Allogeneic stem cell transplantation in patients with aggressive primary cutaneous T-cell lymphoma - a case series of the ADF working group "cutaneous lymphomas".

BACKGROUND: Allogeneic stem cell transplantation (alloSCT) is a treatment option for primary cutaneous T-cell lymphomas that may induce long-lasting complete remissions. Little information is available on safety and efficacy. PATIENTS AND METHODS: We retrospectively reviewed the data from patients with primary cutaneous T-cell lymphoma treated in the Departments of Dermatology of the Universities of Bochum, Mannheim and Cologne who received subsequent alloSCT between 2005 and 2012. RESULTS: Nine patients with aggressive primary cutaneous T-cell-lymphoma received alloSCT. With a follow-up of 14 to 36 months after transplantation, 4 patients are alive and in complete remission. Two patients had recurrent disease post-transplantation, which was successfully treated with donor lymphocyte infusions. Non-relapse mortality was observed in three patients in advanced disease stages within six months after alloSCT. One patient showed only partial remission and died of disease after 32 months and one patient died 26 months after alloSCT with cause of death unknown. CONCLUSIONS: This report documents the possible benefit of a graft-versus-lymphoma effect in primary cutaneous T-cell lymphoma, as has been observed for other T-cell malignancies and emphasizes that alloSCT warrants further studies in this setting.

Association of autoimmune diseases with lichen sclerosus in 532 male and female patients.

Lichen sclerosus is a relatively common chronic inflammatory skin disease that predominantly affects the anogenital area. Accumulating evidence indicates that lichen sclerosus in women may be associated with other autoimmune disease, whereas this association seems to lack in male patients. We retrospectively evaluated the prevalence of autoimmune diseases and serological parameters indicative for autoimmunity in male and female patients with lichen sclerosus. Of the 532 patients (396 women, 136 men; 500 adults, 32 children; mean age: 49 years; range 1-89 years; female:male ratio 3:1), 452 (85%) had genital and 80 (15%) had extragenital disease. In women, lichen sclerosus was significantly more often associated with at least one autoimmune disease as compared to men (odds ratio [OR] 4.3, 95% confidence interval [CI] 1.9-9.6; p<0.0001). Moreover, female patients with lichen sclerosus had sinificantly more often associated autoimmune thyroid diseases (OR 4.7, 95% CI 1.8-11.9; p<0.0002), antithyroid-antibodies (OR 2.7, 95% CI 1.1-6.5; p=0.023), and elevated autoantibodies (OR 4.1, 95% CI 1.9-9.3; p<0.0001) as compared to male patients. This observation is suggestive for a different pathogenetic background in male and female patients.

Coexistence of lichen sclerosus and morphea: a retrospective analysis of 472 patients with localized scleroderma from a German tertiary referral center.

BACKGROUND: The coexistence of lichen sclerosus (LiS) and localized scleroderma (LoS) has sporadically been reported in the literature. Recently, a prospective multicenter study demonstrated a surprisingly high percentage of genital LiS in patients with morphea. OBJECTIVE: The aim of this study was to determine the prevalence of LiS in a cohort of patients with LoS who presented at a tertiary referral medical center for connective tissue diseases in Germany. METHODS: We retrospectively evaluated the prevalence of genital and extragenital LiS in adult and pediatric patients with different subtypes of LoS. Secondary outcome measures included demographic characteristics and prevalence of other concomitant autoimmune diseases. RESULTS: Of the 472 patients (381 adults, 91 children; mean age: 46 years; range, 4-88 years; female to male ratio: 3.5:1 in adults and 8:1 in children) with LoS, 27 (5.7%) also presented with LiS (19 extragenital and 8 genital lesions). LiS exclusively occurred in patients with plaque-type (morphea) and generalized LoS. Twenty-six of the 27 (96.2%) patients with concomitant LoS and LiS were adults. Compared with LiS in the general population, LiS was significantly more frequent in LoS as indicated by an odds ratio of 18.1 (95% confidence interval 2.6-134.2; P < .0001). In all, 38 (8.1%) patients with LoS had other autoimmune disorders (most frequently Hashimoto thyroiditis, rheumatoid arthritis, and alopecia areata). LIMITATIONS: This was a retrospective study. CONCLUSIONS: This large retrospective analysis confirms recent reports of a high prevalence of LiS in patients with LoS. Based on these findings, patients with LoS, especially those with morphea, should be carefully screened for concomitant LiS, including inspection of the anogenital region.

Cytokine and chemokine ligand expression in cutaneous lupus erythematosus.

There is increasing evidence that cytokines as well as chemokines are important players in the pathogenesis of lupus erythematosus (LE). We aimed to compare cytokine and chemokine profiles in different types of cutaneous LE. We investigated lesional mRNA and protein expression of various cytokines and chemokines in patients with chronic discoid LE (CDLE, n=15), subacute cutaneous LE (SCLE, n=11), and lupus erythematosus tumidus (LET, n=21). TNF-α, INF-γ, TGF-ß, IL-6, IL-10, IL-12p40, CXCL9, and CXCL10 mRNA expression were significantly increased in SCLE when compared to CDLE. Moreover, LET also showed significantly increased mRNA expression of TNF-α, TGF-ß, IL-10, IL-12p40 and CXCL9, as compared to CDLE. In all LE subtypes, CXCL9 and CXCL10 mRNA expression significantly correlated with INF-γ mRNA expression, as indicated by r-values ranging from 0.71 - 0.87. Immunohistochemistry for TNF-α, INF-γ, and IL-10 gave support to our RT-PCR results. In conclusion, our results suggest that T helper 1, as well as T helper 2 cytokines are differentially expressed in CDLE, SCLE, and LET. Compared to CDLE, the highest cytokine and chemokine ligand profiles are found in SCLE followed by LET. Our correlation studies also support the importance of an IFN-driven inflammation in cutaneous LE.

RNA polymerase III autoantibodies may indicate renal and more severe skin involvement in systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is a multiorgan autoimmune disorder characterized by sclerosis of the skin and organs as well as the presence of antinuclear autoantibodies. Several types of antinuclear autoantibodies have been described in SSc, associated with distinct disease entities and differences in prognosis. METHODS: The aim of this study was to screen for the presence of antibodies reacting with RNA polymerase III (anti-RNAP3) in a large cohort of patients with SSc treated at a tertiary referral center and to evaluate correlations with disease severity. RESULTS: Anti-RNAP3 antibodies were detected in 11 of 158 patients (7.0%). Eight of the 11 (72.7%) anti-RNAP3-positive patients had diffuse cutaneous SSc (P < 0.01). A higher modified Rodnan skin score, associated with diffuse SSc, correlated with the presence of anti-RNAP3 (P < 0.0001). The detection of anti-RNAP3 antibodies strongly correlated with the presence of renal involvement (P < 0.0001). The odds ratio of RNAP3-positive patients to develop renal involvement was 80.1 (95% CI 9.3-690.1). CONCLUSIONS: This study demonstrates that the detection of anti-RNAP3 antibodies in patients with SSc correlates with renal crisis and severe cutaneous involvement. The possibility to detect specific antibodies with a prognostic value can lead to a better risk management of patients with SSc.

Immunohistochemical analysis of FOXP3+ regulatory T cells in healthy human skin and autoimmune dermatoses.

BACKGROUND: Regulatory T cells (Tregs) play an important role in autoimmune diseases. In skin, the presence of Tregs is thought to be mandatory for suppression of autoreactive T cells. Here, we assess the number of Tregs in skin of healthy subjects and patients with an autoimmune dermatosis. METHODS: Immunohistochemical stainings for CD3 and FOXP3 on skin biopsies of healthy subjects and subjects with psoriasis, vitiligo, pemphigus vulgaris, bullous pemphigoid, and halo nevus to assess the number of T and regulatory T cells, respectively. RESULTS: Low numbers of CD3+ and FOXP3+ cells were seen in the skin of healthy controls (median = 0.5%). A significantly higher frequency of Tregs was seen in lesional skin of patients with psoriasis (median = 12.4%) and patients with bullous pemphigoid (median = 10.1%) as compared to controls. In vitiligo (median = 0.0%), pemphigus vulgaris (median = 5.2%), and halo nevi (median = 5.4%), no significant difference in number of FOXP3+ cells was observed when compared to controls. CONCLUSIONS: As confirmed in the literature, few Tregs were seen in healthy skin. A high number of Tregs were present in lesional skin from patients with psoriasis and bullous pemphigoid. These results support the hypothesis that not a decrease in number but rather a decrease in function of Tregs would be at the basis of autoimmune skin diseases, which could result in unrestrained activation autoreactive T cells in skin of patients with autoimmune dermatoses.

UV-A1 phototherapy vs clobetasol propionate, 0.05%, in the treatment of vulvar lichen sclerosus: a randomized clinical trial.

IMPORTANCE: Topical corticosteroids are the current first-line therapy for vulvar lichen sclerosus (VLS). UV-A1 phototherapy may be a promising alternative treatment option, but controlled studies are lacking. OBJECTIVE: To compare the efficacy of high-potent topical corticosteroids with UV-A1 phototherapy in the treatment of VLS. DESIGN, SETTING, AND PARTICIPANTS: A 2-arm randomized clinical trial was conducted at a university hospital dermatology department according to the intention-to-treat principle with last observation carried forward. The study population comprised 30 female patients with VLS. INTERVENTIONS: Treatment of VLS with clobetasol propionate, 0.05%, ointment applied once daily for 3 months or medium-dose UV-A1 (50 J/cm²) home-based phototherapy, performed 4 times weekly for 3 months. MAIN OUTCOMES AND MEASURES: Mean relative reduction of the total clinician's score (TCS) was considered the primary outcome measure. Secondary outcome measures included the reduction of pruritus and burning and/or pain according to a visual analog scale (VAS), a health-related quality of life score (Skindex-29), 20-MHz ultrasonography, and histopathological analysis before and after 3 months of therapy. RESULTS: Fifteen patients were randomized in each treatment arm, and 2 patients dropped out in both treatment arms. After therapy, both therapies resulted in a significant decrease in mean TCS (51.4% [95% CI, 39.7% to 63.0%] for clobetasol ointment [P < .001] and 35.6% [95% CI, 18.2% to 53.1%] for UV-A1 phototherapy [P = .006]). No significant difference was found between both treatments (P > .05). The Skindex-29 (mean difference [MD], 29.6 [95% CI, 7.9 to 51.2] [P = .009]) and the VAS score for pruritus (MD, 4.6 [95% CI, 1.5 to 7.7] [P = .005]) and burning and/or pain (MD, 4.2 [95% CI, 1.9 to 6.6] [P = .001]) significantly decreased after clobetasol treatment. After UV-A1 phototherapy, the VAS score for burning and/or pain (MD, 3.2 [95% CI, 0.7 to 5.7] [P = .01]) was also significantly reduced; however, there was no significant reduction in pruritus (MD, 2.1 [95% CI, 0.5 to 3.7] [P = .16]) and in the Skindex-29 score (MD, 4.9 [95% CI, -12.6 to 22.4] [P > .99]). A significant reduction of the corium thickness and a significant increase in dermal density in 20-MHz ultrasonography as well as significant histopathological reduction of the inflammatory infiltrate was observed after clobetasol treatment but not after UV-A1 phototherapy. CONCLUSIONS AND RELEVANCE: Although resulting in a significant clinical improvement, UV-A1 phototherapy was inferior to the current gold standard treatment with topical high-potent corticosteroids with respect to practicability, relief of itch, and improvement in quality of life. UV-A1 phototherapy may be considered a potential second-line treatment for VLS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01400022.

Treatment regimens, protocols, dosage, and indications for UVA1 phototherapy: facts and controversies.

During the last three decades, ultraviolet A1 (UVA1) phototherapy has emerged as a specific phototherapeutic modality with distinct modes of action and some well established indications. Atopic dermatitis, localized scleroderma, and systemic lupus erythematosus seem to be the conditions with the best evidence regarding efficacy and safety of UVA1 phototherapy. Further indications for UVA1 include subacute prurigo, lichen sclerosus, dyshidrotic dermatitis, cutaneous T cell lymphoma, urticaria pigmentosa, and pityriasis rosea; nevertheless, there are some unknowns, uncertainties, and controversies concerning short- and long-term side effects, efficacy and dosage regimens of UVA1 phototherapy in some conditions. We describe and discuss treatment regimens, protocols, dosage, and indications for UVA1 phototherapy.

Optical coherence tomography in dermatology: technical and clinical aspects.

Optical coherence tomography (OCT), a fairly new non-invasive optical real-time imaging modality, is an emergent in vivo technique, based on the interference (Michelson interferometry) of infrared radiation and living tissues, that allows high-resolution, 2- or 3-dimensional, cross-sectional visualisation of microstructural morphology of tissues. OCT provides depth-resolved images of tissues with resolution up to a few micrometers and depth up to several millimetres depending on tissue type. The investigations using OCT to assess skin structure in clinical settings started in the past decade and consequently proved that this imaging method is useful in visualizing subsurface structures of normal skin, including the epidermis, dermoepidermal junction, dermis, hair follicles, blood vessels and sweat ducts. An increasing number of papers brought evidence of the utility and the precision of OCT technology, in its different technical variants, in diagnosing and monitoring skin disorders, including malignancies and inflammatory conditions, respectively. The present comprehensive review describes and illustrates technical aspects and clinical applications of OCT methods in dermatology.