Granulomatous reactions after injections of multiple aesthetic micro-implants in temporal combinations: a complication of filler addiction.

BACKGROUND: Granulomatous reaction is a well-known complication following soft filler procedures. However, the diagnosis of filler-induced granulomas may be challenging because of the occasional reluctance of patients to report the previously performed aesthetic procedure. OBJECTIVE: To describe a new clinical situation in which some patients, in the quest for physical perfection, become addicted to multiple sequential cosmetic injections, increasing the risk of adverse reactions. METHODS: We describe three women who developed diffuse facial nodular tumefaction after multiple procedures of filler injections into their face that occurred at different times in the previous years. RESULTS: Histopathology showed a granulomatous reaction including different combined substances that were identified with different types of micro-implants in the same biopsy. CONCLUSIONS: Excessive demand of multiple cosmetic injections may increase the frequency of skin granulomatous reactions and can be included in the spectrum of similar addictive dysmorphophobic behaviours. Histopathology is the best mean to achieve the diagnosis.

Diffuse dermal angiomatosis: a clinical mimicker of vasculitis associated with calciphylaxis and monoclonal gammopathy.

Diffuse dermal angiomatosis is a form of cutaneous reactive angiomatosis characterized clinically by painful erythematous or violaceous lesions with ulcers that may mimic cutaneous vasculitis/vasculopathy. Histologically it shows a benign, diffuse proliferation of endothelial cells with tiny blood vessels in the papillary and reticular dermis. Herein, we report four patients with diffuse dermal angiomatosis in the setting of calciphylaxis and monoclonal gammopathy and review the cases previously published in the literature. Comorbidities and management will also be discussed.

Tinea atypica.

Although usually simple, the diagnosis of dermatophyte infection is sometimes neglected. Variations in clinical presentation (tinea atypica), mimicking other skin diseases depend on many factors, partially due to the dermatophyte's characteristics, and a combination of patient's pathological but often physiological conditions, such as excessive washing or sun exposure. The physician's misdiagnosis and eventual prescription of steroids or other incongruous treatments further induce pathomorphosis (tinea incognito), longstanding disease and delayed recovery. This review describes the morphology of some atypical dermatophyte infections, in an attempt to compare and correlate changes to the normal features of the disease by site of involvement. The risk factors and predisposing conditions are also analysed to provide a reasoned interpretation of morphology and therefore evoke the diagnostic suspect in atypical cases. Periodical training is the clue to improve dermatologist expertise in what is the first-sight ability to make a diagnosis, perform the correct assessments and consequent therapy in daily practice.

Cutaneous adverse drug reactions to allopurinol: 10 year observational survey of the dermatology department--Cagliari University (Italy).

BACKGROUND: Allopurinol is extensively prescribed for conditions associated with urate excess, despite being responsible for severe cutaneous adverse drug reactions (ADR). OBJECTIVE: A cross-sectional survey of allopurinol cases observed at the main Dermatology Department with inpatients facilities in southern Sardinia. (approx 560,836 inhabitants). MATERIAL AND METHODS: Data collection of all consecutive patients referred for ADR between 2001 and 2010. Causality assessment followed the WHO Collaborating Centre for Drug Monitoring criteria; illness severity score was adopted for toxic epidermal necrolysis (SCORTEN). RESULTS: Allopurinol was the culprit drug in 84 of 780 cutaneous ADR cases (10.7%; 8.4 cases/year). Mean age was 74 years, 58% of the patients were female, 95% of patients required hospitalization. Clinical forms were maculo-papular eruptions (34 cases), Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (31 cases), vasculitis (six cases), Drug Rash Eosinophilia and Systemic Symptoms (DRESS) (three cases), Acute Generalized Exanthematous Pustolosis (AGEP) (three cases), Pityriasis rosea-like eruption (three cases), lichenoid dermatitis (two cases), fixed drug eruption (one case), erythroderma (one case). The indication for allopurinol prescription was asymptomatic hyper-uricemia in 95% of the patients. Twelve patients were under allopurinol dosage adjustment according to creatinine clearance. Final causality assessment was definite for 12% of the cases and probable for the remaining 88%. Full recovery was achieved in 88% of subjects; ten SJS/TEN patients died (12% overall mortality; 32% mortality of the SJS/TEN cases). CONCLUSION: Considering the populations size of Southern Sardinia, is plausible that 1.5/100,000 Sardinian will be affected by allopurinol related ADR per year. Advanced age, and inappropriate allopurinol prescription were the main conditions affecting morbidity and mortality.

Upper eyelid necrosis and reconstruction after spider byte: case report and review of the literature.

Spider bites are not very common, especially in the Mediterranean area, and those affecting the ocular-palpebral region involving reconstructive surgery are particularly rare. In May 2010, the case of a Caucasian 24-year-old female patient was brought to the attention of the Dermatology Department, University of Cagliari, Italy. The patient reported she woke up feeling an intense pain with itching and that also she had noticed a spider of an unknown species on her bed. The dermatosis had affected the right orbital region, where there was a considerable red and violet erythema and a hard edema, not foldable. When the necrosis appeared the patient was treated at the Plastic Surgery Unit where she underwent a reconstruction of the eyelid with a full thickness skin graft from the retroauricular area. The post-operative course was regular with a perfect in-take of the skin graft. When the patient was discharged she was sent to an Entomological University Centre to identify the spider species and the possible venom which caused the skin lesion. The spider which caused the injury has been a Loxosceles rufescens (Dufour, 1820). Loxoscelism is a necrotic arachnoidism caused by the poisonous bite of spiders belonging to the Loxosceles species. It is very important to identify what sort of lesion it is and to treat it in a combined way in order to choose the proper timing for surgery to avoid damages to the eyelid functioning.

A case of bullous pemphigoid in infancy treated with local corticosteroids.

Bullous pemphigoid (BP) is an immune-mediated subepidermal vesiculobullous eruption, whose true incidence is unknown, but it is considered extremely rare in children, with a usually indolent course and rare relapses. Diagnosis is often belated, because of the invasive assessment with biopsy for typical immune-pathologic findings to differentiate it from Dermatitis Herpetiformis and Linear IgA bullous dermatosis (LABD), more common in children. A 4-year-old girl presented with one year history of erythematous-edematous and erythematous-bullous eruptions on the genitalia, periocular regions, dorsal and palmo-plantar surfaces. At onset erosions of the month and lips where considered a primary herpes simplex infection from the pediatrician, but repeated courses of systemic antivirals were completely ineffective, while application of a antibiotic-steroidal cream was of partial benefit. Histopathology showed a dermo-epidermal blistering, with a marked eosinophilic infiltrate. Direct immunofluorescence showed a characteristic positive linear IgG and C3 band at the basement membrane zone (BMZ). Complete hematic-chemical and instrumental examinations gave normal results, excluding associated pathologies. Due to paucity of lesions and good response to local treatment with moderate potency cortisones, in agreement with the parents, no systemic therapy was started. No recurrence occurred in the 2 year follow-up after complete remission. The case is reported for the rarity of the childhood form, and the importance of the differential diagnosis for management and treatment. Good response to topical treatment is stressed, avoiding the risks of long-term systemic drug administration.

Clinical outcome evaluation following cyclosporine a treatment in moderate to severe psoriasis: a retrospective study.

This retrospective study was conducted on 193 patients treated in three Italian Psoriasis Units with the aim of evaluating the evolution of psoriasis severity and the safety of cyclosporin A (Sandimmun Neoral) in moderate to severe psoriasis, at the regimens usually employed in common clinical practice. Cyclosporin A (CyA) was administered for a mean period of 14 months, the mean number of treatment courses was 1.6 (range 1-4), and the mean dosage ranged from 1.5 to 3.1 mg/kg/die. Ninety percent of patients obtained complete therapeutic success or clinical remission, defined as complete clearance of lesions or clearance of lesions with residual minor pigmentations respectively, when treated with CyA in monotherapy. The mean Psoriasis Area and Severity Index (PASI) decreased from 23.31 before CyA administration to 5.64 at the end of treatment. The clinicians judgement on CyA tolerability was good/very good in 90 percent of cases. Adverse events occurred in 36 percent of patients, with hypertension being the most commonly reported (17.6 percent). The results of this study indicate that in the common clinical practice CyA in moderate to severe psoriasis is usually employed at low doses, resulting both safe and effective.

Immunoreactivity for alpha-smooth muscle actin characterizes a potentially aggressive subgroup of little basal cell carcinomas.

Basal cell carcinoma (BCC) is a very common malignant skin tumor that rarely metastatizes, but is often locally aggressive. Several factors, like large size (more than 3 cm), exposure to ultraviolet rays, histological variants, level of infiltration and perineural or perivascular invasion, are associated with a more aggressive clinical course. These morphological features seem to be more determinant in mideface localized BCC, which frequently show a significantly higher recurrence rate. An immunohistochemical profile, characterized by reactivity of tumor cells for p53, Ki67 and alpha-SMA has been associated with a more aggressive behaviour in large BCCs. The aim of this study was to verify if also little (<3 cm) basal cell carcinomas can express immunohistochemical markers typical for an aggressive behaviour.

Effect of hyperosmotic stimulation on aquaporins gene expression in chick kidney.

Birds can produce hyperosmotic urine, but their renal morphology differs from that of mammals. Recent studies in mammals, suggested that various aquaporins (AQPs) are present in the kidney and play crucial roles in urine production. To elucidate the role of AQPs in the avian kidney, we first examined for the presence of AQP1, 2, 3, 4, 7 and 9 mRNAs in the chick (Gallus gallus) kidney by RT-PCR analysis. Next, we quantified variations of AQPs mRNAs levels in chick kidney after hyperosmotic stimulation (water-deprivation or salt-loading) by real-time RT-PCR analysis. Our study showed that in addition to AQP1, 2, 3, 4 and 7, chick kidney also expressed AQP9 and that hyperosmotic stimulation induced changes in AQPs expression. In particular, water-deprivation increased AQP2 and AQP3 mRNAs levels, whereas salt-loading induced a significant increase in AQP1, AQP2 and AQP9 mRNAs levels. AQP4 and AQP7 mRNA levels were not affected by any hyperosmotic stimulation. Taken together, these results indicated that the presence of AQPs in chick kidney is similar to that in mammals, that the chick kidney has an additional AQP9 and that AQP1, 2, 3 and 9 may play a crucial but different role in water permeability in this organ.

Enzyme-linked immunosorbent assay in autoimmune blistering diseases: preliminary experience of the Dermatology Department of Cagliari.

AIM: Recent insights on the pathogenesis of autoimmune blistering diseases have pointed out the opportunity of new diagnostic tools, such as enzyme-linked immunosorbent assay (ELISA) for Desmogleins 3 and 1 (Dsg3, Dsg1), and bullous pemphigoid (BP) 180 antigen auto-antibodies. The aim of the present prospective study was to evaluate the diagnostic values of these tests in blind with histopathology and direct immunofluorescence (DIF), the assessment of correlation with clinical presentation and severity of disease, as well as eventual modifications of serum auto-antibodies titres in course of treatment. METHODS: From June 2005 to June 2007, all consecutive patients with clinically blistering diseases presenting to the Dermatology Department of Cagliari were enrolled in the study. Biopsy specimens were performed in all cases and sent for histopathological examinations including haematoxylin-eosin stain and DIF to the Unit of Pathological Anatomy of the same University. Serum samples were tested with Dsg3, Dsg1 and BP180 ELISA in the internal laboratory of the Dermatology Department, and results were worked out many days before histopathology reports. Final diagnosis was established on clinical, histological and immunopathological findings. A selected sample of patients with active autoimmune blistering disease underwent repeated immunosorbent assays at 1-2-6 months from first diagnosis and treatment introduction. RESULTS: Forty-two patients (23 men, 19 women) were enrolled in the study and divided into three groups: pemphigus (N=17), pemphigoid (N=19) and other diseases (OD; N=6), depending on the final diagnosis assessed by histological, immunopathological and serological examinations. In pemphigus group ELISA showed circulating antibodies against Dsg3 in all patients (100%) and against Dsg1 in 13 patients (76.5%). In the pemphigoid group, 16 of 19 sera showed positive scores above the cut-off value (84.2%), but sensibility was higher if considering only the bullous pemphigoid final diagnosis (16/17). None of the other bullous diseases (0%) exceeded the cut-off value for Dsg1, Dsg3 and BP180 ELISA. Correlation with histopathology and direct immunofluorescence was excellent for pemphigus and very good for pemphigoid. Eight patients (6 P; 2 BP) underwent a serial measurement of the autoantibodies levels: two patients (1 PV and 1 BP) showed an ELISA antibodies titres decrease after two months of treatment, in parallel with an excellent clinical response. Whereas in six cases (5 PV and 1 BP) the ELISA titres overstayed high at I and II month. Clinically the disease was active in all six patients, and a treatment adjustment was performed (increased corticosteroid dosage and/or azathioprine initiation in all cases, high dose intravenous immune globulin in one case). At month VI, a decrease on ELISA antibody levels was documented in three patients (3 PV), parallel to a clinical remission. Whereas in other three patients (2 PV, 1 BP), persistent high Dsg3 ELISA titres were related to a still active disease: although clinically improved, blisters flared up at any attempt to taper drugs dosage. CONCLUSION: Dsg3, Dsg1 and BP ELISA is a sensitive, easy and quick reading tool for the diagnosis of the main autoimmune blistering diseases: pemphigus and bullous pemphigoid. More over, autoantibodies titre correlate with disease severity, and is useful to monitor treatment response.

Anatomical and neurochemical definition of the nucleus of the stria terminalis in Japanese quail (Coturnix japonica).

This study in birds provides anatomical, immunohistochemical, and hodological data on a prosencephalic region in which the nomenclature is still a matter of discussion. In quail, this region is located just dorsal to the anterior commissure and extends from the level of the medial part of the preoptic area at its most rostral end to the caudal aspects of the nucleus preopticus medialis. At this caudal level, it reaches its maximal elongation and extends from the ventral tip of the lateral ventricles to the dorsolateral aspects of the paraventricular nucleus. This area contains aromatase-immunoreactive cells and a sexually dimorphic population of small, vasotocinergic neurons. The Nissl staining of adjacent sections revealed the presence of a cluster of intensely stained cells outlining the same region delineated by the vasotocin-immunoreactive structures. Cytoarchitectonic, immunohistochemical, and in situ hybridization data support the notion that this area is similar and is probably homologous to the medial part of the nucleus of the stria terminalis of the mammalian brain. The present data provide a clear definition of this nucleus in quail: They show for the first time the presence of sexually dimorphic vasotocinergic neurons in this region of the quail brain and provide the first detailed description of this region in an avian species.

Topographical distribution of reduced nicotinamide adenine dinucleotide phosphate-diaphorase in the brain of the Japanese quail.

The distribution of reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase activity was histochemically investigated in the Japanese quail brain. This enzyme is now considered responsible for the synthesis of nitric oxide, a novel neural messenger whose distribution has not been described in the avian brain until now. The histochemical technique provides a simple and reliable method for staining selected populations of neurons throughout the avian brain. In the telencephalon several regions showed heavily stained NADPH-diaphorase positive neurons and processes. In particular the paleostriatal-paraolfactory lobe complex showed the greatest presence of both positive cells and processes. Neurons and processes were also observed in several regions of the hyperstriatum as well as in the archistriatal nucleus taeniae. Some regions, such as the ectostriatum and the hippocampus, had no positive elements. In the diencephalon, the magnocellular hypothalamic system, which in mammals shows NADPH-diaphorase activity, did not show any particular accumulation of reaction product. On the contrary, retinorecipient areas, such as the visual suprachiasmatic nucleus and the lateral geniculate complex, displayed a composite structure of both positive neurons and processes. The brainstem revealed a large NADPH-diaphorase positive population extending through the tegmental nuclei to the locus coeruleus and subcoeruleus. A complex organization was also observed in the optic lobe, where fusiform elements were distributed within the stratum griseum and superficialis of the tectum. In the medulla, a dense terminal field was observed at the level of the nucleus of the solitary tract, whereas scattered neurons were located within the reticular nuclei. Although the staining of neurons and tracts was highly selective, the positive cells did not correspond to any single known neurotransmitter, neuropeptide, or neuroactive molecule system. Several sensory pathways were heavily stained for the NADPH-diaphorase, including part of the olfactory, visual, and auditory pathways. The findings of the present study reveal that the NADPH-diaphorase-containing systems in the avian brain are organized according to a pattern comparable, because of its complexity, to that observed in mammals. However, important interspecific differences suggest that this novel neural system might be involved in diverse tasks.

Mapping of neurochemical markers in quail central nervous system: VIP- and SP-like immunoreactivity.

The distribution of cells and fibres containing vasoactive intestinal polypeptide (VIP) and substance P (SP) was investigated in the brain of Japanese quail focussing on the centers involved in reproductive activities. SP-immunoreactive (ir) structures were chiefly present within the ventral telencephalic regions, the periventricular hypothalamus and the dorsal aspects of thalamus. VIP immunopositive structures were rarely associated with recognizable nuclei and they were observed in the organum septi laterale (LSO), the lobus paraolfactorius (LPO), the eminentia mediana (ME), the nucleus striae terminalis (nST) and the area ventralis of Tsai (AVT). SP- and VIP-ir structures were both associated with regions implicated in the control of reproduction. SP was mainly distributed within regions that control male copulatory behavior (the preoptic region, the anterior hypothalamus and the central gray), whereas VIP was prevalently located in the mediobasal hypothalamus that is implicated in the control of female reproductive activities.

Distribution and effects of testosterone on aromatase mRNA in the quail forebrain: a non-radioactive in situ hybridization study.

A number of studies have been devoted to the analysis of the anatomical distribution, control by steroids and functional significance of aromatase (the enzyme metabolizing testosterone into 17beta-estradiol) in the quail brain. In particular, the sexually dimorphic nucleus preopticus medialis has been the main focus of investigation because testosterone aromatization in this structure mediates the activation of male sexual behavior and aromatase activity is itself testosterone-dependent in this nucleus. No information on the anatomical distribution of aromatase gene expression is, however, available so far in this avian species. In the present study we applied a non-radioactive in situ hybridization technique to describe the distribution of aromatase mRNA containing neurons in the quail prosencephalon. We also analyzed, at a neuronal level of resolution, the induction by testosterone of this mRNA in the medial preoptic nucleus. Dense clusters of aromatase gene expressing neurons were observed within the medial preoptic nucleus, the nucleus of the stria terminalis, the ventro-medial hypothalamus and the tuberal region. Scattered neurons expressing lower levels of aromatase mRNA were also found in the dorsal thalamic area and central gray. The specificity of the staining was confirmed by demonstrating the absence of signal in sections that had been hybridized with a sense probe. Moreover, the distribution of the aromatase mRNA containing cells completely overlapped with the distribution of the aromatase-immunoreactive cells. Aromatase-mRNA expression was controlled by testosterone (or its metabolites) in the entire medial preoptic nucleus. Castration resulted in a decrease in the number of aromatase mRNA-containing cells and this effect was totally reversed by testosterone treatment. These data further support the idea that testosterone regulates the rate of its own aromatization by modulating the expression of aromatase rather than by acting at a post transcriptional level.

Sexual differences and effect of photoperiod on melatonin receptor in avian brain.

Several data suggest that melatonin may influence avian reproduction by acting at the level of the hypothalamic-hypophisial-gonadal axis, and/or on neural circuits controlling reproductive behaviours. The action of melatonin is exerted through specific receptors whose distribution and pharmacological properties have been extensively investigated. This review will focus on the distribution, sexual dimorphism, and dependence upon the photoperiod of melatonin binding sites in avian species with a special emphasis on Japanese quail. Melatonin receptors are widely distributed in avian brain. They are mostly present in the visual pathways of all the investigated species and in the song controlling nuclei of oscine birds. Sexual dimorphism of melatonin binding sites (higher density in males than in females) was detected in some telencephalic nuclei of songbirds, in the visual pathways, and in the preoptic area of quail. The last region plays a key role in the activation of male quail copulatory behaviour and it hosts a large population of gonadotropin-releasing hormone-containing neurons. Sexual dimorphism of melatonin-binding sites in the above-mentioned regions suggests a differential role for this hormone in the modulation of visual perception, gonadotropin production, and seasonally activated behaviours in male and female quail. Further studies are necessary to understand interrelationships among photic cues, gonadal steroids, density, and sexually dimorphic distribution of melatonin receptors.

Vasotocinergic innervation of sexually dimorphic medial preoptic nucleus of the male Japanese quail: influence of testosterone.

The distribution of vasotocin (VT)-immunoreactive (IR) fibers was described in the preoptic and septal regions of the male quail brain. The density of VT-IR fibers was measured in the sexually dimorphic preoptic nucleus (POM) and lateral septum (SL) of adult male quail (Coturnix japonica) by means of quantitative image analysis. Experimental manipulations of the hormonal environment in the peripubertal period influenced this distribution. In both regions, the VT immunoreactivity was reduced or absent when males were castrated. The immunoreactivity was restored to its original level in castrated males by Silastic implants of testosterone. These changes were anatomically specific as evidenced by the fact that the density of VT fibers did not vary in the hypothalamo-neurohypohysial tract as a function of the endocrine condition of the subjects. No change was also observed in the number of VT-IR cells in the periventricular region close to the POM. Previously published data show that VT or its mammalian homolog, vasopressin are implicated in the control of a wide range of instinctive behaviors. The steroid-dependent VT afferents to the POM, a key area controlling male copulatory behavior in quail could therefore be involved in the control of the sexual behavior in this species. The outputs of the POM which contains steroid-receptors could therefore be modulated by steroids in two different ways: directly through the steroid receptors it contains and indirectly through its steroid-sensitive peptidergic afferents.

The density of melatonin receptors is dependent upon the prevailing photoperiod in the Japanese quail (Coturnix japonica).

Two groups of Japanese quail (Coturnix japonica) were exposed to two different photoperiods (short and long days: LD 8:16 and LD 16:8, respectively), and their brains examined for the presence and distribution of melatonin receptors by means of quantitative in vitro autoradiography. Animals belonging to the LD 8:16 group expressed a significantly higher melatonin receptor density in the optic tectum and nucleus triangularis, while the LD 16:8 animals had a higher density of receptors in the hyperstriatum and nucleus preopticus dorsalis. These data demonstrate an apparent influence of the photoperiod on the density of melatonin receptors, especially in nuclei of the tectofugal pathway, related to the control of visual pattern and intensity discrimination, localization and orientation.

Distribution and characterization of melatonin receptors in the brain of the Japanese quail, Coturnix japonica.

2-[125I]iodomelatonin was used to study the distribution and properties of the melatonin receptor in the Japanese quail brain. High receptor density was detected in the major targets of direct retinal input (optic tectum, nucleus of the optic basal rout, ventrolateral geniculate nucleus), as well as areas representing terminals in the visual pathways (nucleus rotundus, ectostriatum, thalamo-hyperstriatal pathway). Binding was also found in the piriform cortex, the hypophyseal pars tuberalis, the oculomotorius nucleus and the associated Edinger-Westphal nucleus, and in the nuclei of the third, fourth and sixth cranial nerves. A comparison of the receptor pharmacological profile to that of the mammalian brain demonstrated pharmacological identity of the two binding sites. In the saturation experiments, GPT gamma S decreased the binding affinity, numerical Kd values increasing from approximately 35 pM to approximately 150 pM.

Forebrain Fos responses to reproductively related chemosensory cues in aromatase knockout mice.

Sexually relevant pheromonal cues are detected by the vomeronasal system which includes the posterodorsal part of the medial amygdala, the posteromedial part of the bed nucleus of the stria terminalis and the medial preoptic area. Copulatory behavior is impaired in mice lacking functional aromatase, the enzyme converting testosterone into estradiol. In this study, we used male aromatase knockout (ArKO) mice to investigate the role of aromatase in the differentiation and activation of preference for male- or female-related odorants. Moreover, using Fos immunoreactivity as a marker of neuronal activation we investigated the ability of sex-related pheromonal cues to activate the vomeronasal system. Both gonadally intact wild-type and ArKO mice preferred to investigate urine from females. The lack of estrogens did not reverse odor preferences, i.e. male ArKO mice did not show a preference for male odors. Exposure to soiled bedding from females induced Fos-protein in the posterodorsal part of the medial amygdala, in the posteromedial part of the bed nucleus of the stria terminalis, and in the periventricular part of the medial preoptic area of both the genotypes. Exposure to soiled bedding from intact males induced Fos in the posterodorsal part of the medial amygdala in wild-type mice and in the periventricular medial preoptic area in wild-type and ArKO mice. These results suggest that preference for female-related odors and the Fos-mediated activation of the vomeronasal system do not rely on estradiol. Furthermore, sensitivity to female chemosensory cues and copulatory behavior are uncoupled in this knockout model.