Possible protective role of metformin therapy on colonic polyps in acromegaly: an exploratory cross-sectional study.

CONTEXT: Colonic polyps occur in 30-40% of acromegalic patients, increasing the risk of colon carcinoma. Although debated, there is emerging evidence that metformin may play a protective role in diabetic and non-diabetic patients with colonic polyps and its use in chemoprevention is currently explored. OBJECTIVE: Evaluate the prevalence of colonic polyps in acromegalic patients treated or not with metformin and explore its possible protective role. DESIGN: Exploratory cross-sectional study in two tertiary Italian referral centres. MET: hods: Out of 153 acromegalic patients, we selected 58 patients (36-82 years; f: 33) who had at least one colonoscopy performed within the first 2 years of diagnosis. Presence of colonic polyps/cancer and related risk factors, current metformin and acetylsalicylic acid intake, disease duration, therapies for acromegaly, hormonal and metabolic parameters were assessed. RESULTS: An overall prevalence of 36% polyps was found. Based on the presence of polyps, we identified two groups, comparable for age, BMI, disease duration, glucose, insulin, HOMA-IR, HbA1c, GH and IGF-I levels. Of the patients with polyps (including three adenocarcinomas) only 24% were treated with metformin vs 57% of patients without polyps. Multivariate analysis confirmed a significant negative association between colonic polyps and metformin intake (OR: 0.22, 95% CI: 0.06-0.77, P = 0.01), whereas no significant association was found between polyps and age (P = 0.10), overweight/obesity (P = 0.54), smoking (P = 0.15), acetylsalicylic acid intake (P = 0.99), disease duration (P = 0.96), somatostatin analogues treatment (P = 0.70). CONCLUSIONS: These findings, though deriving from an exploratory study, could suggest a protective role of metformin on the development of colonic polyps in acromegaly, and need to be confirmed in an extended study population.

Telogen effluvium revisited.

Telogen effluvium (TE) is heterogeneous disorder. It can be classified into three main categories: the premature teloptosis, the collective teloptosis and the premature entry into telogen. The last category can be divided in three types: the drug induced TE, TE due to dietary deficiencies and the "autoimmune" TE. Despite this heterogeneity, the large majority of TE that arrive at the dermatologist's observation pertain to the autoimmune type, featuring a standard presentation. The typical patient is a woman claiming to have always had a "full head of hair" and reporting her hair to come out suddenly "by the handful". Usually, she is accurate about the date of onset of her shedding. She is in good health, without signs of anorexia nor nutrient deficiencies. She admits to having been in an anxious state for some months, and felt, occasionally or not, a painful or burning sensation at the scalp (trichodynia). Usually, the course of the disorder is chronic but intermittent, with apparent remissions being irregularly intermitted by relapses. The shed hairs do not exhibit telogen roots, but mostly exogen ones. This distinct entity, shares some analogies with alopecia areata, including the triggering role of emotional stress, trichodynia and the frequent association with Hashimoto's thyroiditis. Methods to assess its severity and to monitor treatment are described. In the absence of a documented etiopathogenesis, no treatment can be endorsed, but a course of topical corticosteroids could be tried.

Aquagenic wrinkling of the palms and cystic fibrosis: an Italian study with controls and genotype-phenotype correlations.

AIMS: The primary aim was to determine the prevalence of aquagenic wrinkling of the palms (AWP) in patients with cystic fibrosis (CF) compared to controls, and secondarily to evaluate genotype-phenotype correlations among CF subjects found to have AWP. METHODS: Fifty-eight patients with CF underwent a hand immersion test in tap water. Twenty-three of their CF carrier relatives and 7 subjects with a negative genetic test for CF were recruited as controls. Secondary analyses explored associations with genotype, pulmonary function, and sweat electrolyte levels in all subjects with and without AWP. Additional information about atopic diathesis, hyperhidrosis of the palms and drug intake were also collected. RESULTS: Thirty-one of the patients with CF (53.4%) exhibited AWP, in contrast to only 2 carriers (8.7%) and none in the control group. No correlation was found between CF genotype and AWP score severity. Twenty-three (39.7%) CF patients reported a history of hyperhidrosis, and in 17 of them (74%) AWP had been provoked. No correlation with history of atopy and lung function was noted. The difference between CF patients with hyperhidrosis and those without was highly significant (p = 0.016). Salt concentrations were significantly higher in patients with AWP. CONCLUSIONS: AWP is linked to CF and its diagnosis should lead the patients to a genetic or sweat test for CF. We found a significant association with hyperhidrosis and sweat electrolytes which supports the 'hyperconcentrated sweat' pathogenetic theory of AWP.

Low somatostatin receptor subtype 2, but not dopamine receptor subtype 2 expression predicts the lack of biochemical response of somatotropinomas to treatment with somatostatin analogs.

OBJECTIVES: To evaluate somatostatin receptor 2A (SSTR2A) and dopamine receptor 2 (DR2) protein expression in somatotropinomas and to relate it to response to somatostatin analogues (SA). DESIGN AND PATIENTS: SSTR2A and DR2 expression was analyzed by immunohistochemistry in 88 somatotropinomas from patients submitted to either pre-surgical or adjuvant SA treatment. Tumors were scored according to percentage of immunostained cells: 0 (< 25%), 1 (25-50%), and 2 (> 50%). Relation between protein expression and response to SA was performed in 66 patients. Response to SA was assessed by percent IGF-I reduction, being considered as an IGF-I per cent reduction higher than 50%. Disease control was also assessed (GH < 1.0 ng/ml and normal IGF-I). RESULTS: SSTR2A and DR2 were expressed in 100% and 98% of tumors, respectively. Biochemical response and disease control rates were 48% and 32%, respectively. Median IGF-I percent reduction after 3 months of SA treatment was lower in the SSTR2A score 0 than in the scores 1 and 2 (p < 0.001, both), and after 6 months in the score 0 than in the score 1 (p = 0.001) and 2 (p < 0.001). Biochemical response and disease control were associated with SSTR2 expression (p < 0.001 and p = 0.004, respectively). A negative predictive value for biochemical response of 100% was found when a SSTR2A expression < 25%of immunostained cells cut-off point was considered. No relation was found between DR2 expression and biochemical response and disease control. CONCLUSION: SSTR2A and DR2 are highly expressed in somatotropinomas. Low SSTR2A, but not DR2, expression is a negative predictive factor to response to SA.

The quality of life in Italian psoriatic patients treated with biological drugs.

AIM: Psoriasis is well known to affect negatively daily activities, occupational and sexual functioning. We investigated whether the improvement of skin lesions obtained with the new biological drugs comes with by a better Quality of Life (QoL) as well. METHODS: Thirty patients with moderate to severe psoriasis treated with either anti-CD11 (13) or anti-TNF-α molecules (17) were studied. The severity of skin lesions was evaluated, before the biological therapy (T0) and after 6 months of treatment (T1), by the Psoriasis Area and Severity Index (PASI) and the Body Surface Area (BSA). QoL was evaluated by the Dermatology Life Quality Index (DLQI) and by the Psoriasis Quality of Life (PsoriQoL). RESULTS: DLQI and PsoriQoL mean scores shifted significantly from 16.5 to 2 respectively. At T0, PASI did not correlate significantly with DLQI. DLQI nor PsoriQoL correlated significantly with age and with the duration of the disease. PASI correlated significantly with DLQI of patients with arthropathy only, but did not with DLQI of patients without arthropathy. At T1, PASI was not correlated significantly with DLQI nor with PsoriQoL. CONCLUSION: The patient affected by psoriasis suffer an impairment of their QoL which seems to be independent from many obvious factors, such as age, duration of the disease and, mainly, its severity. QoL does not seem to be influenced significantly by arthropathy. Other factors, of both genetic or environmental nature, could play a determinant role in depriving psoriatics of a good QoL.

Reliability of hamilton-norwood classification.

BACKGROUND: Hamilton-Norwood scale (HNS) has been largely used to assess clinically the severity of androgenetic alopecia (AGA), especially for therapeutical trials and even to establish its association with important diseases such as ischemic heart disease and prostate cancer. OBJECTIVE: To study HNS reproducibility in the hands of dermatologists and dermatology residents. MATERIALS AND METHODS: Seven dermatologists and 16 residents in dermatology classified 43 photographs of male heads with different degrees of AGA. In a second study, 8 appraisers (3 dermatologists and 5 residents in dermatology) examined 56 pictures with the same procedure and repeated the observation 3 months later. In the first study, the inter-rater agreement was estimated by calculating an intra-class correlation coefficient (ICC). In the second study, for intra-rater repeatability, each rater's scores from session 1 were paired with his/her scores for the same subjects in session 2, and the ordinary least products linear regression was calculated. RESULTS: In the first study, the concordance of appraisers was unsatisfactory (ICC = 0.63-0.68)]. In the second study, repeatability was poor, without any significant difference between dermatologists and dermatology residents. COMMENT: Reliability of HNS is unsatisfactory even in the hands of expert appraisers. To obtain better reliability, the number of classes should be reduced, but with such reduction HNS would be usable to classify patients only in a broad way.

Multiple eruptive dermatofibromas and immunosuppression: report of two cases and review of the literature.

Dermatofibromas are common benign fibrohistiocytic tumors that are most often solitary. The occurrence of multiple eruptive dermatofibromas (MEDF), on the contrary, is a rare event. MEDF have been reported in the setting of autoimmune diseases, treated with immunosuppressive drugs, in the course of HIV infection and in neoplastic diseases. An association with immunosuppression has led to the speculation that they are the result of an abortive immunoreactive process. Here, we describe a patient with Sézary syndrome and a patient with multiple IgA myeloma who developed MEDF. These associations have not been reported previously.

Sympathovagal imbalance in transsexual subjects.

CONTEXT: Autonomic nervous system imbalance is related to cardiovascular risk. Heart rate variability (HRV) indexes are associated with age, race, and sex, but the role of sex hormones is still unknown. OBJECTIVE: To evaluate sympathovagal balance (SB) in transsexuals. PATIENTS: Eighteen transsexual subjects, 12 male-to-female (group 1) and 6 female- to-male (group 2), compared with 34 age-matched controls: 17 males (group 3) and 17 females (group 4). Autonomic testing of SB was performed by Power Spectral Analysis (PSA) of HRV in clinostatism (c) and orthostatism (o). PSA identifies power peaks: high frequency (HF) expresses vagal activity, while low frequency (LF) expresses sympathetic activity. RESULTS: Group 1 showed lower LFc than groups 2, 3, and 4 (p<0.001, p=0.05, p<0.001, respectively), and lower LFo than groups 3 and 4 (p=0.01); HFc was lower than in groups 2, 3, and 4 (p=0.02, p=0.02, p<0.001, respectively), and HFo was lower than in groups 3 and 4 (p<0.001). LFo/HFo ratio was higher in group 1 than in group 4 (p<0.001). No differences emerged between groups 2 and 3. Group 2 showed lower HFo than group 4 (p=0.03), and a higher LFo/HFo ratio (p=0.01). Group 3 showed lower HFo and HFc than group 4 (p=0.02, p=0.05, respectively), and a higher LFo/HFo ratio (p=0.03). CONCLUSION: In this study we found a sympathovagal imbalance due to a reduced sympathetic and parasympathetic influence on heart rate. Sex hormone therapy per se may play a role in this imbalance, and HRV measurement could be useful in detecting cardiovascular risk in transsexuals.

Interobserver reproducibility of histological features in cutaneous malignant melanoma.

AIMS: To assess the interobserver reproducibility of certain histological features proposed for the diagnosis of melanoma. METHODS: In a series of melanomas, 13 histological parameters were analysed: dimension > 6 mm, asymmetry, poor circumscription, irregular confluent nests, single melanocytes predominating, absence of maturation, suprabasal melanocytes, asymmetrical melanin, melanin in deep cells, cytological atypia, mitoses, dermal lymphocytic infiltrate, and necrosis. RESULTS: The agreement (reproducibility) between the nine observers was excellent (kappa > 0.75) for 10 of the 13 examined features (dimension > 6 mm, poor circumscription, irregular confluent nests, single melanocytes predominating, absence of maturation, suprabasal melanocytes, asymmetrical melanin, melanin in deep cells, mitoses, and necrosis). The agreement for asymmetry was very close to excellence (kappa = 0.74), and that for cytological atypia (kappa = 0.65) and dermal lymphocytic infiltrate (kappa = 0.47) was slightly lower, but in the fair to good agreement range. The kappa values obtained by comparison with the majority diagnosis were generally high (> or = 0.85); the mean value of kappa was lower (0.70) for only one parameter (dermal lymphocytic infiltrate). CONCLUSIONS: The parameters investigated showed an overall good reproducibility.

Scar sarcoidosis after hyaluronic acid injection.

A 54-year-old woman presented with a 5-month history of tender nodules in both nasolabial folds that had developed 4 months after the injection of hyaluronic acid (HA) (Restylane) for wrinkles. The patient was treated with 1.5 mg/day betamethasone for 6 days and her lesions disappeared within 1 week. About 8 days after stopping therapy, however, new nodules developed at the same site, on previously healthy buttocks, and on old scars. On examination, nodules of about 0.5-1 cm in size were palpable at the nasolabial folds, and red nodules were present on the buttocks (Fig. 1) and on two old scars. Laboratory tests disclosed an increased protein C reaction (7.9 mg/L; normal value, < 5 mg/L) and acetyl-converting enzyme test (14.5 U/L; normal value, < 9 U/L). A chest X-ray was normal. Lung function tests showed a decreased lung CO diffusion, and chest axial tomography disclosed fibrosis, increased parenchyma density, and calcifications, findings suggestive of a diagnosis of lung sarcoidosis. An X-ray of the hands showed some bone cysts. Interestingly, two granulomatous lesions were observed at the sites of venipuncture. Histology of a gluteal lesion biopsy showed a deep granuloma with epithelioid and Langhans cells in the absence of necrobiosis. Sarcoidosis was diagnosed and the patient was given 50 mg/day prednisone with clear clinical improvement of cutaneous lesions in about 6 months. Decreased parenchyma density was also observed by chest axial tomography.