Elke M. G. J. de Jong

β-Defensin-2 Protein Is a Serum Biomarker for Disease Activity in Psoriasis and Reaches Biologically Relevant Concentrations in Lesional Skin

Background Previous studies have extensively documented antimicrobial and chemotactic activities of beta-defensins. Human beta-defensin-2 (hBD-2) is strongly expressed in lesional psoriatic epidermis, and recently we have shown that high beta-defensin genomic copy number is associated with psoriasis susceptibility. It is not known, however, if biologically and pathophysiologically relevant concentrations of hBD-2 protein are present in vivo, which could support an antimicrobial and proinflammatory role of beta-defensins in lesional psoriatic epidermis. Methodology/Principal Findings We found that systemic levels of hBD-2 showed a weak but significant correlation with beta defensin copy number in healthy controls but not in psoriasis patients with active disease. In psoriasis patients but not in atopic dermatitis patients, we found high systemic hBD-2 levels that strongly correlated with disease activity as assessed by the PASI score. Our findings suggest that systemic levels in psoriasis are largely determined by secretion from involved skin and not by genomic copy number. Modelling of the in vivo epidermal hBD-2 concentration based on the secretion rate in a reconstructed skin model for psoriatic epidermis provides evidence that epidermal hBD-2 levels in vivo are probably well above the concentrations required for in vitro antimicrobial and chemokine-like effects. Conclusions/Significance Serum hBD-2 appears to be a useful surrogate marker for disease activity in psoriasis. The discrepancy between hBD-2 levels in psoriasis and atopic dermatitis could explain the well known differences in infection rate between these two diseases.

Extent and Clinical Consequences of Antibody Formation Against Adalimumab in Patients With Plaque Psoriasis

OBJECTIVES To investigate the extent antibodies to adalimumab are formed in patients with plaque psoriasis and whether these antibodies have clinical consequences. Also, to examine the relationship between antibodies to adalimumab and adalimumab trough titers. DESIGN Prospective observational cohort study. SETTING Two Dutch dermatology departments in university hospitals. PATIENTS All consecutive patients starting a regimen of adalimumab for chronic plaque psoriasis. Patients were screened and fulfilled the Dutch reimbursement criteria for adalimumab to treat psoriasis. INTERVENTION Adalimumab treatment (per label). MAIN OUTCOME MEASURES The titer of antibodies to adalimumab, the adalimumab trough concentration, and the Psoriasis Area and Severity Index at weeks 12 and 24. RESULTS Antibodies to adalimumab were detected in 13 of 29 patients (45%) during 24 weeks of treatment. Differences in response rates among patients with low, high, and no titers of antibodies to adalimumab were significant at weeks 12 and 24 (P = .04 and P < .001, respectively). The median adalimumab trough concentrations varied significantly among patients with low, high, and no titers of antibodies to adalimumab (1.30 [range, 0.01-5.50], 0.0 [range, 0.0-0.0], and 9.6 [range, 0.0-22.6] mg/L, respectively; P < .001). At week 24, the median adalimumab trough concentrations also differed significantly among good responders, moderate responders, and nonresponders (9.7 [range, 0.0-22.6], 8.9 [range, 3.2-12.6], and 0.0 [range, 0.0-13.3] mg/L, respectively; P = .01). CONCLUSION Antibodies to adalimumab are associated with lower serum adalimumab trough concentrations and with nonresponse or loss of response to adalimumab in patients with plaque psoriasis.

Low-dose methotrexate in the treatment of widespread morphea.

BACKGROUND Low-dose methotrexate (MTX) has been shown to be effective in the treatment of systemic sclerosis. OBJECTIVE We evaluated the effect of low-dose MTX on widespread morphea in a 24-week trial. METHODS Oral MTX, 15 mg/week, was administered to nine patients. Clinical records (modified skin score [MSS], durometer score, and the scores on a visual analogue scale (VAS) of feelings of tightness and itching), as well as laboratory data were examined. Serum aminoterminal propeptide of type III procollagen (PIIINP) was determined at weeks 0, 12, and 24. RESULTS At the end of the 24-week treatment period, significant improvement was observed in MSS (P=.01) and the VAS score for tightness (P < .01), whereas the durometer score (P=.07) and the VAS for itching (P=.07) showed a tendency toward improvement. PIIINP level did not alter. No serious adverse events were noted. CONCLUSION These results suggest a beneficial effect of MTX on widespread morphea. Because spontaneous improvements are not uncommon, prospective double-blind, placebo-controlled studies are necessary to determine the usefulness of MTX in this disease.

Biochemical and biophysical assessment of MTX-induced liver fibrosis in psoriasis patients: Fibrotest predicts the presence and Fibroscan predicts the absence of significant liver fibrosis.

Background: Methotrexate (MTX) use is associated with hepatic fibrosis in psoriasis patients. To monitor this serial liver biopsies were performed. The Fibroscan® and the Fibrotest are two novel, non‐invasive methods that might be able to assess MTX‐induced hepatic fibrosis.

Reliability of two methods to assess morphea: skin scoring and the use of a durometer

Please be advised that this information was generated on 2017-04-04 and may be subject to change.

Efficacy of topical tacrolimus 0.1% in active plaque morphea: randomized, double-blind, emollient-controlled pilot study.

AbstractBackground: Tacrolimus, a calcineurin inhibitor, is an immunomodulating and anti-inflammatory drug that inhibits T-cell activation and production of cytokines. The elevated level of cytokines in morphea causes fibroblast proliferation and subsequent overproduction of collagen. Theoretically, tacrolimus could inhibit the pathophysiologic process of morphea. Objective: To assess whether tacrolimus 0.1% ointment is an effective treatment for active plaque morphea in a double-blind, placebo (petroleum emollient)-controlled pilot study. Methods: Ten patients with active plaque morphea were included. All patients were treated with tacrolimus 0.1% ointment and with an emollient (petrolatum) on two selected morphea plaques, applied twice daily for 12 weeks. Initial and final assessment included surface area measurements, photography, durometer scores, and clinical feature scores. Adverse reactions were recorded. Results: The scleroderma plaques treated with topical tacrolimus 0.1% improved, resulting in a significant reduction in durometer and clinical feature scores. Overall, a significant difference could be found between topical tacrolimus and petrolatum with regard to durometer score (p < 0.005) and the clinical feature score (p = 0.019). Conclusion: In this first double-blind, placebo-controlled pilot study comparing tacrolimus 0.1% ointment with petrolatum in active plaque morphea, tacrolimus 0.1% ointment was shown to be an effective treatment for this condition.

Cardiovascular risk factors in high-need psoriasis patients and its implications for biological therapies

Background: The associations between psoriasis and cardiovascular risk factors are reported to be stronger as psoriasis severity increases. This makes studying cardiovascular risk factors in high-need psoriasis patients, eligible for biological therapy, interesting. Objective: To survey the prevalence of cardiovascular risk factors in high-need psoriasis patients and to compare these data to patients with other dermatological diseases. Furthermore, the implications of these findings for treatment with biologics were outlined. Methods: The prevalence of cardiovascular risk factors was investigated in a high-need psoriatic patient cohort and compared to patients with other skin diseases who filled out a questionnaire about the presence of cardiovascular risk factors. Results: A significantly higher prevalence of obesity, smoking, and hypertension was found for the high-need psoriatic patients’ cohort compared with non-psoriatic controls. Striking differences were found with respect to body mass index and obesity, as 35.5% of all high-need psoriatic patients were obese. Conclusions: High-need psoriatic patients show a high prevalence of cardiovascular risk factors, and may consequently be predisposed to cardiovascular diseases. As this is relevant for therapy management in daily clinical practice, especially biologics, cardiovascular risk should be evaluated for each high-need psoriasis patient before and during systemic treatment.

Psychological Distress in Patients With Morphea and Eosinophilic Fasciitis

OBJECTIVE To examine the level of psychological distress and factors contributing to distress in patients with morphea or eosinophilic fasciitis. DESIGN Cross-sectional study. SETTING Dermatology outpatient clinic of a university hospital. PARTICIPANTS Of 120 patients with morphea or eosinophilic fasciitis diagnosed between December 1, 1994, and July 15, 2007, who were enrolled in the study, only 74 completed questionnaires were suitable for data analysis. MAIN OUTCOME MEASURES Self-reported responses on the Impact of Chronic Skin Diseases on Daily Life scale measure psychological distress, specifically anxiety and depressed mood. RESULTS Psychological functioning was generally impaired in patients with skin disease, particularly among patients with generalized morphea and eosinophilic fasciitis. Twenty-eight patients (38%) were at risk of depression or anxiety. Higher levels of psychological distress were significantly related to greater severity of skin disease; more pain and fatigue; impact of disease on daily life; more perceived stigmatization; illness cognitions of greater helplessness; and less acceptance and less perceived social support. CONCLUSIONS Physical and psychosocial aspects play a substantial role in the quality of life for patients with morphea. Physicians should be encouraged to assess the physical and psychosocial factors when treating patients with sclerotic skin diseases. This approach could improve quality of life and ultimately lead to improved dermatological treatment outcomes.

The Burden of Childhood Psoriasis

Abstract:  A pilot study of the effect on quality of life of childhood psoriasis is presented. Of the children interviewed, 65% experienced stigmatization to a certain extent, 71% reported itching, and 43% complained about fatigue. Clinicians should pay attention to these items to initiate patient‐tailored treatment.

Immunohistochemical detection of proliferation and differentiation in discoid lupus erythematosus

Discoid lupus erythematosus lesions show hyperkeratosis and atrophy, which may reflect abnormal epidermal proliferation, differentiation, or both. In this investigation, markers for epidermal proliferation, differentiation and inflammation were studied in cutaneous lesions of discoid lupus erythematosus. Frozen sections of biopsy specimens from 20 patients were examined immunohistochemically regarding Ki-67 staining and keratin 16 expression (parameters for proliferation), and the expression of keratin 10, involucrin, and filaggrin (parameters for differentiation). The inflammatory infiltrate was characterized with the use of antibodies against T lymphocytes, monocytes/macrophages, and Langerhans cells. With these markers, epidermal proliferation was found to be increased in discoid lupus erythematosus. Keratin 10 expression, a marker for early differentiation, showed the pattern of normal skin. Involucrin and filaggrin, markers for terminal differentiation, were expressed already in the lower part of the stratum spinosum, whereas in normal skin these markers were restricted to the stratum granulosum and the upper layers of the stratum spinosum, and the stratum granulosum and stratum corneum, respectively. Infiltrate analysis revealed the well-established picture. We conclude that in cutaneous lesions of discoid lupus erythematosus, hyperproliferation is combined with normal early differentiation and premature terminal differentiation of keratinocytes.