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The American Porphyria Foundation will provide updates and information here, as well as on the main site - http://porphyriafoundation.com .
Monday, September 7, 2015
PCT- Facts from NIH
Phlebotomy, known also as bloodletting or venesection, is a major therapeutic procedure that has been performed by physicians in various civilisations since antiquity up to the present1,2. In the past it was practised using cupping, lancets or by the application of leeches2. This procedure often weakened the patient and resulted in his or her death. A famous example is that of President George Washington who died in 1799 following the removal of approximately 1.7 litres of blood during a bloodletting procedure for acute epiglottitis3. Originally, several thousand years ago, phlebotomy was used for the treatment of various disorders, but in addition to its therapeutic benefits, phlebotomy also had a preventive role. In present day medicine, phlebotomy can be performed in physicians’ offices, at a blood bank or in hospital under the supervision of a doctor after obtaining a medical prescription stating the indication and number of phlebotomy sessions required. Currently, therapeutic phlebotomy is approved for three main indications: haemochromatosis, polycythaemia vera and porphyria cutanea tarda. It has also been used as a treatment alternative for many other diseases in various countries, especially in Chinese medicine, although these indications are not approved by western medicine.
Porphyria cutanea tarda
Porphyria cutanea tarda (PCT) is a rare metabolic disorder caused by uroporphyrinogen decarboxylase deficiency that leads to the accumulation of uroporphyrinogen and highly carboxylated porphyrins in the liver, plasma, urine and sometimes faeces. There are three types of PCT: two familial and one sporadic. Most of the cases are sporadic (80% approximately) and have been associated with several risk factors such as alcohol abuse, hepatitis C, oestrogen use, smoking, hepatic siderosis and human immunodeficiency virus infection55. Hepatitis C is one of the most important risk factors; in a recent systematic review and meta-analysis, 50% of PCT patients were found to have hepatitis C infection suggesting an important role in the pathogenesis of PCT although the pathophysiology is still unclear56,57. HFE gene mutations, especially C282Y homozygosis, has also been found in PCT patients, which explains the iron excess in this disorder, although true haemochromatosis is rare57.
Clinically, PCT is characterised by chronic blistering skin manifestations that include photosensitivity, increased skin fragility with bullae, erosions, and hyper- or hypo-pigmentation that affects sun-exposed areas of the body; however, these skin manifestations are not specific and they do not confirm the diagnosis. Liver involvement is also common especially in the sporadic form with cirrhosis, fibrosis and increased risk of hepatocellular carcinoma54. The diagnosis of PCT requires both clinical and biochemical features. Laboratory investigations include porphyrin chromatographic separation that shows markedly increased uroporphyrins and heptacarboxyl porphyrins in plasma and/or urine, with lesser amounts of penta- and hexa-carboxyl porphyrins. Faecal porphyrins, consisting mainly of isocoproporphyrins, are also increased while the erythrocyte porphyrins are normal57. UROD activity analysis with gene sequencing is essential in familial PCT58.
Liver biopsy is indicated in the event of liver damage demonstrated by markedly increased serum transaminase levels, while skin biopsy is of little benefit because it often only shows sub-epidermal bullae with minimal inflammation54. An important aspect of treatment is the avoidance of any risk factors such as alcohol, excessive iron or oestrogen and hepatitis C that can potentially exacerbate the disorder. Therapeutic phlebotomy has long been considered the treatment of choice in most patients with PCT; hydroxychloroquine is the alternative treatment if phlebotomies cannot be tolerated59. According to Rocchiet al., 450 mL of whole blood should be removed during each phlebotomy session, with sessions repeated every 2 weeks until the haemoglobin level is below 11 g/ dL or until the serum ferritin level is below 20 ng/ mL, which is close to the lower limit of normal. Most patients require 6 months to achieve remission but clinical improvement may be noted during the third month after starting phlebotomy60. Hydroxychloroquine was found to be superior to phlebotomy in decreasing porphyrin production; however, liver disease was more severe in the hydroxychloroquine group61. No difference was seen between therapeutic phlebotomy and desferrioxamine injection62.
Skin blistering was the first sign to disappear in patients, at an average of 2 to 3 months and a maximum of 9 months; this was followed by improvement of skin fragility, hypertrichosis and hyper- or hypo-pigmentation while pseudoscleroderma may improve in some patients59. Urinary porphyrin levels return to normal but although liver function tests may improve following phlebotomy, the extent of liver damage does not improve63,64. Phlebotomy must be stopped after achieving remission or when iron deficiency anaemia occurs; however, relapse may occur during the first 5 years of treatment especially when risk factors are still present, such as excessive alcohol consumption65.
For the full article please use this link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3934278/