Manfred Wolter

Expression of polo-like kinase (PLK1) in thin melanomas: a novel marker of metastatic disease

Background: The maximum thickness of a primary malignant melanoma as measured by Breslows method is currently the most important prognostic factor. However, some thin melanomas (≤ 0.75 mm), which should have an excellent prognosis according to Breslow, can be lethal due to their ability to metastasize.

Incidence and causes of heparin-induced skin lesions

Background: Little is known about the incidence and causes of heparin-induced skin lesions. The 2 most commonly reported causes of heparin-induced skin lesions are immune-mediated heparin-induced thrombocytopenia and delayed-type hypersensitivity reactions. Methods: We prospectively examined consecutive patients who received subcutaneous heparin (most often enoxaparin or nadroparin) for the presence of heparin-induced skin lesions. If such lesions were identified, we performed a skin biopsy, platelet count measurements, and antiplatelet-factor 4 antibody and allergy testing. Results: We enrolled 320 patients. In total, 24 patients (7.5%, 95% confidence interval [CI] 4.7%–10.6%) had heparin-induced skin lesions. Delayed-type hypersensitivity reactions were identified as the cause in all 24 patients. One patient with histopathologic evidence of delayed-type hypersensitivity tested positive for antiplatelet-factor 4 antibodies. We identified the following risk factors for heparin-induced skin lesions: a body mass index greater than 25 (odds ratio [OR] 4.6, 95% CI 1.7–15.3), duration of heparin therapy longer than 9 days (OR 5.9, 95% CI 1.9–26.3) and female sex (OR 3.0, 95% CI 1.1–8.8). Interpretation: Heparin-induced skin lesions are relatively common, have identifiable risk factors and are commonly caused by a delayed-type hypersensitivity reaction (type IV allergic response). (ClinicalTrials.gov trial register no. NCT00510432.)

Leg ulcers in Klinefelter's syndrome – further evidence for an involvement of plasminogen activator inhibitor‐1

An abnormality in platelet aggregability or fibrinolysis, namely elevated activity of plasminogen activator inhibitor‐1 (PAI‐1), has been recently documented in patients suffering from Klinefelters syndrome associated with leg ulceration without underlying venous insufficiency. To determine whether increased PAI‐1 activity is a general feature of Klinefelters syndrome, or more specifically associated with leg ulceration, we investigated PAI‐1 influencing parameters and PAI‐1 activity in two groups of patients: (i) Klinefelter patients suffering from leg ulceration (n=7); and (ii) Klinefelter patients without leg ulceration (n=6). On analysing PAI‐1 influencing parameters such as age, body mass index, triglycerides, C‐reactive protein, testosterone, smoking behaviour, the presence of diabetes mellitus, and artierial hypertension, respectively, we found no statistically significant differences between the two groups. However, PAI‐1 activity in group 1 was highly significantly elevated compared with that in group two patients (P<0.005). We conclude that (i) PAI‐1 activity is not elevated in Klinefelters syndrome in general; (ii) elevation of PAI‐1 activity in patients suffering from Klinefelters syndrome does not appear to be secondary to PAI‐1 influencing parameters; and (iii) elevation of PAI‐1 activity may play a crucial role in the pathogenesis of leg ulceration in Klinefelters syndrome. Therefore, a therapy for leg ulceration in Klinefelters syndrome that aims to return the elevated PAI‐1 activity to normal should be explored.

Sodium thiosulphate as a promising therapeutic option to treat calciphylaxis

A 35-year-old haemodialysis-dependent woman with chronic renal failure developed large, very painful necrotic ulcers and necrosis on the thighs, buttocks and the abdomen with signs of fast progression. The skin biopsy specimens showed a broad necrosis of the epidermis and thrombosed dermal vessels with focal calcium deposits within the wall. In addi tion, laboratory findings presented an increased product of serum calcium and phosphate concentrations. Thus, we diagnosed calciphylaxis on the basis of clinical, biochemical and histopathological criteria. We initiated a therapy in which our patient was treated with intravenous sodium thiosulphate 3 times weekly. Already after 2 weeks of treatment, no new lesions were detectable and there was a dramatic pain relief. In the following 4 weeks, a successive decline of the ulcers and the healing of individual tissue defects could be seen. Four months after the start of the therapy, the patient underwent successful renal transplantation. Thus, the intravenous therapy of calciphylaxis with sodium thiosulphate might be a new effective alternative in the treatment of this life-threatening disease.

Screening for Body Dysmorphic Disorder in Dermatological Outpatients

Background: Although body dysmorphic disorder (BDD) is frequently found in dermatological settings, it often remains unrecognised. The aims of the current study were to validate the Dysmorphic Concern Questionnaire (DCQ) as a screening instrument; and to estimate the frequency of dysmorphic concerns in a dermatological sample of female outpatients. Patients and Methods: Item characteristics and factor structure of the DCQ were analysed on the basis of data from an unselected sample of 156 dermatological outpatients. In addition, to investigate discriminative validity of the DCQ, 65 patients, including 22 patients with BDD, 21 patients with disfiguring dermatological conditions and 21 patients with non-disfiguring, mild dermatological conditions participated in the study. Diagnoses were based on the Body Dysmorphic Disorder Diagnostic Module. Additionally, the Yale-Brown Obsessive Compulsive Scale modified for BDD was applied, and the patients completed a depression questionnaire. Results: The factor structure and internal consistency of the DCQ were satisfactory. Significant correlations with depressive mood and obsessive-compulsive symptoms confirm its convergent validity. The DCQ revealed significant differences between BDD patients, patients with disfiguring disorders, and patients with non-disfiguring disorders, thus demonstrating a high discriminative validity. A cut-off value of ≧14 provided the best balance of sensitivity and specificity and resulted in correct classification of 84.6% of the patients. Of the unselected outpatients sample 9% achieved positive test results that indicate clinically significant dysmorphic concerns. Conclusion: The results confirm the validity of the DCQ as a sensitive and specific screening instrument that can be recommended as a routine assessment instrument in clinical practice.

Diagnostic impact and sensitivity of skin biopsies in Sneddon's syndrome. A report of 15 cases.

Background Sneddons syndrome is defined as a combination of idiopathic livedo racemosa generalisata and symptoms of cerebrovascular defect. The disease usually starts with vascular symptoms in the epidermis, with neurological deficits becoming evident later. For this reason, histological examination of skin biopsies and determination of arteriolar occlusion is of particular importance for reliable categorization and early diagnosis. To date, these methods have been considered to be too insensitive.

Discrimination of facial appearance stimuli in body dysmorphic disorder.

Cognitive-behavioral models of body dysmorphic disorder (BDD) propose that information-processing biases--in particular, selective attention to a defect in ones appearance as well as improved aesthetical perception--might contribute to the development or maintenance of the disorder. In the present study, the authors tested the hypothesis that patients with BDD discriminate facial appearance stimuli more accurately than controls. Sixty female patients from a dermatological clinic participated in the study: 21 patients with BDD, 19 patients with disfiguring dermatological conditions, and 20 patients with nondisfiguring dermatological disorders. Participants rated dissimilarities between pictures of neutral faces that had been manipulated with regard to aesthetic characteristics. Manipulation ratings of participants with BDD were significantly more accurate than those of both control groups. Implications of these results for cognitive theories of BDD are discussed.

Diagnostische Erfassung der Körperdysmorphen Störung Eine Pilotstudie

ZusammenfassungDie diagnostische Erfassung der Körperdysmorphen Störung (KDS) wird aufgrund unscharfer Diagnosekriterien sowie dem Fehlen valider Untersuchungsinstrumente erheblich erschwert. Die vorliegende Pilotuntersuchung überprüft den Beitrag störungsspezifischer Messinstrumente zur Diskrimination von Körperbildstörungen.Studienteilnehmer waren 13 Patienten mit KDS, 13 Patienten mit Gesichtsentstellungen und 21 Patienten ohne Beeinträchtigung des Aussehens. Diese wurden aufgrund eines halbstrukturierten diagnostischen Interviews und eines Ärzteratings der Entstellung rekrutiert. Mittels strukturierter Interviews wurden das Vorliegen von KDS, depressiver Störungen und Soziophobie überprüft und eine Fremdbeurteilung der Zwangssymptome anhand einer modifizierten Form der YBOCS (BDD-YBOCS) vorgenommen. Allen Patienten wurden das Beck-Depressionsinventar sowie die “Social Phobia Scale” und die “Social Interaction Anxiety Scale” vorgelegt.KDS-Patienten unterschieden sich von unbeeinträchtigten und entstellten Patienten bezüglich der Zwangssymptome sowie in der Diskrepanz von Selbst- und Fremdbeurteilung der Entstellung signifikant. Die Depressions- und Sozialphobiefragebogenwerte waren nur gegenüber den unbeeinträchtigten Patienten signifikant höher. Ermittelt wurde eine deutlich erhöhte Komorbidität mit depressiven Störungen. Die Ergebnisse stützen die Nützlichkeit der untersuchten störungsspezifischen Messinstrumente und weisen auf die besondere Bedeutung von Zwangssymptomen bei KDS hin.AbstractThe assessment of body dysmorphic disorder (BDD) is complicated by poorly defined diagnostic criteria and a lack of valid instruments. The present pilot study examines the possible benefit of specific instruments in the discrimination of other body image disorders. Thirteen patients with BDD, 13 with disfiguring defects, and 21 with no significant impairment of appearance participated in the study. The participants were recruited from dermatological outpatients on the basis of semistructured diagnostic interviews and clinical ratings of disfigurement. Furthermore, structured interviews were conducted to determine comorbidity with depressive disorders and social phobia and to obtain a clinical rating of obsessive-compulsive symptoms using the modified version of the YBOCS for body dysmorphic disorders. In addition, the Beck depression inventory, the Social Phobia Scale, and the Social Interaction Anxiety Scale were completed. Patients with BDD differed significantly from disfigured and unimpaired patients in obsessive-compulsive symptoms, in particular obsessions, and the discrepancy between personal and clinical rating of disfigurement. However, depression and social phobia scores were only higher in comparison with unimpaired patients. Comorbidity with depressive disorders was significantly increased. Our results support the utility of the specific diagnostic instruments and indicate the particular importance of obsessive-compulsive symptoms in BDD.

Mid-dermal elastolysis associated with Hashimoto's thyroiditis.

We report the case of a 38‐year‐old Caucasian female presenting asymptomatic plaques of fine wrinkling and perifollicular papular protrusions especially on the trunk. Histological examination evidenced loss of elastic fibers in the mid‐dermis due to elastophagocytosis, with giant cells and granuloma formation. Moreover, elevated titers of thyroid autoantibodies were detected and thyroid ultrasound revealed echo‐poor tissue. These findings met the diagnoses of mid‐dermal elastolysis and Hashimotos thyroiditis. This association has not been reported before. We present a comprehensive overview of the literature and discuss the pathogenetic aspects of mid‐dermal elastolysis and the significance of the association with Hashimotos thyroiditis.

The transformation of pityriasis lichenoides chronica into parakeratosis variegata in an 11‐year‐old girl

Parakeratosis variegata is a rare disorder with unknown aetiology. In a few cases it arises from benign skin diseases such as pityriasis lichenoides et varioliformis acuta (Mucha Habermann disease) or pityriasis lichenoides chronica. However, transformation into malignant diseases such as cutaneous T‐cell lymphoma has been observed. We report an 11‐year‐old girl with a 10‐year history of pityriasis lichenoides chronica now presenting with parakeratosis variegata. Analysis of skin infiltrating T cells showed clonally rearranged T‐cell receptor γ chains occurring with a frequency of more than 2%. This finding is compatible with the clinical observation of parakeratosis variegata transforming into a malignant T‐cell disorder. We therefore suggest that patients suffering from parakeratosis variegata and other diseases such as pityriasis lichenoides et varioliformis acuta or pityriasis lichenoides chronica should be continuously monitored.