Adverse reactions and alleged allergy to local anesthetics: analysis of 331 patients.

The aim of this study was to determine the prevalence of true local anesthetic (LA) allergy among patients referred for suspected hypersensitivity and to describe the main characteristics of adverse drug reactions (ADR) induced by LA in our population. We retrospectively analyzed the medical files of patients referred to the Department of Dermatovenereology, University Hospital Center Rijeka, Rijeka, Croatia, for the investigation of LA hypersensitivity in the period between January 2000 and December 2012. A total of 331 patients underwent skin testing and, in cases of negative results, subcutaneous exposition to LA. In patients with suspected delayed reaction, patch test was performed. Altogether, 331 patients reported 419 independent ADR occurring during 346 procedures. Most commonly, patients reported having only one ADR, but 41 (12.4%) of them had two reactions, 14 (4.2%) had three, five (1.5%) had four and in one patient (0.3%) five ADR to LA were observed. The majority of reactions occurred during dental procedures when most commonly lidocaine and articaine were used. Local reactions were reported in 44 patients, whereas 490 general symptoms occurred during 375 independent ADR in 287 patients. The most common symptoms were cardiovascular system reactions in 89 patients (18.2%). Allergic reaction was detected in three patients (0.91%). One patient showed immediate-type reaction to bupivacaine and two patients had a delayed-type reaction to lidocaine. Adverse reactions to LA are common and are mostly due to their pharmacological properties and drug combinations or psychogenic origin. Allergic accidents to LA are rare.

Molecular and genetic mechanisms in melanoma.

Recent studies have indicated an increasing incidence of melanoma worldwide. Although UV signature mutations are found rarely in melanoma cells, there is some evidence that intense intermittent exposure to sunlight can induce melanocyte tumorigenesis, and this is also observed after UV irradiation in some animals. The purpose of this paper is to review some of the most important mechanisms involved in the pathogenesis of this tumor. Genetic studies showed the familiar melanoma is linked to the mutation or deletion of the suppressor gene CDKN2A, and perhaps to CDK4. Studies showed that BRAF mutation is frequent in primary and metastatic melanoma cells but also in naevocytic nevi. This mutation activates the RAF/MEK pathway. Exposure to UV radiation induces immunosuppression. Recent investigations showed that chemokines, angiogenesis, metalloproteinases can play a role in the mechanism of metastasis. In spite of these advances the initiating events are still not completely understood. In conclusion, the pathogenesis of melanoma is very complex because numerous genetic and epigenetic factors are implicated in its development and progression, but some of the showed mechanisms can be targets for new therapies.

Phytophotodermatitis in Rijeka region, Croatia.

Contact with plants can cause phototoxic or rarely photoallergic reactions. Phototoxic dermatitis (photophytodermatitis) occurs after contact or ingestion of plants containing furocumarins i.e. psoralens and followed by sun exposure. Skin lesions develop usually after 24-48 hours with erythema, bulla formation, itch or pain, followed by a long lasting hyperpigmentation. Furocumarins can be linear i.e. psoralens (5-MOP, 8-MOP), or angular like angelicin and pimpinellin. Their binding to DNA causes cellular damage. This can happen in florists, gardeners, farmers, horticulturists, food handlers, and botanists. The plants causing phototoxic reaction can vary with the local flora but are commonly a member of the family apiaceae (formerly umbelliferae), family rutaceae, leguminosae and moraceae. The authors give special consideration to the phytophotodermatitis that appeared in their region in spring and summer during a three year period.

Occupational skin diseases caused by UV radiation.

This overview highlights the risk of skin diseases arising in workers exposed to ultraviolet radiation (UVR) at their workplace. There is a plethora of skin manifestations in outdoor workers such as seamen, fishermen, farmers after acute intense or long-term exposure to solar UVR, but some cutaneous diseases may also develop in indoor workers exposed to artificial sources. In recent years, investigations of the biological effects and damage caused by UVB and UVA on the skin have improved our understanding of the cellular and molecular mechanisms of photoaging, skin cancer and other skin diseases caused by UVR exposure. The necessity of primary prevention in workers exposed to UVR is emphasized.

Occupational skin diseases caused by solar radiation.

UV radiation is present in sunlight and can be emitted from numerous artificial sources. Outdoor workers are exposed to sunlight in a wide variety of occupations like sailors, fishers, construction workers, farmers, and other. Presented are the skin diseases caused by sunlight exposure. They may be of little medical importance such as stigmata or create problems like photoaging, skin carcinoma, melanoma, phototoxic and photoallergic reactions. Shown are briefly data on skin cancer in the Rijeka region in outdoor occupations, the legislation and necessity for prevention. Psoriatic patients need particular caution because they are exposed to UVR, tars, and immunosuppressive drugs during the treatment.

Photocarcinogenesis--molecular mechanisms.

The carcinogenicity (photocarcinogenicity) of sunlight to human skin has been recognized more than a century ago. Last decades numerous experimental studies show that UV rays damage DNA, cause gene mutations leading to the development of malignant tumors such basal cell carcinomas, squamous cell carcinomas and melanomas. The tumors occur most frequently in fair skinned people, and the mutations typically are found at dipyrimidine sites with C-T or / and CC-TT tandem double mutations. The authors briefly summarize their investigation of the p53 suppressor gene, and expose their hypothesis of hTERT involvement in cancerogenesis. Also their underline the importance of UV induced immunosuppression in photocarcinogenesis. Psoriatic patients are exposed to numerous cancerogens in their treatment. A better understanding of the mechanisms of photocarcinogenesis could provide new ways in the treatment of skin tumors.