Tolerability to romidepsin in patients with relapsed/refractory T-cell lymphoma.

BACKGROUND: Histone deacetylase inhibitor romidepsin has demonstrated durable clinical responses and tolerability in patients with relapsed/refractory peripheral and cutaneous T-cell lymphoma (PTCL, CTCL). Selection of novel drug therapies for patients with relapsed/refractory aggressive lymphoma requires not only considerations regarding efficacy but also careful evaluation of toxicities as well as overall clinical benefit. The purpose of this analysis was to examine common adverse events (AEs) reported in pivotal trials of romidepsin in relapsed/refractory PTCL or CTCL and to more clearly define the overall AE profile in these populations. METHODS: Patients with relapsed/refractory PTCL or CTCL were treated with romidepsin at 14 mg/m(2) as a 4-hour intravenous infusion on days 1, 8, and 15 of 28-day cycles for up to 6 cycles; patients with at least stable disease could extend therapy until progressive disease or another withdrawal criterion was met. All enrolled patients who received ≥ 1 dose of romidepsin were included in the AE analyses. RESULTS: Overall, safety profiles of common AEs were similar, although patients with relapsed/refractory PTCL had more frequent hematologic toxicities and grade ≥ 3 infections. In both patient populations, the greatest incidence of grade ≥ 3 AEs and the majority of discontinuations due to AEs occurred during cycles 1-2. Early discontinuations were primarily related to infection, thrombocytopenia, or electrocardiogram abnormalities, confirming the need to closely monitor patients with poor bone marrow reserve or other comorbidities. Despite this, 28% of patients with relapsed/refractory PTCL and 36% of patients with relapsed/refractory CTCL continued on romidepsin treatment for ≥ 6 cycles. CONCLUSIONS: This study demonstrates that patients with relapsed/refractory PTCL or CTCL have similar AE profiles with romidepsin treatment, although patients with PTCL experienced more frequent and more severe hematologic toxicities and more frequent grade ≥ 3 infections. The greatest incidence of grade ≥ 3 AEs and the majority of discontinuations due to AEs occurred during treatment cycles 1-2. Extended dosing of romidepsin can be tolerated in responding patients. TRIAL REGISTRATION: NCT00426764,NCT00106431.

Freezing fingers syndrome, primary and secondary Raynaud's phenomenon: characteristic features with hand thermography.

The aim of the present study was to establish a thermographic model of healthy subjects' hands and compare it with a model of the hands of patients with freezing fingers syndrome, a group usually regarded as a healthy population. A further aim was to establish the thermographic parameters that distinguish primary Raynaud's phenomenon (RP) from secondary RP. The study was conducted on a group of 74 subjects, divided into 3 groups: patients with freezing hands symptoms (G1), those with primary RP (G2), and those with limited scleroderma (G3). In addition, 69 healthy volunteers served as a control group (G4). The most distinctive features of healthy subjects' hands are the thermal symmetry between left to right measurements (ΔT<0.5°C) and between mean temperatures of the metacarpus and digits (ΔT<0.5°C (1°C maximum)). A negative correlation was found between mean hands temperature and age of subjects in G4 (p<0.0001). All the temperatures observed in G4 subjects were significantly higher than among patients in G1, G2 and G3 (p<0.001). No significant differences were found between mean temperatures in G2 and G3. RP should be suspected when differences between mean temperatures of the metacarpus and digits are ≥to 3ºC. Moreover, we suggest that a cut-off point >1ºC is established for subjects with "freezing" symptoms.

Molecular typing of Trichophyton rubrum clinical isolates from Poland.

The aim of this study was to investigate the intraspecific diversity of Trichophyton rubrum clinical isolates. Thirty clinical isolates of T. rubrum were selected for molecular typing by PCR amplification of two tandemly repetitive elements (TRS-1 and TRS-2) of the rDNA and randomly amplified polymorphic DNA (RAPD) analysis with primers designated 1 and 6. The assignment to the species T. rubrum was achieved by nested PCR of ITS1. Five PCR types were produced from the TRS-1 and three from the TRS-2 locus. Thirteen and 23 individual profiles were obtained by RAPD, with primer 1 and 6 respectively. At the phylogenetic level, 26 (87%) isolates were allocated into four clusters, with each cluster comprising isolates of over 80% similarity. The reproducibility of TRS typing was 100%, whereas that of RAPD was 40% and 30%, when using primer 1 and 6 respectively. Neither correlation between the morphological characteristics and the TRS-1-TRS-2 or RAPD genotype nor between TRS-1-TRS-2 and RAPD genotyping was observed. Although both the TRS amplification and RAPD analysis possess the ability to discriminate between T. rubrum strains, the TRS typing method is particularly valuable as its results are much more reproducible, more easily interpreted and recorded than those generated by RAPD.

Pachydermatous eosinophilic dermatitis.

A case is presented of a female Caucasian patient with chronic peripheral blood eosinophilia and unusual skin manifestations. Within a couple of years, the patient developed multiple hyperkeratotic and hyperpigmented papules and plaques all over the body, palmoplantar keratoderma, pachydermia of acral parts of the body, and generalized pruritus. Generalized lymphadenopathy appeared. Other relevant symptoms were persistent peripheral blood hypereosinophilia and increased level of total IgE. The patient was diagnosed with a very rare condition, pachydermatous eosinophilic dermatitis, and was administered combined therapy with dapsone, oral methylprednisolone and fexophenadine. After one month of treatment, the skin changes markedly improved.

Multicentric reticulohistiocytosis with S100 protein positive staining: a case report.

Multicentric reticulohistiocytosis is a very rare systemic disease that affects skin, mucosa and joints. We reported a case of a woman with multicentric reticulohistiocytosis who presented typical skin syndromes and arthralgia. Immunohistochemical analysis showed positive staining for S100 protein, which was reported negative in the majority of previously presented cases. Other immunohistochemical markers (CD68(+), CD1a(-), lagerin (-) and complete histologic and clinical picture were specific enough to make the definitive diagnosis of multicentric reticulohistiocytosis. The patient was administered prednisone just when arthritis appeared and we believe that this therapy protected her from the development of destructive arthritis. No autoimmune disease or internal malignancy was observed during 12-month follow up.

Electrocardiographic evaluation in patients with systemic scleroderma and without clinically evident heart disease.

BACKGROUND: In patients with systemic scleroderma (SSc), clinically evident cardiac involvement is recognized to be a poor prognostic factor. The aim of the study was to evaluate electrocardiographic changes, parameters of heart rate variability (HRV), and heart rate turbulence (HRT) in patients with SSc without evident symptoms of heart disease. METHODS: A group of 27 patients with SSc were subjected to standard electrocardiography (ECG) examination and 24-hour Holter monitoring. Analysis of HRV in time and frequency domains, HRT, and echocardiography were also performed. RESULTS: Holter monitoring revealed a larger number of premature supraventricular contractions (PSVCs), as well as premature ventricular contractions (PVCs) in the patients with systemic scleroderma, as compared with the control group. Moreover, the SSc patients showed decreased parameters of time and frequency domains, as referred to the controls, especially during night hours. In four patients, abnormal HRT values were present. On echocardiography, only slight changes were found, however in five patients left ventricle diastolic dysfunction was diagnosed. CONCLUSIONS: The noninvasive electrocardiographic methods seems to be useful for detecting early heart involvement in course of SSc and could be recommended for routine used in clinical practice. Significance of HRT analysis in patients with SSc needs further elucidation.

Quality of life in patients suffering from seborrheic dermatitis: influence of age, gender and education level.

Seborrheic dermatitis is a common inflammatory skin condition occurring mostly on the face, scalp and chest. Despite its high frequency, the impact of seborrheic dermatitis on patients' quality of life (QoL) has not been studied well so far. The objectives of this study were to analyse how seborrheic dermatitis affects the patients' QoL and which socio-economic factors could modulate QoL in these patients. A total of 3000 patients with seborrheic dermatitis and/or dandruff were enrolled into the study. All participants were divided into subgroups according to gender, age and education level. A specially designed questionnaire with demographic and clinical details of patients as well as Dermatology Life Quality Index (DLQI) was completed during a patient visit in an outpatient clinic. Data were collected by local dermatologists who were instructed regarding the inclusion and exclusion criteria and the questionnaires were sent back to us upon completion. The mean DLQI score for all patients was 6.92±5.34 points. Patients with dandruff had significantly better QoL than subjects with seborrheic dermatitis (5.34±4.67 points vs. 7.73±5.3 points, respectively; P<0.001) or individuals with dandruff plus seborrheic dermatitis (7.54±5.6 points, P<0.001). In addition, women, younger patients and subjects with higher educational level were more affected than the rest of the patients. Seborrheic dermatitis had significant, negative influence on patients' QoL. Observed discrepancies between subgroups could be explained by different roles played by different patient subgroups in the society. DLQI can be successfully used for the assessment of QoL in large populational studies.

IL-6 and IL-10 promoter gene polymorphisms in psoriasis vulgaris.

Overexpression of IL-6 has been implicated in the pathology of numerous autoimmune and chronic inflammatory diseases, including psoriasis, and relative deficiency of IL-10 in psoriatic patients seems to be important in the development of this disease. The aim of this study was to investigate the association between IL-6 and IL-10 single nucleotide polymorphisms and susceptibility to psoriasis vulgaris. DNA from 78 patients with psoriasis vulgaris and 74 healthy volunteers was investigated. IL-6 promoter gene single nucleotide polymorphisms in position -174, and IL-10 single nucleotide polymorphisms in positions -1082, -819 and -592 were evaluated by polymerase chain reaction using sequence-specific primers. No significant differences were found in the polymorphisms of IL-6 and IL-10 promoter genes between patients with psoriasis and healthy controls.

IFN-gamma promoter gene polymorphism in psoriasis vulgaris.

This study was performed to investigate the association between interferon (IFN)-gamma single nucleotide polymorphism (SNP) and susceptibility for psoriasis vulgaris. DNA from 78 patients with psoriasis vulgaris (54 patients with type I psoriasis, 24 with type II psoriasis) and 74 healthy volunteers was investigated. IFN-gamma promoter gene SNP in position 874 was evaluated by polymerase chain reaction with sequence-specific primers (PCR-SSP) and the results were compared between a group of psoriatic patients, divided into early onset of psoriasis (type I) and late onset of psoriasis (type II) subgroups, and healthy control subjects. A significant difference in the genotype frequencies between psoriasis patients and healthy controls was found (p < 0.02) and no significant differences were observed analyzing subsets of psoriatic patients (gender, type of disease) also in carriage and allele frequencies. The results suggest that IFN-gamma polymorphism is associated with susceptibility to psoriasis vulgaris.

TGF-beta(1) gene polymorphism in psoriasis vulgaris.

Overexpression of TGF-beta(1) has been implicated in the pathology of many inflammatory diseases, including psoriasis. This study was performed to investigate the association between TGF-beta(1) single nucleotide polymorphism and susceptibility for psoriasis vulgaris. DNA from 78 patients with psoriasis vulgaris and 74 healthy volunteers was investigated. Polymorphism of TGF-beta(1) gene in codon 10 (T/C) and codon 25 (G/C) was evaluated by PCR-SSP and the results were compared between group of psoriatic patients, divided into early onset of psoriasis (type I) and late onset of psoriasis (type II) subgroups, and control healthy subjects. Frequencies in genotypes were similar between patients and control group (p >0.7), but between type I and type II psoriasis patients highly significant difference was found (p <0.0003). Higher frequency of CC/GG (intermediate producer) and TC/GG (high producer) was noted in the type I group, but the second high producer genotype (TT/GG) was more common in type II group. Also between type II psoriasis patients and healthy controls statistically significant difference was found (p <0.000001). In analyzing frequencies of carriage and alleles no significant differences were found. TGF-beta(1) gene polymorphism in codon 10 and 25 is not associated with susceptibility to psoriasis vulgaris, but may be important for the type of the disease.

A - 308 promoter polymorphism of tumor necrosis factor alpha gene does not associate with the susceptibility to psoriasis vulgaris. No difference either between psoriasis type I and type II patients.

BACKGROUND: Genes encoded within the MHC complex on chromosome 6 are thought to play an important role in the pathogenesis of psoriasis. A potential candidate is tumor necrosis factor alpha (TNF-alpha) gene. Psoriasis features an increased activity of the proinflammatory cytokine TNF-alpha in affected lesions. TNF-alpha promoter region contains several polymorphisms, including G/A transition at position -308, which influences transcriptional activity of TNF-alpha. This study was performed to investigate the association between TNF-alpha single nucleotide polymorphism and susceptibility for psoriasis vulgaris. MATERIAL AND METHODS: DNA from 78 patients with psoriasis vulgaris and 74 healthy volunteers with no personal and family history of psoriasis was investigated. TNF-alpha promoter gene single nucleotide polymorphism (SNP) in position 308 was evaluated by PCR-SSP. The results were compared between group of psoriatic patients, divided into early onset of psoriasis (type I) and late onset of psoriasis (type II) subgroups, and healthy subjects. RESULTS: There were no significant differences in the polymorphism of TNF-alpha promoter -308 (genotype distribution, allele frequencies) between psoriasis patients and healthy controls. Similar results were obtained analyzing subgroups of psoriasis patients (type I and type II of psoriasis) and gender groups. CONCLUSION: TNF-alpha promoter single nucleotide polymorphism (-308) is not associated with susceptibility to psoriasis vulgaris.

Factors influencing coexistence of toenail onychomycosis with tinea pedis and other dermatomycoses: a survey of 2761 patients.

OBJECTIVE: To evaluate the prevalence and factors influencing the presence of concomitant dermatomycoses in patients with toenail onychomycosis. DESIGN: Prospective study based on a specially designed questionnaire completed by dermatologists. PATIENTS: A total of 2761 patients with toenail onychomycosis. MAIN OUTCOME MEASURES: The diagnosis of fungal skin infections was confirmed by direct microscopic examination or by culture. RESULTS: In 1181 patients (42.8%) with toenail onychomycosis, concomitant fungal skin infections were noted. Tinea pedis was the most common and was found in 933 patients (33.8%). Other concomitant fungal skin infections were fingernail onychomycosis (7.4%), tinea cruris (4.2%), tinea corporis (2.1%), tinea manuum (1.6%), and tinea capitis (0.5%). The presence of concomitant fungal skin infections depended on number of involved toenails; duration of onychomycosis; sex, age, and education level; area of residence; and type of isolated fungus. CONCLUSIONS: The coexistence of toenail onychomycosis with other types of fungal skin infections is a frequent phenomenon. It could be hypothesized that infected toenails may be a site from which the fungal infections could spread to other body areas. Effective therapy for onychomycosis might therefore be essential not only to treat the lesional toenails but also to prevent spreading the infection to other sites of the skin.

Severe acute generalized exanthematous pustulosis in a pregnant woman.

A 23-year-old woman was admitted to the Department of Dermatology 4 days postpartum with multiple disseminated pustules. A week earlier, she had received 500 mg of amoxicillin with 125 mg clavulanic acid for pharyngitis. After three doses, she noticed the first pustules appear on the chest and back, and the antibiotic treatment was discontinued. Three days later, during the 37th gestational week, she delivered her second child prematurely, but in generally good condition. After delivery, her skin lesions began to spread, and the patient developed fever up to 39 degrees C (102.2 degrees F). Her medical history was significant for similar pustular lesions at age five, diagnosed as a bacterial skin infection despite negative skin cultures. Antibiotics were introduced with no clinical improvement over several months. Her skin lesions resolved after discontinuation of antibiotics. No personal or family history of psoriasis was present. On admission, generalized pustules and flaccid blisters with pus on an erythematous background were present (Figure 1). The patient complained of burning of the skin lesions and fever (38.2 degrees C [100.8 degrees F]) but was otherwise in good condition. Laboratory tests revealed leukocytosis (15,000/mL) with granulocytosis (82%) and an extremely high C-reactive protein level (323.4 mg/L; normal range, 0-7 mg/L). Bacteriologic culture of the pus was negative. The histopathology revealed a subcorneal blister filled with neutrophils and a few epidermal cells. In the dermis, a scant perivascular inflammatory cell infiltrate was noted (Figure 2). Direct immunofluorescence revealed small amounts of IgM at the dermoepidermal junction. Because of the very diffuse distribution of pustules, two doses of hydrocortisone 200 mg IV b.i.d. for 2 days was administered, followed by prednisone 40 mg q.d. with rapid tapering. Rapid improvement of skin lesions was observed and the patient's skin practically cleared within 7 days. Corticosteroids were discontinued after 14 days.

Wavelet analysis of scaling properties of gastric electrical activity.

We present a novel approach to the analysis of fluctuations in human myoelectrical gastric activity measured noninvasively from the surface of the abdomen. The time intervals between successive maxima of the wavelet transformed quasi-periodic electrogastrographic waveform define the gastric rate variability (GRV) time series. By using the method of average wavelet coefficients, the statistical fluctuations in the GRV signal in healthy individuals are determined to scale in time. Such scaling was previously found in a variety of physiological phenomena, all of which support the hypothesis that physiological dynamics utilize fractal time series. We determine the scaling index in a cohort of 17 healthy individuals to be 0.80 +/- 0.14, which compared with a set of surrogate data is found to be significant at the level P < 0.01. We also determined that the dynamical pattern, so evident in the spectrum of average wavelet coefficients of the GRV time series of healthy individuals, is significantly reduced in a cohort of systemic sclerosis patients having a scaling index 0.64 +/- 0.17. These results imply that the long-term memory in GRV time series is significantly reduced from healthy individuals to those with systemic sclerosis. Consequently, this disease degrades the complexity of the underlying gastrointestinal control system and this degradation is manifest in the loss of scaling in the GRV time series.

Serum concentrations of transforming growth factor beta 1 in patients with psoriasis vulgaris.

Psoriasis is a common chronic cutaneous disease affecting 1-3% of general population. Its pathogenesis is not fully understood, but the involvement of several cytokines has clearly been established. The aim of the present study was to evaluate serum concentrations of transforming growth factor (TGF)-beta 1 in patients with psoriasis vulgaris and to correlate these concentrations with severity of psoriasis and several other clinical parameters. Sixty patients with psoriasis and 38 healthy persons (control group) were included into the study. TGF-beta 1 was measured by enzyme-linked immunosorbent assay (ELISA) using commercially available kits. Serum concentrations of TGF-beta 1 in patients with psoriasis were significantly increased compared with the controls (42.9+/-9.9 vs. 37.7+/-6.0 ng/mL, respectively, p=0.004). Patients with more severe disease (PASI <24 points) had significantly higher serum concentration of TGF-beta 1 than those with mild psoriasis (PASI<24 points; p<0.001). Moreover, serum TGF-beta 1 concentration significantly correlated with disease severity (p=0.001). In patients with pre-existing infections of the respiratory tract, the concentrations of serum TGF-beta 1 were significantly decreased (p=0.03). Since serum concentrations of TGF-beta 1 are increased in patients with psoriasis, TGF-beta 1 might be used as a marker of psoriasis activity.

Basal cell carcinoma on the eyelids: own experience.

BACKGROUND: Basal cell carcinoma (BCC) is the most common skin malignancy. Eyelids constitute a special location of BCC because of the proximity of the eyeball. OBJECTIVE: This study was undertaken to evaluate the incidence of BCC located on the eyelids, to examine the clinical and histologic types of BCCs in this location, and to present some reconstructive techniques used in the treatment of BCC in palpebral region. METHODS: There were 330 patients with BCC retrospectively included in the study. The comparison was performed between clinical and histologic features of BCCs located on eyelids and in other locations. RESULTS AND CONCLUSIONS: Approximately 16% of all tumors were located on the eyelids. The majority of tumors were situated on the lower eyelid. Noduloulcerative clinical type was observed in 96.3% of tumors. This type was significantly more frequently found on eyelids than on trunk and extremities (p<0.00001). The histologic nodular type was the most common found on eyelids. It was significantly more common on eyelids than on trunk and extremities (p=0.002). The superficial type was significantly less frequently found on the eyelids (p<0.00001). The infiltrative type was significantly more seldom observed on the eyelids compared with other locations of head and neck region (p=0.048). Some technical aspects of reconstructive surgery of the eyelids are presented.

[Diagnostic, prophylactic and therapeutic guidelines in patients with atopic dermatitis. Position paper by the task force of the National Specialists on Dermatology, Venereology and Allergology]. / Postepowanie diagnostyczno-profilaktyczno-lecznicze w atopowym zapaleniu skóry. Konsensus grupy roboczej specjalistów krajowych ds. dermatologii i wenerologii oraz alergologii.

Treatment modalities of patients with atopic dermatitis (AD) are dependent on patient age, on the intensity of both skin symptoms and subjective signs of the disease i.e. itch and sleep disturbances, on the body surface involved with lesions, as well as on the type of sensitizing allergens. The characteristic of these allergens is crucial to start prophylaxis and to make decision about specific immunotherapy. In asymptomatic period of the disease the most important factor is to prevent dryness of the skin using emollients, which reconstruct integrity and continuity of stratum corneum. This procedure prevents penetration of air-borne allergens across damaged skin barrier into the skin. In mild AD cases, pimecrolimus (mainly in children) and corticosteroids of the lowest potency alternatively with their basis should be recommended. In moderate intensity AD either topical treatment with calcineurin inhibitors i.e. tacrolimus and pimecrolimus or topical corticosteroids from 4-5 group of American classification should be applied. In addition, PUVA/UVB phototherapy may be beneficial, as well as immunotherapy with specific airborne allergen/s. Coexisting bacterial skin infections should be treated with systemic antibiotics (macrolides, quinolones, and cephalosporins), viral herpes infection systemically using acyclovir for 5-7 days, and fungal infections applying ketoconazole orally, accompanied by topical treatment with miconazole or other antimycotics. Severe AD is an indication for the systemic use of cyclosporin A (rather than corticosteroids), and antibiotics as mentioned above. Prolonged 3-5 year specific immunotherapy is significant concern for selected cases. Sensitive skin areas such as face, orbicular skin, flexures should be treated with pimecrolimus and tacrolimus rather than with corticosteroids, however, topical corticosteroids are recommended on involved skin of the trunk and the extremities besides of flexures. While the improvement of severe AD is reached, the treatment modalities for benign and mild AD should be observed. In all AD patients with active skin lesions antihistaminic drugs of 2nd generation reactive with H1 receptor are a gold standard (or short treatment with these drugs of 1st generation to achieve a sedative effect, followed by the 2nd generation drug), as well as tranquilizers as the combined treatment. There is no reason for the use of anti-leukotriene drugs.

[Adhesion of Candida to the obturator and oral mucosa as a cause of the presence of inflammation in patients treated surgically for neoplasia]. / Adhesión de Candida al obturador y a la mucosa oral como causa de la presencia de inflamación en pacientes intervenidos quirúrgicamente por neoplasia.

The aim of the investigation was to prove the relationship between Candida species, silicone and the oral mucosa as well as its effect on mutual reinfections of the mucosa and the obturator. Twenty-five patients with post-surgical prostheses in the maxilla were examined. All the prostheses had an obturator with the external part made of Mucopren silicone manufactured by Kettenbach, Germany. The presence of Candida species was investigated by means of electron microscopy visualization of the silicone samples prior to and after disinfection. The microscopic pictures confirmed a strong adherence of Candida species to Mucopren silicone in 90% of cases, which should be considered as the primary reason of unsuccessful elimination of the fungi by means of disinfection.