Riccardo Cavalli

Cardio-facio-cutaneous (CFC) syndrome: Report of an adult without mental retardation

We report on a 25-year-old woman with typical manifestations of the cardio-facio-cutaneous (CFC) syndrome, but without mental retardation. She had valvular and infundibular pulmonic stenosis, brittle and woolly hair with patchy alopecia, scant body hair, dry and hypohydrotic skin, and characteristic facial traits. To our knowledge, this is the first case of CFC syndrome without mental retardation but typical cutaneous findings.

Skin dimpling as a consequence of amniocentesis

No reports of cutaneous lesions after amniocentesis have been published after the advent of real-time ultrasonography. Two infants with multiple skin dimpling caused by needle puncture during fetal life are described. They had pitted scars on the thighs and abdomen that were not associated with internal injury. Both mothers had undergone a diagnostic amniocentesis at the beginning of the second trimester of pregnancy. Real-time ultrasound monitoring of amniocentesis has not completely eliminated the risk of needle puncture scarring of the fetus.

Precalcaneal congenital fibrolipomatous hamartoma

The patients are four unrelated children, one boy and three girls, aged between 3 and 7 months. All the patients were born at term, had normal postnatal development, and were in good general health. Each child presented from birth with a single plantar nodule, between 0.5 and 1.5 cm in diameter, bilaterally and symmetrically localized on the medial side of the plantar surface of both heels ( Fig. 1 ). The nodules were skin‐colored, covered by normal epidermis, unattached to the underlying tissues, of soft and elastic consistency, nonpulsatile, and nontender to touch. They did not transilluminate. The patients’ familial histories were negative for similar disorders.

Neonatal Systemic Lupus Erythematosus Syndrome: a Comprehensive Review

Neonatal lupus erythematosus is an uncommon syndrome, which is caused by transplacental passage of maternal autoantibodies to Sjögren’s syndrome A or B autoantigens. The clinical presentation includes distinctive cutaneous lesions resembling those seen in systemic lupus erythematosus, hepatobiliary disease, and cytopenias, which disappear with the clearance of maternal autoantibodies. The most severe presentation is a total atrioventricular heart block, which begins during the second trimester of gestation and is irreversible. The risk of having a child with neonatal lupus erythematosus in mothers who test positive for autoantibodies to Sjögren’s syndrome autoantigens is approximately 2% for first pregnancies or if previous babies were healthy. The risk increases by approximately tenfold if a previous child had neonatal lupus erythematosus syndrome. The diagnosis of neonatal lupus erythematosus is made when the mother has autoantibodies to Sjögren’s syndrome autoantigens, and the fetus or newborn develops atrioventricular heart block, or the newborn develops the typical rash or hepatic or hematologic manifestations in the absence of other explanation. Fetal echocardiography from the 16th to the 26th week of gestation is advised in mothers with autoantibodies to Sjögren autoantigens. The detection of a slow fetal heart rate or the postnatal diagnosis of atrioventricular heart block warrants immediate maternal testing for these autoantibodies if not previously tested.

Very late antigen (VLA) expression in various forms of epidermolysis bullosa simplex

SummaryThe very late antigen (VLA) glycoproteins are a family of adhesion membrane receptors involved in cell-cell and cell-matrix interactions. In order to investigate the expression of these molecules in inherited epidermolysis bullosa (EB), we studied the reactivity of monoclonal antibodies directed against VLA-1, -2, -3, -4, -5, and -6, and VLAΒ receptors in skin sections from patients affected by several types of EB simplex (EBs) using indirect immunofluorescence. Skin samples were obtained from six patients with generalized type (Koebner), one patient with localized type (Weber-Cockayne) and one patient with Dowling-Meara EBs type and also from two normal controls. No significant modification of the expression of these adhesion receptors was observed. Anti-VLA-2 and anti-VLA-3 stained the whole cytoplasmic membrane of basal keratinocytes and allowed the detection of focal areas of cytolysis in unblistered skin from the Koebner and Dowling-Meara type. In Koebner type blisters anti-VLA-3 stained the cell remnants at the roof of the blister with a linear staining along the epidermal basement membrane on the dermal side. In Dowling-Meara type blisters anti-VLA-3 also stained cell remnants at the bottom of the cavity. Anti-VLA-6 stained the bottom of the blister cavity with the same distribution of bullous pemphigoid serum but with a stronger and more constant reactivity. Our data show that anti-VLA-3 and anti-VLA-6 can usefully be utilized in diagnostic immunomapping studies of EBs.

Plaque-type glomuvenous malformations in a child

In July, 2014, a healthy 1-month-old boy attended for evaluation of lesions on his back that had been present since birth. He had no relevant family history. On examination he had pink plaques on his back with central bluish colouration and depression and some prominent ectatic vessels, surrounded by a dusky halo (fi gure). The plaques were soft, poorly compressible, painless, and more prominent during crying. Musculoskeletal examination was normal, as were blood count, liver enzymes, renal function, and coagulation. The plaques were consistent with a vascular malformation. In infancy, such diff use skin lesions usually result from venous malformations. Common venous malformations usually aff ect the muscles and joints of the lower limbs, head, and neck. Blue rubber bleb naevus syndrome usually aff ects the upper limbs and trunk and is associated with gastrointestinal lesions. Glomuvenous malformations aff ect the limbs and back, with no extracutaneous involvement. Unlike common venous malformations and blue rubber bleb naevus, glomuvenous malformations have a hyperkeratotic cobblestone-like appearance, are not completely emptied by compression, and tend to become painful. Total body MRI showed several varicosities in the subcutaneous tissue of the back but no extracutaneous lesion. The diagnosis of glomuvenous malformation was confi rmed by examination of a biopsy sample, which showed dilated and irregular vascular channels lined by layers of glomus cells that stained positively for smooth muscle α-actin (fi gure). Laser therapy at 6 months old greatly reduced the lesions in size and colour. At last follow-up in March, 2015, the baby was well and had no new lesions. Plaque-type glomuvenous malformation can be sporadic or familial. Relatives of the aff ected individual often have minor lesions, such as one small nodule. The plaques usually appear during the fi rst month of life, grow rapidly, and enlarge to involve adjacent areas, although new lesions can present at diff erent sites during development or after trauma in previously unaff ected areas. Plaque-type glomuvenous malformations are limited to the skin, but can be a cause of concern to parents and are often a diagnostic challenge for physicians.

Psoriasiform cutaneous leishmaniasis

A 54-year-old Caucasian man was admitted to our Institute because of a lesion located on the right elbow. The patient stated that he was in good general health and was not taking any drugs. He also stated that the lesion had appeared approximately 9 months earlier, when he was living in the United Arab Emirates. Before admission to our Institute, the patient was examined in two different hospitals, and a clinical diagnosis of psoriasis was made. Furthermore, he was unsuccessfully treated with topical calcipotriol, tacalcitol and hydrocortisone butyrate. Dermatological examination showed the presence of an erythematous-infiltrated lesion, covered by scaling and crusts, round, 9 cm in diameter, red in color, and with well-defined borders (Fig. 1). The lesion was asymptomatic. Similar lesions were not observed elsewhere. General physical examination did not show anything pathological. Laboratory and instrumental examinations were within normal ranges or negative. Cytological, bacteriological and mycological examinations were negative. The patient was subjected to a biopsy. A histopathological diagnosis of cutaneous leishmaniasis was made (Fig. 2). A typical rose-like (“rosetta”) appearance of Leishmania spp. was observed on Novy-MacNeal-Nicolle medium (Fig. 3). Polymerase chain reaction (PCR) was positive for Leishmania tropica. The patient was treated with intralesional and i.m. Nmethylglucamine antimonate (100 mg/kg/day for 3 weeks), with complete remission of the lesion in approximately 8 weeks. No recurrences were observed in the 12-month follow up.

Management of Syndromes Related to Infantile Hemangiomas

While localized infantile hemangiomas (IHs) are often benign, except when they are located near a noble structure such as the airways or the orbital area, segmental IHs may be associated with birth defects. These cases should be very carefully studied for life-threatening conditions (heart failure, respiratory distress), functional risks (amblyopia, swallowing disorders, digestive and renal alterations, etc.), aesthetic risks (especially IHs of the face), and painful ulcerations. PHACE is an acronym indicating a disorder characterized by the association of posterior fossa malformations, hemangiomas, arterial anomalies, coarctation of the aorta and other cardiac defects, and eye abnormalities. Indeed the ISSVA’s classification separates clearly vascular tumors (the group that includes IHs) from vascular malformations, indicating, at the same time, that errors in angiogenesis or vasculogenesis that occur in embryonic phase may lead to stable lesions (i.e., vascular malformations) but, quite obviously, not to proliferative lesions (i.e., IHs). From this starting point, it was conceptually clear that vascular tumors and vascular malformations could not be present in the same individual, unless by chance. However, despite the fact that the etiopathogenesis of most vascular anomalies is still unknown, the description of many cases of PHACE syndrome and, in parallel, the description of LUMBAR/PELVIS/SACRAL syndrome in other patients, make likely that a pathogenic noxa can provoke either vascular tumors or vascular malformations in the same individual.

Beta-blockers for hemangiomas.

Infantile hemangiomas (IHs) are the most common tumors in infancy. Their typical natural history is characterized by an early rapid growth in the first months of life and by a slow spontaneous involution in the first years of life. Even though spontaneous regression of IHs could suggest therapeutic abstention, systemic treatment is the therapy of choice in many patients in which these situations occur: 1) rapid growth of IHs; 2) location of IHs in aesthetically critic areas; 3) recurrent hemorrhages, ulcerations or infections of IHs; 3) IHs interfering with important physiological functions (breathing, feeding, vision, hearing, etc.); 4) large or multicentric IHs that can cause heart failure. Since 2008, systemic administration of propranolol, an old non‑selective β‑blocker, was found, serendipitously, to improve the treatment of IHs replacing older and more dangerous therapies like oral steroids, vincristine, interferon‑alpha or vascular lasers. At present, oral propranolol has dramatically changed the approach of IHs because its efficacy is almost 100% and its action is rapid, without important side effects. The formal approval by FDA and EMA has been obtained in Spring 2014.

Altered expression of a new antigen of the dermal-epidermal junction (NU-T2 DEJ Ag) in junctional epidermolysis bullosa

NU-T2 antigen (Ag) is a new and recently described antigen of the dermal-epidermal junction, recognized by an anti-CD1b monoclonal antibody denominated NU-T2. We studied NU-T2 Ag expression in junctional epidermolysis bullosa (13 patients) and in other forms of hereditary epidermolysis bullosa (23 patients), comparing the results with nicein expression. In junctional epidermolysis bullosa gravis type no differences were found between the expression of NU-T2 and nicein, both being negative in bullous as well as in non-bullous skin. Interestingly, in mitis type junctional epidermolysis bullosa, NU-T2 Ag was found to be absent or reduced in five of six patients both in lesional and in uncleaved skin. When compared with nicein expression, clearcut differences were found, further suggesting that these two antigens are different. These data confirm that NU-T2 Ag is a novel epitope of the dermal-epidermal junction, probably relevant in dermal-epidermal cohesion, and it could be responsible, together with nicein, 19-DEJ-1 and other adhesion molecules, for the different subtypes of junctional epidermolysis bullosa. Finally, NU-T2 monoclonal antibody is a new relevant tool for the diagnosis, classification, and prenatal diagnosis of junctional epidermolysis bullosa.