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Clin Rev Allergy Immunol 2018 Jun 27. Epub 2018 Jun 27.

Department of Dermatology, The University of Texas Southwestern, 5323 Harry Hines Blvd, Dallas, TX, 75390-9069, USA.

Photo-contact dermatitis (PCD) describes the adverse cutaneous reaction that occurs in some patients as a result of simultaneous exposure to a contactant and to light. PCD can be subdivided into photo-allergic and photo-irritant dermatitis depending on whether the contactant respectively invokes an allergic or irritant reaction. Photo-irritant reactions are commonly caused by plants, psoralens, and medications taken internally, whereas photo-allergic reactions are commonly caused by sunscreens and topical nonsteroidal anti-inflammatory medications. Read More

F1000Res 2017 30;6:1906. Epub 2017 Oct 30.

Scottish Cutaneous Porphyria Service, Scottish Photodiagnostic Unit, Department of Dermatology, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK.

This is an overview of the cutaneous porphyrias. It is a narrative review based on the published literature and my personal experience; it is not based on a formal systematic search of the literature. The cutaneous porphyrias are a diverse group of conditions due to inherited or acquired enzyme defects in the porphyrin-haem biosynthetic pathway. Read More

Acta Derm Venereol 2016 Nov;96(7):868-872

Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, 5000 Odense C, Denmark.

Porphyrias are rare diseases caused by altered haem synthesis leading to the accumulation of different haem intermediates. Neurovisceral attacks may occur in acute porphyrias, while photosensitivity is the presenting symptom in cutaneous porphyrias. We present here an overview of symptoms and a flowchart for the diagnosis of cutaneous porphyrias, with recommendations for monitoring and an update of treatment options. Read More

Hautarzt 2016 Mar;67(3):221-5

Hautklinik und Europäisches Porphyriezentrum, Universitätsklinikum der Heinrich-Heine-Universität Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Deutschland.

Porphyrias comprise a heterogeneous group of predominantly genetically determined metabolic diseases which are due to a dysfunction in heme biosynthesis. Variegate porphyria and hereditary coproporphyria are referred to as neurocutaneous porphyrias because affected patients can develop both cutaneous symptoms on light-exposed body sites and potentially life-threatening acute neurovisceral symptoms, thereby mimicking several other diseases. In this overview, we provide an update on pathogenesis, clinical manifestation, diagnosis, and therapy of these two types of porphyria. Read More

Hautarzt 2016 Mar;67(3):201-6

Hautklinik und Europäisches Porphyriezentrum, Universitätsklinikum der Heinrich-Heine-Universität Düsseldorf, Universitätsklinikum Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Deutschland.

The porphyrias comprise a clinically, biochemically, and genetically heterogeneous group of predominantly hereditary metabolic disorders resulting from a dysfunction along the heme biosynthetic pathway. Whereas most variants can manifest with different cutaneous symptoms, some types only reveal life-threatening acute neurovisceral attacks. Therefore, interdisciplinary care of these patients is advisable. Read More

Curr Protoc Hum Genet 2015 Jul 1;86:17.20.1-26. Epub 2015 Jul 1.

Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, Galveston, Texas.

Porphyria diseases are a group of metabolic disorders caused by abnormal functioning of heme biosynthesis enzymes and characterized by excessive accumulation and excretion of porphyrins and their precursors. Precisely which of these chemicals builds up depends on the type of porphyria. Porphyria is not a single disease but a group of nine disorders: acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), variegate porphyria (VP), δ-aminolevulinic acid dehydratase deficiency porphyria (ADP), porphyria cutanea tarda (PCT), hepatoerythropoietic porphyria (HEP), congenital erythropoietic porphyria (CEP), erythropoietic protoporphyria (EPP), and X-linked protoporphyria (XLP). Read More

Eur J Hum Genet 2016 Jan 25;24(1):66-72. Epub 2015 Mar 25.

Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Bratislava, Slovakia.

Alkaptonuria (AKU) is an autosomal recessive disorder caused by mutations in homogentisate-1,2-dioxygenase (HGD) gene leading to the deficiency of HGD enzyme activity. The DevelopAKUre project is underway to test nitisinone as a specific treatment to counteract this derangement of the phenylalanine-tyrosine catabolic pathway. We analysed DNA of 40 AKU patients enrolled for SONIA1, the first study in DevelopAKUre, and of 59 other AKU patients sent to our laboratory for molecular diagnostics. Read More

Chembiochem 2014 Sep 4;15(14):2024-35. Epub 2014 Sep 4.

Pharmaceutical Chemistry I, Pharmaceutical Institute, University of Bonn, Brühler Strasse 7, 53119 Bonn (Germany).

More than 20 years of research on heme as a temporary effector molecule of proteins have revealed its widespread impact on virtually all primary functions in the human organism. As our understanding of this influence is still growing, a comprehensive overview of compiled data will give fresh impetus for creativity and developing new strategies in heme-related research. From known data concerning heme-regulated proteins and their involvement in the development of diseases, we provide concise information of Fe(II/III) heme as a regulator and the availability of "regulatory heme". Read More

Tidsskr Nor Laegeforen 2014 Apr 29;134(8):831-6. Epub 2014 Apr 29.

Nasjonalt kompetansesenter for porfyrisykdommer (NAPOS) Laboratorium for klinisk biokjemi Haukeland universitetssykehus.

Background: Porphyria is an umbrella term for a group of largely hereditary diseases that are due to defective haem synthesis. The diseases have a varied and partly overlapping range of symptoms and presentations. The commonest forms of porphyria are porphyria cutanea tarda, acute intermittent porphyria and erythropoietic protoporphyria. Read More

Hepatology 2014 Sep 29;60(3):1082-9. Epub 2014 Jul 29.

Division of Gastroenterology and Hepatology, University of Alabama (UAB), Birmingham, AL.

Unlabelled: Porphyrias are a group of eight metabolic disorders, each resulting from a mutation that affects an enzyme of the heme biosynthetic pathway. Porphyrias are classified as hepatic or erythropoietic, depending upon the site where the gene defect is predominantly expressed. Clinical phenotypes are classified as follows: (1) acute porphyrias with neurovisceral symptoms: acute intermittent porphyria; delta amino-levulinic acid hydratase deficiency porphyria; hereditary coproporphyria; and variegate porphyria and (2) cutaneous porphyrias with skin blistering and photosensitivity: porphyria cutanea tarda; congenital erythropoietic porphyria; hepatoerythropoietic porphyria and both erythropoietic protoporphyrias: autosomal dominant and X-linked. Read More

Arch Dermatol Res 2014 May 24;306(4):313-330. Epub 2013 Oct 24.

Department of Dermatology, University of California at Davis, 3301 C Street, Sacramento, CA 95816, USA.

Fibrosis is characterized by the excessive deposition of extracellular matrix components eventually resulting in organ dysfunction and failure. In dermatology, fibrosis is the hallmark component of many skin diseases, including systemic sclerosis, graft-versus-host disease, hypertrophic scars, keloids, nephrogenic systemic fibrosis, porphyria cutanea tarda, restrictive dermopathy and other conditions. Fibrotic skin disorders may be debilitating and impair quality of life. Read More

J Pediatr Hematol Oncol 2013 May;35(4):e167-70

Department of Pediatrics, Lady Hardinge Medical College, Kalawati Saran Children's Hospital, New Delhi, India.

Congenital erythropoietic porphyria is a rare disorder of heme biosynthesis, resulting from decreased enzymatic activity of uroporphyrinogen III synthase. Clinical manifestations are heterogenous, of variable severity, and with occasional phenotypic-genotypic correlation. A 14-month-old boy developed fever, extensive dermatitis, and reddish colored urine. Read More

Clin Neurophysiol 2011 Dec 19;122(12):2336-44. Epub 2011 Aug 19.

School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia.

The porphyrias are inherited metabolic disorders arising from disturbance in the haem biosynthesis pathway. The neuropathy associated with acute intermittent porphyria (AIP) occurs due to mutation involving the enzyme porphobilinogen deaminase (PBGD) and is characterised by motor-predominant features. Definitive diagnosis often encompasses a combination of biochemical, enzyme analysis and genetic testing, with clinical neurophysiological findings of a predominantly motor axonal neuropathy. Read More

Prim Care Companion CNS Disord 2011 ;13(6)

Department of Internal Medicine and Psychiatry (Drs Jain and Resch), Department of Psychiatry (Dr Bennett), and Department of Internal Medicine, Division of Hematology and Oncology, Simmons Cancer Institute (Dr Godwin), Southern Illinois University School of Medicine, Springfield.

Acute porphyrias are often misdiagnosed and most commonly present as atypical neuropsychiatric symptoms or acute abdominal pain. Clinicians should suspect acute porphyrias in patients presenting with variable neuropsychiatric symptoms and unexplained pain. Proper identification can lead to less iatrogenicity associated with porphyrinogenic agents, appropriate management, and a better patient outcome. Read More

Best Pract Res Clin Gastroenterol 2010 Oct;24(5):593-605

Department of Dermatology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.

The porphyrias are predominantly inherited metabolic disorders, which result from a specific deficiency of one of the eight enzymes along the pathway of haem biosynthesis. Historically, they have been classified into hepatic and erythropoietic forms, based on the primary site of expression of the prevailing dysfunctional enzyme. From a clinical point of view, however, it is more convenient to subdivide them into acute and non-acute porphyrias, thereby primarily considering the potential occurrence of life-threatening acute neurovisceral attacks. Read More

Antonie Van Leeuwenhoek 2011 Mar 22;99(3):443-56. Epub 2010 Aug 22.

PROIMI - CONICET, Planta Piloto de Procesos Industriales Microbiológicos, Av Belgrano y Caseros, T4001MVB Tucumán, Argentina.

Microcosm assays with dye-amended culture media under a shot-feeding strategy allowed us to obtain 100 yeast isolates from the wastewater outfall channel of a dyeing textile factory in Tucumán (Argentina). Meanwhile, 63 yeast isolates were obtained from Phoebe porphyria (Laurel del monte) samples collected from Las Yungas rainforest (Tucumán), via a classical isolation scheme. Isolated yeasts, both from dye-polluted and virgin environments, were compared for their textile dye decolourization ability when cultured on solid and liquid media. Read More

Cell Mol Biol (Noisy-le-grand) 2009 Jul 1;55(2):147-51. Epub 2009 Jul 1.

Porphyria Center Saxony, Medizinische Klinik II, Klinikum Chemnitz.

Acute porphyrias are caused by enzyme defects along the heme synthesis pathway. Patients usually present with abdominal pain, impaired intestinal motility, neurological and psychiatric symptoms, hypertension, tachycardia, hyponatriemia and reddish urine. This article gives an overview over drugs that are recommended in patients with acute hepatic porphyrias and represents a compilation of four so far existing lists. Read More

Cell Mol Biol (Noisy-le-grand) 2009 Jul 1;55(2):79-88. Epub 2009 Jul 1.

Dipartimento di Medicina Interna, Università degli Studi di Milano - Fondazione Ospedale Maggiore Policlinico Mangiagalli e Regina Elena IRCCS Milano, Italy.

Variegate Porphyria (VP) is an autosomal dominant disorder found worldwide but is rare in Italy. In this study we provide an overview of clinical, biochemical and genetic background of 33 Italian VP patients diagnosed in the last fifteen years. About 70% of patients had experienced clinical symptoms: 43. Read More

Curr Opin Neurol 2008 Oct;21(5):563-8

Department of Neurology, University of Würzburg, Germany.

Purpose Of Review: To give an overview of recent data on the use of skin biopsy as a diagnostic tool in neuropathies.

Recent Findings: The sensitivity and specificity of skin biopsy in detecting small fiber neuropathy is supported by new data. In many patients with small fiber neuropathy, a treatable disorder can be identified if a full workup is done. Read More

J Inherit Metab Dis 2007 Oct 10;30(5):631-41. Epub 2007 Aug 10.

Federation of Nervous System Diseases, Hôpital de la Salpêtrière, 47 Boulevard de l'Hôpital, 75651, Paris cedex 13, France.

Inborn errors of metabolism (IEMs) may present in adolescence or adulthood as a psychiatric disorder. In some instances, an IEM is suspected because of informative family history or because psychiatric symptoms form part of a more diffuse clinical picture with systemic, cognitive or motor neurological signs. However, in some cases, psychiatric signs may be apparently isolated. Read More

World J Gastroenterol 2007 May;13(17):2467-78

Department of Internal Medicine, University of Florence, Viale Morgagni 85, 50134 Florence, Italy.

Hepatitis C virus (HCV) is a global health problem affecting 3% of the world's population (about 180 million) and a cause of both hepatic and extrahepatic diseases. B-cell lymphoproliferative disorders, whose prototype is mixed cryoglobulinemia, represent the most closely related as well as the most investigated HCV-related extrahepatic disorder. The association between extrahepatic (lymphoma) as well as hepatic malignancies (hepatocellular carcinoma) has justified the inclusion of HCV among human cancer viruses. Read More

Mod Pathol 2007 Feb;20 Suppl 1:S31-9

Pathology Lab, Division of Gastrointestinal Pathology, Minnesota Gastroenterology, Abbott Northwestern Hospital, Minneapolis, MN, USA.

Iron can accumulate in the liver in a variety of conditions, including congenital, systemic iron-loading conditions (hereditary hemochromatosis), conditions associated with systemic macrophage iron accumulation (transfusions, hemolytic conditions, anemia of chronic disease, etc), in some hepatitidies (hepatitis C, alcoholic liver disease, porphyria cutanea tarda), and liver-specific iron accumulation of uncertain pathogenesis in cirrhosis. The anatomic pathologist will be faced with the task of determining whether iron accumulation in the liver is significant and, if so, the nature of the disease that lead to the accumulation (ie diagnosis). The tools available to the pathologist include (most importantly) histologic examination with iron stain, quantitative iron analysis, clinical history, laboratory iron tests (serum iron and iron-binding capacity, serum ferritin) and germline genetic analysis for mutations in genes known to be associated with hemochromatosis (HFE, ferroportin, hepcidin, hemojuvelin, transferrin receptor-2). Read More

Dermatol Nurs 2006 Oct;18(5):425-30

Dermatology, Virginia Commonwealth University Medical Center, Richmond, VA, USA.

Hepatitis C (HCV) is the most common cause of chronic liver disease and hepatocellular carcinoma, as well as the leading indication for liver transplantation in the Western world. For many patients, cutaneous manifestations may be the only, the earliest, or the most apparent sign of the underlying infection. The dermatologic manifestations of HCV infection are reviewed. Read More

Am J Med 2006 Sep;119(9):801.e19-24

Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston 77555-1109, USA.

Background: The acute porphyrias are rare inherited diseases characterized by acute episodes of life-threatening symptoms. Hemin was approved for treating these disorders in 1983. This open-label study of hemin therapy, conducted to demonstrate the safety of hemin manufactured in a new facility, is the largest to date and provides an overview of the use of hemin in clinical practice in the United States. Read More

Dig Liver Dis 2007 Jan 1;39(1):2-17. Epub 2006 Aug 1.

Department of Internal Medicine, Medical School, Center for Research, Transfer and High Education DENOthe, Center for the Study of Systemic Manifestations of Hepatitis Viruses MaSVE, University of Florence, Florence, Italy.

Hepatitis C Virus is associated with a wide series of extrahepatic manifestations. Based on available data the link between the virus and some of these extrahepatic diseases is only suggested and needs further confirmation. Hepatitis C Virus-related lymphoproliferative disorders, whose prototype is mixed cryoglobulinaemia, represent the most closely related extrahepatic manifestations of Hepatitis C Virus. Read More

Exp Dermatol 2006 Sep;15(9):685-91

Department of Dermatology, University Hospital Maastricht, Maastricht, The Netherlands.

The porphyrias are clinically and genetically heterogeneous metabolic diseases, which predominantly result from a hereditary dysfunction in the pathway of haeme biosynthesis. Currently, at least eight different forms of porphyrias can be differentiated, all of them characterized by a specific enzyme deficiency that is either inherited in an autosomal-dominant fashion, autosomal recessively or, in the case of porphyria cutanea tarda, might also be acquired. All genes encoding these enzymes have been cloned and several mutations underlying the different types of porphyrias have been reported. Read More

Semin Respir Crit Care Med 2002 Jun;23(3):191-200

Brown Medical School, Providence, Rhode Island, USA.

A great many neuromuscular disorders affect respiratory function. This article focuses on neuropathic and myopathic disorders that weaken the diaphragm and respiratory muscles. This discussion gives a general overview and attempts to update the reader on recent pathophysiological insights and developments in therapy. Read More

Int Dent J 2005 Apr;55(2):61-6

Porphyria is a diverse group of diseases in which the biosynthesis of heme is disrupted by either genetic defects or environmental factors. This review gives an overview of the different types of porphyria and describes possible causes, clinical signs, diagnosis and therapy. In addition, the oral manifestations of porphyria and the potential implications of the disease for dental management are discussed. Read More

Liver Transpl 2004 Mar;10(3):331-9

Center for Skin Diseases, La Chaux-de-Fonds, Switzerland.

The skin, easily accessible for medical examination, is affected in many ways by liver transplantation. Mucocutaneous manifestations of advanced liver disease and dermatologic conditions associated with specific hepatic diagnoses generally improve after liver transplantation. Vasculitic lesions due to cryoglobulinemia associated with hepatitis C, and photosensitivity due to porphyria are occasional exceptions. Read More

Clin Chim Acta 2002 Nov;325(1-2):17-37

INSERM U409, Faculté de Médecine Xavier Bichat, Université Paris VII, 16, rue Henri Huchard, BP 416-75018, Paris Cedex 18, France.

The human hereditary hepatic porphyrias are diseases due to marked deficiencies of enzymes in the heme biosynthetic pathway. Porphyrias can be classified as either hepatic or erythroid, depending on the major production site of porphyrins or their precursors. The pathogenesis of inherited hepatic porphyrias has now been defined at the molecular level. Read More

Curr Protoc Toxicol 2001 May;Chapter 8:Unit 8.1

University of Utah Medical School, Salt Lake City, Utah, USA.

Biosynthesis of heme is important for both prokaryotes and eukaryotes. The enzymes for this multistep process are distributed between the cytosol and mitochondria in eukaryotes. In humans there are inherited and acquired disorders characterized by over synthesis of one or more enzymes or absence of an enzyme. Read More

Scand J Gastroenterol Suppl 2000 (232):79-85

Dept. of Gastroenterology and Hepatology, Medisch Centrum Leeuwarden, Leeuwarden, P. O. Box 888, 8901 BR The Netherlands.

Background: Erythropoietic protoporphyria (EPP) is an inherited disorder of heme synthesis, causing excess of protoporphyrin in blood, skin, liver and other organs. Protoporphyrin accumulation causes rapidly progressive liver failure in a minority of patients. Many questions concerning liver disease in EPP patients remain to be solved. Read More

Skin Pharmacol Appl Skin Physiol 1998 Nov-Dec;11(6):310-20

Department of Dermatology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.

Variegate porphyria, one of the acute hepatic porphyrias, is characterized by a partial reduction in protoporphyrinogen oxidase, the seventh enzyme of the heme biosynthetic pathway. For a long time, this disease has caused confusion among the porphyrias because it presents with clinical symptoms and biochemical findings that can be similar to those found in other types of porphyrias. Here, we provide an overview of historical, clinical, biochemical, genetical, and other aspects of variegate porphyria that might be helpful in providing more insight into this rare disorder. Read More

Skin Pharmacol Appl Skin Physiol 1998 Nov-Dec;11(6):297-309

Department of Dermatology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.

The porphyrias are disorders that result from the inherited or acquired dysregulation of one of the eight enzymes in the porphyrin-heme biosynthetic pathway. The different types of porphyrias often show overlapping findings with regard to clinical and/or biochemical features. Therefore, the establishment of screening methods for the identification of underlying mutations on the basis of direct DNA analysis may provide a more reliable approach for diagnosis of the different types of porphyrias. Read More

J Dermatol 1995 Nov;22(11):823-8

Department of Dermatology, Hospital Clinic, Barcelona, Spain.

The porphyrias are uncommon diseases caused by enzymatic deficiencies in the heme pathway. In the 25 year period 1969-1994, the Department of Dermatology of the Hospital Clinic of Barcelona has been able to study 793 cases of porphyria (724 cases of PCT, 27 of EPP, 26 of PV, 5 of CEP, 5 of HEP, 5 of AIP, 1 of HCP). Homozygous expression of an enzymatic deficiency in the heme pathway produces severe disease. Read More

Am J Med Sci 1994 Jan;307(1):54-63

Department of Surgery, William Beaumont Army Medical Center, El Paso, Texas.

Chenodeoxycholate (3 alpha, 7 alpha-dihydroxy-5 beta-cholanic acid) is a primary bile acid directly synthesized from cholesterol. It is an amphipathic molecule, possessing both a hydrophobic side and a polar hydrophilic side, giving it the ability to solubilize lipids in a water environment. Bile acids are necessary for the absorption of fats and fat soluble vitamins. Read More

Acta Oncol 1994 ;33(8):895-900

Department of Surgery, Athens Medical Center, Greece.

Hepatocellular carcinoma (HCC) is the seventh most common cancer in men and the ninth most common cancer in women with 500,000 to 1,000,000 new cases per year. Several risk factors (sex hormones, alcohol, thorotrast, aflatoxin B1, hepatitis B or C, haemochromatosis, alpha 1-antitrypsin deficiency, tyrosinemia, porphyria cutanea tarda, acute intermittent porphyria, Wilson's disease) associated with the development of HCC have been identified from epidemiological studies. The diagnosis is usually based on a combination of clinical and laboratory findings together with radiographic and histopathologic characteristics. Read More

Hautarzt 1983 Nov;34(11):539-47

Fourteen monogenic cutaneous disorders of man are compared to similar gene defects in animals. The traits are classified into two groups. In the first group, an identity (homology) of the underlying gene defects is likely. Read More

Semin Liver Dis 1982 May;2(2):87-99

Dtsch Gesundheitsw 1978 ;33(49):2312-8