The status of corticosteroid therapy in dermatology

Therapy with systemic corticosteroids, despite attendant serious risks, is mandatory in diseases such as pemphigus, acute disseminated lupus erythematosus and some cases of exfoliative dermatitis that are ordinarily fatal, for in such cases life may be prolonged and the patients made comfortable. If no contraindications exist, therapy with corticosteroids is desirable, for diseases of short duration-contact dermatitis, serum sickness reactions and drug eruptions of all kinds-provided the causative factors have been removed and the reactions are causing severe distress.On the basis of encouraging reports in the literature corticosteroid therapy may be instituted with justification for a group of unrelated, intractable and discomforting diseases such as maddening pruritus ani, sclerema neonatorum, dermatomyositis, certain cases of sarcoidosis, berylliosis, Behcet's syndrome, universal calcinosis, Reiter's disease and ulcers of sickle-cell anemia. One must always bear in mind the well-defined contraindications to corticosteroid therapy and the hazards of its use, particularly if therapy is to be prolonged. Results from topical hydrocortisone therapy are particularly pleasing in chronic eczematous otitis externa and especially when it is combined with an antibiotic drug. Results are excellent also in nuchal eczema, dermatitis of the eyelids and in pruritus ani. More often than not, hydrocortisone ointment and lotions benefit more than do other standard remedies such diseases as atopic eczema, contact dermatitis, lichen simplex-chronicus and eczematized phases of conditions such as psoriasis and superficial mycotic infections. Preparations containing a combination of hydrocortisone and an antibiotic are more useful than hydrocortisone alone. When used with discrimination, with full attention to the selection of cases and proper concentration in the correct vehicle, hydrocortisone preparations in combination with antibiotics are excellent antieczematous agents.     

Psoriasis Therapy: A Current Perspective

Psoriasis is a common papulosquamous skin disease which frequently presents a therapeutic challenge to physicians. Topical therapy with steroids, coal tars and anthralin are effective when used properly for many patients. More severely affected patients may require phototherapy using coal tars and anthralin plus ultraviolet radiation. Systemic methotrexate administration is indicated for some patients with severe skin and arthropathic psoriasis. Treatment using psoralen and long-wavelength ultraviolet phototherapy has recently been approved and is effective in many patients, but long-term safety remains a question. Synthetic retinoids are experimental drugs currently being evaluated for severe forms of psoriasis.     

Synchronization of oscillations of proliferation of keratinocytes in psoriatic skin by external periodic force: a mathematical model

A mathematical model of mitotic activity of epidermis in normal skin and skin afflicted with psoriasis is presented as a system of two autonomous nonlinear differential equations. Its qualitative analysis was carried out and numerical solutions were obtained at the parameter values corresponding to these states. It was shown that in the norm, a single stable equilibrium of a "focus" type exists in the system; whereas in psoriasis, owing to an increase in the growing fraction, hyperproliferation, and enhanced migration of interacting keratinocytes, a stable limit cycle arises from the state of unstable focus. In this paper we also report on the results of computer modeling of synchronization of self-excited oscillations of keratinocyte population density in psoriatic lesions by an external periodic force. This synchronization is viewed as a possible mechanism of the clinically observed dependence of psoriasis course on some natural factors of cyclic nature.     

Anti-TNF therapies in the management of acute and chronic uveitis

Patients with anterior uveitis may be treated with topical therapy alone but patients with posterior uveitis and those with sight threatening complications of anterior uveitis usually require systemic treatment especially if the disease is bilateral. The mainstay of treatment is corticosteroids and additional immunosuppressive agents such as cyclosporin and mycophenolate are used when necessary. There remains a significant cohort of patients in whom this therapy is either not tolerated or is ineffective. The use of the anti-tumour necrosis factor (TNF) antibodies has been very successful in controlling other immune-mediated disorders such as rheumatoid arthritis and has subsequently been extended to use in other arthritidies and other disorders such as psoriasis and Crohn's disease. TNF is known to play a key role in ocular inflammation as shown by animal studies and its detection in the ocular fluids of inflamed eyes in man. In some disorders all types of anti-TNF antibodies have similar efficacy but that does not appear to be the case with uveitis where infliximab is at present looking to be more effective than etanercept. The data on the use of anti-TNF drugs in uveitis is presented together with new data on its role as a steroid sparing agent.     

Treatment of psoriasis with orally administered 8-methoxypsoralen and long-wavelength ultraviolet radiation.

Between May 1976 and September 1977, 51 patients with severe psoriasis were treated with orally administered 8-methoxypsoralen followed by exposure to high-intensity long-wavelength ultraviolet radiation. Clearing of psoriasis occurred in 40 patients (78%) and marked improvement in 5 (10%). Of the remaining patients three (6%), who had generalized erythroderma, failed to respond to this therapy. The mean number of treatments required for clearing was 37.5. No serious side effects were noted clinically, by ophthalmologic examination or by laboratory testing. This therapy has some advantages over conventional types of treatment now used for severe psoriasis, but also has limitations. It appears to be an effective method of treatment for ambulatory patients. Further long-term follow-up studies are required to evaluate its side effects.     

Corticosteroids: the mainstay in asthma therapy

Inflammation is now marked as a central feature of asthma pathophysiology and aims of current asthma management are not only to treat acute symptoms of wheezing, breathlessness, chest tightness, cough but also to suppress the underlying inflammatory component. Despite the availability of a number of drugs, corticosteroids remain the mainstay in the management of all types of asthma as these are the most potent and effective antiinflammatory agents available so far. Corticosteroids suppress virtually every step in inflammation. However therapeutic doses of oral glucocorticoids are associated with a range of adverse reactions. To overcome these side effects, inhalations have been developed to deliver glucocorticoids directly to the lungs and in the process a number of aerosol preparations have become available, which have advantage of significantly lower toxicity due to low systemic absorption from the respiratory tract and rapid inactivation. Despite considerable efforts by pharmaceutical industry, it has been difficult to develop novel therapeutic agents for asthma management, which could surpass inhaled corticosteroids. Currently the data favours using inhaled corticosteroids as monotherapy in the majority of patients in all kinds of asthma. If combination therapy is recommended to achieve additional control in severe asthma cases, other drugs such as beta-agonists, antileukotrienes, theophylline, etc. are considered as adjunct therapies to corticosteroids. This review discusses the importance of corticosteroids as first line therapy for asthma treatment with the availability of inhaled corticosteroids for chronic treatment and oral formulations for treating acute exacerbations of moderate to severe asthma.     

Psoriasis exacerbation after hormonotherapy in prostate cancer patient—Case report

Psoriasis, as the most common inflammatory skin disorder, affects about 2–3% of the world''s population. Many non-dermatological conditions have been linked with psoriasis, including cardiovascular diseases, depression, inflammatory bowel disorders, and some cancers, i.e. lung, colon and kidney cancers. Among systemic factors are endocrine and metabolic disturbances as well as many drugs. Erythrodermic psoriasis, the most severe form of the disease, is characterized by diffuse erytrema and scaling, often accompanied by fever, chills, and malaise.A 57-year-old Caucasian man was admitted for curative radiation therapy of adenocarcinoma of the prostate after 3 months of initial hormonal therapy. The management comprised the combined androgen blockade (CAB). On admission the patient reported escalation of psoriasis symptoms, which he had been treated for since 2002. Due to a mild course of the disease he had not required any systemic treatment ever before, even during aggravation periods. The last exacerbation started appearing a month after hormonal therapy implementation. The cutaneous eruptions, already existing, become larger with new foci revealing, mainly on upper and lower limbs. During radiotherapy planning, there appeared a diffuse erythema and scaling on hands and feet with accompanying pruritis. We decided to start the previously planned radiation therapy which included the prostate gland with 1.5 cm margin and provided for the total dose of 72 Gy in 36 fractions. The irradiation was conducted with the four-field technique using a megavoltage linear accelerator. During radiotherapy we photo-documented skin lesions.To our best knowledge hormone therapy (androgen deprivation) of prostate cancer patients has not been reported as an aggravating factor. Thus, the aim of our work is to present the case of a prostate cancer patient who experienced psoriasis exacerbation after implementation of hormonal blockade as a neoadjuvant oncological treatment.     

Systemic corticosteroids in alopecia totalis

Two cases of alopecia totalis are presented and some observations made on the course and treatment of the disorder. The stimulus for extensive alopecia areata appears to occur for short periods in at least some cases and may, therefore, be amenable to shorter courses of systemic corticosteroids than was formerly thought possible. Discontinuing systemic therapy does not always result in a rapid recurrence of totalis and bouts of alopecia partialis which may follow its discontinuance may be managed by more conservative means. In addition, areas resistant to 30 mg. of prednisone per day may respond to topical and intralesional therapy even while prednisone is being reduced considerably below this level.     

Synthetic retinoids in dermatology

The potential of vitamin A, or retinol, in the treatment of a variety of skin diseases has long been recognized, but because of serious toxic effects this substance generally could not be used. The recent development and marketing of two relatively nontoxic synthetic analogues, which are known as retinoids, has made it possible to treat some of the diseases that are resistant to standard forms of therapy. Isotretinoin is very effective in cystic and conglobate acne, while etretinate is especially useful in the more severe forms of psoriasis. Good results have also been obtained in other disorders of keratinization. Vitamin A and its derivatives apparently have an antineoplastic effect as well and may come to be used in both the prevention and the treatment of epithelial cancer. In many of these diseases the retinoids act by enhancing the normal differentiation and proliferation of epidermal tissues, but the exact mechanisms are not well understood. Their influence on the intracellular polyamines that control the synthesis of nucleic acids and proteins may be an important factor. Although the retinoids have few serious systemic effects, they are teratogenic, and because they persist in the body their use in women of childbearing potential is limited.     

Changes of immunomodulatory cytokines associated with omalizumab therapy for severe persistent asthma

Omalizumab is an anti-IgE monoclonal antibody that was proven effective for the treatment of severe asthma. IgE plays a central role in allergic asthma, and an anti-allergic effect of omalizumab has been confirmed in terms of its impact on Th2 cytokines. The objective of the present study is to determine the influence of omalizumab on clinical parameters and circulating immuoregulatory cytokines. Patients with severe allergic asthma were enrolled and given four months of omalizumab therapy. Changes of symptoms and other parameters were assessed, including the asthma control test (ACT) score, morning peak expiratory flow (PEF), peripheral eosinophil count, total serum IgE, and pulmonary function tests. The use of corticosteroids and short-acting bronchodilators, as well as the number of unscheduled hospital visits, were monitored. Circulating levels of cytokines were analyzed with a multiplex cytokine immunoassay in patients with or without omalizumab therapy. Asthma symptoms (evaluated by the ACT score and morning PEF) improved with omalizumab treatment, while total IgE was elevated. Use of corticosteroids and short-acting bronchodilators and the number of unscheduled hospital visits for exacerbation of asthma were all reduced by omalizumab treatment. The level of macrophage inflammatory protein 1-δ (MIP1-δ) was significantly reduced after omalizumab therapy and was high in patients without omalizumab. IL-16 also tended to decrease with omalizumab therapy. Both MIP1-δ and IL-16 decreased as asthma improved over the 4-month period of omalizumab therapy. These findings suggest that omalizumab may act via IgE-mediated immunoregulation of MIP1-δ and IL-16.     

Iatrogenic Osteoporosis,Bilateral Hip Osteonecrosis,and Secondary Adrenal Suppression in an Hiv-Infected Man Receiving Inhaled Corticosteroids and Ritonavir-Boosted Highly Active Antiretroviral Therapy

ObjectiveTo report the first case of severe osteoporosis associated with a vertebral pathologic fracture and osteonecrosis of femoral heads in an HIV-infected man receiving inhaled corticosteroids and ritonavir-boosted antiretroviral therapy.MethodsWe describe an HIV-infected man with severe osteoporosis, bilateral hip osteonecrosis, and secondary adrenal suppression, including detailed clinical, laboratory, and radiographic data, and review the related literature.ResultsA 60-year-old man with a 15-year history of HIV infection and a medical history of long-standing bronchiectasis treated with inhaled corticosteroids and hypogonadism treated with testosterone was referred to the endocrinology clinic after experiencing an osteoporotic vertebral fracture. He was taking ritonavir-boosted antiretroviral therapy. Osteonecrosis of both hips was also diagnosed, which required total hip replacement therapy.Laboratory evaluation revealed adrenal insufficiency due to increased effect of exogenous inhaled steroids and no other secondary causes of osteoporosis. A bone densitometry study showed osteoporosis of both hips and the lumbar spine. He was treated with intravenous pamidronate. During treatment, he developed bilateral femoral fractures after minor trauma.ConclusionsGiven the potential for increased serum levels of inhaled corticosteroids in patients taking ritonavirboosted highly active antiretroviral therapy, attention must be paid to the risk of bone loss in HIV-infected patients taking inhaled corticosteroids. Prescribing calcium and vitamin D supplementation and considering early osteoporosis screening are reasonable measures for this patient population. Interaction between inhaled corticosteroids and ritonavir may increase risk of hypothalamus-pituitary-adrenal axis suppression. (Endocr Pract. 2011;17:74-78)     

Role of corticosteroids in female reproduction.

Corticosteroids, ACTH, and stress can exert inhibitory and facilitory effects on reproduction. The purpose of this review is to reconcile the divergent effects of corticosteroids on gonadotropin secretion based on recent work in the area. Whether stimulation or inhibition of gonadotropin secretion is observed appears to depend on two important variables: 1) length of exposure, and 2) background of estrogen priming. The acute administration of ACTH and certain corticosteroids to estrogen-primed animals brings about the release of LH and FSH. Corticosteroids have also been shown by some investigators to cause selective release of follicle-stimulating hormone (FSH) both in vitro and in vivo. This selective facilitation of FSH release by corticosteroids may explain many deleterious effects on reproduction observed after adrenalectomy, and it may have relevance in explaining the beneficial effects of corticosteroids in inducing ovulation in anovulatory patients suffering from polycystic ovarian syndrome. Finally, evidence is presented which suggests that adrenal steroids may participate in initiation and synchronization of the preovulatory LH and FSH surge, as well as the secondary FSH surge seen on estrus in the rat.     

Are there pathological defects of interferon secretion in man?

Interferon is now recognized as an important biological mediator with both antiviral and non-antiviral (including immunoregulatory) functions. In some patients with repeated and severe infections, leucocytes appear to be unable to produce normal levels of interferon after stimulation with soluble antigens or allogeneic lymphoblastoid cells. This defect contrasts with normal immune functions, with the exception of "natural killer" non-specific cytotoxic activity which is usually impaired. This selective defect of interferon secretion may result in a special type of immuno-deficiency with multiple biological consequences, some of which can be reversed by interferon therapy.     

RENAL VASCULAR HYPERTENSION

The use of corticosteroids systemically in dermatology has benefited patients with pemphigus and systemic lupus erythematosus in that they now have a better chance to carry on a productive life. These hormones, used cautiously, can alleviate some of the tremendous suffering during the explosive exacerbations and acute crises of atopic and neurodermatitis. Corticosteroids are useful in the widespread and acute contact dermatitis and drug eruptions; they are contraindicated in the treatment of ordinary psoriasis.Every attempt should be made by history-taking, clinical examination and necessary laboratory studies to reach an accurate diagnosis before corticosteroids are used. If use of them is indicated, then total patient care is required to avoid complications, and a very careful follow-up is mandatory.     

Systematic review of comparative efficacy and tolerability of calcipotriol in treating chronic plaque psoriasis

ObjectivesTo evaluate the comparative efficacy and tolerability of topical calcipotriol in the treatment of mild to moderate chronic plaque psoriasis.DesignQuantitative systematic review of randomised controlled trials.Subjects6038 patients with plaque psoriasis reported in 37 trials.ResultsCalcipotriol was at least as effective as potent topical corticosteroids, calcitriol, short contact dithranol, tacalcitol, coal tar, and combined coal tar 5%, allantoin 2%, and hydrocortisone 0.5%. Calcipotriol caused significantly more skin irritation than potent topical corticosteroids (number needed to treat to harm for irritation 10, 95% confidence interval 6 to 34). Calcipotriol monotherapy also caused more irritation than calcipotriol combined with a potent topical corticosteroid (6, 4 to 8). However, the number needed to treat for dithranol to produce lesional or perilesional irritation was 4 (3 to 5). On average, treating 23 patients with short contact dithranol led to one more patient dropping out of treatment owing to adverse effects than if they were treated with calcipotriol.ConclusionsCalcipotriol is an effective treatment for mild to moderate chronic plaque psoriasis, more so than calcitriol, tacalcitol, coal tar, and short contact dithranol. Only potent topical corticosteroids seem to have comparable efficacy at eight weeks. Although calcipotriol caused more skin irritation than topical corticosteroids this has to be balanced against the potential long term effects of corticosteroids. Skin irritation rarely led to withdrawal of calcipotriol treatment. Longer term comparative trials of calcipotriol versus dithranol and topical corticosteroids are needed to see whether these short term benefits are mirrored by long term outcomes such as duration of remission and improvement in quality of life.     

The psoriatic epidermal lesion and anagen hair growth may share the same "switch-on" mechanism

Based on striking parallels between the cell kinetics in the epidermal lesion of psoriasis and the proliferation of hair matrix keratinocytes during the anagen phase of the hair growth cycle, the hypothesis is proposed that both phenomena may share the same "switch-on" mechanism. Particular emphasis is placed on a comparison between the Koebner phenomenon in psoriasis and wounding-induced anagen hair growth. In discussing alternative theoretical models for the proposed common "switch-on" mechanism, some useful experimental tools are suggested. Research into the mechanisms which control epithelial proliferation in psoriasis and hair growth may provide new insights into other growth processes, such as embryonic organogenesis and neoplasia, in which similar epithelial-mesenchymal interactions play a pivotal role.     

Osteoarthritis of the First Carpometacarpal Joint

The first carpometacarpal (trapeziometacarpal) joints are a frequent site of osteoarthritis in postmenopausal women. This osteoarthritis, which is typically bilateral both clinically and roentgenographically, may be mistaken for tenosynovitis unless its characteristic features are recognized. These features include tenderness, stiffness, crepitus, swelling, and pain on wringing movements or other motions that cause abduction of the thumb. The swelling, radial subluxation of the metacarpal and atrophy of the thenar muscles give the hand a squared appearance.In severe cases, conservative medical therapy is generally unsatisfactory. Intra-articular corticosteroids and local anesthetic give only transient relief. Results of surgical therapy, including excision of the trapezium or arthrodesis of the trapeziometacarpal joint, were in general good. Distinct indications exist for each type of operation.     

A simple method for the evaluation of epidermal thickness variations in psoriasis vulgaris

OBJECTIVE: To evaluate the "variation" of the epidermal thickness and variables such as the mean, maximum, and minimum thickness for the diagnosis and follow-up of some skin diseases such as psoriasis. STUDY DESIGN: A simple quantitative method is described. A series of psoriasis vulgaris cases is provided as an example. Biopsy samples taken before and after topical treatment were used. RESULTS: The mean thickness was higher in lesions compared to the perilesional control skin (p < 0.001) and post-treatment lesional area (p < 0.001). CONCLUSION: The thickness of the epidermis varies due to a multitude of factors. Measuring the mean epidermal thickness may be important. However, this measurement may not be the best way for studies involving a series of patients and a variety of lesion sites. The natural variations in the thickness of the epidermis of different body sites and of different persons may prevent the usage of thickness measurements alone on a wider scale. It is hoped that this method can be used for evaluation of certain skin diseases affecting epidermal thickness where variation of the epidermal thickness is a potentially useful diagnostic and therapeutic variable.     

小型黑光灯治疗斑块型银屑病疗效观察

目的:观察小型黑光灯治疗斑块型银屑病疗效。方法:采用小型黑光灯(电压220V,电流0.34A,功率25.4W,主波峰长365nm,辐照度为1070μW/cm2)治疗76例斑块型银屑病患者,20次为一疗程。结果:小型黑光灯第一疗程和第二疗程临床显效率分别达72.37%和84.21%,未发现明显不良反应。结论:小型黑光灯治疗斑块型银屑病具有治疗方便、疗效好,不良反应小等优点。     

Keratinocytes regain momentum as instigators of cutaneous inflammation

The primary role of skin is to serve as a protective coat and epidermal keratinocytes are responsible for this barrier function. Besides providing structural support, keratinocytes can initiate inflammatory reactions, thereby enhancing healing of skin that follows barrier perturbation. In complex diseases such as psoriasis, in which both barrier function and cutaneous inflammation are dysregulated, it is unclear whether the primary pathogenic disturbance resides in keratinocytes or in immunocytes, which are commingled in psoriatic plaques. Researchers have turned to animal models of cutaneous inflammation to gain insights into the pathogenesis of psoriasis. A recent report in which the inducible epidermal deletion of Jun proteins in adult mice triggered inflammatory skin lesions and destructive arthritis has shifted momentum towards the keratinocyte as a key instigator of cutaneous inflammation. However, because this transgenic mouse model mimics only some features of psoriasis, further studies are required before the prevailing view of psoriasis as a fundamentally immunocyte-driven disease can be replaced by the notion that keratinocytes are the primary pathogenic cells in psoriasis.