Pernicious anemia 538993 225441271 2008-07-13T18:37:13Z Xofc 810252 + [[fr:Maladie de Biermer]] {{Infobox_Disease | Name = Pernicious anemia | Image = | Caption = | DiseasesDB = 9870 | ICD10 = {{ICD10|D|51|0|d|50}} | ICD9 = {{ICD9|281.0}} | ICDO = | OMIM = | MedlinePlus = 000569 | eMedicineSubj = med | eMedicineTopic = 1799 | MeshID = D000752 | }} '''Pernicious anemia''' (also known as ''Biermer's anaemia'' or ''Addison's anaemia'' or ''Addison-Biermer anaemia'') is a form of [[megaloblastic anemia]] due to [[vitamin B-12]] (vitamin B<sub>12</sub>) [[Avitaminosis|deficiency]], caused by impaired absorption of vitamin B-12<ref name="pmid17375844">{{cite journal |author=Kumar V |title=Pernicious anemia |journal=MLO Med Lab Obs |volume=39 |issue=2 |pages=28, 30–1 |year=2007 |pmid=17375844 |doi=}}</ref> due to the absence of [[intrinsic factor]]<ref name="titleUniversity of Chicago Med Ctr: Megaloblastic (Pernicious) Anemia">{{cite web |url=http://www.uchospitals.edu/online-library/content=P00080 |title=University of Chicago Med Ctr: Megaloblastic (Pernicious) Anemia |accessdate=2008-01-27 |format= |work=}}</ref> in the setting of [[atrophic gastritis]], and more specifically of loss of [[stomach|gastric]] [[parietal cell]]s. While the term "pernicious anemia" is sometimes also incorrectly used to indicate [[megaloblastic anemia]] due to ''any'' cause of vitamin B-12 deficiency, its proper usage refers to that caused by atrophic gastritis and parietal cell loss only. It is the most common result of adult vitamin B-12 deficiency.<ref name="pmid18028852">{{cite journal |author=Masnou H, Domènech E, Navarro-Llavat M, ''et al'' |title=Pernicious anaemia in triplets. A case report an literature review |journal=Gastroenterol Hepatol |volume=30 |issue=10 |pages=580–582 |year=2007 |pmid=18028852 |doi=10.1157/13112591|url=http://db.doyma.es/cgi-bin/wdbcgi.exe/doyma/mrevista.pubmed_full?inctrl=05ZI0109&rev=14&vol=30&num=10&pag=580}}</ref> ==Mechanisms and manifestations== ===Pathophysiology=== Vitamin B-12 cannot be produced by the human body, and must therefore be obtained from diet. Normally, dietary vitamin B-12 can only be absorbed by the [[ileum]] when it is bound by the [[intrinsic factor]] produced by [[parietal cell]]s of the [[stomach|gastric]] [[mucosa]]. In pernicious anemia, this process is impaired because of loss of parietal cells, resulting in insufficient absorption of the vitamin, which over a prolonged period of time ultimately leads to vitamin B-12 deficiency and thus megaloblastic anemia. This anemia is a result of the body's inability to produce [[DNA]] in sufficient quantities for blood cell synthesis, due to interruption of a [[biochemical pathway]] that is dependent on vitamin B-12 and/or [[folic acid]] as cofactors, which synthesizes [[thymine]], a DNA component. ===Presentation=== {{seemain|anemia}} {{seemain|megaloblastic anemia}} {{seemain|vitamin B-12}} The presentation of pernicious anemia resembles that of any other form of anemia, but is often accompanied by the manifestations of vitamin B<sub>12</sub> deficiency (notably neurological abnormalities such as [[peripheral neuropathy]]), as well as by other manifestations of autoimmune atrophic gastritis. ==Causes== Most commonly (in temperate climates), the cause for impaired binding of vitamin B<sub>12</sub> by intrinsic factor is [[autoimmune]] [[atrophic gastritis]],<ref name="titleeMedicine - Gastritis, Atrophic : Article by Antonia R Sepulveda, MD, PhD">{{cite web |url=http://www.emedicine.com/med/topic851.htm |title=eMedicine - Gastritis, Atrophic : Article by Antonia R Sepulveda, MD, PhD |accessdate=2008-01-27 |format= |work=}}</ref> in which [[autoantibody|autoantibodies]] are directed against [[parietal cell]]s (resulting in their loss) as well as against the [[intrinsic factor]] itself (rendering it unable to bind vitamin B-12). Less frequently, loss of parietal cells may simply be part of a widespread atrophic gastritis of non-autoimmune origin, such as that frequently occurring in elderly people affected with long-standing chronic [[gastritis]] of any cause (including ''[[Helicobacter pylori]]'' infection). Note that forms of vitamin B-12 deficiency other than pernicious anemia must be considered in the [[differential diagnosis]] of [[megaloblastic anemia]]. For example, a B-12 deficient state which causes megaloblastic anemia and which may be mistaken for classical pernicious anemia, may be caused by infection with the [[tapeworm]] ''Diphyllobothrium latum'', possibly due to the parasite's competition for vitamin B-12, <ref name="titleeMedicine - Diphyllobothrium latum Infection : Article by Robert W Tolan Jr, MD">{{cite web |url=http://www.emedicine.com/ped/TOPIC597.HTM |title=eMedicine - Diphyllobothrium latum Infection : Article by Robert W Tolan Jr, MD, Alia Rai, MD, and Martin Weisse, MD |accessdate=2008-04-11 |format= |work=}}</ref>. ==Symptoms and signs== {{div col}} *Due to [[anemia]]: * 'Fog days' - cognitive impairment ** [[Pallor]] ** [[Fatigue (medical)|Fatigue]] ** Shortness of breath - known as 'the sighs'. ** [[Rapid heartbeat]] * Tongue symptoms: red, burning or sore * Digestive disturbances: ** Upset stomach ** Weight loss ** Loss of appetite ** [[Diarrhea]] ** [[Constipation]] ** Abdominal pain * [[Jaundice]] due to impaired formation of [[blood cells]] * [[Fever]] * [[Malaise]] * [[Paresthesia]]s ** Finger paresthesias ** [[Pins and needles]] ** Tingling or burning fingers ** Numb fingers * Due to low [[muscle tone]]: ** [[Muscle spasms]] ** Unsteadiness ** Movement disorders * Weakness * [[Spasticity]] * Personality changes * [[Chest pain]] {{div col end}} ==Diagnosis== A diagnosis of pernicious anemia first requires demonstration of [[megaloblastic anemia]] (through a [[full blood count]]) which evaluates the [[mean corpuscular volume]] (MCV), as well the [[mean corpuscular hemoglobin concentration]] (MCHC). Pernicious anemia is identified with a high MCV and a normal MCHC (that is, it is a [[macrocytic]], [[normochromic]] anemia). <ref name="titleMosby's Manual of Diagnostic and Laboratory Tests: K.D. Pagana and T.J. Pagana |published 2006, Mosby |format= |work=}}</ref>. Ovalocytes are also typically seen on the blood smear, and a [[pathognomonic]] feature of megaloblastic anemias (which include pernicious anemia and others) is hypersegmented neutrophils. Pernicious anemia can also be diagnosed by evaluating its direct cause, vitamin B-12 deficiency (by measuring B-12 levels in serum). A [[Schilling test]] can then be used to distinguish pernicious anemia from other causes of vitamin B-12 deficiency (notably [[malabsorption]]).<ref name="titleeMedicine - Pernicious Anemia : Article by Marcel E Conrad, MD">{{cite web |url=http://www.emedicine.com/MED/topic1799.htm |title=eMedicine - Pernicious Anemia : Article by Marcel E Conrad, MD |accessdate=2008-01-27 |format= |work=}}</ref> A diagnosis of [[atrophic gastritis]] should be confirmed by [[gastroscopy]] with [[biopsy|biopsies]]. Approximately 90% of individuals with pernicious anemia have antibodies for parietal cells; however only 50% of all individuals in the general population with these antibodies have pernicious anemia. ==Treatment== {{seemain|Vitamin B-12}} Being a manifestation of vitamin B-12 deficiency, pernicious anemia is treated by administering vitamin B-12 supplements. Oral tablets are sometimes used,<ref name="pmid9736106">{{cite journal |author=Lederle FA |title=Oral cobalamin for pernicious anemia: back from the verge of extinction |journal=J Am Geriatr Soc |volume=46 |issue=9 |pages=1125–7 |year=1998 |pmid=9736106 |doi=}}</ref> though if this approach is used, much higher doses are given than normally required in order to overcome the impaired absorption that characterizes pernicious anemia. <ref name="titlePernicious Anemia and B-12 Injections">{{cite web |url=http://healthlink.mcw.edu/article/880000064.html |title=Pernicious Anemia and B12 Injections |accessdate=2008-01-27 |format= |work=}}</ref> If oral tablets are not desired, vitamin B-12 can also be administered via [[Injection (medicine)|injection]],<ref name="pmid16335029">{{cite journal |author=De Paz R, Hernández-Navarro F |title=[Management, prevention and control of pernicious anemia] |language=Spanish; Castilian |journal=Nutr Hosp |volume=20 |issue=6 |pages=433–5 |year=2005 |pmid=16335029 |doi=}}</ref> which is usually given once a month. Often the patient can learn to do this at home with the same syringes and needles used for insulin treatment of diabetes. ==History== Dr. Addison first described the disease, from which it acquired the common name of Addison's Anemia. Dr. Newcastle found that he could regurgitate his own gastric juices and feed it to his patients, also causing disease improvement. However, this was not a sustainable practice. Pernicious anemia was a fatal disease before about the year [[1920]], when Whipple suggested raw [[liver]] as a treatment. After verification of Whipple's results in [[1926]], pernicious anemia victims ate or drank at least 1/2 a pound of raw liver, or drank raw liver juice every day. This continued for several years until a concentrate of liver juice became available after 1928. The first workable treatment for pernicious anemia began with the work of [[George Whipple]] who made the discovery in the course of experiments in which he bled dogs to make them anemic, then fed them various foods to see which would make them recover most rapidly (Whipple was looking for treatments for anemia from bleeding, not pernicious anemia). Whipple discovered that ingesting large amounts of [[liver]] seemed to cure anemia from blood loss, and tried liver ingestion as a treatment for pernicious anemia, reporting improvement there also, in a paper in [[1920]]. [[George Richards Minot|George Minot]] and [[William Murphy]] then set about to partly isolate the curative property in liver and showed that it was contained in raw liver juice (in the process also showing that ironically it was the iron in liver tissue, not the soluble factor in liver juice, which cured the anemia from bleeding in dogs; thus the discovery of the liver juice factor as a treatment for pernicious anemia, had been by coincidence). For the discovery of the cure of a previously fatal disease of unknown [[etiology]] the three men shared the [[1934]] [[Nobel Prize in Physiology or Medicine|Nobel Prize in Medicine]].<ref>http://www.mayoclinicproceedings.com/pdf%2F8106%2F8106sv.pdf</ref> In 1928 chemist [[Edwin Cohn]] prepared a liver extract that was 50 to 100 times more potent than the natural food (liver). The extract could even be injected into muscle, which meant that patients no longer needed to eat large amounts of liver or juice. This reduced the cost of treatment considerably. The active ingredient in liver was unknown until 1948, when it was isolated by two chemists, [[Karl A. Folkers]] of the United States and [[Alexander R. Todd]] of Great Britain. The substance was a [[cobalamin]], which the discoverers named [[vitamin B-12]]. The new vitamin in liver juice was eventually completely purified and characterized in the 1950s, and other methods of producing it from bacteria were developed. It could be injected into muscle with even less irritation, making it possible to treat pernicious anemia with even more ease. Pernicious anemia was eventually treated with either vitamin B-12 injections, or else large oral doses of vitamin B-12, typically between 1 and 4 mg (1000 to 4000 mcg) daily. ==Famous sufferers== *[[Inez Milholland]], American [[Suffragette]]. *[[Alexander Graham Bell]], Scottish scientist and inventor. *[[Annie Oakley]].<ref name="titleAnnie Oakley - MSN Encarta">{{cite web |url=http://encarta.msn.com/encyclopedia_761563729/Annie_Oakley.html |title=Annie Oakley - MSN Encarta |accessdate=2008-01-27 |format= |work=}}</ref> *[[Norman Warne]], Editor/Publisher & fiance of [[Beatrix Potter]]. *[[Yoon Eun Hye]], A South Korean actress *[[Betsie ten Boom]], Sister to [[Corrie ten Boom]], victim of the [[Holocaust]], and in the book, ''[[The Hiding Place]]'' *[[David Hilbert]], German mathematician. *[[Sam Hughes]], Canadian [[Minister of Militia and Defence]]. ==References== {{reflist|2}} ==External links== * [http://www.pernicious-anaemia-society.org/ The Pernicious Anaemia Society], a UK-based charitable organisation *[http://www.pernicious-anemia.net Pernicious anemia symptoms, causes, treatments and background details] *[http://www.antibodypatterns.com/gpc.php Parietal cell antibody] *[http://www.ii.bham.ac.uk/clinicalimmunology/CISimagelibrary/GPC.htm Antibody to GPC] {{Hematology}} [[Category:Hematology]] [[de:Perniziöse Anämie]] [[es:Anemia perniciosa]] [[fr:Maladie de Biermer]] [[it:Anemia perniciosa]] [[nl:Pernicieuze anemie]] [[pl:Niedokrwistość Addisona-Biermera]] [[pt:Anemia perniciosa]] [[sl:Perniciozna naemija]] [[fi:Pernisiöösi anemia]] [[tr:Pernisyöz anemi]] [[uk:Pernicious anaemia]]