID   35258253.
  21. ↑ Staszewski H (June 1997). "Hematological paraneoplastic syndromes". Seminars in Oncology. 24 (3): 329–333. PMID   9208888.
  22. ↑ Zadik Y, Nitzan DW (February 2012). "Tumor induced osteomalacia: a forgotten paraneoplastic syndrome?". Oral Oncology. 48 (2): e9-10. doi:10.1016/j.oraloncology.2011.09.011. PMID   21985764.
  23. ↑ Zell JA, Chang JC (November 2005). "Neoplastic fever: a neglected paraneoplastic syndrome". Supportive Care in Cancer. 13 (11): 870–877. doi:10.1007/s00520-005-0825-4. PMID   15864658. S2CID   23992076.
  24. ↑ Rees JH (June 2004). "Paraneoplastic syndromes: when to suspect, how to confirm, and how to manage". Journal of Neurology, Neurosurgery, and Psychiatry. 75 (Suppl 2): ii43–ii50. doi:10.1136/jnnp.2004.040378. PMC   1765657 . PMID   15146039.
  25. ↑ Darnell RB, Posner JB (June 2006). "Paraneoplastic syndromes affecting the nervous system". Seminars in Oncology. 33 (3): 270–298. doi:10.1053/j.seminoncol.2006.03.008. PMID   16769417.
  26. ↑ Leger S, Picard D, Ingen-Housz-Oro S, Arnault JP, Aubin F, Carsuzaa F, et al. (October 2012). "Prognostic factors of paraneoplastic pemphigus". Archives of Dermatology. 148 (10): 1165–1172. doi: 10.1001/archdermatol.2012.1830 . PMID   22801794.
  27. ↑ Kasperkiewicz M, Ellebrecht CT, Takahashi H, Yamagami J, Zillikens D, Payne AS, Amagai M (May 2017). "Pemphigus". Nature Reviews. Disease Primers. 3: 17026. doi:10.1038/nrdp.2017.26. PMC   5901732 . PMID   28492232.
  28. ↑ Hong MK, Kong J, Namdarian B, Longano A, Grummet J, Hovens CM, et al. (December 2010). "Paraneoplastic syndromes in prostate cancer". Nature Reviews. Urology. 7 (12): 681–692. doi:10.1038/nrurol.2010.186. PMID   21139643. S2CID   25387789.
  29. ↑ Yshii LM, Hohlfeld R, Liblau RS (December 2017). "Inflammatory CNS disease caused by immune checkpoint inhibitors: status and perspectives". Nature Reviews. Neurology. 13 (12): 755–763. doi:10.1038/nrneurol.2017.144. PMID   29104289. S2CID   41673022.
  30. ↑ Querol L, Devaux J, Rojas-Garcia R, Illa I (September 2017). "Autoantibodies in chronic inflammatory neuropathies: diagnostic and therapeutic implications". Nature Reviews. Neurology. 13 (9): 533–547. doi:10.1038/nrneurol.2017.84. PMID   28708133. S2CID   24396478.
  31. ↑ Graus F, Saiz A, Dalmau J (April 2010). "Antibodies and neuronal autoimmune disorders of the CNS". Journal of Neurology. 257 (4): 509–517. doi:10.1007/s00415-009-5431-9. PMID   20035430. S2CID   19651940.
  32. ↑ Hannawi Y, Goldsmith CE, Kass JS, Olar A, Ubogu EE, Kalkonde YV (September 2013). "A case of severe chronic progressive axonal polyradiculoneuropathy temporally associated with anti-CV2/CRMP5 antibodies". Journal of Clinical Neuromuscular Disease. 15 (1): 13–18. doi:10.1097/cnd.0b013e3182a04538. PMID   23965404. S2CID   37917515.
  33. ↑ Lancaster E, Huijbers MG, Bar V, Boronat A, Wong A, Martinez-Hernandez E, et al. (February 2011). "Investigations of caspr2, an autoantigen of encephalitis and neuromyotonia". Annals of Neurology. 69 (2): 303–311. doi:10.1002/ana.22297. PMC   3059252 . PMID   21387375.
  34. ↑ van Sonderen A, Ariño H, Petit-Pedrol M, Leypoldt F, Körtvélyessy P, Wandinger KP, et al. (August 2016). "The clinical spectrum of Caspr2 antibody-associated disease". Neurology. 87 (5): 521–528. doi:10.1212/wnl.0000000000002917. PMC   4970662 . PMID   27371488.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.