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.

Achilles tendon ultrasonography may detect early features of psoriatic arthropathy in patients with cutaneous psoriasis.

BACKGROUND: Psoriatic arthropathy is a progressive and debilitating disease involving reduction of functional activity of the articulations with consequent deterioration of the patient's quality of life. The entheses represent the initial site of articular inflammation and the enthesis of the Achilles tendon is the first to be affected. In some patients with psoriasis, enthesitis may not be diagnosed because it is still asymptomatic. OBJECTIVES: To evaluate whether ultrasonography allows early diagnosis in a larger population and to identify significant alterations of enthesitis beyond increased thickness of the Achilles tendon. MATERIALS AND METHODS: The study was undertaken on 59 patients (16 women, 43 men), with chronic plaque psoriasis and 59 patients with other dermopathies. The patients underwent echographic evaluation of the Achilles heel using a Voluson imaging system. The severity of the psoriasis was evaluated by the Psoriasis Area Severity Index and the enthesitis by the Glasgow Ultrasound Enthesitis Scoring System (GUESS). RESULTS: The GUESS score was higher in those patients with psoriasis compared with patients with other dermopathies. Among psoriatic patients, 22% (13 of 59) presented tendon thickness over 5·29 mm and irregular tendon structure. Other abnormalities affected the tendon in 12 patients. In seven patients (12%) bursitis was also revealed. CONCLUSIONS: Our data confirm that ultrasonography is a sensitive technique which reveals enthesitis more frequently than clinical examination in patients affected by psoriasis. We suggest the use of ultrasonography of the Achilles tendon in early diagnosis of psoriatic arthropathy with the objective of preventing progression of the pathology.

In vitro and ex vivo effect of hyaluronic acid on erythrocyte flow properties.

BACKGROUND: Hyaluronic acid (HA) is present in many tissues; its presence in serum may be related to certain inflammatory conditions, tissue damage, sepsis, liver malfunction and some malignancies. In the present work, our goal was to investigate the significance of hyaluronic acid effect on erythrocyte flow properties. Therefore we performed in vitro experiments incubating red blood cells (RBCs) with several HA concentrations. Afterwards, in order to corroborate the pathophysiological significance of the results obtained, we replicated the in vitro experiment with ex vivo RBCs from diagnosed rheumatoid arthritis (RA) patients, a serum HA-increasing pathology. METHODS: Erythrocyte deformability (by filtration through nucleopore membranes) and erythrocyte aggregability (EA) were tested on blood from healthy donors additioned with purified HA. EA was measured by transmitted light and analyzed with a mathematical model yielding two parameters, the aggregation rate and the size of the aggregates. Conformational changes of cytoskeleton proteins were estimated by electron paramagnetic resonance spectroscopy (EPR). RESULTS: In vitro, erythrocytes treated with HA showed increased rigidity index (RI) and reduced aggregability, situation strongly related to the rigidization of the membrane cytoskeleton triggered by HA, as shown by EPR results. Also, a significant correlation (r: 0.77, p < 0.00001) was found between RI and serum HA in RA patients. CONCLUSIONS: Our results lead us to postulate the hypothesis that HA interacts with the erythrocyte surface leading to modifications in erythrocyte rheological and flow properties, both ex vivo and in vitro.

Adalimumab for treatment of moderate to severe psoriasis and psoriatic arthritis.

Psoriasis and psoriatic arthritis are common diseases associated with considerable morbidity and disability. Their pathophysiology comprises similar processes leading to inflammation of skin, entheses, and joints. Although traditional systemic agents can be effective, their use may be limited by lack of efficacy and concerns regarding adverse effects. The objective of this study was to assess the efficacy and safety of adalimumab, a fully human antitumor necrosis factor (anti-TNF) monoclonal antibody, over 16 weeks. The present authors report their personal experience in 15 patients with severe plaque psoriasis and psoriatic arthritis, refractory to other treatments, in which a decisive regression of joint/skin involvement was obtained. Psoriasis and psoriatic arthritis are chronic inflammatory disorders resulting from a combination of genetic and environmental factors.

Tuberculoid leprosy and Type 1 lepra reaction.

A patient is described with tuberculoid leprosy and Type 1 (lepra) reaction from Sicily a non-endemic region, who lived previously in Manila from 2000 to 2005. The skin lesions became acutely inflamed and edematous. The plaques were painless to touch or pinprick, and there was swelling of the nerves in the fibro-osseous tunnels under the surface of the skin, including both the ulnar nerve at the elbow, and the posterior tibial nerve (medial malleolus). During the course of electro-neurographic studies, conduction velocity in the motory nerves indicated a slowing-down. The diagnosis of leprosy was confirmed by residence in an endemic area for about 5 years, by simultaneous skin lesions and peripheral nerve abnormalities, and by skin biopsy. Outside of endemic areas, diagnosis remains a challenge for physicians for mainly two reasons. Firstly, the incubation period of leprosy is uniquely long among bacterial diseases and varies from a month to over 40 years. Secondly, outside leprosy-endemic areas, the diagnosis of leprosy is usually not considered, and patients are likely to be examined by a wide range of specialists. Physicians outside endemic areas should consider leprosy as a possible differential diagnosis if a patient from leprosy-endemic regions presents with painless skin lesions, nerve enlargement, or persistent skin lesions.

Scalp psoriasis: report of efficient treatment with secukinumab.

Psoriasis is a chronic inflammatory skin disease affecting 2-3% of the population in the world. The scalp is the most common, and frequently the first site of disease involvement. Occasionally it may be the only localization of psoriasis. Treatment of scalp psoriasis is often unsatisfactory, due to limited available topical therapy and reduced efficacy of some systemic drugs. Biologic therapies are recommended for severe psoriasis, resistant to topical treatment, but evidence from randomized, controlled studies is lacking regarding effectiveness on scalp-localized lesions. Several clinical studies have shown the efficacy of secukinumab on plaque psoriasis, and some encouraging experience suggest the use in difficult sites such as the scalp; this article reports effective treatment with secukinumab of a series of patients with plaque and scalp psoriasis.

Myiasis with Dermatobia hominis in a Sicilian traveller returning from Peru.

We report a case of a bot fly infestation of the scalp. A 45-year-old man after returning to Sicily noted a small white "worm" erupting from the upper lesion. Physical examination revealed a superficial furuncular lesion with central pores with sero-sanguineous discharge. The foreign body identified was diagnosed as the larva of the human bot fly, Dermatobia hominis.

Home infusion program with enzyme replacement therapy for Fabry disease: The experience of a large Italian collaborative group.

Fabry disease (FD) [OMIM 301500] is an X-linked lysosomal storage disorder caused by a deficiency of the lysosomal enzyme alpha-galactosidase A, resulting in progressive multisystem accumulation of globotriaosylceramide (Gb3). Although the introduction of Enzyme Replacement Therapy (ERT) resulted in a variety of clinical benefits, life-long intravenous (IV) treatment with ERT with an every other week schedule, may interfere with daily life activities and impact on QoL. We report here a multicentric, observational, longitudinal data analysis on a large cohort of 85 Italian FD patients (45 males, 40 females) from 11 out of 20 Italian regions, who received a cumulative number of 4269 home infusions of agalsidase alfa. For the whole cohort, the average duration of home therapy was 1 year and 11 months (range 3 months-4 years and 6 months), and during this period, compliance to treatment (number of infusions performed vs scheduled) reached 100%. The EQ-5 VAS scale was administered to patients to evaluate the self-reported QoL, 58% of patients showing an increase of EQ-5 VAS score at follow up compared to baseline (home treatment start) or remaining stable. A mild increase of average disease severity, measured through Mainz Severity Score Index (MSSI), was found during hospital treatment (p < 0,007), while it remained stable between the first home therapy infusion and last follow up. Interestingly, 4 out of 7 (57%) patients, showing an improvement in FD-related clinical status after starting home therapy, had previously a sub-optimal compliance to treatment during the period of hospital treatment management. Only 4 adverse non serious reactions (0,093%) were reported totally in 2 patients during home treatment. We conclude that home infusions in eligible patients with FD are safe, contribute to improve treatment compliance and therapeutic clinical outcomes, and may have a positive impact on self-perceived QoL.

Non invasive evaluation of endothelial function in patients with Anderson-Fabry disease.

AIM: Fabry's disease is an X-linked recessive abnormality of glycosphingolipid metabolism. Increased levels of endothelial prothrombotic factors have recently been demonstrated in Fabry's disease, whereas endothelial function has not been studied using high resolution ultrasound. METHODS: We enrolled 6 patients (4 male, 2 female; mean age, 37 years) and 12 sex matched control subjects (mean age, 37 years). Patients' exclusion criteria included a prior history of cardiac disease, diabetes and treated or untreated hypertension. Patients underwent: anamnesis, physical examination, EKG, 2-dimensional echocardiography with tissue Doppler, measurement of body weight and height, blood pressure. Biochemistry variables were also considered: fasting blood sugar, total cholesterol, HDL-C, LDL-C, triglycerides, fibrinogen, C reactive protein and homocysteine. Using high resolution ultrasound, we assessed the brachial vasodilator response to reactive hyperemia (endothelium-dependent) and sublingual nitroglycerin (NTG) (endothelium-independent). Flow-mediated dilatation (FMD) was expressed as percentage change in post-stimulus diameter in comparison with the baseline. RESULTS: In baseline condition, there was no significant difference between patients and controls in the brachial artery diameter (3.5+/-0.55 vs 3.1+/-0.4). After reactive hyperemia, the FMD change was significantly higher in controls than in patients (16.5+/-6.3% vs 9.3+/-6.2%, P<0.05). After NTG, endothelium-independent vasodilation did not show a significant difference between cases and controls (15+/-7.7% vs 13.8+/-7.1%). CONCLUSIONS: Our study demonstrated the presence of endothelial dysfunction in patients with Fabry's disease in comparison to controls. We hypothesized that endothelial dysfunction may contribute to the pathogenesis of ischemic events in patients with Fabry's disease.

Neuropsychiatric effects and type of IFN-alpha in chronic hepatitis C.

Chronic hepatitis is often associated with neuropsychiatric disorders. Interferon (IFN) is the drug most widely used to treat this disease, and its side effects, such as depression, often involve the central nervous system (CNS). Symptoms include a slowing down of psychomotor functions, loss of interest, frontal lobe dysfunction, parkinsonism, and delirium. The occurrence of these complications calls for dropping out of IFN treatment or for a significant dose reduction and administration of antidepressants. Efficacy and side effects vary on the basis of the IFN type employed. The aim of our study was to evaluate if the frequency, form, and degree of depression induced are related to the type of IFN employed. We studied 96 patients with chronic hepatitis C. Our study series was divided into four groups according to the type of IFN-alpha administered. Depression degree was clinically evaluated using the Hamilton Depression Rating Scale (HAM-D). All patients were tested before treatment and 1, 3, and 6 months (15 days after the end of treatment) later. Our results showed that the type of IFN used seemed to influence the depression onset rate, with the leukocyte type inducing the lowest level of depression. However, when a number of symptoms associated with the depression were considered, the results of other types of IFN-alpha were found to be better. Use of the most suitable type of IFN-alpha could thus lead to more personalized treatment, with fewer side effects. The type of IFN used seems to influence the psychological side effects and the adaptation rate to therapy. It would be appropriate to choose the type of IFN on the basis of a neuropsychiatric assessment carried out before treatment.

Mapped auditory evoked potentials before and after interferon treatment.

Neurotoxicity induced by interferon (IFN) is revealed by neurobehavioral changes, such as irritability, somnolence, lack of motivation, and delayed ideation. As these side effects persist throughout IFN-alpha treatment, we studied cerebral mapped auditory evoked potentials (MAEP) in 20 hepatitis C virus antibody (HCV Ab)-positive chronic active hepatitis patients before and after administration of leukocyte IFN-alpha (i.m. 3,000,000 IU). Some of the main components of MAEP, such as morphology, latency, and power spectra, were altered before IFN injection. These parameters changed 7 h after administration as revealed by increased quality and quantity of acoustic signal reaching the brain cortex and appearance of physiologic waves in patients with mild/intermediate liver disease. These effects revealed 48 h after IFN administration.

Efficacy of interferon-based therapy in the treatment of thalassaemic patients with chronic hepatitis C: a meta-analysis.

OBJECTIVE: To identify the interferon-alpha (IFNalpha) treatment protocol most suitable for patients with thalassaemia major who have chronic hepatitis C. DESIGN AND SETTING: This was a meta-analysis of studies in the international literature between 1990 and 1999. METHODS: Studies were identified from a search of Medline and Embase, and analysed by the Mantel-Haenszel-Peto statistical method. RESULTS: We identified 6 nonrandomised trials, 2 of which were controlled, that treated a total of 201 patients. Most studies used the lowest dose level (3 MIU/m(2)), all used a thrice-weekly regimen, and most used IFNalpha-2b, although the use of natural IFNalpha did not induce production of anti-interferon antibodies. The best sustained response and remission rates tended to be achieved with higher doses and longer cycles of IFNalpha. CONCLUSIONS: The best interferon-based therapy to treat polytransfused thalassaemic patients with chronic hepatitis C is represented by the use of natural IFNalpha or IFNalpha-2b, initially at high dosages (5 to 10 MIU/m(2) 3 times weekly) for 6 months, followed by lower dosages (3 MIU/m(2) 3 times weekly) for a further 6 to 9 months.

Interferon, cortisone, and antivirals in the treatment of chronic viral hepatitis: a review of 30 years of therapy.

Over the last 30 years many approaches have been adopted to treat chronic hepatitis. We conducted a meta-analysis to assess the efficacy of various types of treatments. We selected 4 studies of cortisone in chronic hepatitis B; 21 trials of interferon treatment, 6 in chronic hepatitis B, 10 in chronic hepatitis C, and 5 in chronic hepatitis D; and 5 of combined cortisone and interferon treatment in chronic hepatitis B. The Mantel-Haenszel-Peto method was applied to extrapolated data. We completed the study by analyzing four studies of cortisone treatment of chronic hepatitis C, two of cortisone plus interferon alpha (IFN-alpha) for chronic hepatitis C, and antiviral therapy for hepatitis B, C, and D. Trials administering cortisone for chronic hepatitis B had an overall OR of 0.29 (CI 0.12-0.73). No virologic remissions were observed in patients with hepatitis C receiving prednisone, even if those with features of autoimmunity achieved a biohumoral sustained response. Overall ORs in the trials were were as follows: IFN for chronic hepatitis B, 0.27 (CI 0.17-0.46); IFN for chronic hepatitis C, 0.3 (CI 0.21-0.44); IFN for chronic hepatitis D, 0.16 (CI 0.06-0.47); and cortisone plus interferon for chronic hepatitis B, 0.25 (CI 0.15-0.41). Sustained response rates of chronic hepatitis C ranged from 15-24.2%. The only encouraging results were obtained by antivirals. To date the lack of a specific antiviral drug makes it uncertain as to the preferred agent for this disease.

A meta-analysis of interferon-alpha treatment of hepatitis D virus infection.

The severity of chronic hepatitis D infection and its unfavorable progress necessiate research into drugs and protocols capable of changing the natural history of the disease. Over the last few years interferon (IFN)-alpha has been the drug of choice in the management of this infection. We assessed its long-term efficacy by analyzing 5 controlled and 10 uncontrolled trials conducted between 1987 and 1994. The Mantel-Haenszel-Peto method was used in the former to perform statistical analysis. The odds ratio (0.16, confidence interval 0.058-0.476) confirmed the efficacy of IFN-alpha, even if the coefficient was not significant because of the limited number of spontaneous remissions in the trials. Although IFN treatment is fully beneficial in only a small number of patients with chronic hepatitis D infection, at present it is the only available agent.