The clinical spectrum of congenital ichthyosis in Sweden: a review of 127 cases

Congenital ichthyosis comprises a rare group of usually monogenetic diseases that present at birth as a collodion phenotype or as variable degrees of ichtHyosiform erythroderma, with or without superficial blisters. Depending on which gene mutation causes the disease, the skin problems later in life may range from a severe lamellar or bullous ichthyosis to mild or only focally expressed hyperkeratotic lesions. It is obviously important, but sometimes painstakingly difficult, to make a correct diagnosis already in infancy. Fortunately, recent advances in our understanding of the molecular genetics of ichthyosis have led to several new diagnostic tools that are continuously being updated. Based on this development, and on our own 5 years of experience in a national genodermatosis centre, we describe 127 cases of congenital ichthyosis examined in childhood or adulthood. Applying a combination of phenotypic and genotypic criteria, the patients were classified into three main groups: 1) Bullous ichthyosis (epidermolytic hyperkeratosis) and related disorders due to keratin mutations (n = 21); 2) Non-bullous ichthyosiform erythroderma and lamellar ichthyosis mainly due to transglutaminase 1 mutations (n = 80); 3) Syndromic ichthyosis, i.e. systemic (multi-organ) diseases due to many different causes (n = 26). Each group could be further stratified into 4-11 entities using mutation analysis, electron microscopy of epidermis and various other techniques. Our findings are discussed in relation to recent data in the literature emphasizing the clinical usefulness of various diagnostic procedures for ichthyosis.     

New techniques in the evaluation of cutaneous T-cell lymphoma

The prognosis of mycosis fungoides and Sézary syndrome can be improved when antitumor therapies such as total skin electron beam irradiation, topical nitrogen mustard, or systemic cytostatic agents are given as soon as the diagnosis is established. However, differentiation of early lesions of mycosis fungoides and Sézary syndrome from chronic benign dermatoses remains very difficult. To aid in the differential diagnosis, more objective techniques have been developed, including DNA cytophotometry, chromosome analysis, quantitative electron microscopy, and monoclonal antibody staining. Using these methods, skin infiltrates and lymph nodes can be classified more precisely as malignant or benign at an earlier stage of the disease. It must be stressed that these methods can be used only in conjunction with other clinical and histomorphologic criteria. They should never be used alone, however, because reactive processes may sometimes cause problems in interpreting the results.     

Keratosis pilaris: a common follicular hyperkeratosis

Keratosis pilaris (KP) is a common inherited disorder of follicular hyperkeratosis It is characterized by small, folliculocentric keratotic papules that may have surrounding erythema. The small papules impart a stippled appearance to the skin resembling gooseflesh. The disorder most commonly affects the extensor aspects of the upper arms, upper legs, and buttocks. Patients with KP usually are asymptomatic, with complaints limited to cosmetic appearance or mild pruritus. When diagnosing KP, the clinician should be aware that a number of diseases are associated with KP such as keratosis pilaris atrophicans, erythromelanosis follicularis faciei et colli, and ichthyosis vulgaris. Treatment options vary, focusing on avoiding skin dryness, using emollients, and adding keratolytic agents or topical steroids when necessary.     

Analysis of common side effects of isotretinoin

Patients with severe recalcitrant nodular acne that is unresponsive to conventional therapy (including topical and systemic antibiotics) have few alternative effective treatment modalities other than the use of oral isotretinoin (Accutane). The cause of acne vulgaris is multifactorial, but the pathogenesis of this disorder of the pilosebaceous follicles arises mainly from endogenous factors. It is usually, but not always, associated with the onset of puberty. Severe acne, defined by the prevalence of facial and truncal inflammatory lesions, is a disfiguring disease that can often result in significant permanent scarring after the healing of deep inflammatory lesions and other disorders, such as systemic bacterial infections. Topical treatments are considered as the first line of therapy for less severe forms of acne, although systemic treatments such as antibiotics or antiandrogen agents are effective for either mild or moderate forms and sometimes effective for severe acne. However, in many patients with large numbers of nodules, longer treatment periods with these agents are required to reduce the count of inflammatory lesions. It has become increasingly evident that (because topical agents and antibiotic or antiandrogenic therapy have a slow onset of action) even mild or moderate acne that is treated in this way can result in scarring. In addition, the excessive use of systemic antibiotics has led to the detection of increasing numbers of antibiotic-resistant bacteria on the skin of patients with acne.(1) Therefore, because of its relatively rapid onset of action and its high efficacy with reducing more than 90% of the most severe inflammatory lesions, Accutane has a role as an effective treatment in patients with severe acne that is recalcitrant to other therapies.     

Alertas cutáneas en malignidades sistémicas (parte 2)

The skin can be key to early diagnosis of systemic malignancies. In the second part of this review, we present various skin conditions that can, in certain contexts, reveal the presence of malignancy. The skin conditions are presented in groups based on a diverse range of morphological characteristics. Specifically, the following groups are analyzed: erosive and blistering lesions; inflammatory papules and nodules; xerosis, ichthyosis, and generalized exfoliative dermatitis; symptoms such as pruritus; abnormal hair distribution patterns; sweating disorders; benign tumors that can form part of hereditary syndromes associated with a risk of visceral cancer; and finally, oral and nail abnormalities.This review highlights the importance of the skin in the study of systemic malignancies.     

KID syndrome

KID syndrome is a rare congenital disorder characterized by keratitis, ichthyosis, and deafness. We have described a 4-year-old girl who is treated with bland emollients and topical keratolytics such as urea and surprisingly observed marked improvement in skin hyperkeratosis and palmoplantar keratoderma. We think that along with urgent ophthalmologic and otolaryngologic measures, simple topical therapies may improve skin condition in KID syndrome precluding the possible hazards of systemic retinoid therapy.     

Dermatoglyphic characteristics in hereditary ichthyosis

Examination of 530 dermatoglyphic patterns of the palms and fingers in 265 patients with 5 nosologic forms of hereditary ichthyoses (autosomal dominant ichthyosis vulgaris, X-linked, congenital, lamellar, epidermolytic ichthyoses) have revealed significant differences in the pattern intensities and in the incidence rate of certain types of these patterns, associated with this or that form of ichthyosis; abnormalities in the flexor wrinkles of the ridge skin have been observed in all the studied forms of the disease, except the X-linked condition. The studies have revealed an abnormal roughness of the papillae on the epidermal ridges in epidermolytic ichthyosis and an obliterated dermatoglyphic pattern in lamellar ichthyosis. The detected changes in the ridge skin and the dermatoglyphic phenotypes may be useful for the differential diagnosis of these conditions.     

Ichthyoses – Part 2: Congenital ichthyoses

Congenital ichthyoses are a group of genetic disorders with defective cornification, clinically characterized by scaling of the skin. Additionally, distinctive cutaneous inflammation can often be observed. For most of the patients these diseases lead to a significant restriction in quality of life. The diagnostic hallmarks are discussed. The diagnostic criteria include clinical and histological findings, often enhanced or confirmed by specialized tests. Because many of the congenital ichthyoses are extremely rare, their accurate diagnosis is often carried out in specialized centers. After discussing the vulgar ichthyoses as well as the diagnostic and therapeutic options in part one, in this second part we review congenital ichthyoses both with and without associated symptoms, focusing on the common genetic changes and their clinical phenotype. Specific therapies are still not available for most of these disorders. The use of different topical agents (e. g. urea, retinoids and salicylic acid) and baths followed by mechanical keratolysis (sometimes in combination with systemic retinoids) reduce skin symptoms. Patients with uncommon congenital ichthyoses often benefit from interdisciplinary management which involves specialized dermatological centers.     

Ichthyoses in everyday practice: management of a rare group of diseases

Ichthyoses comprise a heterogeneous group of hereditary disorders of keratinization characterized by a highly varied clinical picture. A distinction is made between common hereditary ichthyoses (ichthyosis vulgaris and X‐linked ichthyosis), which usually manifest themselves in the first year of life, and rare, sometimes severe congenital ichthyoses. Patients with very mild symptoms often do not even realize they have ichthyosis. The diagnosis is usually based on clinical evaluation. Molecular genetic testing as well as histological and electron microscopic studies may aid in confirming the diagnosis. Mapping a family tree is also diagnostically useful. Besides skin manifestations, important aspects of the clinical examination and history include disease onset, presence of a collodion membrane at birth as well as the presence of hair anomalies and extracutaneous signs and symptoms. Rigorous hydration of the skin (several times a day) and balneotherapy are the mainstay of ichthyosis treatment. For patients with severe disease, systemic acitretin treatment should be considered on a case‐by‐case basis. While ichthyoses are generally limited to the skin, there are syndromic forms that may affect other organs and that require interdisciplinarity cooperation. Although ichthyoses remain incurable, they can be managed well with symptomatic treatment. However, such treatment is frequently time consuming and expensive. In the future, novel therapeutic approaches might include enzyme replacement and gene therapies as well as antiinflammatory drugs.     

Ocular effects of topical and systemic steroids.

Topical and systemic steroids have proven to be invaluable agents in the treatment of a wide range of disorders, but their use is not without potential complications. Before initiation of therapy with systemic steroids, a personal or family history of cataracts, glaucoma, hypertension, diabetes, hyperlipidemia, renal stones, peptic ulceration, and current infection or pregnancy should be ascertained, because these patients have an increased risk of complications. Prior to long-term therapy with systemic steroids, blood pressure measurement, tuberculin skin test, and anergy panel are recommended. Monthly follow-up may include measurements of weight, blood pressure, electrolytes, and blood sugar and guaiac testing of the stool. To prevent the ocular complications of steroid therapy, routine screening is indicated (Table 1). Screening for cataracts, which occur most commonly as a sequela of continuous systemic steroid use, may be performed by slit-lamp examinations conducted three or four times a year for patients on long-term therapy and twice a year for patients taking intermittent topical ocular or systemic steroids. Glaucoma is more often associated with topical ocular or periocular steroids than with systemic steroids; recommended screening includes a baseline intraocular pressure measurement, then routine pressure measurements taken every few weeks initially, then every few months. Ocular rebound inflammation may develop secondary to rapid tapering or abrupt discontinuation of topical ocular steroid use and is best prevented with gradual tapering. Opportunistic infections of the eye include bacterial, viral, and fungal infections and are most often associated with the use of topical ocular steroids. Ophthalmologic evaluation is indicated promptly if patients treated with ocular steroids develop ocular discharge, pain, photophobia, or redness.     

Atopic dermatitis: systemic immunosuppressive therapy

Atopic dermatitis (AD) is a pruritic, relapsing skin disorder that negatively impacts the quality of life of those affected and that of their families. Treatment options for AD encompass a variety of emollients, topical corticosteroids, topical immunomodulators, phototherapy, and systemic agents. Such agents as systemic corticosteroids, cyclosporine, azathioprine, interferon-gamma, methotrexate, and mycophenolate mofetil have been shown to be efficacious in the treatment of moderate-to-severe AD but are not officially approved for this purpose. In this article, we review some of the data supporting efficacy of these medications and discuss some of the adverse events associated with their use.     

Topical Antibacterial Treatments for Acne Vulgaris

Topical antibacterial agents are an essential part of the armamentarium for treating acne vulgaris. They are indicated for mild-to-moderate acne, and are a useful alternative for patients who cannot take systemic antibacterials. Topical antibacterials such as clindamycin, erythromycin, and tetracycline are bacteriostatic for Propionibacterium acnes, and have also been demonstrated to have anti-inflammatory activities through inhibition of lipase production by P. acnes, as well as inhibition of leukocyte chemotaxis. Benzoyl peroxide is a non-antibiotic antibacterial agent that is bactericidal against P. acnes and has the distinct advantage that thus far, no resistance has been detected against it. Combined agents such as erythromycin/zinc, erythromycin/tretinoin, erythromycin/isotretinoin, erythromycin/benzoyl peroxide, and clindamycin/benzoyl peroxide are increasingly being used and have been proven to be effective. They generally demonstrate good overall tolerability and are useful in reducing the development of antibacterial resistance in P. acnes. The selection of a topical antibacterial agent should be tailored for specific patients by choosing an agent that matches the patient's skin characteristics and acne type. Topical antibacterial agents should generally not be used for extended periods beyond 3 months, and topical antibacterials should ideally not be combined with systemic antibacterial therapy for acne; in particular, the use of topical and systemic antibacterials is to be avoided as far as possible.     

Topical pimecrolimus and tacrolimus and the risk of cancer

In this review the controversy regarding the association between topical pimecrolimus and tacrolimus and the development of tumors is unfolded. After reviewing the literature we conclude that, currently, there is no scientific evidence of an increased incidence of skin cancer, lymphomas or systemic immunosuppression in those patients that use or have used topical calcineurin inhibitors. Published studies lack adequate number of patients and/or the follow-up time is short enough to conclude that topical use of calcineurin inhibitors might be associated with the reported cases of skin cancer and lymphoma. Nevertheless the possibility of long term cutaneous and/or systemic side effects cannot be excluded.     

S1 guidelines for the diagnosis and treatment of ichthyoses – update

Ichthyoses are a group of rare genetic skin disorders that pose numerous clinical challenges, in particular with respect to the correct diagnosis and appropriate management. The present update of the German ichthyosis guidelines addresses recent diagnostic advances that have resulted in the Sorèze consensus classification. In this context, we provide an updated diagnostic algorithm, taking into account clinical features as well as the molecular genetic basis of these disorders. Moreover, we highlight current therapeutic approaches such as psychosocial support, balneotherapy, mechanical scale removal, topical therapy, and systemic retinoid therapy. General aspects such as the indication for physical therapy, ergotherapy, or genetic counseling are also discussed. The present update was consented by an interdisciplinary consensus conference that included dermatologists, pediatricians, human geneticists, and natural scientists as well as representatives of the German patient support organization Selbsthilfe Ichthyose e. V.     

Receptor-Selective Retinoids for Psoriasis

Topical and oral retinoids have been successfully used in antipsoriatic therapy over the last 50 years. Development of more selective agents has led to an improved efficacy and safety profile. The first topical receptor-selective retinoid to be approved for the treatment of plaque psoriasis is tazarotene. Topical tazarotene displays an onset of action and efficacy similar to those of other established antipsoriatic agents. Common adverse events of this agent such as pruritus, burning, local skin irritation, and erythema are limited to the skin and generally mild or moderate in severity. Although effective as monotherapy, evidence is accumulating that combining topical tazarotene with other established antipsoriatic therapies results in enhanced efficacy and reduced adverse events. In particular, concomitant use of topical tazarotene with a mid-potency or high-potency corticosteroid in the treatment of psoriatic plaques enhances efficacy and reduces the risk of corticosteroid-induced skin atrophy. Combination of phototherapy with tazarotene accelerates the clinical response and diminishes the cumulative UVB or psoralen plus UVA (PUVA) exposure load. Recently, an oral form of tazarotene has been developed. The results of completed phase III clinical trials of this agent indicate a beneficial effect in moderate to severe plaque psoriasis. Adverse events are generally of mild severity, and most of those observed, such as cheilitis and dry skin, are typical of hypervitaminosis A. Of note, oral tazarotene appears not to be associated with other adverse events that are typical of oral retinoids, including hypertriglyceridemia and hypercholesterolemia. However, since head-to-head trials with acitretin (the only retinoid currently approved for systemic therapy) have not been conducted, it is unclear whether tazarotene is any safer or more effective than acitretin. Moreover, the major drawback of oral tazarotene is teratogenicity, which may limit its use in female patients. Further studies evaluating long-term clinical outcomes with oral tazarotene and its use in combination therapies are awaited.     

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.     

Oral supplements in atopic dermatitis

Atopic dermatitis (AD) is the most common chronic inflammatory skin disorder. The disease is typified by chronic pruritus, a series of signs and symptoms associated with immune dysfunction (eg, increased immunoglobulin E mediated allergies), and abnormal skin barrier dysfunction (eg, increased response to irritants). Due to the chronic itch and reactivity, patients and parents of affected children will seek therapy. Therapies range from emollients to topical medicaments, including topical corticosteroids, and immunosuppressive agents. Due to concerns about the side effects of the available agents, patients and their loved ones will often seek “natural” agents as therapy. Oral agents that have been tried in (AD) include probiotics, vitamins, oils, and such traditional therapeutics as Chinese herbals and Ayurvedic agents. At this time probiotics may be promising, but there are inadequate data to determine their efficacy. In addition, there are significant concerns for the risks associated with Chinese herbals, which may be associated with liver failure and death, and Ayurvedic agents, which may be tainted with heavy metals. The safest and most effective natural agents are topically applied emollients.     

Widespread use of toxic skin lightening compounds: medical and psychosocial aspects

Hyperpigmentation disorders and skin lightening treatments have a significant impact on the dermatologic, physiologic, psychologic, economic, social, and cultural aspects of life. Skin lightening compounds, such as hydroquinone and topical corticosteroids, are often used to treat hyperpigmentation disorders, such as melasma, or lighten skin for cosmetic purposes. Despite their established effectiveness, a multitude of dermatologic and systemic complications have been associated with these agents. Regulatory agencies have also recognized the adverse effects of skin lighteners and many countries around the world now forbid the production and sale of these compounds, although this prohibition has not significantly curtailed distribution. Dermatologists and users of cosmetic products should be aware of the various components in bleaching compounds, their potential adverse effects, and alternative options for skin lightening.