Carmen Cantisani

Minoxidil use in dermatology, side effects and recent patents.

Minoxidil, a vasodilator medication known for its ability to slow or stop hair loss and promote hair regrowth, was first introduced, exclusively as an oral drug, to treat high blood pressure. It was however discovered to have the important side-effect of increasing growth or darkening of fine body hairs; this led to the development of a topical formulation as a 2% concentration solution for the treatment of female androgenic alopecia or 5% for treating male androgenic alopecia. Measurable changes disappear within months after discontinuation of treatment. The mechanism by which it promotes hair growth is not fully understood. Minoxidil is a potassium channel opener, causing hyperpolarization of cell membranes and it is also a vasodilator, it is speculated that, by widening blood vessels and opening potassium channels, it allows more oxygen, blood and nutrients to the follicle. This can also cause follicles in the telogen phase to shed, usually soon to be replaced by new, thicker hairs in a new anagen phase. It needs to be applied regularly, once or twice daily, for hair gained to be maintained, and side effects are common. The most common adverse reactions of the topical formulation are limited to irritant and allergic contact dermatitis on the scalp. There have been cases of allergic reactions to the nonactive ingredient propylene glycol, which is found in some topical solution especially if they are galenic. Increased hair loss which can occur during Minoxidil use, is due to the synchronization of the hair cycle that the treatment induces. In this review, we described its mechanism of action, use in dermatology and some patents related to alternative treatment of allergic reactions due to its use.

Imiquimod 5% Cream Use in Dermatology, Side Effects and Recent Patents

Imiquimod is an immune response modifier that stimulates the patients own immune system to release various chemical substances, such as interferon and interleukin-12. Although, approved by the United States Food and Drug Administration since 1997 as a topical treatment for genital and perianal warts, investigators have found that this product may offer an alternative treatment for a wide variety of medical conditions, such as for actinic keratoses, molluscum contagiosum, genital herpes, and various skin tumours. Clinical trials are now demonstrating the beneficial effects that its administration may have in treating other immune-related, dermatologic disorders. Understanding the pharmacology of this kind of drug is another step to fully understanding the power of the human immune system. Local reactions occur most frequently and include itching, burning, pain, soreness, flaking, erosions, and crusting. Since, it is administered locally; only a small amount of drug should reach systemic circulation, if used correctly. However, uncommon systemic side effects have been reported including headache, flu-like symptoms, fatigue, nausea, and myalgia. This article reviews imiquimod use in dermatology including its off-label use, side effects, future developments, new molecules related to dermatology and relevant patents.

Psoriasis: new insight about pathogenesis, role of barrier organ integrity, NLR / CATERPILLER family genes and microbial flora.

Psoriasis is a common, inflammatory, chronic, relapsing skin disease. New insight about the etiology of this disease shows the important role played by the epidermal barrier function, its integrity and pathogen responses in combination with microbial environmental factors. A pivotal role in the management of this balance is played by NLR genes, also known as NBD‐LRR or CATERPILLER, that encode important mediators of innate immunity and provide the first line of defense against pathogens. The polymorphism of these genes is implicated in the pathogenesis of several immunological diseases and might be of importance in the pathogenesis of barrier organ disorders. Crohn’s disease is considered archetypal of these kinds of disorders; similarities between Crohn’s disease and psoriasis and their similar pathogenetic mechanisms may support the concept of psoriasis as a barrier organ disorder and common genetic ground lying behind these illnesses. Considering psoriasis as a “barrier organ disease” is not only a mere mental exercise; this consideration may, in fact, open new prospects in the treatment of these disorders just by preventing alterations of microbial flora or regulating the response of the host to infective diseases.

Finasteride, 1 mg daily administration on male androgenetic alopecia in different age groups: 10‐year follow‐up

Finasteride 1 mg is indicated for the treatment of men with androgenetic alopecia (AGA). However, more than 5 years efficacy and safety has not been previously reported. To assess the efficacy over 10 years in different age groups of men with AGA. 118 men, between 20 and 61 years, with AGA receiving finasteride (1 mg/day), were enrolled in this uncontrolled study. Efficacy evaluation was assessed with standardized global photographs at T0,T1,T2,T5,T10. Statistical analysis was made using frequency tables and evaluating the chi‐square index with its p‐value. Better improvements are observed in patients older than 30 years (42.8% aged between 20 and 30 years did not improve also after 10 years) or with higher AGA grades (58.9% for AGA grade IV and 45.4% for AGA grade V had the first improvement just after 1 year). In 21% of cases, the treatment continuation beyond 5 years provided better results. Side effects were referred by 6% of the patients; nevertheless, some of them went on with treatment because of the great results. In our opinion, the result after the first year can help in predicting the effectiveness of the treatment. Its efficacy was not reduced as time goes on; in fact, a big proportion of subjects unchanged after 1 year, improved later on, maintaining a positive trend.

Tacrolimus 0.1% and granuloma annulare: description of three cases

Editor Granuloma annulare is a benign asymptomatic, self-limited papular eruption found in patients of all ages. There are several forms, including localized, generalized, perforating, subcutaneous and actinic. The two most common types are localized, which typically is found on the lateral or dorsal surfaces of the hands and feet; and disseminated, which is widespread. Although it is a self-limited and asymptomatic disease, in most cases, it can become chronic and recalcitrant to therapy. We report our treatment experience with topical tacrolimus in three patients histologically diagnosed as having granuloma annulare. A 37-year-old woman developed disseminated asymptomatic eruption on the buttocks and extremities. The eruption began 2 years previously on the left leg as small papules, gradually spreading to involve the right leg and buttocks. On physical examination a 5-cm erythematous ring was noted on her left central knee and a serpiginous papular erythematous lesion on the medial aspect of the knee. A 55-year-old woman developed ring-shaped, inflammatory, erythematous infiltrates with centrifugal growth tendency and sunken centres on her lower right leg 8 months before. A 43-yearold woman presented with asymptomatic circular, inflammatory, erythematous plaque on her chest appeared 2 months previously (Fig. 1). Laboratory tests were within normal value. Their general health remained good. Full blood count, urinalysis, liver function tests, serum proteins, plasma glucose level, chest X-ray and serology were all normal. A skin biopsy showed interstitial lymphocytic and histiocitic infiltrates with collagenolysis, consistent with granuloma annulare confirming the clinical diagnosis. None of them had a personal or familiar history of diabetes mellitus or any other disease. Patients had undergone several treatments with medium to high potency topical corticosteroids, without improvement. We began treatment with topical tacrolimus for all patients. After 8 weeks, there was a significant improvement of the eruption; thus far, the first patient remains in a satisfactory clinical condition without relapse of lesions. A slight reduction of the inflammation and regression of the infiltrate in the second patient and a complete healing in the third one with short-term disease duration was observed after 8 weeks and is still persisting after a 1-year follow-up (Fig. 2). Medical literature contains limited reliable information on granuloma annulare treatment. Such studies cannot establish treatment effectiveness, particularly with a self-limited disease. Therapy has been largely disappointing despite sporadic reports of limited success with topical, intralesional and systemic steroids.

Superficial basal cell carcinoma successfully treated with ingenol mebutate gel 0.05

Basal cell carcinoma (BCC) is the most common cancer in the world (1). It is typically slow growing and rarely metastatic, usually effectively managed with surgery. However, BCC in some patients is unsuitable for surgery; whereas in other cases, patients may prefer a nonsurgical treatment, especially when they have several lesions (2). Among other already known topical treatments, topical ingenol mebutate gel, a derivate of Euphorbia peplus plant, recently arrived in the Italian market, has begun to show effectiveness in superficial BCC (BCCs). We describe a case of a 79-year-old Caucasian man, skin phototype II, referred to our clinic complaining of severe sun-damaged skin and multiple nonmelanoma skin cancers; he had several actinic keratosis (AKs) for which we chose ingenol mebutate gel 0.05% and we decided to apply this also on the bigger BCCs on his back (FIG. 1). We directly applied the gel for 2 days and we observed only a light erythema on the first day, worsened already on the second day. From the third day, he experienced severe flaking/scaling/dryness extending beyond the application site (FIG. 2). Nonsevere, potentially treatment-related events included: erythema extending beyond the application site, application-site pain, and headache; the local reaction lasted almost 2 weeks and then we observed almost completed resolution that persisted after 3 months from the treatment (FIG. 3). The incidence of nonmelanoma skin cancers is undergoing a drastic global increase. The continuous search for noninvasive treatments has encouraged the development of new therapeutic agents. An understanding of the history, mechanism of action, and recent trial evidence for the emerging therapy can assist physicians in counseling patients on available treatment options and in selecting appropriate therapy. Ingenol mebutate is a new topical drug extract from the latex sap of a plant E peplus that acts by chemoablative and immune-stimulatory properties (3). The sap from E peplus, commonly known as petty spurge in the UK or radium weed in Australia, has been used as a traditional treatment for a number of cancers (4). The incidence of local skin reactions is high, although clinical studies have proven it to be safe and efficacious, leading to the Address correspondence and reprint requests to: Carmen Cantisani, MD, Professor, Department of Dermatology. “Sapienza” University of Rome, Viale del Policlinico 155, 00186 Rome, Italy, or email: carmencantisanister@gmail.com; cantisanicarmen@gmail.com.

Homocysteine plasmatic status in patients with psoriasis

ejd.2011.1455 Auteur(s) : Antonio Giovanni Richetta1 antoniorichetta@hotmail.com, Carlo Mattozzi1, Laura Macaluso1, Carmen Cantisani1, Simona Giancristoforo1, Sara D’epiro1, Monica Salvi1, Marco Scarno2, Stefano Calvieri1 1 Department of Dermatology, Policlinico “Umberto I” University of Rome “La Sapienza”, Viale del Policlinico, 155, 00133 Rome, Italy 2 CASPUR Department of medical statistics, Italy Hyperhomocysteinaemia represents an independent risk factor for atherosclerotic cardiovascular [...]

Ketoprofen allergic reactions.

Topical ketoprofen (KP) is widely used because of its anti-inflammatory effect. Parallel with its popular usage, the number of reported cases of ketoprofen-induced photoallergic contact dermatitis has increased. A review of the literature was made to evaluate the spectrum of cross sensitization in patients with ketoprofen-induced photoallergic contact dermatitis using ketoprofen and other structurally similar chemicals and sunscreens, fragrance components, as well as the presence of prolonged photosensitivity related to it. Furthermore, the distinction between true cross-reactivity and concomitant sensitization may be difficult. Therefore, further investigations are needed to gain a more complete understanding of this important topic. This article also reviews some patents related to alternative treatment of musculoskeletal diseases and/or treatment of allergic reactions due to NSAIDs use.

Management of local skin reactions after the application of ingenol mebutate gel for the treatment of actinic keratosis: four illustrative cases.

Editor Actinic keratosis (AK) is the early phase of a multistep continuum leading to invasive squamous cell carcinoma (SCC). Since the natural history of AK is unpredictable, all patients should be treated and periodically followed-up. Ingenol mebutate (IM), is directed at skin areas presenting multiple AKs with coexisting subclinical lesions. IM is self-administered over either two consecutive days (trunk and extremities) or three consecutive days (face and scalp). IM is effective, safe and acceptable, given its short treatment course, as well as overall intensity and duration of Local Skin Reactions (LSR). Since patients’ beliefs about medications significantly affect treatment adherence, patients, general practitioners and dermatologists should be aware of the clinical course of normal LSRs. We report a series of cases illustrating LSRs course after IM application (Table 1). All patients self-administered IM on a 25 cm skin area delimited with a marker. LSR score was recorded 3, 15 and 29 days after treatment. No patient was treated for LSRs. Case 1 presented five flat, slightly palpable and red AKs on the scalp. The patient had a history of AKs and SCC of the scalp. The initial reaction (LSRs = 11) healed in 15 days. The patient was not worried about LSRs and was very satisfied with the clinical outcome of therapy. Case 2 was treated for 9 AKs on his right cheek (Fig. 1). The initial reaction (LSR = 21) strongly improved in 15 days and completely healed in 29 days. The patient was worried about the initial reaction and possible aesthetic outcome of therapy. The patient felt reassured when informed that the observed LSRs were expected, given IM mechanism of action. He was very satisfied with the outcomes of therapy. Case 3, was treated for 6 palpable, scaly AKs on his right cheek. The initial reaction (LSRs = 23) included erythema and vesicles extending beyond the treated area. The patients felt reassured by dermatologist providing detailed information on the expected clinical course of the LSR. Only a mild erythema and scaling persisted after 29 days. Case 4, was treated for five slightly palpable AKs with a scaly surface on the dorsum of the right hand. Multiple vesicles overlying an erythematous background outside the treated area characterized an otherwise moderate LSR (=12). Moderate erythema and scaling persisted after 15 days and healed in 29 days. The patient was very satisfied with the clinical efficacy and the aesthetic outcome of therapy. This case series represents the spectrum of expected local skin reactions after topical application of IM. In our experience, complete healing was fast and did not require prescription of any treatment. Even severe erosions should be considered an expected reaction provided they are confined to the area of application and there is no sign of infection. Topical antibiotics and emollients might shorten wound repair in complicated cases. Delimiting the treated skin area and formally grading initial LSRs might help monitor their course. Patient–Physician communication is a key aspect of care given that patients self-administer IM and most subjects with moderate/severe reactions were worried that ‘something was going wrong’. Simple yet timely information about the expected course of LSRs reassured the patients and may enhance adherence, reduce phone or outpatient consultations and improve treatment satisfaction. Dermatologists should convey to patients that most LSRs are the clinical manifestation of IM mechanism of action, peak LSRs occur between the 4th and 8th day of treatment and healing is almost complete in 2 weeks even in the most severe cases.

Serum levels of functional T-regs in vitiligo: our experience and mini-review of the literature

Vitiligo is an acquired depigmentary skin disorder due to the loss of cutaneous melanocytes or alteration in melanocyte function, affecting over 0.5% of the world population. The exact cause of melanocyte loss in non-segmental vitiligo is still debatable, but many observations have pointed to the main role of cellular immunity. Earlier evidence has shown that depigmenting vitiligo skin is accompanied by CD8+ T cytotoxic lymphocytes infiltrates at the dermal-epidermal junction. Dysregulation of Tregs may be one of the factors that can break tolerance to melanocyte self-antigens and contribute to the pathogenesis of vitiligo. The objectives of the present study were to provide evidence of the presence of a functional defect and decrease of peripheral regulatory T cells in patients affected by vitiligo, supporting the hypothesis of their involvement in the pathogenesis of the disease, opening new possibilities to advance therapeutic approaches.