Improvement of dermatological symptoms in patients with Bachmann–Bupp syndrome using difluoromethylornithine treatment

Bachmann–Bupp syndrome (OMIM #619075) is a novel autosomal dominant disorder caused by variants in the c-terminus of the ornithine decarboxylase 1 gene, resulting in increased levels of ornithine decarboxylase. This case report includes two patients diagnosed with Bachmann–Bupp syndrome who were treated with difluoromethylornithine through compassionate use approval from the United States Food and Drug Administration. In both patients, treatment with difluoromethylornithine has resulted in improved dermatologic signs, including regrowth of eyebrow and scalp hair and cessation of recurrent follicular cyst development.     

Does fasting during Ramadan affect the use of topical dermatological treatment by Muslim patients in the UK?

Background. Ritual fasting during the Muslim religious festival of Ramadan is one of the ‘Five Pillars’ of Islam, and is widely observed by Muslims. Previous studies have highlighted compliance issues in patients prescribed oral medications during this period. Aim. To assess whether fasting during Ramadan influence the use of topical treatments for skin disease in Muslim patients. Methods. This was a prospective, anonymous, questionnaire survey undertaken in a dermatology centre in a tertiary hospital in the UK. Patients were asked if they would use topical treatment while fasting, and whether they would consider this a breach of their fast. Results. We found that more than one‐third of the people interviewed would not use topical treatment while fasting, and around the same number (> 30%) would also consider this a breach of their fast. Although the majority of these patients thought that using steroid‐based topical products was not acceptable, a significant proportion extended this opinion to use of any cream or emollient, and even to light therapy. Gender, age, or educational level were not useful predictors of patient opinion, but there was a significant association with birthplace and likelihood of using topical treatment during Ramadan; patients born outside the UK were significantly (P < 0.01) less likely than those born in the UK to use topical treatment in the fasting period. Conclusions. Our study indicates that fasting may be a significant and a hitherto unrecognised cause of non‐compliance with topical treatment in Muslim patients in the UK, with potential health, quality and cost implications. Ritual fasting during Ramadan is widely observed by Muslims. Previous studies have highlighted compliance issues in patients prescribed oral medications during this period, and it seems this extends to use of topical treatments for skin disease.     

What is new in the treatment of steroid-induced osteoporosis?

Glucocorticoid-induced osteoporosis (GIOP) is a serious complication resulting from long-term steroid treatment. In addition to several nonpharmacologic therapies recommended by the American College of Rheumatology, various pharmacologic therapies, such as calcium, vitamin D, hormone-replacement therapy, calcitonin, and bisphosphonates, can be used to prevent and/or treat GIOP. Bisphosphonates, which are potent inhibitors of bone resorption, are considered the most effective and first-line agents for increasing bone mineral density and decreasing the risk of fracture. Human parathyroid hormone has emerged as a promising agent for the treatment of severe GIOP when used alone or in combination with a bisphosphonate.     

What is new in the treatment of steroid-induced osteoporosis?

Glucocorticoid-induced osteoporosis (GIOP) is a serious complication resulting from long-term steroid treatment. In addition to several nonpharmacologic therapies recommended by the American College of Rheumatology, various pharmacologic therapies, such as calcium, vitamin D, hormone-replacement therapy, calcitonin, and bisphosphonates, can be used to prevent and/or treat GIOP. Bisphosphonates, which are potent inhibitors of bone resorption, are considered the most effective and first-line agents for increasing bone mineral density and decreasing the risk of fracture. Human parathyroid hormone has emerged as a promising agent for the treatment of severe GIOP when used alone or in combination with a bisphosphonate.     

Stress and quality of life in dermatological patients: Are out-patients&rsquo; needs different?

The debut, progression and maintenance of skin disease are related to stress (acne, alopecia areata, atopic dermatitis, lichen planus, psoriasis, urticaria, vitiligo, herpes, hyperhidrosis, pemphigus, rosacea or seborrheic dermatitis). Environmental, socio-professional, life events are representing external factors. Personality, previous experiences, traits of anxiety are individual factors influencing the state of stress. Perceived stress could be more harmful especially in “high reactors” to stress. Coping abilities to stress could be increased in social programs. There was a recent interest in measuring the quality of life in the last years. There are dermatology and disease specific questionnaires that could help. Out-patients have less time to wait for very sophisticated procedures. They expect faster results. For simple, acute diseases it is important to have a good communication and good understanding of the instructions to get results as soon as possible. For chronic diseases a strong long-term alliance is needed, so the patients should revisit for his benefit and not for giving up. Small questions regarding potential stressful events, impact on the quality of life, stigmatization, the level of symptoms (pruritus), psychiatric comorbidities (anxiety, depression), short questionnaires for quality of life give us a better picture, personalize the doctor-patient relationship and could influence the choice of treatment. Many skin disorders could be seen from a psychosomatic point of view and the final goal, especially for the chronic diseases, is to improve through our treatments the impact on the quality of patient’s life.     

What's new in dermatological therapy?

A review of the medical literature and of the regulatory agencies website was performed to identify new information about dermatological therapy from October 2006 to October 2007. Care was taken to prioritize results from randomized controlled trials and epidemiological studies of acceptable methodology. In the last year, significant advances have been made in the field of psoriasis, pemphigus, prevention of infection with oncogenic papillomaviruses, leg ulcers, evaluation of lasers and photodynamic therapy. The availability of biological agents for the treatment of psoriasis, auto-immune disease and skin cancer will certainly induce major changes in our therapeutic strategies in the near future. The dermatologist needs to keep-up with new therapies in order to address the therapeutic needs of patients with skin diseases.     

Is dermatological lilac really lilac?

Background/Objective

Dermatologists use the word lilac to describe a shade of erythema; especially in lichen planus, morphea, and dermatomyositis. The aim of this study to determine whether or not there is a color really consistent with a lilac color, when they perceive it.

What's new in dermatological research?

Dermatology research has been very rich this year, once again. The physiopathological mechanisms of paradoxical reactions to anti-TNF are better understood and new therapeutic targets for psoriasis have been evidenced. Targeted therapy in oncodermatology have shown their potential usefulness clinically but fundamental data have also clarified their mechanisms of action as well as their limits. The key role played by the immune system in nonsegmental vitiligo has also been clearly demonstrated. Fibroblasts as well as visible light seem to play a key role that has been poorly understood to date within the complex mechanisms of cutaneous pigmentation. Specific receptors of pruritus have been reported and foster hope for the development of more effective antipruriginous treatments in the near future. Other studies report new potential targets for diseases such as fungoid mycosis, atopic dermatitis, or scleroderma. Finally, physiopathological explanations have contributed to a variety of domains such as greying hair, axillary odors, HIV and herpes virus interrelations, and the teratogenicity of thalidomide.     

What's new in dermatological treatments?

Although the isolated clinical cases published are sometimes helpful in individual situations in which the therapeutic options have been exhausted, this type of publication cannot be generalized. For this reason, the selection presented covering the period from November 2009 to October 2010 is to a very large extent based on controlled trials, either because they contribute important information or because they raise great hope for a significant number of patients. For the first time in cutaneous oncology, a treatment (ipilimumab) has significantly increased overall survival in patients with metastatic melanoma (phase III), although this gain remains modest (4-6 months) and adverse immunological effects are frequent (30-40%). A phase I trial with treatment specifically targeting the mutant BRAF protein has shown an objective response in 81% of the patients treated in the metastatic phase of melanoma, thus allowing its development to be pursued. Grouping two studies in a rare tumor such as dermatofibrosarcoma also gives hope with imatinib as a neoadjuvant treatment when the initial tumor is inoperable, with, however, an inconsistent response of approximately 50% and only if the tumor presents reorganization of chromosomes 17 and 22. Cutaneous inflammatory diseases are still dominated by dual therapies in psoriasis, with, notably, an effectiveness trial on etanercept at different doses not showing a difference in efficacy depending on dose for the joint component of psoriasis, but also by the publication of a direct comparison of two dual therapies, ustekinumab versus etanercept. In atopic dermatitis, a controversial article invites one to reflect upon the progress made in the management of children by clinical nurses, as in the Netherlands and in Great Britain, in an attempt to contend with the shortage of dermatologists. Since the use of biotherapies is not the prerogative of psoriasis, infliximab was assessed in a phase II trial in Verneuil disease without demonstrating significant efficacy on the main criterion, but it did show a tendency to reduce the score used. This trial suffered from a weakness both in methodology and statistical power, thus precluding any conclusion. The rarity of therapeutic trials on drug eruptions warrants their mention. A French phase II study gives a glimpse of a trend toward efficacy in terms of survival in the treatment of toxic epidermal necrolysis with cyclosporine. As for infectious dermatosis and sexually transmitted infections, a French multicenter study has shown significantly higher efficacy with ivermectin than with malathion in treating pediculosis without increasing the side effects. Today, however, this systemic treatment cannot be a first-line treatment outside of certain specific situations. A large cohort study (somewhat unsatisfactory in its methodology) has not demonstrated the teratogenicity of antiherpes treatments in 830,000 infants. In prevention of HIV transmission, no microbicidal gel had shown efficacy to date. This has now been accomplished in South Africa with a 1% tenofovir gel. The results of a preliminary trial on therapeutic vaccination against HPV16 proposed to women who are carriers of cervical intraepithelial neoplasia opens the way for wide vaccine therapy of cutaneous virus-induced neoplasia. In conclusion, several articles analyzing the dermatology literature provide an opportunity to reflect on the quality of such articles, Boutron's being absolutely in-dis-pen-sa-ble!     

What's new in dermatological research?

Dermatological research has been very active this year. Most of the numerous fields investigated involve the mechanisms of cutaneous regeneration and barrier function. A novel target of early ultraviolet-induced skin photodamage, the Syk kinase, has been recently identified. Synergistic relationship between telomere damage and cutaneous progerin production during cell senescence may also participate in the natural skin aging process. Interestingly, ultraviolet radiation induces an inhibitory effect on subcutaneous lipogenesis. Androgenetic alopecia or common baldness is not characterized by loss of hair follicle stem cells but by a defect in the conversion of hair follicle stem cells into active progenitor cells. It has been shown that the cornified envelope functions not only as a physicomechanical barrier, but also as both a biochemical line of antoxidant defense and an immunological line of defense. Like human papillomaviruses, Merckel cell polyomavirus belongs to the skin microbiome and different studies have demonstrated the protective role of epidermal resident microflora through the activation of innate immunity. Production of antimicrobial peptides and the activation of inflammasome and plasmacytoid dendritic cells are involved in the modulation of the cutaneous barrier function. Results from different studies suggest that IL-22 and IL-36 may be common mediators of both innate and adaptive immune responses. All these pathways interact not only to maintain cutaneous homeostasis and integrity (wound healing) but also to regulate autoinflammatory and autoimmune dermatoses (psoriasis, lupus, rosacea, atopic dermatitis, etc...). In addition, molecular mechanisms that regulate T helper type 2 differentiation and the retention at the site of inflammation of Th2 cells have been identified. New promising therapeutic targets for different chronic dermatosis are thus suggested. Mechanobiology and mechanotransduction are also emerging fields that investigate mechanical interactions between living cells and their environment and the conversion of mechanical cues into biochemical signals. Electronic second skin is now a current concept through bio-integrated epidermal electronics platforms used for different monitoring and stimulations of body functions.     

What's new in dermatological therapy?

Several good-quality randomised trials brought useful information on how to manage severe skin infections and develop anti-staphylococcus strategies. Trials on common warts did not bring any valuable solution. Rituximab and omalizumab have seen their indications becoming more precise or broadened. Meta-analyses have been particularly numerous, but most of the time with no decisive conclusion, since this methodology presents strong limitations for studying safety data. Most important work has been rather directed toward analysing safety data rather than efficacy. Among the most important results, are those from a retrospective cohort of patients taking isotretinoin: suicidal risk has to be linked to severe acne itself, rather than to the drug.     

What is the most promising strategy for the treatment of metastasizing melanoma?

The treatment of patients with metastasizing melanoma, still one of the most deadly diseases in modern medicine, ranks among the greatest challenges that a clinician has to face. Metastatic melanoma also is one of the most profound sources of clinical frustration, since it provides far more ultimately defeating experiences than clinical victories. At the same time, the fascinating biology of melanoma has invited the study of this neuroectodermal tumor as a model system for dissecting many of the key problems of modern oncology, ranging from molecular oncogenesis via the controls of tumor proliferation, apoptosis, invasion, metastasis, and angiogenesis to tumor immunosurveillance and tumor drug resistance. Together with the dire need to develop more effective treatment modalities for improving both life expectancy and quality of life of affected patients, this has made metastatic melanoma a favorite model for the exploration of innovative strategies for tumor management. Encouragingly, many of these have already generated very promising results in animal models. However, this impressive level of research progress in conquering melanoma in the animal room contrasts rather pitifully with the actual progress made on the ward. This CONTROVERSIES feature, therefore, critically and soberly reviews the state of the art of treating metastatic melanoma today (distinguishing between nodal and distant metastases), and sharply defines unresolved or comparatively neglected key problems. In addition, this feature highlights several novel, provocative, hitherto underappreciated, yet potentially promising treatment approaches that deserve systematic exploration. Hopefully, this will offer further inspiration for the design and pursuit of innovative anti-melanoma strategies off-the-beaten-track.     

Should all patients with psoriasis receive statins? Analysis according to different strategies

BackgroundDifferent strategies have been proposed for the cardiovascular risk management of patients with psoriasis.ObjectiveTo estimate the cardiovascular risk and evaluate two cardiovascular prevention strategies in patients with psoriasis, analyzing which proportion of patients would be candidates to receive statin therapy.MethodsA retrospective cohort was selected from a secondary database. All patients >18 years with psoriasis without cardiovascular disease or lipid-lowering treatment were included. The atherosclerotic cardiovascular disease calculator (2018 American College of Cardiology/American Heart Association guidelines) and the Systematic Coronary Risk Evaluation risk calculator (2016 European Society of Cardiology/European Society of Atherosclerosis guidelines) were calculated. The SCORE risk value was adjusted by a multiplication factor of 1.5. The recommendations for the indication of statins suggested by both guidelines were analyzed.ResultsA total of 892 patients (mean age 59.9 ± 16.5 years, 54.5% women) were included. The median atherosclerotic cardiovascular disease calculator and Systematic Coronary Risk Evaluation values were 13.4% (IQR 6.1–27.0%) and 1.9% (IQR 0.4–5.2), respectively. According to the atherosclerotic cardiovascular disease calculator, 20.1%, 11.0%, 32.9%, and 36.4% of the population was classified at low, borderline, moderate, or high risk. Applying the Systematic Coronary Risk Evaluation, 26.5%, 42.9%, 20.8%, and 9.8% of patients were stratified as having low, moderate, high, or very high risk, respectively. The proportion of subjects with statin indication was similar using both strategies: 60.1% and 60.9% for the 2018 American College of Cardiology/American Heart Association and 2016 European Society of Cardiology/European Society of Atherosclerosis guidelines, respectively.Study limitationsThis was a secondary database study. Data on the severity of psoriasis and pharmacological treatments were not included in the analysis.ConclusionThis population with psoriasis was mostly classified at moderate–high risk and the statin therapy indication was similar when applying the two strategies evaluated.