Expression of adhesion molecules in atopic dermatitis is reduced by tacrolimus, but not by hydrocortisone butyrate: a randomized immunohistochemical study

Topical tacrolimus represents an effective and well-tolerated treatment for atopic dermatitis (AD). Its known effects include reduced production of proinflammatory cytokines and reduced chemokine gradient. We performed lesional skin biopsies on adult patients affected by moderate-to-severe AD. Then, patients were randomized to receive local treatment with tacrolimus ointment 0.1% and hydrocortisone butyrate ointment 1%. On the 21st day of treatment, another skin specimen was taken. Nine patients treated with tacrolimus and seven treated with hydrocortisone successfully concluded the trial. By immunohistochemistry (alkaline phosphatase/antialkaline phosphatase method), we demonstrated that endothelial leucocyte adhesion molecule (ELAM)-1, vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 showed different intensities and patterns of expression in untreated AD lesions. Tacrolimus-treated specimens featured a significant reduction of the expression of ELAM-1, VCAM-1 and ICAM-1, while hydrocortisone-treated lesions did not. Inhibition of adhesion molecule expression may represent another selective mechanism of action of topical tacrolimus in AD.     

Dermatitis herpetiformis: Novel advances and hypotheses

Dermatitis herpetiformis (DH) is a gluten-sensitive autoimmune blistering disorder with a chronic-relapsing course. Very recently, several Authors reported atypical cases of patients with DH, suggesting that different clinical subsets may exist at least among different ethnicities and that the classical picture of DH probably need a significant revision. Moreover, different pathogenetic aspects of the disease are currently under investigation, including the role of epidermal transglutaminase, apoptosis and inflammatory cells in the occurrence of skin lesions, in order to explain why only a subgroup of celiac patients will develop DH. Finally, although gluten-free diet is still regarded as the only curative approach to the disease, it is very hard to comply with and even small amounts of gluten can re-activate the disease. Therefore, different therapeutical approaches for the spectrum DH/celiac disease are still under investigation. In the present paper, the most recent advances in DH will be discussed, and a novel interpretation of the disease based on the data emerging from the Literature will be proposed.     

Cutis marmorata telangiectatica congenita and chronic autoimmune urticaria in a young man

A 20-year-old man with mental impairment, was referred to us for evaluation of recurring idiopathic urticaria episodes, characterized by a diffuse spreading of wheals and severe itching lacking response to traditional antihistamines. Upon physical examination, he showed a persistent, generalized, reticular, red-bluish vascular skin pattern in association with diffuse arborizing telangiectasias. Such lesions were present from an early age. Laboratory and instrumental tests, performed in order to exclude any condition associated with livedo did not evidence pathological results. He was found to be positive for antinuclear autoantibodies (ANA; 1:640). Histopathologically, numerous dilated capillary vessels associated with sparse extravasated erythrocytes were observed in the upper dermis. We performed an autologous serum skin test (ASST), which resulted in a positive, suggesting an autoimmune basis of the condition. On the basis of clinical and histopathological findings, and in the absence of other clinical and laboratory data suggesting other neoplastic, immunological or systemic diseases, the diagnosis of cutis marmorata telangiectatica congenita (CMTC) associated with chronic autoimmune urticaria (CAIU) was made. CMTC is a rare congenital vascular disorder, consisting in an anomalous, persistent, red-bluish marbling of the skin, that can be associated with a wide spectrum of cutaneous and extracutaneous anomalies. In our case, neither physical examination nor instrumental investigation demonstrated any of these anomalies, with the exception of cognitive impairment. We report this case because of the rarity of a diagnosis of CMTC in an adult patient, because this condition has almost always previously been diagnosed in infancy, or it comes to observation because of the presence of associated disorders, as in our case for chronic urticaria.     

A case of lichenoid drug eruption associated with sildenafil citratus

A 53-year-old man developed lichenoid lesions on the upper chest, posterior surfaces of the trunk, and abdominal region about three months before his first visit. Physical examination and laboratory findings were normal; histopathology showed vacuolar degeneration of basal keratinocytes in association with a dense lympho-histioid infiltrate arranged in a lichenoid pattern with a few melanophages and eosinophils. The fact that our patient had been irregularly taking sildenafil citratus (Viagra) led to the hypothesis of a lichenoid drug-induced eruption. Our hypothesis was confirmed by clinical resolution three weeks after discontinuation of sildenafil citratus; moreover, the patient avoided the drug for about four months, and the eruption didn't reappear. Subsequently, we performed a challenge test with the drug, and the patient developed similar lichenoid lesions. Lichenoid eruptions are rather common dermatoses that can be induced by a great number of environmental agents and are clinically but not pathogenetically well defined. We report the present case because, despite the great number of drugs that can be implicated in the development of lichenoid eruptions, the association of such dermatoses and sildenafil citratus had been described only once previously in the literature until now. Furthermore, we wish to remark on the significance of a detailed anamnestic history to make the correct differential diagnosis between lichenoid drug-induced eruptions and lichen planus. This has a great clinical importance because simple discontinuation or substitution of the drug causes lichenoid drug-induced eruption resolution.     

Occupation and lung cancer risk in the province of Trieste: a case-control study]

To investigate the relationship between occupation and lung cancer, a case-control study was performed in the province of Trieste, Italy, where metallurgical and mechanical industries, dock activities and shipbuilding and ship repairing are predominant. Through the local Cancer Registry, pathology records of 938 men who died of primary lung cancer (ICD 162) in a five-year period were examined. Residential, smoking and occupational histories were obtained from interviews of next of kin of 756 cases and 756 age-matched male controls (+/- 2 years). Occupational exposures to lung carcinogens were assessed according to a job-title based approach, identifying industries/occupations with well-recognized lung carcinogen exposures (list A) and industries/occupations with suspected lung carcinogen exposures (list B). Exposure to asbestos was classified as absent, possible or definite. After adjustment for cigarette smoking (four levels) and residence (three levels), a significant association was found between lung cancer and occupations in list A (RR = 2.28, 95% CI = 1.70-3.07) and in list B (RR = 1.33, 95% CI = 1.04-1.71). A significant excess risk was found for workers with definite exposure to asbestos when compared to those with no exposure to lung carcinogens (RR = 1.99, 95% CI = 1.43-2.76). A very high relative risk was observed among heavy smokers with definite exposure to asbestos (RR = 42.8). A stratified analysis showed that the combined effect of asbestos and smoking was compatible with that expected under a multiplicative model. The overall attributable risk in the population (ARp) for cigarette smoking was found to be 87.6%. The ARp fraction for occupations with well-established exposures to lung carcinogens (list A) was 16.2%. The ARp fraction increased to 25.5% (85% CI = 1.4-34.6) when occupations with suspected exposure to lung carcinogens (list B) were included. The ARp fraction for possible or definite exposure to asbestos was 20.1% (95% CI = 11.6-28.6).