Epidermal growth factor (EGFR)-inhibitors have emerged as the primary therapy in advanced solid tumor malignancies because of improvement in survival with overall favorable side effect profile. However, 50–90% of patients treated with EGFR-inhibitors develop a follicular or acneiform rash, which can be symptomatic and source of psychosocial distress, negatively impacting quality of life. As this acneiform rash is a well-recognized cutaneous toxicity of EGFR-inhibitors, a treatment algorithm has been proposed for management based on severity. However, treatment options for EGFR-inhibitor induced rash may not be generalizable to African Americans whose differences in skin biology and sensitivity present pathophysiologic challenges. Herein, we present a case of an African American patient who developed this acneiform rash while on cetuximab. We also review the few cases that have been reported in the literature of EGFR-inhibitor rash in African Americans, highlighting important management considerations in this patient population. J Drugs Dermatol. 2020;19(9):894-896. doi:10.36849/JDD.2020.5275.

The vast majority of atopic dermatitis follows a mild, chronic relapsing course. In this article, we highlight the art and practice of treating atopic dermatitis based upon a foundation of maintenance care and a ladder of therapy that can teach patients and their families how to best tailor their pharmaceutical options to optimize the management of their disease.

CME EDUCATIONAL OBJECTIVES: 1.Identify the clinical presentation of granuloma annulare.2.Describe the differential diagnosis for granuloma annulare.3.Discuss the appropriate management for granuloma annulare. A 12-year-old healthy male presented to the dermatology clinic for evaluation of lesions on his feet. The lesions were bilateral and had been present for at least 6 months. Multiple topical treatments had been prescribed in the past, including miconazole nitrate 2% cream, oxiconazole 1% cream and alclometasone dipropionate 0.05% ointment. Each had been used for several weeks without improvement. Because of this, the referring doctor prescribed griseofulvin microsize 250 mg twice daily for 4 weeks and referred the patient to dermatology. The patient denied pruritus or pain. Review of systems, medical history, and family history were unremarkable.

We recently used micro attenuated total reflection infrared (ATR-IR) spectroscopy to conduct imaging analysis of ointments and evaluate the distributions of the active pharmaceutical ingredient (API) and excipients. An alclometasone dipropionate (ALC) ointment was used as a model product. Almeta, a brand-name product, had a domain with absorbance at 1656 cm(-1) attributable to the carbonyl group of ALC, the API. Absorbances at 1040 and 3300 cm(-1) were also noted in this domain, indicating the presence of the solubilizer, propylene glycol. Data also suggested the presence of benzyl alcohol in this domain. More detailed analysis showed the distribution of surfactants and other excipients in the base. Similar results were obtained for Vitra, a generic version of Almeta. Imaging analysis with micro ATR-IR confirmed that both ointments are liquid droplet dispersions with ALC dissolved in propylene glycol and dispersed in a base. However, minor differences in the ingredient distributions of the two ointments were detected and reflect differences in excipient concentrations and type, or manufacturing differences. In summary, we used micro ATR-IR for imaging analysis of an original ointment, Almeta, and its generic form Vitra, and established a method for visually evaluating the distributions of the API and excipients in these ointments.

Tacrolimus (FK506) ointment is widely used in the treatment of patients with atopic dermatitis. The drug exerts its action by down-regulating antigen-specific T-cell activities and associated proinflammatory cytokine production. A number of clinical studies have evaluated the efficacy and safety of 0.1% tacrolimus ointment compared with vehicle or topical corticosteroids in adult patients with atopic dermatitis. These studies have suggested that topical tacrolimus has a rapid onset of action and exerts sustained therapeutic effects, with an efficacy similar to that of moderate to potent topical corticosteroids, but without causing skin atrophy. Two phase III randomised, controlled clinical trials have been conducted in Japanese adult patients with atopic dermatitis to compare the efficacy and safety of topical 0.1% tacrolimus with topical corticosteroid ointments. In the first study, patients with moderate or severe atopic dermatitis on the trunk and extremities were randomised to 3 weeks of treatment with topical 0.1% tacrolimus or the mid-potency topical corticosteroid 0.12% betamethasone valerate. Over 90% of the patients in each study group experienced at least a moderate improvement at the end of the study. In the second study, patients with moderate or severe atopic dermatitis on the head or neck were randomised to 1 week of treatment with 0.1% tacrolimus or the mild-potency corticosteroid 0.1% alclometasone dipropionate. Significantly greater improvements in individual symptom scores were observed with topical tacrolimus compared with alclometasone dipropionate, with overall global improvement at 1 week being statistically superior with tacrolimus. Furthermore, in a long-term open-label study involving 568 patients, at least a moderate global improvement in symptoms was observed in 85% of patients at 6 weeks, increasing to 91% at both 26 weeks and 52 weeks; this rate was maintained throughout the 2-year duration of the study. 0.1% tacrolimus ointment was considered to be safe in the majority of patients. The most prevalent adverse reactions were local application site irritations, which generally resolved with continued therapy. In summary, these findings suggest that 0.1% tacrolimus ointment is an effective and safe nonsteroidal alternative therapy for adult patients with atopic dermatitis.

Isolated, hyperpigmented lesions arising on the skin of the head and neck in the elderly rarely prompt consideration of connective tissue diseases. Histologic evaluation, however, may reveal changes compatible with chronic cutaneous lupus erythematosus (CCLE). A retrospective review of cutaneous biopsies compatible with CCLE evaluated by the Vanderbilt University Division of Dermatopathology over a five-year period (1998-2002) was undertaken. Cases with isolated lesions arising on the head and neck in patients 40 years or older were selected and the histopathology was confirmed. Patients were interviewed by phone and their charts were reviewed. A total of 11 cases were found, including nine women and two men. These patients averaged 68 years of age and presented with single, hyperpigmented macular lesions. Photosensitivity was rare and no associated stigmata of lupus erythematosus were noted. Response to topical application of corticosteroid preparations was excellent.

Currently, topical glucocorticosteroids are the most frequently used drugs in dermatologic practice. Over the years, research has focused on strategies to optimize potency and, in particular, the anti-inflammatory and immunosuppressive capacity of these drugs, while minimizing adverse effects. However, 'ideal' topical corticosteroids have not yet been synthesized. They should be able to permeate the stratum corneum and reach adequate concentrations in the skin without reaching high serum concentrations. Such characteristics can be obtained by increasing the natural lipophilicity of corticosteroids, e.g. by esterification. In the past, many structural modifications have been made to improve the efficacy of topical corticosteroids to produce drugs with greater potency, although this has often been associated with a higher likelihood of adverse effects. Betamethasone dipropionate and clobetasol propionate, known as fifth-generation corticosteroids, are a typical example of potent molecules that can control specific dermatoses very rapidly, but which are associated with a high risk of topical and systemic adverse effects. Recently, steroid components have been synthesized that aim to have adequate anti-inflammatory effects and minimal adverse effects. The newest topical corticosteroids used for the treatment of different dermatoses and allergic reactions of the respiratory tract (in particular asthma) are budesonide, mometasone furoate, prednicarbate, the di-esters 17,21-hydrocortisone aceponate and hydrocortisone-17-butyrate-21-propionate, methylprednisolone aceponate, alclometasone dipropionate, and carbothioates such as fluticasone propionate. These new topical corticosteroids are evaluated in the current review, which compares the risk/benefit ratio of each molecule with established agents. The new molecules, compared with the well known and established corticosteroids, generally have a higher anti-inflammatory effect, good compliance among patients (only a once-daily application is needed), rarely induce cross-sensitivity reactions and have weak atrophogenicity.

Tacrolimus (FK506) ointment showed remarkable efficacy against atopic dermatitis in animal models and clinical trials. The suppressive effect of tacrolimus on the production of the cytokines involved in atopic dermatitis (IL-2, IL-3, IL-4, IL-5, IFN-gamma and GM-CSF) from human peripheral blood mononuclear cells (PBMC) was investigated. We constructed a new cytokine production system in which T cells are activated by direct stimulation in vitro with anti-CD3/CD2 or anti-CD3/CD28 antibody combination. Tacrolimus inhibited the production of these cytokines by both stimulations. In a comparative study with steroids (alclometasone dipropionate and betamethason valerate) in anti-CD3/CD2 system, tacrolimus and both steroids inhibited Th1 cytokines (IL-2, IFN-gamma), Th2 cytokines (IL-4, IL-5) and IL-3, GM-CSF (produced by both Th1 and Th2). The suppressive effect of tacrolimus on cytokine production was stronger than that of alclometasone dipropionate and equal to or stronger than that of betamethason valerate. The effective dose of tacrolimus (IC50, 0.02-0.11 ng/ml) is almost the same as for Th1 and Th2 cytokines, and 1 ng/ml of tacrolimus suppressed all cytokines completely. These results suggest that tacrolimus suppresses the allergic cytokines from T cells, and that tacrolimus ointment is effective against atopic dermatitis through the inhibition of cytokine production.

The effects of FK506 (tacrolimus hydrate) ointment on cutaneous allergic reactions in mice and rats were investigated. FK506 ointment showed significant suppressive effects on delayed allergic reactions in both species, and especially in rats, its inhibitory action was much stronger than that of alclometasone dipropionate, a so-called medium class steroid ointment. On the other hand, FK506 ointment did not inhibit the immediate allergic reaction in rats. FK506 ointment suppressed the delayed allergic reactions in locally passively sensitized mice to the same degree as that in actively sensitized mice. Accordingly, it is speculated that FK506 ointment inhibits the activation of sensitized T lymphocytes (Th1 cells) already accumulated in the dermis.

The metabolic fate of alclometasone dipropionate (ADP or S-3460) has been studied in rats, rabbits, and mice, with consideration of their interspecies differences. Several reference compounds related to ADP were synthesized for the determination and identification of the metabolites. After sc administration of 14C-labeled ADP, the metabolites in plasma, bile, and urine were separated and analyzed using TLC-ARG (autoradiography) and HPLC in comparison with the reference compounds. The metabolites identified, fully or tentatively, by MS and 1H-NMR totaled 11. The metabolic transformations were: hydrolysis of the side chain esters, dehydrochlorination leading to the formation of delta 6-double bond, 6 beta-hydroxylation, 6 beta, 7 beta-epoxides from 6 beta-hydroxylated metabolites, side chain oxidation to 21-oic and 20-oic acids in the 6 beta-hydroxylated metabolites, and conjugation to glucuronides and sulfates. The metabolic pathway, postulated on the basis of the identified and quantitated metabolites, was a rapid hydrolysis of 21-ester of ADP to the corresponding alcohol, M-1, after systemic uptake. This M-1 was a main metabolite in plasma of animals studied, and due to its relatively longer life time in the media, it seemed to allow a variety of metabolism to occur, giving the oxidative and conjugative metabolites mentioned above.

This is a randomized single blind parallel comparison of alclometasone dipropionate cream 0.1% vs hydrocortisone butyrrate in 39 geriatric patients (greater than 60 years old) with steroid sensible skin diseases. The regimen consisted of dosing patients with two applications of the two drugs every day for 4 weeks. Follow-up evaluations have been done weekly, and subjective and objective clinical symptoms, adherence to the study protocol, evolution of the disease, onset of adverse reactions including atrophy have been recorded. Furthermore possible side-effects on hypophysis-adrenal axis have been monitored in baseline conditions, after 7 days and at the end of therapy. In most patients bioptic skin patterns for histomorphometric examination have been drawn before and after therapy to be evaluated by a blind examinator. Alclometasone has reduced initial skin lesions by 82.2%, the extent as hydrocortisone butyrrate. In five patients the complete clearance of the disease has been obtained. Study drugs have been tolerated well by all patients, nor clinical signs of atrophy have been observed. Fluctuations of blood cortisol levels ranged between the normal values. In patients treated with alclometasone histomorphometry revealed a better skin trophism than in patients treated with hydrocortisone butyrrate.

The effect of successive administration of the corticosteroid alclometasone dipropionate (ACM) on the hepatic drug-metabolizing system was examined using male and female rats. Although some pharmacological changes such as increases in plasma enzyme activity, lipid level and protein concentration appeared similarly in ACM-treated male and female rats, the activities of 7-alkoxycoumarin O-dealkylase, especially the O-depropylation activity, decreased dose-dependently by ACM administration only in male rats. ACM did not affect the hepatic drug-metabolizing activity in female rats and mice of both sexes. Also, ACM did not inhibit androgen-independent aniline hydroxylase activity even in male rats. The time course of changes of the drug-metabolizing system in male rats showed a rapid decrease in cytochrome P-450 content and O-depropylation activity following successive treatments with ACM, but there was a slow onset in the decreases of the O-demethylation and O-deethylation activities of 7-alkoxycoumarin. When ACM was withdrawn, the O-demethylation and O-deethylation activities rapidly returned to their control levels, while recovery of the O-depropylation activity was slow. These results suggested that ACM inhibits the hepatic drug-metabolizing enzyme activity associated with a specific form(s) of androgen-dependent cytochrome P-450 in male rats.

In this study, the antiproliferative activity of a 0.05% alclometasone ointment (Alc, Delonal) on the epidermis of the mouse tail was investigated. We have found that Alc thins the epidermis to approximately the same extent as hydrocortisone acetate (1%), but has an extremely slighter epidermal thinning effect than betamethasone (betametasone-17,21-dipropionate, 0.064%, Diprosis). The incorporation rate of 3H-thymidine triphosphate into the DNA was inhibited to almost the same extent. In conclusion the small antiproliferative effect of Alc shows no correlating effects compared with its high vasoconstrictory efficacy.