RESUMO
Epidermolysis bullosa simplex (EBS) is a group of autosomal dominant inherited skin diseases caused by mutations in either the keratin 5 (K5) or the keratin 14 (K14) genes and characterized by development of intraepidermal skin blisters. The three major subtypes of EBS are Weber-Cockayne, Koebner, and Dowling-Meara, of which the Dowling-Meara form is the most severe. We have investigated five large Danish families with EBS and two sporadic patients with the Dowling-Meara form of EBS. In the sporadic Dowling-Meara EBS patients, a novel K14 mutation (N123S) and a previously published K5 mutation (N176S) were identified, respectively. A novel K14 mutation (K116N) was found in three seemingly unrelated families, whereas another family harbored a different novel K14 mutation (L143P). The last family harbored a novel K5 mutation (L325P). The identified mutations were not present in more than 100 normal chromosomes. Six polymorphisms were identified in the K14 gene and their frequencies were determined in normal controls. These polymorphisms were used to show that the K14 K116N mutation was located in chromosomes with the same haplotype in all three families, suggesting a common ancestor. We observed a strict genotype-phenotype correlation in the investigated patients as the same mutation always resulted in a similar phenotype in all individuals with the mutation, but our results also show that it is not possible to predict the EBS phenotype merely by the location (i.e., head, rod, or linker domains) of a mutation. The nature of the amino acid substitution must also be taken into account.
Assuntos
Epidermólise Bolhosa Simples/genética , Queratinas/genética , Dinamarca , Saúde da Família , Feminino , Ligação Genética , Genótipo , Haplótipos , Humanos , Queratina-14 , Masculino , Mutação , Linhagem , Fenótipo , Polimorfismo GenéticoRESUMO
The ultrastructure of human affected and unaffected psoriatic epidermis was studied in skin biopsies from 5 patients and 3 normal controls. Transmission electron microscopic investigations revealed abnormalities in all cell layers of the affected epidermis. Common to psoriatic keratinocytes from affected epidermis was the reduction of tonofilaments. The essential ultrastructural changes were located in the stratum granulosum and stratum corneum. Thus, absence of the fusion between the keratohyalin granules and the tonofilaments was found in stratum granulosum. The keratinocytes of the stratum corneum showed a large accumulation of ribosomes and vesicles resembling lipid vesicles.
Assuntos
Epiderme/ultraestrutura , Psoríase/patologia , Citoesqueleto de Actina/ultraestrutura , Adulto , Epiderme/patologia , Humanos , Queratinas/biossíntese , Microscopia Eletrônica , Pessoa de Meia-IdadeRESUMO
alpha1-Antitrypsin (alpha1-AT) deficiency is an autosomal recessive inherited disease. The serum concentration of the protease inhibitor (Pi) alpha1-AT is controlled by a set of codominant allelic genes, constituting the so-called Pi system. Abnormal conditions reported in connection with severe alpha1-AT deficiency of the PiZZ type have been, in the newborn, cholestasis and progressive juvenile cirrhosis, and in adults, panacinar pulmonary emphysema and liver disease. Skin changes have not been described previously in connection with this disease picture. The case is persistent cutaneous vasculitis in a 2-year-old child with alpha1-AT deficiency of the PiZZ type, heterozygosity for the Duarte variant of galactose-1-phosphate uridyl transferase, and neonatal liver disease. A pathogenetic relationship may exist between the biochemical defects and both the skin and liver diseases.
Assuntos
Hepatopatias/complicações , Vasculite/complicações , Deficiência de alfa 1-Antitripsina , Pré-Escolar , Feminino , Imunofluorescência , Humanos , Imunidade Celular , Hepatopatias/imunologia , Dermatopatias , Vasculite/imunologia , alfa 1-Antitripsina/genéticaRESUMO
The relative importance of genetic factors in the origin, age at onset, clinical type, course, and severity of psoriasis was evaluated on the basis of an unbiased sample of twins, ie, the Danish Twin Register, which covers the total population of twins born in Denmark. All verified and probable cases of psoriasis in twins, born 1891 through 1920, were ascertained. Results are presented of an examination of all members of index pairs in which both partners were alive on a certain date. Fourteen monozygotic and 22 dizygotic, like-sexed pairs were found to include at least one partner with unquestionable psoriasis. Zygosity determination was mainly based on extensive serological examinations. The analyses show that the manifestation of psoriasis depends almost exclusively on the presence of the specific genotype. The age at onset, clinical type, course, and severity are also mainly determined by the genetic constitution. Association with certain HLA antigens of the B series has been confirmed, but the fact that many of the twins (including several of the concordant monozygotic pairs) possess neither of these antigens shows the corresponding genes to be important, but not decisive, elements in the predisposition. We conclude that psoriasis is a genetically determined disorder that may, to a limited extent, be modified by environmental influences.
Assuntos
Doenças em Gêmeos , Psoríase/genética , Adolescente , Adulto , Idoso , Artrite/complicações , Criança , Pré-Escolar , Métodos Epidemiológicos , Feminino , Antígenos HLA/análise , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Gravidez , Psoríase/diagnóstico , Psoríase/etiologia , Psoríase/imunologia , Gêmeos Dizigóticos , Gêmeos MonozigóticosRESUMO
Lymphomatoid papulosis is usually considered to have a benign course, but many reports of subsequent evolution into systemic lymphoma have been reported. By measuring single-cell DNA content by flow cytometry, it may be possible to predict those cases that have the potential for the development of a malignant neoplasm. Two cases that differ from classic benign lymphomatoid papulosis had a more "malignant" clinical picture, with nodules and tumors, and the finding of aneuploidy (abnormal DNA content) from several skin lesion specimens and also from a lymph node specimen in one of the cases. Clinically evident malignant neoplasms have not yet developed in the two patients, but we suggest that the finding of aneuploidy predicts those cases that later could become malignant.
Assuntos
Linfoma/patologia , Dermatopatias/patologia , Neoplasias Cutâneas/patologia , Linfócitos T/patologia , Adulto , Aneuploidia , DNA/análise , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Linfócitos T/ultraestruturaRESUMO
A 63-year-old man had acrokeratosis paraneoplastica (Bazex' syndrome) characterized by violaceous erythema and scaling of the fingers, toes, nose, and aural helices. Severe nail dystrophy was present. Extensive examination of the patient for malignant neoplasms a few months after the initial appearance of the skin changes disclosed no abnormalities, but one year after onset, an epidermoid carcinoma of the lung was found.
Assuntos
Extremidades , Ceratose/patologia , Síndromes Paraneoplásicas/patologia , Carcinoma de Células Escamosas/patologia , Dermatite/etiologia , Humanos , Ceratose/terapia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Síndromes Paraneoplásicas/terapiaRESUMO
BACKGROUND: The aim of the study is to evaluate the diagnostic sensitivity of a 16S ribosomal RNA-based PCR on clinical specimens from patients with erythema migrans (EM) and neuroborreliosis and to compare the sensitivities with those obtained by in vitro culture and serological testing. A semiquantitative detection system, representing the input amount of specific DNA and thus the density of spirochetes in clinical specimens, indicated the preferred clinical sample to obtain for PCR testing. METHODS AND RESULTS: Skin biopsy and urine samples from 31 patients with EM and cerebrospinal fluid (CSF) and urine samples from 30 patients with neuroborreliosis were investigated. Borrelia burgdorferi DNA was detected in 71% of the skin biopsy specimens and 13% of the urine samples from patients with EM. Forty-one percent of the patients with EM were found to have B burgdorferi-specific antibodies in serum, and B burgdorferi was cultured in 29% of the EM specimens. For patients with neuroborreliosis, the diagnostic sensitivities in CSF and urine samples were 17% and 7%, respectively. Specific intrathecal antibody production was found in 90% of the patients, and 87% showed elevated B burgdorferi antibodies in serum. In general, PCR of skin biopsy samples yielded very high amounts of amplicons versus low amounts for CSF and urine samples. CONCLUSIONS: PCR of skin biopsy specimens is currently the most sensitive and specific test for the diagnosis of patients with EM, superior to culture and serological testing. For B burgdorferi-specific CSF disgnosis in patients with neuroborreliosis, the measurement of specific intrathecal antibody synthesis is superior to PCR. However, in patients with a short duration of disease (<14 days), PCR may be a useful diagnostic supplement. PCR of urine samples cannot be recommended at the present time for routine diagnosis of patients with EM or neuroborreliosis.
Assuntos
Grupo Borrelia Burgdorferi/isolamento & purificação , DNA Bacteriano/análise , Eritema Migrans Crônico/diagnóstico , Neuroborreliose de Lyme/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Grupo Borrelia Burgdorferi/genética , Grupo Borrelia Burgdorferi/imunologia , Contagem de Colônia Microbiana , DNA Bacteriano/líquido cefalorraquidiano , DNA Bacteriano/urina , Feminino , Genes de RNAr , Humanos , Imunoglobulina G/biossíntese , Imunoglobulina M/biossíntese , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , RNA Ribossômico 16S/genética , Sensibilidade e Especificidade , Pele/microbiologia , Pele/patologia , Spirochaetales/genética , Spirochaetales/isolamento & purificaçãoRESUMO
Three identical case histories consisting of circular delimited petechial purpura around the mouth and chin in children aged 13-15 years are presented. This form of purpura was undoubtedly due to self-mutilation by establishing of a vacuum over the skin produced by a tumbler from which the air had been partially aspirated. This is regarded as a symptom of hysterical conversion on account of stressing conditions at home or in school. Strategies for making the patient and the parents aware of the causal connection and the possibilities for intervention are mentioned.
Assuntos
Dermatoses Faciais/etiologia , Púrpura/etiologia , Automutilação , Adolescente , Dermatoses Faciais/patologia , Dermatoses Faciais/psicologia , Feminino , Humanos , Masculino , Púrpura/patologia , Púrpura/psicologia , Estresse Psicológico/complicaçõesRESUMO
We present a case of a 75-year old woman, who developed scalp necrosis as a result of giant cell arteritis in the temporal arteries. This is a very rare, but serious complication of temporal arteritis, which implies an increased risk of visual loss and other catastrophic sequelae. Healing of the ulceration was achieved after cortico-steroid therapy supplemented with split skin transplantation.
Assuntos
Arterite de Células Gigantes/complicações , Dermatoses do Couro Cabeludo/etiologia , Idoso , Feminino , Arterite de Células Gigantes/patologia , Glucocorticoides/administração & dosagem , Humanos , Necrose , Prednisolona/administração & dosagem , Couro Cabeludo/patologia , Dermatoses do Couro Cabeludo/tratamento farmacológico , Dermatoses do Couro Cabeludo/patologia , Dermatoses do Couro Cabeludo/cirurgia , Transplante de Pele , Úlcera Cutânea/tratamento farmacológico , Úlcera Cutânea/etiologia , Úlcera Cutânea/patologia , Úlcera Cutânea/cirurgiaRESUMO
Nowadays about 15% of a birth cohort develops atopic dermatitis of varying severity, while only about 3% were affected in the sixties. The pathogenesis of the disease is multifactorial, based on genetic (polygenic inheritance) and environmental factors, the latter presumably accounting for the rising incidence. Several genes of importance for the immune pathogenesis of atopic diseases, including atopic dermatitis, have been identified. Exogenous factors, for instance air humidity and colonization of the skin with Staphylococcus aureus and Pityrosporum ovale are also important in the pathogenesis. Specific allergies, for instance dust mite allergy and food allergy, may be contributory causes. Treatment is directed against the dry skin, the eczematous reaction, skin infections and potential, specific allergies. Information given to patients and parents through "eczema schools" might be an important part of therapy with focus on atopic diseases, treatment strategy and prevention.
Assuntos
Dermatite Atópica , Pré-Escolar , Dinamarca/epidemiologia , Dermatite Atópica/epidemiologia , Dermatite Atópica/genética , Dermatite Atópica/imunologia , Dermatite Atópica/microbiologia , Humanos , Lactente , Recém-NascidoRESUMO
Trichothiodystrophy is a neuroectodermal syndrome with features of a specific hair dysplasia associated with disorders in organs derived from ectoderm and neuroectoderm. The key finding is brittle hair with low sulfur content. Polarizing microscopy shows alternating dark and light bands with trichoscisis and absent or defective cuticle. Patients with trichothiodystrophy have short, sparse, dry and easily broken hair. Growth retardation and mental retardation are almost obligatory findings. The skin and the nails are very often affected; other neuroectodermal disorders are associated, but none is a constant feature. The disease is transmitted as an autosomal recessive trait.
Assuntos
Doenças do Cabelo/patologia , Cabelo/patologia , Criança , Pré-Escolar , Dinamarca , Feminino , Doenças do Cabelo/congênito , Doenças do Cabelo/genética , Humanos , Masculino , Síndrome , Turquia/etnologiaRESUMO
Cholesterol microemboli are caused by cholesterol crystals released from arteriosclerotic plaques in the major arteries. The clinical picture is illustrated by two case histories with symptoms in the form of myalgia, livedo reticularis and gangrene. The diagnoses were verified by demonstration of cholesterol crystals in the affected tissue. The pathogenesis is illustrated and, on the basis of the literature, it is emphasized that cholesterol microemboli are probably often overlooked clinically and that an increasing incidence must be anticipated on account of the increasing frequency of invasive procedures and treatments of arteriosclerotic vascular disease.
Assuntos
Colesterol , Embolia/patologia , Idoso , Arteriosclerose/complicações , Arteriosclerose/patologia , Cristalização , Embolia/etiologia , Feminino , Gangrena , Humanos , Dedos do Pé/patologiaRESUMO
A case of epididymitis developed in a 33 year old man after treatment with the anti-arrhythmic agent, amiodarone, for approximately 18 months. No signs of bacterial infection or anatomical abnormalities were found. Amiodarone as the cause of epididymitis has only previously been described on a few occasions. We stress the importance of considering this adverse effect of amiodarone therapy as a differential diagnosis in the etiology of epididymitis.
Assuntos
Amiodarona/efeitos adversos , Epididimite/induzido quimicamente , Adulto , Humanos , MasculinoRESUMO
Porphyria cutanea tarda (PCT), the most common porphyria disease, is characterized by blistering and skin fragility of sun-exposed skin. The symptoms are caused by lowered activity of uroporphyrinogen decarboxylase (URO-D) resulting in accumulation of water-soluble porphyrins in the skin. Most PCT cases are sporadic but can be familiar due to mutations in the URO-D gene located on chromosome number 1. The disease may be exacerbated by environmental factors. Iron accumulation is a characteristic finding and there is an association to hereditary haemochromatosis. Therapeutic venesection reduces the iron load and the uroporphyrins are mobilized by treatment with hydroxychloroquine. An increased risk of liver cirrhosis and hepatocellular carcinoma may presumably be reduced by early diagnosis and treatment.
Assuntos
Porfiria Cutânea Tardia , Humanos , Porfiria Cutânea Tardia/diagnóstico , Porfiria Cutânea Tardia/tratamento farmacológico , Porfiria Cutânea Tardia/patologiaRESUMO
The object of this investigation was to evaluate the suitability of unlinked anonymous HIV screening of persons visiting one of eight out of the nine Danish clinics for venereal diseases in the national HIV surveillance. Data were collected during the period July 1, 1990-March 31, 1991 and included: gender, sexual orientation, history of intravenous drug use (IVDU), syphilis testing and HIV testing. A total of 7,455 persons participated of whom 75% were tested for HIV antibodies. The HIV test activity was significantly higher among male IVDUs than homo/bisexuals, and higher among female IVDUs than heterosexuals. The overall HIV prevalence among tested individuals was 0.6%, ranging from 0.1% among heterosexual women to 5.3% among female IVDUs. A total of 81% were tested for syphilis with an overall HIV prevalence of at least 1.1%, ranging from 0.2% among heterosexuals to 9.3% among homo/bisexual men. Since the non-participation is great and the venereological clientele is very heterogeneous, using blood taken for syphilis serology from this group for unlinked anonymous HIV screening, would not be particularly important as a supplement to the Danish HIV surveillance.
Assuntos
Soropositividade para HIV/epidemiologia , Soroprevalência de HIV , Dinamarca/epidemiologia , Feminino , Humanos , Masculino , Assunção de Riscos , Comportamento Sexual , Sífilis/complicações , Sífilis/epidemiologia , Sífilis/imunologiaRESUMO
The rapid development in human genome research has resulted in a tremendous increase in our understanding of the molecular basis of many genetic skin diseases. One outstanding example of this is diseases caused by mutations in keratin genes, which comprise several disorders of the epidermis, as for example the different types of epidermolysis bullosa simplex. In this respect, the most important questions have been to 1. Define the molecular defect. 2. Unravel the pathophysiological mechanisms that lead to the characteristic phenotype and 3. Design of new therapeutic strategies. Molecular research has contributed significantly to the first two issues whereas a therapeutic break-through has yet to appear.
Assuntos
Queratinas/genética , Dermatopatias Genéticas/genética , Epidermólise Bolhosa Simples/genética , Epidermólise Bolhosa Simples/patologia , Epidermólise Bolhosa Simples/fisiopatologia , Epidermólise Bolhosa Simples/terapia , Humanos , Hiperceratose Epidermolítica/genética , Hiperceratose Epidermolítica/patologia , Hiperceratose Epidermolítica/fisiopatologia , Hiperceratose Epidermolítica/terapia , Ceratodermia Palmar e Plantar/genética , Ceratodermia Palmar e Plantar/patologia , Ceratodermia Palmar e Plantar/fisiopatologia , Ceratodermia Palmar e Plantar/terapia , Mutação , Doenças da Unha/genética , Doenças da Unha/patologia , Doenças da Unha/fisiopatologia , Doenças da Unha/terapia , Dermatopatias Genéticas/patologia , Dermatopatias Genéticas/fisiopatologia , Dermatopatias Genéticas/terapiaRESUMO
Epidermolysis bullosa simplex (EBS) is a group of autosomal dominant inherited skin disorders caused by mutations in the keratin genes K5 or K14. We examined five Danish families with EBS-Weber-Cockayne (WC) or EBS-Koebner (K) and two sporadic cases of EBS-Dowling-Meara (DM) in order to investigate the mutational spectrum and evaluate the genotype-phenotype correlation in Danish patients. Three new K14 mutations, one new and one previously described K5 mutation were identified by DNA sequence analysis. The positions of the EBS-DM mutations were consistent with previous studies, whereas the EBS-WC and EBS-K mutations were found in regions of the keratin genes not typically associated with this type of EBS mutations. In conclusion, we found a strict genotype-phenotype correlation. Furthermore, we found that the position of the mutation in the keratin gene is not the only determinant for severity of the disease; the nature of the amino acid substitution should also be considered when predicting the severity of the EBS disorder.