Effectiveness and safety of apremilast in biologic-naïve patients with moderate psoriasis treated in routine clinical practice in Greece: the APRAISAL study.

BACKGROUND: Apremilast is an oral phosphodiesterase-4 inhibitor indicated for patients with moderate-to-severe chronic plaque psoriasis and active psoriatic arthritis. OBJECTIVES: To examine the effectiveness of apremilast on Dermatology Life Quality Index (DLQI), Psoriasis Area and Severity Index (PASI) and nail, scalp and palmoplantar involvement, when administered prior to biologics. METHODS: This 52-week real-world study included biologic-naive adults with moderate psoriasis (psoriasis-involved body surface area 10% to <20%, or PASI 10 to <20 and DLQI 10 to <20). Apremilast was initiated ≤7 days before enrolment. Data from the first 100 eligible patients who completed 24 weeks (W24) of observation (or were prematurely withdrawn) are presented in this interim analysis using the last-observation-carried-forward imputation method. RESULTS: Eligible patients (mean age: 49.9 years; 71.0% males; median disease duration: 8.0 years) were consecutively enrolled between April and October 2017, by 18 dermatology specialists practising in hospital outpatient settings in Greece. Baseline DLQI (median: 12.0) and PASI (median: 11.7) scores improved (P < 0.001) at all postbaseline timepoints (Weeks 6, 16 and 24; W24 median decreases: 9.0 and 9.4 points respectively). At W24, DLQI ≤5, DLQI 0 or 1, and PASI-75 response rates were 63.0%, 25.0% and 48.0% respectively. The Nail Psoriasis Severity Index score in patients with baseline nail involvement (n = 57) decreased at all postbaseline timepoints (P < 0.001; W24 median decrease: 20.0 points). At W24, 50.0% and 51.7% of patients with baseline scalp (n = 76) and palmoplantar (n = 29) involvement respectively achieved postbaseline Physician's Global Assessment (PGA) score of 0 or 1 if baseline score was ≥3, or 0 if baseline score was 1 or 2. The adverse drug reaction rate was 21.0% (serious: 2.0%). CONCLUSIONS: These interim results indicate that through 24 weeks, apremilast improved quality of life and reduced disease severity in biologic-naive patients with moderate plaque psoriasis, while demonstrating safety consistent with the known safety profile.

The clinical significance of an incidentally detected open internal inguinal ring.

INTRODUCTION AND OBJECTIVE: An open internal inguinal ring (IIR) may be discovered incidentally either in the context of correcting pathology involving the contralateral side or at the time of surgical exploration for reasons unrelated to a patent processus vaginalis (PPV). The aim of this study is to determine the evolution of an incidentally encountered open IIR in patients undergoing laparoscopy for reasons not associated with unilateral inguinal hernia or cryptorchidism. MATERIALS AND METHODS: The authors conducted a prospective study of all patients who underwent laparoscopic surgery in the department of pediatric surgery at Agios Loukas hospital between 2004 and 2013 for various indications. Patients operated for inguinal hernia and cryptorchidism were excluded. During this period, 572 patients underwent laparoscopy for reasons not related to PPV. The median age at time of initial laparoscopy was 9,4 years (range 2 days-16 years). The IIRs were always inspected. No attempt was made to repair the open IIRs, as they were asymptomatic. Parents were informed after the operation, and instructions were given to inform us, in case that inguinal hernia symptoms manifested. The duration of the follow-up was 4 years. RESULTS: Among these 572 patients, 39 patients with 44 open IIRs were found (6,82%). From the 39 patients, 35 were male and four were female; 22 had a right open IIR, 12 had a left one, and five of them a bilateral open IIR. The median age was 7,82 years (3-14 years). Four patients were lost during follow-up. Of the remaining 35 patients with 40 open IIRs, four developed an inguinal hernia (11,43%) and were operated on with laparoscopically assisted (subcutaneous endoscopically assisted ligation [SEAL]) technique at the time of diagnosis. The study results are demonstrated on Fig. 1. DISCUSSION: The percentage of an incidentally discovered open IIR in this study is lower in comparison with studies including patients with PPV pathologies. There is a possibility, in those patients, of underlying pathology which can affect both sides. It is also lower in comparison with previous studies including younger patients. However, gender and side predominance is in accordance with most published studies. In this study group, the possibility of developing a symptomatic hernia from an asymptomatic open IIR is rather small. CONCLUSIONS: An incidentally discovered open IIR in patients without symptoms, excluding those with contralateral inguinal hernias or cryptorchidism, has relatively low chance of developing an inguinal hernia. Thus, the authors support the strategy of close follow-up in these patients.

Correction of concealed penis with preservation of the prepuce.

INTRODUCTION: By definition, congenital concealed penis presents at birth. Children are usually referred to physicians because of parental anxiety caused by their child's penile size. OBJECTIVE: Several surgical procedures have been described to treat this condition, but its correction is still technically challenging. The present study reports a simple surgical approach, which allows preservation of the prepuce. PATIENTS AND METHODS: During the last 6 years, 18 children with concealed penis (according to the classification by Maizels et al.) have been treated in the present department (mean age 4.5 years, range 3-12 years). Patients with other conditions that caused buried penis were excluded from the study. The operation was performed through a longitudinal midline ventral incision, which was extended hemi-circumferentially at the penile base. The dysgenetic dartos was identified and its distal part was resected. Dissection of the corpora cavernosa was carried down to the suspensory ligament, which was sectioned. Buck's fascia was fixed to Scarpa's fascia and shaft skin was approximated in the midline. Penoscrotal angle was fashioned by Z-plasty or V-Y plasty. RESULTS: The median follow-up was 24 months (range 8-36). The postoperative edema was mild and resolved within a week. All children had good to excellent outcomes. The median pre-operative to postoperative difference in penile length in the flaccid state was 2.6 cm (range 2.0-3.5). No serious complications or recurrent penile retraction were noted. DISCUSSION: Recent literature mostly suggests that concealed penis is due to deficient proximal attachments of dysgenetic dartos. Consequences of this include: difficulties in maintaining proper hygiene, balanitis, voiding difficulties with prepuce ballooning and urine spraying, and embarrassment among peers. Surgical treatment for congenital concealed penis is warranted in children aged 3 years or older. The basis of the technique is the perception that in boys with congenital concealed penis, the penile integuments are normal but they have abnormal attachments, and that incision of the skin and dartos will allow the shaft to extend. Furthermore, incisions of the fundiform and suspensory ligaments facilitate this maneuver. With this technique, the blood supply of the penile skin is not interrupted and postoperative lymphedema, a difficult complication to deal with, is prevented. One major advantage is the preservation of the prepuce, giving a normal penile appearance and an excellent cosmetic result. CONCLUSION: The method proposed here is simple and has no serious complications. It is suggested that this condition be treated in pre-school-aged children in order to prevent psychological impairment.

Perspectives for integrated municipal solid waste management in Thessaloniki, Greece.

Local authorities need updated and reliable data on the quantity and the quality of the waste generated in their area, in order to establish an integrated solid waste management system capable of fulfilling regional and national waste management targets. This paper presents information about the quantity and the characteristics of the municipal solid waste generated in Thessaloniki, which is the second largest city in Greece. It is based on the results of three research programs investigating the evolution of municipal solid waste. The investigations were carried out over the last 20 years at the landfill of Thessaloniki by the same research group using statistically acceptable practices for sampling and hand sorting. The results show a great increase in the incoming quantities during the last years and a significant increase of the per capita generation. There is also a significant change in the composition, demonstrated mainly by a decrease in the organic fraction followed by an increase of packaging materials (paper and plastic).

The epidemiology of onychomycoses in Crete, Greece, between 1992 and 2001.

BACKGROUND: Onychomycosis represents the most frequently encountered nail disease, which is difficult to eradicate with drug treatment. Epidemiological studies concerning onychomycosis have been performed in many countries worldwide. Differences in the incidence of onychomycosis have been reported not only for various geographical areas, but also for different regions of the same country. OBJECTIVE: This survey was undertaken to determine the epidemiology of onychomycosis in the population of Crete, Greece. METHODS: In a prospective study, the fingernails and toenails of all new patients presenting to the outpatient Dermatology Department of the University Hospital of Crete were examined by certified dermatologists. If they appeared abnormal, nail material was obtained for mycologic examination. RESULTS: A total of 23,477 patients were examined during the study period (1992-2001). Of them, 19,556 (83.3%) participated in the investigation. Clinical abnormal nails were observed in 2098 (10.7%) patients, 36.7% males and 63.3% females. Mycologically confirmed onychomycosis was detected in 511 (24.3%). Toenail onychomycosis was found in 283 (55.4%) patients, fingernail onychomycosis in 210 (41%), and both toenail and fingernail onychomycosis in 18 (3.6%). In the toenail infections, dermatophytes were most frequently isolated (52%), followed by yeasts (24.7%) and moulds (15.5%); 7.8% of the infections were mixed. In the fingernail infections, yeasts were most often isolated (82.9%), followed by dermatophytes (10%), and moulds (1.9%); 5.2% of the infections were mixed. CONCLUSION: Because the pattern of onychomycoses in a country is changing with time, epidemiological studies are necessary for determining the prevalence and the causative agents of the infection.

Cutaneous alternariosis revealing acute myeloid leukaemia in an adult patient.

We report a case of cutaneous alternariosis in a 69-year-old male patient. During hospitalization for treatment of the skin disorder, acute myeloid leukaemia was diagnosed. He received multiple chemotherapeutic agents but the leukaemia remained refractory to therapy and the patient died. The clinical picture, diagnosis and treatment of cutaneous alternariosis will be discussed and a review of the literature regarding patients with haematological diseases will be given.

Early development of multiple epithelial neoplasms in Netherton syndrome.

We report a case of Netherton syndrome manifested as congenital ichthyosiform erythroderma, trichorrhexis invaginata and atopy, who in early adulthood developed multiple, aggressive epithelial neoplasms in sun-exposed areas of the skin, in areas with papillomatous skin hyperplasia and at the left parotid region. The occurrence of cutaneous neoplasia has been reported in syndromes with congenital ichthyosis and suggests that the underlying genetic defects may cause the development of cancer in prone patients.

Langerhans' cell histiocytosis and haemophagocytic lymphohistiocytosis in an elderly patient.

We present a case of a 78-year-old man suffering from a chronic psoriasiform eruption, with rapid deterioration over the previous 8 weeks. Langerhans' cell histiocytosis with skin and bone involvement was diagnosed, and there was evidence of liver and lung dysfunction. The patient was treated with prednisolone and etoposide, and initially experienced a partial improvement. Three weeks later, haemophagocytic lymphohistiocytosis and subsequently a large pulmonary abscess with sepsis attributed to opportunistic gram-negative enterobacteriaceae Serratia marcescens developed, and the patient died. The present case of Langerhans' cell histiocytosis is of particular interest because of the previously unreported development of haemophagocytic lymphohistiocytosis in the elderly population.

Cutaneous alternariosis in a patient with idiopathic pulmonary fibrosis.

A 78-year-old farmer presented with symptomless skin lesions for evaluation. Two years prior, he had developed idiopathic pulmonary fibrosis (IPF) and had been treated thereafter with oral prednisolone 20 mg/day and occasionally with colchicine 1 mg/day. On examination, erythematoviolaceous, slightly infiltrated plaques, measuring approximately 5 x 9 cm, rubbery in consistency, intermingled with pustules, sometimes eroded, with distinctive borders, were noted on the dorsum of both hands and on the extensor surface of both forearms. The lesions had developed over a 20-day period. The skin of these areas was atrophic or eroded with multiple ecchymoses (Fig. 1). The abnormal laboratory findings included an elevated white blood cell count of 17,100/mm3, with 79% neutrophils, 16% lymphocytes, and 5% monocytes, C-reactive protein of 33.15 mg/dL (normal, <0.8 mg/dL), and immunoglobulin G of 598 mg/dL (normal, 701-1545 mg/dL). Other blood and urine tests performed were within normal limits. The diagnosis of IPF was reconfirmed through radiology, high-resolution computed tomography, and spirometry, as well as bronchoscopy and bronchoalveolar lavage fluid analysis. Coexistence of presumptive pulmonary alternariosis was excluded. Hematoxylin and eosin stained sections of the excised cutaneous specimen showed focal ulceration of the epidermis adjacent to a mainly intradermal abscess cavity. Within the latter, remnants of a partly destroyed hair follicle were seen amongst degenerating polymorphonuclear leukocytes, as well as many histiocytes and a few Langhans-type multinucleated giant cells. Minute collections of polymorphonuclear leukocytes were seen in the adjacent epidermis. Periodic acid-Schiff (PAS) and Gomori's silver methenamine stains showed a multitude of broad branching fungal hyphae and large spores within the aforementioned cavity, both free and within the cytoplasm of giant cells (Fig. 2). Immunohistochemistry was performed by means of the alkaline phosphatase anti-alkaline phosphatase (APAAP) method. Sections showed that the infiltrate consisted of an almost equal number of B and T lymphocytes, whereas histiocytes and the few giant cells were labeled with anti-CD68 antibodies. Skin smears and biopsy specimens taken twice from all lesions were used for mycologic examination. Wet mounts revealed numerous, brownish, septate hyphae and ovoid Skin smears and biopsy specimens taken twice from all lesions were used for mycologic examination. Wet mounts revealed numerous, brownish, septate hyphae and ovoid structures. Biopsy material was plated on Sabourand's dextrose agar with cloramphenicol (0.05 mg/mL). After 7 days at 27 degrees C, dark, gray-white colonies with a dark brown underside appeared. Microscopic examination of the colonies revealed hyphae with typical conidia having transverse and longitudinal septa. Based on macroscopic and microscopic examination, the isolates were identified as Alternaria alternata (Fig. 3). Treatment with prednisolone was reduced to 10 mg/day and the patient received oral itraconazole (200 mg/day). This resulted in progressive improvement of alternariosis, and the lesions healed completely within 3 months, when treatment was interrupted. Two years later, there is no evidence of recurrence.

Ultrasonography of the pancreas, as a function index, in children with beta-thalassemia.

Increased echogenicity of the pancreas, due to hemosiderosis, is a frequent laboratory finding in children and adolescents with beta-thalassemia. The aim of this study was to investigate whether increased echogenicity of the pancreas is associated with dysfunction. The ultrasonic image of the pancreas was examined in 34 children aged 12+/-3.8 years old and was compared to the endocrine and exocrine functioning of the gland. Oral glucose tolerance test (OGTT) was performed with simultaneous measurement of insulin and serum trypsin. Twenty-six of the 34 patients (76.5%) presented increased echogenicity, while 8 (23.5%) had a normal ultrasonic pancreatic image. 77% of the patients with increased echogenicity had abnormal OGTT, 46%, with subnormal or increased insulin values, and 32.5% manifested low levels of trypsin. Among the patients with normal ultrasound, 25% had abnormal OGTT and 37.5% abnormal insulin values. Statistical analysis with Student's t-test revealed that patients with increased echogenicity had significantly higher glucose values on OGTT at 60: 7.6 +/- 1.8 mmol/l (137.3 +/- 33.7 mg/dl) as compared to the patients with normal ultrasound: 6.1 +/- 1.2 mmol/l (110.75 +/- 21.72 mg/dl) (p<0.05). Insulin values were significantly affected at 30, 60, and 90 min: 570+/-301, 332+/-156, 294+/-158 pmol/l (79.54 +/- 42, 46.4 +/- 21.8, 41.04 +/- 22 mU/l) respectively in patients with increased echogenicity in comparison to those with normal ultrasonographic image of the gland: 301 +/- 170, 192 +/- 52, 135 +/- 63 pmol/l (42 +/- 23.7, 26.85 +/- 7.36, 18.9 +/- 8.8 mU/l) (p<0.05). No statistical significance was observed between the two groups regarding trypsin levels, even though abnormal values were observed in more children with increased echogenicity than in patients with a normal ultrasound. The above findings confirm that increased echogenicity of the pancreas is associated with disturbance of its function. This simple imaging method could be used as a rough early index of detection of an increased risk for developing diabetes mellitus in patients with beta-thalassemia.

Low molecular weight heparin; a novel alternative therapeutic approach for lichen planus.

Heparin analogues in low doses have antiproliferative and immunomodulatory properties. The aim of this study was to evaluate the effect of low-dose enoxaparin administered subcutaneously in lichen planus (LP). Eighteen patients with various types of LP were treated in an open study for 6-13 weeks. Efficacy and safety data were recorded. Complete remission was observed in 11 of 18 patients (61%) and marked improvement in two (11%). Widespread cutaneous involvement and reticulated oral LP had the best response, while in LP of the scalp the response was poor. Enoxaparin is a promising alternative therapy for various types of LP.