Ustekinumab therapy for Netherton syndrome.

Netherton syndrome (NS) is a rare disorder of cornification associated with high morbidity. It is caused by bi-allelic mutations in SPINK5 encoding the serine protease inhibitor LEKTI. Previous studies have shown Th17 skewing with IL-23 upregulation in NS, raising the possibility that targeting these inflammatory pathways may alleviate disease manifestations. We ascertained the therapeutic efficacy of six doses of ustekinumab administered to three patients with NS over a period of 13 months using the Ichthyosis Area and Severity Index (IASI), the Dermatology Life Quality Index (DLQI), a visual analogue scale (VAS) for itch and the peak-pruritus numeric rating scale (PP-NRS). Histopathology analysis including CD3, CD4, CD8 and interleukin 17 (IL-17) immunostaining, was performed at baseline and 4 weeks following the last ustekinumab dose. Total IASI scores were reduced by 28% in two patients at week 16 with sustained response by week 56. No consistent improvement in DLQI, VAS for itch and PP-NRS scores was observed. The inflammatory infiltrate and the degree of acanthosis were slightly reduced at week 56 as compared to baseline. No significant change in immunostaining of the various inflammatory markers was observed at week 56. In conclusion, this case series did not demonstrate a significant therapeutic effect of ustekinumab in NS.

Food-seeking behavior is triggered by skin ultraviolet exposure in males.

Sexual dimorphisms are responsible for profound metabolic differences in health and behavior. Whether males and females react differently to environmental cues, such as solar ultraviolet (UV) exposure, is unknown. Here we show that solar exposure induces food-seeking behavior, food intake, and food-seeking behavior and food intake in men, but not in women, through epidemiological evidence of approximately 3,000 individuals throughout the year. In mice, UVB exposure leads to increased food-seeking behavior, food intake and weight gain, with a sexual dimorphism towards males. In both mice and human males, increased appetite is correlated with elevated levels of circulating ghrelin. Specifically, UVB irradiation leads to p53 transcriptional activation of ghrelin in skin adipocytes, while a conditional p53-knockout in mice abolishes UVB-induced ghrelin expression and food-seeking behavior. In females, estrogen interferes with the p53-chromatin interaction on the ghrelin promoter, thus blocking ghrelin and food-seeking behavior in response to UVB exposure. These results identify the skin as a major mediator of energy homeostasis and may lead to therapeutic opportunities for sex-based treatments of endocrine-related diseases.

Skin exposure to UVB light induces a skin-brain-gonad axis and sexual behavior.

Ultraviolet (UV) light affects endocrinological and behavioral aspects of sexuality via an unknown mechanism. Here we discover that ultraviolet B (UVB) exposure enhances the levels of sex-steroid hormones and sexual behavior, which are mediated by the skin. In female mice, UVB exposure increases hypothalamus-pituitary-gonadal axis hormone levels, resulting in larger ovaries; extends estrus days; and increases anti-Mullerian hormone (AMH) expression. UVB exposure also enhances the sexual responsiveness and attractiveness of females and male-female interactions. Conditional knockout of p53 specifically in skin keratinocytes abolishes the effects of UVB. Thus, UVB triggers a skin-brain-gonadal axis through skin p53 activation. In humans, solar exposure enhances romantic passion in both genders and aggressiveness in men, as seen in analysis of individual questionaries, and positively correlates with testosterone level. Our findings suggest opportunities for treatment of sex-steroid-related dysfunctions.

Pulse-Dye Laser Followed by Betamethasone-Calcipotriol and Fractional Ablative CO2-Laser-Assisted Delivery for Nail Psoriasis.

BACKGROUND: Nail psoriasis is a common and potentially debilitating condition for which no effective and safe nonsystemic therapy is currently available. Recently, laser-assisted drug delivery (LADD) is being increasingly used to facilitate transcutaneous penetration of topical treatments. OBJECTIVES: We set to assess the efficacy and safety of combined pulse-dye laser and fractional CO2 laser-assisted betamethasonecalcipotriol gel delivery for the treatment of nail psoriasis. MATERIAL AND METHODS: We conducted a prospective, intrapatient comparative study in a series of 22 patients with bilateral fingernail psoriasis. Nails on the randomized hand were treated with 3 monthly sessions of pulse-dye laser to the proximal and lateral nail folds followed by fractional ablative CO2 laser to the nail plate. Between treatments and one month following the last treatment, the participants applied betamethasone propionate-calcipotriol gel once daily to the nail plate. Clinical outcome was ascertained using nails photography, the Nail Psoriasis Severity Index (NAPSI) and patient satisfaction. RESULTS: Seventeen completed the study. Three participants withdrew from the study because of treatment-associated pain. Treatment was associated with a statistically significant improvement of the NAPSI scale (p < .002). Patient satisfaction was high. CONCLUSION: Combined PDL and fractional ablative CO2-LADD of betamethasone-calcipotriol gel should be considered for the treatment of nail psoriasis.

Prevalence of Nonradiographic Sacroiliitis in Patients With Psoriatic Arthritis: A Real-life Observational Study.

OBJECTIVE: To establish the prevalence of nonradiographic sacroiliitis within a real-life sample of patients with psoriatic arthritis (PsA), using pelvic radiographs and magnetic resonance imaging (MRI) of sacroiliac joints (SIJs). METHODS: This cross-sectional study included 107 consecutive adults with PsA (Classification Criteria for Psoriatic Arthritis criteria). Participants completed clinical and laboratory evaluation, pelvic radiographs scored for radiographic sacroiliitis according to the modified New York (mNY) criteria, and noncontrast MRI of SIJs, scored by the Berlin score and categorized into active sacroiliitis using the 2016 Assessment of Spondyloarthritis international Society (ASAS) criteria and the presence of structural sacroiliitis. RESULTS: Radiographic sacroiliitis/mNY criteria were detected in 28.7% (n = 29), confirmed by MRI-detected structural lesions in 72.4% (n = 21). Active sacroiliitis was detected by MRI in 26% (n = 28) of patients, with 11% (n = 11) qualifying for nonradiographic sacroiliitis. Patients with radiographic and nonradiographic sacroiliitis had similar clinical characteristics, except for a longer duration of psoriasis (PsO) and PsA in the radiographic subgroup (PsO: 23.8 ± 12.5 vs 14.1 ± 11.7 yrs, P = 0.03; PsA: 12.3 ± 9.8 vs 4.7 ± 4.5 yrs, P = 0.02, respectively). Inflammatory back pain (IBP) was reported in 46.4% (n = 13) with active sacroiliitis and 27% (n = 3) with nonradiographic sacroiliitis. The sensitivity of IBP for detection of nonradiographic sacroiliitis was low (27%) and moderate for radiographic sacroiliitis (52%), whereas specificity ranged from 72% to 79% for radiographic and nonradiographic sacroiliitis, respectively. CONCLUSION: The prevalence of active sacroiliitis among a real-life population of patients with PsA was 26%. However, the prevalence of nonradiographic sacroiliitis was low (11%) compared to the radiographic sacroiliitis (28.7%) seen in patients with longer disease duration. IBP was not a sensitive indicator for the presence of early-stage sacroiliitis that was commonly asymptomatic.

Comorbidities in patients with palmoplantar plaque psoriasis.

BACKGROUND: Psoriasis has been shown to be associated with several comorbidities. Whether the palmoplantar subtype of plaque psoriasis carries similar risks for comorbidities as generalized plaque psoriasis remains to be defined. OBJECTIVE: To examine the association between palmoplantar plaque psoriasis and comorbidities known to be associated with generalized plaque psoriasis. METHODS: We retrospectively compared the prevalence of comorbidities previously found to be associated with generalized plaque psoriasis among 163 patients with palmoplantar plaque psoriasis who had been treated with topical psoralen and ultraviolet A from 2009 to 2017 and a cohort of 781 control individuals. Each patient with psoriasis was matched according to sex and age (±1 year) with up to 5 control individuals. Conditional logistic regression was used to evaluate the associations after matching. RESULTS: Diabetes mellitus (odds ratio [OR], 2.296), cardiovascular disease (OR, 1.797), and most remarkably, mood disorders (OR, 6.232) were significantly associated with palmoplantar plaque psoriasis. Dyslipidemia, hypertension, and psoriatic arthritis were more frequent among patients with palmoplantar plaque psoriasis, but those associations did not reach statistical significance. LIMITATIONS: The retrospective nature of this study, the fact that some data were collected through a survey questionnaire, and the relatively small sample size suggest the need to validate the present data in a prospective manner. Additionally, within the psoriasis group, patients were assessed for the presence of comorbidities during the whole follow-up period, whereas the comorbidities of individuals in the control group were assessed during a baseline visit. CONCLUSIONS: Several comorbidities known to be associated with psoriasis vulgaris were also found to be prevalent in a series of patients with plaque palmoplantar psoriasis. Individuals affected with plaque palmoplantar psoriasis showed a particularly high risk for mood disorders.

Prevalence of high-sensitivity cardiac troponin T in real-life cohorts of psoriatic arthritis and general population: a cross-sectional study.

Patients with psoriatic arthritis (PsA) are at increased risk of cardiovascular disease (CVD). High-sensitivity cardiac troponin T (hs-cTnT) is a novel biomarker of CVD. The objective of this study is to determine the prevalence of circulating hs-cTnT in patients with PsA compared to the general population and to characterize a PsA subset with detectable hs-cTnT. A cross-sectional analysis of serum hs-cTnT levels was performed in 116 consecutive patients with PsA and the Tel-Aviv Medical Center Inflammatory Survey cohort of the general population (n = 6052) as a control group. The level and prevalence of hs-cTnT (ng/L) were similar in the entire study population: 4.94 ± 4.4, 30.2% in PsA, 5.17 ± 6.7, 34.2% and 5.38 ± 4.3, 37.9% in unmatched and matched control groups according to age, gender and cardiovascular risk factors, respectively. Factors associated with detectable hs-cTnT in PsA included male gender (p = 0.002), age (p = 0.007), hypertension (p < 0.001), diabetes mellitus (p < 0.001), and smoking (p = 0.001). Axial disease, present in 25% of patients with PsA, was significantly associated with detectable hs-cTnT (p = 0.004). This association remained significant after adjusting for age, gender and traditional cardiovascular risk factors. No correlation between hs-cTnT levels and disease characteristics, PsA activity indices, C-reactive protein levels, or treatments for PsA was found. In summary, serum hs-cTnT was detectable in about the third of the PsA and control cohorts. In PsA, axial disease was significantly associated with detectable hs-TnT, warranting a particular attention to cardiovascular risk assessment in this sub-group. The role of hs-cTnT as a biomarker for CVD in PsA should be further investigated in prospective studies.

The Effect of the Presence of Fibromyalgia on Common Clinical Disease Activity Indices in Patients with Psoriatic Arthritis: A Cross-sectional Study.

OBJECTIVE: To study the effect of the presence of fibromyalgia (FM) on common clinical disease activity indices in patients with psoriatic arthritis (PsA). METHODS: Seventy-three consecutive outpatients with PsA (mean age 51.7 yrs; 42 females, 57.5%) were enrolled in a prospective cross-sectional study. FM was determined according to American College of Rheumatism criteria (2010 and 1990). All patients underwent clinical evaluation of disease activity and completed the Health Assessment Questionnaire (HAQ), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Dermatology Life Quality Index, and the Leeds Enthesitis Index (LEI). Disease activity was evaluated using the Composite Psoriatic Disease Activity Index (CPDAI), minimal disease activity (MDA), and the Disease Activity Index for Psoriatic Arthritis (DAPSA) scores. RESULTS: The overall prevalence of FM was 17.8% (13 patients), and all but 1 were women (12 patients, 92.3%, p = 0.005). CPDAI and DAPSA scores were significantly higher in patients with coexisting PsA and FM (9.23 ± 1.92 and 27.53 ± 19.23, respectively) than in patients with PsA only (4.25 ± 3.14 and 12.82 ± 12.71, respectively; p < 0.001 and p = 0.003). None of the patients with FM + PsA met the criteria for MDA, whereas 26 PsA-only patients did (43.3%, p = 0.003). HAQ, BASDAI, and LEI scores were significantly worse in patients with PsA and associated FM. CONCLUSION: Coexisting FM is related to worse scores on all tested measures in patients with PsA. Its influence should be taken into consideration in the treatment algorithm to avoid unnecessary upgrading of treatment.

NB-UVB phototherapy for generalized granuloma annulare.

Granuloma annulare (GA) is a benign, usually self-limited, granulomatous skin disease of unknown etiology. The generalized form of the disease shows a more chronic, relapsing course, rare spontaneous resolution, and poorer response to therapy. Psoralen plus UVA phototherapy has been reported to be effective for GA. However, little is known regarding the efficacy of narrowband UVB phototherapy. Our goal was to determine the efficacy of NB-UVB phototherapy in generalized GA. We carried out a retrospective study of patients with generalized GA treated with NB-UVB phototherapy over a period of 3 years. On completion of treatment, outcome was assessed as complete response (complete clearance of the lesions), partial response (>50% clearance of the lesions), and poor response (<50% clinical response). Therapy was stopped if no improvement was seen after 20 treatments. Thirteen patients were included in the study. 54% of patients treated with NB-UVB had a complete/partial response by the end of the treatment period. NB-UVB phototherapy was well-tolerated, with no serious adverse effects. NB-UVB phototherapy is effective in a substantial portion of patients with generalized GA. To determine the true efficacy of this therapeutic modality, a prospective study comparing it to PUVA is warranted.

Immunogenicity and safety of vaccination against seasonal 2012 influenza virus among patients with psoriatic arthritis and psoriasis.

OBJECTIVES: We aimed to assess the immunogenicity and safety of vaccination against seasonal influenza in psoriatic arthritis (PsA) and psoriasis (Pso) patients. METHODS: Patients with PsA or Pso and healthy controls were vaccinated with the Sanofi Pasteur vaccine recommended by the WHO in 2012. Clinical and laboratory assessments were performed on the day of the vaccination and 4-6 weeks later. The immunogenicity of the vaccine was evaluated by haemagglutination inhibition assay. RESULTS: The study included 63 consecutive PsA patients and 4 Pso patients (mean age 50.1, 37 females, 30 males, 55.2% treated with tumour necrosis factor alpha blockers [TNF-α], 31.3% on disease-modifying anti-rheumatic drugs [DMARDs]) and 30 healthy controls. The geometric mean titers increased significantly in all participants for each of the subtypes tested. A substantial and similar proportion of patients in both groups responded to the vaccine. The response rate was not affected by parameters such as age, gender, disease activity or the use of TNF-α blockers or DMARDs. There were no significant changes in the patients' 68 tender and 66 swollen joint counts, dactylitis, PASI, global evaluation of the patient and physician and ESR, while there was a rise in CRP levels. CONCLUSIONS: Vaccination against seasonal influenza is safe and induces an appropriate response in patients with PsA, similar to healthy controls.

Prevalence of TNF-α blocker immunogenicity in psoriatic arthritis.

OBJECTIVE: The longterm use of tumor necrosis factor (TNF)-α blockers is limited by the formation of neutralizing antibodies. To the best of our knowledge, immunogenicity in psoriatic arthritis (PsA) has not been investigated in depth. Our objective was to evaluate the prevalence and significance of TNF-α blocker immunogenicity in PsA. METHODS: Consecutive patients with PsA treated with either infliximab (IFX), adalimumab (ADA), or etanercept (ETN) > 3 months participated in our cross-sectional study. Their demographic and clinical characteristics, skin and joint disease activity, and records of use of methotrexate (MTX) and other medications were collected. Drug levels (ELISA) and antidrug antibodies (ADAb; Bridging ELISA) were evaluated before the next injection or infusion. RESULTS: A total of 93 patients with PsA were recruited (48 receiving ADA, 24 IFX, and 21 ETN), with a mean age of 53 years (range 21-83 yrs), composed of 53% women. One-fourth of the patients were concomitantly treated with MTX. Altogether, 77% of the patients demonstrated therapeutic drug levels. High levels of ADAb were found in 29% of patients taking ADA, 21% taking IFX, and 0% taking ETN. ADAb significantly correlated with lower drug levels, higher 28-joint Disease Activity Scores, and higher global assessments. MTX use correlated significantly with a lower prevalence of ADAb. CONCLUSION: Significant levels of ADAb were present in up to 29% of patients with PsA treated with ADA or IFX. ADAb clearly correlated with low therapeutic drug levels and higher disease activity variables. The use of MTX significantly decreased ADAb prevalence, and its use should be strongly considered in combination with TNF-α blocker antibodies in patients with PsA.

Phototherapy for psoriasis: what to choose and how to use: facts and controversies.

In dermatologic practice, phototherapy is restricted mainly to the use of ultraviolet radiation. When used in combination with a photosensitizing chemical, it becomes photochemotherapy. Discussion of these therapeutic modalities includes mode of use, indications, and unwanted effects.

Normal levels and function of endothelial progenitor cells in patients with psoriatic arthritis.

Endothelial progenitor cells (EPCs) are a population of bone marrow derived cells which have been attributed with the ability to migrate into areas of tissue ischemia and to posses reparative qualities. EPCs have been shown to be decreased in level and function in various inflammatory disorders. Psoriasis and psoriatic arthritis are associated with an increase in cardiovascular morbidity. The aim of the study was to investigate the number of EPCs among patients suffering from psoriasis and psoriatic arthritis. Patients suffering from active psoriasis and psoriatic arthritis were recruited as well as healthy controls. Disease activity was assessed with the DAS-28, BASDAI and PASI scores. Peripheral blood mononuclear cells were isolated and EPC numbers evaluated by FACS analysis using the CD34/133 and CD34/KDR. No significant difference was found between numbers of EPCs between healthy controls, patients with psoriasis and psoriatic arthritis. A significant correlation was found between levels of VGEF and the BASDAI score. The results of the current study do not support a significant role for EPCs in the pathogenesis of psoriasis and psoriatic arthritis.

UV light and its interaction with cutaneous receptors.

Phototherapy (UV-A and UV-B) has become one of the most commonly used modalities for the treatment of a variety of skin diseases, although the action mechanisms have not been fully understood. Inhibition of DNA synthesis by UV radiation may be one of the therapeutic effects in proliferating skin diseases; however, phototherapy is also used for the treatment of allergic or autoimmune diseases.

Vitiligo.

Vitiligo is an acquired depigmentary disorder of the skin that results from the selective destruction of melanocytes. The etiology of vitiligo is poorly understood. There appears to be a genetic predisposition, but additional factors are probably involved. The purpose of this article is to outline the factors that might play a role in the development of vitiligo. These include trauma such as vaccination, radiotherapy, and sun exposure, malignancies and treatment of malignancies like lymphoma or melanoma, bone marrow transplantation, interferon, interleukin, and other drugs, psychological factors, endocrine disease and cytotoxic compounds that cause contact vitiligo. We hope future research will shed more light on the subject and identify the precipitating factors, since in the majority of vitiligo cases the contributing factors are as yet unidentified.

Telangiectasia macularis eruptiva perstans: unusual presentation and treatment.

A 41-year-old woman presented with a 2-month history of pruritus and a generalized dermatitis that developed initially on the head and spread to the trunk, legs, and buttocks. The pruritus caused extreme discomfort and was not relieved by antihistamines or topical steroid treatment. The patient denied flushing, syncope, and vomiting. Her medical history included asthma treated with salmeterol/fluticasone propionate inhaler, and status post silicone breast augmentation. Physical examination revealed a papular dermatitis on the trunk and extremities composed of lesions up to 0.5 cm in diameter, surrounded by excoriation marks (Figure 1). There was no hepatosplenomegaly or lymphadenopathy. Darier's sign was negative. Results of complete blood count, peripheral blood film examination, and liver function tests were all with normal limits. A biopsy specimen taken from a lesion and stained with hematoxylin-eosin showed telangiectasias, with an increased number of mast cells around blood vessels (Figure 2). Positive Giemsa (Figure 3) and c-kit stain (Figure 4) indicated an increased number of mast cells. Bone marrow aspiration and total body CT performed to rule out systemic involvement showed no pathology. Protein electrophoresis was normal. Serum tryptase and histamine were within normal limits, and 24-hour urine collection for histamine was normal. Narrow-band UV-B treatment was begun 3 times weekly, reduced to twice weekly after 2 months, and then stopped. The first few treatments resulted in significant relief of the pruritus and regression of lesions. After 3 months without treatment, the patient remained free of pruritus and lesions.

Drug Rash with eosinophilia and systemic symptoms versus Stevens-Johnson Syndrome--a case that indicates a stumbling block in the current classification.

A 43-year-old man developed a skin eruption characterized by 'macules with blisters' typical to Stevens-Johnson syndrome, as well as erosions of the lips and buccal mucosa, 2 weeks after he had started treatment with lamotrigine. He had a fever (39.6 degrees C), elevated liver enzymes and atypical lymphocytes in the peripheral blood. This undoubtedly reflects a case of Stevens-Johnson syndrome induced by lamotrigine, but it can also fulfill the criteria of anticonvulsant hypersensitivity syndrome or drug rash with eosinophilia and systemic signs. A case that precisely fits the definition of two syndromes that have different characteristics, different treatments and different prognoses indicates that there is a flaw in the classification.

The Blue Peel: how to do it less expensively and faster.

One well accepted and popular method worldwide for trichloroacetic acid peels is the Obagi Blue Peel technique (Obagi Medical Products, Long Beach, CA). The peel solution is prepared by mixing a fixed volume of 30% trichloroacetic acid with the commercially available Blue Peel base. The authors suggest modifications for performing the peeling faster and less expensively: 1) preparing a larger volume of peel solution from each tube of Blue Peel base; 2) using higher concentrations of peel solution to reduce the number of coats necessary for reaching the desired depth of peel; and 3) storing the solution, as there is no need to adhere to the manufacturer's instructions to prepare the solution immediately before conducting the peel procedure to ensure homogeneity of the solution. The prepared solution can be stored at least 1 year.