Győző Szolnoky

Lipedema: an overview of its clinical manifestations, diagnosis and treatment of the disproportional fatty deposition syndrome - systematic review.

Lipedema is a disproportionate, symmetrical fatty swelling characterized by pain and bruising existing almost exclusively among women. We undertook a systematic review of the available literature about lipedema, given the lack of knowledge and little evidence about this disorder especially among obesity experts. Diagnosis of lipedema is usually based on clinical features. Symmetrical edema in the lower limbs with fatty deposits located to hips and thighs usually appears at puberty and often affects several members of the same family. Main disorders considered for differential diagnosis are lymphedema, obesity, lipohypertrophy and phlebedema. Treatment protocols comprise conservative (decongestive lymphatic therapy) and surgical (liposuction) approaches. Early diagnosis and treatment are mandatory for this disorder otherwise gradual enlargement of fatty deposition causes impaired mobility and further comorbidities like arthrosis and lymphatic insufficiency.

Pathophysiological dilemmas of lipedema

Lipedema is a common, but often underdiagnosed masquerading disease of obesity, which almost exclusively affects females. There are many debates regarding the diagnosis as well as the treatment strategies of the disease. The clinical diagnosis is relatively simple, however, knowledge regarding the pathomechanism is less than limited and curative therapy does not exist at all demanding an urgent need for extensive research. According to our hypothesis, lipedema is an estrogen-regulated polygenetic disease, which manifests in parallel with feminine hormonal changes and leads to vasculo- and lymphangiopathy. Inflammation of the peripheral nerves and sympathetic innervation abnormalities of the subcutaneous adipose tissue also involving estrogen may be responsible for neuropathy. Adipocyte hyperproliferation is likely to be a secondary phenomenon maintaining a vicious cycle. Herein, the relevant articles are reviewed from 1913 until now and discussed in context of the most likely mechanisms leading to the disease, which could serve as a starting point for further research.

Towards an effective management of chronic lymphedema

Lymph conduit perturbation causes lymph stasis and the local accumulation of interstitial fluid. Lymphedema, a chronic and debilitating disorder, remains incurable despite the advances in the description of its pathomechanism and the improvement of conservative and nonsurgical treatments. The gold standard of lymphedema treatment is multicomponent decongestive physiotherapy. Manual lymph drainage, compression bandaging, skin care, and exercises constitute the therapeutic regimen that could be adjusted with intermittent pneumatic compression. Prophylaxis could give a major benefit to risk group patients; however, the assessment of preventive approaches postulates further clinical trials. Surgery represents an emerging stakeholder in lymphedema care, although, the partnership with adjunctive nonsurgical therapy is still alive. Liposuction proved to be one of the most promising technique with the clearance of the lymph stasis-related adipose tissue. Regeneration of lymphatic tunnels with lymphovenous anastomoses or the transplantation of lymph vessels or small veins is based on long-term experience. The success of lymph node transplantation is still under evaluation, but this novel technique has produced notable improvements.

The expression of inflammatory cytokines, TAM tyrosine kinase receptors and their ligands is upregulated in venous leg ulcer patients: a novel insight into chronic wound immunity

The systemic host defence mechanisms, especially innate immunity, in venous leg ulcer patients are poorly investigated. The aim of the current study was to measure Candida albicans killing activity and gene expressions of pro‐ and anti‐inflammatory cytokines and innate immune response regulators, TAM receptors and ligands of peripheral blood mononuclear cells separated from 69 venous leg ulcer patients and 42 control probands. Leg ulcer patients were stratified into responder and non‐responder groups on the basis of wound healing properties. No statistical differences were found in Candida killing among controls, responders and non‐responders. Circulating blood mononuclear cells of patients overexpress pro‐inflammatory (IL‐1α, TNFα, CXCL‐8) and anti‐inflammatory (IL‐10) cytokines as well as TAM receptors (Tyro, Axl, MerTK) and their ligands Gas6 and Protein S compared with those of control individuals. IL‐1α is notably overexpressed in venous leg ulcer treatment non‐responders; in contrast, Axl gene expression is robustly stronger among responders. These markers may be considered as candidates for the prediction of treatment response among venous leg ulcer patients.

Differential Diagnosis – Lipedema

Lipedema is an infrequently recognized and often neglected clinical entity that nearly always affects women. It poses a diagnostic challenge as one of the common disorders that is easily confused with lymphedema.

Rigid body rotation of the left ventricle in hidradenitis suppurativa (a case from the three-dimensional speckle-tracking echocardiographic MAGYAR-Path Study)

In healthy subject, the left ventricular (LV) apex rotates in counterclockwise direction, while the LV base shows a clockwise rotation resulting in a towel-wringing-like motion called LV twist (1). However, this is a very sensitive motion, which could be altered early by several pathological states.

Adult Atopic Dermatitis is Associated with Increased Aortic Stiffness

We read with interest the article by Kwa and Silverberg [1] entitled ‘‘Association Between Inflammatory Skin Disease and Cardiovascular and Cerebrovascular Co-morbidities in US Adults: Analysis of Nationwide Inpatient Sample Data’’ published in this journal. In their extensive survey, the authors give paramount clinical data that chronic inflammatory dermatologic disorders obviously raise the incidence of cardiovascular diseases in large patient cohorts. Besides that current study, recently published, large, population-based surveys have also reached the same conclusion that arterial hypertension was the most common feature of atopic dermatitis (AD)-related increased cardiovascular morbidity [2, 3]. However, none of these studies attempted to clarify the underlying causes. Interestingly, aortic stiffness measurement-directed interdisciplinary trials among psoriatic patients have proved that psoriasis is associated with increased aortic stiffness compared with ageand gender-matched, otherwise healthy controls [4]. So far AD has not been investigated in a similar way. In general cardiology practice, stiffness is considered a pivotal marker of aortic elastic properties that independently predicts cardiovascular disease morbidity and mortality [5]; thus the determination of aortic stiffness among atopic patients (as was done for psoriatic persons) seemed to be a logical approach to elucidate the cardiovascular interference of AD. We measured aortic stiffness parameters (aortic stiffness index, strain and distensibility) in young adult probands with AD [mean age 30.5± 10.8 years, 11 women and eight men, body mass index (BMI) 28.3± 3.5 kg/m] and without AD (mean age 29.3± 2.9 years, 11 women and eight men, BMI 29.5± 4.8 kg/m). AD disease severity was evaluated with the SCORing Atopic Dermatitis (SCORAD) index [6]. Although none of the AD patients or controls had known hypertension or were on antihypertensive treatment, three out of 19 AD patients and two out of 19 controls had high blood pressure values at the time of examination. A total of 16% (n = 3), 68% (n = 13), 16% (n = 3) of AD patients were classified as having mild (SCORAD\35), moderate (35\SCORAD\60) and severe (SCORAD[60) stages of AD, respectively. Each participant underwent physical examination, systolic and diastolic blood pressure (SBP and DBP, respectively) measurement, electrocardiography (ECG) measurements and transthoracic two-dimensional echocardiography (2DE). 2DE was accomplished with Toshiba Artida echocardiography equipment (Toshiba, Tokyo, Japan) in the left lateral decubitus position from multiple windows. Systolic and diastolic ascending aortic diameters (SD and DD, respectively) were measured on M-mode tracings at a level 3 cm above the aortic valve & Gy}oz}o Szolnoky szolnokygyozo@gmail.com

What can vasculitic leg ulcers implicate

Dear Editors, A 76-year-old woman presented with multiple irregular necrotic leg ulcers surrounded by palpable purpurae on the right leg, persisting for 2 years (Figure 1). Three years before, her left leg was amputated because of ulceration and concomitant septicemia. The patient had pallor, xerostomy, xerophthalmia, distal limb numbness without parotido-, lymphadenoor hepatomegaly. Haematoxylin–eosin-stained sections of the ulcer showed leucocytoclastic vasculitis with erythrocyte extravasation; direct immunofluorescence showed granular IgG and complement factor 3 depositions. Laboratory tests showed marked hypoproteinaemia, hypoalbuminaemia, elevated erythrocyte sedimentation rate, mild pancytopenia, high carbamide, creatinine, uric acid and C-reactive protein levels. Proteinuria, microscopic haematuria, granular, hyalin and cell cylinders suggested glomerular involvement. Autoimmune serology found positive anti-nuclear antibody, a robust elevation of anti-SS-A and rheumatoid factor and a moderate increase in anti-SS-B levels. Cryoprecipitation showed massive cryoglobulinaemia. Immunofixation electrophoresis detected non-quantifiable IgMκ biclonal and IgMλ monoclonal bands, and serum-free light chain assay showed very high κ level and abnormal κ:λ ratio (Table 1). Review of CT images revealed splenomegaly, but no lytic bone lesions related to multiple myeloma. Ultrasound and CT examinations showed bilateral parenchymal atrophy of the kidneys. Bone marrow trephine biopsy revealed discrete interstitial B-cell population suggestive of indolent B-cell lymphoproliferation, but no evidences of B-cell monoclonality was detected by PCR-based immunoglobulin heavy chain gene rearrangement analysis.

Chronic Nonhealing Wounds: Could Leg Ulcers Be Hereditary?

Background. A number of well-known acquired and putative inherited etiological factors contribute to the development of venous leg ulcer (VLU). Aim. In this study we set out to perform a meta-analysis of putative genetic and acquired factors predisposing to VLU development. Methods. VLU patients () were divided into three subgroups in accordance with their acquired etiological factors. The frequencies of four genetic factors were determined: the R506Q (Leiden) mutation of the F5 gene, the G20210A mutation of the F2 (prothrombin) gene, the 2451 A/G SNP of the fibroblast growth factor receptor 2 (FGFR2) 3′ UTR, and the −308 G/A SNP of the tumor necrosis factor α (TNFA) promoter. Results. The −308 TNFA SNP exhibited a higher frequency among VLU patients without known acquired predisposing factor in their history, than among patients with thrombosis or soft tissue infection in their history (Fisher ). Conclusions. This study has demonstrated that the group of VLU patients is heterogeneous in their genetic predisposing factors. Further large-scale studies are needed to delineate the associations among genetic and acquired etiological factors with regard to VLU development and to integrate the consequences of the already known genetic factors to the management of VLU.