Treatment of Refractory Chronic Urticaria

Chronic spontaneous urticaria is a distressing disease encountered frequently in clinical practice. The current mainstay of therapy is the use of second-generation, non-sedating antihistamines. However, in patients who do not respond satisfactorily to these agents, a variety of other drugs are used. This article examines the available literature for frequently used agents including systemic corticosteroids, leukotriene receptor antagonists, dapsone, sulfasalazine, hydroxychloroquine, H2 antagonists, methotrexate, cyclosporine A, omalizumab, autologous serum therapy, and mycophenolate mofetil, with an additional focus on publications in Indian literature.     

Evidence - Based Pharmacological Treatment of Atopic Dermatitis: An Expert Opinion and New Expectations

Atopic dermatitis (AD) is one of the most common skin diseases with a complex multifactorial background. The clinical presentation, the aggravating factors and the complications vary according to the age of the patients. Most cases, approximately 60-80%, present for the 1^st time before the age of 12 months. Adult-onset AD has been observed as a special variant. Pruritus is the worst sign of AD, which also often indicates an exacerbation and is considered to be the most annoying symptom of AD. Treatment is preferably started based on the severity of AD. In only 10% of the cases, AD is so severe that systemic treatment is necessary. Systemic treatment including topical wet-wrap treatment is indicated in the worst and recalcitrant cases of AD. Systemic treatment of AD is discussed with regards to the evidence-based efficacy and safety aspects. I prefer wet-wraps as a crisis intervention in severe childhood cases, whereas UV and systemic treatments are the choices in patients older than 10 years. Probiotics are not useful in the treatment. If they have any effect at all it may only be in food-allergic children with AD. Finally, anti-histamines are not effective against pruritus in AD. They are only effective against urticarial flares and in cases with food-allergy. This article consists of an expert opinion on evidence-based pharmacological treatment of AD, but it is not a systemic review.     

Systemic Side-Effects of Topical Corticosteroids

With the introduction of topical corticosteroids, a milestone has been achieved in dermatologic therapy; owing to its potent anti-inflammatory and ant proliferative effects, it became possible to treat some hitherto resistant dermatoses. But this magic drug can cause enough mischief if used inappropriately. Children are more susceptible to the systemic adverse effects because of enhanced percutaneous absorption through their tender skin. So, systemic side effects should be kept in mind while prescribing this therapeutically valuable topical medicament.     

Topical treatment of pyoderma gangraenosum

The treatment of pyoderma gangraenosum (PG) is still a therapeutic challenge. Although several drugs such as corticosteroids, dapsone, clofazimine, azathioprine, tacrolimus and cyclosporine A have been shown to be effective in this disease, side-effects of these agents limit their systemic use in seriously ill patients. In recent years, topical treatment of the disease has gained attention. Several reports show an improvement of cutaneous lesions of PG following topical treatment. These earlier reports as well as our own observations suggest that topical therapeutic regimens can be a useful and safe alternative to systemic immunosuppressive therapy in the treatment of PG. We give a review about these topically used drugs and the mechanisms probably involved.     

Zinc-responsive acral hyperkeratotic dermatosis—A novel entity or a subset of some well-known dermatosis?

Background:

We are reporting a series of interesting cases, which presented to us with psoriasiform lesions distributed over the acral regions of the body. The cases are unusual because they were resistant to conventional treatment modalities like topical corticosteroids, tacrolimus and oral methotrexate but showed significant improvement on oral zinc therapy.

Materials and Methods:

Ten patients with characteristic clinical features of distinctive hyperkeratotic plaque in the acral areas, who were resistant to treatment by different modalities including potent topical steroids and oral methotrexate, were included for detailed investigations. A proper history was taken and relevant laboratory investigations were done which included blood count, urine, liver function, renal function, hepatitis-C virus serology and serum zinc levels. Patients were followed up every 2 weeks. Histopathological examinations of the lesional tissue were done at baseline and after 6 weeks of therapy. Patients were given oral zinc daily and no other treatment during the 6 weeks course.

Results:

All our patients were non-reactive to hepatitis-C. Of the ten patients only one patient (10%) showed low titer of serum zinc, another (10%) showed higher zinc level, while the rest of the patients had normal zinc level. Five of our patients had chronic renal failure, one had Grave''s disease and the remaining had no associated systemic illness. Histopathology mostly showed hyperkeratosis, acanthosis, prominent granular layer, spongiosis and dermal infiltrate. After 6 weeks of follow up, all patients showed rapid and remarkable therapeutic response with zinc.

Conclusions:

We here report a series of patients, discernible because of their uniform clinical presentation of acral hypekeratotic plaques and in showing a noticeable response to zinc. Clinical, histopathological and laboratory investigations were done to rule out diseases of similar morphology including psoriasis, acral necrolytic erythema and lichen simplex chronicus. Authors understand that further studies with greater number cases and more detailed investigations are required to establish exact etio-pathogenesis and nomenclature of this distinct subset of patients.     

Chronic urticaria

Chronic urticaria (CU) is a disturbing allergic condition of the skin. Although frequently benign, it may sometimes be a red flag sign of a serious internal disease. A multitude of etiologies have been implicated in the causation of CU, including physical, infective, vasculitic, psychological and idiopathic. An autoimmune basis of most of the 'idiopathic' forms is now hypothesized. Histamine released from mast cells is the major effector in pathogenesis and it is clinically characterized by wheals that have a tendency to recur. Laboratory investigations aimed at a specific etiology are not always conclusive, though may be suggestive of an underlying condition. A clinical search for associated systemic disease is strongly advocated under appropriate circumstances. The mainstay of treatment remains H1 antihistaminics. These may be combined with complementary pharmacopeia in the form of H2 blockers, doxepin, nifedipine and leukotriene inhibitors. More radical therapy in the form of immunoglobulins, plasmapheresis and cyclophosphamide may be required for recalcitrant cases. Autologous transfusion and alternative remedies like acupuncture have prospects for future. A stepwise management results in favorable outcomes. An update on CU based on our experience with patients at a tertiary care centre is presented.     

Updosing of Nonsedating Anti-histamines in Recalcitrant Chronic Urticaria

Chronic urticaria (CU) is a persistent, debiliating condition that causes severe impairment on the quality of life (QoL) of patient by interrupting work productivity. Current guidelines recommend second-generation (nonsedating) anti-histamines for the treatment for all forms of urticaria. In patients who do not respond adequately to conventional doses of anti-histamines, it is recommended to increase the dose to up to four times to obtain control. But there are only few controlled studies that have assessed the efficacy and safety of nonsedating anti-histamines. Though sedating histamines are frequently used as an add-on therapy in severe cases, they have a negative impact on QoL by compromising sleep and performance. The use of other suggested therapeutic options (omalizumab, cyclosporine A, montelukast and dapsone) is also limited by paucity of data on their efficacy and adverse effect profile. Second-generation anti-histamines which are relatively safer require more proven data to support their judicious use to improve disease in patients with CU.     

Management of Chronic Paronychia

Chronic paronychia is an inflammatory disorder of the nail folds of a toe or finger presenting as redness, tenderness, and swelling. It is recalcitrant dermatoses seen commonly in housewives and housemaids. It is a multifactorial inflammatory reaction of the proximal nail fold to irritants and allergens. Repeated bouts of inflammation lead to fibrosis of proximal nail fold with poor generation of cuticle, which in turn exposes the nail further to irritants and allergens. Thus, general preventive measures form cornerstone of the therapy. Though previously anti-fungals were the mainstay of therapy, topical steroid creams have been found to be more effective in the treatment of chronic paronychia. In recalcitrant cases, surgical treatment may be resorted to, which includes en bloc excision of the proximal nail fold or an eponychial marsupialization, with or without nail plate removal. Newer therapies and surgical modalities are being employed in the management of chronic paronychia. In this overview, we review recent epidemiological studies, present current thinking on the pathophysiology leading to chronic paronychia, discuss the challenges chronic paronychia presents, and recommend a commonsense approach to management.     

Treatment of keloids and hypertrophic scars

Clinicians always find it difficult to treat hypertrophic scars and keloids. Various treatment modalities are available. Intralesional corticosteroids, topical applications, cryotherapy, surgery, laser therapy, and silicone sheeting are the widely used options. Radiation therapy can also help in cases of recalcitrant keloids. Most recently, pulsed-dye laser has been successfully used to treat keloids and hypertrophic scars. There are no set guidelines for the treatment of keloids. Treatment has to be individualized depending upon the distribution, size, thickness, and consistency of the lesions and association of inflammation. A combination approach to therapy seems to be the best option.     

S2k guideline for treatment of cutaneous lupus erythematosus – guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV)

Cutaneous lupus erythematosus (CLE) is a rare inflammatory autoimmune disease with heterogeneous clinical manifestations. To date, no therapeutic agents have been licensed specifically for patients with this disease entity, and topical and systemic drugs are mostly used ‘off‐label’. The aim of the present guideline was to achieve a broad consensus on treatment strategies for patients with CLE by a European subcommittee, guided by the European Dermatology Forum (EDF) and supported by the European Academy of Dermatology and Venereology (EADV). In total, 16 European participants were included in this project and agreed on all recommendations. Topical corticosteroids remain the mainstay of treatment for localized CLE, and further topical agents, such as calcineurin inhibitors, are listed as alternative first‐line or second‐line topical therapeutic option. Antimalarials are recommended as first‐line and long‐term systemic treatment in all CLE patients with severe and/or widespread skin lesions, particularly in patients with a high risk of scarring and/or the development of systemic disease. In addition to antimalarials, systemic corticosteroids are recommended as first‐line treatment in highly active and/or severe CLE. Second‐ and third‐line systemic treatments include methotrexate, retinoids, dapsone and mycophenolate mofetil or mycophenolate acid, respectively. Thalidomide should only be used in selected therapy‐refractory CLE patients, preferably in addition to antimalarials. Several new therapeutic options, such as B‐cell‐ or interferon α‐targeted agents, need to be further evaluated in clinical trials to assess their efficacy and safety in the treatment of patients with CLE.     

Assessing the autoantibody levels in relation to disease severity and therapy response in pemphigus patients

Background:

In pemphigus, autoantibodies are directed against adhesion molecules, which make the junctions between keratinocytes, and thus determining their level can reflect the disease activity.

Aim:

The purpose of this study is to determine the clinical significance of the autoantibody levels in pemphigus management.

Materials and Methods:

The clinical features of 47 pemphigus vulgaris patients were assessed and patients′ sera were investigated by indirect immunofluorescence using monkey esophagus as a substrate for autoantibody levels.

Results:

We found a significant correlation between antibody titers and mucosal severity scores. Initial antibody titers of the patients with at least one mucosal lesion at the end of the first month of the therapy were found significantly higher than the patients who had no mucosal lesion. With the therapy, lesions resolved earlier than the antibody titers.

Conclusion:

In patients with pemphigus, especially in cases who were not treated before, sera antibody levels are a valuable tool in evaluating disease severity and choosing initial treatment. In patients who had been taking any systemic treatment, it is difficult to make a relationship between antibody levels and disease severity, because therapy improves disease earlier than the antibody titers. However, estimating antibody levels can be helpful for clinicians in disease management, in reducing or ceasing treatment dosage and anticipating recurrence.     

Treatment of Eosinophilic Annular Erythema: Retrospective multicenter study and literature review

BackgroundEosinophilic annular erythema (EAE) is a rare eosinophil-related skin disease which typically manifests with annular erythematous plaques and severe pruritus. Besides the diagnosis, the treatment of EAE is challenging since relevant published data are sparse.MethodsThe aim of this study was to assess the underlying diseases, treatments and outcomes of patients with EAE. To this end, we conducted a retrospective multicenter study and a systematic review of the MEDLINE database.ResultsWe included 18 patients with EAE followed in 8 centers. The MEDLINE database search yielded 37 relevant publications reporting 55 cases of EAE with 106 treatment sequences. The most common and efficient treatments included topical or systemic corticosteroids, hydroxychloroquine and dapsone. In refractory patients, a combination of systemic corticosteroids with hydroxychloroquine was associated with 88% of complete clinical response.DiscussionTo improve the management of EAE patients, we discuss the following treatment strategy: in topical steroid-resistant patients, hydroxychloroquine can be given as first-line systemic treatment. Dapsone, hydroxychloroquine or systemic corticosteroids are second-line options to consider. Last, monoclonal antibodies or JAK inhibitors targeting type 2 inflammation could represent promising last-resort options in refractory patients.     

Treatment of eosinophilic cellulitis (Wells syndrome) – a systematic review

Eosinophilic cellulitis (Wells syndrome) is a rare inflammatory skin disease defined by erythematous, tender, sometimes urticarial plaques, possibly with vesicles and bullae, and granulomatous eosinophilic infiltrates in the dermis. Usually the disease has a benign course with spontaneous remission within a few weeks. Nevertheless, recurrences are quite frequent and may occur for several years. The objective of this study was to review the so far reported treatment options for Wells syndrome in a systematic manner. This systematic review is based on a search on Medline, Embase and Cochrane Central Register for English and German articles from 1970 to 2015. Advices on the treatment of Wells syndrome are limited predominately to case reports or to small case series. There are no randomized controlled trials, and control groups are missing. A variety of treatment options for Wells syndrome were reported including topical and systemic corticosteroids, antihistamines, cyclosporine, dapsone, azathioprine, griseofulvin, doxycycline, minocycline, antimalarial medications, oral tacrolimus/topical tacrolimus, sulfasalazine, interferon alpha and gamma, TNF alpha inhibitors, colchicine and PUVA therapy. As well‐designed, randomized controlled trials are missing, no guidelines for the treatment of this disease can be given. Due to the small number of patients and the frequent misdiagnosis of this clinical entity, the aim of this systematic overview is to call attention to this rare condition and to help clinicians to diagnose and treat Wells syndrome effectively. Due to the good prognosis and tendency to resolve, systemic treatment should be limited to cases resistant to local therapy or with widespread lesions.     

Erosive pustular dermatosis of the scalp: causes and treatments

Erosive pustular dermatosis of the scalp is a rare condition which primarily affects older women after local trauma and has historically been treated with topical steroids. As it is a rare entity and resembles other dermatologic conditions, it may easily be misdiagnosed. Identifying the causes and evaluating the efficacy of treatments of erosive pustular dermatosis of the scalp (EPDS) is of great importance to both avoid misdiagnosis and ensure optimal treatment of this rare condition. There are numerous causes. In addition to surgeries and physical injuries, topical and procedural treatments for actinic keratoses and androgenetic alopecia can trigger the development of lesions. There are also documented associations with several autoimmune and systemic conditions. Besides corticosteroids, topical tacrolimus and photodynamic therapy were the most commonly used treatments for EPDS. They were effective with few recurrences and adverse effects. Other successful treatment options were topical dapsone, silicone gels, calcipotriol, acitretin, and isotretinoin. Oral dapsone can be used in cases of disseminated disease. Zinc sulfate should be considered with low‐serum zinc levels. While cyclosporine was effective, there were adverse effects that may limit its use. It is important for dermatologists to be aware of the wide array of potential causes of erosive pustular dermatosis and include it on their differential. Additionally, although high‐potency topical steroids have been historically used as the first‐line treatment, there are many other effective treatments that may avoid recurrence and skin atrophy, particularly in the elderly population.     

Male Genital Lichen Sclerosus

Male genital lichen sclerosus (MGLSc) is a chronic inflammatory skin disease responsible for male sexual dyspareunia and urological morbidity. An afeared complication is squamous cell carcinoma (SCC) of the penis. The precise etiopathogenesis of MGLSc remains controversial although genetic, autoimmune and infective (such as human papillomavirus (HPV) hepatitis C (HCV), Epstein-Barr virus (EBV) and Borrelia) factors have been implicated: Consideration of all the evidence suggests that chronic exposure of susceptible epithelium to urinary occlusion by the foreskin seems the most likely pathomechanism. The mainstay of treatment is topical ultrapotent corticosteroid therapy. Surgery is indicated for cases unresponsive to topical corticosteroid therapy, phimosis, meatal stenosis, urethral stricture, carcinoma in situ (CIS) and squamous cell carcinoma.     

Exogenous Ochronosis

Exogenous ochronosis (EO) is a cutaneous disorder characterized by blue-black pigmentation resulting as a complication of long-term application of skin-lightening creams containing hydroquinone but may also occur due to topical contact with phenol or resorcinol in dark-skinned individuals. It can also occur following the use of systemic antimalarials such as quinine. EO is clinically and histologically similar to its endogenous counterpart viz., alkaptonuria, which, however, exhibits systemic effects and is an inherited disorder. Dermoscopy and in vivo skin reflectance confocal microscopy are noninvasive in vivo diagnostic tools. It is very difficult to treat EO, a cosmetically disfiguring and troubling disorder with disappointing treatment options.     

Nail Psoriasis: The Journey So Far

Nail involvement is an extremely common feature of psoriasis and affects approximately 10-78% of psoriasis patients with 5-10% of patients having isolated nail psoriasis. However, it is often an overlooked feature in the management of nail psoriasis, despite the significant burden it places on the patients as a result of functional impairment of manual dexterity, pain, and psychological stress. Affected nail plates often thicken and crumble, and because they are very visible, patients tend to avoid normal day-to-day activities and social interactions. Importantly, 70-80% of patients with psoriatic arthritis have nail psoriasis. In this overview, we review the clinical manifestations of psoriasis affecting the nails, the common differential diagnosis of nail psoriasis, Nail Psoriasis Severity Index and the various diagnostic aids for diagnosing nail psoriasis especially, the cases with isolated nail involvement. We have also discussed the available treatment options, including the topical, physical, systemic, and biological modalities, in great detail in order to equip the present day dermatologist in dealing with a big clinical challenge, that is, management of nail psoriasis.     

Cicatricial Pemphigoid (Mucous Membrane Pemphigoid)

The treatment of cicatricial pemphigoid, also called mucous membrane pemphigoid (MMP), poses a great challenge, because the condition often takes an intransigent course despite all therapeutic efforts. Because of its diverse clinical manifestations, patients with MMP often have to be treated by a variety of specialists, including dermatologists, ophthalmologists, ear, nose, and throat specialists, and dentists. Since there are almost no randomized, controlled, double-blind studies comparing the use of various therapeutic agents in this condition, treatment decisions still rely heavily on individual clinicians' experience. Many different therapeutic regimens have been described in the literature, but only a few seem to hold up as valid alternatives. Systemic corticosteroids are still the agent of first choice, especially as rescue medication, for curtailing acute exacerbations. However, because of their well known long-term adverse effects, corticosteroids must be combined with immunosuppressive and/or anti-inflammatory agents. To determine which drug to choose, it is helpful to categorize patients -- as recommended by the First International Consensus -- in terms of high- and low-risk depending on the site and severity of their disease and on how rapidly it progresses. The recommended treatment for high-risk patients (i.e. patients with ocular, genital, laryngeal, esophageal or nasopharyngeal involvement) is a combination of prednisone and cyclophosphamide, or alternatively azathioprine. Once clinical improvement is evident, the corticosteroids should be slowly tapered. Dapsone is another alternative that may be used in high-risk patients, but patients who do not show any short-term improvement on this regimen should be switched to cyclophosphamide. Intravenous immunoglobulins are another effective, but expensive, treatment option in high-risk patients. Low-risk patients may well be managed with topical therapy alone, such as corticosteroids or cyclosporine. Other systemic options include dapsone, tetracycline, and nicotinamide as well as azathioprine in combination with low doses of corticosteroids. Various other systemic and topical agents, and recently biologics such as etanercept, have been reported to be effective in the treatment of MMP. However, most of the reported cases consisted of only small patient numbers and the true benefit of such agents in the condition is therefore not yet clear.     

Acne vulgaris treatment : the current scenario

Acne Vulgaris is one of the most common skin disorders which dermatologists have to treat. It mainly affect adolescent, though may present at any age. In recent years, due to better understanding of the pathogenesis of acne, new therapeutic modalities and various permutation and combinations have been designed. In topical agents; benzoyl peroxide, antibiotics, retinoids, etc are the mainstay of treatment; can be given in combinations. While systemic therapy includes oral antibiotics, hormonal therapy, and isotretinoin, depending upon the need of patients it has to be selected. Physical treatment in the form of lesion removal, photo-therapy is also helpful in few of them. Since various old and new topical and systemic agents are available to treat acne, it sometime confuse treating dermatologist. To overcome this, panel of physicians and researchers worked together as a global alliance and task force to improve outcomes in acne treatment. They have tried to give consensus recommendation for the treatment of acne. Successful management of acne needs careful selection of anti-acne agents according to clinical presentation and individual patient needs.