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Thilo Gambichler

Publications and source records attributed to Thilo Gambichler.

At least 37 records · Page 2Linked to original sources
PubMed2005

Applications of optical coherence tomography in dermatology.

Histology represents the gold standard for morphological investigation of the skin, though biopsy may alter the original morphology, is non-repeatable on the same site and always requires an iatrogenic trauma. In the past decade, advances in optics, fibre as well as laser technology have enabled the development of a novel non-invasive optical biomedical imaging technique, optical coherence tomography (OCT). The latter is based on a classic optical measurement method known as low-coherence interferometry that enables non-invasive, high resolution, two- or three-dimensional, cross-sectional imaging of microstructural morphology in biological tissue in situ. Using conventional OCT with a lateral resolution of 10-15 microm, the stratum corneum of glabrous skin (palmoplantar), the epidermis and the upper dermis can usually be identified, as well as skin appendages and blood vessels. For example, non-invasive monitoring of cutaneous inflammation, hyperkeratotic conditions and photoadaptive processes is possible by means of OCT. Furthermore, the development of high-output broadband light sources, e.g. femtosecond Ti:sapphire laser, might soon enable ultrahigh image resolutions of about 1 microm in order to investigate skin tissue on the cellular level, which could potentially allow the differentiation between benign and malignant tissues. Beyond a high resolution morphology in OCT images, tissue characterization by additional local physical parameters, such as the scattering coefficient and refractive index may be of great value, in particular in cosmetics and the pharmaceutical industry. Functional OCT imaging based on spectroscopy, tissue birefringence, elastography and Doppler flow reveals further information on tissue properties and represents an important progress of OCT technique in the field of dermatology. Therefore, the advanced versions of OCT technique might not only lead to significant new insights in skin physiology and pathology, but also in diagnosis and therapeutic control of cutaneous disorders with respect to non-invasive diagnosis of conditions and monitoring of disease activity in addition to treatment effects over time.

Humans↗
PubMed2005

Pulsed high-dose corticosteroids combined with low-dose methotrexate in severe localized scleroderma.

OBJECTIVE: To evaluate the efficacy of pulsed high-dose corticosteroids combined with orally administered low-dose methotrexate therapy in patients with severe localized scleroderma (LS). DESIGN: A prospective, nonrandomized, open pilot study. SETTING: Dermatology department at a university hospital in Bochum, Germany. Patients Fifteen patients with histologically confirmed severe LS. Interventions Oral methotrexate (15 mg/wk) combined with pulsed intravenous methylprednisolone (1000 mg for 3 days monthly) for at least 6 months. MAIN OUTCOME MEASURES: Treatment outcome was evaluated by means of a clinical score, 20-MHz ultrasonography, and histopathologic analysis. Safety assessment included the monitoring of adverse effects and clinical laboratory parameters. RESULTS: One patient discontinued therapy. In most of the remaining 14 patients, significant elimination of all signs of active disease (inflammation) and remarkable softening of formerly affected sclerotic skin that resulted in a decrease of the mean +/- SD clinical score from 10.9 +/- 5.3 at the beginning to 5.5 +/- 2.5 at the end of therapy was observed (P < .001). Clinical improvement was confirmed by histologic and ultrasonographic assessments. No serious adverse effects were noted. CONCLUSIONS: These data suggest that pulsed high-dose corticosteroids combined with orally administered low-dose methotrexate therapy is beneficial and safe in the treatment of patients with LS. This treatment regimen should especially be considered for severe forms of LS in which conventional treatments have failed.

Administration, Oral↗
PubMed2005

Narrowband UVB phototherapy in skin conditions beyond psoriasis.

BACKGROUND: Narrowband (NB) UVB phototherapy has been proven to be clearly more effective than broadband UVB and safer and/or more practicable than psoralen-UVA in the management of psoriasis. However, the role of NB UVB seems to be less clear in the management of skin conditions beyond psoriasis. OBJECTIVES: We sought to give an update on clinical experiences in NB UVB of nonpsoriatic skin conditions, and to establish its current position within the spectrum of competing photo(chemo)therapeutic options. METHODS: The computerized bibliographic database PubMed, without time limits, and other sources were screened for clinical trials on NB UVB. Included were research articles of randomized controlled trials, open prospective studies, and retrospective observations on NB UVB in skin disorders other than psoriasis. RESULTS: A total of 28 articles met our eligibility criteria including 6 randomized controlled studies, 16 open prospective studies, and 6 retrospective observations. NB UVB is effective in patients with chronic atopic dermatitis (AD) (n = 719) and generalized vitiligo (n = 305) and appears to have some advantages over competing photo(chemo)therapeutic regimens. NB UVB also seems to be effective in patients with polymorphic light eruption (n = 25), early stages of cutaneous T-cell lymphoma (n = 108), chronic urticaria (n = 88), lichen planus (n = 15), pruritus associated with polycythemia vera (n = 10), seborrheic dermatitis (n = 18), actinic prurigo (n = 6), and acquired perforating dermatosis (n = 5). The quality of evidence determined for the aforementioned diagnoses ranged from high to moderate to very low. CONCLUSIONS: The best currently available data on NB UVB in nonpsoriatic conditions exist for AD and generalized vitiligo. In view of its efficacy, benefit/risk profile, and costs, NB UVB may be considered the first-line photo(chemo)therapeutic option for moderately severe AD and widespread vitiligo. In the treatment of most other nonpsoriatic conditions, NB UVB appears to be effective, but current data allow no definitive conclusions as to whether NB UVB should be preferred to competing photo(chemo)therapeutic options such as UVA1 and psoralen-UVA regimens. Because NB UVB may have a wider indication spectrum, including AD, vitiligo, and early-stage T-cell lymphoma, and appears to be equally effective or even more effective than broadband UVB, a switch from broadband UVB to NB UVB seems to be justified.

Dermatitis, Atopic↗
PubMed2005

Changes in venous refilling time from childhood to adulthood in subjects with apparently normal veins.

OBJECTIVE: Measuring venous refilling time by photoplethysmography is one of the most commonly used methods in venous diagnostics. Numerous studies have been done in adults to investigate its suitability to assess the overall venous calf pump function and to discriminate healthy subjects from patients with venous disease. The present study investigated any changes in the behavior of venous calf pump function from childhood to adulthood in subjects with healthy veins. METHODS: The study population consisted of 73 healthy (CEAP clinical classes C0 and C1) subjects (52 females, 21 males) who were all of the same age group (10 to 12 years old). It was a representative selection of the participants in a comprehensive longitudinal vein study known as the Bochum study (BO). The data of this study were obtained from (original) pupils of 11 secondary schools in the city of Bochum, Germany at four different periods (BO I 1982-1983, 10 to 12 years; BO II 1986-1987, 14 to 16 years; BO III 1991, 18 to 20 years; and BO IV 2001-2002, 29 to 31 years), 1990 RESULTS: The distribution patterns of venous refilling time showed a successive shift to the right from childhood to adulthood. The distribution peak was in the range of 10.1 to 20 seconds in BO I, broadened to 10.1 to 30 seconds in BO II, and changed to 40.1 to 50 seconds in BO III and BO IV. The median values increased from 24 seconds to more than 45 seconds. When we compared the two subgroups classified as C0 and C1, there was no significant difference in the behavior of their venous refilling time. CONCLUSIONS: To our knowledge, this is the first time the physiologic changes of venous calf pump function have been documented in a longitudinal study in young volunteers with healthy veins. The median venous refilling time successively lengthened, corresponding to a maturing of the venous calf pump function during adolescence and then stayed on a stable level. Therefore, measurements of venous calf pump function are not a means for assessing malfunction of the venous system during childhood and adolescence.

Adolescent↗
PubMed2005

Liposomal pegylated doxorubicin versus low-dose recombinant interferon Alfa-2a in the treatment of advanced classic Kaposi's sarcoma; retrospective analysis of three German centers.

BACKGROUND: Classic Kaposi's sarcoma (KS) is a rare neoplasm, predominantly occurring in older subjects of Eastern Europe or Mediterranean descent. While single lesions may be treated by simple excision, laser therapy, cryotherapy, or intralesional therapy, advanced or disseminated disease requires systemic treatment. Several studies reported the effectiveness of pegylated liposomal doxorubicin (PLD) and low-dose recombinant interferon alfa-2a (IFNalpha) in the treatment of AIDS-associated KS. OBJECTIVE: The aim of this retrospective analysis of three German centers was to compare the effectiveness and tolerability of PLD with IFNalpha in patients with advanced classic KS. METHODS: Retrospective analysis of 18 Caucasian patients who had been treated for histologically proven classic KS, with either with PLD or IFNalpha was performed. Twelve patients received 20 mg/m2 of PLD monthly, and the number of cycles was adapted to the clinical response. Dose reduction or increased cycle length was conducted if toxicity intervened. In 6 patients, 3 million U of IFNalpha was injected subcutaneously 3 times a week. IFNalpha -therapy was adapted according to the clinical response. RESULTS: In the 12 KS patients treated with PLD, complete response (CR) was achieved in 8 (67 percent), major response (MR) in 3 (25 percent), and minor response (mR) in 1 (8 percent). Stable disease (SD) or progression of disease (PD) was not observed. An initial response was noted after 4-16 weeks of treatment (mean 8.6 weeks), the mean cumulative dose of PLD was 571.5 mg/m2 (range, 40 to 1496 mg/m2), and the mean follow-up was 13 months. Neutropenia (33 percent) related to PLD was the most common adverse event (4/12). Vomiting occurred in 3 (25 percent) patients; none of these were severe. Six patients were treated with IFNalpha. MR was achieved in 1 (17 percent), mR in 4 (67 percent) and SD in 1 of 6 patients (17 percent), neither had CR or PD. An initial response was observed after 8-17 weeks of treatment (mean 12.7 weeks). Fever occurred in 4 patients (67 percent). Flu-like symptoms in 3 patients (50 percent) related to IFNalpha were the most common adverse events. Mean follow-up was 6.3 months. The differences in response to treatment between PLD and IFNalpha, in general, were significant with p < 0.05 (T-test for independent samples). Comparing weeks to respond and treatment efficiency data were significant with p < 0.001 (Fisher's exact): response to PLD was up to one-third faster than IFNalpha. Calculating different stages of response (MR, CR, etc.), PLD also was clearly superior (p = 0.018) to IFNalpha (Fisher's exact). CONCLUSION: This retrospective analysis of patients with classic KS confirms the efficacy and safety of PLD. The benefits of PLD, including the monthly application, the high response even after previous treatments have failed, and the low rate of side effects even in elderly individuals, outweigh the risks. PLD is superior to IFNalpha and should be considered as an promising option in the treatment of advanced classic KS.

Adult↗
PubMed2004

Pimecrolimus 1% cream for anogenital lichen sclerosus in childhood.

BACKGROUND: Lichen sclerosus is a chronic inflammatory disease with a predilection of the anogenital region. Because of the potential side effects of repeated local application of potent glucocorticosteroids, equally-effective, safer therapeutic options are required, especially in the treatment of children. CASE PRESENTATIONS: We report on the efficacy of twice-daily application of pimecrolimus 1% cream in four prepubertal girls (range of age: 4 to 9 years) who suffered from anogenital lichen sclerosus. After three to four-month treatment, all patients had almost complete clinical remission including relief from itch, pain and inflammation. Only minor improvement was observed for the white sclerotic lesions. No significant side effects have been observed. CONCLUSIONS: Topical pimecrolimus appears to be an effective and safe treatment for children with anogenital lichen sclerosus. The clinical benefits observed in the four patient presented particularly include relief of pruritus, pain and inflammation. Vehicle-controlled studies on a larger number of patients are now warranted to substantiate our promising findings, and to investigate long-term efficacy and safety of topical pimecrolimus in anogenital lichen sclerosus.

Administration, Cutaneous↗
PubMed2004

UVA/UVA1 phototherapy and PUVA photochemotherapy in connective tissue diseases and related disorders: a research based review.

BACKGROUND: Broad-band UVA, long-wave UVA1 and PUVA treatment have been described as an alternative/adjunct therapeutic option in a number of inflammatory and malignant skin diseases. Nevertheless, controlled studies investigating the efficacy of UVA irradiation in connective tissue diseases and related disorders are rare. METHODS: Searching the PubMed database the current article systematically reviews established and innovative therapeutic approaches of broad-band UVA irradiation, UVA1 phototherapy and PUVA photochemotherapy in a variety of different connective tissue disorders. RESULTS: Potential pathways include immunomodulation of inflammation, induction of collagenases and initiation of apoptosis. Even though holding the risk of carcinogenesis, photoaging or UV-induced exacerbation, UVA phototherapy seems to exhibit a tolerable risk/benefit ratio at least in systemic sclerosis, localized scleroderma, extragenital lichen sclerosus et atrophicus, sclerodermoid graft-versus-host disease, lupus erythematosus and a number of sclerotic rarities. CONCLUSIONS: Based on the data retrieved from the literature, therapeutic UVA exposure seems to be effective in connective tissue diseases and related disorders. However, more controlled investigations are needed in order to establish a clear-cut catalogue of indications.

Adult↗
PubMed2004

Contact dermatitis and other skin conditions in instrumental musicians.

BACKGROUND: The skin is important in the positioning and playing of a musical instrument. During practicing and performing there is a permanent more or less intense contact between the instrument and the musician's skin. Apart from aggravation of predisposed skin diseases (e.g., atopic eczema or psoriasis) due to music-making, specific dermatologic conditions may develop that are directly caused by playing a musical instrument. METHODS: To perform a systematic review on instrument-related skin diseases in musicians we searched the PubMed database without time limits. Furthermore we studied the online bibliography "Occupational diseases of performing artist. A performing arts medicine bibliography. October, 2003" and checked references of all selected articles for relevant papers. RESULTS: The most prevalent skin disorders of instrumental musicians, in particular string instrumentalists (e.g., violinists, cellists, guitarists), woodwind players (e.g., flautists, clarinetists), and brass instrumentalists (e.g., trumpeters), include a variety of allergic contact sensitizations (e.g., colophony, nickel, and exotic woods) and irritant (physical-chemical noxae) skin conditions whose clinical presentation and localization are usually specific for the instrument used (e.g., "fiddler's neck", "cellist's chest", "guitar nipple", "flautist's chin"). Apart from common callosities and "occupational marks" (e.g., "Garrod's pads") more or less severe skin injuries may occur in musical instrumentalists, in particular acute and chronic wounds including their complications. Skin infections such as herpes labialis seem to be a more common skin problem in woodwind and brass instrumentalists. CONCLUSIONS: Skin conditions may be a significant problem not only in professional instrumentalists, but also in musicians of all ages and ability. Although not life threatening they may lead to impaired performance and occupational hazard. Unfortunately, epidemiological investigations have exclusively been performed on orchestra musicians, though the prevalence of instrument-related skin conditions in other musician groups (e.g., jazz and rock musicians) is also of interest. The practicing clinician should be aware of the special dermatologic problems unique to the musical instrumentalist. Moreover awareness among musicians needs to be raised, as proper technique and conditioning may help to prevent affection of performance and occupational impairment.

Dermatitis, Allergic Contact↗
PubMed2004

Low-dose UVA1 phototherapy in systemic sclerosis: effects on acrosclerosis.

BACKGROUND: Increased collagen synthesis, vascular damage, and T-lymphocytic infiltration contribute to the development of systemic sclerosis. Preliminary studies revealed the effectiveness of low-dose UVA1 phototherapy in acrosclerosis. OBJECTIVE: We sought to confirm data of a pilot study revealing the efficacy of low-dose UVA1 irradiation in acrosclerosis in a larger number of patients. METHODS: Symptoms of 18 patients receiving low-dose UVA1 phototherapy were evaluated clinically and biometrically in an open, nonrandomized study. A number of pretherapeutic and posttherapeutic biopsy specimens were tested immunohistochemically for matrix-metalloproteinase-1. RESULTS: UVA1 irradiation led to softening of former stiffness reflected by a significant decrease of the hand score, increase of total skin distension, and reduction of skin thickness. Posttherapeutically, matrix-metalloproteinase-1 immunolabeling revealed a significant dermal elevation of collagenase. CONCLUSION: Low-dose UVA1 phototherapy is a capable treatment option for acrosclerosis. Its beneficial effect may be mediated by the induction of collagenases and a reduction of collagen deposition and cellular infiltration.

Adult↗
PubMed2004

Pimecrolimus 1% cream for cutaneous lupus erythematosus.

Topical treatment of cutaneous lupus erythematosus usually includes potent glucocorticosteroids. However, prolonged use causes adverse side effects including skin atrophy as the foremost concern. In contrast to glucocorticosteroids, the anti-inflammatory and immunosuppressive macrolactam pimecrolimus has no atrophogenic potential. Affected areas of 11 patients with different forms of lupus erythematosus were treated with pimecrolimus 1% cream under semiocclusive conditions twice daily for 3 weeks. Skin involvement before and after therapy was assessed by means of a clinical score. In all patients, significant regression of skin lesions was observed after therapy (P <.001). This was an open and uncontrolled study on a limited number of cases. We suggest that pimecrolimus 1% cream could be an efficacious and safe treatment option for cutaneous lupus erythematosus.

Administration, Cutaneous↗
PubMed2004

Pulsed intravenous immunoglobulin therapy in livedoid vasculitis: an open trial evaluating 9 consecutive patients.

BACKGROUND: Livedoid vasculitis (LV) usually presents with painful, slowly healing ulcerations of the lower limbs. The precise pathophysiology of this relatively rare disease remains obscure. Therapeutic strategies usually include rheologic, anti-inflammatory, or immunosuppressive agents. However, no continuing benefit has been reported in any of these modalities. Recently, encouraging case reports about the successful use of intravenous immunoglobulin (IVIg) in LV have been published. METHODS: We initiated an open single center trial to investigate the efficacy and safety of IVIg in LV. Nine patients with LV, 7 of whom were refractory to other treatment modalities, were included. Therapy with IVIg at a dose of 0.5 g/kg body weight per day over 2 or 3 consecutive days was performed monthly. Skin involvement before and after therapy was assessed by means of a clinical score. RESULTS: In all patients, significant regression of skin lesions was observed after therapy resulting in a decrease of the clinical score (including differential semiquantitative assessment of erythema, ulceration, and pain) from 6.5 +/- 1.7 at the beginning to 1.3 +/- 1.2 after therapy (P <.001). IVIg was well tolerated and therapy was finished in all patients. CONCLUSION: In all patients clinical evaluation revealed a marked improvement of erythema, pain, and healing of areas of active ulceration. Although this was an open non-controlled study, we propose that IVIg is a promising therapeutic option in LV refractory to other treatment modalities.

Adult↗
PubMed2003

Premature keratinocyte death and expression of marker proteins of apoptosis in human skin after UVB exposure.

Epidermal keratinocytes undergo a process of terminal differentiation or cornification that in many aspects resembles apoptosis. It is characterized by the elimination of cell nuclei within the granular layer, whereas the cytoplasm is transformed into horn cells. Premature death of keratinocytes can be induced by extrinsic factors such as UV irradiation. We investigated the time-dependent expression of apoptotic marker proteins in the skin of one healthy human volunteer after irradiation with a fourfold minimal erythema dose (MED) of UVB. The data were supplemented by including healthy skin areas of biopsies from patients UVB-irradiated for therapeutic reasons. Punch biopsies were analysed by in situ end-labelling (ISEL) for DNA strand breaks and by immunohistochemistry for expression of p53, bcl-2, active caspase-3 and its proform, and deoxyribonuclease I (DNase I). Keratinocytes with pyknotic nuclei were first detected 6 h after UVB exposure, and apoptotic keratinocytes (sunburn cells) 12 h after exposure. These aggregated to sunburn bodies after 24 h. In control skin, nuclei with DNA strand breaks were only occasionally detected in the granular layer but 6 h after UVB irradiation in the spinous layer. After 12 h, many sunburn cells were ISEL-positive and positively stained for active caspase-3, P53, and DNase I. Morphometric evaluation of the immunohistochemical data demonstrated that maximal upregulation of P53, DNase I and activation of caspase-3 occurred 12 h after irradiation and in advance of the peak of apoptotic cell death reached after 24 h as verified by ISEL. In contrast, strong Bcl-2 immunostaining appeared restricted to presumed melanocytes and basal cells but was not increased after UVB irradiation.

Adult↗
PubMed2003

Metastatic cutaneous squamous cell carcinoma arising from a previous area of chronic hypertrophic lichen planus.

Malignant transformation of cutaneous lichen planus is a rare event. We report a 34 year old Caucasian male who presented with an exophytic tumor on the right foreleg. The tumor gradually developed within previous areas of histologically proven hypertrophic lichen planus that had existed for about 10 years. However, the current histological examination of the excised tumor revealed highly differentiated squamous cell carcinoma with a depth of tumor invasion of 10 mm. At that time, neither sentinel lymph node biopsy nor further imaging diagnostics revealed evidence for metastatic spreading. Nevertheless, five months after surgery inguinal lymph node metastases were detected. Initial chemotherapy and inguinal lymph node dissection were unable to stop the spread of the tumor. One year later, parailiacal lymph node metastases were detected by computed tomography. Further cycles of chemotherapy resulted in significant reduction of the parailiacal tumor masses. This report indicates that the long-standing hypertrophic form of lichen planus seems to have a considerable propensity for malignant transformation, even in young patients.

Adult↗
PubMed2002

Successful treatment of recalcitrant cutaneous sarcoidosis with fumaric acid esters.

BACKGROUND: Sarcoidosis is a multisystem disease of unknown origin characterized by the formation of noncaseating granulomas, in particular in the lungs, lymph nodes, eyes, and skin. Systemic treatment for cutaneous sarcoidosis can be used for large disfiguring lesions, generalized involvement, or recalcitrant lesions that did not respond to topical therapy. CASE PRESENTATIONS: We report three patients with recalcitrant cutaneous sarcoidosis who were treated with oral fumaric acid esters (FAE). Three female patients presented with cutaneous sarcoidosis that have proved to be refractory to various therapies, including corticosteroids and chloroquine. We treated the patients with FAE in tablet form using two formulations differing in strength (Fumaderm initial, Fumaderm). Dosage of FAE was performed according to the standard therapy regimen for psoriasis patients. After treatment with FAE (4-12 months), a complete clearance of skin lesions was achieved in the three patients. The side effects observed in this trial correspond to the well-known spectrum of adverse effects of FAE (flush, minor gastrointestinal complaints, lymphopenia). CONCLUSIONS: On the basis of our findings FAE therapy seems to be a safe and effective regimen for patients with recalcitrant cutaneous sarcoidosis. Nevertheless further investigations are necessary to confirm our preliminary results.

Adult↗
PubMed2002

Modulation of cathepsin G expression in severe atopic dermatitis following medium-dose UVA1 phototherapy.

BACKGROUND: During the last decade, medium-dose UVA1 phototherapy (50 J/cm2) has achieved great value within the treatment of severe atopic dermatitis (AD). The purpose of our study was to investigate to what extent UVA1 irradiation is able to modulate the status of protease activity by the use of a monoclonal antibody labeling cathepsin G. METHODS: In order to further elucidate the mechanisms by which medium-dose UVA1 irradiation leads to an improvement of skin status in patients with AD, biopsy specimens from 15 patients before and after treatment were analyzed immunohistochemically for proteolytic activation. RESULTS: Compared to lesional skin of patients with AD before UVA1 irradiation, the number of cells positive for cathepsin G within the dermal infiltrate decreased significantly after treatment. The decrease of cathepsin G+ cells was closely linked to a substantial clinical improvement in skin condition. CONCLUSIONS: In summary, our findings demonstrated that medium-dose UVA1 irradiation leads to a modulation of the expression of cathepsin G in the dermal inflammatory infiltrate in patients with severe AD. Cathepsin G may attack laminin, proteoglycans, collagen I and insoluble fibronectin, to provoke proinflammatory events, to degrade the basement membrane, to destroy the tissue inhibitor of metalloproteinases and to increase the endothelial permeability. Therefore, its down-regulation by UVA1 phototherapy may induce the reduction of skin inflammation as well as improvement of the skin condition.

Biopsy↗