Retinoid therapy for aging skin and acne

Primary care physicians should be familiar with the effects and appropriate uses of retinoids. Topical tretinoin (Retin-A) can reverse photoaging of the skin, although some transient, undesirable side effects usually occur. In patients with acne vulgaris, topical tretinoin and systemic isotretinoin (Accutane) are the only agents that act upon the apparent underlying causes. Recurrence is unlikely after successful results are achieved. Chronic hypervitaminosis A presents insidiously, and physicians must maintain a high index of suspicion. Complete history taking should always include questions about the patient's use of vitamin supplements.     

An ultrastructural study of the retention hyperkeratosis of experimentally induced comedones in rabbits: the effects of three comedolytics

The precise pathologic processes of comedo formation in acne are not well understood. Retention hyperkeratosis may play an important role. To evaluate the effects of three topical comedolytics, 20% azelaic acid, 0.1% tretinoin and 5% benzoyl peroxide, on the retention hyperkeratosis of experimentally induced comedones (EIC), an ultrastructural study was done. After formation of EIC with 50% oleic acid in paraffin oil on the external ears of rabbits, each comedolytic was applied for 4 weeks. Biopsies were taken every week and, using a Hitachi H-600 transmission electron microscope, morphologic observations were done in the upper portion of the follicular epithelium. In EIC, after application of each comedolytic, the markedly thinned horny layer was loosely adhered by extremely few desmosomes and desmosomal bodies. The number and size of tonofilaments and keratohyaline granules decreased, but the number of variable sized Odland bodies increased in the upper epidermis. These findings appeared 1 week after application of either azelaic acid or benzoyl peroxide, and 3 weeks after application of tretinoin. For the first 2 weeks of tretinoin application, EIC showed rather compact hyperkeratosis with more desmosomes and desmosomal bodies than before. Azelaic acid tretinoin and benzoyl peroxide increased the number of Odland bodies, and the horny cells became less adhesive. This lysis of retention hyperkeratosis resulted in comedolysis. During 4 weeks of treatment with these three comedolytics, only tretinoin normalized the keratinization process.     

On choosing a detergent for solution NMR studies of membrane proteins

Acne is a common condition seen routinely by both primary care physicians and dermatologists. Most patients have no underlying pathology and respond to traditional treatment; others, however, require more individualized evaluation and aggressive therapy. New information regarding the pathogenesis and treatment of acne is now available. This update discusses the proper evaluation of early childhood acne, the emergence of Propionibacterium acnes resistance, and the rare but serious side effects occasionally seen with minocycline. Advances in the topical treatment of acne, the use of oral contraceptives in acne, and the use and efficacy of isotretinoin are also addressed.     

Current options for the topical treatment of acne vulgaris

The etiopathogenesis of acne vulgaris, a common disorder of youth and adolescence, includes four primary processes: hyperkeratinization (plugging) of the pilosebacous follicles, increased testosterone levels, bacterial colonization with Propionibacterium acnes, and inflammation. No single agent has yet been developed that addresses all of these factors. Combination regimens, therefore, which usually include an antibiotic and an agent to reduce follicular plugging, have become the mainstay of treatment. Despite a relative dearth of new treatments for almost a decade, recent research has produced a number of new significant oral and topical agents. Azelaic acid, a naturally occurring dicarboxylic acid analogue, has shown promise, and a group of retinoids that include adapalene, tazarotene, and reformulations of tretinoin represent new and forthcoming agents for topical treatment of acne vulgaris. Some studies indicate that several of these agents are associated with less skin irritation than previous formulations while they retain potent comedolytic activity. Adapalene also possesses significant anti-inflammatory activity.     

Okadaic acid enhances prostaglandin E1-induced alkaline phosphatase activity in osteoblast-like cells: regulation at a point downstream from protein kinase A

A variety of pharmacologic agents have been known to induce pustular psoriasis. We describe a patient with a positive personal and family history of psoriasis who developed an extensive annular pustular eruption 3 weeks after starting hydroxychloroquine (Plaquenil) for arthritis. The drug was discontinued, and she received 3 weeks of systemic and topical corticosteroids; in spite of the therapeutic intervention, showers of new lesions appeared daily, and progressed to involve 75% of the body. The development of new lesions stopped, and the older lesions began to clear after one dose of 7.5 mg of methotrexate. Subsequently, methotrexate therapy was stopped because of mild transaminase elevation; the pustular lesions then flared. New lesions stopped appearing after four doses of weekly methotrexate. The patient remains clear of lesions 6 months later.     

Treatment of acne with a combination clindamycin/benzoyl peroxide gel compared with clindamycin gel, benzoyl peroxide gel and vehicle gel: combined results of two double-blind investigations

BACKGROUND: It has previously been shown that a combination of erythromycin and benzoyl peroxide is superior to either ingredient when used alone in the treatment of acne. A clindamycin/benzoyl peroxide combination gel might have an advantage over erythromycin/benzoyl peroxide gel because the former does not require refrigeration after it is dispensed. OBJECTIVE: Our purpose was to determine the efficacy and safety of a combination clindamycin/benzoyl peroxide gel when compared with benzoyl peroxide, clindamycin, or vehicle gels. METHODS: In two double-blind, randomized, parallel, vehicle-controlled trials, patients were treated for 11 weeks with once-nightly application of one of the above preparations. Evaluations were performed at 2, 5, 8, and 11 weeks and included lesion counts and assessment of global responses and irritant effects. RESULTS: A total of 334 patients completed the study. All three active preparations were significantly superior to the vehicle in global improvement and in reducing inflammatory lesions and noninflammatory lesions. The combination gel was significantly superior to the two individual agents in global improvement and reduction of inflammatory lesions and also to the clindamycin gel in reducing noninflammatory lesions. There was no significant difference in tolerance to the active gels versus the vehicle gel. CONCLUSION: In the treatment of acne, topical clindamycin/benzoyl peroxide combination gel is well tolerated and superior to either individual ingredient.     

Isotretinoin for acne vulgaris--10 years later: a safe and successful treatment

The purpose of this study was to assess the long-term benefit of isotretinoin in otherwise therapy-resistant acne. We also assessed risk factors which might influence the long-term outcome. We studied 88 patients (mean age 20.8 years), most of whom had suffered from acne for many years (mean 7.4 years). They received isotretinoin in an initial dose of 0.5 or 1.0 mg/kg/day. The dose was subsequently adjusted according to response and side-effects. Most patients only required 4 months' therapy to produce at least 85% clinical improvement. The patients were seen up to 10 years post-therapy (mean 9 years). Sixty-one patients were still virtually clear of disease. Of the others, 16% required further treatment with conventional antibiotics and 23% required a second course of isotretinoin. Of those who relapsed, 96% did so within 3 years of stopping therapy. The patients' age, sex, and duration of acne did not influence outcome. However, in patients with predominantly truncal acne, especially when severe, there was an increased incidence of relapse. Sebum excretion is known to correlate with acne severity, but the long-term degree of sebum suppression was found not to be related to relapse. The dose schedule, in particular cumulative dose, was an important factor in determining relapse rate. Those patients who received 0.5 mg/kg daily, or a cumulative dose of < 120 mg/kg, had a significantly higher relapse rate than patients receiving a larger dose. We did not elicit any long-term systemic or biochemical side-effects. We conclude that isotretinoin is a safe and effective therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficacy and safety of azelaic acid and glycolic acid combination therapy compared with tretinoin therapy for acne

We conducted a 12-week, multicenter, randomized, double-masked, parallel-group study of the efficacy, safety, and tolerability of azelaic acid 20% cream and glycolic acid lotion compared with tretinoin 0.025% cream and a vehicle lotion to treat mild-to-moderate facial acne vulgaris. Patients treated with azelaic/glycolic acid experienced a significantly greater reduction in the number of papules, as well as a greater reduction in the number of inflammatory lesions, than those treated with tretinoin. Overall global improvement was approximately 25% in both groups. In the physician evaluations, treatment with azelaic/glycolic acid was found to cause significantly less dryness, scaling, and erythema than tretinoin. Patients also reported significantly less dryness, redness, and peeling with azelaic/glycolic acid. Significantly more patients in the azelaic/glycolic acid group than the tretinoin group reported that they felt attractive. The combination of azelaic acid and glycolic acid is a useful alternative to tretinoin, being at least as efficacious as the latter, while offering a superior tolerability and patient approval profile.     

Transdermal absorption of clindamycin and tretinoin from topically applied anti-acne formulations in man

The percutaneous absorption of clindamycin was studied in healthy male volunteers, comparing two investigative clindamycin (% w/v)/tretinoin (0.025% w/v) gels, containing clindamycin phosphate ester and clindamycin HCl, respectively, relative to a clindamycin phosphate lotion (1% clindamycin; Dalacin T). Formulations were applied daily for 5 days on the face, according to a balanced complete block design. Redness of the skin was scored visually, and blood and urine were collected. Clindamycin plasma levels did not exceed the limit of quantification (5 ng mL(-1)) with the clindamycin phosphate formulations, but one volunteer who received the clindamycin HCl/tretinoin gel showed plasma levels of up to 13 ng mL(-1). Clindamycin urinary excretion for 12 h after application of the clindamycin phosphate/tretinoin gel was comparable to the values of the reference lotion, whereas the clindamycin HCl/tretinoin gel gave significantly higher values. Erythema appeared to be associated with increased urinary excretion. The formulations were tolerated well. In a separate clinical pilot study in acne patients, the transdermal uptake of tretinoin and clindamycin from the clindamycin phosphate/tretinoin gel was monitored. Plasma samples were collected after 4 and 12 weeks of daily treatment. None of the study plasma samples contained measurable tretinoin levels. Clindamycin levels were not quantifiable in the majority (87%) of samples, the highest plasma level was 11 ng mL(-1). The chemical form of clindamycin proved to modulate skin irritation and percutaneous uptake of clindamycin from a gel formulation in healthy subjects. There was no indications for a notable transdermal uptake of tretinoin during daily application of the gel in patients, nor for an enhancing effect of tretinoin on clindamycin uptake.     

Development of an experimental model of Microsporum canis infection in cats

An experimental infection model was developed for reliable induction of Microsporum canis skin infections in cats, using a defined number of macroconidia harvested from the fungus in culture. The strain of M. canis used produced highly fluorescent hairs under ultraviolet illumination. Kittens 8 to 9 weeks of age (n = 6) received 10(5) macroconidia applied topically to a closely-shaved area of skin. Sites were dressed with an occlusive bandage for 3 days, then grooming was restricted for an additional 4 weeks. Lesions were first observed 2 weeks after inoculation, enlarged over the following 6 to 8 weeks, then decreased in size and appeared healed at 12 to 14 weeks after inoculation. Cats often developed satellite lesions on the face, ears, or other body regions. The experimental infections strongly resembled moderately severe cases of naturally-occurring feline dermatophytosis in clinical patients. This experimental infection model will be useful for evaluation of topical and systemic treatments for feline M. canis infection.     

Retinoids and sebaceous gland activity

BACKGROUND AND OBJECTIVE: The marked efficacy of isotretinoin in the treatment of acne is undoubtedly due to its potential to inhibit sebaceous gland activity. The question arises if the anti-acne effect of new oral retinoids can be predicted by using the currently available experimental models. METHODS: We reviewed the effects of various oral retinoids on sebum excretion in humans and their efficacy in acne. The human data were compared to the results obtained from in vitro and animal models. RESULTS: Oral retinoids such as etretinate, acitretin and the so-called arotinoids were not able to inhibit the sebum production in humans and were ineffective against acne. In various animal models (i.e. sebum production in rats, flank organ size in hamsters, ear sebaceous gland size in hamster, most of these retinoids were shown to be effective. Furthermore, in addition to isotretinoin, some retinoids were able to suppress the proliferation of human sebocytes in vitro. CONCLUSIONS: The elucidation of the mechanism of action of isotretinoin on the sebocyte biology is critical for the search of more reliable models and for the discovery of new retinoids with anti-acne activity.     

Double-blind, vehicle-controlled, multicenter comparison of two 0.025% tretinoin creams in patients with acne vulgaris

BACKGROUND: Preclinical study and human patch tests indicate polyolprepolymer-2 may reduce cutaneous tretinoin-induced irritation. OBJECTIVE: This study compared the clinical efficacy and safety of a 0.025% tretinoin cream containing polyolprepolymer-2 and its vehicle to a commercially-available 0.025% tretinoin cream. METHODS: In this 12-week multicenter, double-blind, parallel group study in patients with mild to moderate acne, objective lesion counts and the investigators' global evaluations evaluated efficacy. Subjective evaluations of skin irritation were used to study safety. RESULTS: A total of 271 patients were enrolled. The active treatments demonstrated comparable efficacy that was statistically significantly greater than that of the vehicle. Safety evaluations of cutaneous and noncutaneous adverse events also indicated comparable results of the active treatments. CONCLUSION: The commercially-available 0.025% tretinoin cream and the 0.025% tretinoin cream containing polyolprepolymer-2 demonstrated comparable efficacy and safety.     

Therapy of acne vulgaris

Acne is an eminently curable disease. If therapeutic intervention sets in timely, scar formation can be prevented. Therapeutic modalities include the topical agents that should always be combined, and systemic agents, of which Isotretionoin is of particular importance. Isotretinoin is the only agent that can induce a complete clearing of acne lesions in 60 to 80% of cases. Adjuvant therapies, such as local injections, incisions, and peelings, are valuable tools in everyday practice and may accelerate the clearing of acne lesions. The treatment of acne is a long term endeavour that needs to be individually tuned to each patients' needs.     

O'Brien's actinic granuloma: response to isotretinoin

We describe a 75-year-old man demonstrating the florid clinical features of actinic granuloma of O'Brien. This rare disfiguring condition is believed to result from a granulomatous reaction of the dermis to solar-induced elastosis and is poorly responsive to topical steroids. Twelve weeks' treatment with isotretinoin prevented the development of new granulomata and produced almost complete resolution of established lesions.     

Effect of topical tretinoin under occlusion on atypical naevi

Atypical naevi are potential precursors of melanoma and markers of increased melanoma risk. To examine the possibility of chemoprevention of melanoma by retinoids, we studied the effect of topical tretinoin 0.1% (all-transretinoic acid; vitamin A acid) and tretinoin 0.1% with hydrocortisone on atypical naevi. Thirty patients with atypical naevi were enrolled in a prospective randomized double blind study. For each patient three comparable naevi were selected and randomized to receive tretinoin 0.1% (T), tretinoin 0.1% with hydrocortisone 1% (C) or a placebo cream (P) once a week under Actiderm occlusion for 4 months. Baseline views of the naevi, taken with a videomicroscope (magnification 20 x), were assessed for morphological changes compared with views taken 2 months after the beginning of treatment, 1 week after completion of treatment and 6 months later. After completion of the study all naevi in the T and C groups and six naevi in the P group were removed and evaluated histologically for the presence of atypia. The number of naevi that had changed in colour or size was significantly higher in the T and C groups compared with the placebo group. A size reduction took place in 42.9% (T) and 40.0% (C) of the naevi and the colour changed in 75.0% (T) and 66.7% (C). The effect of treatment, in general subtle, did not differ significantly between groups T and C, but naevi treated with C became significantly less irritated. Histologically, 75.0% of the naevi treated with T and 69.6% of the naevi treated with C were atypical. Therefore, no major change was seen in the clinical aspect of atypical naevi after treatment with tretinoin 0.1% or tretinoin with hydrocortisone 1%, and most of the treated naevi still met the histological criteria for atypia after the treatment period. The current management of follow-up of atypical naevi and excision when change to melanoma is suspected is therefore still recommended. Nevertheless, some response was seen, which may justify a further exploration of tretinoin and hydrocortisone 1% therapy for a longer treatment period in combination with research to clarify its mechanism.     

Eruptive epithelioid hemangioendothelioma with spindle cells

A 39-year-old white man presented with four discrete dermal nodules in his right upper arm. Biopsy revealed superficial dermal well-circumscribed nodules composed of solid areas and vascular spaces lined by epithelioid endothelial cells and a similar nodule composed of spindle and epithelioid cells. A moderate mitotic count of 3-4 mitoses/10 hpf was present. Multiple lesions erupted 1 month later distally and proximally to the original lesions. Magnetic resonance imaging of the right arm demonstrated a lesion in the humerus. Biopsy of the humerus showed a vascular tumor with similar histologic features to the overlying skin lesions. The differential diagnosis included epithelioid vascular tumors, bacillary angiomatosis, pyogenic granuloma, and Kaposi sarcoma. Vascular lesions containing epithelioid and spindle cells span a spectrum from benign to malignant. We believe these tumors belong in the category of hemangioendothelioma and propose the name eruptive epithelioid hemangioendothelioma with spindle cells. Our case emphasizes that eruptive cutaneous vascular lesions do not always suggest immunosuppression or malignancy. Additionally, it highlights the association between epithelioid vascular lesions of the skin and bone.     

Microsatellite analysis reveals deletion of a large region at chromosome 8p in conventional renal cell carcinoma

We describe the case of a 33-year-old Caucasian male with follicular mucinosis successfully treated with isotretinoin. Follicular mucinosis is a primary idiopathic disease or a secondary, lymphoma-associated dermatosis. An effective standard therapy for this disease is unknown. In our case, isotretinoin led to a dramatic improvement of the skin lesions in about two weeks. To the best of our knowledge, the benefits of isotretinoin in the treatment of follicular mucinosis have never been reported previously. The efficacy of this drug could be mediated by a regulatory effect on the infiltrating cells and/or by a modulation of the target organ (skin) response to the infiltrating cells.     

Erythematous bullous lesions on the dorsa of the hands due to contact exposure to ibutilide fumarate for injection

While waiting to observe the response to ibutilide fumarate by a patient with atrial fibrillation, a nurse preparing the intravenous solution inadvertently spilled the drug on the hands of a medical resident. The resident immediately wiped his hands dry with disposable paper towels. Several hours later he sensed tingling and itching over the area, and the next day two erythematous bullous lesions were present on the dorsal surfaces of both hands. A single application of topical steroid was applied to the affected areas. The lesions were kept clean and dry, and healed completely in approximately 10 days. This is an unusual allergic reaction due to contact with ibutilide fumarate.     

Lameness and leg weakness in rapidly growing turkeys associated with hip lesions

A form of epidemic lameness affecting rapidly growing broadbreasted turkeys of different breeds was investigated in 16 flocks. The condition commenced when birds were between eight and 14 weeks old and was consistenly associated with the development of lesions in the hip. Affected birds first showed leg weakness and ataxia and later chronic postural changes involving the hip. The post mortem lesions were those of inflammation, oedema, ulceration, fibrosis and complensatory hypertrophy of localised areas associated with the hip articulation. The cause was not established but the anatomical features of affected birds, their nutritional status and their apparent freedom from recognised infectious diseased are discussed.     

Evaluation of antismoking advertising campaigns

BACKGROUND: Steroid acne is a folliculitis that can result from systemic or topical administration of steroid, and has been described as showing a similar clinical picture to Pityrosporum folliculitis, but there have been few reports about the incidence of Pityrosporum ovale and the effect of antimycotic drugs in steroid acne and other acneiform eruptions. Our purpose was to describe the association between steroid acne and P. ovale, and to confirm the superior efficacy of oral antifungal drugs over anti-acne drugs in the treatment of steroid acne. METHODS: The history, clinical features direct microscopy, histopathologic analysis, and therapeutic results of 125 cases with steroid acne or other acneiform eruptions were described and compared. RESULTS: Over 80% of patients with acneiform eruption receiving systemic steroid revealed significant numbers of P. ovale in the lesional follicle. Furthermore, oral antifungal drug (itraconazole) showed significantly better clinical and mycologic effects than any other group of medications used in this study. CONCLUSIONS: Steroid acne and other acneiform eruptions showing discrete follicular papules and/or pustules localized to the upper trunk and acneiform facial skin lesions associated with multiple acneiform lesions on the body in the summer period should be suspected as Pityrosporum folliculitis. In addition, oral antifungal drugs recommended for Pityrosporum folliculitis; however, it will require a larger case-control study to confirm the superiority of antifungal therapy over anti-acne treatment.