Search

Background: Dyskeratotic cells in Darier's disease (DD) are thought to represent apoptotic keratinocytes. Bcl-2 gene family proteins play a major role in the regulation of apoptosis of epidermal keratinocytes and reveal pleiotropic interactions with intracellular Ca2+ homeostasis. The latter is impaired in DD because of mutations of ATP2A2 gene that encodes the type 2 isoforms of the sarcoplasmic/endoplasmic reticulum (ER) Ca++ ATPase 2 (SERCA2) pump., Methods: The expression of Bcl-2, Bax, and Bcl-x(L) proteins was investigated in the epidermis of 11 patients with DD and of 11 sex- and age-matched healthy controls by immunohistochemistry., Results: The expression of Bcl-2 and Bcl-xL was clearly reduced in the lesional epidermis of the patients, as compared with the normal epidermis of healthy controls, whereas the expression of Bax remained unaltered., Conclusions: The alterations in the expression of Bcl-2 gene family proteins could be a crucial event for the activation of the apoptotic process in the lesional epidermis of DD patients and for the occurrence of the characteristic dyskeratotic keratinocytes. The question as to whether these alterations are associated with the ER Ca2+ depletion in DD or represent secondary phenomena unrelated to the genetic defect of this genodermatosis remains to be elucidated.

Accumulating evidence suggests the involvement of neurogenic inflammation in the pathogenesis of psoriasis. Moreover, the concomitant occurrence of peripheral neuropathy has been reported in several psoriatic patients. Thus, the aim of the present study was to answer the question whether an impairment of peripheral large nerve fibre function may exist in psoriasis. Thirty-two patients with severe and generalized chronic plaque psoriasis and 32 sex- and age-matched healthy controls were evaluated by detailed clinical neurological and standard neurophysiological examination. The latter included motor nerve conduction study of one nerve in the upper and one in the lower extremities and sensory nerve conduction study of one nerve in the upper and two in the lower extremities. Neurological examination failed to demonstrate any clinical evidence of large fibre neuropathy. Furthermore, all values of the examined neurophysiological parameters were within normal limits; comparisons of the corresponding mean values in the patient and the control group showed no statistically significant differences. These findings demonstrate no measurable abnormalities of the peripheral large nerve fibres in psoriatic patients and therefore an association of psoriasis with peripheral large fibre neuropathy cannot be suggested.

Down syndrome, a common chromosome aneuploidy, has been associated with an increased incidence of cutaneous disorders. The simultaneous occurrence with Ehlers-Danlos syndrome (EDS) is rare. We report here the clinical case of a 19-year-old female patient with Down syndrome (trisomy 21) who was also affected by EDS type IV. She died from spontaneous bleeding due to rupture of nonaneurysmal abdominal aorta. Since the affected chromosomes in these two syndromes are different (21 and 2, respectively), the concomitant appearance of Down syndrome and EDS type IV in our patient, though clinically intriguing, most likely represents a co-occurrence. However, the possibility that a presently unknown link may exist between these syndromes cannot be ruled out.

We report a 72-year-old male patient with a 47,XYY/45,X/46,XY mosaicism associated with short stature, exostoses, type E brachydactyly, gynecomastia, cryptorchidism, mild mental retardation, and a paranoid personality and conversion disorder. Since his prevalent cell line was 47,XYY (about 75%), our patient could be karyotypically classified as a case of 47,XYY syndrome. In view of the striking similarity of the clinical features of this case and those of a XYY case previously reported by Ikegawa et al (1992), it seems reasonable to suggest that these patients are representatives of a novel syndrome with a XYY karyotype.

The case of a 35-year-old man is reported who developed a spontaneous anaphylactic shock as the only clinical manifestation of hepatic hydatidosis. Dermatologists should consider asymptomatic hydatid disease in the differential diagnosis of anaphylactic reactions, particularly in patients from regions in which echinococcosis is endemic.

The purpose of this study was to investigate the carbohydrate residue composition of cell surface in the developing epidermis and to define the chronological sequence of its alterations in human fetuses from the 10th to the 20th weeks of gestation and at the 23rd week of gestation, using a panel of six biotinylated lectins: Concanavalin A, Ulex europaeus agglutinin-I, Ricinus communis agglutinin-I, Peanut agglutinin, Wheat germ agglutinin, and Dolichos biflorus agglutinin. Distinct qualitative and quantitative alterations in the expression of cell surface carbohydrate residues were found during epidermal morphogenesis prior to keratinization (10th to 20th weeks). At the 23rd week of gestation, the already keratinized fetal human epidermis revealed a pattern of cell surface glycosylation very similar to that of the adult human epidermis. Further studies are now warranted to answer the question regarding whether the glycosylation pattern in the developing human epidermis is disturbed in fetuses with genodermatoses and whether these disturbances might be important for prenatally diagnosing the latter.

Heat shock protein 27 (Hsp27), apart from its protective function in response to stress, is implicated in the regulation of cell growth, differentiation and apoptosis. Data on the expression of Hsp27 in the developing human epidermis are sparse and partially conflicting. Thus, the purpose of the present study was to investigate Hsp27 expression during the morphogenesis of human epidermis. Skin biopsies and dispase-separated epidermal sheets obtained from 7 human embryos (7 and 8 weeks estimated gestational age, EGA), from 79 human fetuses (9-23 weeks EGA) and from 10 healthy adult volunteers were investigated by immunohistochemistry and Western blotting, respectively. The earliest detection of Hsp27 expression was found by immunohistochemistry at the 12th week EGA (basal and intermediate layer) and by Western blotting at the 9th week EGA. From the 16th to the 23rd week EGA immunoreactivity was not detectable in the basal layer, whereas in the overlying layers it revealed a differentiation-related pattern. The simultaneous onset of epidermal stratification and Hsp27 expression (9th week EGA) and the alterations of the latter in the subsequent stages of development, suggest that this stress protein may be involved in the molecular events underlying human epidermal morphogenesis.

Objective: The objective of this study is to identify early patients who are at-risk for major depression (MD) induced by interferon-alpha (IFN-alpha) and evaluate the response of depressive symptoms to antidepressants., Methods: Thirty-six consecutive patients were treated with IFN-alpha. Psychiatric evaluations were performed prior to, and at 1 and 2 months after onset of therapy and upon completion of the study. Diagnoses were made according to DSM-IV criteria, and the severity of depressive symptoms was determined by the Hamilton Depression Rating Scale score (HDRSS)., Results: Of the 36 patients studied, 7 (19%) had MD before IFN-alpha treatment, 6 of which manifested a worsening of the depressive symptomatology during treatment. Of the remaining 29 patients, 9 (31%) developed MD during treatment. The median time required for the appearance or worsening of the depressive symptoms was 15 days (range 7-25). The median HDRSS before IFN-alpha in the 36 patients was 3 (range 1-20), whereas after 1 month of therapy, it was 10 (range 1-24; P=.000004). There was a strong positive correlation in the HDRSS before and 1 month after the initiation of treatment (r=.863). Of the 14 patients with a HDRSS of 1-2 before IFN-alpha treatment, only 1 (7%) developed MD, whereas of the 15 patients with a score >3, 8 (53%) developed MD. Antidepressants resulted in a decrease of the HDRSS to the IFN-alpha pretreatment values., Conclusion: One third of those treated with IFN-alpha developed MD. The HDRSS before treatment reveals the high- and low-risk patients for developing MD. Psychiatric evaluation should be performed prior to IFN-alpha treatment.

We present here the course of clinical response of a 53-year-old haemodialysed Fabry patient who received recombinant human alpha-galactosidase A at a dose of 1 mg/kg every other week over a period of 1 year. The therapy was well tolerated by the patient, who revealed an impressive favourable cutaneous, gastrointestinal, neurological and psychiatric response and a dramatic improvement in his quality of life, but no improvement in cardiac and renal function.

A 57-year-old female patient with widespread chronic plaque psoriasis and a 32-year-old male patient with severe oral lichen planus are reported, who developed sensory symptoms in the extremities 3 and 4 months after the onset of oral acitretin therapy, respectively. Both patients showed clinical and electrophysiological evidence of a sensory peripheral neuropathy, which completely resolved 2 and 2.5 years after discontinuation of oral acitretin administration, respectively., (Copyright 2003 S. Karger AG, Basel)

A panel of six biotinylated lectins was applied in order to study the composition and distribution of plasma membrane carbohydrate residues in 83 primary cutaneous melanomas (MMs) and in 85 melanocytic nevi (MN) with the avidin-biotin peroxidase technique. No clear-cut differences between MN and MMs were observed with regard to the staining with lectins. In MN and MMs derived from different patients, the lectin-binding pattern was variable and heterogeneous even within the individual nevi or melanomas. It seems reasonable, therefore, to assume that the lectin-binding pattern cannot be regarded as a reliable histochemical marker for the differentiation of MN from MMs. Moreover, because the pattern reveals no statistically significant correlation with the thickness or the depth of invasion of MM, it seems to lack prognostic significance.

Objectives: To evaluate the therapeutic efficacy and safety of systemic recombinant interferon alpha-2a (IFN-alpha) in patients with Behcet's disease (BD) and to determine the incidence of episodes in complete responders during the one-year pretreatment period and follow-up., Design: An open clinical study., Setting: Departments of Dermatology and Ophthalmology, University of Patras, Greece and Department of Dermatology, Heinrich-Heine University of Düsseldorf, Germany., Subjects: Twelve patients (aged 23-52 years) with active BD who had previously been unsuccessfully treated with systemic steroids and/or immunosuppressives., Interventions: IFN-alpha was administered subcutaneously at a dose of 6 X 10(6) IU per day 3 times per week for 2 months., Main Outcome Measures: Change of area or number of mucocutaneous lesions, grading score for thrombophlebitis and ocular inflammation, haematological and biochemical parameters and number of episodes during the pretreatment period and the follow-up. Evaluation of IFN-alpha side effects., Results: Nine patients (75.0%) revealed a complete remission, two (16.6%) a partial remission and one patient (8.3%) showed no response. During the follow-up in five out of the nine complete responders (55.5%) no episodes of BD were seen, whereas, the other four patients (44.5%) had 1-2 episodes, as compared to 5-8 and 5-12 episodes, respectively, during the pretreatment period. An influenza-like syndrome (fever, nausea and myalgias) appeared during the early phase of therapy in all (but one) patients. No patient had to discontinue IFN-alpha because of intolerance., Conclusions: Subcutaneous human recombinant interferon alpha-2a appears to be an effective and fairly well tolerated therapy for BD.

Using a new computerized methodological procedure a separate analysis and a quantitative determination of the viscous and elastic parameters of the scalp hair shaft were performed in 37 neonates of both sexes with a gestational age of 28-29 weeks (n = 16) and 39-40 weeks (n = 21), respectively. A statistically significant (p < 0.001) decrease in the values of modulus of elasticity (E alpha) was found in the hair shaft of premature neonates, as compared to the full-term ones, whereas the values of post yield slope (E beta) and of SDIS/SSTOR (viscous parameter) did not significantly differ in the two groups. The decrease in modulus of elasticity in the hair shaft of premature neonates may be interpreted in terms of an insufficient number of disulphide bonds between the alpha-helical keratin units of the hair cortex or of a disordered arrangement of microfibrils within the matrix. Further studies are now warranted to determine the pattern of mechanical parameters of the scalp hair shaft in large numbers of newborn infants of different gestational ages and to answer the question as to whether this pattern might be useful in the accurate postnatal assessment of fetal maturation.

The histological similarities of seborrhoeic keratoses and common warts led to the investigation of the possible occurrence of human papillomavirus DNA (HPV-DNA) in a large number of nongenital seborrhoeic keratoses using the in situ hybridization technique. All specimens derived from normal skin (n = 173) were negative for the applied HPV-DNA probe, whereas the HPV genome was detected in 34 of 173 seborrhoeic keratosis specimens (19.65%). Of 34 HPV-positive specimens, 15 contained types 6/11 and 14 types 31/33/35, and 5 showed no positive reaction to the applied types. These results suggest that a considerable percentage of nongenital seborrhoeic keratoses may be related to an HPV infection.

A patient with a Buschke-Loewenstein tumour associated with human papillomavirus type 6/11 is reported. He was intralesionally treated with human recombinant alpha-2b interferon (9 x 10(6) IU/day) three times weekly. The tumour completely disappeared within 5 months of continuous treatment which was well tolerated. Sixteen months after completion of therapy the patient remains well and free of disease.

Adult female Wistar rats (n = 48) divided into four groups of 12 were treated orally with 3 mg/kg per day thalidomide, a 0.05% hexachlorobenzene (HCB)--containing diet, with both drugs together and with the vehicles (controls) over periods of 10 and 60 days. The protein and P450 contents and the activities of aminopyrine-N-demethylase (ADM) and 7-ethoxyresorufin-O-deethylase (7-ERO-D) were determined in the liver microsomes. The activity of 7-ERO-D was also determined in the skin microsomes and total porphyrins were measured in the urine of the animals. Thalidomide increased the hepatic P450 content, caused distinct changes in the activities of the hepatic and cutaneous microsomal isozymes, modified their induction by HCB and inhibited the porphyrogenic activity of HCB. These findings indicate an interaction between thalidomide and HCB with regard to their effects on the P450 isozymes and the metabolism of porphyrins.