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C Sunderkötter

Publications and source records attributed to C Sunderkötter.

At least 19 recordsLinked to original sources
PubMed2007

[Transient global amnesia (TGA) during an oral provocation test].

After the oral administration of the COX 2 inhibitor rofecoxib (Vioxx) as part of an oral provocation test, a 64-year-old woman developed acute anterograde and retrograde amnesia which lasted for several hours. The patient did not show symptoms of anaphylaxis. Neurological examination did not reveal focal symptoms or an epileptic seizure. Diffusion-weighted magnetic resonance imaging only showed a small region of increased signal intensity in the left hippocampus. The patient thus had no anaphylactic drug reaction, but a transient global amnesia (TGA) or amnestic episode. TGA is an acute, reversible, cerebral dysfunctional state which lasts from 1 h up to maximally 24 h and which is associated with anterograde and retrograde amnesia. While about half of the cases appear to occur spontaneously, other cases are preceded by physically or emotionally stressful events. In our patient it may have been the emotional distress caused by the oral provocation testing that has triggered the TGA. When TGA occurs during oral challenge of drugs, we recommend repeating the oral challenge of the tested drug.

Administration, Oral↗
PubMed2006

[Raynaud phenomenon in dermatology. Part 1: Pathophysiology and diagnostic approach].

Raynaud phenomenon (RP) is characterized by recurrent spasms of small digital arterioles/arteries at fingers and toes, usually triggered by cold and emotional stress. Clinically a sudden pallor of individual digits is followed by reactive hyperemia, in severe cases also by cyanosis. One distinguishes between primary RP, i.e. RP without an underlying disease or drug intake, and secondary RP, which is causally related to an underlying disease or to intake of certain drugs (e.g. interferon, cisplatin). Primary RP is frequent (prevalence of about 13-20% in northern or central Europe), while secondary RP is rare, but the major presenting symptom for systemic sclerosis (SSc). Differential diagnosis includes cold-induced pallor, acute embolic events, paroxysmal hematoma of the finger or erythromelalgia. Vasoconstrictive mechanisms outweigh vasodilatory ones in endothelial cells and vascular smooth muscle. Although soluble mediators such as endothelin or certain prostaglandins have been exploited successfully for therapy, the extent of their involvement in the initial pathophysiology of RP is unclear. Secondary RP (associated with SSc) additionally features morphological alterations with compromise of the vessel lumen. As RP can result in severe discomfort and complications, timely diagnosis and treatment is essential.

Humans↗
PubMed2006

[Raynaud phenomenon in dermatology : Part 2: therapy].

While primary Raynaud phenomenon (RP) only rarely leads to complications, secondary RP when associated with systemic sclerosis (SSc) frequently results in necrosis, ulcers or even gangrene. Therefore timely therapeutic intervention is required. Management of RP includes physical therapy, avoidance of triggers, and a variety of medications, depending on the disease severity. On the basis of published studies and of our own experience we suggest: a) for primary and uncomplicated secondary RP, calcium channel blockers in adequate doses; b) for SSc-associated secondary RP with hypertension, cardial or renal involvement, drugs which interfere with angiotensin; c) in case of concomitant depression, exploitation of the vasodilatory effects of serotonin reuptake inhibitors, d) in presence of ulcers or marked trophic alterations, intravenous administration of iloprost, e) for recalcitrant cases and endangered digits, sildenafil, f) for prevention of severe relapses, the endothelin-receptor antagonist bosentan. The drugs mentioned in c-f are not approved for RP and used off-label. In patients with secondary SSc-associated RP, timely therapy can reduce the percentage of complications such as ulcers or amputations. In addition, timely treatment of RP possibly retards ensuing fibrotic processes.

Humans↗
PubMed2006

Pathophysiology and clinical consequences of Raynaud's phenomenon related to systemic sclerosis.

According to the so-called vascular hypothesis, Raynaud's phenomenon (RP) is one initial event in the pathophysiological cascade leading to sclerosis in systemic sclerosis (SSc). It is characterized by recurrent, reversible spasms of small arterioles and digital arteries, usually triggered by cold and emotional stress. Clinical signs of RP are a sudden pallor of single digits of fingers followed by reactive hyperaemia and in severe cases also by cyanosis. Besides imbalances between vasoconstrictive and vasodilatory processes, structural alterations of the involved vessels are fundamental to secondary RP in SSc. The latter is the reason why secondary RP in SSc, in contrast to primary RP, often leads to ischaemia and re-perfusion injuries. New insights into the pathophysiology of RP feature a special role for alpha2c-adrenoreceptors, Rho-kinase signalling pathways and soluble mediators. They have resulted in promising therapeutic options, including antagonism of endothelin receptors, inhibition of phosphodiesterases or selective blockade of alpha2c-adrenoreceptors. They should also have a positive impact on the course of SSc in general.

Fibrosis↗
PubMed2006

Vasoactive therapies in systemic sclerosis.

In systemic sclerosis (SSc), vasculopathy is a central mechanism and is a major initial event in the process of sclerosis and causing different complications such as Raynaud's phenomenon, ulcer(s) or pulmonary hypertension, the latter being life threatening. Therefore, vasoactive therapies are important when taking care of patients with SSc. However, as treatment has been difficult, numerous therapeutic modalities have been suggested. Until now, the interpretation of most studies is limited due to the heterogeneity of patient groups, the low number of patients, the short duration of the treatments and, possibly, further pathogenic mechanisms such as autoimmunity. Several drugs are now available with effects on vasculopathy and, furthermore, on specific pathogenic mechanisms in SSc. Prostacyclins, endothelin receptor antagonists and phosphodiesterase-5 inhibitors have potential effects on fibrosis, inflammation and endothelial cells, suggesting a disease-modifying capacity in systemic sclerosis. This review summarizes evidence-based therapy recommendations.

Endothelin Receptor Antagonists↗
PubMed2006

Phototherapy: a promising treatment option for skin sclerosis in scleroderma?

In systemic sclerosis (SSc; scleroderma) fibrosis of the skin can lead to considerable morbidity. No significant improvement has been reported from studies investigating antifibrotic therapies so far. In dermatology, phototherapy with ultraviolet (UV) irradiation is successfully used for treatment of several diseases because of its anti-inflammatory as well as immunosuppressive mechanisms, and its low-risk profile. In addition, the UVA spectrum in particular exerts antifibrotic effects as it leads to reduction of procollagen synthesis and expression of collagenase-1 in vitro. Accordingly, treatment with long-wavelength UVA-1 irradiation or photochemotherapy with UVA plus the photosensitizer psoralen (PUVA) have been successfully used to reduce skin fibrosis in localized scleroderma (morphea). There are only in particular few reports on treatment of skin sclerosis in SSc, but the results are in concordance with the good experience that have been observed at our and other dermatological centres. Phototherapy is able to stop or inhibit the fibrotic processes and to induce softening of sclerotic skin, especially in limited SSc. Phototherapy thus represents a therapeutic alternative for antifibrotic treatment with a low rate of adverse effects, which should be applied before the sclerotic process has proceeded too far.

Fibrosis↗
PubMed2006

Elevated serum levels of calcium-binding S100 proteins A8 and A9 reflect disease activity and abnormal differentiation of keratinocytes in psoriasis.

BACKGROUND: The expression of calcium-binding S100 molecules organized within the epidermal differentiation complex on chromosome 1q21 is disturbed in hyperproliferative skin diseases such as psoriasis. OBJECTIVES: We studied whether serum levels of S100 proteins A8 (S100A8) and A9 (S100A9) are elevated in psoriasis, correlated their amounts with disease activity and identified potential cellular sources. METHODS: Serum obtained from psoriasis patients or from healthy individuals was studied for S100A8 and S100A9 levels by enzyme-linked immunosorbent assay. Data were correlated to disease activity as reflected by the Psoriasis Area and Severity Index (PASI). Cellular sources of S100A8 and S100A9 were identified by in situ hybridization and immunohistochemistry of lesional psoriatic and nonlesional, nonpsoriatic skin. RESULTS: A significant increase of S100A8/S100A9 serum levels was found in patients with psoriasis compared with healthy controls. Grading the patients into two groups of severity, individuals with a PASI of <15 showed serum levels of 705+/-120 ng mL-1 (mean+/-SEM, n=18), those with a PASI of >or=15 showed levels of 1315+/-150 ng mL-1 (n=32) while controls presented with 365+/-50 ng mL-1. Performing in situ hybridization of lesional psoriatic skin we detected a dramatic induction of both S100A8 and S100A9 mRNA and protein primarily in the suprabasal layers of the epidermis while expression was negligible in nonlesional, nonpsoriatic interfollicular epidermis. CONCLUSIONS: Our data demonstrate that hyperproliferation and abnormal differentiation of psoriatic skin is associated with a massive upregulation and secretion of S100A8 and S100A9, suggesting not only a prominent role of these molecules during intracellular calcium-dependent signalling but also implying distinct extracellular functions.

Acute Disease↗
PubMed2005

Management of leukocytoclastic vasculitis.

Leukocytoclastic vasculitis (LcV) is the most common form of vasculitis of the skin and usually results from deposition of immune complexes at the vessel wall. It presents in different forms and in association with different diseases. When IgA is the dominant immunoglobulin in immune complexes, systemic involvement is likely in both children and adults (Henoch-Schönlein purpura--HSP). LcV due to IgG- or IgM-containing immune complexes has less systemic involvement and a better prognosis than HSP. Other forms of LcV include cryoglobulinaemic, urticarial and ANCA-associated LcV as well as LcV associated with vasculopathy and coagulopathy in SCLE/SLE or in bacteraemia/sepsis. The aim of diagnostic guidelines is to determine the specific type and systemic involvement of LcV and to identify an underlying cause. Basic work-up should encompass history of drug intake and of preceding infections, biopsy with immunofluorescence, differential blood count, urine analysis and throat swabs. Therapy of immune complex LcV often does not require aggressive therapy due to a usually favourable course. It includes avoidance or treatment of eliciting agents and use of compression stockings to reduce purpura. There are no large prospective randomized controlled studies. Corticosteroids are indicated when there are signs of incipient skin necrosis. In chronic or relapsing LcV we suggest colchicine as a first-line and dapsone as a second-line therapy. Corticosteroids may reduce the incidence of severe renal insufficiency in children according to some studies, but there is no study showing such an effect in adults. Severe systemic vasculitis requires immunosuppressive strategies.

Humans↗
PubMed2004

Metabolic disturbances during short exercises in dermatomyositis revealed by real-time functional 31P magnetic resonance spectroscopy.

OBJECTIVE: (31)P magnetic resonance spectroscopy (MRS) is useful for evaluating metabolic disturbances in dermatomyositis (DM). However, short-term alterations of metabolic parameters such as Pi/PCr (inorganic phosphate/phosphocreatine) have not been assessed in detail, although they may reveal insights into the origin of the known long-term changes. We therefore performed real-time functional (31)P MRS to find out if there are characteristic short-term alterations of metabolic dynamics during muscular exercise and if they are of diagnostic relevance. METHODS: MRS measurements were performed on lower calf muscles of 10 DM patients and 18 healthy subjects throughout five short (1 min) cycles of submaximal exercise (50% maximum voluntary contraction). RESULTS: Pi/PCr ratios during exercise increased in patients and controls. They rapidly returned to baseline values in the controls, but both Pi and PCr remained above baseline values in patients and resulted in irregular Pi/PCr ratios. This was true for each individual patient, but resulted in broad variation in individual Pi/PCr values. To compare groups with limited patient numbers, it was therefore more appropriate to use a recovery index, i.e. the quotient of the Pi/PCr ratio during and after exercise, which was independent of individual parameters, such as age and the work/energy cost ratio. CONCLUSION: Evaluation of short-term changes by real-time functional (31)P MRS provides insight into alterations of Pi/PCr ratios and could improve diagnostic parameters in DM.

Adenosine Triphosphate↗
PubMed2004

[Leukocytoclastic vasculitis].

Leukocytoclastic vasculitis (LcV) is the most common form of cutaneous vasculitis. Often LcV results from deposition of immune complexes in the vascular wall. When IgA is the dominant immunoglobulin in these complexes, systemic involvement is likely (Henoch-Schönlein purpura), being more severe in adults. LcV in which immune complexes are composed of IgG or IgM are more often limited to the skin and may additionally show minor systemic involvement. In other forms of LcV additional pathophysiological factors play a role. LcV can also be a presenting or accompanying symptom of severe systemic ANCA-associated vasculitis. In some cases, LcV is a sign of bacteriemia. The aim of diagnostic procedures is to determine the specific type of vasculitis and degree of systemic involvement as well as possible causes. If no trigger or cause can be found, uncomplicated cases of LcV should be treated symptomatically. Corticosteroids are indicated at initial signs of necrosis or ulceration. Chronic recurrent LcV may respond to dapsone or colchicine. Severe systemic vasculitis requires immunosuppressive therapy.

Adolescent↗
PubMed2004

Lymphogranuloma venereum - a rare cause of genital ulcers in central Europe.

Lymphogranuloma inguinale, caused by Chlamydia trachomatis serovar L1-L3 is rare in patients from western countries but needs yet to be considered in the differential diagnosis of genital ulcers. We report a case of a young male patient without any eventful travel history who presented with a genital ulcer at the sulcus coronarius and painfully enlarged lymph nodes in the right inguinal area. The typical clinical picture and serum IgM and IgG antibody titers of 1:16 and 1:512, respectively, against C. trachomatis were suggestive of infection with C. trachomatis serovar L1-L3. The diagnosis was confirmed by isolation of the organisms from the ulcer ground and subsequent sequence analysis of the omp1 gene which led to identification of C. trachomatis genotype L2 with 99% homology to a reference strain of C. trachomatis serovar L2. The lesion healed rapidly under treatment with doxycycline for 3 weeks, and the lymph nodes did not ulcerate. Thus, clinical suspicion was confirmed by genotyping of the isolated strain allowing timely diagnosis and treatment of lymphogranuloma inguinale.

Adult↗
PubMed2003

[Comèl-Netherton syndrome with bacterial superinfection].

A 10-year old boy, the child of unrelated Bosnian parents presented with a superinfected ichthyotic erythroderma. The clinical features, histological findings and hair analysis led to the diagnosis of the autosomal-recessive inherited Comel-Netherton syndrome witch bacterial superinfection. Under careful therapy with small amounts of topical tacrolimus (Protopic 0.1% ), he improved and had longer disease-free intervals. Tacrolimus was administered intermittently and not during acute flares, thus avoiding systemic resorption even after long-time treatment despite the disturbed epidermal barrier in Comel-Netherton syndrome. Staphylococcus aureus producing enterotoxin C was isolated during flares which were sometimes accompanied by marked bacterial superinfection. It is possible, that this super antigen is involved in the observed aggravation of disease. The topical therapy with tacrolimus is an easy, flexible therapeutic option for this rare genodermatosis.

Anti-Bacterial Agents↗
PubMed2003

Alpha-melanocyte stimulating hormone prevents lipopolysaccharide-induced vasculitis by down-regulating endothelial cell adhesion molecule expression.

The neuroendocrine hormone alpha-melanocyte stimulating hormone (MSH) has profound antiinflammatory and immunomodulating properties. Here we have examined the possibility that alpha-MSH may interfere with the expression and function of cell adhesion molecules (CAMs) expressed by human dermal microvascular endothelial cells (HDMECs) in response to lipopolysaccharide (LPS) or TNFalpha in vitro and in vivo. In HDMEC, alpha-MSH (10(-8)/10(-12) M) profoundly reduced the mRNA and protein expression of E-selectin, vascular CAM (VCAM)-1, and intercellular CAM (ICAM)-1 induced by LPS or TNFalpha as determined by semiquantitative RT-PCR, ELISA, and fluorescence-activated cell sorter analysis. In addition, alpha-MSH significantly impaired the LPS-induced ICAM-1 and VCAM-1-mediated adhesion of lymphocytes to HDMEC monolayer in a functional adhesion assay. Likewise, alpha-MSH effectively inhibited the transcription factor nuclear factor-kappaB activation in HDMEC, which is required for CAM gene expression. Importantly in vivo, in murine LPS-induced cutaneous vasculitis (local Shwartzman reaction), a single ip injection of alpha-MSH significantly suppressed the deleterious vascular damage and hemorrhage by inhibiting the sustained expression of vascular E-selectin and VCAM-1. This persistent expression has been implicated in the dysregulation of diapedesis and activation of leukocytes, which subsequently leads to hemorrhagic vascular damage. Our findings indicate that alpha-MSH may have an important therapeutical potential for the treatment of vasculitis, sepsis, and inflammatory diseases.

Animals↗
PubMed2003

[Atypical erythema gyratum repens secondary to bronchogenic carcinoma].

Erythema gyratum repens (EGR) is an obligate paraneoplastic eruption that indicates an underlying malignancy, most commonly cancer of the lung or breast. The characteristic clinical finding is a rapidly expanding, mildly scaling dermatosis with a 'wood-grain' pattern. This typical concentric erythema is not seen in all patients. Other findings may include pruritus, palmoplantar keratoderma and/or blood eosinophilia. We report a case of EGR where the diagnosis was suggested less by the wood-grain pattern than by the dynamics of the lesions.

Adult↗
PubMed2002

Vascular endothelial growth factor causally contributes to the angiogenic response upon ultraviolet B irradiation in vivo.

BACKGROUND: Ultraviolet (UV)-B irradiation has been shown to be an inducer of vascular endothelial growth factor (VEGF) in primary keratinocytes and epidermal cell lines in vitro. OBJECTIVES: To determine the expression pattern and the causal role of VEGF in the UVB-mediated angiogenic response in vivo in human skin and in a mouse model. METHODS: Skin biopsies or epidermal lysates thereof were studied for VEGF expression following UVB irradiation at a dose of 50 or 60 mJ cm-2, respectively, using immunostaining and a VEGF-specific highly sensitive sandwich enzyme-linked immunosorbent assay. The VEGF-dependent increase in vessels upon repetitive UVB irradiation was studied in skh-1 hairless mice using immunostaining for factor VIII-related antigen (FVIII RAG) in the presence and absence of intraperitoneally injected neutralizing VEGF antibodies. RESULTS: VEGF was found to be induced in the epidermis following UVB irradiation of human and mouse skin. Repetitive UVB irradiation of skh-1 hairless mice resulted in an increase in FVIII RAG positive vessels in the skin. UVB-induced angiogenic response could be partly abrogated by neutralizing antibodies against VEGF, while isotype-matched IgG control antibodies did not reveal any suppressive effect. CONCLUSIONS: Our results support previous in vitro data and show the in vivo relevance of VEGF as a paracrine inducer of cutaneous vessels after UVB irradiation.

Animals↗
PubMed2002

Upregulation of epidermal surface molecule expression in primary and ultraviolet-induced lesions of lupus erythematosus tumidus.

BACKGROUND: Lupus erythematosus tumidus (LET), a photosensitive skin disorder with characteristic clinical and histological features, has not been generally accepted as a subset of cutaneous lupus erythematosus (CLE). OBJECTIVES: To analyse the expression of epidermal surface molecules in skin biopsy specimens from patients with LET and to relate the results to other variants of CLE, such as discoid lupus erythematosus (DLE) and subacute CLE (SCLE). METHODS: In total, 45 patients with different subtypes of CLE were included in the study, and cryostat sections from primary and ultraviolet (UV) A- and UVB-induced skin lesions were investigated using immunohistochemical methods. RESULTS: In contrast to healthy controls, skin lesions of LET showed upregulation of intercellular adhesion molecule-1 (ICAM-1) and histocompatibility class II molecules (HLA-DR), with an expression pattern resembling that seen in DLE and SCLE. Furthermore, staining with a monoclonal antibody against 27E10, a distinct marker for cell activation and differentiation, revealed intense focal or band-like labelling of all epidermal layers independent of the type of lesion. CONCLUSIONS: Expression of epidermal surface molecules such as ICAM-1, HLA-DR and 27E10 is equally upregulated in primary and UV-induced lesions of patients with LET, DLE and SCLE. These results support our recent clinical findings that LET represents a distinct subset of CLE with a similar immunopathomechanism rather than a different disease.

Adult↗