Individuals: Part 19

not that I want to beat a dead horse, but while I am on the subject...your loving and disdainful mobe has found more information for the data-philes out there who like to crunch terms and numbers. I have been looking online for over a year and everyday come up with new information regarding the genetics and such as well as some interesting stories of how my and mini mobe's, Laurel's, disease progresses. The differences between the two are a unique case study because she is a child receiving treatment whereas her mother, yours truly, did not for nearly four decades. EPP hurts. EPP can kill, though rarely and in extreme circumstances (gee, I wonder if I would be considered one of those circumstances-you think?) EPP is genetic and you can have the gene allele without having EPP and not know your family line carries it forward some hundred years before someone shouts out! Here is some more information so please read what you want and save some for later and click open any links that work. As you know my strengths are the arts and writing and not in technology but I will do my best to get you websites at least. People need to have access to this and should have a one-place pit-stop for their basic "shopping for information" needs...

found on the site:http://emedicine.medscape.com/article/1104061-overview credits for authors will be found from clicking this link and there is a list of resources to be had underneath the disease name starting with a small but incomplete list of doctors. It is too long to place here as this is all too much to begin with.

Erythropoietic protoporphyria is a genetic disorder most often arising from impaired activity of ferrochelatase, the ultimate enzyme of heme biosynthesis.^{[1, 2]} The resultant accumulated excess of its substrate, protoporphyrin, causes 2 principal manifestations: (1) a distinctive acute cutaneous photosensitivity typically appearing in childhood and (2) hepatobiliary disease.^{[1, 3, 4, 5]}

The predominant genotype associated with phenotypic expression is one mutant ferrochelatase allele encoding a defective enzyme protein with little or no function, coupled with a normal variant allele with low gene expression.^{[6, 7]} Infrequently, 2 deleterious mutations are found in symptomatic individuals; this recessively inherited form of protoporphyria appears to impart a higher risk for hepatic dysfunction.^{[8, 9]}

A recently described X-linked dominant form of protoporphyria arises from C-terminal deletions in the gene encoding the erythroid-specific enzyme 5-aminolevulinic acid synthase-2; increased function of this enzyme leads to overproduction of protoporphyrin with associated acute photosensitivity and increased risk for liver disease.^[10]

Rarely, acquired somatic mutation or deletion of a ferrochelatase gene secondary to myelodysplastic or myeloproliferative disorders leads to an adult-onset protoporphyric disorder.^{[11, 12, 13]}

Pathophysiology

Protoporphyrin is a lipophilic molecule capable of transformation to excited states by absorption of light energy. Excited-state protoporphyrin mediates photoxidative damage to biomolecular targets in the skin,^[14] resulting in immediate phototoxic symptoms variously described as tingling, stinging, or burning that may be followed by the appearance of erythema, edema, and purpura.^{[3, 14]} Excess protoporphyrin is formed during maturation of erythroid cells in the bone marrow and is present at the highest levels in reticulocytes and young erythrocytes.^[15] Protoporphyrin escapes from red blood cells into the plasma, from which it is cleared by the liver and secreted into bile. Protoporphyrin-rich bile facilitates gallstone formation.^[16] Toxic effects of protoporphyrin deposition in the liver may lead to life-threatening hepatic dysfunction.^{[16, 17, 18]}

Epidemiology

Frequency

United States

Until a recently established registry for erythropoietic protoporphyria sponsored by the American Porphyria Foundation collects sufficient data, accurate enumeration in the United States cannot be provided, but is probably similar to data from European countries.

International

Estimates of 1 case in 75,000-200,000 population have been reported for some western European populations and in the South African population of European ancestry.^{[2, 5, 19]}

***mobe's note: There are even fewer in the United States as this is and English/Aussie/NZ study and data collective***

Mortality/Morbidity

Painful cutaneous photosensitivity reduces the sunlight tolerance of individuals with erythropoietic protoporphyria and may influence their lifestyles over entire lifetimes.^[3]

An increased prevalence of cholelithiasis in both men and women can result in signs and symptoms of gallstone disease at relatively early ages.^[3]

Hepatotoxic effects of excess protoporphyrin deposition have led to liver dysfunction that progressed to life-threatening severity in approximately 2-5% of known cases.^[5]

Race

Erythropoietic protoporphyria has been reported most often in people with European heritage, but it has also been reported in people with Japanese, Chinese, East Indian, or north or central African ancestry.

Sex

Protoporphyria occurs equally in males and females.

Age

Photocutaneous symptoms usually appear during childhood,^[3] but they also may be noted for the first time in adult life.^{[11, 12, 13]} Gallstones may become symptomatic in young adulthood or in middle age.^[3] Liver failure and its complications, sufficiently severe to result in liver transplantation and/or death, may develop in children and adolescents as well as adults.^{[16, 18, 20, 21, 22]}

History

Uncomfortable sensations in skin exposed to sunlight typically begin during infancy or childhood, most often involving dorsal hands, the face and ears, and, occasionally, legs and dorsal feet, after short periods of exposure. If exposure is promptly discontinued, visible skin lesions may not ensue. Longer exposure, or multiple exposures on sequential days, can elicit swelling with or without redness in the exposed skin that evolves into sheets of petechiae. This exquisitely painful reaction resolves over several days to leave skin that may appear normal. Eventually, chronic changes may develop that are highly suggestive, but, when subtle, can be overlooked.

Individuals with protoporphyria who report skin pain but have minimal objective findings may be considered malingerers until an acute reaction is observed. Gallstones may remain silent or evoke reports of indigestion and/or right upper quadrant abdominal pain consistent with symptomatic cholelithiasis. Individuals with protoporphyria associated with hepatotoxicity may report loss of appetite, nausea, vomiting, weakness and fatigue, anorexia, malaise, weight changes, increasing abdominal girth, pain in the epigastrium or right upper quadrant and back, jaundice, and increasing photosensitivity.

Physical

The acute phototoxic reaction typically includes edema, erythema, and petechiae. Blisters, crusted erosions, and scarring may occur but are less florid and less frequent than in other porphyrias. Chronic changes include shallow, elongated depressions in facial skin, especially over the nose; perioral furrowing; and prematurely aged, thickened, or coarsely textured skin of the dorsal hands, often most prominent over the knuckles. In more severe cases, sclerodermalike waxy induration or a cobblestone texture of the face and hands develops. Mechanical fragility, when present, is less severe than in other porphyrias; hypertrichosis is infrequent.

With progressive liver dysfunction, hepatosplenomegaly and jaundice may develop, as may signs of increasing cutaneous photosensitivity. End-stage liver disease is signaled by intense jaundice, ascites, vomiting, fever, encephalopathy, axonal polyneuropathy that may progress to paresis and respiratory failure, hemorrhage from esophageal varices, and extreme photosensitivity.

Causes

The ferrochelatase gene is located on band 18q21.3.^[23] Ferrochelatase mutations listed at the Human Gene Mutation Database numbered 124 as of May 2010.

Loss of ferrochelatase activity by as much as 50% as the result of 1 mutant gene is generally insufficient to cause overt disease when its complementary allele has normal function.^[6] Ferrochelatase genotypes composed of either 2 mutant alleles (approximately 4% of cases) or 1 mutation and a nonmutant allele with a specific intronic single nucleotide polymorphism (IVS3-48C) (approximately 94% of cases) have been found in most symptomatic individuals.^{[8, 9, 24]} This polymorphism enhances aberrant splicing and rapid degradation of ferrochelatase mRNA, with resultant low expression.^[7] The allele frequency of this polymorphism varies widely in diverse populations studied, as follows:

• Japanese - 43.3%^[9]
• Southeast Asian - 31%^[9]
• White French - 11.3%^[9]
• North African - 2.7%^[9]
• Black West African - < 1%^[9]
• United States - 3.5%^[25]
• South Africans of European descent - 8.6%^[2]
• United Kingdom - 6.5%^[8]
• Chinese (3 different regions) - 28-41.4%^[26]
• Swedish - 8%^[27]

The pairing of a mutated allele encoding a severely impaired enzyme protein with this low-expressing polymorphic allele typically yields enzyme activity diminished to less than 30% of normal, low enough to cause protoporphyrin accumulation. Individuals heteroallelic or homoallelic for this polymorphism do not have sufficiently diminished ferrochelatase activity to cause clinical abnormalities, although their erythrocyte protoporphyrin levels may be mildly abnormal.^[2]

Adult-onset protoporphyric photosensitivity and increased protoporphyrin levels have been associated with an acquired somatic mutation or deletion of a ferrochelatase gene due to myelodysplastic or myeloproliferative disorders.^{[11, 12, 13]}

Eight families have been described recently with a protoporphyric disorder indistinguishable clinically from the predominant form of the disease, but without ferrochelatase mutations.^[10] Two different C-terminal deletions in the gene encoding the erythroid-specific isoform of aminolevulinic acid synthase were identified among these families. The locus for this gene is on the X chromosome, and the inheritance pattern in the families was consistent with X-linked dominant transmission. Both mutations caused a marked increase in activity of aminolevulinic acid synthase 2 that eventuated in large accumulations of erythrocyte-free protoporphyrin and zinc-protoporphyrin. Seventeen percent of affected individuals in that study exhibited overt liver disease, a significantly greater number than the 2-5% of individuals with ferrochelatase-deficient protoporphyria who develop this complication.

***mobe's note: By refusal of family members to participate in a case study it is difficult to assess as to what genome-type I am by mere assumption. They know it is genetic and that all relations from here on need to know about it and their likely-hood to inherit it but all have refused and/or lied regarding getting tested. It's a shame really because the more support and research done the better the lives of these people, yes me too, to have then on***

Laboratory Studies

Protoporphyrin concentration is elevated in red blood cells, plasma, bile, and feces. The diagnosis is usually made by finding the abnormal levels in erythrocytes and plasma. Urinary porphyrin levels are normal in patients without liver dysfunction. Abnormal coproporphyrinuria develops when liver function is deteriorating.^{[28, 29]}

Erythrocyte and plasma protoporphyrin levels are increased several-fold over the reference range. Fecal protoporphyrin excretion may be increased, but, in many patients, it remains within the reference range. In impending liver failure, the dynamic equilibrium between rates of protoporphyrin production and excretion is altered, producing progressively rising erythrocyte and plasma porphyrin levels and progressively diminishing fecal porphyrin excretion.^{[28, 30]}

Obtain a complete blood cell count and serum liver function panel at diagnosis. Monitor serum indices of liver function at 6- to 12-month intervals if baseline values are normal. If liver function is abnormal, complicating factors (eg, gallstones, viral hepatitis, alcohol or drug abuse, other toxic, infectious, immunologic, or metabolic storage disorders) should be excluded by appropriate testing.

Perform a hematological assessment of anemia. Individuals with protoporphyria often have mildly lowered hemoglobin and hematocrit levels, which do not cause symptoms and do not require treatment.^{[3, 31]} The mean corpuscular volume may be below the normal limit.

***mobe's note: The levels of my diseases toxins were high enough to have accumulated and shown present in a urinary 24hr collection used for diagnosing generic porphyrias. EPP does not ordinarily show up on these tests excepting in extremely rare situations and the elevation of erythrocyte/protoporphyrins is astronomical***

Imaging Studies

If cholelithiasis is suspected, abdominal ultrasonography or other imaging procedures are indicated.

Other Tests

Impending liver failure may be signaled by progressively rising levels of urinary coproporphyrin.^[29] Urinary porphyrin levels are within normal limits in persons with uncomplicated erythropoietic protoporphyria. Protoporphyrin, being lipophilic, is not excreted by renal mechanisms and does not normally appear in urine. Coproporphyrin, which accumulates as a result of liver disease, has intermediate water solubility, and levels become abnormally elevated in the urine of patients developing protoporphyrin-induced hepatotoxicity.^[28]

Measurement of ferrochelatase enzyme activity remains a research procedure. Mutation analysis of the ferrochelatase gene (ie, DNA testing) is performed at several porphyria research units in various countries and is now commercially available in the United States. See the American Porphyria Foundation for further information.

Procedures

In the event of overt liver dysfunction, liver biopsy is indicated. Some experts suggest that individuals with genotypes associated with higher risk of liver disease, such as a "null-allele" ferrochelatase mutation that encodes an enzyme with essentially no residual activity, mutations of both ferrochelatase alleles, one of the aminolevulinic acid 2 increased-function mutations, or with a family history of protoporphyric liver disease, may warrant liver biopsy even before liver function tests become abnormal.^{[18, 19]} The presence of other risk factors for liver disease, such as viral hepatitis, hemochromatosis, or alcoholic or nonalcoholic fatty liver, increases the weight of argument for earlier liver biopsy.

Liver transplantation may be life saving, but it does not cure protoporphyria because the source of most of the excess protoporphyrin is the bone marrow. Continued overproduction of protoporphyrin eventually leads to protoporphyrin deposition in the engrafted liver, which may again become dysfunctional.^[22]While bone marrow transplantation is potentially curative, its risks have warranted its application in only a few cases to date.^{[12, 21, 32]} Research in animal models has shown promising developments in gene therapy strategies that may eventually be transferrable to humans.

Histologic Findings

Light microscopy examination of the acute skin reaction shows perivascular and interstitial neutrophilic dermal infiltrates. Ultrastructural findings in the acute reaction include damage of endothelial cells with extravasation of intravascular contents and degranulated mast cells.^[33]

Biopsy specimens of chronically damaged skin show deposition of hyaline masses in the upper dermis and markedly thickened walls of upper dermal capillaries.^[34] Ultrastructural findings in chronically damaged skin include replicated basal laminae around dermal vessels, degranulated mast cells, and amorphous dermal deposits.^[34] Direct immunofluorescence studies show deposition of immunoglobulins and complement in and around upper dermal vessel walls and, to a lesser extent, at the dermoepidermal junction.^[34]

Liver biopsy typically reveals brown pigment in hepatocytes, Kupffer cells, portal macrophages, and small biliary structures.^{[16, 22]} Many of these protoporphyrin deposits are crystalline when examined under electron microscopy and birefringent when examined under polarization microscopy.^{[16, 22]} Cirrhotic changes are seen in advanced disease, including fibrous expansion of portal areas and regenerative nodules.^{[16, 22]}

Medical Care

For protoporphyria uncomplicated by hepatobiliary disease, the major problem is lifelong cutaneous photosensitivity. Anemia, if present, typically is mild and rarely requires specific therapy. Cholelithiasis is managed surgically. Liver dysfunction is an ominous development for which medical remedies are not consistently effective. Progressive intractable liver insufficiency is an indication for liver transplantation.^{[16, 18, 35]}

Note the following treatment measures for photosensitivity:

• Shield skin from sunlight by using protective clothing and lifestyle adjustments.
• Because the wavelengths of light causing porphyrin-sensitized phototoxicity are chiefly in the visible spectrum, window glass is not an effective barrier. Plastic films that attenuate transmission of portions of the visible light and long UV spectra are available and can be applied to window or windshield glass.^[36]
• Topical sunscreens are not effective unless transmission of long UV and visible light rays is reduced by their use. Sun-blocking formulations containing zinc oxide or titanium dioxide reflect visible light and may be helpful.^[36]
• Topical sunless tanning gels or creams containing dihydroxyacetone produce superficial pigmentation that blocks some of the offending wavelengths.^[36]
• Induction of endogenous melanin by exposure of skin to broad- or narrow-band UV-B lamps or to UV-A in conjunction with a psoralen UV-A photosensitizer also may increase tolerance to natural sunlight.^[37]
• Afamelanotide, an alpha-melanocyte–stimulating hormone analogue that increases melanin production in the skin, is a novel injectable photoprotective agent currently in clinical trials in Australia and several European countries. It has recently become available by prescription in Italy.
• Oral beta-carotene reduces photosensitivity in some, but not all, patients.^{[3, 38, 39]}
• Attenuation of photosensitivity using oral cysteine^[40] or pyridoxine^[41]has been reported but not widely confirmed.
• H1-receptor antagonists can mitigate histamine-mediated components of the acute reaction, but they rarely suppress all signs and symptoms.^[42] Suppression of heme synthesis by inhibition of cytochrome P-450 formation and of heme oxygenase activity is a mechanism proposed for transient improvement of isolated cases of various porphyrias after H2-receptor antagonist use that remains unproven.^[43]

Although adverse reactions to porphyrinogenic drugs known to exacerbate acute hepatic porphyrias are not characteristic of protoporphyria, avoid or administer with caution drugs with cholestatic properties, such as estrogenic hormones. Assess the risk-to-benefit ratio for each individual with protoporphyria when considering use of cholestatic therapies.

Immunization against viral hepatitis agents should be offered.

Medical approaches to reversing protoporphyric liver dysfunction are not well established, owing to inconsistent or uncertain efficacy and experience in relatively few cases. Note the following:

• Orally administered cationic exchange resins or activated charcoal aimed at reducing enterohepatic recirculation of porphyrin and/or bile acids to enhance hepatic porphyrin excretion may have some level of efficacy in selected patients.^{[28, 44, 45]}
• Hypertransfusion to slow erythropoiesis^[46] and intravenous infusion of heme analogues to repress endogenous porphyrin production^{[47, 48]}have been beneficial in some cases.
• Administration of iron with the rationale of enhancing protoporphyrin conversion to heme appeared beneficial in one case,^[49] but aggravated the disease in others.^[50]
• Reduction in erythrocyte protoporphyrin levels and improved liver function followed administration of vitamin E to a protoporphyric patient with cirrhosis.^[51]
• Plasmapheresis^[48] or exchange transfusion^[52] to reduce the circulating protoporphyrin burden appeared helpful in a small number of advanced cases.
• Medical regimens are often used in combination or rapid sequence in progressively deteriorating patients and are best instituted by experts in a referral center for advanced liver disease.
  
  

  Surgical Care

  Surgical removal of gallstones usually poses no more risk for individuals with protoporphyria than for the general population, although phototoxic sequelae from high-intensity operating room lighting is a theoretical possibility. Adverse reactions to anesthetic agents problematic in acute hepatic porphyrias are not characteristic of protoporphyria. Failure of medical reversal of protoporphyrin-induced hepatic decompensation warrants liver transplantation. Operating room lamps have caused acute phototoxic damage to skin and internal organs during transplantation.^{[53, 54]} Preoperative exchange transfusions, plasmapheresis, and/or infusion of a heme analogue may lower the circulating burden of protoporphyrin in the blood, reducing intraoperative phototoxic potential.^[55] These treatments may also aid postoperatively in retarding the development of protoporphyrin hepatotoxicity in the engrafted liver.^{[47, 48]}

  Consultations

  Consultation with a hematologist should be sought for management of anemia or if hypertransfusion, exchange transfusion, or plasmapheresis is considered. Rarely, bone marrow transplantation may have a role in the management of selected patients with severe manifestations.^{[21, 32]}

  Referral to specialists at a comprehensive liver center should be arranged at the earliest signs of liver decompensation for assistance in evaluation and management of progressive liver dysfunction. If liver transplantation becomes necessary, a successful outcome is more likely if the procedure is performed before the patient is gravely debilitated.

  Referral to a medical geneticist can aid in counseling patients and families about risks of inheriting or transmitting the mutations and polymorphisms associated with the disease.^{[56, 57]}

  Preoperative consultation with anesthesiologists and biomedical engineers concerning operating room lighting is essential. The intense visible light emitted by surgical lamps can cause intraoperative burns of the skin and internal organs due to the massive protoporphyrin tissue accumulations that result from failure of hepatic excretory mechanisms.^{[53, 54]} Filtering operating room lamps appropriately can block the most harmful portions of the visible light spectrum.^[55]

  Diet

  Do not severely curtail carbohydrate intake; a beneficial glucose effect may be modulating abnormal heme synthesis.^[58] Limit use of ethanol; alcohol excess has been implicated in fatal protoporphyria associated with liver failure..^[59] 

  ^{***mobe's note:} I like this section as it points out that a decent carbohydrate rich diet can aide in benefit. My own mother denied me sugar and such under Münchhausen's Syndrome trying to get attention with claims that I was diabetic. I am NOT diabetic but do take Metformin for a hormonal compound it holds and has been proven to help with fertility issues and amenorrhea which I also suffer from. She very well may have contributed to her own insecurities as a mother when doing this as it made me more unmanageable which is her sole claim for the abuse and neglect I suffered as she could not "soothe" me because "I cried from the moment the sun came up until it fell" long into toddler-hood. I soon learned by four years of age that crying got me nowhere and haven't "cried" for my disease since...until the day I diagnosed myself and found it MYSELF and knew I was "home" and that I have spared my own child the torment I have had.***

  Activity

  ***mobe's note: Another good article as it shows to doctors that it is imperative that I refrain from all sun exposure. Other articles to come reflect that indoor lighting as well can cause problems for the more severe cases such as mine to which my recent stay in a medical center would not make conditions for my disability. My own family has a hard time with this one as they see I have to go to the doctors and such during day, when the world was not created for my kind and feel I can subsequently go outdoors to the benefit and betterment of their needs and wants.I will admit to "enjoying" sunshine for a rare occasion if only to make my kid feel normal but I, and I ALONE, reserve the right to decide what sun exposure I will have and for what benefit-no one else!***

  Sunlight avoidance is mandatory. Recommend adjustment of outdoor activities to avoid midday sunlight. Stylish and comfortable sun-protective clothing is commercially available that can reduce time constraints on many outdoor sports or activities. Specialized programs for photosensitive children can be found that offer safe and healthy recreational experiences, even a summer camp organized by the Xeroderma Pigmentosum Society. SeeCamp Sundown.

  Medication Summary

  The only oral photoprotective agent approved by the US Food and Drug Administration and widely used for the treatment of protoporphyria is a synthetic beta-carotene formulation now available over the counter as Lumitene. Cysteine has shown benefit in clinical trials. Pyridoxine was reported effective in 2 cases. H1-receptor blockade may reduce symptoms due to mast cell histamine release during acute phototoxic reactions if established prior to exposure. Whether H2-receptor antagonists reproducibly slow porphyrin production in various porphyrias remains unproven.

  Liver dysfunction warrants individualized design of therapeutic regimens that may include the administration of enteric sorbents to promote protoporphyrin excretion, bile acids to enhance porphyrin clearance from the liver, and hematin to repress porphyrin production. Combinations of these and other adjunctive agents and modalities may moderate the urgency presented by a failing organ, allowing orderly preparation for an optimal transplantation.

  ***mobe's note: Lumitene is not available except at a high price to which our insurance companies in this country do not recognize, just as they do not recognize the disease. I also take the metabolic order of medications to aide in digestion and set up protocol for evacuation of the protoporphyrins I am CURRENTLY producing. It CANNOT remove the build-up/edematous effect of long term accumulation leading to hepatic failure, bone marrow loss and other organic failure as a result of hepatic function working overtime and the body's propensity for rerouting necessary work for it by shutting down what IT considers secondary function ie: digestion in the stoma, hormone production, renal function, etc. I was "found" at this severe state and have been on Reglan to make my stomach "rumen" my own food(which used to sit and rot, because the stomach refused to do its job, for days. I literally ate 2-3 times a week but was big as a house from my own natural curvaceous figure and edematous propensity as a direct result from organ failure causing chronic inflammatory disease as a secondary and lesser known effect of this disorder in most severe cases. I have been attacked openly for my size for 40years and suffered immensely the shame associated with obesity and come out to you today telling you I weigh 420lbs and look like I weigh slightly over half that. Yes I am fat, but much of what is carried through the legs and hip/gluteus areas are lymphatic pooling(aka-edema)that gravity took great hold of.) and I take Cholestyramine to absorb protoporphyrins in my bile, stomach and digestive tract that are newly produced. Without the Reglan and Cholestyramine I am unable to eat beyond one decent meal every 2-3days and sugary fluids in between for energy as needed as well as a caffeine uptake for alertness. I took good care of myself without medicine for a long time past what others have expired under by listening to my body. Which to this day baffles the doctors as to how long I went "unchecked" and without treatment.***

  Photoprotectants

  Class Summary

  Beta-carotene is a scavenger of singlet-exited oxygen and is believed to interfere with the efficiency of porphyrin-sensitized photoxidative damage in the skin. Ingestion of beta-carotene at recommended doses produces carotenodermia after several weeks. Increasing tolerance of sunlight develops during this loading period. Tolerance diminishes over several weeks when treatment is stopped.

  View full drug information

  Vitamin A (Lumitene)

   

  Exact mechanism of action not completely elucidated. Patient must become carotenemic before effects are observed. More than one internal light screen may be responsible for effects. May provide a limited level of photoprotection. Causes yellowing of skin (carotenoderma). Any photoprotection afforded increases slowly over 4- to 6-wk period after drug is commenced. When discontinued, skin color and benefit fade over several weeks.

  ***mobe's notes: So who wants to look like an OOMPA LOOMPA? Carotenodermia is just that as you WILL turn orange but does NOT guarantee 100% of users as to its usefulness as an agent to protect against the light exposure.***

  Antihistamines

  Class Summary

  H1-receptor antagonists modulate effects of histamine in skin. If taken prior to anticipated strong sunlight exposure that cannot be avoided, acute reactions may be attenuated to some extent; minimal benefit is expected if taken afterward.

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  Fexofenadine (Allegra)

   

  Nonsedating second-generation medication with fewer adverse effects than first-generation medications. Competes with histamine for H1 receptors on GI tract, blood vessels, and respiratory tract, reducing hypersensitivity reactions. Does not sedate. Available in qd and bid preparations.

  Enteric adsorbents

  Class Summary

  Agents that bind protoporphyrin in the intestinal lumen promote its excretion by interrupting enterohepatic recirculation, thereby reducing the porphyrin load presented to the liver for clearance.

  View full drug information

  Cholestyramine (Questran)

   

  Polymeric resin that binds bile acids, porphyrins, and other molecules to form nonabsorbable complexes that are excreted unchanged in feces. Adsorbs many drugs and nutrients; long-term use requires proper timing of oral drugs and may warrant supplementation of vitamins D, E, A, and K.

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  Activated charcoal (Actidose)

   

  Prevents absorption by adsorbing porphyrin in intestine. Multidose charcoal may interrupt enterohepatic recirculation and enhance elimination by enterocapillary exsorption. Does not dissolve in water. Adsorbs many medications and nutrients; long-term use requires proper timing of oral drugs and may warrant supplementation of vitamins D, E, A, and K.

  Antihistamines, H2 blocker

  Class Summary

  Produce blockade of H2 receptors.

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  Cimetidine (Tagamet)

   

  H2 antagonist, which, when combined with an H1-type, may be useful in treating itching and flushing in urticaria. Porphyria-specific usage for inhibiting overproduction of porphyrins is experimental.

  Gallstone dissolution agents

  Class Summary

  Increasing bile flow enhances secretion of protoporphyrin by the liver into the enteric tract and clearance from the body.

  View full drug information

  Ursodiol (Actigall)

   

  Shown to promote bile flow in cholestatic conditions associated with a patent extrahepatic biliary system. Decreases cholesterol content of bile, therefore reduces bile stone and sludge formation.

  Heme analogues

  Class Summary

  Intravenous infusion of a heme analogue may repress heme synthesis in liver and bone marrow cells, thereby reducing rate of protoporphyrin overproduction.

  Hemin (Panhematin)

   

  Enzyme inhibitor derived from processed red blood cells and is an iron-containing metalloporphyrin. Previously known as hematin, a term used to describe the chemical reaction product of hemin and sodium carbonate solution.

  Has anticoagulant effect and may cause thrombophlebitis at infusion site. Must be reconstituted from lyophilized powder. Reconstitute with human serum albumin 25% (132 mL of 25% human serum albumin to 1 vial of hemin [301 mg heme]).

  Heme arginate

   

  A heme analogue not available in the United States that would have similar uses to hemin as described above.

  ***mobe's note: The best medicine money can buy but not covered by insurance in the United States. I have some of these available to me as they are not for the sole treatment of my disorder(lucky that huh?)and the rest are too expensive, like the clothing and other lifestyle necessities that most patients of meager to poverty levels cannot afford. (I'm just saying)***

  
  
  
  
  ...THIS DOES NOT REPRESENT A TOTAL DIALOGUE OF INFORMATION AND DATA REGARDING ERYTHROPOIETIC PROTOPORPHYRIA AND IS MERELY ONE OBJECTIVE STUDY PRESENTED AT THIS TIME, MORE TO FOLLOW ON LATER DATES...This is too much to absorb at once so feel free to chew on it. I am going to spend the weekend bringing you this information because you are not my only readers out there. I know full well what kind of "candy" and dirty little secret my blog has become and I have no "ill" feelings on the matter, as I am rather flattered by just one reader at all. I do have my medical staff who do look at this site form time to time and I will make note to them to look for this end of the month for the information they seem to have a hard time finding and searching online and in textbooks. I don't even have their clout as far as obtaining this information, but looks like I didn't do too bad. For now I will leave you with my regular cup of love...~mobe's love to her all and her all to her loves! 
  
  
  ps. Any questions about the material you can email me at mobiuschic@gmail.com as I do expect some of this is overwhelming and hard to understand unless you have read it as often as I have or a medical professional. I will be happy to explain in laymen's terms on an "as per" basis.-most of you know most of this already from my wonderful disdain filled entries here.