Lichen sclerosus (LS), frequently reported in the dermatologic literature as lichen sclerosus et atrophicus, is a chronic inflammatory skin disease of unknown etiology that leads to substantial discomfort and morbidity. It commonly affects adult woman in the genito-anal region (Figure 1A) but also occurs elsewhere.^1-4 Lichen sclerosus has clinical and histological similarities with morphea, and some investigators consider this entity a superficial variant of morphea, an opinion supported by its frequent coincidence with morphea.^5,6 Lichen sclerosus shares similarities and common features with acrodermatitis chronica atrophicans (ACA), a chronic form of borreliosis, particularly histological findings such as an infiltrate of lymphocytes admixed with some plasma cells, an increase in fibrocytes and fibroblasts, and a diffuse dermal fibrosis to sclerosis (Figure 1B and C).⁷ These observations have led several investigators to consider the possibility of Borrelia burgdorferi sensu lato as a common etiologic factor for both diseases. Since the first proposal of Bburgdorferi as a causative agent by Aberer and Stanek⁸ in 1987, conflicting results have been obtained by different studies using serological, immunohistochemical, culture, and polymerase chain reaction (PCR) approaches. Borrelia species have frequently been detected in Europe, but not in cases from the United States. Studies reporting a positive association between B burgdorferi infection and LS found evidence of the organism in 10% to 68% of cases; on the other hand, there are reports in which no positive cases could be identified (Table 1).^8-20

Metallothioneins (MT) are ubiquitous, intracellular small proteins with high affinity for heavy metal ions. In the last decades, it was shown that MT overexpression in a variety of cancers is associated with resistance to anticancer drugs and is combined with a poor prognosis. In this prospective study, we examined the role of MT overexpression in melanoma patients as a prognostic factor for progression and survival. Between 1993 and 2004, 3386 patients with primary cutaneous melanoma were investigated by using a monoclonal antibody against MT on routinely fixed, paraffin-embedded tissues. In all, 1270 patients could be followed up for further statistical analysis (Fisher's exact test, Mantel–Haenszel χ² test, Kaplan–Meier curves). The MT data of disease-free interval and overall survival were compared univariately and multivariately in Cox regression analysis. Immunohistochemical overexpression of MT in tumour cells of patients with primary melanoma (310 of 1270; 24.4%) was associated with a higher risk for progression (117 of 167; 70.1%) and reduced survival (80 of 110; 72.7%) of the disease (P<0.0001). Similarly, Kaplan–Meier curves gave highly significant disadvantages for the MT-positive group. Univariate analysis (relative risk 7.4; 95% confidence interval (CI) 5.2–10.2; P<0.0001 for progression; relative risk 7.1; 95% CI 4.7–10.9; P<0.0001 for survival), as well as multivariate analysis with other prognostic markers resulted in MT overexpression as a highly significant and independent factor for prognosis in primary melanoma.

Objective. To investigate the efficacy of the endothelin receptor antagonist, bosentan, in patients with RP secondary to SSc without pre-existing digital ulcers. Methods. Single-centre, randomized, prospective, double-blinded comparison of bosentan and placebo. Patients received either 62.5 mg bosentan twice daily for 4 weeks, followed by 125 mg twice daily for 12 weeks or matching doses of placebo. Results. Of the 17 patients enrolled, 16 completed the study and 1 withdrew from the study due to the reversible development of peripheral oedema. Compared with placebo, bosentan did not improve the frequency, duration, pain or severity of RP attacks. However, in contrast to placebo, bosentan significantly improved the functional scores. With respect to baseline, the scleroderma HAQ disability index changes were in favour of bosentan at Weeks 12 (P = 0.03) and 20 (P = 0.01), and the United Kingdom functional score changes at Weeks 8 (P = 0.038) and 16 (P = 0.039). Conclusions. Bosentan is not effective in SSc-related RP without pre-existing digital ulcers, but it might benefit functional impairment in those patients. Trial Registration. European Union Drug Regulating Authorities Clinical Trials, https://eudract.emea.europa.eu, EudraCT-Nr 2004-002686-21.