Rocco De Pasquale

Nevus vascularis mixtus (cutaneous vascular twin nevi) associated with intracranial vascular malformation of the Dyke–Davidoff–Masson type in two patients

The term twin spotting refers to phenotypes characterized by the spatial and temporal co‐occurrence of two (or more) different nevi arranged in variable cutaneous patterns, and can be associated with extra‐cutaneous anomalies. Several examples of twin spotting have been described in humans including nevus vascularis mixtus, cutis tricolor, lesions of overgrowth, and deficient growth in Proteus and Elattoproteus syndromes, epidermolytic hyperkeratosis of Brocq, and the so‐called phacomatoses pigmentovascularis and pigmentokeratotica. We report on a 28‐year‐old man and a 15‐year‐old girl, who presented with a previously unrecognized association of paired cutaneous vascular nevi of the telangiectaticus and anemicus types (naevus vascularis mixtus) distributed in a mosaic pattern on the face (in both patients) and over the entire body (in the man) and a complex brain malformation (in both patients) consisting of cerebral hemiatrophy, hypoplasia of the cerebral vessels and homolateral hypertrophy of the skull and sinuses (known as Dyke–Davidoff–Masson malformation). Both patients had facial asymmetry and the young man had facial dysmorphism, seizures with EEG anomalies, hemiplegia, insulin‐dependent diabetes mellitus (IDDM), autoimmune thyroiditis, a large hepatic cavernous vascular malformation, and left Legg‐Calvé‐Perthes disease (LCPD) [LCPD‐like presentation]. Array‐CGH analysis and mutation analysis of the RASA1 gene were normal in both patients.

High mobility group box 1 contributes to wound healing induced by inhibition of dipeptidylpeptidase 4 in cultured keratinocytes

Dipeptidyl peptidase 4 (DPP4) is expressed in various tissues, including the skin, and DPP4 inhibitors, that are currently used for the treatment of diabetes, may be effective also for complications of diabetes that affect the skin. To assess the role of DPP4 in keratinocytes, after creating a scratch wound in a monolayer of NTCC 2544 cells, we evaluated DPP4 expression and monitored wound repair over time, after treatment with the DPP4 inhibitor 1(((1-(hydroxymethyl)cyclopentyl)amino)acetyl)2,5-cis-pyrrolidinedicarbonitrile (DPP4-In). Expression of DPP4 increased early and was maintained up to 48 h following the scratch as shown by western blot and immunostaining. Treatment with 10 μM DPP4-In reduced DPP4 expression and significantly accelerated wound repair. This effect did not involve enhanced cell proliferation as shown by MTT proliferation assay, the lack of changes of cell cycle profiles and the slight inhibition of ERK phosphorylation. Enhancement of wound repair by DPP4 inhibition was prevented by the non-specific MMPs inhibitor GM6100 (5 μM). Treatment with DPP4-In increased the expression of high mobility group box 1 (HMGB1), a substrate of this enzyme, and exposure of NCTC 2544 cells to DPP4-In and exogenous HMGB1 (10 nM) produced a non-additive effect. Finally the healing promoting effect of DPP4-In was prevented by pretreatment with a neutralizing anti-HMGB1 antibody. The present results suggest that DPP4 inhibition contributes to enhanced wound healing by inducing keratinocytes to migrate into a scratched area. This effect seems to be independent of cell proliferation and involves enhanced production of HMGB1.

Non malignant superior vena cava syndrome

A 62‐year‐old woman was admitted to our clinic for the evaluation of 2.5‐year history of progressive exertional facial flushing, and swelling of the head, face, and neck. Three years earlier, she had undergone implantation of a definitive pacemaker with an endocardial ventricular lead for a severe bradycardia. Physical examination revealed facial swelling and erythema including the periorbital areas, distended neck and edema of the region above the lower margins of the rib cage. Numerous dilated cutaneous venules were present on the ventral upper thoracic wall interspersed with patches of intense flush and large areas of normally colored skin ( Fig. 1 ). There had been no weight loss within the previous months. History of angioedema, allergic reactions, autoimmune diseases, or medication was negative. Enlarged lymph nodes were not detected. Complete blood cell count, fibrinogen, Quicks test for prothrombin, antithrombin III, C‐reactive protein, lipidic profile, renal functions, urinanalysis, and thyroid function test were within normal ranges. Standard X‐ray and sectional radiography of the chest revealed no lung diseases or alterations of the mediastinum. Doppler examination of the supraaortic trunks and chest CT scan showed normal findings. A diagnosis of superior vena cava syndrome (SCVS) was suspected and a cavography was performed, by injecting contrast medium simultaneously through the basilic veins, that revealed marked narrowing of the confluence of the two brachiocephalic veins at the junction of the internal jugular and right subclavian veins with a total obliteration of the right brachiocephalic vein ( Fig. 2 ). The diagnosis of pacemaker‐induced SVCS was confirmed and the woman was referred for angiosurgery.

Multiple and Clustered Eruptive Epidermoid Cysts following Treatment with Topical Imiquimod

A 61-year-old woman developed multiple and clustered eruptive epidermoid cysts at the site of treatment of a basal cell carcinoma located on her nose with imiquimod 5% cream (5 times/week for 6 weeks). Clearing was achieved after topical treatment with tretinoin 0.025% cream (1 application/day for 1 month).

Unusual Clinical and Pathological Features in Pemphigus Vulgaris: A Potential Diagnostic Pitfall

We describe the case of a 67-year-old woman affected by pemphigus vulgaris with a dry whitish scaly lesion in the upper lip. Clinically, this lesion resembled an actinic keratosis. Although histological examination revealed a focal acantholysis, the finding of a moderate-to-severe dysplastic epithelium was consistent with the diagnosis of acantholytic actinic keratosis with moderate/severe dysplasia. Nevertheless, the complete resolution of the lip lesion after systemic therapy for pemphigus vulgaris led us to reconsider the possibility that we were dealing with a pemphigus vulgaris with unusual clinical and histological features. The previously reported cytological dysplasia was better regarded reactive rather than neoplastic, likely as the result to the inflammatory injury.

Vulvar Melanoma Associated with Lichen Sclerosus in a Child: Case Report and Literature Review

The authors describe the sixth pediatric case to date of primary vulvar melanoma associated with lichen sclerosus and propose a practical management for such a rare cancer.

Juvenile elastoma without germline mutations in LEMD3 gene: A case of Buschke-Ollendorff syndrome?

We report the case of a 6‐year‐old Caucasian girl with clinical and histopathologic features of Buschke‐Ollendorff syndrome. Histologic examination of skin lesions showed thick, curly, elastic fibers in the derma. Bone lesions compatible with Buschke‐Ollendorff syndrome were found in the girls mother. Mutations in LEMD3 are pathogenic for Buschke‐Ollendorff syndrome. Analysis of all exons and exon‐intron junctions of LEMD3 did not reveal any germline mutations.

Evaluation of hyaluronic acid‑P40 conjugated cream in a mouse model of dermatitis induced by oxazolone

P40 is a particulate fraction or fragment isolated from Corynebacterium granulosum, which exhibits a wide spectrum of pharmacological functions including antitumor, antibacterial, phagocytic, antiviral and cytokine induction effects. In the present study, the immunomodulatory potential of P40-conjugated with hyaluronic acid was assessed in a mouse model of dermatitis induced by oxazolone. Oxazolone-induced allergic contact dermatitis is a T cell-mediated Th2-like hypersensitivity reaction, which mimics the corresponding reaction in humans. Female cluster of differentiation-1 mice were sensitized on days 0 and 1 by the application of 2% oxazolone onto a shaved back. The disease was induced by re-challenge on day 7 using 15% oxazolone in the inner and outer of the left ears of the mice. Mice were topically treated with hyaluronic acid-P40 conjugate cream or with placebo to the inner and outer surface of the left ear for 7 consecutive days starting from 1 h after the sensitization. A significant reduction in ear thickness and weight and in edema and leukocyte recruitment were observed in the mice treated with hyaluronic-P40 conjugate cream compared with mice treated with the cream base alone (P<0.05). Thus, P40-conjugated with hyaluronic acid may constitute an innovative dermatitis treatment.

Identification of novel chemotherapeutic strategies for metastatic uveal melanoma

Melanoma of the uveal tract accounts for approximately 5% of all melanomas and represents the most common primary intraocular malignancy. Despite improvements in diagnosis and more effective local therapies for primary cancer, the rate of metastatic death has not changed in the past forty years. In the present study, we made use of bioinformatics to analyze the data obtained from three public available microarray datasets on uveal melanoma in an attempt to identify novel putative chemotherapeutic options for the liver metastatic disease. We have first carried out a meta-analysis of publicly available whole-genome datasets, that included data from 132 patients, comparing metastatic vs. non metastatic uveal melanomas, in order to identify the most relevant genes characterizing the spreading of tumor to the liver. Subsequently, the L1000CDS2 web-based utility was used to predict small molecules and drugs targeting the metastatic uveal melanoma gene signature. The most promising drugs were found to be Cinnarizine, an anti-histaminic drug used for motion sickness, Digitoxigenin, a precursor of cardiac glycosides, and Clofazimine, a fat-soluble iminophenazine used in leprosy. In vitro and in vivo validation studies will be needed to confirm the efficacy of these molecules for the prevention and treatment of metastatic uveal melanoma.

La visita dermatologica

La visita dermatologica, ai fini della valutazione del paziente per la formulazione diagnostica, si fonda su due tappe consecutive, la prima costituita dall’anamnesi (raccolta della storia) e la seconda dall’esame obiettivo locale (verifica della storia), che procede attraverso l’ispezione e la palpazione delle lesioni presenti a livello della cute e delle mucose visibili.