Riccardo Pellicano

Genetic susceptibility to fixed drug eruption : evidence for a link with HLA-B22

BACKGROUND Our observation of familial cases of fixed drug eruption (FDE) prompted us to consider a genetic predisposition to this disease. OBJECTIVE Our purpose was to determine whether there is any association between FDE and any of the major histocompatibility complex class I or II alleles. METHODS HLA class I and II typing was performed by lymphocytotoxicity assay in 36 unrelated patients with FDE. RESULTS Significantly higher (p < 0.0001) frequencies of the B22 and Cw1 antigens were found in the 36 patients with FDE. CONCLUSION Our data are the first to suggest a genetic predisposition to FDE.

Fixed drug eruptions with feprazone are linked to HLA-B22

The pathogenesis of fixed drug eruption (FDE) is unknown, but recent studies suggest that FDE could be an immunologic reaction mediated by T lymphocytes. 1-3 The observation of a familial case of FDE prompted us to hypothesize a genetic predisposition to this disease. 4 In a series of 36 unrelated patients with FDE we found significantly higher frequencies of the human leukocyte antigen (HLA)-B22 and -Cwl antigens. The HLA-B22 antigen appeared to be common in patients with FDE provoked by the pyrazolone derivative feprazone. 5 We present data on H L A typing in a new series of 40 unrelated FDE cases and in seven familial cases of FDE. To test the hypothesis of a possible inheritance of an altered FDE gene in linkage with the HLA-B locus, we consmacted extended haplotypes in the two most representative FDE families with the following markers: DQo~, tumor necrosis factor--~, and D6S258.

Total body skin examination for skin cancer screening in patients with focused symptoms

BACKGROUND The value of total body skin examination (TBSE) for skin cancer screening is controversial. OBJECTIVE We sought to determine whether TBSE could be helpful in patients with focused skin symptoms who would not otherwise have undergone TBSE. METHODS In a prospective, multicenter, cross-sectional study consecutive adult patients were recruited during a period of 18 months. Physicians first inspected problem areas and uncovered areas and then performed TBSE. Equivocal lesions detected in both steps were excised or biopsied. Primary outcomes were the absolute and relative risks of missing skin cancer and the number of patients needed to examine to detect melanoma or another malignancy. A secondary outcome was the proportion of false-positive results obtained by TBSE. RESULTS We examined 14,381 patients and detected 40 (0.3%) patients with melanoma and 299 (2.1%) with at least one nonmelanoma skin cancer by TBSE. In 195 (1.3%) patients equivocal lesions found by TBSE turned out to be benign. We calculated that 47 patients need to be examined by TBSE to find one skin malignancy and 400 patients to detect one melanoma. The risk of missing one malignancy if not performing TBSE was 2.17% (95% confidence interval 1.25-3.74). Factors significantly increasing the chance to find a skin cancer were age, male gender, previous nonmelanoma skin cancer, fair skin type, skin tumor as the reason for consultation, and presence of an equivocal lesion on problem/uncovered areas. LIMITATIONS The impact of TBSE on skin cancer mortality was not evaluated. CONCLUSIONS TBSE improves skin cancer detection in patients with focused skin symptoms and shows a low rate of false-positive results.

Impact of body mass index on retention rates of anti-TNF-alfa drugs in daily practice for psoriasis

Abstract Background: Psoriasis is a chronic inflammatory skin disease which often requires life-long treatment. Objective/aim: Our objective was to assess the role of the body mass index (BMI) on the retention rates of anti-TNF-alfa therapies in patients with moderate to severe plaque psoriasis. Material and methods: Retrospective observational study of psoriasis patients included in local databases of three public Italian hospitals. All patients, who received anti-TNF-alfa treatment in referral centers, were included. Only patients with at least 1-year follow-up were considered eligible. The outcome was the conservation of the treatment at 1 and 2 years of follow-up. Results: 194 patients were enrolled. 307 treatment courses with a minimum follow-up of 12 months and 263 with a follow-up of 24 months were analyzed. The proportion of patients receiving the same treatment at months 12 and 24 was 67.43% and 42.21%, respectively. The proportion steadily decreased with increased values of BMI. Conclusions: The overall efficacy of TNF-alfa inhibitors diminishes with time. The BMI affects the long-term survival rate of anti-TNF-alfa in psoriatic patients. A high BMI can be considered a potential predictor of drug discontinuation.

Dermoscopy of Cutaneous Sarcoidosis

Background: The clinical variability of cutaneous sarcoidosis (CS) often makes its correct diagnosis challenging. Although traditionally employed for the diagnosis of skin tumors, during the past years dermoscopy also gained increasing interest as an aid in the clinical diagnosis of inflammatory and infectious skin manifestations in general dermatology. Objective: Our purpose was to evaluate the usefulness of dermoscopy in the differential diagnosis of CS. Methods: This was a retrospective analysis of 7 clinical and dermoscopic images of CS that were collected at dermatology clinics in France and Italy between 2005 and 2009. Results: Retrospective dermoscopic evaluation revealed small grouped, translucent orange globular structures associated with linear vessels of variable diameter in all 7 cases. In 5 cases, additional central scar-like areas were seen. Conclusion: Lesions showing dermoscopically translucent yellow to orange globular-like or structureless areas associated with linear vessels should raise the suspicion of a granulomatous skin disease, including CS.

IgE recognition of bullous pemphigoid (BP)180 and BP230 in BP patients and elderly individuals with pruritic dermatoses.

Bullous pemphigoid (BP) is the most common autoimmune bullous disease of the elderly and is associated with IgG and IgE autoantibodies against the hemidesmosomal proteins, BP180 and BP230. The purpose of this study was to characterize the epitope specificity of IgE against defined regions of BP180 and BP230 in 32 BP patients and 21 elderly patients with pruritic disorders who did not yet fulfill all the criteria of BP by immunoblot (IB), ELISA and indirect immunofluorescence microscopy. Our findings show that IgE from BP sera preferentially targets the COOH-terminus of BP230 (IB: 16/32, ELISA: 12/32) and, to a lesser extent, the BP180-NC16A domain (IB: 11/32, ELISA: 9/32). Noteworthy, a subgroup of elderly patients with pruritic dermatoses also showed IgE recognition of BP180-NC16A (IB: 1/21, ELISA: 4/21) and less frequently of BP230 (IB: 2/21, ELISA: 2/21). Thus, IgE recognition of the BP autoantigens is presumably an early pathogenetic event in BP.

Dermoscopy of Necrobiosis Lipoidica and Granuloma Annulare

Background: Dermoscopy is traditionally used for the diagnosis of skin tumors, but it has also gained increasing interest as an adjunct in the clinical diagnosis of inflammatory skin diseases. Objective: To evaluate the dermoscopic patterns of necrobiosis lipoidica (NL) and granuloma annulare (GA) and to compare these findings with other granulomatous skin disorders. Methods: This is a retrospective analysis of patient data and clinical and dermoscopic images of histopathologically diagnosed cases of NL and GA. Results: A total of 24 cases, including 12 cases of NL and 12 cases of GA, were evaluated. In all cases of NL, dermoscopy revealed evident, sharply focused, elongated and serpentine telangiectasias, which were typically located over a whitish, structureless background. In contrast, all cases of GA were dermoscopically typified by peripheral, structureless orange-reddish borders, which were associated in 5 cases with isolated, unfocussed small vessels. Conclusion: Our study suggests that NL and GA reveal different dermoscopic patterns, which may aid the correct diagnosis. In addition, the dermoscopic patterns of NL and GA appear to differ from other forms of granulomatous diseases.

Granuloma faciale: a case report on long‐term treatment with topical tacrolimus and dermoscopic aspects

Granuloma faciale (GF) is an uncommon, benign form of chronic leukocytoclastic vasculitis, which predominantly affects the face and which is notoriously resistant to several therapies. Besides a range of therapeutic modalities, tacrolimus has been recently reported in the successful treatment of GF. Herein we describe the clinical, dermoscopic and histopathological findings in a patient affected by GF and its response to long‐term topical treatment with tacrolimus 0.1% cream.

A new case of acromegaloid facial appearance (AFA) syndrome with an expanded phenotype.

A patient presenting with the findings of Acromegaloid Facial Appearance (AFA) syndrome is reported. This case also shows pericardial effusion and skin lesions that both enlarge the spectrum of the phenotype and lump AFA syndrome with another proposed distinct condition [Irvine et al., (1996) J med Genet 33:972-974].

Melanoma onset after estrogen, thyroid, and growth hormone replacement therapy.

BACKGROUND Acute sun exposure is the main risk factor for the development of melanoma, especially if associated with a large number of benign melanocytic nevi. Although epidemiologic studies have investigated the effects of exogenous triggers, particularly hormones, our understanding of melanoma is still inadequate. OBJECTIVE The aim of this study was to report a case of melanoma that developed after hormonal therapy. CASE SUMMARY We report a case of a 26-year-old white woman (weight, 48 kg; Fitzpatrick skin phototype IV; no previous pregnancy) who was referred to the Department of Dermatology, Casa Sollievo della Sofferenza Hospital-IRCCS, San Giovanni Rotondo, Italy, with a malignant melanoma on the left thigh. At the age of 18 years (year 2000), the patient presented with amenorrhea, but no therapy was initiated until 2004. At this time, insufficiency of the gonadal, thyroid, and growth hormone (GH) axes was diagnosed without evidence of hypothalamic-pituitary anatomic damage or of congenital or acquired causes. The patient had an inadequate level of GH (base: 0.8 g/mL; peak: 1.0 ng/mL) during an insulin tolerance test, low levels of thyroid hormones, and a blunted response of luteinizing hormone (base: 0.2 mIU/mL; peak: 10 mIU/mL) and follicle-stimulating hormone (base: 2.6 mIU/mL; peak: 18.5 mIU/mL) to a gonadotrophinreleasing hormone stimulation test. Consequently, replacement therapy with ethinyl estradiol (20 microg) plus progestin (75 microg) (once daily for 21 days/month), levothyroxine (25 microg once daily), and recombinant human GH (0.8 mg SC once daily) was initiated. GH replacement therapy was discontinued after 2 years (June 2006), and thyroid and estrogen replacement therapy were discontinued after 4 years (February 2008). The patient reported first noticing the pigmented lesion 8 months after GH withdrawal, during treatment with the estrogen/progestin combination. CONCLUSION We report a case of melanoma onset in a patient who had received hormonal substitutive therapy, where the role of GH therapy alone or in combination with other hormones could not be ruled out.