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Biomedical subjects

T Ruzicka

Publications and source records attributed to T Ruzicka.

At least 127 records · Page 7Linked to original sources

Phototesting in lupus erythematosus tumidus--review of 60 patients.

Photosensitivity is an important characteristic feature of several forms of lupus erythematosus (LE), and induction of skin lesions by UV-A and UV-B irradiation has been proved to be an optimal model for evaluating light sensitivity in patients with this disease. Because lupus erythematosus tumidus (LET) has rarely been documented in the literature and is often difficult to differentiate from other photodermatoses such as polymorphous light eruption, we performed photoprovocation tests in 60 patients with LET according to a standardized protocol. Areas of uninvolved skin on the upper back were irradiated with single doses of UV-A (100 J/cm2) and/or UV-B (1.5 minimal erythema dose) daily for three consecutive days. Interestingly, patients with LET are more photosensitive than those with subacute cutaneous lupus erythematosus, and in our study experimental phototesting revealed characteristic skin lesions in 43 patients (72%). Because of the latency period in developing positive phototest reactions, it might be difficult for these patients to link sun exposure with their skin lesions. Furthermore, our data revealed a positive correlation of antinuclear antibodies and positive provocative phototest reactions in these patients as seen for other forms of LE. In conclusion, the high incidence of positive phototest reactions in correlation with the clinical findings, history of photosensitivity and antinuclear antibodies enable the classification of LET as the most photosensitive type of LE.

Diagnosis, Differential↗

Aminolevulinic acid (Levulan) in photodynamic therapy of actinic keratoses.

The role of photodynamic therapy (PDT) in the treatment of in situ neoplasias and tumors of the skin is steadily increasing. Its principles of photodynamic action include an intratumoral enriched photosensitizer and light activation. Aminolevulinic acid (ALA) has demonstrated highest efficacy in topical PDT, and has become the most clinically useful. For actinic (solar) keratoses, topical ALA-PDT using Levulan Kerastick (20% topical solution, DUSA Pharmaceuticals) is already postulated to be the treatment of choice. In December 1999, the US FDA approved this topical product for the treatment of actinic keratoses. Levulan is well tolerated and leads to excellent cosmetic results with only minor side effects.

Administration, Topical↗

Up-regulation of macrophage inflammatory protein-3 alpha/CCL20 and CC chemokine receptor 6 in psoriasis.

Autoimmunity plays a key role in the immunopathogenesis of psoriasis; however, little is known about the recruitment of pathogenic cells to skin lesions. We report here that the CC chemokine, macrophage inflammatory protein-3 alpha, recently renamed CCL20, and its receptor CCR6 are markedly up-regulated in psoriasis. CCL20-expressing keratinocytes colocalize with skin-infiltrating T cells in lesional psoriatic skin. PBMCs derived from psoriatic patients show significantly increased CCR6 mRNA levels. Moreover, skin-homing CLA+ memory T cells express high levels of surface CCR6. Furthermore, the expression of CCR6 mRNA is 100- to 1000-fold higher on sorted CLA+ memory T cells than other chemokine receptors, including CXCR1, CXCR2, CXCR3, CCR2, CCR3, and CCR5. In vitro, CCL20 attracted skin-homing CLA+ T cells of both normal and psoriatic donors; however, psoriatic lymphocytes responded to lower concentrations of chemokine and showed higher chemotactic responses. Using ELISA as well as real-time quantitative PCR, we show that cultured primary keratinocytes, dermal fibroblasts, and dermal microvascular endothelial and dendritic cells are major sources of CCL20, and that the expression of this chemokine can be induced by proinflammatory mediators such as TNF-alpha/IL-1 beta, CD40 ligand, IFN-gamma, or IL-17. Taken together, these findings strongly suggest that CCL20/CCR6 may play a role in the recruitment of T cells to lesional psoriatic skin.

Antigens, Differentiation, T-Lymphocyte↗

Cutting edge: the orphan chemokine receptor G protein-coupled receptor-2 (GPR-2, CCR10) binds the skin-associated chemokine CCL27 (CTACK/ALP/ILC).

We recently reported the identification of a chemokine (CTACK), which has been renamed CCL27 according to a new systematic chemokine nomenclature. We report that CCL27 binds the previously orphan chemokine receptor GPR-2, as detected by calcium flux and chemotactic responses of GPR-2 transfectants. We renamed this receptor CCR10. Because of the skin-associated expression pattern of CCL27, we focused on the expression of CCL27 and CCR10 in normal skin compared with inflammatory and autoimmune skin diseases. CCL27 is constitutively produced by keratinocytes but can also be induced upon stimulation with TNF-alpha and IL-1beta. CCR10 is not expressed by keratinocytes and is instead expressed by melanocytes, dermal fibroblasts, and dermal microvascular endothelial cells. CCR10 was also detected in T cells as well as in skin-derived Langerhans cells. Taken together, these observations suggest a role for this novel ligand/receptor pair in both skin homeostasis as well as a potential role in inflammatory responses.

Amino Acid Sequence↗

Enzyme plus light therapy to repair DNA damage in ultraviolet-B-irradiated human skin.

Ultraviolet-B (UVB) (290-320 nm) radiation-induced cyclobutane pyrimidine dimers within the DNA of epidermal cells are detrimental to human health by causing mutations and immunosuppressive effects that presumably contribute to photocarcinogenesis. Conventional photoprotection by sunscreens is exclusively prophylactic in nature and of no value once DNA damage has occurred. In this paper, we have therefore assessed whether it is possible to repair UVB radiation-induced DNA damage through topical application of the DNA-repair enzyme photolyase, derived from Anacystis nidulans, that specifically converts cyclobutane dimers into their original DNA structure after exposure to photoreactivating light. When a dose of UVB radiation sufficient to induce erythema was administered to the skin of healthy subjects, significant numbers of dimers were formed within epidermal cells. Topical application of photolyase-containing liposomes to UVB-irradiated skin and subsequent exposure to photoreactivating light decreased the number of UVB radiation-induced dimers by 40-45%. No reduction was observed if the liposomes were not filled with photolyase or if photoreactivating exposure preceded the application of filled liposomes. The UVB dose administered resulted in suppression of intercellular adhesion molecule-1 (ICAM-1), a molecule required for immunity and inflammatory events in the epidermis. In addition, in subjects hypersensitive to nickel sulfate, elicitation of the hypersensitivity reaction in irradiated skin areas was prevented. Photolyase-induced dimer repair completely prevented these UVB radiation-induced immunosuppressive effects as well as erythema and sunburn-cell formation. These studies demonstrate that topical application of photolyase is effective in dimer reversal and thereby leads to immunoprotection.

Adult↗

Lupus erythematosus tumidus--a neglected subset of cutaneous Lupus erythematosus: report of 40 cases.

BACKGROUND: Lupus erythematosus tumidus (LET) is characterized clinically by erythematous, succulent, edematous, nonscarring plaques in sun-exposed areas. Results of histological examination show perivascular and periadnexal lymphocytic infiltration and interstitial mucin deposition. The main differential diagnoses are polymorphous light eruption, Jessner's lymphocytic infiltration of the skin, reticular erythematous mucinosis, and pseudolymphoma. Since its first description in 1930, LET has been documented rarely in the literature, and its clinical importance has not been fully appreciated. OBSERVATIONS: We characterized 40 patients with clinical and histological features of LET observed at our department from 1984 through 1998. The onset of the disease clustered in summer because of sun exposure, and 28 (70%) of the patients showed a remarkable photosensitivity confirmed by results of provocative phototesting. A complete resolution of the skin lesions was seen after systemic therapy with antimalarials and, in some cases, with local corticosteroids or spontaneously without any treatment. In 4 (10%) of the patients, antinuclear antibodies were detected; however, there was no evidence of underlying systemic involvement in any of the patients. CONCLUSIONS: Our data constitute the largest number of patients with LET collected until now. The clinical picture, extreme photosensitivity, histological findings, and effective treatment with antimalarials are so characteristic that LET should be considered as a separate entity and differentiated from other variants of cutaneous LE. Arch Dermatol. 2000;136:1033-1041

Adolescent↗

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↗

[Combination of antimalarial drugs mepacrine and chloroquine in therapy refractory cutaneous lupus erythematosus].

Antimalarials represent the first line in treatment of cutaneous lupus erythematosus (LE). However, some patients show no improvement on monotherapy with chloroquine or hydroxychloroquine. A 30-year-old female patient had treatment-resistant cutaneous LE exhibiting features of both LE tumidus and subacute cutaneous LE. Previously, the patient had been unsuccessfully treated with chloroquine, hydroxychloroquine, dapsone, and azathioprine, each in combination with variable doses of prednisolone. However, the LE lesions increased during these therapeutic regimens. A combination of chloroquine and mepacrine therapy led to improvement and then total clearing after 4 months of treatment.

Adult↗

[Annular erythema in Sjögren syndrome. A variant of cutaneous lupus erythematosus?].

Annular erythema has been recognised as a cutaneous manifestation of Sjögren's syndrome in the Asian literature and has been assumed to represent a distinct clinical entity. Since there are common pathophysiologic mechanisms, mainly the presence of anti-Ro/SSA or anti-La/SSB antibodies, it is difficult to separate the annular erythema from subacute cutaneous lupus erythematosus. Histological examination may reveal dermal mucin deposition resembling lupus erythematosus tumidus. We present a Chinese patient with widespread annular erythema, keratoconjunctivitis sicca, and anti-Ro/SSA antibodies. Clinical, histopathological, and immunogenetic findings are discussed reviewing the current literature, and the differences between annular erythema associated with Sjögren's syndrome and cutaneous lupus erythematosus are emphasized.

Adult↗

[Acral necroses after therapy with quinine sulfate for calf cramps].

The most common cause of acral cyanosis is vascular spasm which can be induced by several drugs. An 87-year-old woman developed red and livid skin lesions on the fingers of both hands and several toes one month after beginning treatment with quinine sulfate 200 mg daily. The skin lesions progressed to necrosis in some areas. Quinine sulfate is a widely prescribed drug for nocturnal cramps. The following side effects may develop, particularly in the elderly: exanthems, pruritus, urticaria, erythema multiforme, purpura and photosensitivity. Our case points to the possibility of acral necrosis and demonstrates the efficacy of vasodilator treatment.

Acrodermatitis↗

[Thromboangiitis obliterans].

Thromboangiitis obliterans (Buerger disease) is a rare vascular disease, characterized by a multilocular, segmental, non-arteriosclerotic, thrombotic inflammation of small and medium size arterial and venous vessels and nerves. The precise etiology is unknown, but there is a cause-effect relationship with tobacco smoking. Autoimmunological, immunogenetic, infectious and hemostatic processes have been discussed as pathogenetic factors. The clinical picture is typically characterized by acrally localized, non-healing ulcerations, which frequently prompt patients to see a dermatologist. We present two patients with thromboangiitis obliterans and discuss the clinical features, the resulting differential diagnostic spectrum and possible therapeutic approaches.

Adult↗

[Presternal verrucous carcinoma].

Verrucous carcinomas represent rare, highly differentiated variants of squamous cell carcinoma. They preferentially develop on the oropharyngeal mucosa (Ackerman tumor), the urogenital mucosa (Buschke-Loewenstein tumors), and the soles of the feet (epitheliomata cuniculata). Various synonyma have been coined for these tumors. We report the uncommon occurrence of a large verrucous carcinoma on apparently uninvolved chest skin of a 79-year old patient. The tumor was excised radically. Complete extirpation was confirmed histologically and there was no sign of recurrence during a 3 month observation period. The clinical appearance, histomorphological features, epidemiological aspects, differential diagnosis, therapy, and nomenclature of verrucous carcinomas are discussed.

Aged↗

[Rare cutaneous manifestaions of lupus erythematosus. A clinical overview].

Lupus erythematosus (LE) is a disease with a wide spectrum of cutaneous and systemic manifestations and has been the subject of many studies over several decades. Clinical features of patients with LE show a great variation, and for this reason it is difficult to develop a unifying concept of this disease. Consequently, this has led to the identification of subsets which have been defined by constellations of clinical and photobiological features, histological changes as well as laboratory abnormalities. Besides the characteristic classical forms such as systemic LE (SLE), subacute cutaneous LE (SCLE), and discoid LE (DLE), there are uncommon variants of LE which often lead to diagnostic difficulties. Bullous LE (BLE) and urticarial vasculitis are listed as characteristic but non-specific manifestations of systemic LE. LE tumidus (LET), LE hypertrophic/verrucous (LEHV), chilblain LE, and LE profundus (LEP) are uncommon subtypes of chronic cutaneous LE. Annular erythema and papulonodular mucinosis are further uncommon cutaneous manifestations of LE. This clinical review summarizes the typical features of the uncommon forms of LE in order to improve clinical diagnostic precision and to achieve a better differentiation of the subtypes.

Diagnosis, Differential↗

Allelic losses on chromosome arm 10q and mutation of the PTEN (MMAC1) tumour suppressor gene in primary and metastatic malignant melanomas.

Malignant melanomas frequently show loss of alleles on the long arm of chromosome 10. The PTEN (MMAC1) gene has been identified as a tumour suppressor gene at 10q23.3 that is mutated in various types of advanced human cancers. We have investigated a series of 40 sporadic melanomas from 37 patients (15 primary cutaneous melanomas and 25 melanoma metastases) for allelic losses on chromosome 10, as well as for deletion and mutation of the PTEN gene. Microsatellite analysis revealed loss of heterozygosity at loci located on 10q in tumours from 15 of 34 patients investigated (44%). Somatic PTEN mutations were identified in melanomas from 4 of 37 patients (11%), all of whom had metastatic disease. In two of these patients, the tumours had additionally lost one PTEN allele, indicating complete loss of wild-type PTEN in the tumour cells. Our findings corroborate that loss of heterozygosity on chromosome 10 is a frequent aberration in malignant melanomas and implicate PTEN as a tumour suppressor gene inactivated by somatic mutation in a fraction of these tumours.

Adult↗

Applications of tacrolimus for the treatment of skin disorders.

During the last decades, systemic and topical glucocorticosteroids assumed a dominant role in immunosuppressive therapy in dermatology. However, their administration is limited because of numerous adverse effects. Consequently, there is a large need for alternative non-steroidal anti-inflammatory therapeutics with a superior risk/benefit ratio. In recent years, a new class of anti-inflammatories, the macrolide lactones, has attracted special interest. During the last decade, a member of this class, tacrolimus, proved to be a powerful suppressor of the immune system. Introduced into clinical practice to prevent allograft rejection, it is now routinely used in organ transplantation. Recently, several placebo-controlled multicenter studies showed the therapeutic efficiency of systemic and topical tacrolimus in common inflammatory skin diseases such as psoriasis and atopic eczema.Short-term tacrolimus ointment therapy disclosed significant efficacy vs. placebo and a safety profile with only few local side effects in patients with atopic eczema. Further clinical trials including greater extent of exposure (experienced by children), and comparison between tacrolimus ointment and glucocorticosteroids are being conducted and the results will show whether this drug opens a new era in the treatment of inflammatory skin disorders. The aim of this review is to summarize the current knowledge regarding the pharmacokinetic properties, adverse effects and therapeutic indications of tacrolimus in dermatology.

Administration, Topical↗

Photopatch testing: the 12-year experience of the German, Austrian, and Swiss photopatch test group.

BACKGROUND: In 1984, the German, Austrian, and Swiss Photopatch Test Group was founded to standardize the photopatch test procedure and to investigate photoallergic reactions, as well as the epidemiology of photoallergy, in central Europe. Therefore in a first test period from 1985-1990, 32 test substances were applied on the backs of patients suspected to be photosensitive. After evaluation of these data, some substances were dismissed, and others were additionally integrated into the test tray. Thus a modified test tray comprising 26 test substances was used for the second test period (1991-1997). OBJECTIVE: According to the standard photopatch test procedure defined in the first test period, the aim of this multicenter study was to apply compounds from the modified second test tray to a large group of photosensitive patients. After evaluation of the second test period (1991-1997), the outcome was compared with the results of the first period. On the basis of these results and influenced by concurrently published case reports, a third modified photopatch test tray has been established. METHODS: After the application of a duplicate test tray for 24 hours, one test site was irradiated with 10 J/cm(2) UVA, and the other test site served as the control area. Readings were performed immediately and 24, 48, and 72 hours after irradiation. Test reactions were qualitatively graded according to a 4-point scale and classified by the investigators of the participating centers. In 49 participating clinics 1261 photopatch tests were performed. All data were subjected to computer-assisted analysis by using a specially developed software to classify all positive test reactions as plain contact or photoinduced reactions (nonspecific, toxic, or allergic photoreactions) and to define substance-specific reaction patterns. RESULTS: In test period 1 data of 1129 patients were evaluated. From 2859 positive test reactions, 28.6% were excluded as plain contact reactions, 71.4% were found to be photoinduced reactions, and 3.8% were classified as photoallergic. In test period 2 data of 1261 patients were evaluated. One thousand four hundred fifteen positive test reactions were observed, and of these, 28.7% were excluded as plain contact reactions, 71.3% were classified as photoinduced reactions, and 8.1% were classified as photoallergic reactions. In both test periods nonsteroidal anti-inflammatory drugs, disinfectants, and phenothiazines represented the leading photoallergens in the evaluated central European region. By using computer-assisted reaction pattern analysis, substance-specific reaction patterns could be distinguished. These substance-specific reaction patterns comprised 4 main categories: the well-known decrescendo (phototoxic) and crescendo (photoallergic) reaction patterns, as well as a combined and a plateau pattern. CONCLUSION: The test modification after the first test period led to a notably reduced number of positive (mainly nonphotoallergic and thus nonrelevant) test reactions per patient in the second test period (from 2.6 to 1.1). In contrast, the percentage of photoallergic reactions increased significantly from 3.8% to 8.1% of all positive test reactions. Test modifications after the first test period led to a remarkably improved specificity of the photopatch test. Furthermore, substance-specific reaction patterns observed in test period 1 were confirmed in test period 2.

Adult↗