New treatments for old diseases

Hyaluronic acid for oral ulcers

JEADV 2008; May

Dermatologic applications of Hyaluronic acid (HU) now encompass its usage as a filler and also for the stimulation of wound healing and as a drug vehicle in topical formulations. A clinical study done in Korea has shown that topical application of 0.2% HA gel is safe and effective in treating patients with recurrent oral ulcers....

Botulinum Toxin for psoriasis

JEADV 2008; April

In a study done by Zanchi et al, Botulinum toxin type-A (BoNTA) reported to be effective in treating 15 patients with inverse psoriasis. It targets the neuroglandular junction to reduce local sweating, thereby preventing the resulting skin maceration and secondary infection, but it may also inhibit the liberation of neuropeptides....

Pregabalin; another drug for intractable pruritus

Am Acad Dermatol 2008; February

Pregabalin, a new anticonvulsant drug has been used successfully in treating 3 patients with chronic generalized pruritus. It seems that this beneficial effect is mediated through its counteracting effect on the central sensitization processes...

Oxymethazoline for the treatment of erythema and flushing of rosacea

 Am Acad Dermatol 2008; February, AB9, P400

Oxymethazoline is a potent selective alpha adrenergic receptor agonist. Anecdotal reports have shown that topical applications of Oxymethazoline 0.05% solution is an effective treatment for erythematotelangiectatic rosacea….

 A new RAMBA for treatment of psoriasis

JEADV 2007; September

Complete resolution of recurrent calciphylaxis with long-term intravenous sodium thiosulfate

Authors: Subramaniam, Kavitha; Wallace, et al.

Source: Australasian Journal of Dermatology, Volume 49, Number 1, January 2008 , pp. 30-34(5)

Abstract  

A 35-year-old morbidly obese woman on home haemodialysis presented with painful indurated subcutaneous nodules histologically characteristic of calciphylaxis. After failing to respond to conventional treatment, she was commenced on an intravenous infusion of 25 g of sodium thiosulfate three times per week. Two weeks after commencing sodium thiosulfate, the pain resolved completely. By 12 weeks, the lesions had healed and the infusions were ceased. Two months later, skin lesions recurred, but resolved again within 3 months of recommencement of sodium thiosulfate treatment, which was continued for 8 months. The treatment was well tolerated. There has been no recurrence of lesions in the 18 months since the cessation of sodium thiosulfate. Clinical trials to determine the optimum dose and duration of therapy for sodium thiosulfate treatment of calciphylaxis should be given priority because of its high rate of success in treating what is otherwise a severe and mostly lethal condition.

PEComa

Liegl B et al.

 Am J Surg Pathol 2008 Apr; 32:608.

Abstract  

Perivascular epithelioid cell tumors (PEComas) are apparently benign mesenchymal tumors that can easily be misdiagnosed as malignant melanoma. These authors performed a retrospective analysis and describe the clinicopathologic spectrum of 10 primary cutaneous PEComas.

Ten patients (8 female; age range, 15–82), none with tuberous sclerosis, presented with painless, slowly growing dermal nodules or plaques. Eight tumors were located on the legs and two on the back. Most tumors involved the dermis, with extension to the subcutis. The median size was 1.5 cm. The tumors had a nested or trabeculated growth pattern of epithelioid or epithelioid/spindle cells in a background rich in vessels. The proliferative cells ranged from clear to palely eosinophilic or granular cytoplasm. Mitotic activity was <1 per 10 high-powered fields. The cells were positive for HMB-45, Melan A and microphthalmia transcription factor. Epithelial markers (pan-keratin and epithelial membrane antigen) were negative. The investigators also noted smooth-muscle differentiation, with positive desmin and smooth-muscle actin.

In 20% of patients, the tumors had been misdiagnosed as malignant melanomas; eight tumors with positive margins were completely excised, and two were partially excised. One patient with a melanoma misdiagnosis underwent sentinel lymph node biopsy, with negative results. After a median follow-up of nearly 4 years, no recurrences were observed.

Comment: Although PEComas are frequently identified in the retroperitoneum, abdominal viscera, and pelvic sites, only about 20 cases have been described in the literature. No definitive association of these neoplasms with the tuberous sclerosis complex has been made. PEComas and malignant melanomas may have overlapping histologic and immunohistochemical features. Awareness of primary cutaneous PEComas will increase the identification of this apparently benign entity and avoid inappropriate treatment.

Relationship between the atopy patch test and clinical expression of the disease in children with atopic eczema/dermatitis syndrome and respiratory symptoms

Authors: Fuiano, Nicola; Incorvaia, Cristoforo; Prodam, Flavia; Procaccini, Deni A.; Bona, Gianni

Source: Annals of Allergy, Asthma and Immunology, Volume 101, Number 2, August 2008 , pp. 174-178(5)

Abstract  

Background: The atopy patch test (APT) may be the only positive skin test result in patients with either atopic eczema/dermatitis syndrome (AEDS) or respiratory abnormalities with or without AEDS.

Objective: To investigate the possible significance of APT to dust mite by comparing the positive result to this test with that of the skin prick test (SPT) in patients with different characteristics.

Methods: A total of 297 individuals (178 boys and 119 girls) aged 5 to 221 months (mean [SD] age, 64.5 [42.1] months; median age, 58 months) were included in this study. Participants were divided into 4 groups: current AEDS, current AEDS and respiratory symptoms, past AEDS and respiratory symptoms, and respiratory symptoms with neither current nor past AEDS (control group). All the patients underwent SPT and APT using house dust mite extract. Results: In the study groups, the rate of positivity was significantly higher for APT, whereas in the control group, there were significantly more positive results to SPT (P < .001 for both). Multivariate analysis showed that there was a high probability of a positive APT result in patients with AEDS (odds ratio [OR], 17.4), with AEDS and respiratory disease (OR, 21.9), and with past AEDS and respiratory disease (OR, 22.8).

Conclusions: These patients with AEDS showed 2 different patterns of allergic response to allergens, one IgE mediated (as evaluated by positive SPT results) and the other cell mediated (as evaluated by positive APT results). The former seems to follow the so-called atopic march model, and the latter persists even after the disappearance of AEDS and is likely to be implicated in the pathogenesis of respiratory allergy.

Change in prevalence of atopic dermatitis between 1986 and 2001 among children

Stensen, Lise et al.
Allergy and Asthma Proceedings, Volume 29, Number 4, 7/8 2008 , pp. 392-396(5)

Abstract  

The prevalence of atopic dermatitis (AD) has increased during the last decades. Whether the prevalence is still increasing or has reached a stable level during the 1990s is still not certain. The purpose of this study was to compare the prevalence of AD in two different random samples of Danish children studied in 1986 and 2001 and to examine the associations between AD and other atopic outcomes. Two samples of children and adolescents living in urban Copenhagen were drawn at random from the civil registration list in 1986 and 2001. A total of 527 and 480 subjects participated in 1986 and 2001, respectively. Subjects were classified as AD cases when responding affirmatively to the question "Do you have, or have you ever had, significant and recurrent episodes of eczema in the folds of your elbows or knees?" Immunoglobulin E (IgE) measurements, skin-prick tests, and airway responsiveness tests were performed. The prevalence of AD increased from 17.3% in 1986 to 27.3% in 2001. For male subjects, the prevalence of AD was 16.4% in 1986 compared with 25.7% in 2001. For female subjects, the prevalence of AD was 18.1% in 1986 compared with 28.7% in 2001. Elevated levels of IgE, airway hyperresponsiveness (AHR), and rhinitis were statistically significant predictors of AD. The prevalence of AD has increased significantly from 1986 to 2001 in urban Copenhagen, Denmark. In addition, we found that AD was significantly associated with AHR, rhinitis, and elevated levels of IgE, supporting the idea of the atopic triad.

Treatment Following an Evidence-Based Algorithm versus Individualised Symptom-Oriented Treatment for Atopic Eczema
A Randomised Controlled Trial

Jochen Schmitt et al.

Dermatology 2008;217:299-308

Abstract  

Background: Evidence-based treatment algorithms, successfully established for asthma, are missing for atopic eczema (AE). Objectives: To investigate whether treatment according to an evidence-based algorithm is an effective and applicable concept for the management of AE.

Methods: Based on a systematic literature review, we developed an evidence-based severity-score-oriented treatment algorithm for AE and compared its effectiveness to that of an individualised symptom-oriented treatment (individual therapy) in a randomised controlled trial. Sixty-three participants were randomised to algorithm (n = 32) or individual therapy (n = 31) and treated accordingly for 12 months. Study end points included difference between baseline SCORAD and mean SCORAD under treatment (primary end point), quality of life and treatment utilisation. Analysis was by intention to treat (registration: ClinicalTrials.gov:NCT00148746).

Results: No statistically significant differences in clinical or subjective response were observed between groups. Treatment following the algorithm and individual treatment both effectively controlled AE. Mean SCORAD reductions were 47% (95% confidence interval, CI = 38-55; algorithm) and 42% (95% CI = 29-54; individual). Clinical response was paralleled by improved quality of life in both groups. Physicians adhered to the algorithm option in 93% of their treatment decisions.

Conclusion: Treatment following an evidence-based algorithm is an effective and applicable concept for the management of AE but does not show clear advantages compared to individualised treatment in a dermatological setting.

Rituximab in refractory autoimmune bullous diseases

Schmidt, E.; Hunzelmann, N et al.

Clinical and Experimental Dermatology, Volume 31, Number 4, June 2006, pp. 503-508(6)

Abstract  

Treatment of autoimmune blistering diseases consists of systemic glucocorticosteroids usually in combination with additional immunosuppressants such as azathioprine and mycophenolate mofetil or immunomodulators such as dapsone, antibiotics, intravenous immunoglobulins, and immunoadsorption. In some patients, these treatment regimens are not sufficient to control disease activity and/or lead to intolerable adverse events. Rituximab, originally developed for the treatment of non-Hodgkin's lymphoma, is an anti-CD20 humanized monoclonal antibody leading to transitory B-cell depletion. For this indication, rituximab is widely employed, and severe side-effects rarely observed. Subsequently, the B-cell-depleting effect of rituximab has been exploited successfully in various autoimmune disorders, including autoimmune blistering diseases. Here, we review the effect of rituximab in such diseases. To date, application of rituximab has been reported in 26 treatment-resistant patients with the vulgaris, foliaceus, and paraneoplastic variants of pemphigus as well as in bullous pemphigoid and epidermolysis bullosa acquisita. All but a single patient showed clinical improvement with reduction of lesion formation. In about a third, a clinical remission requiring further immunsuppressive medication was achieved, and in about a quarter, complete remission was induced. In addition, the mode of action and adverse events of rituximab as well as adjuvant immunosuppressive treatments, and the effect on levels of circulating autoantibodies in these patients are discussed.

Thyroid Eye Disease Presenting After Cosmetic Botulinum Toxin Injections

Andrew R. Harrison, MD

The American Society of Ophthalmic Plastic and Reconstructive Surgery
2006, Vol. 22, No. 5, pp 388–403

Abstract  

A 53-year-old woman with left periorbital swelling 4 days after botulinum toxin injection in the lateral
canthal area presented after noticing left eye prominence.
Physical examination demonstrated proptosis and eyelid retraction. Computed tomography of the orbits confirmed
extraocular muscle enlargement consistent with thyroid eye disease. In this case, the patient had development of proptosis
after receiving botulinum toxin injections. Although the proptosis may represent progression of the patients'
thyroid eye disease, it is worthwhile to consider incitation by botulinum toxin as a possible cause given its widespread
use.

Thyroid eye disease (TED) is the most common cause for unilateral or bilateral proptosis in adults.1 Previous studies
have reported the induction of proptosis by medications such as corticosteroids and rosiglitazone and the presentation of TED
after ocular surgery.2–4 The cosmetic use of botulinum toxin (BTX) has grown during the past decade as the result of the
relative lack of side effects. Common periocular injection sites include glabella and lateral canthal rhytids.5 We describe a
patient who had periorbital swelling and proptosis 4 days after receiving periocular BTX injections.

Vitamin D Intake and the Risk for Pancreatic Cancer in Two Cohort Studies
 

Halcyon G. Skinner et al.

Cancer Epidemiology Biomarkers & Prevention

Vol. 15, 1688-1695, September 2006 (c) 2006 American Association for Cancer Research

Abstract  

Lichenoid paraneoplastic pemphigus in the absence of detectable antibodies.

 

Cummins DL, et al.

JAAD: 2007 Jan;56(1):153-9. Epub 2006 Sep 14

Abstract  

Paraneoplastic pemphigus (PNP) has been described as an antibody-mediated mucocutaneous disease occurring almost exclusively in patients with lymphocytic neoplasms. We describe 4 patients with the clinical features of the lichenoid variant of PNP in the absence of detectable autoantibodies. On the basis of these findings, we conclude that the spectrum of PNP likely includes patients with disease predominantly or exclusively mediated by cytotoxic T cells rather than autoantibodies. The pathophysiology and range of PNP disease are likely more complex than was initially believed.

Effect of selenium intake on the prevention of cutaneous epithelial lesions in organ transplant recipients
 

Author(s) : B Dréno, S Euvrard, C Frances, D Moyse, A Nandeuil

European Journal of Dermatology. Volume 17, Number 2, 140-5, March-April 2007, Investigative report

Abstract  

Organ graft recipients have a high rate of pre-malignant and malignant epithelial lesions. Selenium directly influences the number of Langerhans cells. In several studies selenium has shown its role in preventing various carcinomas, it was worth investigating whether it could prevent skin cancer linked to human papilloma virus (HPV). A multicentre, randomised, placebo-controlled, parallel group study in 184 recent organ transplant recipients was undertaken. Patients were treated for 3 years with 200 µg/day selenium (91 patients) or a matching placebo (93 patients), and then monitored for 2 years. Occurrence rates of warts and various keratoses (main criterion) and of skin cancers (secondary criterion) were compared in the two groups, using Kaplan-Meyer analyses.
There was no difference between the two groups for the main criterion (odds-ratio 1.09, p \=
0.72) or the secondary criterion (odds-ratio 3.08\; p \= 0.15). When both arms were pooled, phenotype and age were not found to be discriminatory factors, whereas a previous history of an actinic keratosis significantly increased the risk of developing a skin cancer by 17.5%. Safety was good and similar in both groups. Selenium was not shown to prevent the occurrence of skin lesions linked to HPV. The occurrence of skin cancer was higher if there had been a previous actinic keratosis, highlighting the importance of early dermatological follow-up of the transplanted population. This was demonstrated by the high rate of epithelial lesions detected, which was more than twice the rate usually reported in the literature.

"Unknown Risks" of non-steroid topical medications for atopic dermatitis

McNeill, Anne Marie; Koo, John Y. M.
International Journal of Dermatology, Volume 46, Number 6, June 2007 , pp. 656-658

Abstract  

Tacrolimus ointment is a nonsteroid treatment for atopic dermatitis which is both effective and has a minimal side-effect profile.
However, some clinicians may be reluctant to use tacrolimus ointment due to the "unknown risks", meaning those that have not been uncovered in human studies conducted thus far. Therefore, the available animal data regarding the "unknown risks" of topical tacrolimus therapy are reviewed, and a discussion of the interpretation of this available but limited data is presented.

Animal studies:
Some of the fear on the part of clinicians regarding the use of topical tacrolimus may come from the results of animal studies which showed an increase in lymphoma and UV-induced skin cancer after treatment with topical tacrolimus in animal models of carcinogenesis.
However, rigorous assessment of these studies suggest that it is somewhat likely that these represent a species-specific response to tacrolimus in an animal already predisposed to tumor formation, and therefore may not be relevant in assessing the possibility of an increased human health risk.

Conclusions:
Animal and human studies suggest that topical tacrolimus is a safe alternative to topical steroids, with the major known adverse effect being a transient burning sensation, compared with the known adverse effects of topical steroids, including long-lasting ones. Therefore, in the opinion of the authors, currently available data, including animal studies, does not suggest that "unknown risks" of topical tacrolimus need be any more concerning than the known side-effects of the topical steroids.

Is metronidazole 0.75% gel effective in the treatment of seborrhoeic dermatitis? A double-blind, placebo controlled sudy

Hamdi Ozcan, Muammer Seyhan, Saim Yologlu

European Journal of Dermatology Volume 17 Issue 4  - July-August 2007
 

Abstract  

The study aimed to evaluate the effectiveness of metronidazole 0.75% gel in patients with mild and moderate seborrhoeic dermatitis. Sixty-seven patients with seborrhoeic dermatitis were enrolled. Cases were randomly treated with metronidazole 0.75% gel or placebo for four weeks and were additionally followed up for another four weeks. Patients were evaluated by scoring before the treatment, once a week during the treatment and twice after the cessation of the treatment within a 15-day interval. Furthermore, patient satisfaction and doctor global evaluation were done at the end of the treatment and of the study as well. In the metronidazole group 33 patients (median age: 26, total severity score: 15.0 ± 11.0 (median ± interquartile range) and in the placebo group 34 patients (median age: 26, total severity score: 13.0 ± 7.5) were enrolled in the study. Three patients from the metronidazole group and four patients from the placebo group did not attend to follow-up visits. Erythema, scales, papule, pruritus and the total severity scores in both group decreased significantly during the treatment when compared with the basal levels . There was no difference between the two groups in terms of efficacy . Total severity scores were found as 7.33±1.08 and 6.43±0.93 in the metronidazole and placebo groups at the end of the treatment, respectively. After the cessation of the treatment, all scores had increased rapidly. Total severity scores were 10.40±1.54 and 11.20±1.53 in the metronidazole and placebo groups one month after the cessation of the treatment, respectively. Both metronidazole 0.75% gel and the placebo were well tolerated by the patients.

In conclusion, in the treatment of seborrhoeic dermatitis, administration of metronidazole 0.75% gel is well tolerated but it is only as effective as placebo and the disease severity quickly returns to the basal levels after the cessation of treatment. 

Vitamin D and the skin: an ancient friend, revisited

Reichrath J,

Experimental Dermatology, July 2007

Abstract  

Most vertebrates need vitamin D to develop and maintain a healthy mineralized skeleton. However, 1,25-dihydroxyvitamin D3 [1,25(OH)(2)D(3)], the biologically active vitamin D metabolite, exerts a multitude of important physiological effects independent from the regulation of calcium and bone metabolism. We know today that the skin has a unique role in the human body's vitamin D endocrine system. It is the only site of vitamin D photosynthesis, and has therefore a central role in obtaining a sufficient vitamin D status. Additionally, the skin has the capacity to synthesize the biologically active vitamin D metabolite 1,25(OH)(2)D(3), and represents an important target tissue for 1,25(OH)(2)D(3). In keratinocytes and other cell types, 1,25(OH)(2)D(3) regulates growth and differentiation. Consequently, vitamin D analogues have been introduced for the treatment of the hyperproliferative skin disease psoriasis. Recently, sebocytes were identified as 1,25(OH)(2)D(3)-responsive target cells, indicating that vitamin D analogues may be effective in the treatment of acne. Other new functions of vitamin D analogues include profound effects on the immune system as well as in various tissues protection against cancer and other diseases, including autoimmune and infectious diseases. It can be speculated that the investigation of biological effects of vitamin D analogues will lead to new therapeutic applications that, besides cancer prevention, may include the prevention and treatment of infectious as well as of inflammatory skin diseases. Additionally, it can be assumed that dermatological recommendations on sun protection and health campaigns for skin cancer prevention will have to be re-evaluated to guarantee a sufficient vitamin D status.
 

Preprandial vs. postprandial pharmacokinetics of cyclosporine in patients with psoriasis

International Journal of Dermatology, Volume 46, Number 8, pages 880-882, August 2007
Abstract  

Pimecrolimus cream 1% for papulopustular rosacea: a randomized vehicle-controlled double-blind trial.

Weissenbacher S et al.

Br J Dermatol. 2007 Apr;156(4):728-32.

Abstract  

Geographic Variation and Risk of Skin Cancer in US Women

Abrar A. Qureshi, MD, MPH; Francine Laden, ScD; Graham A. Colditz, MD, DrPH; David J. Hunter, MBBS, DrPH

Arch Intern Med. 2008;168(5):501-507.

Abstract 

Background  Occurrences of melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) have been associated with varying geography. Our goal was to evaluate differences in risk of these skin cancers according to residence at varying UV indices at 3 time points.

Methods  Prospective 1984-2002 study of 84 836 female nurses who lived in different UV index regions of the United States at birth and at 15 or 30 years of age. The outcome measure was diagnosis of melanoma, SCC, or BCC.

Results  During the 18-year study, 420 cases of melanoma, 863 cases of SCC, and 8215 cases of BCC occurred. At 30 years of age, age-adjusted risks for SCC were 1.47 (95% confidence interval [CI], 1.22-1.76) and 1.90 (95% CI, 1.51-2.36) for women residing in states with a UV index of 6 (medium) and 7 or more (high), respectively. Although elevated, the age-adjusted risk of BCC at 30 years of age associated with residence in these states was substantially less. Although the risk of melanoma was not elevated for women living in these states at 30 years of age, it was significantly elevated among women living in states with UV indices of 6 at birth and at 15 years of age. There was no material change in risk estimates with multivariate adjustment. For women who reported living in states with UV indices of 7 or more at all 3 time points, the multivariate risk of SCC was highest.

Conclusions  The risk of SCC is independently affected by residence in locations with medium and high UV indices; the gradient of risk is weaker for BCC; and the risk of melanoma does not change significantly across this gradient.