Di Lernia V.,Dermatology Unit
Medical Hypotheses | Year: 2017
Immunoglobulin A (IgA) nephropathy (IgAN) may sometimes be related to exposure to pharmacological agents, among which anti-Tumor Necrosis Factor (TNF)-alpha agents. The characteristic pathological feature is a deposition of IgA-containing immune complexes in vessel walls in the kidney mesangium. The link between TNF-alpha blockers and IgAN may be hypothesized examining diseases which share pathologic features. In this respect, idiopathic IgAN and Henoch Schonlein Purpura have been the object of studies revealing a pathogenetic role of aberrant glycosylation of IgA1 molecules. The Authors suggest that anti-drug antibodies against glycan structures of TNF-alpha inhibitors may cross react against serum aberrant IgA1 leading to large antigen-antibody complexes. These large polymeric IgA complexes are then able to deposit in the mesangium and activate the complement cascade. Such hypothesis may be tested by measuring serum levels of galactose-deficient IgA1 of patients developing IgAN following introduction of TNF-alpha blockers. Such a test would be useful also before administration of anti-TNF alpha agents. The presence of aberrant IgA1 may represent a contraindication for treatment with TNF blockers. © 2017 Elsevier Ltd
Di Lernia V.,Dermatology Unit |
Bardazzi F.,University of Bologna
Drug Design, Development and Therapy | Year: 2016
The outlook for patients with psoriasis has improved significantly over the last 10 years with the introduction of targeted therapies. Cytokines exert their effects by activating intracellular signaling and transcription pathways, among which there are Janus kinases (JAKs) and signal transducers and activators of transcription (STAT) pathways. JAKs are intracellular second messengers that are crucial for transmitting extracellular cytokine signals to the cell. JAK inhibition interrupts intracellular signaling and can suppress immune cell activation and inflammation in T-cell-mediated disorders, such as psoriasis. Consequently, JAKs are the subject of intensive research activity, since they represent possible therapeutic targets. Tofacitinib is an orally available compound belonging to a novel category of nonbiologic drugs, the “JAK inhibitors”, which target JAKs. Recently, oral and topical formulations of tofacitinib have been demonstrated to be safe and effective for the treatment of plaque psoriasis in randomized clinical trials. In particular, a 10 mg bid dose of tofacitinib was shown to be noninferior to etanercept 50 mg subcutaneously twice weekly. Questions remain unresolved regarding the safety risk beyond the 5 mg bid dose. This review, assessing the available scientific literature, focuses on the profile of tofacitinib, as investigational compound in the treatment of plaque psoriasis. An overview of the efficacy and safety data from randomized clinical trials is provided. In addition, the authors highlight future potential applications of tofacitinib in other skin diseases, in particular alopecia areata and vitiligo. © 2016 Di Lernia and Bardazzi.
Caresana G.,Dermatology Unit |
Giardini R.,Pathology Unit
Journal of the European Academy of Dermatology and Venereology | Year: 2010
Background: In basal cell carcinoma (BCC), excision margins between 3 and 10 mm, according to site, size, borders, previous treatment and histology, can allow for radical excision in at least 95% of cases. Objective: The objective was to ascertain whether dermoscopy can detect more accurately the lateral borders in BCCs than clinical examination alone, and allow us to obtain radical excision in more than 95% of cases with only 2-mm excision margins. Methods: A prospective study was performed of 200 consecutive BCCs of the head and neck removed with 2-mm dermoscopically detected excision margins. Morpheaform BCC, deeply recurrent BCC, BCC in Gorlin-Goltz syndrome, BCC located in sites not accessible through dermoscopy and superficial multifocal BCC were excluded. All cases of excised BCC were submitted to a uniform method of histological examination of the whole specimen with serial parallel sections at 2-mm intervals. Results: In only three cases did surgical excision with 2-mm margins prove to be inadequate; in the remaining 197 cases, the excision margins were tumour-free. The comparison of clinical and dermoscopic extension measurement showed concordance in 131 cases (65.5%). In 69 cases (34.5%), dermoscopic evaluation showed a larger peripheral extension. Conclusions: These results indicate that 2-mm dermoscopically detected excision margins can achieve histologically confirmed complete excisions in 98.5% of cases. © 2010 European Academy of Dermatology and Venereology.
Lipozencic J.,University of Zagreb |
Wolf R.,Dermatology Unit
Clinics in Dermatology | Year: 2010
We conducted a systematic Medline search of the literature (1998-2008) on the criteria for performing the skin prick test and atopy patch testing (APT) to determine their utility in atopic dermatitis (AD). The skin prick, scratch, and skin patch tests are performed to identify which allergen is causing eczematous skin symptoms in patients with AD, or sneezing, nasal congestion, itchy eyes, wheezing, skin rash, and swelling. Many allergens in foods, drugs, and environmental substances (eg, ragweed and fungus), as well as contact allergens, can elicit eczematous skin reactions after epicutaneous application. Because no gold standard exists for aeroallergen provocation in AD, the APT is currently used to evaluate allergen without comparison with another accurate and reliable method. The APT is presumed to reflect delayed-phase clinical reactions. Even with delayed onset of symptoms (more than 2 hours after food ingestion), APT findings were not consistent among AD children. The APT could be used in children with gastrointestinal reactions to foods as well as AD. After standardization, the APT may provide further diagnostic information in addition to the skin prick test and serum immunoglobulin E values and may be able to evaluate the actual clinical relevance of immunoglobulin E-mediated sensitizations for eczematous lesions. The European APT model used with standardization of allergen concentration and vehicle may provide an important diagnostic tool to select patients for avoidance and for procedures of allergen-specific immunotherapy, but the clinical relevance of positive APT reactions awaits standardized provocation and avoidance testing. © 2010 Elsevier Inc. All rights reserved.
Di Lernia V.,Dermatology Unit
Expert Opinion on Therapeutic Targets | Year: 2015
Introduction: Recent data about atopic dermatitis (AD) pathogenesis postulate that T cells and their related cytokines and chemokines are primarily responsible for the inflammatory responses.Areas covered: AD, the primary complex disease associated with filaggrin deficiency, is characterized by cutaneous inflammation driven by type 2 helper T (TH2) cells. TH2-related molecules, such as IL-4, IL-13, dominate the immune infiltrate. Experimental evidences suggest that these cytokines may be considered attractive therapeutic targets in AD, particularly in extrinsic AD with IgE overproduction. Recently, a fully human monoclonal antibody directed against the IL-4 receptor α subunit blocking IL-4 and IL-13 signaling has been evaluated in Phase I and Phase II clinical trials in patients with moderate-to-severe AD with significant improvement in disease severity. Phase III trials are ongoing.Expert opinion: Treatment of AD represents a therapeutic challenge. TH2 cytokine-targeted therapies represent promising treatment options that could improve the therapeutic armamentarium for AD. These therapies are likely to become future therapeutic options in AD, particularly in the extrinsic AD. © 2015 Informa UK, Ltd.
Madarasingha N.P.,Dermatology Unit
The Ceylon medical journal | Year: 2011
The new case detection rate of leprosy and new cases among children remain high in Sri Lanka indicating ongoing transmission. Identification of the positive contacts and the source of infection would break this chain of transmission. Contact tracing is known to identify early disease and thus prevent disabilities. However, in the recent past little emphasis has been laid on contact tracing by the health care providers. This study looked at the household contacts of children with leprosy to identify the-rate of positive contacts within the household. The study was conducted at the Lady Ridgeway Hospital, Colombo, Sri Lanka, during a period of one year and nine months from January 2007. The index cases were defined as children of less than 12 years who were presently on anti leprosy treatment or who were newly diagnosed with leprosy. A total of 311 contacts of 100 index cases were examined for evidence of leprosy. The total of positive contacts was 51 per 100 index cases. 33% of the index cases had a positive contact within the household. 11% had more than one member affected. 83.2% of positive contacts were of tuberculoid type. 20.8% of the contacts were less than 15 years of age. When considering the relationship to the index case, most (33.3%) were siblings while 25.0% were parents and 20.8% were grandparents. Twenty five persons (8.0%) out of 311 household contacts were de novo cases. This study highlights the value of contact screening of leprosy patients.
Landau M.,Dermatology Unit
Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.] | Year: 2015
BACKGROUND: Most of the complications associated with hyaluronic acid (HA) fillers can be addressed by hyaluronidase. Extensive experience with this enzyme was accumulated in ophthalmology and anesthesia. In dermatologic use multiple aspects still remain controversial.OBJECTIVE: To elucidate questions with regard to hyaluronidase use in HA-induced complications, including appropriate dosage, timing, and technique of delivery, differences in the activity of hyaluronidases of different origins, interaction between the enzymes and different HA gels, and safety issues.MATERIALS AND METHODS: Extensive review of the relevant literature was conducted. The conclusions are based on this review and personal author's experience.RESULTS: FDA-approved hyaluronidases provide predictable results and can be used interchangeably. A physician has to be closely familiar with specific characteristics of other hyaluronidases. Different brands of HA fillers have different sensitivity to degradation by hyaluronidase. For filler overcorrection or misplacement, low dose of the enzyme has to be injected directly into the palpable HA mass. In case of vascular accident, flushing of the ischemic area with high doses of hyaluronidase is required. Hypersensitivity reactions to hyaluronidase are so far not reported in dermatologic literature.CONCLUSION: With increased popularity of HA fillers, hyaluronidase had become an indispensable tool in dermatology office. It is safe and reliable for treatment of HA-induced complications.
Lal K.,York College |
Di Lernia V.,Dermatology Unit
Clinical and Experimental Dermatology | Year: 2015
Linear whorled naevoid hypermelanosis (LWNH) is a rare skin condition, characterized by swirls and whorls of hyperpigmented macules distributed in a reticulate pattern along the lines of Blaschko. We report a 2-year-old boy who presented with linear and whorled hyperpigmentation on his trunk and limbs, following the lines of Blaschko. Hyperkinesia and developmental speech-language impairment were also present. A biopsy specimen showed increased pigmentation within the basal keratinocytes without incontinentia pigmenti. No chromosomal abnormality was found in peripheral blood samples. Chromosomal analysis of skin fibroblasts detected trisomy 4 mosaicism. This case shows for the first time an association of LWNH with trisomy 4 mosaicism. LWNH should not be considered a single entity, but a cutaneous expression of mosaicism. © 2014 British Association of Dermatologists.
Wolf R.,Dermatology Unit |
Davidovici B.,Dermatology Unit
Clinics in Dermatology | Year: 2010
Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are uncommon but extremely serious and often life-threatening mucocutaneous reactions characterized by extensive epithelial sloughing and systemic symptoms. There is no effective evidence-based treatment for severe cutaneous adverse reactions (SCAR) to drugs and no consensus on how to treat these patients. This contribution presents some of the controversies concerning the treatment of SCAR patients, including where and by whom, as well as the issue of the value of treatment with corticosteroids and intravenous immunoglobulin. Investigators agree that more studies are needed and that there are insufficient data to draw definite conclusions. The spectrum of disagreement is wide and the debate is ongoing. At the end, the important question is should we wait with our decisions until all these controversies are settled and we have more or full evidence. This question, as well as all others, is open for debate, evidently a "toxic" debate on toxic epidermal necrolysis. © 2010 Elsevier Inc.
Landau M.,Dermatology Unit
Plastic and Reconstructive Surgery | Year: 2015
Loss of viscoelasticity is one of the primarily signs of skin aging, followed by appearance of visible wrinkles. Hyaluronic acid (HA)-based fillers are widely used to fill wrinkles and compensate for volume loss. Recent clinical observations demonstrate persistence of the filling effect longer than the biological availability of the filler. Stimulation of new collagen by cross-linked HA and up-regulation of elastin have been suggested as possible explanation to this observation and have been supported experimentally. Cross-linked HA substitutes for fragmented collagen in restoring extracellular matrix required for normal activity of fibroblasts, such as collagen and elastin production. To restore extracellular matrix efficiently, serial monthly treatments are required. Boosting of facial and nonfacial skin through fibroblast activation is a new indication for HA-based products. Injectable HA has also been recently registered in Europe as agents specific for the improvement of skin quality (Restylane Skinboosters). Further explanation of the possible mechanisms supported by long-term clinical examples is presented herein. Copyright © 2015 by the American Society of Plastic Surgeons.