Treatment of refractory adult‐onset pityriasis rubra pilaris with TNF‐alpha antagonists: a case series

Background Pityriasis rubra pilaris (PRP) is a rare inflammatory dermatosis with frequent clinical presentation as erythroderma. Conventional systemic treatment is often unsatisfactory and limited by long‐term toxicity. The use of tumour necrosis factor (TNF) antagonists has been reported previously in single cases, but lacking long‐term follow‐up or comparison between different biological agents. Objectives To assess the long‐term efficacy and safety of TNF‐alpha antagonist, infliximab and etanercept, either in monotherapy or in combination therapy of severe, refractory adult‐onset PRP. Methods Seven patients of adult‐onset PRP, six newly diagnosed type‐I and 1 type‐II, which were resistant or ineligible to conventional systemic treatment, received a single course of infliximab or etanercept therapy, alone or in combination with low‐dose acitretin (>0.25 mg/kg/daily). After complete remission and treatment discontinuation, a follow‐up period of 12 months was evaluated for relapses. Results Six patients obtained complete remission after a single course of anti‐TNF‐alpha therapy: mean therapy duration was 19.3 weeks (range 6–48 weeks). All patients obtained significant clearing (>75% of body surface area) of skin lesions at week 12. Two patients with marked keratoderma developed localized disease recurrence during treatment. During follow‐up, only a single patient, affected by type II PRP, had disease relapse. Conclusions Both TNF‐alpha antagonists proved successful for the treatment of refractory, adult‐onset PRP, yielding complete and persistent clinical responses in type‐I PRP. Infliximab was associated with a more rapid onset of action, while treatment duration was comparable with etanercept. PRP type II warranted long‐term therapy and showed relapse after drug discontinuation.     

Pityriasis rubra pilaris in association with laryngeal carcinoma

Pityriasis rubra pilaris (PRP) is a rare group of hyperkeratotic, papulosquamous diseases that can be acquired or inherited. Cases of PRP associated with malignancy have been rarely reported. We report a case of 46‐year‐old man who presented with rapidly progressing PRP as a possible initial cutaneous symptom of a previously undiagnosed laryngeal carcinoma. Microlaryngoscopy was performed because of the patient’s hoarseness, and this revealed leucoplakia on the left vocal cord. Histopathological examination led to the diagnosis of squamous cell carcinoma in situ. After surgical treatment, the clinical signs of PRP began to resolve, and the patient was free of skin lesions at follow‐up. This case represents a rare coexistence of PRP with malignancy, and indicates that PRP can occur as paraneoplastic dermatosis associated with laryngeal cancer.     

Increased stratum corneum serine protease activity in acute eczematous atopic skin

Background Atopic dermatitis (AD) is a chronic inflammatory disease associated with changes in stratum corneum (SC) structure and function. The breakdown of epidermal barrier function in AD is associated with changes in corneocyte size and maturation, desquamation, lipid profiles, and some protease activities. Objectives The purpose of this study was: (i) to examine physiological changes in lesional (L) skin of acute eczematous AD, compared with nonlesional (NL) AD skin and healthy (H) skin, using sequential tewametry and SC protein analysis to estimate SC thickness; and (ii) to assess which serine proteases might be involved in pathogenesis. Methods Six subjects with H skin, six AD patients with NL skin and six AD patients with mild to moderate eczema (L skin) were enrolled. Skin was assessed using several noninvasive techniques but SC thickness was estimated using tewametry and SC protein content of D‐Squame strippings. SC integrity was determined by sequential tape stripping (D‐Squame) and infrared densitometry. Kallikreins, plasmin, urokinase and leucocyte elastase protease activities together with a novel SC tryptase‐like enzyme activity were quantified. Results Transepidermal water loss (TEWL) levels after D‐Squame stripping were elevated in L compared with NL and H skin at all sampling points (P < 0·05). Conversely, the amount of SC removed by sequential tape stripping was decreased in L skin, indicating increased intracorneocyte cohesion (P < 0·05). By correlating 1/TEWL values and SC removed as an estimate of SC thickness, a significantly thinner SC was observed in L compared with NL and H skin (P < 0·05). Elevated extractable serine protease activity was measured in AD skin in the order: SC tryptase‐like enzyme (45×), plasmin (30×), urokinase (7·1×), trypsin‐like kallikreins (5·8×) and chymotrypsin‐like kallikreins (3·9×). Leucocyte elastase activity was not detected in H and NL skin but was observed in AD SC samples (L skin). All enzymes were elevated in the deeper layers of L SC compared with NL and H SC samples. All consistently elevated SC protease activities were significantly correlated with the bioinstrumental data. Conclusions We report increased serine protease activities in acute eczematous AD, especially in deeper layers of the SC, including SC tryptase‐like enzyme, plasmin, urokinase and leucocyte elastase activities. These elevations in protease activities were associated with impaired barrier function, irritation, and reduced skin capacitance. Increased SC cohesion was apparent despite elevated TEWL during tape stripping, which would indicate reduced SC thickness in acute eczematous lesions of AD. Indeed, this was observed using an estimate of SC thickness.     

Off-label use of fumarate therapy for granulomatous and inflammatory skin diseases other than psoriasis vulgaris: a retrospective study

Background Fumarates are approved for the systemic treatment of moderate and severe psoriasis vulgaris in Germany. However, a number of studies and case reports indicate their efficacy in the treatment of further inflammatory skin disorders or granulomatous skin diseases. Objectives To examine the efficacy and safety of fumarates for the treatment of granulomatous and inflammatory skin diseases other than psoriasis vulgaris. Patients and methods The therapeutic efficacy and side‐effects of fumarate therapy were analysed retrospectively in patients with granuloma annulare (GA, n = 4), cutaneous sarcoidosis (SA, n = 1), lichen planus (LP, n = 3), pityriasis rubra pilaris (PRP, n = 1) or chronic discoid lupus erythematosus (CDLE, n = 1). Results Six patients (GA: 3/4; LP: 2/3; PRP: 1/1) showed complete clearance and two patients (GA: 1/3; SA: 1/1) had a partial response, and the CDLE patient showed stable disease under a combination therapy with hydroxychloroquine. Side‐effects associated with fumarate therapy were seen in seven of ten patients and resolved spontaneously upon dose reduction or discontinuation of the therapy. Conclusion According to this data, fumarates may represent a new approach in the treatment of granulomatous and inflammatory skin diseases other than psoriasis vulgaris. For the first time, the successful treatment of LP and CDLE with fumarates is reported. Side‐effects are not limiting in most cases, but can hamper a dose escalation.     

The effect of CD34+ cell‐containing autologous platelet‐rich plasma injection on pattern hair loss: a preliminary study

Background Mobilized CD34+ cells in peripheral blood have angiogenic potential, which is an important factor in active hair growth. In addition, activated autologous platelet‐rich plasma (PRP) has been reported to induce the proliferation of dermal papilla cells. Objectives To investigate the clinical efficacy of interfollicular injection of CD34+ cell‐containing PRP preparation for pattern hair loss. Patients and methods CD34+ cell‐containing PRP preparation was injected on the scalps of 13 patients with pattern hair loss, and 13 patients were treated with interfollicular placental extract injection as a control. The numbers of platelets in PRP were microscopically counted and CD34+ cells were evaluated with flow cytometry. Results Three months after the first treatment, the patients presented clinical improvement in the mean number of hairs, 20.5 ± 17.0% (P < 0.0001), mean hair thickness, 31.3 ± 30.1% (P < 0.0001), and mean two‐point score, 84.4 ± 51.7% (P < 0.0001) compared with baseline values. At 6 months, the patients presented clinical improvement in mean hair count, 29.2 ± 17.8% (P < 0.0001), mean hair thickness, 46.4 ± 37.5% (P < 0.0001), and mean two‐point score, 121.3 ± 66.8% (P < 0.0001) compared with baseline. The MIXED procedure revealed that CD34+ cell‐containing PRP treatment presented a higher degree of improvement than placental extract treatment in hair thickness (P = 0.027) and overall clinical improvement (P = 0.023). Conclusion Our data suggest that the interfollicular injection of autologous CD34+ cell‐containing PRP preparation has a positive therapeutic effect on male and female pattern hair loss without remarkable major side‐effects.     

Pityriasis rubra pilaris in children

BACKGROUND: Pityriasis rubra pilaris (PRP) is an uncommon dermatosis in children. Few long-term studies on the treatment and prognosis of PRP in children have been performed. OBJECTIVE: Our purpose was to retrospectively review the clinical course and treatment of all cases of PRP in children 19 years or younger who were seen at the Mayo Clinic. METHODS: The clinical courses of the 30 patients with PRP seen at the Mayo Clinic between 1975 and 1997 were reviewed. RESULTS: The most common presenting form of PRP in children is the type III juvenile form (Griffiths' criteria). Treatment ranged from topical steroids, tar, and ultraviolet B to systemic retinoids and methotrexate. The best response was obtained with isotretinoin; 5 of 6 patients showed 90% to 100% clearing within 6 months of treatment. Follow-up information was obtained by questionnaire and was available for 83% of patients. Overall, 43% had 90% to 100% resolution of their disease, 23% had a moderate response (30%-90% improvement), and 17% had a poor response (<30% improvement). One patient reported spontaneous resolution. Seventeen percent of those who had total clearing had recurrence of PRP within 1 year. CONCLUSION: PRP in children is a noninherited dermatosis with no sex predilection, occurring mainly in the type III classic juvenile form. Retinoids should be considered as first-line treatment for PRP. Recurrence rate, previously thought to be rare, was about 17% in our population.     

Investigation of new co‐factors in 49 patients with pyoderma gangrenosum

Background: Pyoderma gangrenosum is a rare, destructive, ulcerative neutrophilic dermatosis of unknown origin that has been investigated insufficiently in clinical studies. According to current textbooks, it is often associated with chronic inflammatory bowel diseases or other autoimmune disorders. Patients and methods: We retrospectively analyzed data from 49 patients with pyoderma gangrenosum. Results: Our results showed that although only 6.1 % of patients had chronic inflammatory bowel disease, 22.4 % patients had a malignancy, 18.4 % had chronic renal insufficiency, and 42.8 % had anemia. A potentially relevant aspect that has received little attention is an association with endocrine diseases in 38.8 % of patients. 28.6 % of patients had diabetes. Given that 32.6 % of patients were obese, a potential association with metabolic syndrome may be considered as a possible new risk factor for pyoderma gangrenosum. Conclusions: The clinical data from the present study are insufficient for drawing any firm conclusions. We did, however, observe an association between pyoderma gangrenosum and certain as yet unreported co‐factors, in particular metabolic syndrome. This should be considered in further studies.     

Paraneoplastic pityriasis rubra pilaris: case report and literature review

Pityriasis rubra pilaris (PRP; MIM 173200) is an uncommon papulosquamous inflammatory dermatosis. Only a few cases of PRP associated with an underlying malignancy have been documented. We investigated a 59‐year‐old patient presenting with a fulminant form of PRP recalcitrant to systemic retinoid therapy, in whom the skin disease heralded a diagnosis of cholangiocarcinoma. We searched the MEDLINE database to find articles reporting on similar associations of PRP with malignancies. We identified 10 studies linking PRP and malignancies, but an association between PRP and cholangiocarcinoma has not yet been reported.     

Efficacy of oral methotrexate (MTX) monotherapy vs oral MTX plus narrowband ultraviolet light B phototherapy in palmoplantar psoriasis

Palmoplantar psoriasis (PPP) is a chronic, inflammatory dermatosis of the palms and/or soles with significant morbidity. It is notoriously difficult to treat and unresponsive to traditional topical agents. We aim to compare the effect of oral methotrexate (MTX) monotherapy vs MTX plus narrowband ultraviolet light B (NB‐UVB) in the treatment of recalcitrant PPP. This was a comparative clinical trial involving 90 patients of PPP. Eligible patients were randomly assigned to one of the two treatment groups. We aim patients in group A received 10 mg oral MTX weekly, and patients in group B received oral MTX 10 mg weekly and NB‐UVB sessions twice weekly for 12 weeks. There was a statistically significant difference in reduction of modified PPP Area Severity Index (m‐PPPASI) of patients in MTX plus NB‐UVB at week 12. The mean m‐PPPASI at week 12 was 3.66 ± 2.11 in MTX plus NB‐UVB group and 6.51 ± 2.04 in MTX only group (P < .001). Marked improvement (m‐PPPASI 75) was achieved in 20 (44.44%) patients in MTX plus NB‐UVB group compared with 6 (13.3%) in MTX monotherapy group (P < .001). Combination of MTX and NB‐UVB phototherapy helps to attain a better clinical response (reduction in m‐PPPASI score) than MTX monotherapy in the treatment of recalcitrant PPP.     

Efficacy and safety of systemic methotrexate vs. acitretin in psoriasis patients with significant palmoplantar involvement: a prospective,randomized study

Background Palmoplantar psoriasis (PP) is a chronic, inflammatory and proliferative dermatosis of the palms and/or soles with significant morbidity. It is notoriously difficult to treat and unresponsive to traditional topical agents. Material and methods This was a prospective, randomized study involving 111 patients of psoriasis with significant palmoplantar disease. Patients meeting the eligibility criteria were randomly assigned to one of the two treatment groups. Patients in Group I received methotrexate in doses of 0.4 mg/kg weekly, and patients in Group II received acitretin in doses of 0.5 mg/kg daily. Patients were evaluated by modified PPPASI (m‐PPPASI) score for palm and sole involvement at baseline, at two weekly intervals for the first 4 weeks and then four weekly for next 8 weeks. Treatment protocol was continued for a period till patient achieved 75% reduction in m‐PPPASI from baseline or 12 weeks whichever was earlier. Results There was a statistically significant difference in reduction of m‐PPPASI of patients on methotrexate at weeks 8 and 12. The mean m‐PPPASI at week 8 was 15.38 ± 6.08 in methotrexate group and 17.23 ± 5.25 in acitretin group (P = 0.04). The mean m‐PPPASI at week 12 was 10.30 ± 5.97 in methotrexate group and 12.40 ± 5.31 in acitretin group (P = 0.03). Marked improvement (m‐PPPASI 75) was achieved in 12 (24%) patients in methotrexate group compared with 4 (8%) in acitretin group which was statistically significant (P = 0.029). Adverse events were generally mild and were seen in 14 patients in methotrexate group and 15 patients in acitretin group (P = 0.080). Conclusion Methotrexate is relatively inexpensive, safe and efficacious drug for the treatment of psoriasis patients with significant palmoplantar involvement. Acitretin can be used as an alternative therapy and with a good safety profile.     

Association of the novel susceptible locus rs9266150 with clinical features of psoriasis vulgaris in the Chinese Han population

Psoriasis is a chronic multifactorial disease and is considered to be strongly associated with the major histocompatibility complex (MHC) region. We have discovered an independent, novel and susceptible psoriasis risk HLA loci, rs9266150; P = 4.52 × 10^?9 for the first time. In this study, we aimed to verify the relationship between the susceptible locus and the subphenotypes of psoriasis vulgaris (PV), including geographic location, gender, age of onset, family history and present skin lesion types (chronic plaque and guttate). To investigate the distribution and association of the rs9266150 gene with clinical phenotypes of PV in Chinese Han population, we conducted an analysis in case‐control and case‐only subjects in the 9906 controls and 8744 cases by MHC targeted sequencing stratified analysis in this study. Significant associations were found with a northern geographic location in the case‐only (P = 1.97 × 10^?4) and the subphenotype‐control analyses (P = 5.57 × 10^?5), males in the case‐only (P = 4.77 × 10^?3) and the subphenotype‐control analyses (P = 7.31 × 10^?4), and guttate psoriasis in the case‐only (P = 4.08 × 10^?3) and the subphenotype‐control analyses (P = 1.27 × 10^?3). There were no significant differences observed between the age of onset (OR = 1.062, 95% CI: 0.9725‐1.16, P = 1.8 × 10^?1) and the family history of psoriasis (OR = 0.981, 95% CI: 0.9048‐1.064, P = 6.43 × 10^?1). The recessive model provided the best fit for rs9266150 (P = 4.38 × 10^?7). Our results implied that rs9266150 might not only play an important role in the development of psoriasis, but also be positively associated with the geographic location, gender and present skin lesion in the Chinese population.     

Vitamin D deficiency in patients with cutaneous lupus erythematosus is prevalent throughout the year

Background Vitamin D mediates immunomodulatory functions and its deficiency has been associated with an increased prevalence of immunological diseases including systemic lupus erythematosus (SLE). Chronic discoid or subacute cutaneous lupus erythematosus (CLE) are ultraviolet (UV)‐triggered skin diseases. As vitamin D is mostly UV‐derived and not from nutrition, its deficiency is frequent especially during the UV‐deprived winter months. Objective To compare the vitamin D status of patients with CLE with patients with type I allergy and healthy individuals during the summer or winter months. Methods The vitamin D status of patients with CLE (n = 41) was compared with patients with type I allergy (n = 24), healthy individuals (n = 25) and a reference pool (n = 1951) by means of concentrations of circulating storage metabolite 25‐hydroxyvitamin D in the summer and winter. Results Serum 25‐hydroxyvitamin D concentrations were lower during the winter in the reference population, and type I allergic and healthy individuals (29·2–35·5 nmol L^?1) compared with the summer months (56·3–89·8 nmol L^?1) and paralleled by the prevalence of vitamin D deficiency (serum 25‐hydroxyvitamin D < 50 nmol L^?1; winter: 70·8–73·4%, summer: 34·9–39·4%). In contrast, vitamin D deficiency in patients with CLE was prevalent throughout the year (summer: 85·7%, winter: 97·1%). In patients with CLE with concomitant prednisolone treatment, the 25‐hydroxyvitamin D serum levels were comparable with (mean daily intake 877 IU) or without vitamin D supplementation during summer or winter (P = 0·75 and P = 0·14, respectively). Conclusions  Our data identify vitamin D deficiency in patients with CLE throughout the year and indicate that monitoring and correcting the vitamin D status should be considered to prevent bone demineralization and fractures and to modulate beneficially immunological dysfunction.     

Variants in SELL,MRPS36P2, TP63, DDB2, CACNA1H,ADAM19, GNAI1, CDH13 and GABRG2 interact to confer risk of acne in Chinese population

Acne vulgaris is a common skin disease characterized by chronic inflammation of the pilosebaceous unit resulting from androgen‐induced increased sebum production, altered keratinization, inflammation and bacterial colonization of hair follicles by propionibacterium acnes. Our previous genome‐wide association study on acne has identified two new susceptibility loci. To search for potential gene–gene interactions and investigate the best‐fit association models for the single nucleotide polymorphisms (SNP) from these interacting genes, we implemented logistic regression analysis in the combined sample of 2916 cases with severe acne and 4716 controls. The most significant association evidence was observed under an additive model for rs6896064 and under a dominant model the rest of these SNP. Significant interactions between these SNP were observed in this study: the SELL × MRPS36P2 (P_adjusted = 4.15 × 10^?10), TP63 × DDB2 (P_adjusted = 7.62 × 10^?08), DDB2 × CACNA1H (P_adjusted = 1.89 × 10^?07), ADAM19 × GNAI1 × CDH13 (P_adjusted = 1.22 × 10^?04) and ADAM19 × GABRG2 × GNAI2 × CDH13 (P_{ad justed} = 6.33 × 10^?05). These results may contribute to our understanding of acne genetic etiology and account for the additional risk of certain patients.     

Plasma dermcidin levels in acne patients,and the effect of isotretinoin treatment on dermcidin levels

Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit. Dermcidin (DCD) is an antimicrobial peptide released from eccrine sweat glands and sebaceous glands. Studies investigating the role of DCD expression in acne development are scarce. The aim of this study was to determine the relationship between DCD expression and acne vulgaris and the effect of oral isotretinoin treatment on DCD levels. Two groups (one patient group and one control group) were included in the study. The patient group consisted of 30 patients with acne vulgaris who were given oral isotretinoin treatment for 6 months until the cumulative dose was attained. Plasma DCD levels were investigated before and 6 months after treatment. The control group comprised 30 volunteer individuals without acne vulgaris or any inflammatory dermatosis. Of the patients, 24 (80%) had Grade 3, 3 (10%) had Grade 1, and 3 (10%) had Grade 4 acne vulgaris, as determined according to the Pillsbury scoring method. The DCD levels in the control group were significantly higher than those in pretreatment patients (39.53 ± 20.2 vs. 28.60 ± 20.12, p = .004). Additionally, pretreatment DCD levels were significantly increased after 6 months of isotretinoin treatment in the patient group (28.60 ± 20.12 vs. 35.07 ± 24.02, p = .012). The mean pretreatment global acne grading system score of 20.86 ± 4.43 was decreased to 5.17 ± 1.91 in patients after treatment (p < .001). This study indicated that DCD plays an important role in the pathogenesis of acne. It demonstrates anti‐inflammatory properties in acne vulgaris. Moreover, it was shown that isotretinoin treatment may improve acne vulgaris by increasing DCD levels.     

Long-term results of the treatment of pregnancy-induced striae distensae using a 1550-nm non-ablative fractional laser

Background: Striae distensae (SD) are a type of dermal scarring that is quite common and difficult to treat. Two forms are known: striae rubrae (SR) and striae albae (SA). Objective: We compared the long-term clinical effectiveness of a 1550-nm non-ablative fractional laser (NAFL) in treating SR and SA. Materials and methods: We included 16 female patients (8 with SR and 8 with SA) who had developed abdominal SD during pregnancy. All underwent five moderately high-energy sessions of 1550-nm NAFL treatment at 4-week intervals. The strial widths and lengths were measured before, and 1 month and 1 year after treatment. Results: The mean strial width decreased from 6.94 mm before treatment to 3.25 mm at the first follow-up visit (p = 3.95 × 10^?5) and to 3.13 mm at the second follow-up visit (p = 2.44 × 10^?5). Similarly, the mean strial length decreased from 6.06 to 2.88 cm at the first follow-up visit (p = 1.7 × 10^?4) and to 2.75 cm at the second follow-up visit (p = 9.52 × 10^?5). Conclusion: NAFL treatment was effective long term in both SR and SA patients.     

Impact of adalimumab treatment on cardiovascular risk biomarkers in psoriasis: Results of a pilot study

Psoriasis is a chronic systemic immune‐mediated inflammatory dermatosis associated with several comorbidities. Psoriasis patients are at increased risk of developing cardiovascular diseases (CVD), namely, coronary heart disease, stroke or peripheral vascular disease, and psoriasis seems to be an independent cardiovascular risk factor. Antipsoriatic systemic therapy, especially anti‐tumor necrosis factor (TNF)‐α, seems to exert a beneficial effect on these comorbidities. The purpose of this study was: (i) to measure the level of cardiovascular serum markers in psoriasis patients in comparison with healthy volunteers; and (ii) to compare the serum level of the same markers in patients before and 3 months after adalimumab therapy. We investigated six biomarkers connected to CVD: C‐reactive protein (measured high sensitively, hsCRP), oxidized low‐density lipoproteins (oxLDL), oxLDL/β‐glycoprotein I complex (oxLDL/β2GPI), vascular endothelial adhesion molecule 1 (VCAM‐1), E‐selectin and interleukin (IL)‐22. These biomarkers were measured in 21 patients with moderate/severe psoriasis before and after treatment with adalimumab and in healthy volunteers. hsCRP (P < 0.05), oxLDL‐β2GPI complex (P < 0.05), E‐selectin (P < 0.001) and IL‐22 (P < 0.001) were significantly increased in comparison with healthy controls, whereas oxLDL and VCAM‐1 were also higher in psoriasis patients but the difference did not reach statistical significance. A decrease of E‐selectin (P < 0.001) and IL‐22 (P < 0.001) was observed after 3 months of adalimumab therapy. Inhibition of TNF‐α seems to not only improve psoriasis but also decreases serum cardiovascular biomarkers. E‐selectin and IL‐22 could serve for monitoring of the efficacy of antipsoriatic systemic therapy on cardiovascular risk.     

Atypical fibroxanthoma: a series of 25 cases

Objective Atypical fibroxanthoma is a rare mesenchymal tumour of skin that develops on skin of elderly patients. We analysed our patients with atypical fibroxanthoma over the last 8 years. Patients and methods We analysed the pathology files of our hospital for the period 2001–2009. In all cases, histology and immunohistology were performed. Data on co‐morbidities, treatment and outcome were obtained. Results We identified 25 patients (except two female patients, the rest were men) aged 52–95 years (mean: 79.5 years; standard deviation ± 9.06 years). All tumours were localized in the head and neck region, except a single tumour on the shoulder. Fourteen patients had a cancer history, six had actinic keratoses or Bowen’s disease (n = 1). Five patients had cardiac surgery or pacemaker, one each had a renal transplant, systemic sarcoidosis or non‐Hodgkin’s lymphoma. Medical history was positive for radiotherapy or chemotherapy in four patients. Histology showed a spindle‐shaped dermal and subcutaneous tumour growth intermingled with multinucleated giant cells. The phenotype of tumour cells was vimentin‐positive, but S100‐ and keratin‐negative. Some tumours showed a focal expression of CD68. Complete microhistographic controlled surgery (‘Mohs like’) was possible in all cases followed by mesh‐graft transplantation in three patients. Eighteen patients showed a complete remission. Four patients had a relapse within 2 years of follow‐up treated by surgery. One patient is still under radiotherapy. All patients with a safety margin of 2 cm had no recurrence or relapse during follow‐up. Conclusions Micrographic controlled surgery with wide 2 cm safety margins is the treatment of choice. A regular follow‐up for the next 5 years is recommended.     

Efficacy and safety of secukinumab in the treatment of moderate‐to‐severe plaque psoriasis: a randomized,double‐blind,placebo‐controlled phase II dose‐ranging study

Background Conventional systemic therapies for plaque psoriasis have not fully met the needs of patients, and although current biologic treatments are generally well tolerated, concerns exist with respect to long‐term safety. Interleukin (IL)‐17A is believed to be an important effector cytokine in the pathogenesis of psoriasis and is produced by Th17 cells, a class of helper T cells that act outside the established Th1/Th2 paradigm for regulation of innate and adaptive immunity. Objectives To assess the efficacy and safety of different doses of secukinumab, a fully human anti‐IL‐17A IgG1κ monoclonal antibody, in patients with moderate‐to‐severe plaque psoriasis. Methods Patients (n = 125) were randomized 1 : 1 : 1 : 1 : 1 to receive subcutaneous doses of placebo (n = 22) or secukinumab [1 × 25 mg (n = 29), 3 × 25 mg (n = 26), 3 × 75 mg (n = 21) or 3 × 150 mg (n = 27)] at weeks 0, 4 and 8. After the 12‐week treatment period, patients entered a follow‐up period of 24 weeks. The primary efficacy outcome was at least 75% improvement from baseline in the Psoriasis Area and Severity Index score (PASI 75); secondary outcomes included the Investigator’s Global Assessment (IGA) and PASI 90 and 50 response rates. Results After 12 weeks of treatment, secukinumab 3 × 150 mg and 3 × 75 mg resulted in significantly higher PASI 75 response rates vs. placebo (82% and 57% vs. 9%; P < 0·001 and P = 0·002, respectively). Higher PASI 75 response rates compared with placebo were maintained throughout the follow‐up period with these dosages [week 36, 26% (n = 7) and 19% (n = 4) vs. 4% (n = 1), respectively], with a gradual decline of PASI 75 response over time after the dosing period. IGA response rates were significantly higher in the 3 × 150 mg group vs. placebo at week 12 (48% vs. 9%; P = 0·005) and were consistently higher for the 3 × 150 mg and 3 × 75 mg groups vs. placebo at all time points from week 4 onward. The PASI 90 response rate was significantly higher in the 3 × 150 mg group vs. placebo (52% vs. 5%) at week 12 and remained higher during the follow‐up period. Secukinumab was well tolerated. Two cases of neutropenia (≤ grade 2) were reported in the 3 × 150 mg cohort. Conclusions Treatment with subcutaneous secukinumab 3 × 75 mg and 3 × 150 mg met the primary outcome of PASI 75 response achievement after 12 weeks, demonstrating efficacy in moderate‐to‐severe psoriasis.     

Ustekinumab treatment of pityriasis rubra pilaris: A report of five cases

Pityriasis rubra pilaris (PRP) is a rare, chronic, inflammatory skin disease of unknown etiology. Patients refractory to conventional therapies have been treated successfully with biologic drugs such as anti‐tumor necrosis factor agents. Recently, a role of the interleukin‐23/T‐helper 17 axis in PRP has been described. Our objective was to assess the effectiveness of ustekinumab in five patients with adult‐onset PRP refractory to conventional therapies. In the present study, four patients had type I and one patient type II adult‐onset PRP. They were treated with three s.c. doses of ustekinumab at weeks 0, 4 and 16. Clinical response was evaluated monthly during treatment up to a 15‐month follow‐up period. All patients promptly showed a decrease in erythema, follicular hyperkeratosis and scaling. After three injections, complete remission of skin lesions was achieved in four out of five cases and a significant clinical improvement was shown in one case. To the best of our knowledge, this is the largest case series reported on ustekinumab treatment in PRP. Our results, in addition to previous studies from other groups, suggest that ustekinumab may be a possible first‐line treatment for PRP patients refractory to conventional therapies.