Brodalumab for the treatment of moderate-to-severe plaque-type psoriasis: a real-life, retrospective 24-week experience.

BACKGROUND: Brodalumab was efficacious and safe in moderate-to-severe plaque-type psoriasis in the AMAGINE trials; published reports under real-life conditions are limited. OBJECTIVES: To evaluate the effectiveness and safety of brodalumab in patients with moderate-to-severe plaque-type psoriasis in a real-world setting. METHODS: This observational, retrospective study enrolled adult patients (≥18 years) with moderate-to-severe plaque-type psoriasis who underwent 24 weeks of treatment with brodalumab at 17 Italian dermatological centres. Baseline data included demographics, comorbidities, age of onset and duration of psoriasis and previous treatments. Psoriasis Area and Severity Index (PASI), Physician Global Assessment (PGA), static PGA of Genitalia, Dermatology Life Quality Index and patient satisfaction were assessed at weeks 0, 4, 12 and 24; adverse events were recorded. RESULTS: Seventy-eight patients (mean age 47.9 years, 71.8% male, average disease duration 16.8 years) were enrolled. A rapid and significant reduction in mean PASI score was observed after 4 weeks of treatment, decreasing further at weeks 12 and 24 (all P < 0.0001 vs. baseline). A higher number of cardiometabolic comorbidities and previous therapies were negatively associated with the achievement of PASI 90 at all assessments. Brodalumab was effective in bio-experienced patients, including those who had failed on anti-interleukin (IL)-17 therapies. Quality of life and patient satisfaction increased significantly during treatment (P < 0.0001 and P < 0.01 vs. baseline, respectively). Treatment was interrupted in 9 (11.5%) patients due to adverse events (n = 4), lack of efficacy (n = 3), lost to follow-up (n = 1) and surgical procedure (n = 1). CONCLUSIONS: Brodalumab is effective and safe in the treatment of moderate-to-severe psoriasis in a real-world setting, including in patients with failure to anti-IL17 therapies.

HIDRAdisk: validation of an innovative visual tool to assess the burden of hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, relapsing, inflammatory skin disease characterized by painful inflamed nodules, recurrent abscesses and fistulas located in apocrine gland-bearing body sites. The negative impact of HS on patient's quality of life (QoL) has been reported to be greater than other dermatologic conditions as psoriasis and atopic eczema, and its improvement is an important goal in disease management. Nowadays, there are no specific validated QoL instruments available for HS and generic dermatologic questionnaires are used. OBJECTIVE: The objective of this study was to demonstrate the validity, reliability and responsiveness of HIDRAdisk, a new innovative tool designed for rapid assessment of HS burden and, at the same time, an intuitive graphic visualization of the measurement outcome. METHODS: A multicentre, longitudinal, observational study was conducted to validate the HIDRAdisk compared with other validated questionnaires [Skindex-16, Dermatology Life Quality Index (DLQI), Work Productivity and Activity Impairment-General Health (WPAI:GH)] and to evaluate its correlation with disease severity in Italian patients with any degree of HS severity, as measured by Hurley stage and HS Physician Global Assessment (HS-PGA). RESULTS: A total of 140 patients (59% women; mean age 34.9 ± 11.0 years) were enrolled in 27 dermatologic centres. HIDRAdisk showed a strong correlation with Skindex-16 and DLQI, and a good one with WPAI:GH (correlation coefficient: 0.7568, 0.6651 and 0.5947, respectively) and a statistically significant correlation with both Hurley stage and HS-PGA. Very good internal consistency (Cronbach coefficient >0.80; intraclass correlation coefficient >0.6), with correlation between the 10 items, good test-retest reliability (Spearman correlation coefficient, 0.8331; P < 0.0001) and responsiveness to changes were demonstrated. CONCLUSION: Our study shows that HIDRAdisk, a short and innovative visual HS QoL instrument, has been psychometrically validated in Italian language and it may help improve the management of HS once implemented in routine clinical practice.

Tinea capitis mimicking tufted hair folliculitis.

We report a case of tinea capitis mimicking tufted hair folliculitis in a 56-year-old European man, who presented with a 4-year history of pain and erythema in an area of scarring alopecia of the occipital scalp, with scales and tufts of hair emerging from individual follicles. Histological examination showed hair plugging, and a dense perifollicular infiltrate of plasma cells, lymphocytes, and neutrophils. There was widespread scarring and fibrosis. Bacterial cultures were negative for Staphylococcus aureus, but fungal cultures and periodic-acid-Schiff stain were positive for Trichophyton tonsurans. Videodermatoscopy of the lesion showed a pattern consistent with folliculitis decalvans. Diagnosis was made on the basis of the clinical, histological, microbiological and videodermatoscopy data. After 30 days of systemic antifungal treatment, there were a substantial clinical improvement and disappearance of pain. After 5 months, a residual cicatricial area was seen with some hair tufts emerging from a single orifice.

Pemphigus vulgaris after coxsackievirus infection and cephalosporin treatment: a paraviral eruption?

Pemphigus is an autoimmune disease that results from the interaction between predisposing genetic factors and exogenous agents, mainly drugs and viruses. Herein we report the case of a 66-year-old woman referred to our department for the onset of painful oral erosions and bullous lesions on the torso. Clinical, laboratory and histopathological investigations led to the diagnosis of pemphigus vulgaris. Two weeks before the outbreak of the lesions, the patient had suffered from a viral pharyngitis, subsequently diagnosed as herpangina, and had been taking an oral cephalosporin (cefixime) for 1 week to prevent possible bacterial complications. A relationship between the onset of pemphigus and coxsackievirus infection or cefixime administration or both was supposed. The case may represent a peculiar paraviral eruption, where a predisposing pemphigus-prone genetic background paved the way for the acantholytic autoimmune disorder as a consequence of the combined effect of the coxsackievirus infection and the cephalosporin treatment.

Crohn's disease and skin.

Crohn's disease is a chronic inflammatory bowel disease potentially involving any segment of the gastrointestinal tract. Extra-intestinal manifestations may occur in 6%-40% of patients, and disorders of the skin are among the most common. This manuscript will review skin manifestations associated to Crohn's disease, with a particular focus on lesions associated to anti-tumour necrosis factor therapy.

Helicobacter pylori infection but not small intestinal bacterial overgrowth may play a pathogenic role in rosacea.

BACKGROUND AND AIMS: Recent studies suggest a potential relationship between rosacea and Helicobacter pylori (H. pylori) infection or small intestinal bacterial overgrowth (SIBO), but there is no firm evidence of an association between rosacea and H. pylori infection or SIBO. We performed a prospective study to assess the prevalence of H. pylori infection and/or SIBO in patients with rosacea and evaluated the effect of H. pylori or SIBO eradication on rosacea. METHODS: We enrolled 90 patients with rosacea from January 2012 to January 2013 and a control group consisting of 90 patients referred to us because of mapping of nevi during the same period. We used the (13)C Urea Breath Test and H. pylori stool antigen (HpSA) test to assess H. pylori infection and the glucose breath test to assess SIBO. Patients infected by H. pylori were treated with clarithromycin-containing sequential therapy. Patients positive for SIBO were treated with rifaximin. RESULTS: We found that 44/90 (48.9%) patients with rosacea and 24/90 (26.7%) control subjects were infected with H. pylori (p = 0.003). Moreover, 9/90 (10%) patients with rosacea and 7/90 (7.8%) subjects in the control group had SIBO (p = 0.6). Within 10 weeks from the end of antibiotic therapy, the skin lesions of rosacea disappeared or decreased markedly in 35/36 (97.2%) patients after eradication of H. pylori and in 3/8 (37.5%) patients who did not eradicate the infection (p < 0.0001). Rosacea skin lesions decreased markedly in 6/7 (85.7%) after eradication of SIBO whereas of the two patients who did not eradicate SIBO, one (50%) showed an improvement in rosacea (p = 0.284). CONCLUSIONS: Prevalence of H. pylori infection was significantly higher in patients with rosacea than control group, whereas SIBO prevalence was comparable between the two groups. Eradication of H. pylori infection led to a significant improvement of skin symptoms in rosacea patients.

Common human leukocyte antigen alleles in pemphigus vulgaris and pemphigus foliaceus Italian patients.

Pemphigus refers to a group of autoimmune blistering skin diseases, mainly identified as pemphigus vulgaris and pemphigus foliaceus, both characterized by the presence of autoantibodies against keratinocyte adhesion molecules, leading to loss of cell-cell adhesion with consequent blister formation. Pemphigus vulgaris is reported to be associated with human leukocyte antigen DR4 and/or DR6 whereas no data are available on pemphigus foliaceus, except for the endemic Brazilian form (fogo selvagem), which is reported to be associated with DR1 and DR4. We here report human leukocyte antigen molecular typing on a total of 87 patients, 61 with pemphigus vulgaris and 26 with pemphigus foliaceus, versus 128 healthy matched controls. Generic typing showed an increase of DRB1*04 and DRB1*14 and a decrease of DRB1*07 in both pemphigus vulgaris and pemphigus foliaceus patients. Molecular subtyping of DR4+ and DR14+ subjects showed a highly significant association between the DRB1*1401 and both pemphigus vulgaris (p < 0.0001) and pemphigus foliaceus patients (p < 0.0001) together with a significant increase of the linked DQB1*0503 (pemphigus vulgaris p < 0.0001; pemphigus foliaceus p < 0.0001). Moreover, whereas the association between DRB1*0402 and pemphigus vulgaris (p < 0.0001) has been confirmed, no significant association between a specific allele of the DR4 group and pemphigus foliaceus, has been found. Therefore, at least in Italian patients, pemphigus vulgaris and pemphigus foliaceus share DRB1*1401 and DQB1*0503, as susceptible human leukocyte antigen alleles, whereas DRB1*0402 is only found associated with pemphigus vulgaris. The observation that both diseases, pemphigus vulgaris and pemphigus foliaceus, carry the same susceptible human leukocyte antigen alleles has been interpreted as a common genetic background predisposing to pemphigus as, like in other autoimmune disorders, it is not sufficient to explain the onset of the disease on the basis of the sole aforementioned alleles. Other linked genes and/or environmental factors should play a facilitating role in the outbreak of pemphigus, either pemphigus vulgaris or pemphigus foliaceus.

[Keratoacanthoma centrifugum marginatum. Possible etiological role of papillomavirus and therapeutic response to etretinate]. / Kératoacanthome centrifuge marginé. Rôle étiologique possible d'un papillomavirus et réponse thérapeutique à l'étrétinate.

INTRODUCTION: Keratoacanthoma centrifugum marginatum is an uncommon keratoacanthoma of unknown etiology. We report a case suggesting a possible etiological role for a papillomavirus. Etretinate was an effective treatment. CASE REPORT: A 65-year-old woman had keratoacanthoma centrifugum marginatum of the antero-inferior aspect of the lower third of the right leg for 5 years. Fifteen years earlier, an infection had occurred at the same site after a trauma and was treated by oral antibiotics. Surgical exeresis was difficult due to the wide spread of the lesion. Etretinate given at an initial dose of 1 mg/kg/d for 6 weeks then reduced by half for 2 months led to nearly complete cure. DISCUSSION: Keratoacanthoma centrifugum marginatum, verrucous carcinoma and epidermal carcinoma have some histological characteristics in common, suggesting a possible common etiological agent which could be certain strains of the human papillomavirus (HPV). In our case etretinate provided cure, possibly due to its antitumoral activity and perhaps due to its antiviral activity. The presence of koilocytes suggested HPV infection which was confirmed by PCR. This test does not however provide proof of the etiological role of HPV. We are currently studying the presence of HPV in keratoacanthomas and their possible etiological role.

[Yersinia enterocolitica in fresh and packaged meats]. / Ricerca di Yersinia enterocolitica in carni fresche ed insaccate.

In these last years it was observed an increased frequency of human infections by Y. enterocolitica supported mostly in Europe by serotype 0:3 and 0:9, and by serotype 0:8 in U.S.A. As far as it is concerned the transmission form to man, in addition to the possible infection between men, the one from animal to man and the one consequent on water use, most important suspicions are about foods derived from infected animals or however contaminated by man (fresh or preserved or processed meat, milk and its products; the produce of sea). Y. enterocolitica was isolated from all the animals for slaughter (especially from the swine's pharynx and excrement, where pathogenic serotypes for man were isolated), this ascertainment has led the Authors to research the microorganism in foods of animal kind. It is a facultative anaerobe and this characteristic allows it to survive and multiply also in packed products kept in the refrigerator. For this reason the A.A. carry out a research of Y. enterocolitica on 484 samples of fresh meats and sausages as follows: beef (150 samples), superficial scratching of ox's skeleton (150 samples), minced meat (20 samples), sausages (164 samples). Sausages and beef were bought in some butcher's shops, the other samples were drawn from slaughter-houses of Messina province. The results have pointed out that none of the analysed samples is found contaminated by these microorganisms.

Ulcerative colitis associated with leukocytoclastic vasculitis of the skin.

Ulcerative colitis may be associated with a number of skin lesions such as erythema nodosum and pyoderma gangrenosum. We here describe an unusual case of a 33-year-old-caucasian male with ulcerative colitis and skin lesions diagnosed as leukocytoclastic vasculitis. An initial treatment with oral deflazacort led to little benefit, while treatment with oral mesalazine caused remission of the skin and intestinal manifestations in 2 weeks.

Effects of gemfibrozil on in vitro cultured normal human skin explants.

BACKGROUND: Several lipid-lowering agents, when given topically, show a profound effect on skin morphology. Because of low bioavailability of these drugs for keratinocytes, the incidence is extremely low clinically. The most appropriate way to study the effect of hypolipidemic drugs on keratinocytes is by artificial exposure of the skin to high drug concentrations. OBJECTIVE: To study the effects of gemfibrozil on the morphology of in vitro cultured normal human skin explants. As gemfibrozil induces barrier disruption by inhibiting epidermal sterologenesis, essential for a competent permeability barrier, it is interesting to investigate the morphologic changes associated with this phenomenon. Studying the epidermal changes induced by lipid-lowering agents is important, not only because it might lead to a better understanding of the effects of these drugs on keratinocytes, but as it might also unlock the door to a wider knowledge of the pathomechanism of disorders of cornification. METHODS: Normal human skin from patients undergoing mastectomy was cultured in the presence of 2, 5, and 10 mM of gemfibrozil for 4 days The morphologic changes were evaluated by three blinded observers. Their reports were matched and collated. RESULTS: The cultured skin in the presence of gemfibrozil showed cell crowding of keratinocytes in the lower part of the epidermis, indicating epidermal hyperplasia and increased proliferation. Intercellular edema with the formation of small cavities in the epidermis, intracellular edema, and vacuolar alteration of keratinocytes in the upper portion of the epidermis were also observed. The intensity of these changes tended to parallel the gemfibrozil concentration. Some dermo-epidermal detachments did not correlate with the gemfibrozil concentration, but rather with tissue characteristics peculiar to each explant. CONCLUSIONS: The morphologic changes caused by gemfibrozil to normal human skin were not characteristic of psoriasis, and included intracellular and intercellular edema in the upper portion of the epidermis and cell crowding, indicating epidermal hyperplasia in the lower portion of the epidermis. The present experimental study gives further support to the hypothesis that hypolipidemic drugs cause an initial break in the barrier function of the epidermis, followed by a physiologic epidermal response, aimed at barrier restoration. This rather nonspecific stimulus to epidermal proliferation may trigger psoriasis in predisposed patients.