Stefano Calvieri

Treatment of cutaneous and pulmonary sarcoidosis with thalidomide

Many therapeutic agents have been proposed for treatment of steroid-resistant sarcoidosis. Because administration of low doses of thalidomide has been successful in treating other inflammatory diseases, it was used in a patient with systemic sarcoidosis who was unresponsive to corticosteroids and in a patient with pulmonary sarcoidosis, in whom Kaposis sarcoma developed after a course of corticosteroid therapy. Thalidomide, 200 mg/day for 2 weeks followed by 100 mg/day for 11 weeks, was given. This treatment was effective in both patients. No adverse reactions were observed. Thalidomide, 100 mg on alternate days, is still being administered. No relapse has occurred. Thalidomide, particularly because of its inhibition of the macrophage function, may be a useful alternative therapy in steroid-resistant cases. In addition, the correlation between the angiotensin-converting enzyme level and the clinical improvement observed in our patients suggests a direct parallel between angiotensin-converting enzyme and the activity of the granulomatous process.

Fatty acid synthase expression in melanoma.

Background: Fatty acid synthase (FAS), the key enzyme responsible for the synthesis of fatty acids, is weakly expressed in some normal human tissues. Recently, FAS has been demonstrated to be overexpressed in many non‐neoplastic highly proliferative lesions and in aggressive carcinomas with poor outcome, including colon, breast and ovary carcinomas.

Survivin, bcl-2, bax, and bcl-X Gene Expression in Sentinel Lymph Nodes From Melanoma Patients

PURPOSE The expression of apoptosis-related genes, such as survivin, bcl-2, bcl-X, and bax, has been evaluated by reverse transcriptase polymerase chain reaction (RT-PCR) and by immunohistochemistry in sentinel lymph nodes (SLNs) from melanoma patients and then correlated to the outcome of patients. PATIENTS AND METHODS Thirty-six SLNs were examined. After RNA extraction, an RT-PCR followed by Southern blot hybridization was performed to detect survivin, bcl-2, bcl-X, and bax mRNA. bcl-2, survivin, and bax gene expression was evaluated, whenever possible, also by immunohistochemistry at the protein level. RESULTS We found a significant correlation (P <.005) between survivin expression and outcome of patients; in fact, 61.5% of patients expressing survivin gene progressed or died because of the disease, whereas 38.5% are currently disease-free. Among patients negative for survivin expression, 100% are disease-free after a median follow-up time of 52.9 months. We did not find a significant correlation between bcl-2, bax, and bcl-X gene expression and outcome of patients. In fact, these genes were found equally expressed in patients with disease progression and in disease-free patients. CONCLUSION Our findings show a variable expression of apoptosis-related genes in SLNs of melanoma patients; more interestingly, we found that survivin expression correlates to outcome of patients in a statistically significant way, whereas the expression of other genes, such as bcl-2, bax, and bcl-X, did not seem to correlate to progression of disease. We suggest that the detection of survivin gene expression by RT-PCR in SLNs may be a useful prognostic indicator.

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.

Comparison of diagnostic methods in the diagnosis of dermatomycoses and onychomycoses

Direct microscopic examination of potassium hydroxide (KOH)‐prepared specimens is the simplest, cheapest method used for the diagnosis of mycotic infections of the skin. However, KOH preparations have been reported to have 5–15% of false‐negative results, possibly because of the low visibility of scant, scattered fungal material of the nail scrapings and because the detection of fungal elements depends on the skill of the observer [Arch Dermatol133 (1997) 1317; Clin Microbiol Rev8 (1995) 240]. We compared two different KOH‐based staining methods in order to obtain reliable results in shorter time than expected for cultures. A total of 124 patients with suspect diagnosis of dermatomycosis or onychomycosis were enrolled. Two scrapings from the same lesion of each patient were stained with KOH‐Chlorazole and KOH‐Acridine Orange (AO), respectively; cultural examination of the same specimen was considered as diagnostic gold standard. The two methods showed neither significantly different sensitivity nor specificity; however, for onychomycoses, we observed a slightly higher sensitivity for KOH‐Chlorazole and a higher specificity for KOH‐AO. We suggest the use of both techniques in order to improve detection of fungal infection, especially for onychomycoses.

Gastrointestinal and Retroperitoneal Manifestations of Type 1 Neurofibromatosis

BackgroundType 1 neurofibromatosis (NF1) is a genetic disease characterized by neoplastic and not neoplastic disorders, involving tissues of neuroectodermal or mesenchymal origin. The mainly involved districts are skin, central nervous system, and eye, and there is a wide range of severity of clinical presentations.Data sourcesAbdominal manifestations of NF1 comprehend five categories of tumors: neurogenic with neurofibromas, malignant peripheral nerve sheath tumors and ganglioneuromas, neuroendocrine with pheochromocytomas and carcinoids, non-neurogenic gastrointestinal stromal tumors, i.e., GISTs, and embryonal tumors and miscellaneous.ConclusionsEarly diagnosis of these abdominal manifestations is very important given the risk of malignancy, organic complications such as in the case of pheochromocytomas or hemorrhagic-obstructive complications such as in the case of the tumors of the gastrointestinal tract (GISTs and neurofibromas). The importance of an annual clinical evaluation on the part of a multidisciplinary pool of clinicians in highly specialized centers allows early detection of complications and of neoplastic transformation.

Total Spontaneous Regression of Advanced Merkel Cell Carcinoma after Biopsy: Review and a New Case

The clinical behavior is characterized by high incidence of local recurrence (27%–60%), of lymph node metastases (45%–91%), and of distant metastases in the liver, bone, brain, lung, or skin (18%–52%). The incidence of disease-related death is as high as 35% to almost 50%. Despite its highly malignant nature, spontaneous regression has occasionally been reported. The first recorded case of spontaneous regression (CSR) of MCC was described in 1986; since then, other such cases have been reported, bringing the total to 14. Of the total number of 14 cases, 12 cases can be classified as complete spontaneous regression after only the performance of a biopsy.

Health-Related Quality of Life in Patients with Neurofibromatosis Type 1

Background/Aims: Neurofibromatosis type 1 (NF1), a genetic condition most commonly characterized by the presence of dermal neurofibromas and café au lait macules, has a significant impact upon quality of life (QoL). The study aimed to assess the impact of NF1 on QoL. Methods: A total of 129 patients with NF1 completed the study questionnaires in an Italian academic dermatological centre and a neurofibromatosis clinic at the University of Rome. Results: All domains of general-health-related QoL were affected.Patients with serious cosmetic problemsreported a greater impact on the emotional domain. Conclusion: In our study, the impact of the cosmetic features on QoL had the greatest importance. This survey demonstrates the usefulness of QoL measurements in supplementing clinical assessments.

Association of Human Papillomavirus Type 11 with Carcinoma of the Penis

Human papillomaviruses (HPVs) are epithelium-tropic viruses associated with several cutaneous, epithelial, and mucosal lesions. The oncogenic potential varies considerably among the more than 70 different genotypes so far identified. HPV 6 and 11 are generally found in benign genital condilomata or laryngeal papillomas, but they have been sporadically associated with genital malignancies. Polymerase chain reaction (PCR) primed by degenerated consensus oligonucleotides (from a late region of the HPV genome) allows one to amplify a broad spectrum of HPV, whereas the amplification with specific primers is restricted to a limited number of HPVs. Therefore, the restriction fragment length polymorphism assay permits one to identify the HPV type present in the PCR product. We report a case of an invasive verrucous carcinoma of the penis associated with HPV 11, a type previously considered noncarcinogenic.

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.