Search PubMed⌕ Search

Biomedical subjects

S Jablonska

Publications and source records attributed to S Jablonska.

At least 37 records · Page 2Linked to original sources

Superficial granulomatous pyoderma gangrenosum of the face, successfully treated by ciclosporine: a long-term follow-up.

We report a case of the superficial granulomatous (vegetating) form of pyoderma gangrenosum, involving the forehead and the left temporal area in a 44-year-old woman. No association with other pathologies could be found. Lesions responded dramatically to systemic ciclosporine (5 mg/kg/day), and complete healing was reached after 6 months. Doses were tapered progressively. Treatment was discontinued after 4.5 years. Discontinuation was not followed by recurrence of the disease. Healing is maintained after another 4.5 years of follow-up.

Administration, Oral↗

Safety and efficacy of 1 year of tacrolimus ointment monotherapy in adults with atopic dermatitis. The European Tacrolimus Ointment Study Group.

OBJECTIVE: To investigate the safety and efficacy of using 0.1% tacrolimus ointment for long-term treatment of atopic dermatitis. DESIGN: Open-label, noncomparative study with 6 to 12 months of follow-up. SETTINGS: Outpatient departments in 30 study centers in 11 European countries. PATIENTS: We enrolled 316 patients aged 18 years and older with moderate to severe atopic dermatitis, 200 for 6 months and 116 for 12 months; 77.5% of patients completed the study. INTERVENTION: Twice-daily application of 0.1% tacrolimus ointment on all affected skin. Visits were scheduled on day 1; after 1, 2, and 4 weeks of treatment; and monthly thereafter. MAIN OUTCOME MEASURES: Safety assessments included monitoring of adverse events, clinical laboratory values, and tacrolimus blood concentrations. Efficacy end points included a combined score (modified Eczema Area and Severity Index) and an investigator's global assessment. RESULTS: Local irritation, adverse events such as burning sensation (47% of patients), pruritus (24% of patients), and erythema (12% of patients) were common but tended to occur only when initiating treatment. Laboratory values showed no marked changes over time. Systemic absorption was minimal, with the maximum tacrolimus blood concentration being less than 1 ng/mL in 76% of patients. All efficacy end points showed improvement. The mean (SD) modified Eczema Area and Severity Index score was 23.7 (12.6) at day 1, 13.5 (11.3) at week 1, 6.1 (9.2) at month 6, and 6.1 (8.1) at month 12. Marked or excellent improvement or clearance of disease was reported in 54%, 81%, and 86% of patients at week 1, month 6, and month 12, respectively. CONCLUSION: Up to 1 year of tacrolimus ointment use was safe and effective in patients with atopic dermatitis. Arch Dermatol. 2000;136:999-1006

Administration, Topical↗

Telomerase activity in melanocytic lesions: A potential marker of tumor biology.

Telomerase activation, being a cardinal requirement for immortalization, is a crucial step in the development of malignancy. With a view toward diagnostic and biological aspects in melanocytic neoplasia, we investigated the relative levels of telomerase activity in 72 nevi and 16 malignant melanomas by means of a modified telomeric repeat amplification protocol (TRAP) assay, including an internal amplification standard. We further compared telomerase activity with the expression of two different proliferation-specific proteins, Ki-67 and repp86, a protein expressed exclusively in the cell cycle phases S, G2, and M. Telomerase activity was associated with the overall growth fraction (Ki-67) but showed a closer correlation with the expression of repp86. Both telomerase activity and proliferation indices discriminated clearly between malignant melanomas and nevi, but not between common and dysplastic nevi. Nonetheless, a portion of nevi exhibited markedly elevated telomerase activity levels without proportionally increased proliferation. This was independent of discernible morphological changes. Clinicopathological correlations showed an association between high telomerase activity and early metastatic spread in melanomas, linking telomerase to tumor biology. Our results provide arguments in favor of an occasional progression from nevi to melanomas and imply that proliferation measurements in combination with telomerase assays may help to elicit early malignant transformation that is undetectable by conventional morphology.

Adolescent↗

A novel missense mutation (C622G) in the zinc-finger domain of the human hairless gene associated with congenital atrichia with papular lesions.

Congenital atrichia with papular lesions is a rare, recessively inherited form of hair loss characterized by a complete absence of all body hair shortly after birth. Mutations in the human ortholog of the mouse hairless (hr) gene have been implicated in the pathogenesis of this disorder. In this study, we screened, by direct sequence analysis, the hairless gene in a family of Polish descent and identified a novel missense mutation (C622G). The mutation alters the third of four invariant cysteins in the zinc-finger domain, which has high homology to the C-X-X-C-(X)17-C-X-X-C structure of the zinc-fingers of the GATA family of transcription factors. The human hairless gene encodes a putative transcription factor with restricted expression in the brain and skin, which is involved in the regulation of apoptosis during catagen remodeling in the hair cycle.

Alopecia↗

Erythema gyratum repens-like psoriasis.

A 28-year-old man was admitted to our department for investigation in 1992. He presented with a red, scaly, centrifugally spreading eruption, which had appeared in 1990, beginning on the neck and thorax, and later extending to the trunk and limbs. The cutaneous lesions, located mainly on the trunk and proximal upper limbs, were arranged in rings, with a slightly raised prominent scaling edge (Fig. 1a). The characteristic feature was the presence of rings or waves within already existing rings, whereas the central part was flattened, with the texture of normal skin. The concentric figurate lesions resembled a wood grain pattern (Fig. 1b). The clinical picture was strikingly similar to tinea imbricata; there was, however, no itching, and repeated mycologic studies did not disclose Trichophyton concentricum. The histology was not characteristic. The epidermis, which was slightly edematous, was covered with a heavy crust. In the dermis, a sparse inflammatory infiltrate, somewhat more pronounced in the subpapillary areas, was composed of lymphocytes with some eosinophils. Periodic acid-Schiff (PAS) and other stains for mycotic infection were negative. The general condition was not affected and laboratory studies did not show any abnormalities, except for low serum protein (5.1 g/L) and decreased gamma globulins (10.5%). Cell-mediated immunity was preserved. Immunofluorescence studies (direct and indirect) were negative. In spite of repeatedly negative mycotic examinations and due to the striking similarity to tinea imbricata, we applied various antimycotic therapies (terbinafine, itraconazole), with no effect. The figurate pattern, with normal skin in between, altered from day to day, while new concentric rings appeared within the cleared skin. The migrating rate was about 2-3 cm per 2 weeks. The patient had undergone a thorough search for internal malignancy. During the follow-up period of 1992-98, cutaneous involvement slowly became almost generalized (1996), and the confluent lesions formed large plaques, but still with pronounced concentric rings. Transitional blood eosinophilia (27% in 1993 and 11% in 1996) regressed with no therapy. Since 1995, antibodies to HBs and HBc have been present with no clinical symptoms of liver disease. The blood proteins increased to 7.0 g/L, and gamma globulins to 17.2% (normal). The histology, studied repeatedly, started to display some signs of psoriasis from 1996 and, in 1998, was already consistent with the disease (Fig. 2). RE-PUVA (0.8 mg/kg acitretin and UVA 0.8 J/cm2 ) was applied for 2 weeks before the patient interrupted the therapy. In spite of this, there was further improvement and, in 1999, the patient was almost free of lesions with some abortive rings left. From time to time, single vesicles appeared within the elevated borders of the rings. The histology of such vesicles was consistent with abortive pustular psoriasis (Fig. 3).

Adult↗

Communication: papillomavirus DNA in basal cell carcinomas of immunocompetent patients: an accidental association?TITLE.

DNA of human papillomaviruses has frequently been detected in nonmelanoma skin cancers, raising the question of a possible causal contribution of these tumor viruses to skin carcinogenesis. Basal cell carcinomas are the most common nonmelanoma skin cancers; however, so far they are only poorly analyzed with regard to human papillomavirus infection. We searched for human papillomavirus-DNA in 69 biopsies from 61 immunocompetent basal cell carcinoma patients from two geographic locations in Europe using six different polymerase chain reaction primer systems. We could demonstrate human papillomavirus-DNA in 43.5% of the tested tumors. Human papillomavirus positivity did not seem to correlate with the duration of disease or patients' age. The vast majority of virus types in the biopsies belonged to the group of epidermodysplasia verruciformis-associated human papillomavirus. Of 31 sample pairs tested for human papillomavirus-DNA in tumors as well as in perilesional healthy skin, seven carried viral sequences in lesional and healthy skin and three only in the basal cell carcinoma. Six of the seven human papillomavirus-positive basal cell carcinoma/healthy skin pairs contained identical human papillomavirus types in tumors and histologically normal tissue. Forty basal cell carcinoma patients were additionally analyzed for IgG antibodies against virus-like particles of three representative epidermodysplasia verruciformis-human papillomavirus types: 8, 15, and 36. No statistically significant differences could be detected between human papillomavirus antibody prevalences of basal cell carcinoma patients and of dermatologically healthy individuals. Moreover, serologic findings did not correlate with the detection of specific human papillomavirus types in tumors. Our results seem to suggest that the occurrence of human papillomavirus-DNA in basal cell carcinoma does not reflect a major etiologic role of human papillomavirus in this cancer.

Aged↗

Antibodies to human papillomavirus type 5 are generated in epidermal repair processes.

We reported previously that patients with psoriasis harbored at a very high frequency DNA sequences of the oncogenic human papillomavirus type 5 (HPV5) associated with epidermodysplasia verruciformis. Moreover anti-HPV5 antibodies were detected in 25% of the cases. Our aim was to find out whether keratinocyte hyperproliferation and/or autoimmunity could be responsible for HPV5 expression in psoriasis. We found that epidermal repair in patients with extensive second degree burns (n = 19) is frequently associated with the generation of anti-HPV5 antibodies. In patients with autoimmune bullous diseases (n = 118), a condition in which keratinocyte proliferation is involved in repair mechanisms, the prevalence of anti-HPV5 antibodies (15%-25%) was similar to that reported in psoriasis and significantly higher than that (5%) observed in individuals with no known history of human papillomavirus infection (n = 119). A high detection rate (57.9%) of HPV5 DNA was observed in patients with bullous diseases. Anti-HPV5 antibodies were found in patients with autoimmune connective tissue disorders with cutaneous involvement (n = 40) as frequently as in patients with bullous diseases. HPV5 DNA was detected in one of the 10 patients studied. In contrast, the prevalence of anti-HPV5 antibodies in patients with autoimmune neurological disorders (n = 47) and in patients with common warts (n = 28) or invasive carcinomas of the skin (n = 40) was as low as in the general population. It is worth stressing that a similar prevalence of antibodies against HPV1 was found in all groups studied. Our data strongly suggest that extensive keratinocyte proliferation is a major factor for the generation of anti-HPV5 antibodies and that autoimmunity may contribute to this phenomenon. It remains to be determined whether HPV5 and other human papillomavirus genotypes associated with epidermodysplasia verruciformis contribute to the hyperproliferation of keratinocytes occurring in epidermal repair and in psoriasis.

Antibodies, Viral↗

Congenital fascial dystrophy: abnormal composition of the fascia.

BACKGROUND: A scleroderma-like genetic disease, congenital fascial dystrophy, probably a variant of stiff skin syndrome described by Esterly and McKusick, was found to be related to genetically determined fascial abnormalities. Our previous electronmicroscopic study disclosed as a main pathologic finding presence of giant amianthoid-like collagen fibrils in the affected fascia. OBJECTIVE: The aim of the present study was to disclose the collagen abnormalities in the affected and control fascias and in the patient's fibroblast cultures derived from the skin and fascia. METHODS: The study was performed by histologic, immunohistochemical, and electronmicroscopic techniques. Immunohistochemical studies were done with the use of monoclonal antibodies: anti-collagens I, III, IV, and VI, anti-laminin, anti-fibronectin, anti-desmin, anti-spectrin, anti-vimentin, anti-laminin, anti-heparan sulfate, and anti-alpha-actinin. Electronmicroscopic studies were performed on the fascia sections and on cultured fibroblasts. RESULTS: The main abnormality leading to giant collagen fibril formation was presence of myofibroblasts, absence of collagen III, and overproduction of spectrin and collagen type VI, mainly its filamentous form. CONCLUSION: Our findings suggest that the abnormal composition of the fascia could depend on modulation of fibroblasts into myofibroblasts capable of producing spectrin and long-spacing collagen.

Child↗

Desmoglein 1 and desmoglein 3 are the target autoantigens in herpetiform pemphigus.

OBJECTIVE: To determine the cell surface autoimmune target of herpetiform pemphigus (HP). DESIGN: Serum samples of HP were examined by immunoblot studies with human epidermal extracts, enzyme-linked immunosorbent assay with baculovirus-expressed recombinant desmoglein (rDsg) 1 and rDsg3, and immunoadsorption assay with rDsg. PATIENTS: Twenty serum samples were obtained from patients with HP who have typical clinical and histological features. All serum samples showed positive staining against keratinocyte cell surfaces by indirect immunofluorescence studies with healthy human skin. RESULTS: Immunoblot results showed that of 17 HP serum samples, only 5 reacted with a 160-kd band and 1 reacted with a 130-kd band. Results of enzyme-linked immunosorbent assays with rDsg1 and rDsg3 demonstrated that of 20 HP serum samples, 16 were positive against Dsg1 and 4 were positive against Dsg3. No serum samples reacted with both. Furthermore, in 19 of 20 HP serum samples, immunoreactivity against keratinocyte cell surfaces was completely removed by preincubation with rDsg1 and rDsg3 as shown by indirect immunofluorescence, excluding a possibility that these HP sera contain autoantibodies against other cell surface molecules. CONCLUSIONS: Dsg1 and Dsg3 are the major cell surface target molecules of HP, suggesting that most cases of HP are clinical variants of pemphigus foliaceus and that the rest might be variants of pemphigus vulgaris.

Autoantigens↗

Scleroderma overlap syndromes.

The most common scleroderma overlap syndromes are mixed connective tissue disease (MCTD), scleromyositis and synthetase syndrome. There is controversy concerning MCTD as a separate entity due to heterogeneous clinical manifestations, not infrequent transformation into definite CTD and various classification criteria. Our study of 94 adult patients and 20 children, classified according to the criteria of Alarcon-Segovia, and especially a 5, 9-year follow-up showed transformation into SLE or SSc in over 20% of patients, less frequently than reported by others, whereas over half of the cases remained undifferentiated CTD. In several cases ARA criteria for both SSc and SLE were fulfilled, and there is no consensus whether such cases should be recognized as coexistence of both definite diseases or as MCTD. High titers of U1 RNP antibodies to 70 kD epitope were invariably present, whereas, by transformation into distinctive CTD there appeared, in addition, antibodies characteristic of these CTD. Of 108 cases positive for PM-Scl antibody, 83% were associated with scleromyositis. This scleroderma overlap syndrome differed from MCTD by coexistent features of dermatomyositis (myalgia, myositis, Gottron sign, heliotrope rash, calcinosis) with no component of SLE, characteristic of MCTD. The course was also chronic and rather benign, as in MCTD, and all cases responded to low or moderate doses of corticosteroids. A not infrequent complication was deforming arthritis of the hands. Our immunogenetic study showed an association of cases positive for PM-Scl antibody with HLA-DQA1x0501 alleles in 100% and with HLA-DRB1x0301 in 94% of cases. Synthetase syndrome, associated with anti-histidyl-tRNA synthetase antibodies, studied in 29 patients with myositis and interstitial lung disease (ILD), only in single cases had scleroderma-like features. These cases differed from SSc by acute onset with fever, and by response to moderate doses of corticosteroids. We also studied overlap of localized scleroderma with other CTD: 21 cases of progressive facial hemiatrophy and linear scleroderma, and 55 (39.5%) of atrophoderma Pasini-Pierini (APP) and morphea. As in other autoimmune disorders, two or more connective tissue diseases (CTD) may develop concurrently or sequentially in the same patient. In such overlap syndromes ARA criteria must be fulfilled for each of the disease, and the clinical presentation has features of both. However more frequently overlap syndromes only combine some manifestations of more than one CTD, and present a highly heterogeneous group of disorders with prevailing clinical features of SSc.

Adolescent↗

Paraneoplastic pemphigus associated with Castleman tumor, myasthenia gravis and bronchiolitis obliterans.

BACKGROUND: Cases of paraneoplastic pemphigus (PNP) have been reported associated with various lymphoproliferative malignancies and benign Castleman tumors, with the most severe course and fatal outcome seen in patients with bronchiolitis obliterans. OBJECTIVE: The aim was to establish immunologic associations by coexistence of Castleman tumor, myasthenia gravis, and bronchiolitis obliterans and to evaluate the treatment modalities. METHODS: Clinical studies included computed tomography of the mediastinum, computed tomography and magnetic resonance imaging of the abdominal cavity, and quantitative electromyography. Direct and indirect immunofluorescence on various substrates, immunoblot analysis, immunoprecipitation, and specific enzyme-linked immunosorbent assay using recombinant desmogleins (Dsg) were performed as immunologic assays. RESULTS: Direct and indirect immunofluorescence including rat bladder showed intercellular antibodies. Immunoblotting disclosed antibodies to envoplakin (210 kd protein) and periplakin (190 kd protein); in addition, immunoprecipitation detected antibodies to desmoplakin I (250 kd protein). Antibodies to Dsg3 (pemphigus vulgaris antigen) were detected by specific enzyme-linked immunosorbent assay. Myasthenia gravis was controlled by drugs; however, mucocutaneous changes were not fully responsive to corticosteroids and cyclophosphamide pulses, cyclosporine, and intravenous immunoglobulins. The surgical removal of Castleman tumor did not change the course of the disease. The fatal outcome was the result of bronchiolitis obliterans that occurred after the surgery and was only transitionally controlled by plasmapheresis. CONCLUSION: This is the first case of paraneoplastic pemphigus associated with Castleman tumor, myasthenia gravis, and bronchiolitis obliterans. Despite a benign character of the tumor the patient died, as do all patients with bronchiolitis obliterans. Massive plasmapheresis has only a transient effect. We confirmed the presence of antibodies to Dsg 3, in addition to the set of specific paraneoplastic pemphigus antibodies against various proteins of plakin family.

Adult↗

Double-blind, multicentre analysis of the efficacy of borage oil in patients with atopic eczema.

Although gamma-linolenic acid (GLA) has been shown to correct deficiencies in skin lipids associated with reduced delta-6-desaturase activity which should result in improvement of dysregulation of inflammation and immunity in atopic eczema, clinical studies with evening primrose oil containing 10% GLA have yielded contradictory results. We have therefore examined the effect of a higher percentage (at least 23%) GLA-containing borage oil in adults with stable atopic eczema of moderate severity in a double-blind, multicentre study. One hundred and sixty patients were randomized to take daily either 500 mg of borage oil-containing capsules or the bland lipid miglyol as a placebo over a 24-week period. Use of topical diflucortolone-21-valerate cream was allowed as rescue medication, with the amount used until response being defined as primary, and clinical improvement as secondary efficacy criteria. Although several clinical symptoms improved compared with placebo, the overall response to borage oil did not reach statistical significance. Significant differences in favour of borage oil were, however, observed in a subgroup excluding patients who failed to show increased erythrocyte dihomo-gamma-linolenic acid levels and in whom adherence to inclusion criteria and the study protocol were questionable. GLA metabolites increased in borage oil-treated patients only, and serum IgE showed a trend to decrease on overall and subgroup analysis. No substance-related adverse effects were observed. This study shows no overall efficacy of GLA-containing borage oil in atopic eczema, with steroid use being the primary response parameter, although it suggests that a subgroup of patients may benefit from this well-tolerated treatment.

8,11,14-Eicosatrienoic Acid↗