Colchicine in the treatment of refractory aphthous ulcerations: Review of the literature and two case reports.

Colchicine has been known and used for over a millennium for its anti-inflammatory properties, being the treatment of choice for gout and familial Mediterranean fever. A tricyclic alkaloid extracted from the herbaceous plant, Colchicum autumnale, colchicine blocks multiple inflammatory pathways, and has antimitotic and antifibrotic action. Although there are insufficient data on the beneficial mechanism of action, colchicine is a widely used treatment in dermatology, one of the morbid conditions with more evidence of efficacy being recurrent aphthous stomatitis (RAS), a disorder with incompletely known etiopathogenesis and, consequently, with poorly defined treatment. Colchicine is considered as the first therapeutic line in complex or severe aphthoses, significantly relieving pain, decreasing the number of lesions, increasing the free interval between eruptive episodes, without inducing noticeable side effects. We examined the treatment efficacy of colchicine in two cases of chronic, severe RAS, evolving in different morbid contexts, who did not respond to other therapeutic measures. The two cases presented with recurrent aphthous stomatitis with herpetiform aphthae; one patient with Turner syndrome and one patient with major Sutton ulcers.

High serum level of interleukin-6 is linked with dyslipidemia in oral lichen planus.

Oral lichen planus (OLP) is a complex chronic inflammatory disorder in which autocytotoxic CD8+ T cells, locally present in the affected tissue, induce basal keratinocyte apoptosis, through the release of several cytokines, such as interleukin-6 (IL-6). IL-6 is a proinflammatory cytokine that is related to alterations in lipid metabolism in psoriasis patients. Impaired lipid metabolism together with high serum levels of triglycerides have been found in association with OLP. However, the correlation between serum levels of IL-6 and dyslipidemia has not yet been studied in this disorder. The present study aimed to demonstrate the association between OLP, systemic inflammation through increased release of inflammation mediators such as IL-6 and alteration of lipid metabolism, in order to support the concept of OLP as a marker of systemic inflammation and a potential risk factor of cardiovascular morbidities. For this purpose, we designed a case-control study using a cohort of 18 patients with different clinical forms of OLP compared with 18 control group patients with other oral conditions, to identify a potential correlation between serum levels of IL-6 and serum lipid levels. High plasma serum levels of IL-6 were found to be correlated with cholesterol, high density lipoprotein cholesterol and triglyceride serum levels in the patients with OLP. There was a significant association between erosive and atrophic clinical forms of OLP and the pathological serum values of IL-6 and triglycerides, respectively, making these two parameters good predictive factors of the clinical form of OLP. Further studies of other biomarkers of systemic inflammation using larger cohorts of OLP patients are necessary in order to consider LP as a marker of systemic inflammation and to support the screening of these patients for lipid metabolism changes and treatment with specific antagonists in order to prevent cardiovascular events.

Use of imaging techniques for melanocytic naevi and basal cell carcinoma in integrative analysis (Review).

Early detection of skin cancer is essential in order to obtain an improved prognosis. Clinicians need more objective and non-invasive examination methods to support their decision whether to biopsy or not tumoral lesions. These may include several imaging techniques such as dermoscopy, videodermoscopy, also known as sequential digital dermoscopy (SDD), computer-aided diagnosis (CAD), total body photography, imaging and high-frequency ultrasonography (HFUS), reflectance confocal microscopy, multiphoton tomography, electrical impedance spectroscopy, Raman spectroscopy, stepwise two-photon-laser spectroscopy and quantitative dynamic infrared. This review summarizes the current developments in the field of melanocytic lesions, such as naevi and basal cell carcinoma (BCC) imaging techniques. The aim was to collect and analyze data concerning types, indications, advantages and disadvantages of modern imaging techniques for in vivo skin tumor diagnosis. Two main methods were focused on, namely videodermoscopy and HFUS, which can be included in daily dermatologists' practice. In skin tumors HFUS allows the assessment of tumoral lesions with depth smaller than 1.5 cm, being described a correlation between ultrasonographic depth and the histologic index.

Aspects concerning patient adherence to anti-TNFα therapy in psoriasis: A decade of clinical experience.

Non-adherence to psoriasis treatment has an important impact in controlling chronic disease evolution and the occurrence of systemic comorbidities. Biologic therapy represents a revolutionary treatment, many of the undesirable psychological and socio-economical consequences of conventional topical or systemic therapies being avoided. Nevertheless, the discontinuation of biological therapy may occur due to facts related to the patient, to the lack of good communication between the patient and the physician or to the adverse or paradoxical reactions. We studied the non-adherence reasons to anti-TNFα agents (Infliximab, Adalimumab, Etanercept) used for treating 84 cases with moderate-severe psoriasis. The results of our study over the past 10 years showed a 76.2% adherence rate, lowest in patients treated with Etanercept (70.9%). Relative to the anti-TNF agent used, the highest adherence rate was recorded in Adalimumab (80.8%), followed by Infliximab (76.5%) and Etanercept (70.9%). We have noticed differences between the rates of adhesion to therapy with different anti-TNFα agents, but with no statistical significance. The main adverse effects that occurred during anti-TNFα therapy were: local reaction to the drug, mild infectious events, allergic reactions, cardiotoxicity, alopecia areata, pancreatitis, eosinophilia, thrombocytopenia. Anti-TNF therapy was discontinued in one case of endocarditis, one case with tuberculous laryngitis and another one with polydiscitis (Adalimumab), a case of colon cancer and one of pregnancy (Etanercept) and one paradoxical reaction (Infliximab).

Biosimilars in dermatology: The wind of change.

Biosimilars are new drugs, highly similar copies of biological medicines, equally effective and safe but at lower prices. The aim of this brief review is to provide the current status of biosimilars approved in the European Union for dermatological use. We used PubMed for literature search up to June 2018. The keyword 'biosimilars' was searched and 1,691 items were found. From the 1,691 studies, we included 34 articles in our review. Biologics, biosimilars and generics are different types of drugs. Biosimilars are complex molecules produced by a difficult manufacturing process, and changes in product quality may affect its safety and efficacy. Now, there are 9 biosimilar medicines approved by European Medicines Agency (EMA) for plaque psoriasis and hidradenitis suppurativa: Amgevita, Solymbic, Cyltezo, Imraldi, Benepali, Erelzi, Flixabi, Inflectra and Remsima, and the number is increasing. In 2005, EMA issued the first guidelines for approval of biosimilars. Next-generation biologics, called 'biobetters', have the same target or mechanism of action as previously approved biologics, but they have structural changes and an improved formulation. The debate over the future of biosimilars is far from being finished. The explosive development of biological therapy and the emergence of biosimilars represent a significant success in the effort to provide advanced healthcare to patients all over the world.

Imaging techniques in the diagnosis and monitoring of psoriasis.

Plaque psoriasis is a chronic, immune-mediated disease, which has a multifactorial etiopathogenesis. Practical non-invasive techniques to monitor plaque psoriasis progression and treatment are necessary. Imaging techniques available for psoriasis assessment may vary in terms of resolution, depth of penetration and visual representation. This review summarizes the current developments in the field of psoriasis non-invasive imaging techniques, such as dermoscopy, conventional ultrasound and high frequency ultrasonography (HFUS), videocapillaroscopy (VC), reflectance confocal microscopy (RCM), optical microangiography (OMAG), laser Doppler imaging (LDI), multiphoton tomography (MPT) and optical coherence tomography (OCT). The aim was to collect and analyze data concerning types, indications, advantages and disadvantages of modern imaging techniques for in vivo psoriasis assessment. We focused on two main methods, videodermoscopy and HFUS, which can be included in daily dermatologists' practice and which may assist in establishing diagnosis, as well as monitoring response to topical and/or systemic therapy of psoriasis. Dermoscopy may be useful for a first evaluation and may offer an understanding of the type and distribution of blood vessels, as well as the color of the scale and the background of the lesion. Videodermoscopy allows magnification and offers a detailed evaluation of the vessel type. The utility of HFUS consists mainly in monitoring therapy response. These methods may be comparable with virtual histopathology.

T-cell primary cutaneous lymphomas. A clinicopathological and immunohistochemical study.

Within the large framework of the lymphoproliferative diseases, the primary cutaneous lymphomas are distinct pathologic conditions, defined by particular morphologic, immunologic, genetic, and clinic criteria. The study aimed to create the first clinicopathological and immunohistochemical profile of primary cutaneous lymphoma for a Romanian region. We investigated a series of 16 cases (diagnosed during a 5-year period) in accordance with the general principles of primary cutaneous lymphoma management. The methods included the clinic and morphologic exams, the latter relying on standard and immunohistochemical staining. The results revealed that all studied cases were T-type lymphomas, in terms of the WHO-EORTC classification. Most of these cases were diagnosed as mycosis fungoides; the group also included cases of Sezary syndrome, as well as rare entities such as: mycosis fungoides associated with follicular mucinosis and subcutaneous panniculitis-like T-cell lymphoma. Our discussions focused on the role of the clinicopathological assessment for the primary cutaneous lymphoma diagnosis and emphasized the importance of the immunohistochemical investigation. Compared with the previous Romanian researches on this topic, presenting only isolated cases, the current study develops a new level of analysis, based on the rigorous monitoring of a relatively large geographical area, for a long time horizon.

Subcutaneous Granuloma Annulare.

Dear Editor, Subcutaneous granuloma annulare (SGA) is considered a rare clinical variant of granuloma annulare, a common self-healing chronic inflammatory disorder that may appear in childhood as well as in adult age (1-3). A 29-year-old female patient reported the onset of several small subcutaneous nodules on the dorsal aspect of the second interphalangeal joint of the left medius finger and the left elbow, accompanied by vague joint pain, had occurred 13 years ago. Specific markers for rheumatoid arthritis were negative, leading to a diagnosis of sero-negative rheumatoid arthritis, for which treatment with methotrexate was initiated. No clinical benefit was obtained and the treatment was abandoned. New nodules continued to appear on several distal joints of the fingers of both hands and, in the last 6 months, on the second right toe. The course of the disease included spontaneous remission of some of the nodules. Personal medical history was significant for a thyroid nodule, surgically removed at the age of 22. A general physical exam did not reveal pathological changes. A clinical dermatological exam at the time of presentation revealed several round to oval, deep subcutaneous, indurated, asymptomatic, discreetly pigmented lesions with a diameter of 4-6 mm, located on the dorsal aspect of the interphalangeal joints of the fingers of both hands (Figure 1) and the second right toe. Hematologic and biochemical tests were within normal limits, as well as the serological tests for rheumatoid factor, ANCA, ANA, and anti-CCP antibody. Hand radiographs did not show geodes, marginal erosions, or narrow joint spaces. A pathological exam of a subcutaneous nodule showed focally altered collagen surrounded by fibroblasts, phagocytes, rare lymphocytes, and neutrophils, as well as small capillaries (Figures 2-5), compatible with the diagnosis of a pseudorheumatoid nodule or benign rheumatoid nodule in the clinical and paraclinical context. SGA is considered a rare clinical and histological variant of granuloma annulare that predominantly affects children and occasionally young adults (1-6). In 1941, Ziegler first described a case of subcutaneous nodules that appeared concomitantly with classical cutaneous lesions of granuloma annulare, as well as the histological aspect of these nodules similar to that of rheumatoid nodules (RN) (7). Since then, several case reports in the literature refer to the subcutaneous lesions of GA as "pseudorheumatoid nodules", "deep granuloma annulare" or "palisading granuloma" (3,4,8). Most reported cases of SGA occur in the first three decades of life: 98% according to Muhlemann, 79% according to Andersen and Verdich, 62% according to Studer; most cases occur in children between 2 and 6 years of age (9). Lesions often regress spontaneously, but recurrences are common in 19%-75% of the patients, often on the same anatomical areas (9,10). Reported SGA cases in adult patients predominantly affected women, and typically involved multiple lesions located on the hands, feet, ankles, and inferior pretibial area (4-6). The etiology and pathogenesis of SGA are not completely understood. Precipitating factors such as insect bites, infections with Borellia spp., herpetic virus, EBV, Streptococcus spp., PUVA-therapy, several drugs, physical trauma, acute phlebitis, and post-surgery sepsis have been considered (8). There is evidence for the pathogenic involvement of an immunological mechanism, possibly a delayed type hypersensitivity reaction mediated by T-cells that triggers a panniculitis-type inflammatory response (8,10). Correlations between SGA and systemic diseases such as diabetes mellitus, sarcoidosis, HIV infection, or autoimmune diseases have not been found (8). A positive diagnosis of pseudorheumatoid nodules relies on clinical and anamnestic data. Differential diagnosis includes rheumatoid nodules, benign rheumatoid nodules, foreign body reactions, hematomas, abscesses, and infectious granulomas (3,5). Pseudorheumatoid nodules and SGA have a low risk of progression to a systemic connective tissue disorder. In the presence of subcutaneous nodular lesions with an uncertain clinical diagnosis, cutaneous biopsy, hematological and immunological tests, and imaging may be performed to establish a positive diagnosis. Skin biopsy is the most useful test for the diagnostic approach because, even though it is sometimes difficult to interpret, a pathological exam may offer important data to distinguish between rheumatoid and pseudorheumatoid nodules. Necrobiosis may be identified in the deep dermis and subcutaneous tissue, and rarely in the deep soft tissues. Necrobiosis is less important and less deep than in rheumatoid nodules, as well as less extensive and less diffuse than in lipoidic necrobiosis (6). Anomalies in the morphology of the deep cutaneous structures may coexist with typical changes in classical granuloma annulare. Immunohistochemical studies using specific histiocyte markers such as CD68/PGM1 proved to be occasionally useful in differentiating SGA from other granulomatous conditions (11). Several tests are necessary to exclude an association with a systemic disease: hemoleucogram (absence of leucocytosis), ESR (normal values), acute phase reactants (negative fibrinogen, RCP), autoantibodies (negative ANA), and rheumatoid factor (negative). SGA is a benign disorder with esthetic implications and sometimes functional impairment. Surgical excision is only required for juxta-articular nodules causing functional impairment. Partial therapeutic benefit was reported after the administration of dapsone, clorambucil, isotretinoin, potassium iodide, or intralesional/topical steroids. Even though the risk of systemic involvement is low, periodical follow-up of these patients is required given the reported cases of associated systemic connective tissue disorders (8,12).

Eosinophilia--A rare possible adverse reaction during anti-tumor necrosis factor-alpha therapy for psoriasis.

The current use of tumor necrosis factor (TNF)-alpha inhibitors in rheumatological, dermatological and gastroenterological diseases has increased considerably in recent years. Different reports have been communicated regarding specific risks and side effects during treatment with TNF-alpha inhibitors. Eosinophilia has been linked to TNF-alpha inhibitors by several recent reports, although it is not listed as a possible adverse reaction in the product information of the drug. The aim of the present study was to evaluate the eosinophil count in patients diagnosed with psoriasis and treated with adalimumab. Based on the results of the present study, eosinophilia remains a rare adverse reaction during psoriasis treatment with TNF-alpha antagonists.

Epidemiological and pathological aspects of skin cancer in North East of Romania.

UNLABELLED: In the last years skin cancer has become the most frequent cancer in humans, with the majority made up of two tumors: malignant melanoma (MM) and non-melanoma skin cancer (NMSC). AIM: To provide for the first time in the North East region of Romania, descriptive epidemiological data of melanoma and non-melanoma skin cancers. MATERIAL AND METHODS: We undertook a retrospective study over a five year period on the most frequent forms of skin cancer, basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and MM, which included a total number of 1231 patients, hospitalized and treated in the Plastic Surgery Department of "St. Spiridon" Emergency Clinical Hospital, Iasi from 2008 until 2012. Results: BCC was diagnosed in a total of 675 patients, representing 54.9%. SCC was found in 217 patients, representing 17.6% and melanoma was diagnosed in 119 cases, a percent of 9.7% of the total number. The predominance of cutaneous malignancies waried with age, major site distribution was face and neck for BCC and SCC and the trunk for MM. RESULTS: This article describes the most common forms of skin cancer in our region, BCC (almost 55%), SCC (17.6%), and less in number MM (near to 10%); these results are similar to those published abroad in the last years. CONCLUSIONS: Future more elaborate interventional studies are necessary to identify the main risk factors in order to design the best preventive methods and, according to the skin cancer trend to specify the needs for dermatology network in our country.

Pruritus in the elderly. Pathophysiological, clinical, laboratory and therapeutic approach.

Generalized pruritus is a common symptom in elderly, patients, with severe impact on the quality of life. The diagnosis of senile idiopathic pruritus is made after the exclusion of a systemic disease such as chronic renal disease, hepatobilliary disease with cholestasis, thyroid dysfunctions, drug-induced hypersensitivity reactions, visceral or hematological neoplasia, and primitive dermatological distinct conditions. The pathophysiological mechanisms are still unclear. A critical role is considered to be played by changes related to skin aging, cutaneous nerve supply and other nervous system components. The clinical approach requires a thorough assessment of general health status. In primary skin conditions, a biopsy and direct immunofluorescence (DIF) are required, while in pruritus associated with a systemic disorder, the assessment of hematological, biochemical and immunological parameters and imaging are necessary. The treatment of a patient with chronic pruritus is often palliative and individualized, with emollients, sedating and non-sedating antihistamines, tricyclic antidepressants, gabapentinum, and narrow-band UVB phototherapy. Pruritus associated with systemic disease may be alleviated by etiologic treatment.

Correlation between lymphatic vessel density and microvessel density in cutaneous malignant melanoma.

BACKGROUND: Malignant melanoma is an aggressive neoplasm, known for its propensity to early metastatic spread, via lymphatic as well as blood vessels. Tumor progression to an aggressive phenotype is associated with angiogenesis. Tumor lymphangiogenesis may represent a marker for assessing the risk of metastasis in the regional lymph nodes. MATERIALS AND METHODS: We studied the lymphatic vessel density in peritumoral and intratumoral areas compared to overall microvessel density in 12 cases of malignant melanoma of the face. All cases were primary invasive melanomas, with a Clark level of invasion III and IV. Lymphatic vessels were marked with D2-40 murine monoclonal antibody and their density evaluated through hot-spot method by examination on optic microscopy (200×). Overall microvessel density was assessed using the same method, vascular endothelial cells being visualized using CD31 monoclonal antibody. Statistical analysis was made using SPSS 17.0 software package (Pearson correlation test and Student's t-test). RESULTS: The disposition and aspect of the lymphatic vessels were different in peritumoral and intratumoral areas. Thus, in peritumoral areas lymphatics were generally regular, large, dilated vessels whereas intratumoral lymphatic vessels were smaller, with an irregular lumen. Lymphatic vessel density was generally higher in peritumoral areas. Intratumoral lymphatic vessel density was lower, but significantly correlated to overall microvessel density in these areas. Overall microvessels density was increased in thick cutaneous melanoma. Vessels in the peritumoral areas were larger and more numerous compared to those found in normal tissue. In cases with a dense peritumoral inflammatory infiltrate, we found the highest vascular density. Intratumoral angiogenesis was moderate in most cases, with irregular, smaller or collapsed vessels. CONCLUSIONS: Evaluation of the lymphatic vessel density may prove to be useful for the prognostic assessment in malignant melanoma, as it may predict the patients with a risk of developing lymph node metastasis.

[Drug-induced dermatological pathology in renal transplantation patients]. / Patologia dermatologica iatrogena la pacientii cu transplant renal.

The broad spectrum of muco-cutaneous manifestations of renal transplantation patients correlates mainly with immunosuppressive therapy. Our study refers to 56 patients with renal transplantation (29 women and 27 men) followed up in the Dialysis and Renal Transplantation Center of Parhon University Hospital Iasi from November 2000 till October 2003. The most frequent muco-cutaneous manifestations were: infectious complications in 18 cases (32.1%), gum hyperplasia in 14 cases(25%), acne in 11 cases (19.6%), skin hyperpigmentation in 7 cases (12.5%), oral candidiasis in 6 cases (10.7%), vascular fragility in 5 cases (8.9%), hypertrichosis in 5 cases (8.9%), itching in 3 cases (5.3%), facial erythema in 3 cases (5.3%), full-moon facies in 3 cases (5.3%). These manifestations, often with unclear pathogenesis, are dose-related and almost unavoidable.

[Surgery experience regarding the pathology of the greater omentum]. / Morfopatologia omentumului mare chirurgical.

This study followed the evaluation of the surgical pathology of the greater omentum. From the casuistry of Urology Surgery Clinic in Hospital 2 Iasi, we have selected 1500 omentum pathologic specimens (inflammatory, traumatic, tumoral) that were investigated macroscopically and microscopically. The specimens were harvested during 1993-2000. Acute inflammatory involvement of the greater omentum recognizes a primitive etiology in 8-10% cases and secondary one in 90-92% cases; these lesions are associated to some inflammatory processes of peritoneal viscera by direct or indirect mechanisms. Non-tumoral pathology was signaled in 201 cases, malignant and benign tumors were found in 198 cases. Acute catarrhallis and phlegmonous omentitis were identified in: peritonitis by digestive perforation (240 cases), bladder perforation (12 cases), broken pyosalpinx (18 cases), acute calculosic colecystitis (260 cases), hernia (75 cases), strangled eventration (65 cases). The conclusion of our study is that there is a specific pathology for the omentum but also the latter is largely involved in the emergency and iterative abdominal surgical pathology.

Tolerance to penicillin in Staphylococcus pyogenes isolated from skin infections.

The tolerance to penicillin of S. pyogenes has been mentioned in pharyngeal strains and associated by some authors with penicillin treatment failure in streptococcal angina. In this study we followed the presence of tolerance in S. pyogenes strains isolated from children hospitalized in the Clinic of Infantile Surgery and Clinic of Dermatology Iasi for skin infections. From 138 samples of pus examined we isolated 14 strains of S. pyogenes. In 7 strains we pointed out the tolerance to penicillin by both, beta-lactamase disc test and time-killing curve methods. We did not correlate to our cases the tolerance presence with penicillin treatment failure.