Primary upper-limb lymphoedema.

BACKGROUND: Lymphoedema is a general term used to designate pathological, regional accumulation of protein-rich fluid. It can be either primary or secondary, and mainly occurs after cancer treatment. OBJECTIVES: To analyse the clinical and lymphoscintigraphic characteristics of primary upper-limb lymphoedema (ULL). METHODS: All of the patients with ULL were recruited at a single Department of Lymphology between January 2007 and December 2011. RESULTS: In total, 60 patients (33 female, 27 male) were enrolled. For the 54 noncongenital lymphoedemas, the mean age at onset was 38·5 (range 3-82) years. Lymphoedema was unilateral in 51 patients (85%). It always affected the hand, and less often the forearm (55%) or upper arm (23%). Eleven patients (18%) developed cellulitis after onset of lymphoedema, and 21 patients (35%) had associated lower-limb lymphoedema (LLL). Forty-six patients (with 49 lymphoedematous limbs) underwent lymphoscintigraphy: axillary lymph node uptake was diminished in 18 (37%), absent in 24 (49%) and normal in seven limbs (14%). Among the 43 patients with unilateral lymphoedema and lymphoscintigraphy, 28 had epitrochlear node visualization, suggesting a rerouting through the deep lymphatic system, with 15 only on the lymphoedematous limb and 22 on the contralateral nonlymphoedematous limb. The median follow-up period was 103 months, and 57/60 patients (95%) considered their lymphoedema to be stable. CONCLUSIONS: Primary ULL appears later in life than LLL, without predominance in either sex. Infectious complications are rare and patients considered the lymphoedema volume stable throughout life.

Complications of autologous lymph-node transplantation for limb lymphoedema.

OBJECTIVE: This study aims to assess potential complications of autologous lymph-node transplantation (ALNT) to treat limb lymphoedema. DESIGN: Prospective, observational study. METHOD: All limb-lymphoedema patients, followed up in a single lymphology department, who decided to undergo ALNT (January 2004-June 2012) independently of our medical team, were included. RESULTS: Among the 26 patients (22 females, four males) included, 14 had secondary upper-limb lymphoedema after breast-cancer treatment and seven had secondary and five primary lower-limb lymphoedema. Median (interquartile range, IQR) ages at primary lower-limb lymphoedema and secondary lymphoedema onset were 18.5 (13-30) and 47.4 (35-58) years, respectively. Median body mass index (BMI) was 25.9 (22.9-29.3) kg m⁻². For all patients, median pre-surgery lymphoedema duration was 37 (24-90) months. Thirty-four ALNs were transplanted into the 26 patients, combined with liposuction in four lower-limb-lymphoedema patients. Ten (38%) patients developed 15 complications: six, chronic lymphoedema (four upper limb, two lower limb), defined as ≥2-cm difference versus the contralateral side, in the limb on the donor lymph-node-site territory, persisting for a median of 40 months post-ALNT; four, post-surgical lymphocoeles; one testicular hydrocoele requiring surgery; and four with persistent donor-site pain. Median (IQR) pre- and post-surgical lymphoedema volumes, calculated using the formula for a truncated cone, were, respectively, 1023 (633-1375) ml (median: 3 (1-6) months) and 1058 (666-1506) ml (median: 40 (14-72) months; P = 0.73). CONCLUSION: ALNT may engender severe, chronic complications, particularly persistent iatrogenic lymphoedema. Further investigations are required to evaluate and clearly determine its indications.

Lymphedema and Kaposi sarcoma: A narrative review.

BACKGROUND: Kaposi sarcoma (KS), due to HHV-8 infection is classified in 4 subtypes: epidemic, endemic, HIV-related and iatrogenic essentially after organ transplant. Lymphedema is a complication of KS. We reviewed the interactions between HHV-8 infection and lymphedema according an analysis of the literature. MAIN BODY: HHV-8 can infect different types of cells, among them a privileged tropism for lymphatic endothelial cells. It induces multi-centric endothelial proliferation leading to the occlusion of lymphatic vascular lumen. Lymphatic obstruction progressively lead to the blockage of lymphatic drainage, lymph stasis and lymphedema. Lymphedema mostly involved the lower limb affected by KS. It can then develop simultaneously or after the appearance of KS lesions but also be the first sign of KS, a long time before KS skin lesion onset. Lymphedema diagnosis is clinical and lymphoscintigraphy can confirm it if necessary. Lymphedema may be associated with active lesions of KS or non-evolutive, with only cicatricial lesions. KS should be treated according to the KS subtype, aggressive form, with local or systemic treatments associating with causal treatment, such as HIV infection or reducing immuno-suppressive drugs in transplant patients. In most of the cases, KS treatment may slightly reduce (or not) lymphedema volume which remains a chronic disease. Lymphedema management should be associated in order to reduce the volume and then stabilizing it. Low-stretch bandage, elastic garments and skin care are the cornerstone of treatment. CONCLUSION: Lymphedema is a frequent complication of KS, and may reveal KS or occurs throughout its course. Association of KS and lymphedema must be known because lymphedema is a chronic disease affecting the quality of life. Beyond the treatment of KS, its management must be specific including a long follow-up to optimize the patient's observance required to maintain the best lymphedema control.

[Pretibial myxedema after Graves' disease: A differential diagnosis of lymphedema]. / Myxœdème prétibial pseudo-tumoral après une maladie de Basedow : un diagnostic différentiel du lymphœdème.

INTRODUCTION: Pretibial myxedema is a rare manifestation of Graves' disease, and pseudotumoral forms may be confused with lower limb lymphedema. OBSERVATIONS: We reported 3 cases of pretibial myxedema in 2 women and 1 man, aged 72, 66, and 49 years, treated for Graves' disease 3, 25 and 32 years previously. Two patients were active smokers. Lymphedema diagnosis of the lower limbs was suspected in the presence of bilateral pseudotumoral lesions of the feet, toes and ankles and the presence of a Stemmer's sign (skin thickening at the base of the 2nd toe, pathognomonic of lymphedema). Lymphoscintigraphy in one case was normal, not confirming lymphedema. CONCLUSION: Pretibial pseudotumoral myxedema is a differential diagnosis of lower limb lymphedema. This diagnosis is confirmed by questioning the patient about preexisting Graves' disease, the underlying etiology, to decide the appropriate treatment and to encourage cessation of smoking, which is a risk factor for pretibial myxedema.

[Blue toe syndrome as an initial manifestation of metastatic prostate cancer : A case report with literature review]. / Un syndrome des orteils bleus révélant un cancer de la prostate métastatique : une observation avec analyse de la littérature.

INTRODUCTION: Cutaneous and vascular manifestations of cancer are numerous. Among paraneoplastic acral vascular syndrome, we report a case of blue toe syndrome as the first manifestation of a prostate cancer following with analysis of this syndrome according literature. OBSERVATION: A 56-year-old man, with Raynaud's phenomenon of the upper limbs for 2 to 3 years, had 4 blue toes of the left foot evolving for 18 months, without ulceration, the pulses being present. Vascular and cardiac explorations (ultrasound, angio-MRI) were normal. There was no biological or immunological abnormality except an elevated PSA level. Prostate biopsies confirmed diagnosis and abdomino-pelvic CT scan proved the bone and lymph node metastasis. CONCLUSION: The revelation of a prostate cancer with bone metastases by a blue toe syndrome is a rare situation. In a patient with a blue toe syndrome with no obvious clinical or biological abnormality, especially atheromatous, investigations should include a search for cancer, which can be revealed by blue toes.

A novel missense mutation and two microrearrangements in the FOXC2 gene of three families with lymphedema-distichiasis syndrome.

Lymphedema-distichiasis (LD) syndrome is a rare autosomal dominant disorder of the FOXC2 gene, which codes for a forkhead transcription factor. Most of the mutations described in this gene to date are deletions or insertions, suggesting a mechanism of haploinsufficiency. We studied three independent families with LD presenting with both lymphedema and distichiasis. Two microrearrangements (one 8-bp deletion and one 7-bp duplication) occurring in a GC-rich genomic region (c.893-930) known to be prone to mutations were identified. A new missense mutation (p.Lys132Glu) located in a highly conserved sequence, the forkhead domain, was also identified. Mutations in this domain have been previously shown to impair FOXC2 transactivation ability. At a genetic level, this study confirms the heterogeneity of mutations responsible for LD and is consistent with a mechanism of haploinsufficiency. At a clinical level, it reinforces the importance of genetic testing in subjects with familial lymphedema or distichiasis, since measures can be taken at an early stage to prevent complications and to reduce the progression of lymphedema or delay its occurrence.

[Puffy hand syndrome: A little-known diagnosis]. / Le syndrome des grosses mains : un diagnostic méconnu.

INTRODUCTION: Puffy hand syndrome is a rare complication of intravenous drug addiction. Diagnosis is based on the patient's history and clinical examination. OBSERVATIONS: A woman and two men, aged 42, 39 and 36 years old, are described. All had a history of intravenous drug use of heroin and oral buprenorphine misuse. Puffy hand syndrome appeared during drug addiction (n = 2) or after its withdrawal (n = 1). It was associated with acrocyanosis (n = 1) or injection scars (n = 1). Upper limb ultrasonography showed sequelae of venous (n = 3) or arterial (n = 1) thrombosis. An upper limb lymphoscintigraphy in one patient showed decreased radionuclide uptake of axillary lymph node and subdermal reflux tracer in the forearm. Treatment was based on low-stretch bandages to reduce the volume and then elastic compression sleeve for long-term stabilization. CONCLUSION: Puffy hand syndrome seen in intravenous drug addicts is poorly understood. It is a chronic complication despite the cessation of drug use. This syndrome has to become more widely known because its management is mandatory, although symptomatic.

[Inflammation, adipokines and obesity]. / Inflammation, adipokines et obésité

In obese subjects, there is a "low grade" inflammatory state characterized by the moderate but chronic systemic rise of a panel of molecules (adipokines), which carry out, in addition to pro- or anti-inflammatory actions, several immune or metabolic functions, associated with a macrophagic infiltration in adipose tissue. These two factors provide a better understanding of the pathophysiology of obesity and its potential metabolic, cardiovascular or hepatic complications. A small or even moderate reduction of weight significantly reduces circulating inflammatory markers, modulates adipose tissue profile of inflammatory genes and the risks associated with obesity.

[Puffy hand syndrome]. / Le syndrome des grosses mains.

Puffy hand syndrome is an unrecognized complication of intravenous drug abuse. This painless syndrome appears during or after a long period of drug addiction. It involves the hands and sometimes the forearms, and may cause functional, aesthetic and social disturbances when the hand volume is important. Physiopathological mechanisms of the puffy hand syndrome are unclear and include venous and lymphatic insufficiencies, infectious complications and direct toxicity of injected drugs and their adulterants. Low-stretch bandage and elastic garment, usually used in lymphedema treatment, are proposed to treat the puffy hand syndrome.

[General practitioner questionnaire concerning upper limb lymphedema after breast cancer]. / Enquête en médecine générale sur les lymphœdèmes du membre supérieur après cancer du sein.

INTRODUCTION: In France, breast cancer is the most frequent cancer in women. Lymphedema, the main complication, is poorly known. The objective of this study was to assess the state of knowledge of upper limb lymphedema (risk factors, complications, treatment) after treatment of breast cancer among general practitioners from the Haute-Normandie and Île-de-France regions. MATERIALS AND METHODS: A cross-sectional study with 23 closed questions was sent by email to 490 practicing doctors. RESULTS: One hundred and sixty-two questionnaires (33%) could be analyzed. Among the participating physicians (men: 55%), 46% were aged over 50 and 75% were from the Haute-Normandie region; 86% of them followed at least 5 women who had breast cancer. Risk factors for lymphedema were: axillary dissection (89%), risk reduction with sentinel lymph node (82%), radiotherapy (81%), mastectomy (45%) and overweight/obesity (42%). For 54% of physicians, lymphedema appeared within 6 months after cancer treatment and was diagnosed upon examination (clinical signs, perimeter measurements) in 78%, without the need for radiological examinations (100%). Physicians with more than 10 years of experience searched for more lymphedema (86% vs. 62%, P<0.0001). Prescriptions included: elastic compression during the day (77%), manual lymphatic drainage (74%), overnight compression (36%) and consultation in a specialized lymphology department (8%). Six percent of physicians had never managed lymphedema and 22% sent patients to an oncologist. Advice given was: prevention of infectious risk (80%), weight loss (42%), avoidance of sports involving the affected limb (22%), and regular arm elevation (14%). Physicians recommended avoiding blood sampling (75%), measuring blood pressure (66%) on the limb ipsilateral to cancer, while 20% did not prohibit any action on the limb. CONCLUSION: Lymphedema knowledge in general practitioners is generally adequate although the number of women followed by each of them was low. It seems necessary to optimize the training of generalists on lymphedema in order to improve patient management.

[Lower limb lymphedema: A rare manifestation of spondyloarthropathy]. / Lymphœdème des membres inférieurs : une manifestation rare des spondyloarthrites.

INTRODUCTION: Spondyloarthritis include articular (axial, peripheral or enthesitic) and extra-articular manifestations. We reported three cases of limb lymphedema associated with a spondyloarthritis. CASE REPORTS: We report on two men and one female aged of 75, 52 and 39 years, respectively. The rheumatic disease was an ankylosing spondylitis HLA B27 positive in two patients and a psoriatic arthritis in the remaining one. Lymphedema, always unilateral, confirmed by the Stemmer's sign, involved the whole lower limb (n=2) or only the foot and calf (n=1). Lymphedema occurred 3 months, 40 and 9 years after the onset of spondyloarthritis. Lower limb lymphoscintigraphy was abnormal in all cases: decrease (n=2) or absence (n=1) of inguinal lymph node uptake, and visualization of the popliteal lymph node related to deep lymphatic pathway (n=1). Treatment of the spondyloarthritis did not improve lymphedema. Both the low-stretch bandage and elastic compression treatment allowed its reduction and stabilization. CONCLUSION: Limb lymphedema is a rare extra-articular manifestation of spondyloarthritis. Its course appears to be independent of joint disease. Its management is specific and should be associated to that of the rheumatologic disorder.

[Lymphedema in patients treated with sirolimus: 15 cases]. / Lymphœdèmes associés à la prise de sirolimus : à propos de 15 patients.

BACKGROUND: Sirolimus is a mammalian target of rapamycin (mTOR) inhibitor used after organ transplantation and to treat vascular malformations. Among its adverse effects, limb lymphedema has been described. OBJECTIVE: The aim of this study was to analyze the clinical features, lymphoscintigraphy and lymphedema outcome in patients treated with sirolimus. PATIENTS AND METHODS: Monocentric retrospective study from January 2008 to September 2017 analyzing all consecutive patients having lymphedema occurring with sirolimus. RESULTS: Fifteen patients (7 men, 8 women), mean age at the first visit, 56 years (range: 38-76), had a kidney transplant (n=12), liver transplant (n=1), or lymphangioleiomyomatosis (n=2) treated with sirolimus at a mean daily dose of 1.8mg were included. Lymphedema involved one (n=4), or both (n=1) lower limbs, upper limb (n=9), lower limbs and upper limb (n=1). Lymphedema affected the whole limb (n=10), or the distal part (n=5). The median time between lymphedema onset and the beginning of sirolimus was 52 weeks (range: 8-232). Lymphoscintigraphy in 7 patients (lower limb: 3, superior: 4) showed no inguinal or axillary nodal fixation (n=6) or decreased uptake (n=1). Sirolimus was discontinued in 7 cases without lymphedema improvement with a median follow-up of 12 months and maintained in 8 cases. CONCLUSION: Sirolimus is associated with upper and/or lower limb lymphedema, without predominance of sex, and without disappearance after sirolimus discontinuation. Pathophysiological mechanisms remain unclear. Lymphedema management is based on low-stretch bandages and compression.

[Qualitative analysis of prescription of elastic garment in lower limb venous and lymphatic diseases]. / Analyse qualitative des prescriptions de compressions élastiques pour pathologies veineuses et lymphatiques des membres inférieurs.

INTRODUCTION: Elastic garments are usually used in various venous and lymphatic diseases of the lower limbs. Precise indications are required to facilitate prescription and delivery. The aim of our article was to analyse the precision of the prescription. MATERIAL AND METHOD: We analysed all the consecutive prescriptions in March 2007 at the time of purchase of elastic stocking. Following data were anonymously recorded: patient characteristics, indication of prescription, physician (generalist or vascular). Precision of prescription was defined if type and strength of elastic garment were clearly mentioned. RESULTS: One hundred and thirty-eight prescriptions from 106 different physicians (38 vascular, 61 generalists) were analysed. Mean age of patients was 61+/-16 years (28-97), concerning 108 women (78%). It was a first prescription in 44 cases (32%). Indications of prescription were varicose veins and leg heaviness. Class II was the main mentioned strength in all indications except for plane or car travels (class I). Strength of elastic garment was defined from I to IV, but in eight cases we noted the use of the word "light", "low" or "mean". To analyse the precision of prescriptions, we selected only the first one of the same physician. Prescription was not written on a separate sheet as recommended in five of the 38 vascular physicians and nine of the 68 others (NS). Class or type of elastic garment was missing in two prescriptions of vascular physicians versus 15 of the others (P<0.05). The most mentioned type was the below knee compression garment and then full leg garment. CONCLUSION: Prescriptions of elastic garment are sometimes imprecise with a risk of error at the time of purchasing. Physicians have to learn to ameliorate the precisions of prescriptions.