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Acquired ichthyosis (AI) is a relatively rare cutaneous entity characterized by transient, generalized scaling and pruritus in the absence of family history of ichthyosis or atopic disease. The hyperkeratosis in AI can range from the mild, white-to-brown scaling resembling that in ichthyosis vulgaris (IV) to the more prominent dark brown scaling phenotype, similar to that found in lamellar ichthyosis. The disease can wax and wane in relation to endogenous and/or exogenous factors. Histopathology of AI is similar to that found in IV. AI is usually of cosmetic concern to patients but can, in some cases, reflect the presence of more serious conditions, including malignancies, autoimmune diseases or metabolic disorders. In some cases, AI can be an adverse effect of a medication or the cutaneous symptom of a toxic exposure. Other conditions, such as severe xerosis or eczema, can present with clinical findings similar to AI, making diagnosis a challenge. Furthermore, cases of AI are sporadic throughout the literature and have been documented across a wide variety of medical settings distinct from dermatology, which often contribute to misdiagnosis of this disease. Definitive management requires prompt identification and treatment of the inciting factors combined with conservative therapies, which can include topical emollients, keratolytics, retinoids or corticosteroids, and in rare cases, oral retinoids., (© 2022 European Academy of Dermatology and Venereology.)

Data on clinical use of ponatinib are limited. This prospective registry aimed to evaluate outcomes of ponatinib treatment in routine practice over 3 years (2016-2019) in Belgium (NCT03678454). Patients with chronic myeloid leukemia (CML) or Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) were treated with ponatinib per current label. Fifty patients (33 CML and 17 Ph+ ALL) were enrolled. Fifty-five percent of CML and 29% of Ph+ ALL patients had received ≥3 prior tyrosine kinase inhibitors (TKIs). Reasons for starting ponatinib were intolerance (40%), relapse or refractoriness (28%) to previous TKIs, progression (16%), or T315I mutation (16%). Median follow-up was 15 months for CML and 4.5 months for Ph+ ALL patients. Best response was a major molecular response in 58% of CML and 41% of Ph+ ALL patients. Of 20 patients who started ponatinib due to intolerance to previous TKIs, 9 (64%) CML and 4 (67%) Ph+ ALL achieved a major molecular response. Three-year estimates of overall survival were 85.3% and 85.6%, respectively, in CML and Ph+ ALL patients; estimated progression-free survival was 81.6% and 48.9%. Adverse reactions were reported in 34 patients (68%); rash (26%) and dry skin (10%) were most common. Reported cardiovascular adverse reactions included vascular stenosis (3), arterial hypertension (2), chest pain (1), palpitations (1), and vascular occlusion (1). This Belgian registry confirms results from the PACE clinical trial and supports routine ponatinib use in CML and Ph+ ALL patients who are resistant or intolerant to previous TKIs or with the T315I mutation.

Introduction: Transient acantholytic dermatosis has been frequently reported in patients with malignancies. While paraneoplastic cases have rarely been reported, most eruptions occur in the setting of chemotherapeutic agents. Management is based on limited data and primarily with topical steroids and topical emollients. A subset of patients exhibits recalcitrant disease and require alternate therapeutic approachesMethods: This systematic review consisted of identifying records in PubMed using the medical subject headings (MeSH) terms “chemotherapy” AND “Grover”, “chemotherapy” AND “Grover’s”, “cancer” AND “Grover”, “cancer” AND “Grover’s”, “malignancy” AND “Grover”, “malignancy” AND “Grover’s”, as well as a free text search for “Grover” OR “Grover’s” OR “Grover disease” OR “Grovers disease” OR “Grover’s disease” OR “transient acantholytic dermatosis” OR “transient acantholytic” to identify case reports, case series, systematic reviews, review articles, meta-analyses, clinical trials, brief commentaries, and original articles. The titles and abstracts of all results were reviewed. Full texts of relevant results were then read in their entirety and applicability was determined., Results: Overall, Grover disease has rarely been reported in the setting of malignancy. When it occurs, it is generally in the setting of chemotherapy use. Chemotherapy-associated Grover disease is reported most frequently in association with cytotoxic chemotherapies, followed by small molecule inhibitors. The first line treatment for this complication is the use of topical agents. When these provide inadequate relief, alternate therapies have been rarely reported, with novel treatments proposed based on the type of chemotherapy agent and its mechanism of action., Conclusions: Chemotherapy-associated Grover disease is an uncommon complication of cancer treatment. While most cases of chemotherapy-associated Grover disease can be treated with topical steroids and topical emollients, certain cases require a more specialized approach. This could include adjuvant adjuvant therapies, or novel treatments that are directly related to the mechanism of action of the chemotherapy involved. J Drugs Dermatol. 2020;19(11):1056-1064. doi:10.36849/JDD.2020.5648.

Grover disease (GD) is an acquired, nonfamilial, nonimmune mediated, transient or persistent acantholytic dermatosis. Herein, we present a 72-year-old man who had clinical and histopathologic findings of GD following two weeks of treatment with vemurafenib without MEK inhibitor. The patient was successfully treated with topical emollients and a high-potency corticosteroid. Meanwhile, vemurafenib was temporarily discontinued. Drug-induced GD has increasingly been reported in patients on BRAF inhibitor monotherapy as an immune-related adverse event. The cutaneous side effects seem to arise secondary to a paradoxical activation of the mitogen-activated protein kinase signaling of BRAF inhibitor treatment, leading to keratinocyte proliferation. Although the pathogenesis of GD has not been delineated, there is suggestion of activation of T lymphocytes, particularly helper cells under the action of pro-inflammatory cytokines, resulting in proliferation of keratinocytes. Combination therapy with a MEK inhibitor appears to prevent BRAF-induced GD. Given that there is a higher prevalence of GD in patients with hematologic malignancy, a direct causal relationship between the initiation of vemurafenib therapy and development of GD in this case may be difficult to establish.

A 79-year-old man with a recent diagnosis of acute myeloblastic leukemia received induction chemotherapy with daunorubicin and cytarabine, plus moxifloxacin and fluconazole prophylaxis. Approximately 2 weeks later, an asymptomatic eruption appeared on his trunk. He then developed a neutropenic fever and was started on aztreonam, vancomycin, voriconazole, and amikacin and was transferred to our facility from an outside hospital. Micafungin was subsequently added, and the patient defervesced within a few days.

Cutaneous adverse events are commonly experienced with use of tyrosine kinase inhibitors in the treatment of leukemia and typically include nonspecific cutaneous eruptions and xerosis. We report the case of a man who experienced an ichthyosiform drug eruption while taking ponatinib, a third-generation tyrosine kinase inhibitor. Disruption of epidermal growth pathways through inhibition of various receptor tyrosine kinases by ponatinib may offer insights into the pathophysiologic mechanisms behind acquired ichthyosis.

Background: Acantholytic dyskeratosis under BRAF inhibitors are dermatological diseases rarely reported to date., Patients and Methods: We report 2 cases of acantholytic dyskeratosis, reaching the trunk and the seborrheic zones, not itchy, appeared one month after the introduction of vemurafenib. The histological analysis was typical of a "Grover-like rash" for the 2 patients., Discussion: The appearance of acantholytic dyskeratosis under vemurafenib, a BRAF inhibitor, seems related with a paradoxical activation of the MAP-kinases pathway and with a growth acceleration of lesions in which RAS mutations of keratinocytes. Theses dermatoses seem also to occur with dabrafenib., Conclusion: The patients treated by BRAF inhibitors (vemurafenib and dabrafenib) can present acantholytic dyskeratosis. The arisen of this mild dermatosis does not question, of course, the continuation of the treatment. These cutaneous manifestations can be managed with emollients., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Skin toxicities are the most common side effects associated with the epidermal growth factor receptor inhibitor erlotinib, occurring in most patients receiving the drug. Clinical trials evaluating erlotinib for the treatment of non-small cell lung cancer have reported a range of skin disorders, the most common being acneiform rash, xeroderma (dry skin), pruritus, and paronychia. Although in the majority of cases these effects are mild and transient, they can have a considerable impact on a patient's quality of life and, if particularly severe and persistent, may necessitate treatment interruption or cessation and compromise treatment outcome. This coupled with recent evidence to suggest a positive correlation between the incidence and severity of rash and clinical outcome among erlotinib-treated patients with advanced or metastatic non-small cell lung cancer highlights the importance of adequately managing epidermal growth factor receptor inhibitor--related skin disorders. Clear treatment strategies are therefore necessary to ensure the prevention and optimal management of erlotinib-related skin toxicities thereby enabling patients to continue erlotinib treatment. In this review we present a practical approach for the treatment of erlotinib-related cutaneous side effects in Japanese patients with advanced non-small cell lung cancer providing details of specific treatment interventions, according to symptom severity, for each of the common skin disorders. In addition, the importance of preventive skin care measures--namely maintaining cleanliness, moisturization, and protection from external stimuli--in preventing the development of serious skin disorders is discussed and guidelines for the practice of proper skin care are presented., (Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Background: Mammalian target of rapamycine (mTOR) inhibitors are being increasingly prescribed as antitumoural drugs, and associated adverse cutaneous effects are frequent but poorly described. The aim of this study was to describe such adverse effects and to assess the quality of life of patients experiencing them., Patients and Methods: Over a period of 18 months, 18 patients treated with mTOR inhibitors for renal carcinoma were included and 77 dermatological examinations performed. Wherever a cutaneous adverse event was present, quality of life was evaluated using the Skindex 30 questionnaire., Results: Fifteen of the 18 patients included presented adverse cutaneous events, consisting of buccal ulcers (61.1%), xerosis (55.5%), distal onycholysis (50%), acneiform eruption (38.8%), paronychia (22.2%) and pruritus (22.2%). Buccal ulcerations and perionyxis had an especially marked impact on quality of life, which was greatest in terms of physical score (19%), followed by emotional (9%) and functional (6%) scores., Conclusion: Cutaneous adverse effects of mTOR inhibitors are frequent and have a considerable impact on quality of life, particularly as regards physical scores. Dermatological examination appears useful to allow early management of cutaneous adverse effects and improve the quality of life of these patients., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

The RAF inhibitors vemurafenib and dabrafenib are emerging as the standard of care for Val600 BRAF-mutant metastatic melanoma. These drugs have shown clinical benefit over the standard care (dacarbazine); however, they are associated with frequent cutaneous adverse events, which can be concerning to the patient and their physician. Herein, we review the range of cutaneous disorders that seem to be induced by RAF inhibitors, including cutaneous squamous-cell carcinoma, hyperkeratotic lesions, Grover's disease, keratosis pilaris-like reactions, and photosensitivity. These disorders often affect patients' quality of life; therefore, dermatological assessment and timely management is essential to ensure that patients continue to use RAF inhibitors., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Vitamin A is required for the proper functioning of many important metabolic and physiologic activities, including vision, gene transcription, the immune system and skin cell differentiation. Both excessive and deficient levels of vitamin A lead to poor functioning of many human systems. The biologically active form, retinoic acid, binds to nuclear receptors that facilitate transcription that ultimately leads to it's physiological effects. Retinoids are derivatives of vitamin A that are medications used to treat acne vulgaris, psoriasis, ichthyosis (and other disorders of keratinization), skin cancer prevention as well as several bone marrow derived neoplasias. Systemic retinoids are teratogenic and have to be prescribed with caution and close oversight. Other potential adverse events are controversial. These include the relationship of retinoid derivatives in sunscreens, their effects on bone mineral density, depression and suicidal ideation and inflammatory bowel disease. These controversies will be discussed in detail., (Copyright © 2012. Published by Elsevier Inc.)

We present the case of a 79-year-old woman with a history of breast cancer who developed Grover disease (transient acantholytic dermatosis) following initiation of an aromatase inhibitor, anastrozole, as adjunctive treatment of her breast cancer. A number of drugs have been associated with this condition; however, to our knowledge, this case is the first report of anastrozole-induced Grover disease.

Introduction: Recently, there have been new antiseptics for surgical scrub that do not require brushing. One of them contains 1% chlorhexidine gluconate and 61% ethyl alcohol; within its benefits, it may offer a low potential for skin sensitization, as well as cost savings and less use of water., Objectives: To evaluate satisfaction levels, washing time, safety, cost and amount of water between the traditional surgical scrub technique (group A) and brush-free surgical scrub procedure (group B)., Material and Methods: One hundred clean and clean-contaminated surgeries with four hundred members of surgical teams were included. Satisfaction levels, hand-washing time, skin disorders and problems associated with placement of gloves were evaluated. Hands cultures were taken in 20% of the population and the amount of water used by patients in group A was measured. Total costs and wound infections were analyzed., Results: Satisfaction scale in group A was 9.1 +/- 1.39 and 9.5 +/- 1.54 in group B (p = 0.004). The mean hand-washing time was 3.9 +/- 1.07 min in group A and 2.0 +/- 0.47 min in group B (p = 0.00001). Thirteen patients had dry skin in group A and four in group B (6.5% vs. 2%; p = 0.02). There were ten positives cultures in group A and five in group B (25% vs. 12.5%, p = 0.152). Wound infection rate was 3%. On average, five-hundred eighty liters of water were used by the former group, and the estimated hand-washing cost was lower in the second group., Conclusions: The handwashing technique with CGEA is as effective as traditional surgical scrub technique, and it is associated with less washing time, dry skin, cost and use of water.

Background: Sulfur mustard (SM) - a chemical agent - has both acute and chronic effects on skin. Xerosis, which is deemed to be due to the damage of hydrolipidic barrier of the skin, is the most common complaint of veterans exposed to the chemical. This study was designed to evaluate skin sebum and elasticity in veterans with a history of SM contact., Methods: Three hundred and ten subjects were enrolled in this study and were divided into four groups: SM-exposed patients with current skin lesions (n=87); SM-exposed patients without skin lesions (n=71); patients with dermatitis (n=78); and normal controls (n=74). The skin sebum and elasticity were measured in four areas (forehead, suprasternal, palm and back of the hands) using a Sebumeter and a Reviscometer., Results: Skin sebum was higher in participants who presented with dermatitis and had history of contact with SM than others; the difference was only statistically significant on the forehead. There was no significant difference in the skin elasticity between the four groups., Conclusion: While SM may increase skin sebum in long term, there is no evidence that it has a substantial effect on skin elasticity.

Epidermal growth factor receptor (EGFR) inhibitors such as cetuximab, erlotinib, panitumumab und gefitinib, are increasingly used for the treatment of advanced, metastatic, or recurrent tumours like colorectal carcinoma, non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN) and pancreatic cancer. For this reason the treatment of common cutaneous side effects of EGFR inhibitors has become important: they stigmatize the patient in daily life and may lead to efficacious therapie being discontinued. Depending on the particular EGFR inhibitor, an acneiform rash occurs in 30 to 90 % of patients. Severity, site, stage of eruptions and individual response influence the decision of treatment in the given case. It follows the forms of treatment for acne and rosacea, including topical and systemic antibiotics for their antimicrobial effect and anti-inflammatory effect, sometimes in combination with topical steroids. After several weeks additional sebostatic skin reactions, paronychia and changes in the hair structure may occur, calling for individualized treatment. Only multidisciplinary collaboration between oncologists, radiotherapist and dermatologists may provide an optimal patient care. This article gives an overview of the occurrence and latest treatment options of the cutaneous side effects caused by treatment with EGFR inhibitors., (Georg Thieme Verlag KG Stuttgart.New York.)

There are many anatomical and functional differences between the skin of young children and adult skin. As a consequence, the skin is more easily irritated by topical agents. There is also increased transcutaneous absorption; the latter effect is amplified by underlying conditions such as ichthyoses and atopic dermatitis with defects of the epidermal barrier. Common topical agents such as salicylic acid and lactic acid can cause life-threatening intoxications. The relevance of transcutaneous absorption of "hidden" ingredients such as polyethylene glycol and preservatives is unknown at present. By emulsifying endogenous barrier lipids, emulsifiers can promote skin dryness. We review the effects of common emollients and their suitability for skin care in children, particularly with the aim to reduce exposure to potential contact allergens and inadvertent emollient activity.

Objectives: We evaluated patient and medication treatment factors associated with self-reported oral health status in patients diagnosed with serious mental illness (SMI) in a large, national sample of patients in the Veterans Affairs (VA) health system., Methods: 4,769 patients (mean age = 55, 7.8 percent women) were included from the VA's 1999 National Psychosis Registry (NPR) for whom the oral health information gathered by the VA's Large Health Survey of Veterans was available. Current (1999) psychotropic medication data were ascertained from the NPR. Multivariable logistic regression analyses were used to determine the patient factors (e.g., sociodemographic, enabling, and treatment factors) associated with poor or fair overall dental health, and with having tooth or mouth problems that made it difficult to eat., Results: While 61.0 percent of persons with SMI self-reported fair to poor dental health, 34.1 percent reported that oral health problems made it difficult for them to eat. Patients who were not employed, experiencing financial strain, who smoked, who were prescribed tricyclic antidepressants, or prescribed selective serotonin reuptake inhibitors were more likely to report poor or fair dental health. These variables were also associated with having tooth or mouth problems., Conclusions: Suboptimal oral health was self-reported with substantial prevalence among patients with SMI, a problematic finding given its consequences for general health, social functioning, and quality of life. Greater efforts are needed to improve oral health outcomes among patients with SMI by facilitating access to dental care and addressing mutable factors such as smoking and medication side effects.

Lamivudine is widely used for the treatment of chronic hepatitis B infection because of it's remarkable antiviral efficacy and safety. We report a case of severe skin eruption caused by lamivudine. A 47-year-old female was admitted because of jaundice and itching sensation. She was diagnosed as chronic hepatitis B infection a few years ago but did not receive any specific treatment. Laboratory data showed acute deterioration of chronic hepatitis B infection. We prescribed lamivudine as a rescue therapy. Her general condition improved and lab data showed improvement in liver function test thereafter. However, she complained of severe skin eruption and itching sensation a few days after the discharge. We stopped lamivudine because the symptoms did not improve despite the use of anti-histamine. Skin biopsy showed interface dermatitis. After stopping lamivudine, her symptoms improved. However, the skin eruption developed again after lamivudine was restarted. Adefovir was used instead, and the patient did not experience any further skin problems since then.

Objectives: To discuss the mechanism by which epidermal growth factor receptor (EGFR)-targeted agents work, the resulting cutaneous toxicities, the pathophysiology of the unique rash associated with these agents, and the management of these skin problems., Data Sources: Published scientific papers, review articles, book chapters, and clinical experiences., Conclusion: These new targeted agents result in unique cutaneous toxicities. Researchers and clinicians have made numerous suggestions for managing the various side effects, although there is currently no research to guide evidence-based practice., Implications for Nursing Practice: With any new treatment option, it is imperative that nurses understand how agents work to enrich their own knowledge base, as well as have a strong foundation for patient education. It is important that nurses understand potential side effects of these agents, know of possible interventions, and participate in research to identify effective interventions.

Epidermal barrier function to water loss is maintained by lipid membrane domains located in the interstices of the stratum corneum. Exposure of the epidermis to a dry environment or UV irradiation stimulates barrier lipid synthesis and accumulation of the organic osmolyte taurine in the outermost granular keratinocyte layer. In this work we studied a possible relationship between these two different epidermal responses to environmental challenges. As a model system we selected anionic surfactant-induced barrier perturbation. Incubation of reconstructed epidermis with taurine inhibited cytotoxic and proinflammatory effects induced by sodium dodecyl sulfate including (i) a decrease in interleukin-1 alpha and prostaglandin E2 release, (ii) stabilization of keratinocyte membrane integrity, and (iii) improvement of keratinocyte viability. Repeated exposure of human skin to sodium dodecyl sulfate induced an increase in transepidermal water loss, inflammation, and hyperplasia. Topical application of taurine significantly decreased transepidermal water loss after repeated exposure to sodium dodecyl sulfate. Moreover, taurine significantly stimulated the synthesis of all three classes of barrier lipids (ceramides, cholesterol, and fatty acids) in reconstructed epidermis. In conclusion, our data suggest a role for taurine in preventing surfactant-induced dry and scaly skin by modulating the proinflammatory response and stimulating epidermal lipid synthesis.

The side-effects of antiretroviral agents have been widely reported in the literature. Lamivudine is an antiretroviral agent, and skin eruption because of this agent has been rarely reported. Previous reports regarding these few side-effects of lamivudine include angioedema, urticaria, anaflactoid reactions, allergic contact dermatitis and alopecia. There is no report of an ichthyosiform eruption associated with lamivudine. The authors present a case of 43-year-old female patient presenting with an ichthyosiform eruption during lamivudine therapy for chronic hepatitis-B for the first time.

Hydroxyurea is an anti-tumour agent most commonly used to treat chronic myeloproliferative disorders in doses up to 4 g per day. Dermatological adverse effects reported so far have been observed predominantly in these patients. As we are treating selected psoriasis patients with low dose hydroxyurea we attempted to define the spectrum and chronology of dermatological adverse effects in this group of patients prospectively. Of the 29 evaluable patients, 19 (65.5%) developed a mucocutaneous adverse reaction after a mean duration of 6.4 weeks of treatment. Pigmentation of nails, skin or mucosa was the most common observation and was seen in 17 (58.6%) patients. Other less common findings were xerosis, diffuse alopecia, oedema of the legs, oral ulcers and actinic psoriasis. Adverse effects subsided in 11 (57.9%) patients during a mean follow up of 18 weeks. Three hitherto unreported side-effects - scleral pigmentation, acquired ichthyosis and pigmentation of lunula of the nails - were noted. This first study of dermatological adverse effects of hydroxyurea therapy on Asian psoriatic patients reveals several new findings. Pigmentation of skin, nails and mucosa appears to be very common and occurs early. Serious dermatological side-effects probably do not occur with low dose (up to 1.5 g per day) hydroxyurea in patients with psoriasis.

Scleroderma (SSc) is a fibrosing connective tissue disease that is poorly responsive to any treatment, including immune suppression. SSc shares many characteristics with chronic graft-versus-host disease (GVHD). Because the immunomodulatory drug thalidomide has proven beneficial in chronic GVHD, we studied the immune response and clinical effects of thalidomide in SSc patients. We treated 11 SSc patients with thalidomide in an open label, dose escalating, 12 week study. Histologic comparison of skin biopsies showed changes in skin fibrosis and an increase in epidermal and dermal infiltrating CD8(+) T cells with thalidomide treatment. In thalidomide-treated SSc patients, plasma levels of IL-12 and TNF-alpha increased, while plasma IL-5 and IL-10 levels remained unchanged. These changes were associated with clinical effects, including dry skin, dermal edema, transient rashes, decreased gastroesophageal reflux symptoms, and healing of digital ulcers. When SSc PBMCs activated by anti-CD3 mAb were exposed to thalidomide, increases in both production of IL-2, IL-3, GM-CSF, and IFN-gamma and T cell expression of CD40L were observed. Thalidomide therefore appears to induce immune stimulation in SSc patients in association with clinical changes. However, it remains to be shown whether long-term enhancement of immune responses in SSc patients is clinically beneficial., (Copyright 2000 Academic Press.)

The purpose of this article is to discuss treatment of side effects that can occur during lithium therapy. Side effects from lithium are common but generally benign. For this article, I have divided the side effects into those that occur early, those that are late appearing, side effects related to drug interactions, and lithium toxicity. Side effects can decrease compliance. Lithium is a very effective drug for the stabilization of mood disorder in bipolar patients. Since side effects can affect compliance, recognition and treatment of early and late-appearing side effects are important aspects of lithium pharmacotherapy.

We have previously reported 18 cases of an ichthyosiform contact dermatitis caused by antiseptic solutions containing 3% cetrimide and 0.3% chlorhexidine. The reaction was traced to cetrimide, a mixture of quaternary ammonium compounds that are widely used as disinfectants and detergents. Quaternary ammonium compounds are known irritants. To elucidate the pathogenesis of the abnormal keratinization caused by cetrimide, electron microscopy was performed on biopsied lesions from five patients and on specimens from rabbits in which a mild reaction had been induced by closed patch with Savlon, cetrimide, and chlorhexidine. The patients' samples revealed hyperkeratosis with striking vesiculation of lamellar bodies in the granular cells and upper spinous cells, premature secretion of lamellar bodies, and abundant remnants of lamellar bodies and retention of desmosomes between the corneocytes. Similar lamellar bodies changes were induced in rabbit skin after 48 hours of closed patch with Savlon 1:30 and cetrimide 0.1%, but not with chlorhexidine 3%-further indication that cetrimide was the cause of the dermatitis. We conclude that the abnormal keratinization can be attributed, at least in part, to dysfunction of lamellar bodies resulting from the direct effects of cetrimide on the lipids and enzymes of lamellar bodies. Vesiculation with dysfunction of lamellar bodies may be an important pathogenetic mechanism in irritant dermatitis caused by quaternary ammonium compounds.

We assessed possible long-term side-effects of isotretinoin therapy in 720 patients who had received one or more courses of treatment, and had a mean follow-up period of 4.9 years (range 2-12 years). Most patients (442) had received a total cumulative dose of 120-200 mg/kg body weight. One hundred and sixty-two patients received a cumulative dose of < 120 mg/kg body weight, and 116 received a cumulative dose > 200 mg/kg. Fifty-two patients (7.2%) reported persistent symptoms during the follow-up period. No correlation was found between age, sex, cumulative dose, or number of courses of isotretinoin and occurrence of reported possible side-effects. The reported symptoms were predominantly musculoskeletal (2%) or mucocutaneous (4.8%), and were mild in all cases. Xeroderma, dry eye syndrome, arthralgia, and possible exacerbation of eczema, were considered to be infrequent but probable long-term side-effects. The findings of this study indicate that isotretinoin in the treatment of acne is a safe drug, with no serious long-term side-effects.

Many of the ichthyotic disorders have characteristic ocular findings. These disorders include X-linked ichthyosis, lamellar ichthyosis, Sjögren-Larsson syndrome, KID syndrome, Refsum's disease, neutral lipid storage disease, chondrodysplasia punctata, and Richner-Hanhart syndrome. A knowledge of the ocular manifestations may provide a valuable aid to diagnosis in difficult cases. In some cases, knowledge of the ocular complications results in early referral for optimal ophthalmologic care.

A 37-year-old woman developed ichthyosiform desquamation of the skin and a severe diffuse alopoecia 3 weeks after taking the antidepressant maprotilin. No signs of inflammation were present. Histology revealed acanthosis with preserved stratum granulosum, follicular hyperkeratosis and dystrophic changes of the hair follicle. Electron microscopy revealed rarefication of tonofilaments and necrobiotic changes of epidermal keratinocytes with vacuolar degeneration of the cytoplasm and disorganization of the organelles. Pathogenetically this disease represents a drug-induced transitory disorder to keratinization, which had resulted in desquamation of the stratum corneum and alopecia. The authors propose the designation corneolysis for this pathogenetic principle.

Heavy chronic consumption of kava (Piper methysticum) is associated with a pellagroid dermopathy that has been attributed to niacin deficiency. Over 200 male kava drinkers in the Tonga Islands were interviewed and examined regarding the characteristic skin changes. A scaly rash suggestive of ichthyosis and eye irritation were present in some heavy kava drinkers. 29 kava drinkers with prominent skin changes were randomised to receive either 100 mg oral nicotinamide or placebo daily for three weeks. Skin examinations and photographs showed clinical improvement in 5/15 of the nicotinamide group and 5/14 of the placebo group. These data, along with history and physical examination findings, suggest that niacin deficiency is not responsible for the rash, which is more characteristic of an acquired ichthyosis.

A phase I study of 13-cis-retinoic acid was done in 16 patients with head and neck malignancies using a modified Fibonacci search scheme, with individual doses ranging from 20 to 120 mg/m2. Drug doses greater than 60 mg/m2 induced intense headaches, urethritis, desquamative dermatitis, vertigo, and ataxia. The severity of these side effects precludes the use of 13-cis-retinoic acid as a potential chemopreventive agent at doses greater than 60 mg/m2.