Antibody-Negative Paraneoplastic Autoimmune Multiorgan Syndrome (PAMS) in a Patient with Follicular Lymphoma Accompanied by an Excess of Peripheral Blood CD8+ Lymphocytes.

Paraneoplastic autoimmune multiorgan syndrome (PAMS) is a life-threatening autoimmune disease associated with malignancies. Here, we present a patient initially misdiagnosed with "chronic" Stevens-Johnson syndrome. Over a year later, the patient was diagnosed with stage IV follicular lymphoma and treated with an anti-CD20 antibody. At this time, his skin condition had significantly worsened, with erythroderma and massive mucosal involvement, including in the mouth, nose, eyes, and genital region. Histopathology revealed lichenoid infiltrates with interface dermatitis, dyskeratoses, necrotic keratinocytes, and a dense CD8+ infiltrate with strong epidermotropism. Direct and indirect immunofluorescence tests for autoantibodies were negative. Remarkably, we retrospectively discovered a chronic increase in peripheral CD8+ lymphocytes, persisting for over a year. Consequently, the patient was diagnosed with antibody-negative PAMS. Three weeks later, he succumbed to respiratory failure. This dramatic case highlights the challenges in diagnosing PAMS, particularly in cases where immunofluorescence assays are negative. Importantly, we observed, for the first time, a chronic excess of CD8+ peripheral blood lymphocytes, associated with PAMS, consistent with the systemic, autoreactive T-cell-driven processes that characterize this condition.

Determining the origin of superficial venous reflux in the groin with duplex ultrasound and implications for varicose vein surgery.

OBJECTIVE: The purpose of this paper was to describe patterns of superficial reflux in the groin with respect to the terminal valve (TV), which is located at the saphenous opening to the common femoral vein, the great saphenous vein, and its tributary veins. METHODS: This study included 2019 legs with chronic venous insufficiency that received endoluminal varicose vein treatment because of varicosities with insufficiency of the saphenofemoral junction (SFJ). In a preoperative duplex ultrasound investigation of the superficial vein system, reflux after provocation in the SFJ, great saphenous vein, cranial veins (superficial external pudendal vein, superficial epigastric vein, superficial circumflex iliac vein), and anterior and posterior accessory saphenous veins was recorded and classified on the basis of the origin of reflux. RESULTS: In 1348 legs (66.8%), the reflux had its origin exclusively in the common femoral vein. In 170 legs (8.4%), the reflux had its origin in the common femoral and cranial veins. In 430 legs (21.3%), the insufficiency was due to saphenocranial reflux only. In 71 legs (3.5%), the origin of reflux could not be determined. CONCLUSIONS: Reflux in the SFJ does not involve the TV in 24.8% of the legs, implying that routine high ligation and ablation close to the TV might be overtreatment in these patients.

Squamous cell carcinomas in chronic venous leg ulcers. Data of the German Marjolin Registry and review.

BACKGROUND: Secondary squamous cell carcinoma (SCC) is a rare complication of chronic venous leg ulcers. So far, little is known about its pathophysiology and clinical behavior. Initiated by the working group "Wound Healing" (AGW) of the German Society of Dermatology (DDG), it is the objective of the current Marjolin registry to collect cases of SCC arising in venous ulcers, in order to evaluate diagnostic characteristics. PATIENTS AND METHODS: All members of the AGW received questionnaires inquiring about basic patient data, ulcer characteristics, and therapy conducted. RESULTS: From 2010 to 2013, 30 patients (20 women, 10 men) from six tertiary wound care centers were registered. Mean age was 76.17 years. The average duration of venous leg ulcers prior to SCC diagnosis was 15.93 years. Suspicious wound characteristics primarily included: pain (n = 3), therapy resistance (n = 27), and fetor (n = 12) as well as clinical appearance (n = 10) with atypical morphology, nodular wound bed, and hypergranulation. CONCLUSIONS: Atypical morphology or changes in appearance as well as therapy resistance despite optimal care (6-12 weeks) should prompt physicians to take spindle-shaped, if necessary multiple and serial, biopsies. Primary risk factors for malignant transformation include patient age and ulcer duration.

Occlusion rate, venous symptoms and patient satisfaction after radiofrequency-induced thermotherapy (RFITT®): are there differences between the great and the small saphenous veins?

BACKGROUND: Previous studies on the therapy of insufficient saphenous veins mainly compare different treatment methods. Only a few investigate differences of a specific treatment option between the great (GSV) and the small saphenous vein (SSV). The aim of this study was to evaluate the efficacy, clinical improvement and patient satisfaction after radiofrequency-induced thermotherapy (RFITT®) with regard to the treated vein. PATIENTS AND METHODS: We included 65 patients (40 women, 25 men; mean age 54.75 years) who were treated with RFITT® for incompetent saphenous veins (n = 83: 62 GSV, 21 SSV). Occlusion rates were determined by duplex-sonography. Additionally, we performed a prospective analysis of venous symptoms and signs by means of a standardized questionnaire and of patient satisfaction using a semi-quantitative rating (1 = very good, 6 = insufficient). RESULTS: The GSV group showed a significantly greater reduction of venous symptoms in comparison to the SSV group (p = 0.005) despite no significant differences in long term occlusion rates (mean time after operation: 22 months) of 90 % in the GSV group and 81.8 % in the SSV group (p = 0.598). Following the procedure, detailed analysis revealed significantly more swelling (p = 0.022), feeling of heavy legs (p = 0.002) and nightly calf cramps (p = 0.001) in the SSV group. Additionally, RFITT® led to a significant improvement in patient satisfaction in the GSV group (from 1.93 at day 1 - 3 to 1.41 after 6 - 12 months, p = 0.009) but not in the SSV group (from 2.29 to 2.07, p = 0.43). CONCLUSIONS: With regard to the improvement of venous symptoms and patient satisfaction, the benefit of RFITT® is greater for patients with incompetent GSV compared to those with incompetent SSV.

A novel epidermal growth factor--containing wound dressing for the treatment of hard-to-heal venous leg ulcers.

OBJECTIVE: To evaluate the efficacy, tolerability, and safety of a novel wound dressing containing epidermal growth factor (EGF) in a collagen-gel matrix on hard-to-heal venous leg ulcers. PATIENTS AND METHODS: The authors included 33 hard-to-heal venous leg ulcers found on 31 patients. The EGF-containing dressing was applied 3 times while best practice conservative wound treatment was continued. Patients were followed up with after 1, 2, and 3 months to evaluate (a) the wound size, (b) the ease of application and dissolution of the dressing, and (c) the wound dressing by means of a scale ranging from 1 to 5 (1 = best, 5 = worst). RESULTS: The protocol was completed by 25 of 31 patients. The reasons for discontinuation were wound infection, pain, and lost to follow-up (n = 2 each, respectively). After 3 months, the average wound surface was significantly reduced (from 33.69 cm to 18.94 cm, P = .023). On a scale from 0 to 100, the wound dressing was evaluated as very easy to apply and highly dissolvable (mean value of 97.14 and 98.11, respectively; 100 = very easy to apply or 100% dissolution). The dressing was generally well tolerated and scored a mean overall rating of 2.16 by healthcare specialists and 2.40 by patients. CONCLUSION: The authors' results demonstrate that the novel EGF-containing wound dressing was generally well tolerated and safe. Combined with the significant wound surface reduction, it can be regarded as an adequate novel treatment option for patients with hard-to-heal venous leg ulcers.

Foam sclerotherapy with enoxaparin prophylaxis in high-risk patients with postthrombotic syndrome.

BACKGROUND: According to the current guidelines for sclerotherapy hypercoagulability and thrombophilia with or without deep venous thrombosis are seen as relative contraindication for this treatment. But often such patients have an indication for a sclerotherapy. Recommendations for additional anticoagulation for sclerotherapy are missing. PATIENTS AND METHODS: In this retrospective analysis (2009 - 2010), 54 patients with deep venous thrombosis and/or pulmonal embolism in their medical history that had had foam-sclerotherapy of truncal or tributary veins with polidocanol 0.5 - 3 % without prior anticoagulation therapy were included. In addition to compression treatment (23 - 32 mmHg) for 3 weeks patients were treated with enoxaparin 40 mg once a day for 3 days after sclerotherapy. Clinical and duplex controls were conducted before every treatment and 2 - 3 weeks after the last injection. RESULTS: Sclerotherapy was done on one (30/54) or on both (24/54) legs. In 2/54 legs a truncal vein and in all patients tributaries were treated. The volume per treatment session averaged 3.3 ml foam (2 - 6 ml). The patients had undergone an average of 4.9 treatments (1 - 11); altogether 262 sessions. There were no cases of deep venous thrombosis or symptomatic pulmonary embolism. In 7/262 treatments (2.7 %) symptomatic localized phlebitis occurred and in 2/262 (0.8 %) patients an ascending phlebitis beyond the sclerotherapy region was observed. CONCLUSIONS: Based on current data, foam sclerotherapy can be regarded as safe in patients with anamnestic thromboembolism when co-treated with compression therapy (23 - 32 mmHg) and enoxaparin 40 mg once per day for 3 days post sclerotherapy. The current study is the first with a standardized regime. In view of the limitations of this study there should be further randomized controlled trials.

Impact on wound healing and efficacy of various leg ulcer debridement techniques.

AIM: To evaluate the evidence on the impact of different debridement techniques on healing and their efficacy in the treatment of leg ulcers. METHODS: Web-based search (PubMed) for trials investigating surgical, enzymatic, autolytic, osmotic, ultrasound-assisted, and biosurgical wound debridement on leg ulcers with regard to healing and efficacy. RESULTS: Both surgical and hydrosurgical methods proved to be effective debridement techniques. For conventional surgical debridement, a significantly greater reduction of the wound surface area and a higher healing rate were reported. Studies on autolytic, osmotic, and enzymatic wound debridement showed effective debridement for krill enzymes, dextranomer and manuka honey. Only for manuka honey was there a significantly greater reduction of the wound surface area compared to standard treatment. One study comparing fibrinolysin/DNAse with placebo and one comparing autolytic with enzymatic debridement showed no significant differences between the respective techniques. Trials on ultrasound-assisted wound debridement reported a positive impact on healing. A significant wound surface area reduction was demonstrated in one of them. Maggot therapy led to effective debridement. The largest trial showed no significantly improved healing. CONCLUSIONS: Further studies are needed to strengthen the evidence for a significant impact of wound debridement on the healing of leg ulcers.

Subtype and genotypic resistance analysis of HIV-1 infected patients in Austria.

BACKGROUND: Analysis of HIV-1 subtypes and genotypic resistance have been shown to be relevant for epidemiologic and therapeutic studies or for vaccine development. In Europe, the majority of HIV-1 isolates belong to subtype B. Due to migration an increasing incidence for additional subtypes and complex recombinant forms are expected. OBJECTIVES AND STUDY DESIGN: To evaluate the prevalence of HIV-1 subtypes in Austria, 188 plasma samples of treatment experienced patients were investigated. For phylogenetic analysis protease and reverse transcriptase genes were amplified and sequenced. Subtypes were determined by comparing reference sequences. For genotypic resistance determination, the Resistance-Algorithm-Comparison from Stanford University was used. RESULTS: Non-B subtypes were found in 20.2% of all patients with a dominant prevalence (50%) in the Southern provinces of Austria. With 85% CRF01_AE and CRF02_AG are the predominant circulating recombinant forms in Austria. When resistance mutations were analyzed, 57.4% of all patients were susceptible to all three groups of antiretroviral drugs, whereas in 12.2% resistance against all three classes of antiretroviral drugs was found. CONCLUSION: HIV-1 subtype B is still dominant in major parts of Austria. However, a significantly increasing percentage of non-B subtypes and recombinant forms are observed in the Southern provinces.