Yellow Nail Syndrome: Analysis of 23 Consecutive Patients and Effect of Combined Fluconazole-Vitamin-E Treatment.

INTRODUCTION: Yellow nail syndrome (YNS), a very rare disorder of unknown etiology, is characterized by a triad associating yellow nails, respiratory manifestations, and lymphedema. YNS treatment remains non-codified. METHOD: This retrospective study was conducted from January 2008 to December 2022 in a single tertiary department exclusively dedicated to lymphatic diseases. All consecutive patients with YNS were included. RESULTS: Thirteen men and 10 women were included. Three patients had yellow nails at birth or during childhood. For the other 20 patients, median (Q1-Q3) age at first sign was 50.8 (43-61) years, with first-YNS-sign-to-diagnosis interval of 17 (10-56) months. For 4 patients, YNS was associated with primary intestinal lymphangiectasia. The first YNS sign was chronic cough (45.5%), followed by yellow nails (27.3%), chronic sinusitis (18.2%), and lymphedema (9.1%). At first consultation for all patients, 69.6% had the complete triad, all had yellow nails and cough, 82.6% had chronic sinusitis, and 69.6% had lymphedema. Twelve patients' lymphedema involved only the lower limb(s), 2 the lower and upper limbs, and 2 the lower and upper limbs and face. Nineteen (82.6%) patients were prescribed fluconazole (100 mg/day [n = 8] or 300 mg/week [n = 11]) combined with vitamin E (1,000 mg/day) for a median of 13 months. Responses were complete for 4 (21.1%) patients, partial for 8 (42.1%), and therapeutic failures for 7 (36.8%). CONCLUSIONS: YNS is a rare disease that almost always starts with a chronic cough. Despite inconstant efficacy, fluconazole-vitamin E in combination can be prescribed to treat yellow nails.

Multiple Lymphaticovenular Anastomoses for Chyluria in Klippel-Trenaunay Syndrome.

ABSTRACT: Klippel-Trenaunay syndrome (KTS) is characterized by port-wine stains, mixed vascular malformations, and soft tissue and bone hypertrophy. Klippel-Trenaunay syndrome is occasionally complicated by chyluria, for which there is no effective treatment currently. We report a case of KTS complicated by intractable chyluria and hematuria due to a lymphatic-ureteral fistula. The patient was successfully treated with multiple lymphaticovenular anastomoses (LVAs).A 66-year-old woman with an enlarged left lower extremity since childhood was diagnosed with KTS. At 60 years of age, she developed chyluria (urine albumin, 2224 µg/mL) and hematuria. Lymphoscintigraphy showed a lymphatic-ureteral fistula near the ureterovesical junction. Conservative treatment was ineffective. She also developed left lower extremity lymphedema, which gradually worsened. Leg cellulitis and purulent pericarditis developed because of hypoalbuminemia (minimum serum albumin level, 1.3 g/dL).We performed 14 LVAs in 2 surgeries to reduce lymphatic fluid flow through the lymphatic-ureteral fistula. The chyluria and hematuria resolved soon after the second operation, and the urine albumin level decreased (3 µg/mL). After 28 months, she had no chyluria or hematuria recurrence and her serum albumin level improved (3.9 g/dL). Multiple LVAs can definitively treat chyluria caused by a lymphatic-ureteral fistula in patients with KTS.

Phenotypical characterization, and antibiotics susceptibility patterns of skin bacteria found in podoconiosis patients in the North West Region of Cameroon.

BACKGROUND: Podoconiosis, a non-infectious disease originating from long-term exposure of bare feet to irritant red clay soil is a lifelong, disabling disease with no specific diagnostic tool, classified into 5 stages based on the severity of leg swelling (lymphoedema). Secondary bacterial infections have been suggested to cause acute dermatolymphangioadenitis (ADLA) attacks and drive disease progression. Although the North West Region of Cameroon has a proven history of podoconiosis endemicity, the bacterial composition of lymphoedema due to this condition has not been studied. Thus, this study investigated the leg bacterial diversity of patients who suffered from the lymphoedema and their susceptibility pattern to selected antibiotics. METHODS: A cross-sectional study was carried out in which podoconiosis affected and non-lymphoedema individuals living in the same community were purposively selected. Samples were collected by swabbing the skin between the toes and around the anklebone, then cultured and sub-cultured on nutrient agar to obtain pure isolates. The cultured isolates were then morphologically and biochemically classified using microscopy and analytic profile index test kits, respectively. The disk diffusion technique was used to determine antibiotic susceptibility. RESULTS: Thirty-three participants were recruited, and 249 bacterial isolates were characterized into 29 genera, 60 species; with 30 (50%) being gram positive rods, 19 (31.7%) gram positive cocci, and 11 (18.3%) gram negative rods. Thirteen gram positive rods, fifteen gram positive cocci, and eight gram negative rods of bacterial species were found only in podoconiosis individuals among which Cellulomonas spp / Microbacterium spp. (2.8%), Staphylococcus lentus (3.3%), and Burkholderia cepacia (4.0%) dominated. 90% (90%) of the bacterial isolates were sensitive to doxycycline, whereas ampicillin had a high level of intermediate resistance, and penicillin G had the greatest resistant profile. CONCLUSION: Our findings show that 94 (37.8%) out of 249 described bacterial isolates were exclusively found in the legs of podoconiosis individuals, and their susceptibility pattern to antibiotics was similar to that of others.

Persistent chylothorax associated with lymphatic malformation type 6 due to biallelic pathogenic variants in PIEZO1.

PIEZO1 is required for lymphatic valve formation, and several lymphatic abnormalities have been reported to be associated with autosomal recessive PIEZO1 pathogenic variants including neonatal hydrops, lymphedema involving various body regions, and chylothorax. Persistent or recurrent chylothorax has been infrequently described in association with pathogenic variants in the PIEZO1 gene. We present a 4-year-old female with bilateral pleural effusions detected prenatally, who was diagnosed with bilateral chylothoraces post-partum. She subsequently had recurrent pleural effusions involving both pleural cavities, which tended to improve with restriction of her fat intake, and, one occasion, subcutaneous octreotide. She also had bilateral calf, and intermittent cheek swelling. Genetic testing revealed two deleterious variants in PIEZO1: c.2330-2_2330-1del and c.3860G > A (p.Trp1287*), both of which were classified as likely pathogenic. This supported a diagnosis of Lymphatic Malformation Type 6 (OMIM 616843), also known as Hereditary Lymphedema Type III. Hereditary Lymphedema type III can be associated with persistent chylothorax that can vary in size over time.

Postoperative swelling after elbow surgery: influence of a negative pressure application in comparison to manual lymphatic drainage-a randomized controlled trial.

PURPOSE: Postoperative soft tissue swelling is a significant factor influencing outcomes after elbow surgery. It can crucially affect important parameters such as postoperative mobilization, pain, and subsequently the range of motion (ROM) of the affected limb. Furthermore, lymphedema is considered a significant risk factor for numerous postoperative complications. Manual lymphatic drainage is nowadays part of the standardized post-treatment concept, basing on the concept of activating the lymphatic tissue to absorb stagnated fluid from the tissue into the lymphatic system. This prospective study aims to investigate the influence of technical device-assisted negative pressure therapy (NP) on early functional outcomes after elbow surgery. NP was therefore compared to manual lymphatic drainage (MLD). Is a technical device-based NP suitable for treatment of lymphedema after elbow surgery? METHODS: A total of 50 consecutive patients undergoing elbow surgery were enrolled. The patients were randomized into 2 groups. 25 participants per group were either treated by conventional MLD or NP. The primary outcome parameter was defined as the circumference of the affected limb in cm postoperative up to seven days postoperatively. The secondary outcome parameter was a subjective perception of pain (measured via visual analogue scale, VAS). All parameters were measured on each day of postoperative inpatient care. RESULTS AND CONCLUSION: NP showed an overall equivalent influence compared to MLD in reducing upper limb swelling after surgery. Moreover, the application of NP showed a significant decrease in overall pain perception compared to manual lymphatic drainage on days 2, 4 and 5 after surgery (p < 0.05). CONCLUSION: Our findings show that NP could be a useful supplementary device in clinical routine treating postoperative swelling after elbow surgery. Its application is easy, effective and comfortable for the patient. Especially due to the shortage of healthcare workers and physical therapists, there is a need for supportive measures which NP could be.

Microdeletion of 16q24.1-q24.2-A unique etiology of Lymphedema-Distichiasis syndrome and neurodevelopmental disorder.

Interstitial deletions of 16q24.1-q24.2 are associated with alveolar capillary dysplasia, congenital renal malformations, neurodevelopmental disorders, and congenital abnormalities. Lymphedema-Distichiasis syndrome (LDS; OMIM # 153400) is a dominant condition caused by heterozygous pathogenic variants in FOXC2. Usually, lymphedema and distichiasis occur in puberty or later on, and affected individuals typically achieve normal developmental milestones. Here, we describe a boy with congenital lymphedema, distichiasis, bilateral hydronephrosis, and global developmental delay, with a de novo microdeletion of 894 kb at 16q24.1-q24.2. This report extends the phenotype of both 16q24.1-q24.2 microdeletion syndrome and of LDS. Interestingly, the deletion involves only the 3'-UTR part of FOXC2.

Ulcerating nodules on a background of lower leg lymphoedema.

A patient presented with a 3-month history of a rapidly enlarging ulcerated tumour on his lower leg, occurring on a background of chronic idiopathic lymphoedema of approximately 10 years' duration. Histology revealed extensive infiltration of the dermis by a vascular tumour with pleomorphic and hyperchromatic endothelial cells, which stained positive for vascular markers CD31, CD34 and ERG. A diagnosis of lymphoedema-associated angiosarcoma was reached and our patient was treated with isolated limb perfusion with high-dose melphalan and tumour necrosis factor-alfa.

A Case of CD5-Positive Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type Secondary to Chronic Lymphedema.

ABSTRACT: Primary cutaneous lymphoma occurring at the site of lymphedema is a rare complication. A total of 13 cases of primary cutaneous lymphoma associated with chronic lymphedema have been reported in international studies. We reported a case of cutaneous diffuse large B-cell lymphoma (DLBCL) (leg type) secondary to chronic lymphedema of the lower limbs. Histopathology showed hyperkeratosis of epidermis, acanthosis, and significant edema in the superficial dermis, with diffuse mononuclear infiltration in the dermis. Immunohistochemical studies revealed the expression of CD5, CD20, Pax-5, Bcl-2, Bcl-6, MUM-1, c-myc, and Ki-67. Therefore, the diagnosis of cutaneous DLBCL (leg type) was made. The study further confirmed the association between lymphoma and lymphedema. Especially, it showed CD5 expression. CD5-positive DLBCLs is a specific subgroup of DLBCLs, only approximately 10% of DLBCLs express CD5.

MYC gene amplification by fluorescence in situ hybridization and MYC protein expression by immunohistochemistry in the diagnosis of cutaneous angiosarcoma: Systematic review and appropriate use criteria.

BACKGROUND: Secondary angiosarcoma (AS) most commonly follows breast cancer and includes postirradiation AS (PRAS) and lymphedema-associated AS. The frequent amplification of MYC (8q24.21) in secondary AS and the rising incidence of PRAS and atypical vascular lesions (AVLs) have prompted interest in the diagnostic and prognostic utility of MYC in AS. METHODS: Retrospective series with ≥2 cases of cutaneous AS and describing the use of fluorescence in situ hybridization (FISH) for MYC amplification or immunohistochemistry (IHC) for MYC overexpression were included. RESULTS: Sixteen studies met inclusion criteria. Overall, 93% of cases evaluated by FISH and IHC were concordant. The sensitivity of FISH in primary AS was only 6.8%, and protein overexpression occurred without amplification in sun-damaged skin. FISH and IHC were over 78% sensitive in secondary AS but negative in over 98% of AVLs. MYC amplification and FLT4 coamplification were associated with shorter overall survival in secondary AS. CONCLUSION: FISH for MYC amplification and IHC for MYC overexpression are useful in distinguishing PRAS from AVLs and may also have prognostic value in secondary AS. In contrast, these methods have little diagnostic or prognostic value in primary AS and should not be used to distinguish primary AS from benign vascular neoplasms.

Biallelic mutation of FBXL7 suggests a novel form of Hennekam syndrome.

Hennekam lymphangiectasia-lymphedema syndrome is an autosomal recessive disorder characterized by congenital lymphedema, intestinal lymphangiectasia, facial dysmorphism, and variable intellectual disability. Known disease genes include CCBE1, FAT4, and ADAMTS3. In a patient with clinically diagnosed Hennekam syndrome but without mutations or copy-number changes in the three known disease genes, we identified a homozygous single-exon deletion affecting FBXL7. Specifically, exon 3, which encodes the F-box domain and several leucine-rich repeats of FBXL7, is eliminated. Our analyses of databases representing >100,000 control individuals failed to identify biallelic loss-of-function variants in FBXL7. Published studies in Drosophila indicate Fbxl7 interacts with Fat, of which human FAT4 is an ortholog, and mutation of either gene yields similar morphological consequences. These data suggest that FBXL7 may be the fourth gene for Hennekam syndrome, acting via a shared pathway with FAT4.

Free gastroepiploic lymph nodes and omentum flap for treatment of lower limb ulcers in severe lymphedema: Killing two birds with one stone.

BACKGROUND AND OBJECTIVES: In patients with lymphedema, the disruption of the lymphatic network increases skin turgor and fibrosis of subcutaneous tissue, delays wound healing, causing recurrent ulcerations and infections. In these cases, management of ulcers can be challenging. METHODS: Between January 2016 and June 2018, patients presenting with lymphedema were enrolled at our Institution. We selected patients with severe lymphedema and ulcers of lower limbs and we performed a surgical approach, involving free gastroepiploic lymph nodes and omentum flap, harvested through laparoscopy. RESULTS: We enrolled 135 patients presenting for lymphedema. Among them, 10 eligible cases underwent excision of the ulcer and reconstruction with omentum flap. Mean age was 57.8 years and average follow-up 24.1 months. Circumferences and skin tonicity significantly decreased from the preoperative period. Lymphoscintigraphy showed improvement of the lymphatic drainage and restoration of lymphatic network. No episodes of infection were recorded in the postoperative period. CONCLUSIONS: Our combined procedure merges free flap techniques and lymphedema surgery: omentum covers the defect while providing a new source of lymph nodes, improving the lymphatic networks of the affected limb. This technique can highly increase the quality of life of the patient in a single-stage operation with fast recovery and low donor site morbidity.

Successful treatment of lymphedema in a vasculopath and neuropathic patient.

This is a case report of a 68-year-old male with stage III right lower extremity lymphedema following right inguinal lymph node dissection and adjuvant chemoradiotherapy for Hodgkin's lymphoma. He developed peripheral neuropathy and radiation-induced right femoral artery thrombosis, treated with saphenous vein graft. He underwent three vascularized lymph node transfers (VLNTs) to the upper medial thigh, posterior calf, and ankle with placement of nanofibrillar collagen scaffolds. Three months after surgery, he had volume reduction, less neuropathic pain, and improved ambulation.

Intralymphatic Rosai-Dorfman Disease Associated With Vulvar Lymphedema: A Case Report of an Extremely Rare Phenomenon.

Sinus histiocytosis with massive lymphadenopathy, also known as Rosai-Dorfman disease (RDD), is a self-limited histiocytic disorder of unclear etiology which most commonly presents with cervical lymphadenopathy. Purely extranodal presentation of RDD is uncommon, and isolated intralymphatic/intravascular confinement of this entity has not previously been described. We report a 16-yr-old female who presented with vaginal swelling and mass-like enlargement of the right labia. The mass had been present for nearly a year without pain or tenderness. Clinically, the lesion was thought to be a Bartholin gland cyst. Following surgical resection, histologic examination demonstrated a hypocellular myxedematous stroma with a mixture of ectatic thin and thick-walled vessels within which there were numerous collections of histiocytes, lymphocytes, and plasma cells. The histopathologic differential diagnosis included localized vulvar lymphedema, a specialized genital tract neoplasm, and childhood asymmetric labium majus enlargement. The histiocytes showed occasional plasma cells and lymphocytes within their cytoplasm, consistent with emperipolesis. Immunohistochemical studies showed that the histiocytes expressed CD163 and S100, while ERG and D2-40 highlighted their intralymphatic confinement, ultimately leading to the diagnosis of intralymphatic RDD. Intralymphatic RDD may present as vulvar lymphedema and can potentially mimic other myxedematous neoplasms of the vulvovaginal region.

Exploring the association between diabetes and breast cancer morbidity: considerations for quality care improvements among Latinas.

OBJECTIVE: Cancer and diabetes are two severe chronic illnesses that often co-occur. In cancer patients, diabetes increases the risk for treatment complexities and mortality. Yet patient-reported outcomes with co-occurring chronic illness are understudied. DESIGN: This preliminary study investigated the association of diabetes with breast cancer-related morbidity among underserved Latina breast cancer survivors (BCS). PARTICIPANTS: 137 Latina BCS were recruited from the California Cancer Registry and hospitals.Setting and Main Outcome Measure(s): BCS completed a self-administered mailed questionnaire assessing demographic and medical characteristics e.g. Type2 diabetes mellitus (T2DM). RESULTS: 28% Latina BCS reported co-occurring T2DM at twice the general population rate. Diabetes was most prevalent among Latina BCS > 65 years (43%). Latina BCS with diabetes were more likely to report advanced cancer staging at diagnosis (P = 0.036) and more lymphedema symptoms (P = 0.036). Results suggest non-significant but lower general health and greater physical functioning limitations among BCS with T2DM. CONCLUSIONS: This study has relevance for precision population medicine by (i) consideration of routine diabetes screening in Latina BCS, (ii) underscoring attention to disease co-occurrence in treatment planning and care delivery and (iii) informing follow-up care and survivorship care planning e.g. patient self-management, oncology and primarily care surveillance and specialty care. Our findings can inform providers, survivors and caregivers about the impact of disease co-occurrence that influence clinically and patient responsive care for both initial treatment and long-term follow-up care to address disparities.

Angiosarcoma arising in massive localized lymphedema.

We report a case of a 70-year-old woman with a BMI of 58 who developed cellulitis refractory to treatment, within an area of massive localized lymphedema. Biopsy showed angiosarcoma. MRI showed multiple lobulated, low T1, high T2 masses within a background of prominent soft tissue septal stranding, dilated lymphatic channels, and skin thickening. CT also showed the mass well, within the background lymphedema. Massive localized lymphedema is increasing in prevalence due to the worsening obesity epidemic. Radiologists should be aware that the presence of a nodule within an area of massive localized lymphedema is suspicious for sarcoma.

Primary and secondary cutaneous angiosarcoma: Distinctive clinical, pathological and molecular features.

Angiosarcomas are ubiquitous neoplasms involving both cutaneous and soft tissue and visceral locations. Accumulating biomolecular evidences suggest that cutaneous angiosarcomas are distinctive entities with molecular, clinical and pathological peculiarities. Despite several ongoing clinical trials with promising therapeutic agents, the prognosis of cutaneous angiosarcomas is dismal and survival still rely on early diagnosis and surgery. An accurate diagnosis and the knowledge of the underlying molecular landscape are therefore essential to improve the prognosis. We detail the molecular, clinical, dermoscopic, morphological and prognostic features of cutaneous angiosarcoma. Although the molecular landscape of cutaneous angiosarcoma is not completely understood, accumulating evidences suggest that there are characteristic molecular alterations including dysregulation of angiogenesis and several complex molecular pathways. Secondary cutaneous angiosarcomas, arising in correlation with chronic lymphedema and ionizing radiation, have different molecular hallmarks, which are also leading to the first diagnostic applications. The diagnosis of cutaneous angiosarcoma may be challenging, as well-differentiated forms can be hard to distinguish from benign and low-grade vascular neoplasms, while poorly differentiated forms can be easily confounded with other non-vascular high-grade neoplasms. An accurate and early diagnosis, which is mandatory to ensure the best survival for the patients, is mainly based on morphological hallmarks.

[Hidradenitis suppurativa/acne inversa in the genitoanal region]. / Hidradenitis suppurativa/Acne inversa in der Genitoanalregion.

Hidradenitis suppurativa/acne inversa (HS/AI) is a chronic inflammatory skin disease. Several studies showed that perianal, perineal and gluteal involvement is more common in men. Axillary, submammary and inguinal localizations seem to be more prevalent in women. Involvement of the genitoanal region is associated with a higher reduced quality of live and sexual health compared to other locations. Moreover HS/AI in the genitoanal region can lead to serious complications. The knowledge of perianal fistula formation, pubogenital lymphedema and squamous cell carcinoma, which are three of the most severe complications, is critical for adequate treatment.

The Long-term Patency of Lymphaticovenular Anastomosis in Breast Cancer-Related Lymphedema.

BACKGROUND AND OBJECTIVES: Lymphedema is a condition that can greatly affect patient's quality of life. Promising results have been described with lymphaticovenular anastomosis (LVA) in the treatment of lymphedema. It is currently unknown at what rate anastomoses remain functional after a longer follow-up. The aim of this study was to determine LVA patency at 1-year follow-up. METHODS: Retrospective chart review was performed on patients who underwent LVA surgery. Patients who had indocyanine green lymphography performed at 12 months' follow-up after LVA were included in this study. Volume measurements were performed prior to surgery and at 6 and 12 months' follow-up. Patients quality of life was measured prior to surgery and at 6 months' follow-up. RESULTS: Twelve patients met inclusion criteria. In total, 15 (56.5%) of 23 LVAs were considered patent. In 8 patients (66.7%), at least 1 patent LVA was visible. The volume difference between the healthy and affected arms decreased 32.3% on average. Quality of life increased with 1.4 points on average. CONCLUSIONS: This study is, to our knowledge, the first to evaluate long-term patency of LVA in upper limb lymphedema. Our study demonstrates that at least 56.5% of the anastomoses created are patent after 1-year follow-up.

Round-knit or flat-knit compression garments for maintenance therapy of lymphedema of the leg? - Review of the literature and technical data.

To date, there have been no studies comparing flat-knit and round-knit compression garments for maintenance therapy of lymphedema of the leg. According to expert opinion, flat-knit fabrics are generally recommended for this purpose. Given the differences in the clinical presentation of lymphedema in terms of disease stage and location as well as patient adherence, and, last but not least, for economic reasons, it seems questionable whether all patients with lymphedema of the leg actually do require flat-knit compression garments. Considering technical aspects, published data and our own clinical experience, it seems reasonable that the choice of compression stockings be based on clinical findings and not on the diagnosis. Typical indications for flat-knit garments include significant differences in leg circumference as well as deep skin folds and edema of the toes/forefoot. However, there are also patients with lymphedema who benefit from round-knit fabrics with a high degree of stiffness. In any case, prior to maintenance therapy, it is essential to adequately decongest the legs using compression bandages and/or adaptive compression systems.