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1.
J Dtsch Dermatol Ges ; 20(3): 316-333, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35304948
2.
J Dtsch Dermatol Ges ; 20(3): 316-331, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35304965

RESUMEN

The porphyrias are clinically variable and genetically heterogeneous, predominantly hereditary metabolic diseases, which are caused by a dysfunction of specific enzymes in heme biosynthesis. Here, we provide an overview of the etiopathogenesis, clinic, differential diagnosis, laboratory diagnostics and therapy of these complex metabolic disorders and cover in detail the most common form of porphyria worldwide (porphyria cutanea tarda), the most frequent childhood porphyria (erythropoietic protoporphyria), and the most common neurocutaneous porphyria (variegate porphyria).


Asunto(s)
Porfiria Cutánea Tardía , Porfiria Variegata , Porfirias , Niño , Diagnóstico Diferencial , Humanos , Porfiria Cutánea Tardía/diagnóstico , Porfiria Cutánea Tardía/terapia , Porfiria Variegata/diagnóstico , Porfiria Variegata/terapia , Porfirias/clasificación , Porfirias/diagnóstico , Porfirias/terapia
3.
J Hepatol ; 62(3): 734-8, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25445397

RESUMEN

Variegate porphyria (VP) and acute intermittent porphyria (AIP), the two most common types of acute porphyrias (AHPs), result from a partial deficiency of protoporphyrinogen oxidase (PPOX) and hydroxymethylbilane synthase (HMBS), respectively. A rare but serious complication in the AHPs is hepatocellular carcinoma (HCC). However, the underlying pathomechanisms are yet unknown. We performed DNA sequence analysis in cancerous and non-cancerous liver tissue of a VP and an AIP patient, both with HCC. In samples of both cancerous and non-cancerous liver tissues from the patients, we identified the underlying PPOX and HMBS germline mutations, c.1082dupC and p.G111R, respectively. Additionally, we detected a second somatic mutation, only in the cancer tissue i.e., p.L416X in the PPOX gene of the VP patient and p.L220X in the HMBS gene of the AIP patient, both located in trans to the respective germline mutations. Both somatic mutations were not detected in 10 non-porphyria-associated HCCs. Our data demonstrate that in the hepatic cancer tissue of AHP patients, somatic second-hit mutations result in nearly complete inactivation of the enzymes catalyzing major steps in the heme biosynthetic pathway. Both PPOX and HMBS, which might act as tumor suppressors, play a crucial role in the development of HCC in these individuals.


Asunto(s)
Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/genética , Flavoproteínas/genética , Hidroximetilbilano Sintasa/genética , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/genética , Proteínas Mitocondriales/deficiencia , Proteínas Mitocondriales/genética , Mutación , Porfiria Intermitente Aguda/complicaciones , Porfiria Intermitente Aguda/genética , Porfiria Variegata/complicaciones , Porfiria Variegata/genética , Protoporfirinógeno-Oxidasa/genética , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/enzimología , Femenino , Mutación de Línea Germinal , Humanos , Neoplasias Hepáticas/enzimología , Porfiria Intermitente Aguda/enzimología , Porfiria Variegata/enzimología , Proteínas Supresoras de Tumor/deficiencia , Proteínas Supresoras de Tumor/genética
4.
J Invest Dermatol ; 133(6): 1467-71, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23673504

RESUMEN

Photosensitivity is the clinical hallmark of both erythropoietic protoporphyria (EPP) and X-linked dominant protoporphyria (XLDPP). Both disorders result from a hereditary dysfunction in heme biosynthesis. Disease onset is usually in early childhood. However, rare patients with late-onset EPP in association with a myeloproliferative disorder or myelodysplastic syndrome have been reported. In this issue, Livideanu et al. describe the first patient with late-onset XLDPP.


Asunto(s)
5-Aminolevulinato Sintetasa/genética , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Trastornos por Fotosensibilidad/genética , Protoporfiria Eritropoyética/genética , 5-Aminolevulinato Sintetasa/deficiencia , Femenino , Humanos , Masculino
5.
Ned Tijdschr Geneeskd ; 155(30-31): A2636, 2011.
Artículo en Holandés, Inglés | MEDLINE | ID: mdl-22085504

RESUMEN

We present a 49-year-old man seen at the dermatology outpatient department with a 3-year history of painful swollen digits of hands and feet. On enquiry he reported dysuria. On examination we saw extensive swelling of the digits, keratosis of the nails, and some psoriasiform skin lesions on the soles of the feet. The differential diagnosis included acrodermatitis continua suppurativa, reactive arthritis and psoriatic arthritis. Radiographic imaging revealed the presence of arthritis. Testing proved negative for rheumatoid factor and positive for HLA-B27 making spondyloarthropathy the most likely diagnosis, either in the form of reactive arthritis or psoriatic arthritis. The patient was treated with combination therapy of doxycycline, methotrexate and folic acid. Because of insufficient response to therapy, the methotrexate dose was raised and eventually etanercept was added. During the last visit to the outpatient clinic, the patient still showed insufficient response to therapy.


Asunto(s)
Fármacos Dermatológicos/uso terapéutico , Espondiloartropatías/diagnóstico , Artritis Psoriásica/diagnóstico , Artritis Psoriásica/tratamiento farmacológico , Artritis Reactiva/diagnóstico , Artritis Reactiva/tratamiento farmacológico , Diagnóstico Diferencial , Doxiciclina/uso terapéutico , Ácido Fólico/uso terapéutico , Humanos , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Espondiloartropatías/tratamiento farmacológico , Insuficiencia del Tratamiento
6.
J Invest Dermatol ; 131(11): 2249-54, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21734717

RESUMEN

The simultaneous dysfunction of two enzymes within the heme biosynthetic pathway in a single patient is rare. Not more than 15 cases have been reported. A woman with a transient episode of severe photosensitivity showed a biochemical porphyrin profile suggestive of hereditary coproporphyria (HCP), whereas some of her relatives had a profile that was suggestive of variegate porphyria (VP). HCP and VP result from a partial enzymatic deficiency of coproporphyrinogen oxidase (CPOX) and protoporphyrinogen oxidase (PPOX), respectively. DNA analysis in the index patient revealed mutations in both the CPOX and PPOX genes, designated as c.557-15C>G and c.1289dupT, respectively. The CPOX mutation leads to a cryptic splice site resulting in retention of 14 nucleotides from intron 1 in the mRNA transcript. Both mutations encode null alleles and were associated with nonsense-mediated mRNA decay. Given the digenic inheritance of these null mutations, coupled with the fact that both HCP and VP can manifest with life-threatening acute neurovisceral attacks, the unusual aspect of this case is a relatively mild clinical phenotype restricted to dermal photosensitivity.


Asunto(s)
Coproporfirinógeno Oxidasa/genética , Porfirias/clasificación , Porfirias/genética , Protoporfirinógeno-Oxidasa/genética , Eliminación de Secuencia/genética , Coproporfiria Hereditaria/genética , Análisis Mutacional de ADN , Femenino , Humanos , Masculino , Persona de Mediana Edad , Linaje , Trastornos por Fotosensibilidad/genética , Porfiria Variegata/genética , Porfirias/diagnóstico
8.
Best Pract Res Clin Gastroenterol ; 24(5): 593-605, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20955962

RESUMEN

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. Unrecognised or untreated, such an acute porphyric attack is associated with a significant mortality of up to 10%. The acute hepatic porphyrias comprise acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and δ-aminolevulinic acid dehydratase deficiency porphyria. Making a precise diagnosis may be difficult because the different types of porphyrias may show overlapping clinical and biochemical characteristics. To date, the therapeutic possibilities are limited and mainly symptomatic. In this overview we report on what is currently known about pathogenesis, clinic, diagnostics, and therapy of the acute hepatic porphyrias. We further point out actual and future challenges in the management of these diseases.


Asunto(s)
Porfirias Hepáticas/terapia , Animales , Carcinoma Hepatocelular/etiología , Coproporfiria Hereditaria/genética , Terapia de Reemplazo Enzimático , Femenino , Terapia Genética , Humanos , Hidroximetilbilano Sintasa/uso terapéutico , Neoplasias Hepáticas/etiología , Trasplante de Hígado , Porfiria Intermitente Aguda/genética , Porfiria Intermitente Aguda/metabolismo , Porfirias Hepáticas/clasificación , Porfirias Hepáticas/complicaciones , Porfirias Hepáticas/diagnóstico , Porfirias Hepáticas/genética , Embarazo , Complicaciones del Embarazo/terapia , Proteínas Recombinantes/uso terapéutico , Insuficiencia Renal/complicaciones
9.
Best Pract Res Clin Gastroenterol ; 24(5): 735-45, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20955974

RESUMEN

Porphyria cutanea tarda (PCT) is the most frequent type of porphyria worldwide and results from a catalytic deficiency of uroporphyrinogen decarboxylase (UROD), the fifth enzyme in heme biosynthesis. At least two different types of PCT are currently distinguished: an acquired variant, also referred to as sporadic or type I PCT, in which the enzymatic deficiency is limited to the liver; and an autosomal dominantly inherited form, also known as familial or type II PCT, in which there is a decrease of enzymatic activity in all tissues. The cutaneous findings include increased photosensitivity, skin fragility, blistering, erosions, crusts, and miliae on the sun-exposed areas of the body. Additionally, hyperpigmentation, hypertrichosis, sclerodermoid plaques, and scarring alopecia might be observed. In patients with type I PCT, there is a significant association with liver disease that can be triggered by genetic and environmental factors, such as alcohol abuse, iron overload, haemochromatosis, polychlorinated hydrocarbons, and hepatitis C virus infection. The diagnosis of PCT can be made based on the skin symptoms, a characteristic urinary porphyrin excretion profile, and the detection of isocoproporphyrin in the feces. In red blood cells of individuals with type II PCT, UROD activity is decreased by approximately 50% due to heterozygous mutations in the UROD gene. Here we provide an update on clinical, diagnostic and therapeutic aspects of PCT, a disorder that affects both skin and liver.


Asunto(s)
Porfiria Cutánea Tardía/diagnóstico , Animales , Fungicidas Industriales/efectos adversos , Hemo/biosíntesis , Hemo/genética , Hemocromatosis/epidemiología , Hemocromatosis/genética , Hexaclorobenceno/efectos adversos , Humanos , Hierro/sangre , Cirrosis Hepática/epidemiología , Porfiria Cutánea Tardía/epidemiología , Porfiria Cutánea Tardía/genética , Porfiria Cutánea Tardía/metabolismo , Porfiria Cutánea Tardía/terapia , Uroporfirinógeno Descarboxilasa/genética
10.
Acta Derm Venereol ; 90(5): 512-5, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20814629

RESUMEN

Variegate porphyria is an acute hepatic porphyria resulting from a partial deficiency of protoporphyrinogen oxidase, the penultimate enzyme in haem biosynthesis. Cutaneous symptoms and acute neurovisceral attacks are well-known clinical characteristics of the disease. Less studied, however, is the risk of developing hepatocellular carcinoma, an aggressive type of liver cancer. We describe here two Swiss patients with variegate porphyria and this serious complication. Common risk factors, including alcohol over-consumption or chronic hepatitis, were absent in both patients. Interestingly, one patient carried mutation 1082-1083insC in the PPOX gene, a prevalent sequence deviation in the Swiss variegate porphyria population, which was also found in a French patient with variegate porphyria and hepatocellular carcinoma. Recent studies indicate that individuals with acute hepatic porphyria have a 36- to 61-fold increased risk of manifesting hepatocellular carcinoma. The incidence rate ratio in the Swiss population was estimated to be 34, comparable with those found in the French and Finnish populations. Because this tumour is associated with a rising mortality, we suggest regular screening for hepatocellular carcinoma in all patients with variegate porphyria.


Asunto(s)
Carcinoma Hepatocelular/etiología , Neoplasias Hepáticas/etiología , Porfiria Variegata/complicaciones , Anciano de 80 o más Años , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Análisis Mutacional de ADN , Resultado Fatal , Femenino , Flavoproteínas/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Proteínas Mitocondriales/genética , Mutación , Cuidados Paliativos , Porfiria Variegata/genética , Porfiria Variegata/patología , Protoporfirinógeno-Oxidasa/genética , Piel/patología , Suiza , Resultado del Tratamiento
11.
Exp Dermatol ; 19(8): e326-8, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20163457

RESUMEN

Porphyria cutanea tarda (PCT) results from decreased activity of hepatic uroporphyrinogen decarboxylase (UROD). Both sporadic and familial forms are characterised by typical cutaneous lesions triggered by genetic/environmental factors. Studies in rodents showed that cytochrome P4501A2 (CYP1A2) plays a central role in the synthesis of a competitive inhibitor of hepatic UROD, but there is little evidence in humans. The impact of smoking and CYP1A2 g-163C > A allelic variant upon first appearance of clinical signs was investigated in 102 patients (80 sporadic-PCT) and 150 healthy donors from Spain. We found an increase in the frequency of CYP1A2 g-163A allele in patients with PCT when compared with controls, although the more inducible A/A genotype had no effect on the onset age. In sporadic-PCT, smoking leads to earlier onset of clinically overt disease in moderate-to-heavy smokers (>or=10 cigarettes/day). In conclusion, this study provides evidence that smoking hastens the onset of cutaneous symptoms in sporadic-PCT patients.


Asunto(s)
Alelos , Citocromo P-450 CYP1A2/genética , Variación Genética/genética , Homocigoto , Porfiria Cutánea Tardía/genética , Fumar/efectos adversos , Adulto , Estudios de Casos y Controles , Frecuencia de los Genes/genética , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Persona de Mediana Edad , Porfiria Cutánea Tardía/etnología , Porfiria Cutánea Tardía/etiología , España
12.
Exp Dermatol ; 18(2): 185-91, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19146581

RESUMEN

Hair follicle tumors show a broad range of phenotypic variability and diverse histopathological characteristics. To date, different genes and signalling cascades have been implicated in the development and growth of these tumors including the sonic hedgehog, nuclear factor kappa-B and wingless pathway. While the former three have received ample attention, little is known about the possible role of mammalian target of rapamycin (mTOR) in trichofollicular tumorigenesis. Here, we delineate how mTOR can link the various signalling pathways, thereby proposing a unifying model for hair follicle tumor formation.


Asunto(s)
Proteínas Quinasas/fisiología , Transducción de Señal/fisiología , Neoplasias Cutáneas/fisiopatología , Folículo Piloso , Proteínas Hedgehog/fisiología , Humanos , FN-kappa B/fisiología , Serina-Treonina Quinasas TOR , Proteínas Wnt/fisiología
13.
Int J Dermatol ; 47 Suppl 1: 7-9, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18986476

RESUMEN

Pyoderma gangrenosum is an ulcerative skin disease with variable clinical outcomes. The diagnosis is based on clinical features and exclusion of other ulcerative diseases. To date, a specific treatment is not known. Since the disease can be destructive, aggressive treatment is preferable. Here, we present a patient with a penile pyoderma gangrenosum who was successfully treated with low-dose colchicine.


Asunto(s)
Colchicina/uso terapéutico , Enfermedades del Pene/tratamiento farmacológico , Piodermia Gangrenosa/tratamiento farmacológico , Moduladores de Tubulina/uso terapéutico , Adulto , Humanos , Masculino , Enfermedades del Pene/patología , Pene/patología , Piodermia Gangrenosa/patología , Piel/patología
14.
Int J Dermatol ; 47 Suppl 1: 25-8, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18986481

RESUMEN

Tumor necrosis factor-alpha (TNF-alpha) inhibitors such as adalimumab are increasingly used in the treatment of chronic inflammatory diseases, including rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. In Europe, this group of drugs also has been approved for therapy of moderate to severe psoriasis recently. With increased application of adalimumab, the possible adverse effects occurring in the course of treatment steadily gained more attention. Among these, infection and localized skin eruptions are the most common. Usually, the cutaneous symptoms rapidly resolve after discontinuation of the drug. Here, however, we report on a woman with rheumatoid arthritis who developed a therapy-refractory, generalized pustular rash during treatment with adalimumab. After different unsuccessful therapeutic attempts, only a combined treatment with prednisone, methotrexate, and cyclosporinee eventually led to marked improvement. To the best of our knowledge, this is the first report on a generalized, therapy-resistant pustulosis as an adverse effect of adalimumab.


Asunto(s)
Anticuerpos Monoclonales/efectos adversos , Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Erupciones por Medicamentos/tratamiento farmacológico , Erupciones por Medicamentos/patología , Adalimumab , Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales Humanizados , Biopsia , Ciclosporina/uso terapéutico , Quimioterapia Combinada , Epidermis/patología , Femenino , Humanos , Inmunosupresores/uso terapéutico , Metotrexato/uso terapéutico , Persona de Mediana Edad , Prednisolona/uso terapéutico
15.
Int J Dermatol ; 47 Suppl 1: 32-4, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18986483

RESUMEN

Maculopapular exanthemas have a particular high incidence among patients treated with autologous hematopoietic stem cell transplantation (HSCT). In most cases, a viral or drug induced origin is easily identified. However, the transplantation itself may also induce similar skin changes. These exanthemas are known under various names, such as autologous graft-versus-host disease (GVHD), engraftment syndrome (ES) or eruption of lymphocyte recovery (ELR). Given the clinical and histopathological similarities of these disorders, it can prove difficult to establish a diagnosis. Here, we describe a patient who developed a maculopapular exanthema after autologous stem cell transplantation for multiple myeloma, diagnosed as autologous GVHD. We also briefly review the current knowledge of the pathogenesis of autologous GVHD, ES, and ELR. Based on these data we would like to suggest that the latter two do not reflect own disease entities but rather different presentations of autologous GVHD.


Asunto(s)
Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Mieloma Múltiple/terapia , Enfermedades de la Piel/etiología , Biopsia , Femenino , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/patología , Humanos , Linfocitos/inmunología , Linfocitos/patología , Persona de Mediana Edad , Piel/patología , Enfermedades de la Piel/inmunología , Enfermedades de la Piel/patología
16.
Int J Dermatol ; 47 Suppl 1: 38-41, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18986485

RESUMEN

Flegel's disease, also known as hyperkeratosis lenticularis perstans, is a rare skin disease characterized by small, red-brown, hyperkeratotic, papules that are usually located on the lower extremities. The diagnosis is based on the clinical appearance in association with the typical histologic features of orthohyperkeratosis and a subepidermal band-like infiltrate. Treatment is difficult and rarely fully effective. We report on a woman with Flegel's disease who responded to a topical corticosteroid therapy with betamethasone dipropionate.


Asunto(s)
Antiinflamatorios/administración & dosificación , Betametasona/análogos & derivados , Queratosis/tratamiento farmacológico , Dermatosis de la Pierna/tratamiento farmacológico , Administración Tópica , Betametasona/administración & dosificación , Biopsia , Femenino , Humanos , Queratosis/patología , Dermatosis de la Pierna/patología , Persona de Mediana Edad
18.
Eur J Dermatol ; 18(3): 285-8, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18474456

RESUMEN

An 18-year-old man presented multiple asymptomatic reddish-brown papules with a segmental distribution pattern confined to the left side of the trunk. These lesions had arisen two years before while the rest of the integument was unaffected. His further medical and family history was unremarkable. Histopathology revealed the characteristic features of syringoma. Since familial occurrence of syringoma with autosomal dominant inheritance has been described previously, we propose that the clinical phenotype observed in this patient reflects a type 1 segmental manifestation of familial syringoma and, thus, a cutaneous mosaicism.


Asunto(s)
Enfermedades Cutáneas Genéticas/patología , Neoplasias Cutáneas/genética , Siringoma/genética , Adolescente , Adulto , Anciano , Niño , Femenino , Genes Dominantes , Humanos , Masculino , Persona de Mediana Edad , Mosaicismo , Fenotipo , Piel/patología , Enfermedades Cutáneas Genéticas/clasificación , Neoplasias Cutáneas/patología , Siringoma/patología
19.
Int J Dermatol ; 46 Suppl 3: 3-5, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17973877

RESUMEN

A 62-year-old man with testis carcinoma was treated with bleomycin, cisplatin, and etoposide (BEP). During the second cycle of this chemotherapeutic regimen, he developed nonpruritic, linear erythematous lesions in a flagellate-like fashion on the trunk and extremities. After a short-term oral prednisone therapy and ceasing bleomycin administration, these lesions completely resolved. Herein, the characteristic cutaneous side effects of bleomycin are discussed.


Asunto(s)
Antibióticos Antineoplásicos/efectos adversos , Bleomicina/efectos adversos , Erupciones por Medicamentos/etiología , Erupciones por Medicamentos/patología , Humanos , Masculino , Persona de Mediana Edad
20.
Int J Dermatol ; 46 Suppl 3: 13-5, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17973880

RESUMEN

A 47-year-old male developed both longitudinal melanonychia and periungual hyperpigmentation 6 months after initiation of hydroxycarbamide (synonym: hydroxyurea) therapy for chronic myeloproliferative disease. Based on the clinical symptoms observed in this patient, the broad differential diagnostic spectrum of hyperpigmentation of the nails is briefly reviewed here. In individuals who undergo hydroxycarbamide treatment, melanonychia might sometimes be seen as side effect and always has to be differentiated from subungual malignant melanoma.


Asunto(s)
Hidroxiurea/efectos adversos , Hiperpigmentación/inducido químicamente , Enfermedades de la Uña/inducido químicamente , Inhibidores de la Síntesis del Ácido Nucleico/efectos adversos , Humanos , Masculino , Persona de Mediana Edad
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