China
Africa
Explore chapters and articles related to this topic
Metabolic disorders and reticulohistiocytic proliferative disorders
Published in Rashmi Sarkar, Anupam Das, Sumit Sethi, Concise Dermatology, 2021
Porphyria cutanea tarda (PCT) is the most common of all porphyrias and results from the deficiency of uroporphyrinogen decarboxylase (UROD) enzyme, the fifth enzyme in the haem biosynthesis pathway. (A schematic diagram representing haemosynthesis and the enzymes involved is given in Figure 16.1.) This results in the accumulation of haem precursors, called uroporphyrins and coproporphyrins, in the blood, stool, and urine. These substances are responsible for photosensitization. This enzyme defect is acquired/sporadic and is seen only in the hepatocytes in the majority of the cases; however, inherited forms where the enzyme defect is present in all tissues also do occur. A wide variety of factors, especially hepatotoxins, are known to trigger the clinical features of PCT, including alcohol, estrogens, iron, polychlorinated hydrocarbons, and viral infections, like hepatitis C and HIV.
Epidermolysis bullosa acquisita
Published in Lionel Fry, Atlas of Bullous Diseases, 2020
Porphyria cutanea tarda produces blisters and scarring on the back of the hands. However, other exposed areas such as the face are not usually involved in EBA. In addition, porphyrin studies and immunofluorescent studies will distinguish between the two conditions. If EBA presents as a widespread bullous eruption it will have to be distinguished from bullous pemphigoid and linear IgA disease (LAD). Immunofluorescent studies using the split-skin technique will distinguish EBA from bullous pemphigoid, as in the latter the deposits are in the roof of the blister. The distinction from LAD is made by the class of immunoglobulin, although IgG as well as IgA may be found in LAD and deposits may also be found in the floor of the blister.
Inborn errors of metabolism
Published in Angus Clarke, Alex Murray, Julian Sampson, Harper's Practical Genetic Counselling, 2019
The acute porphyrias form the most striking exception to the rule of recessive inheritance for most inborn errors due to enzyme defects. Acute intermittent porphyria, porphyria variegata, hereditary coproporphyria and protoporphyria all follow autosomal dominant inheritance. Careful investigation of urine and faecal porphyrins, enzyme studies and, where possible, molecular analysis are needed to exclude subclinical disease. Now that specific enzyme and gene defects are known, prenatal diagnosis may be possible but is rarely requested. The severe congenital erythropoietic porphyria follows autosomal recessive inheritance. Porphyria cutanea tarda, the most common of the group, is usually sporadic, with low recurrence risk for family members. This can be dominant or recessive. Much the commonest type is a ‘dominant’ disorder but of low penetrance and that requires adverse environmental factors such as alcoholic liver damage and/or homozygosity (or compound heterozygosity) for iron overload susceptibility variants in the haemochromatosis gene, HFE. Its common representation in textbooks as being inherited in a typically autosomal recessive fashion is misleading.
Expert consensus statement on acute hepatic porphyria in Belgium
Published in Acta Clinica Belgica, 2022
Axelle Gilles, Sebastian Vermeersch, Pieter Vermeersch, Fleur Wolff, Frederic Cotton, Sebastien Tilleux, David Cassiman
Diagnosis and treatment decisions for all types of porphyria, including AHP, are definitely not routine practice outside the context of expert centers as treatment decisions can be impactful or even harmful (e.g. repetitive ‘prophylaxis’ with IV hemin treatment), or life-saving (e.g. evaluation of the indication for liver transplantation for AHP, liver and bone marrow transplantation for EPP (Erythropoietic protoporphyria)). The Belgian expert centers for porphyria have seen various examples of misdiagnoses and incorrect treatment decisions for porphyria: patients without porphyria receiving costly and venotoxic repetitive hemin infusions, patients with VP receiving chloroquine (the treatment sometimes applied in PCT (Porphyria cutanea tarda)), patients with EPP receiving hemin (not indicated), patients with AIP ‘treated’ with repetitive phlebotomy (contraindicated, phlebotomy is only sometimes indicated for PCT). Especially with the advent of new treatments for porphyria (afamélanotide for EPP [34], givosiran for AHP, several drug development trials in the field ongoing) it is not only crucial from a patient safety perspective, but also from a cost containment perspective, that initiation of these treatments remains restricted to EPNET Porphyria Expert Clinical Centers, with identifiable diagnostic and clinical expertise.
Porphyria: awareness is the key to diagnosis!
Published in Acta Clinica Belgica, 2022
Benjamin Heymans, Wouter Meersseman
Porphyria Cutanea Tarda (PCT) is the most frequent form of porphyria. It is caused by a reduction in the activity of the enzyme uroporphyrinogen decarboxylase (UROD) to less than 20%. In the majority of cases, there is no genetic defect present; only around 20% of patients have a mutation in one of the alleles of the UROD-gene. The latter is however not enough to cause PCT by itself because the UROD-activity is only decreased by 50%. Hence, additional susceptibility factors are required before PCT develops. In the first place, more than half of the patients with PCT are carrier of a mutation in the hemochromatosis gene HFE, whether or not together with the presence of the disease itself [8]: iron, after all, facilitates the conversion of uroporphyrinogen to uroporphomethene, an inhibitor of UROD activity. Other factors associated with PCT are infection with hepatitis C or HIV1, alcohol, tobacco and estrogen. The PCT susceptibility factors cause iron accumulation or they increase the oxidative stress in the hepatocytes. It is important to note that none of these factors alone is sufficient to explain the development of PCT. In general, at least two of them should be present before symptoms of this disease will arise.
System for administering and monitoring hydroxychloroquine prophylaxis for COVID-19 in accordance with a national advisory: preliminary experience of a tertiary care institute in India
Published in Expert Review of Anti-infective Therapy, 2021
Praveen Kumar-M, Ritin Mohindra, Ashish Bhalla, Nusrat Shafiq, Vikas Suri, Deepa Kumari, Avaneesh Kumar Pandey, Ankur Gupta, Parul Chawla Gupta, Amol Patil, Ashish Kumar Kakkar, Samir Malhotra
All asymptomatic HCWs providing a written informed consent for HCQ administration and/or monitoring under the registry and working in areas devoted to suspected or confirmed COVID19 patients were considered eligible. The contraindications to HCQ prophylaxis that led to exclusion of participants were (1) Hypersensitivity to CQ/HCQ, 2) Cardiomyopathy, clinically relevant cardiac rhythm disturbance and, prolonged QTc [Males, >450 ms and Females >460 ms]. For doubtful electrocardiogram, consultation was sought from cardiologist (AG). Electrocardiograms were evaluated for rate, rhythm, or any other abnormality. QTc interval was calculated from the automated 12 lead ECG or using Bazzett’s formula if the ECG conducted did not have this value. (2) History of Porphyria Cutanea Tarda, epilepsy, Myasthenia gravis, psoriasis or myopathy of any cause 3) Serious hepatic or renal disease. (4) History of Glucose-6-Phosphate (G6PD) deficiency. (5) Severe depression/psychosis. (6) On concomitant medication which could possibly lead to clinically significant drug interaction. Potential for drug interaction with an ongoing medication (for any chronic or acute illness) was evaluated with clinical pharmacologists (NS and SM) and Internal Medicine consultant (RM). In case of any queries, Lexicomp database through UpToDate was also queried [23].