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| | __NOTOC__ |
| | {{Porphyria}} |
| | {{CMG}}; {{AE}} |
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| | {{SK}}Acute intermittent porphyria; hereditary coproporphyria; congenital erythropoietic porphyria; erythropoietic protoporphyria |
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| | '''For patient information click [[{{PAGENAME}} (patient information)|here]]''' |
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| {{Infobox_Disease | | | {{Infobox_Disease | |
| Name = Porphyria | | | Name = Porphyria | |
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| MeshNumber = C17.800.849.617 | | | MeshNumber = C17.800.849.617 | |
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| {{CMG}}
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| | ==[[Porphyria overview|Overview]]== |
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| ==Overview== | | ==[[Porphyria historical perspective|Historical Perspective]]== |
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| '''Porphyrias''' are a group of inherited or acquired disorders of certain [[enzyme]]s in the [[heme]] biosynthetic pathway (also called [[porphyrin]] pathway). They are broadly classified as '''hepatic porphyrias''' or '''erythropoietic porphyrias''', based on the site of the overproduction and mainly accumulation of the porphyrins (or their chemical precursors). They manifest with either skin problems or with neurological complications (or occasionally both).
| | ==[[Porphyria classification|Classification]]== |
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| The term derives from the [[Greek language|Greek]] πορφύρα, ''porphura,'' meaning "purple pigment". The name is likely to have been a reference to the purple discolouration of some body fluids in patients during an attack.<ref name=Lane>Lane, N. ''Born to the purple: the story of porphyria'' [[Scientific American]] [http://www.sciam.com/article.cfm?articleID=000B1BEF-C051-1DF8-9733809EC588EEDF Fulltext].</ref> Although original descriptions are attributed to [[Hippocrates]], the disease was first explained biochemically by [[Felix Hoppe-Seyler]] in 1874,<ref>Hoppe-Seyler F. Das Hämatin. ''Tubinger Med-Chem Untersuch'' 1871;4:523–33</ref> and acute porphyrias were described by the Dutch physician B.J. Stokvis in 1889.<ref>Stokvis BJ. Over twee zeldzame kleurstoffen in urine van zieken. ''Nederl Tijdschr Geneeskd'' 1889;2:409-417.</ref><ref name=Lane/>
| | ==[[Porphyria pathophysiology|Pathophysiology]]== |
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| == Epidemiology and Demographics == | | ==[[Porphyria causes|Causes]]== |
| The acute attack is 5 times more common in females.
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| == Risk Factors == | | ==[[Porphyria differential diagnosis|Differentiating Porphyria from other Diseases]]== |
| The two most common precipitants are drugs and menstrual cycle. Alcohol, infection, steroid hormones and fasting are also known precipitants.
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| == Pathophysiology & Etiology== | | ==[[Porphyria epidemiology and demographics|Epidemiology and Demographics]]== |
| ===Types of Porphyria===
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| The 8 porphyrias are:
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| # Acute intermittent Porphyria (AIP)
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| # ALA dehydratase deficiency
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| # Porphyria cutanea tarda (PCT)
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| # Congenital Erythropoetic Porphyria (CEP)
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| # Hepatoerythropoetic Porphyria (HEP)
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| # Erythopoetic Protoporphyria (EPP)
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| # Hereditary coproporphyria (HCP)
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| # Variegate Porphyria (VP)
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| These disorders can also be divided based on the type of precursors that accumulate and the subsequent manifestations that occur. ALA dehydratase deficiency (Plumboporphyria) and AIP are characterized by the accumulation of -aminolevulinic acid (ALA) and Porphobilinogen (PBG). Their manifestations are primarily neuropathic. PCT, CEP, HEP and EEP are characterized by accumulation of porphyrin and have cutaneous manifestations only. HCP and VP have accumulation of porphyrin precursors and porphyrins. They have both neuropathic and cutaneous manifestations.
| | ==[[Porphyria risk factors|Risk Factors]]== |
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| In [[human]]s, [[porphyrin]]s are the main precursors of [[heme]], an essential constituent of [[hemoglobin]], [[myoglobin]], [[catalase]], [[peroxidase]], respiratory and P450 liver [[cytochrome]]s.
| | ==[[Porphyria screening|Screening]]== |
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| [[Image:Heme synthesis.png|thumb|left|Heme synthesis—note that some reactions occur in the [[cytoplasm]] and some in the [[mitochondrion]] (yellow)]]
| | ==[[Porphyria natural history|Natural History, Complications and Prognosis]]== |
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| Deficiency in the enzymes of the porphyrin pathway leads to insufficient production of heme. Heme function plays a central role in cellular [[metabolism]]. This is not the main problem in the porphyrias; most heme synthesis [[enzymes]]—even dysfunctional enzymes—have enough residual activity to assist in heme biosynthesis. The principal problem in these deficiencies is the accumulation of porphyrins, the heme precursors, which are toxic to tissue in high concentrations. The chemical properties of these intermediates determine the location of accumulation, whether they induce [[photosensitivity]], and whether the intermediate is excreted (in the [[urine]] or [[feces]]).
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| There are eight [[enzyme]]s in the heme biosynthetic pathway, four of which—the first one and the last three—are in the [[mitochondria]], while the other four are in the [[cytosol]]. Defects in any of these can lead to some form of porphyria.
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| The [[hepatic porphyria]]s are characterized by acute neurological attacks ([[seizure]]s, [[psychosis]], extreme [[back pain|back]] and [[abdominal pain]] and an acute [[polyneuropathy]]), while the [[Erythropoietic porphyria|erythropoietic forms]] present with skin problems, usually a light-sensitive blistering rash and [[hypertrichosis|increased hair growth]].
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| ''[[Variegate porphyria]]'' (also ''porphyria variegata'' or ''mixed porphyria''), which results from a partial deficiency in [[PROTO oxidase]], manifests itself with skin lesions similar to those of porphyria cutanea tarda combined with acute neurologic attacks. All other porphyrias are either skin- or nerve-predominant.
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| {| cellpadding=3 cellspacing=0 border=1 style="border-collapse:collapse" | align=center
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| |bgcolor="#eeeeee"| '''[[Enzyme]]'''
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| |bgcolor="#eeeeee"| '''Location of enzyme'''
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| |bgcolor="#eeeeee"| '''Associated porphyria'''
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| |bgcolor="#eeeeee"| '''Type of porphyria'''
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| |-
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| | [[ALA synthase|δ-aminolevulinate (ALA) synthase]]
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| | Mitochondrion
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| | [[X-linked]] [[sideroblastic anemia]] (XLSA)
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| | Erythropoietic
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| | δ-aminolevulinate (ALA) dehydratase
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| | Cytosol
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| | Doss porphyria/[[ALA dehydratase deficiency]]
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| | Hepatic
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| | [[Porphobilinogen deaminase|hydroxymethylbilane (HMB) synthase]] (or PBG deaminase)
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| | Cytosol
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| | [[acute intermittent porphyria]] (AIP)
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| | Hepatic
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| | [[Uroporphyrinogen III synthase|uroporphyrinogen (URO) synthase]]
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| | Cytosol
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| | [[Congenital erythropoietic porphyria]] (CEP)
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| | Erythropoeitic
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| | [[Uroporphyrinogen III decarboxylase|uroporphyrinogen (URO) decarboxylase]]
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| | Cytosol
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| | [[Porphyria cutanea tarda]] (PCT)
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| | Hepatic | |
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| | [[Coproporphyrinogen III oxidase|coproporphyrinogen (COPRO) oxidase]]
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| | Mitochondrion
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| | [[Hereditary coproporphyria]] (HCP)
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| | Hepatic
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| | [[Protoporphyrinogen oxidase|protoporphyrinogen (PROTO) oxidase]]
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| | Mitochondrion
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| | [[Variegate porphyria]] (VP)
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| | Mixed
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| | [[Ferrochelatase]]
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| | Mitochondrion
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| | [[Erythropoietic protoporphyria]] (EPP)
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| | Erythropoietic
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| |}
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| == Genetics ==
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| Evaluation of family members is necessary to identify latent porphyria. All acute porphyrias are autosomal dominant except for ALA-D which is autosomal recessive.
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| ==Diagnosis== | | ==Diagnosis== |
| ===Signs and symptoms===
| | [[Porphyria history and symptoms|History and Symptoms]] | [[Porphyria physical examination |Physical Examination]] | [[Porphyria laboratory findings|Laboratory Findings]] | [[Porphyria electrocardiogram|Electrocardiogram]] | [[Porphyria x ray|X Ray]] | [[Porphyria CT|CT]] | [[Porphyria MRI|MRI]] | [[Porphyria ultrasound|Ultrasound]] | [[Porphyria other imaging findings|Other Imaging Findings]] | [[Porphyria other diagnostic studies|Other Diagnostic Studies]] |
| ====Acute porphyria====
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| The cutaneous sensitivity to light is due to excitation of accumulated porphyrins in the skin by UV light. This leads to progressive damage, scarring and deformation.
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| The “ Acute porphyrias ”: AIP, VP, CP and ALA-dehydratase deficiency are characterized by acute attacks . The acute attack is characterized by:
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| * Severe abdominal pain (90%), back, buttock and thigh pain.
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| * Autonomic dysfunction: tachycardia, hypertension, ileus, bladder dysfunction, vomiting, sweating
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| * Dehydration is common.
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| * Seizures
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| * Hyponatremia (thought to be caused by ADH) can be severe.
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| * Motor neuropathies predominate but almost any neuropathy can be seen. The neuropathic effects can progress and become severe leading to irreversible neurologic damage, a Guillian-Barre type syndrome with paralysis, bulbar dysfunction, respiratory failure and death.
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| The hepatic porphyrias primarily affect the [[nervous system]], resulting in [[abdominal pain]], [[vomiting]], acute [[neuropathy]], [[seizure]]s and mental disturbances, including [[hallucination]]s, [[clinical depression|depression]], [[anxiety]] and [[paranoia]]. [[Cardiac arrhythmia]]s and [[tachycardia]] (fast heart rate) may develop as the [[autonomic nervous system]] is affected. Pain can be severe and can, in some cases, be both acute and chronic in nature. [[Constipation]] is frequently present, as the nervous system of the gut is affected, but [[diarrhea]] can also occur.
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| Given the many presentations and the relatively uncommon occurrence of porphyria the patient may initially be suspected to have other, unrelated conditions. For instance, the polyneuropathy of acute porphyria may be mistaken for [[Guillain-Barré syndrome]], and porphyria testing is commonly recommended in those scenarios.<ref>Albers JW, Fink JK. Porphyric neuropathy. ''Muscle Nerve'' 2004;30:410-22. PMID 15372536.</ref> [[Lupus erythematosus]] features photosensitivity, pain attacks and shares various other symptoms with porphyria.<ref>Roelandts R. The diagnosis of photosensitivity. ''Arch Dermatol'' 2000;136:1152-7. PMID 10987875.</ref>
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| Not all porphyrias are genetic, and patients with liver disease who develop porphyria as a result of liver dysfunction may exhibit signs of their conditions, such as [[jaundice]].
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| Attacks of the disease can be triggered by drugs (e.g. [[barbiturate]]s, [[alcohol]], sulfa drugs, [[hormonal contraception]], [[sedative]]s and certain [[antibiotic]]s), other chemicals and certain foods. Fasting can also trigger attacks.
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| Patients with hepatic porphyrias (PCT, AIP, HCP, VP) are at increased risk over their life for [[hepatocellular carcinoma]] (primary liver cancer) and may require monitoring. Other typical risk factors for liver cancer need not be present, such as hepatitis B or C, iron overload or alcoholic cirrhosis.
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| ====Cutaneous porphyria====
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| The erythropoietic porphyrias primarily affect the [[skin]], causing [[photosensitivity]] ([[photodermatitis]]), [[blister]]s, necrosis of the skin and gums, itching, and swelling, and increased hair growth on areas such as the forehead. Often there is no abdominal pain which distinguishes it from other porphyrias.
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| In some forms of porphyria, accumulated heme precursors excreted in the urine may cause various changes in color, after exposure to sunlight, to a dark reddish or dark brown color. Even a purple hue or pink urine may be seen. Heme precursors may also accumulate in the teeth and fingernails, giving them a reddish appearance.
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| ===Laboratory Findings===
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| ====Porphyrin studies====
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| === Electrolyte and Biomarker Studies ===
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| Increased urinary PBG is diagnostic. ALA is somewhat increased. Screening test is Watson-Schwartz test. PBG reacts with Ehrlich’s reagent in acidic solution to form red pigment. ALA-D will only have an elevation of ALA. A negative test rules out porphyria. The results can be confirmed with a quantitative test for fecal and plasma porphyrins and a 24 hour urine sample. The type of acute porphyria is determined based on measurement of fecal and plasma porphyrins. HCP and VP will have coproporphyrin III in feces. VP will also have protoporphyrin and plasma will have an emission peak at 624-26 nm on fluorescence spectroscopy.
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| Porphyria is diagnosed through [[spectroscopy]] and biochemical analysis of [[blood]], [[urine]], and [[stool]].<ref name=Thadani>Thadani H, Deacon A, Peters T. Diagnosis and management of porphyria. ''BMJ'' 2000;320:1647-51. [http://bmj.bmjjournals.com/cgi/content/full/320/7250/1647 Fulltext]. PMID 10856069.</ref> In general, urine estimation of porphobilinogen (PBG) is the first step if acute porphyria is suspected. As a result of feedback, the decreased production of heme leads to increased production of precursors, PBG being one of the first substances in the porphyrin synthesis pathway.<ref name=Anderson>Anderson KE, Bloomer JR, Bonkovsky HL, Kushner JP, Pierach CA, Pimstone NR, Desnick RJ. Recommendations for the diagnosis and treatment of the acute porphyrias. ''Ann Intern Med'' 2005;142:439-50. PMID 15767622.</ref> In nearly all cases of acute porphyria syndromes, urinary PBG is markedly elevated except for the very rare ALA dehydratase deficiency or in patients with symptoms due to [[lead poisoning]] or [[tyrosinemia|hereditary tyrosinemia type I]].
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| Repeat testing during an attack and subsequent attacks may be necessary in order to detect a porphyria, as levels may be normal or near-normal between attacks. The urine screening test has been known to fail in the initial stages of a severe life threatening attack of acute intermittent porphyria.
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| The bulk (up to 90%) of the genetic carriers of the more common, dominantly inherited acute hepatic porphyrias (acute intermittent porphyria, hereditary coproporphyria, variegate porphyria) have been noted in DNA tests to be latent for classic symptoms and may require DNA or enzyme testing. The exception to this may be latent postpuberty genetic carriers of hereditary coproporphyria.
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| As most porphyrias are [[rare disease|rare conditions]], general hospital labs typically do not have the expertise, technology or staff time to perform porphyria testing. In general, testing involves sending samples of blood, stool and urine to a reference laboratory.<ref name=Thadani/> All samples to detect porphyrins must be handled properly. Samples should be taken during an acute attack, otherwise a [[false negative]] result may occur. Samples must be protected from light and either refrigerated or preserved.<ref name=Thadani/>
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| ====Additional tests====
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| Further diagnostic tests of affected organs may be required, such as [[nerve conduction studies]] for neuropathy or an [[medical ultrasonography|ultrasound]] of the liver. Basic biochemical tests may assist in identifying liver disease, [[hepatocellular carcinoma]], and other organ problems.
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| ==Treatment== | | ==Treatment== |
| ===Acute porphyria===
| | [[Porphyria medical therapy|Medical Therapy]] | [[Porphyria surgery|Surgery]] | [[Porphyria primary prevention|Primary Prevention]] | [[Porphyria secondary prevention|Secondary Prevention]] | [[Porphyria cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Porphyria future or investigational therapies|Future or Investigational Therapies]] |
| ;Carbohydrates and heme
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| Often, empirical treatment is required if the diagnostic suspicion of a porphyria is high since acute attacks can be fatal. A high-carbohydrate diet is typically recommended; in severe attacks, a [[glucose]] 10% infusion is commenced, which may aid in recovery.
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| [[Hematin]] and [[heme arginate]] are the drugs of choice in acute porphyria, in the United States and the United Kingdom, respectively. These drugs need to be given ''very early'' in an attack to be effective; effectiveness varies amongst individuals. They are not curative drugs but can shorten attacks and reduce the intensity of an attack. Side effects are rare but can be serious. These heme-like substances theoretically inhibit ALA synthase and hence the accumulation of toxic precursors. In the United Kingdom, supplies of this drug are maintained at two national centers. In the United States, one company manufactures Panhematin for infusion. The American Porphyria Foundation has information regarding the quick procurement of the drug.
| | ==Acknowledgements== |
| | | Source of Initial Content: Resident report notes prepared by Duane S. Pinto, M.D. and {{CMG}} |
| Any sign of low blood sodium (hyponatremia) or weakness should be treated with the addition of hematin or heme arginate as these are signs of impending syndrome of inappropriate antidiuretic hormone (SIADH) or peripheral nervous system involvement that may be localized or severe progressing to bulbar paresis and respiratory paralysis.
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| ;Precipitating factors
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| If drugs or hormones have caused the attack, discontinuing the offending substances is essential. [[Infection]] is one of the top causes of attacks and requires vigorous treatment.
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| ;Symptom control
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| Pain is ''extremely severe'', frequently out of proportion to physical signs and almost always requires the use of opiates to reduce it to tolerable levels. Pain should be treated early as medically possible due to its severity. [[Nausea]] can be severe; it may respond to phenothiazine drugs but is sometimes intractable. Hot water baths/showers may lessen nausea temporarily, though caution should be used to avoid burns or falls.
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| ;Early identification
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| Patients with a history of acute porphyria and even genetic carriers are recommended to wear an alert bracelet or other identification at all times in case they develop severe symptoms or in case of accidents where there is a potential for drug exposure: a result of which may be they cannot explain to healthcare professionals about their condition and the fact that some drugs are absolutely [[Contraindication|contraindicated]].
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| ;Neurologic and psychiatric issues
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| Patients who experience frequent attacks can develop chronic [[neuropathic]] pain in extremities as well as chronic pain in the gut. Gut dysmotility, ileus, [[Intussusception (medical disorder)|intussusception]], hypoganglionosis, [[encopresis]] in children and intestinal pseudo-obstruction have been associated with porphyrias. This is thought to be due to axonal nerve deterioration in affected areas of the nervous system and vagal nerve dysfunction.
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| In these cases treatment with long-acting [[opioids]] may be indicated. Some cases of chronic pain can be difficult to manage and may require treatment using multiple modalities. Opioid dependence may develop.
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| [[Clinical depression|Depression]] often accompanies the disease and is best dealt with by treating the offending symptoms and if needed the judicious use of [[anti-depressant]]s. Some psychotropic drugs are porphyrinogenic, limiting the pharmacotherapeutic scope.
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| ;Seizures
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| [[Seizure]] often accompany this disease. Most seizure medications exacerbate this condition. Treatment can be problematic: [[barbiturate]]s especially must be avoided. Some [[benzodiazepine]]s are safe, and, when used in conjunction with newer anti-seizure medications such as [[gabapentin]] offer a possible regime for seizure control.
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| Magnesium sulfate and bromides have also been used in porphyria seizures, however, development of status epilepticus in porphyria may not respond to magnesium alone. The addition of hematin or heme arginate has been used during status epilepticus.
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| ;Underlying liver disease
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| Some liver diseases may cause porphyria even in the absence of genetic predisposition. These include [[hemochromatosis]] and [[hepatitis C]]. Treatment of iron overload may be required.
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| ;Hormone treatment
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| Hormonal fluctuations that contribute to cyclical attacks in women have been treated with oral contraceptives and luteinizing hormones to shut down menstrual cycles. However, oral contraceptives have also triggered photosensitivity and withdrawal of oral contraceptives has triggered attacks. Androgens and fertility hormones have also triggered attacks.
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| ===Erythropoietic porphyrias===
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| These are associated with accumulation of porphyrins in erthrocytes and are rare. The rarest is Congenital erythropoetic porphyria (C.E.P) otherwise known as Gunther's disease. Its rarity is partially due to its [[autosomal recessive]] mode of inheritance. The signs may present from birth and include severe photosensitivity, brown teeth that fluoresce in ultraviolet light due to deposition of type one porphyrins and later [[hypertrichosis]]. Haemolytic anaemia usually develops. Pharmaceutical-grade [[beta carotene]] may be used in its treatment.<ref> Martin A Crook.2006. Clinical chemistry and Metabolic Medicine. seventh edition. Hodder Arnold. ISBN 0-340-90616-2</ref>
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| The pain, burning, swelling and itching that occur in erythropoietic porphyrias generally require avoidance of bright sunlight. Most kinds of [[sunscreen]] are not effective, but SPF-rated long-sleeve shirts, hats, bandanas and gloves can help. [[Chloroquine]] may be used to increase porphyrin secretion in some EPs.<ref name=Thadani/> [[Blood transfusion]] is occasionally used to suppress innate heme production.
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| ==Culture and history==
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| Porphyrias have been detected in all races, multiple ethnic groups on every continent including Caucasians, Asians, Africans, Peruvian/Mexican Hispanics, Native Americans, Laplanders and Australian aborigines. There are high incidence reports of AIP in areas of India and Scandinavia and over 200 genetic variants of AIP, some of which are specific to families, although some strains have proven to be repeated mutations.
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| The Scandinavian source of porphyria has been traced to the Sámi ethnic group. Their language, as well as the languages of Finland, Estonia, Hungary, Transylvania, and Bulgaria have ties to languages in small groups of people living in Russia on both sides of the Urals and are branches of Uralic languages and Altaic languages (the Finno-Ugric Languages).
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| The links between porphyrias and mental illness have been noted for decades. In the early 1950s patients with porphyrias (occasionally referred to as "Porphyric Hemophilia"<ref>Denver, Joness. "An Encyclopaedia of Obscure Medicine". Published by University Books, Inc., 1959.</ref>) and severe symptoms of depression or catatonia were uselessly and inappropriately treated with electroshock.
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| ===Vampires and werewolves=== | |
| Porphyria has been suggested as an explanation for the origin of vampire and werewolf legends, based upon a number of similarities between the condition and the folklore that was first speculated upon by biochemist [[David Dolphin]] in 1985. His ruminations gave rise to a popular urban legend which accepts this association as factual, though it is historically and factually baseless. [[Porphyria cutanea tarda]] presents clinically as a pathological sensitivity of skin exposed to light causing scarring, hair growth and disfiguration. Additionally, it was believed that the patients' missing heme could be absorbed through the stomach, correlating with the legends' hematophagy.<ref>Adams C. Did vampires suffer from the disease porphyria--or not? ''The Straight Dope'' 7 May 1999 [http://www.straightdope.com/classics/a990507.html Article].</ref>
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| ===Historical patients===
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| The insanity exhibited by King George III evidenced in the regency crisis of 1788 has inspired several attempts at retrospective diagnosis. The first, written in 1855, thirty-five years after his death, concluded he suffered from acute mania. M. Guttmacher, in 1941, suggested manic-depressive psychosis as a more likely diagnosis, The first suggestion that a physical illness was the cause of King George's mental derangements came in 1966, in a paper "The Insanity of King George III: A Classic Case of Porphyria"<ref>Ida Macalpine & Richard Hunger, "The Insanity of King George III: A Classic Case of Porphyria", ''British Medical Journal'', 1966, pp. 65-71.</ref>, with a follow-up in 1968, "Porphyria in the Royal Houses of Stuart, Hanover and Prussia"<ref>Ida Macalpine, Richard Hunger, & Claude Rimington, "Porphyria in the Royal Houses of Stuart, Hanover and Prussia: A Followup Study of George III's Illness", ''British Medical Journal'', 1968, pp. 7-18.</ref>. The papers, by a mother/son psychiatrist team, were written as though the case for porphyria had been proven, but the response demonstrated that many, including those more intimately familiar with actual manifestations of porphyria, were unconvinced. The theory is treated in ''Purple Secret''<ref>Röhl, John C.G., Warren Martin,& David Hunt, ''Purple Secret'', Bantam Press, London, 1998 ISBN 0-593-04148-8</ref>, which documents the ultimately unsuccessful search for genetic evidence of porphyria in the remains of royals suspected to suffer from it.<ref>The authors demonstrated a single point mutation in the PPOX gene, but not one which has been associated with disease.</ref> In 2005 it was suggested that [[arsenic]] (which is known to be porphyrogenic) given to George III with [[antimony]] may have caused his porphyria.<ref>Cox TM, Jack N, Lofthouse S, Watling J, Haines J, Warren MJ. King George III and porphyria: an elemental hypothesis and investigation. ''Lancet'' 2005;366(9482):332-5. PMID 16039338.</ref> Despite the lack of direct evidence, the notion that George III (and other members of the royal family) suffered from porphyria has achieved such popularity that many forget that it is merely a hypothesis. The insanity of George III is the basis of the plot in ''The Madness of King George'', a 1994 British film based upon the 1991 Alan Bennett play, ''The Madness of George III''. The closing credits include the comment that the illness suffered by King George has been attributed to porphyria.
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| It is suspected that Mary, Queen of Scots--George III's grandmother six times removed--also suffered from acute intermittent porphyria, although this is subject to much debate. It is assumed she inherited the disorder, if she had it, from her father, James V of Scotland; both father and daughter endured well-documented attacks that some believe fall within the constellation of symptoms of porphyria.
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| Other commentators have suggested that Vincent van Gogh may have suffered from acute intermittent porphyria.<ref>Loftus LS, Arnold WN. Vincent van Gogh's illness: acute intermittent porphyria? ''BMJ'' 1991;303:1589-91. PMID 1773180.</ref>
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| It has also been imagined that King Nebuchadnezzar of Babylon suffered from some form of porphyria (cf. Daniel 4).<ref>Beveridge A. The madness of politics. ''J R Soc Med'' 2003;96:602-4. PMID 14645615.</ref> The symptoms of the various porphyrias are so wide-ranging that nearly any constellation of symptoms can be attributed to one or more of them.
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| The poet Robert Browning, also, notoriously wrote a poem called Porphyria's Lover, which aside from a literal interpretation of the word also compares love itself to a form of disorder.
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| Paula Frias Allende, the daughter of the Chilean novelist Isabel Allende, fell into a porphyria-induced coma in 1991 which inspired Isabel Allende to write the autobiographical book ''Paula'', dedicated to her daughter.
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| ==References== | | ==References== |
| <div class="references-small"><references/></div>
| | {{reflist|2}} |
| <div class="references-small">
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| * Kauppinen R. ''Porphyrias''. [[The Lancet|Lancet]] 2005;365:241-52. PMID 15652607.
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| </div>
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| == Acknowledgements ==
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| Source of Initial Content: Resident report notes prepared by Duane S. Pinto, M.D. and {{CMG}}
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| ==External links==
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| * [http://www.porphyriafoundation.com/ American Porphyria Foundation]
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| * [http://www.porphyria-europe.com/ European Porphyria Initiative]
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| * [http://www.porphyrin.net/mediporph/porphyria.html Porphynet - site on porphyrins and the porphyrias]
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| * [http://www.drugs-porphyria.org/ The Drug Database for Acute Porphyria - comprehensive database on drug porphyrinogenicity]
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| {{Endocrine, nutritional and metabolic pathology}} | | {{Endocrine, nutritional and metabolic pathology}} |
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| [[Category:Porphyrias| ]] | | [[Category:Disease]] |
| [[Category:Genetic disorders]] | | [[Category:Endocrinology]] |
| [[Category:Hematology]] | | [[Category:Hematology]] |
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| [[de:Porphyrie]]
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| [[es:Porfiria]]
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| [[io:Porfirio]]
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| [[he:פורפיריה]]
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| [[nl:Porfyrie]]
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| [[ja:ポルフィリン症]]
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| [[pl:Porfiria]]
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| [[pt:Porfiria]]
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| [[ru:Порфирия]]
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| [[simple:Porphyria]]
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| [[sr:Порфирија]]
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| [[fi:Porfyria]]
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