Digital Ulcers in Systemic Sclerosis.

Digital ulcers (DU) are one of the most common complication of Systemic Sclerosis (SSc)-related vasculopathy and represent an important burden for the patients as well as for the society. Still today there is no agreement on the definition, classification and cathegorization of DU even if they are of pivotal importance in clinical practice, for treatment choice and prognostic outcomes, as well as for clinical trials. DU management requires a dedicated multidisciplinary team, that must remain ever vigilant for the development of infective complications and gangrene throughout their disease course, as well as patient education that is crucial to obtain the best compliance to assure the success of the treatment. Currently several drugs are available for DU treatment but in the future, more investigations will be needed to ameliorate the approach and the systemic and local therapies.

Validating the Italian Version of the International Skin Tear Advisory Panel Classification System.

OBJECTIVE: To validate the International Skin Tear Advisory Panel (ISTAP) Classification System in Italian. METHODS: In collaboration with the ISTAP, the classification system was translated into Italian using a forward-back translation process. To validate the translated system, a convenience sample of 212 health professionals classified 30 photographs of skin tears originally used by ISTAP. The wound images were labeled type 1, 2, or 3 as described by the classification system. The resulting scores were compared with the ISTAP classification, and the reliability of agreement was calculated with Fleiss κ. RESULTS: Complete data were obtained from 209 healthcare professionals. When the image classifications were compared with the original ISTAP indications, 72.5% of all classifications were correct. Data indicated a moderate level of agreement (Fleiss κ = 0.466, range = 0.41-0.60). Data analysis showed similar agreement levels between nurses (n = 197, Fleiss κ = 0.466) and nonnurses (n = 12, Fleiss κ = 0.46). CONCLUSIONS: The study validates the Italian version of the ISTAP skin tear classification system. Further studies are necessary to confirm the system's usability in Italian research and clinical settings.

Correlation between capillaroscopic classifications and severity in systemic sclerosis: results from SCLEROCAP study at inclusion.

OBJECTIVES: We assessed the correlation between severity of systemic sclerosis (SSc) and current staging systems based on nailfold capillaroscopy. METHODS: SCLEROCAP is a multicenter prospective study including consecutive scleroderma patients who have a yearly routine follow-up with capillaroscopy and digital blood pressure measurement. Capillaroscopy images were read by two observers blinded from each other, then by a third one in the case of discordance. A follow-up of 3 years is planned. The present study assessed the correlation between severity of systemic sclerosis (SSc) and current staging systems based on nail fold capillaroscopy at enrollment in the SCLEROCAP study. Univariate and multivariate logistic regression analysis was performed for both the Maricq and Cutolo classifications. RESULTS: SCLEROCAP included 387 patients in one year. Maricq's active and Cutolo's late classifications were very similar. In multivariate analysis, the number of digital ulcers (OR for 2 ulcers or more, respectively 2.023 [1.074-3.81] and 2.596 [1.434-4.699]) and Rodnan's skin score >15 (OR respectively 32.007 [6.457-158.658] and 18.390 [5.380-62.865]) correlated with Maricq's active and Cutolo's late stages. Haemoglobin rate correlated with Cutolo's late stage (hemoglobin<100 vs. >120 g/dl: OR 0.223 [0.051-0.980]), and total lung capacity with Maricq's active one: increase in 10%: OR0.833 [0.717-0.969]. CONCLUSIONS: The correlations found between capillaroscopy and severity of SSc are promising before the ongoing prospective study definitively assesses whether capillaroscopy staging predicts complications of SSc. Only two capillaroscopic patterns seem useful: one involving many giant capillaries and haemorrhages and the other with severe capillary loss.

Classification, categorization and essential items for digital ulcer evaluation in systemic sclerosis: a DeSScipher/European Scleroderma Trials and Research group (EUSTAR) survey.

BACKGROUND: A consensus on digital ulcer (DU) definition in systemic sclerosis (SSc) has been recently reached (Suliman et al., J Scleroderma Relat Disord 2:115-20, 2017), while for their evaluation, classification and categorisation, it is still missing. The aims of this study were to identify a set of essential items for digital ulcer (DU) evaluation, to assess if the existing DU classification was useful and feasible in clinical practice and to investigate if the new categorisation was preferred to the simple distinction of DU in recurrent and not recurrent, in patients with systemic sclerosis (SSc). METHODS: DeSScipher is the largest European multicentre study on SSc. It consists of five observational trials (OTs), and one of them, OT1, is focused on DU management. The DeSScipher OT1 items on DU that reached ≥ 60% of completion rate were administered to EUSTAR (European Scleroderma Trials and Research group) centres via online survey. Questions about feasibility and usefulness of the existing DU classification (DU due to digital pitting scars, to loss of tissue, derived from calcinosis and gangrene) and newly proposed categorisation (episodic, recurrent and chronic) were also asked. RESULTS: A total of 84/148 (56.8%) EUSTAR centres completed the questionnaire. DeSScipher items scored by ≥ 70% of the participants as essential and feasible for DU evaluation were the number of DU defined as a loss of tissue (level of agreement 92%), recurrent DU (84%) and number of new DU (74%). For 65% of the centres, the proposed classification of DU was considered useful and feasible in clinical practice. Moreover, 80% of the centres preferred the categorisation of DU in episodic, recurrent and chronic to simple distinction in recurrent/not recurrent DU. CONCLUSIONS: For clinical practice, EUSTAR centres identified only three essential items for DU evaluation and considered the proposed classification and categorisation as useful and feasible. The set of items needs to be validated while further implementation of DU classification and categorisation is warranted. TRIAL REGISTRATION: Observational trial on DU (OT1) is one of the five trials of the DeSScipher project (ClinicalTrials.gov; OT1 Identifier: NCT01836263 , posted on April 19, 2013).

Cutaneous Lymphoproliferative Disorders: What's New in the Revised 4th Edition of the World Health Organization (WHO) Classification of Lymphoid Neoplasms.

Cutaneous lymphoproliferative disorders remain a challenging aspect of dermatopathology, in part due to the rarity of the entities and extreme variability in clinical outcomes. Although many of the entities remain unchanged, the approach to some of them has changed in the new 2016 classification scheme of the World Health Organization. Chief among these are Epstein-Barr virus-associated lymphoproliferative disorders such as Epstein-Barr virus-associated mucocutaneous ulcer and hydroa vacciniforme-like lymphoproliferative disorder, primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma, primary cutaneous acral CD8+ T-cell lymphoma, primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder, and breast implant-associated anaplastic large cell lymphoma. In addition, translocations and gene rearrangements such as those involving the 6p25.3 locus have started to inform diagnosis and classification of anaplastic large cell lymphoma and lymphomatoid papulosis. In this review, we will examine what is new in the diagnostic toolbox of cutaneous lymphoproliferative disorders.

Utility of Skin Biopsy and Culture in the Diagnosis and Classification of Chronic Ulcers: A Single-Institution, Retrospective Study.

In the United States, chronic ulcers affect 6.5 million people, with a cost of ≈$20 million annually. The most common etiology of chronic ulcers in the United States is venous stasis, followed by arterial insufficiency and neuropathic ulcers. Less common causes of chronic ulcers include infection, inflammatory etiologies such as vasculitis and pyoderma gangrenosum, and neoplastic causes. Obtaining skin biopsy and tissue culture can be helpful in diagnosing unusual causes of chronic ulcers; however, there are little data on the diagnostic utility of skin biopsy in rendering a definitive diagnosis of the etiology of chronic ulcers. A retrospective study of all skin ulcers biopsied during a 10-year period at the University of Washington was undertaken. Re-excisions and surgical wounds were excluded. A total of 270 ulcer biopsy specimens were included. In 48% of cases, no specific diagnosis could be rendered histologically. 44.8% of chronic ulcers biopsied were due to atypical causes, with neoplasms (basal cell carcinoma, squamous cell carcinoma, melanoma, and cutaneous T-cell lymphoma) being the most common. Vasculitis and pyoderma gangrenosum each represented 1.5% of rendered diagnoses. Concomitant skin culture was performed in 28.9% of cases, and special stains [acid-fast bacilli, Brown and Brenn (B&B), Grocott's methenamine silver, and periodic acid-Schiff stains] were performed in 34.0%. Although more than half (49 of 78) of tissue cultures were positive, only 6.8% (12 of 175) of special stains on tissue sections were positive. We conclude that although the etiology of many ulcers cannot be determined by routine histology alone, skin biopsy of ulcers remains a critical part of the workup given that when a specific cause can be determined, atypical etiologies, including neoplasms, represent a significant proportion of chronic ulcers. Limitations of our study include referral bias. Our results also confirm the higher diagnostic yield of conventional tissue culture compared with special tissue stain biopsies of skin ulcers.

French Canadian translation and the validity and inter-rater reliability of the ISTAP Skin Tear Classification System.

OBJECTIVE: To adapt the International Skin Tear Advisory Panel (ISTAP) skin tear classification system into French Canadian, and to test the content validity and inter-rater reliability of the translated version. METHOD: Phase one included the translation of the ISTAP skin tear classification system into French Canadian, using a forward-back translation method. Following this the translated version was tested for content validity and inter-rater reliability with registered nurses from a French acute care hospital in Ottawa, Canada. RESULTS: The French Canadian translation of the ISTAP skin tear classification system was evaluated by 92 nurses without in-depth wound care training. The adapted version obtained a substantial level of agreement between users, (Fleiss' Kappa = 0.69). CONCLUSION: The study tested the content validity and inter-rater reliability of the French Canadian version of the ISTAP skin tear classification system. The results support previous studies and further validate the classification system as a reliable method for classifying skin tears. The study supports ISTAP's goal of establishing a global language for describing and documenting skin tears.

Pyoderma Gangrenosum: A Critical Appraisal.

GENERAL PURPOSE: To provide information about pyoderma gangrenosum (PG), including pathophysiology, diagnostic criteria, and treatment. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant should be better able to: ABSTRACT: Pyoderma gangrenosum (PG) is an uncommon cutaneous disease, presenting with recurrent painful ulcerations most commonly on the lower extremities. The diagnosis is made according to a typical presentation, skin lesion morphology, skin biopsy, histopathology, and the exclusion of other etiologies. Classically, PG presents with painful ulcers with well-defined violaceous borders; other variants including bullous, pustular, and vegetative/granulomatous can also occur. Treatment of PG involves a combination of topical and systemic anti-inflammatory and immunosuppressive medications, wound care, antimicrobial agents for secondary infections, and treatment of the underlying etiology. This article is a continuing education review of the literature with a focus on the clinical application of the pathophysiology, diagnosis, and treatment of this challenging disease.

Clinical study on single-organ cutaneous small vessels vasculitis (SoCSVV).

Leukocytoclastic vasculitis (LCV) is a heterogenous group of disorders that may manifest as a mild disease isolated to the skin or be a part of life-threatening systemic vasculitis. According to the 2012 Chapel Hill Consensus Conference nomenclature, patients presenting symptoms of LCV confined only to the skin should be defined as suffering from a single-organ cutaneous small vessel vasculitis (SoCSVV). SoCSVV is a benign disease with a good clinical outcome but with a significant risk of relapse and skin ulcer formation.The aim of the current study was to characterize SoCSVV and to identify factors that may be associated with the risk of recurrence and skin ulcers.Medical records of patients with LCV hospitalized at the Department of Dermatology at University Hospital in Cracow in the years 2010 to 2015 were analyzed.A total of 24 patients fulfilled criteria of SoCSVV. Drugs and preceding infections were identified as precipitating factors in 40% and 20% of cases, respectively. Skin lesions other than palpable purpura (i.e., macules, urticarial vasculitis, or ulcers) were identified in almost half of the patients. Interestingly, the presence of macules independently increased the risk of skin ulcer formation (odds ratio = 16; 95% confidence interval: 1.5-176.6; P = 0.0075) in the multivariate logistic regression analysis. One-quarter of patients with SoCSVV experienced relapse during the 6-month follow-up. The greater number of affected skin areas was an independent risk factor of recurrence (odds ratio = 5; 95% confidence interval: 2-45; P = 0.02).SoCSVV was usually associated with drugs and preceding infections. The disease relapses in approximately one-quarter of the patients. The more severe the skin involvement in the course of SoCSVV, the higher is the risk of recurrence.

Elucidating the burden of recurrent and chronic digital ulcers in systemic sclerosis: long-term results from the DUO Registry.

OBJECTIVES: Digital ulcers (DUs) occur in up to half of patients with systemic sclerosis (SSc) and may lead to infection, gangrene and amputation with functional disability and reduced quality of life. This study has elucidated the burden of SSc-associated DUs through identification of four patient categories based on the pattern of DU recurrence over a 2-year observation period. METHODS: Patients with SSc-associated DUs enrolled in the Digital Ulcers Outcome Registry between 1 April 2008 and 19 November 2013, and with ≥2 years of observation and ≥3 follow-up visits during the observation period were analysed. Incident DU-associated complications were recorded during follow-up. Work and daily activity impairment were measured using a functional assessment questionnaire completed by patients after the observation period. Potential factors that could predict incident complications were identified in patients with chronic DUs. RESULTS: From 1459 patients, four DU occurrence categories were identified: 33.2% no-DU; 9.4% episodic; 46.2% recurrent; 11.2% chronic. During the observation period, patients from the chronic category had the highest rate of incident complications, highest work impairment and greatest need for help compared with the other categories. Independent factors associated with incident complications included gastrointestinal manifestations (OR 3.73, p=0.03) and previous soft tissue infection (OR 5.86, p=0.01). CONCLUSIONS: This proposed novel categorisation of patients with SSc-associated DUs based on the occurrence of DUs over time may help to identify patients in the clinic with a heavier DU burden who could benefit from more complex management to improve their functioning and quality of life.

Grading of shoulder ulcerations in sows by biopsies.

Shoulder ulcerations can be graded postmortem from 0 to 4 on a pathoanatomical scale. However, veterinarians and farmers express difficulties evaluating the grade of the lesions antemortem. Accurate grading is needed in order to comply with veterinary instruction in relation to the Danish legislation, stating that sows with shoulder ulcers grade 3 or 4 must be kept loose and have access to soft bedding. Thus, the aim of the present study was to evaluate if biopsies from the center of a shoulder ulcer can be used to point out animals for which an intervention must be initiated. Postmortem, a punch biopsy was sampled from the center of the ulceration or from the tissue overlaying the tuber spina scapula. Afterward, the shoulders were cross-sectioned and evaluated grossly and histologically ("gold standard"). In total, 121 shoulders were included in the study, and the diagnostic value of a punch biopsy in grading shoulder ulcerations was evaluated. The results showed a sensitivity of 0.78, a specificity of 0.98, a positive likelihood ratio of 38.36, and a negative likelihood ratio of 0.22. The agreement between the cross-section evaluation and the punch biopsy was found to be 0.90 by calculating the Cohen kappa value. In conclusion, a single punch biopsy from the center of an ulcer is useful for determining the grade of a shoulder ulcer and can be used to facilitate the identification of sows with ulcers requiring an intervention.

Consensus opinion of a North American Working Group regarding the classification of digital ulcers in systemic sclerosis.

The objectives of this study were to develop a standard classification of digital ulcers (DUs) in systemic sclerosis (SSc) for use in observational or therapeutic studies and to assess the reliability of these definitions as well as of the measurement of ulcer area. Ten North American rheumatologists with expertise in SSc reviewed multiple photos of DUs, examined four SSc subjects with DUs, and came to a consensus on the definitions for digital, active, healed, and indeterminate ulcers. These ten raters then examined the right hand of ten SSc subjects twice and the left hand once to classify ulcers and to measure ulcer area. Weighted and Fleiss kappa were used to calculate intra- and interrater agreement on classification of ulcers, and intraclass correlation coefficient (ICC) was used to assess agreement on ulcer area. Because the traditional ICC calculations relied on a small number of ulcers, ICCs were recalculated using the results of linear mixed models to evaluate the variance components of observations on all the data. Intrarater kappa for classifying DU as not an ulcer/healed ulcer versus active/indeterminate ulcer was substantial (0.76), and interrater kappa was moderate (0.53). The ICC for ulcer area using the linear mixed models was moderate both for intrarater (0.57) and interrater (0.48) measurements. A consensus for the classification of DUs in SSc was developed, and after a training session, rheumatologists with expertise in SSc are able to reliably classify DUs and to measure ulcer area.

A Delphi exercise and cluster analysis to aid in the development of potential classification criteria for systemic sclerosis using SSc experts and databases.

OBJECTIVES: Since the 1980 ACR classification criteria for systemic sclerosis (SSc) do not identify 20% with SSc, revised criteria are necessary. METHODS: Suggested new criteria from the literature were sent in random order to 96 SSc experts. A 3-round Delphi Consensus eliminated criteria. Then cluster analysis reduced items. The Canadian Scleroderma Research Group (CSRG) database was used to determine the prevalence of each item. RESULTS: Seventy-one of 96 (71%) completed all 3 rounds; 47 items were expanded to 76 in round 2. Thirty items had at least 50% consensus and 18 had >75% agreement to include (a priori cut point). Clustering occurred for 4 categories: proximal to MCP skin involvement, vascular abnormalities, autoantibodies and tissue damage. Proximal to MCPs skin involvement identified 80% of patients. Adding one item from each of the other 3 categories or 1 or more items from 2 of 3 remaining categories increased the proportion of patients classified to 94% in CSRG patients. Categories included (1) Vascular (dilated capillaries, telangiectasia, Raynaud's phenomenon [RP]), (2) Autoantibodies (anticentromere [ACA] or antitopoisomeraseI [Topo1]) and (3) Fibrosis/damage (esophogeal dysmotility dysphagia, sclerodactyly, digital ulcers). In the CSRG, 98% were identified if using proximal skin involvement; or sclerodactyly plus one of: RP, ACA or Topo1. CONCLUSIONS: This is a first step toward developing new SSc classification criteria. A Delphi exercise alone cannot suffice for item reduction. Also, validation prospectively in SSc patients and diseases that mimic SSc is needed in order to calculate sensitivity and specificity of future criteria.

Classification of color images of dermatological ulcers.

We present color image processing methods for the analysis of images of dermatological lesions. The focus of the present work is on the application of feature extraction and selection methods for classification and analysis of the tissue composition of skin lesions or ulcers, in terms of granulation (red), fibrin (yellow), necrotic (black), callous (white), and mixed tissue composition. The images were analyzed and classified by an expert dermatologist into the classes mentioned above. Indexing of the images was performed based on statistical texture features derived from cooccurrence matrices of the RGB (Red, Green, and Blue), HSI (Hue, Saturation, and Intensity), L*a*b*, and L*u*v* color components. Feature selection methods were applied using the Wrapper algorithm with different classifiers. The performance of classification was measured in terms of the percentage of correctly classified images and the area under the receiver operating characteristic curve, with values of up to 73.8% and 0.82, respectively.