-
[show abstract]
[hide abstract]
ABSTRACT: Lymphoedema is a clinical condition caused by impairment of the lymphatic system, leading to swelling of subcutaneous soft tissues. As a result, accumulation of protein-rich interstitial fluid and lymphostasis often causes additional swelling, fibrosis and adipose tissue hypertrophy leading to progressive morbidity and loss of quality of life for the patient. Lymphoedema can be distinguished as primary or secondary. Lymphoedema is a complication frequently encountered in patients treated for cancer, especially after lymphadenoectomy and/or radiotherapy based on destruction of lymphatics. However, although lymphatic impairment is sometimes caused by obstructive solid metastasis, we present three cases of secondary lymphoedema with minor dermatological features without detectable solid metastasis. Sometimes this type of lymphoedema is mistakenly called malignant lymphoedema. All patients were previously treated for cancer without clinical signs of recurrence, presented with progressive lymphoedema and minor dermatological features of unknown origin. Clinical and histopathological examination of the skin revealed diffuse lymphangitis carcinomatosa, leading to secondary lymphoedema and adjustment of the therapeutic approach and prognosis. We reviewed literature on these rare presentations of cancer recurrence and recommend, where appropriate, consulting a dermatologist when discrete skin abnormalities are seen in patients with a history of cancer and developing lymphoedema.
European Journal of Cancer Care 09/2010; 19(5):669-75. · 1.17 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Mutations in the FOXC2 gene that codes for a forkhead transcription factor are associated with primary lymphedema that usually develops around puberty. Associated abnormalities include distichiasis and, very frequently, superficial and deep venous insufficiency. Most mutations reported so far either truncate the protein or are missense mutations in the forkhead domain causing a loss of function. The haplo-insufficient state is associated with lymphatic hyperplasia in mice as well as in humans. We analyzed the FOXC2 gene in 288 patients with primary lymphedema and found 11 pathogenic mutations, of which 9 are novel. Of those, 5 were novel missense mutations of which 4 were located outside of the forkhead domain. To examine their pathogenic potential we performed a transactivation assay using a luciferase reporter construct driven by FOXC1 response elements. We found that the mutations outside the forkhead domain cause a gain of function as measured by luciferase activity. Patient characteristics conform to previous reports with the exception of distichiasis, which was found in only 2 patients out of 11. FOXC2 mutations causing lymphedema-distichiasis syndrome reported thus far result in haplo-insufficiency and lead to lymphatic hyperplasia. Our results suggest that gain-of-function mutations may also cause lymphedema. One would expect that in this case, lymphatic hypoplasia would be the underlying abnormality. Patients with activating mutations might present with Meige disease. © 2009 Wiley-Liss, Inc.
Human Mutation 11/2009; 30(12):E1002 - E1009. · 5.69 Impact Factor
-
Phlebology 10/2009; 24(5):238. · 2.07 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The incidence of arm lymphoedema after treatment for breast cancer ranges from 1 to 49 per cent. Although most women can be treated by non-operative means with satisfying results, end-stage lymphoedema is often non-responsive to compression, where hypertrophy of adipose tissue limits the outcome value of compression or massage.
This was a prospective study of 37 women with unilateral non-pitting lymphoedema. After initial conservative treatment for 2-4 days, circumferential suction-assisted lipectomy was used to remove excess volume. Limb compression was resumed after surgery with short-stretch bandages, followed by flat-knit compression garments.
The mean preoperative excess arm volume was 1399 ml. The total aspirate volume was 2124 ml with 93 per cent aspirate adipose tissue content. After 12 months, the mean reduction in excess volume was 118 per cent. The percentage reduction in excess volume after 12 months was linearly related to the preoperative excess volume but showed no linear relationship with the duration of lymphoedema or surgeon experience.
Circumferential lipectomy combined with lifelong compression hose is an effective technique in end-stage lymphoedema after treatment for breast cancer.
British Journal of Surgery 09/2009; 96(8):859-64. · 4.61 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Mutations in the FOXC2 gene that codes for a forkhead transcription factor are associated with primary lymphedema that usually develops around puberty. Associated abnormalities include distichiasis and, very frequently, superficial and deep venous insufficiency. Most mutations reported so far either truncate the protein or are missense mutations in the forkhead domain causing a loss of function. The haplo-insufficient state is associated with lymphatic hyperplasia in mice as well as in humans. We analyzed the FOXC2 gene in 288 patients with primary lymphedema and found 11 pathogenic mutations, of which 9 are novel. Of those, 5 were novel missense mutations of which 4 were located outside of the forkhead domain. To examine their pathogenic potential we performed a transactivation assay using a luciferase reporter construct driven by FOXC1 response elements. We found that the mutations outside the forkhead domain cause a gain of function as measured by luciferase activity. Patient characteristics conform to previous reports with the exception of distichiasis, which was found in only 2 patients out of 11. FOXC2 mutations causing lymphedema-distichiasis syndrome reported thus far result in haplo-insufficiency and lead to lymphatic hyperplasia. Our results suggest that gain-of-function mutations may also cause lymphedema. One would expect that in this case, lymphatic hypoplasia would be the underlying abnormality. Patients with activating mutations might present with Meige disease.
Human Mutation 09/2009; 30(12):E1002-9. · 5.69 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Three patients are described who developed irreversible lymphedema of the arm following mastectomy because of breast cancer. Despite maximal conservative treatment, a difference in volume between the affected arm and the healthy arm remained (900-1500 ml). The patients underwent reductive surgery by means of circumferential suction assisted lipectomy, involving removal of hypertrophied adipose tissue. This was the first experience with this procedure in the Netherlands. The differences in arm volume were neutralised completely with a significant improvement of the shoulder function. In order to make the results lasting, the patients have to wear medical elastic stockings day and night for the rest of their lives. Long-term volume measurements are essential.
Nederlands tijdschrift voor geneeskunde 06/2008; 152(18):1061-5.
-
[show abstract]
[hide abstract]
ABSTRACT: Erysipelas is a common skin infection that is usually caused by beta-haemolytic group A streptococci. After having had erysipelas in an extremity, a significant percentage of patients develops persistent swelling or suffers from recurrent erysipelas. We hypothesize that in cases of erysipelas without a clear precipitating agent, subclinical pre-existing congenital or acquired disturbances in the function of the lymphatic system are present. The persistent swelling after erysipelas is then most likely caused by lymphoedema.
We designed a study to examine if erysipelas of unknown origin is associated with a pre-existent insufficiency of the lymphatic system. If our hypothesis is correct, patients with erysipelas of unknown cause without previously evident lymphoedema should have evidence of disturbed lymphatic transport in the unaffected extremity.
A prospective study, in which lymphoscintigraphy of both legs was performed in patients 4 months after presenting with an episode of erysipelas only in one leg. No patient had any known risk factor for erysipelas, such as diabetes mellitus, chronic venous insufficiency or clinical signs of lymphoedema. Lymphoscintigraphy was performed in 40 patients by subcutaneous injection of Tc-99m-labelled human serum albumin in the first web space of both feet. After 30 and 120 min, quantitative and qualitative scans were performed using a computerized gamma camera. During the lymphoscintigraphy, the patients performed a standardized exercise programme. Lymph drainage was quantified as the percentage uptake of Tc-99m-labelled human serum albumin in the groin nodes at 2 h after injection. Groin uptake of < 15% is pathological; uptake between 15-20% is defined as borderline, and uptake of > 20% as normal.
The mean +/- SD percentage uptake in the groin nodes in the affected limbs was 9.6 +/- 8.5% vs. 12.1% +/- 8.9% in the nonaffected limbs. The mean paired difference in uptake between the nonaffected vs. affected side was 2.5% (95% confidence interval 1.1-3.9%). This indicates that lymphatic drainage in the nonaffected limb was only slightly better than in the affected limb despite the infectious event in the latter. Of 33 patients with objective impairment of lymph drainage in the affected limb, 26 (79%) also had impaired lymph drainage in the nonaffected limb. Agreement in qualitative measurements between affected and nonaffected leg was less pronounced: 21 patients had abnormal qualitative results in the affected leg of whom nine also had impairment of the nonaffected leg (43%).
Erysipelas is often presumed to be purely infectious in origin, with a high rate of recurrence and a risk of persistent swelling due to secondary lymphoedema. In this study, we show that patients presenting with a first episode of erysipelas often have signs of pre-existing lymphatic impairment in the other, clinically nonaffected, leg. This means that subclinical lymphatic dysfunction of both legs may be an important predisposing factor. Therefore, we recommend that treatment of erysipelas should focus not only on the infection but also on the lymphological aspects, and long-standing treatment for lymphoedema is essential in order to prevent recurrence of erysipelas and aggravation of the pre-existing lymphatic impairment. Our study may change the clinical and therapeutic approach to erysipelas as well as our understanding of its aetiology.
British Journal of Dermatology 06/2008; 158(6):1210-5. · 3.67 Impact Factor
-
J de Korte,
P G M van der Valk,
M A G Sprangers, R J Damstra,
A C M Kunkeler,
R L P Lijnen,
A P Oranje,
M A de Rie,
F B de Waard-van der Spek,
C W Hol,
P C M van de Kerkhof
[show abstract]
[hide abstract]
ABSTRACT: Calcipotriol ointment and short-contact dithranol cream therapy are well-established topical treatments for psoriasis. Quality of life, i.e. the physical, psychological, and social functioning and well-being of the patient, has become an essential outcome measure in chronic skin disease.
To compare the quality-of-life outcomes of calcipotriol ointment with that of short-contact dithranol cream in a supervised treatment regimen, and to determine the degree of improvement in quality of life these topical treatments can accomplish.
In a multicentre randomized controlled trial in six centres in the Netherlands, 106 patients with chronic plaque psoriasis were included, 54 receiving calcipotriol ointment twice daily and 52 dithranol cream once daily in a 12-week intensive treatment programme. Patients were treated at the day-care centre, using the care instruction principle of daily visits during the first week and twice-weekly visits subsequently for up to 12 weeks. Quality of life was assessed with the Skindex-29 and the Medical Outcomes Study 36-item Short-Form General Health Survey (SF-36).
At the end of treatment, no statistically significant differences were found between the calcipotriol and the dithranol group in any of the quality-of-life domains or scales of the Skindex-29 and the SF-36. Over time, a significant improvement of quality of life was found on all three scales of the dermatology-specific Skindex-29, predominantly of a moderate magnitude. In the calcipotriol group, a significant change of a small magnitude was found in the Physical Component Summary of the SF-36. No significant changes were found in the Mental Component Summary (or on any of the eight scales composing the questionnaire) of the SF-36.
The hypothesis was confirmed, that no statistically significant differences in improvement of quality of life could be found between calcipotriol ointment and dithranol short-contact cream in a day-care setting. Given this result, both calcipotriol and dithranol can be welcome alternatives for the patient. Calcipotriol, being more practical and patient friendly, can be considered as a first-line approach in clinical practice. However, in patients recalcitrant to calcipotriol and/or other topical treatments, preference should be given to the dithranol regimen. Topical treatment in combination with interventions explicitly focusing on improvement of coping behaviour and psychosocial functioning may further increase the degree of improvement in the psychosocial domains of quality of life. The results of this study are likely to give further evidence to the notion that the generic SF-36 is little or not responsive to small to moderate changes in quality of life in mild to moderate psoriasis.
British Journal of Dermatology 03/2008; 158(2):375-81. · 3.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Lymphoedema (LE) is a disorder characterized by persistent swelling caused by impaired lymphatic drainage because of various aetiologies, including lymphatic injury and congenital functional or anatomical defects.
Literature review and expert opinion about diagnosis and treatment of LE in children.
LE is rare in children, with a prevalence of about 1.15/100,000 persons, 20 years old. The management of LE in children differs considerably from adults in terms of origin, co-morbidity and therapeutic approach. The objective of this presentation is to discuss practical issues related to clinically relevant information on the diagnosis, aetiology, work-up and treatment of LE in children. In contrast to adults, who usually experience secondary LE because of acquired lymphatic failure, most cases in children have a primary origin. The diagnosis can be made mainly on the basis of careful personal and family history, and physical examination. LE in children can be part of a syndrome if there are other concomitant phenotypic abnormalities and if a genetic defect is recognizable. Treatment of LE is mostly conservative utilizing decongestive LE therapy including compression therapy, directed exercises, massage and skincare. In the neonate, initial observation alone may be sufficient, as delayed lymphatic development and maturation can result in spontaneous improvement. The role of parents is crucial in providing the necessary input.
We present a review emphasizing a practical approach to treating a child with LE according to current publications and our own experience.
Phlebology 02/2008; 23(6):276-86. · 2.07 Impact Factor
-
J. De Korte,
P.G.M. Van Der Valk,
M.A.G. Sprangers, R.J. Damstra,
A.C.M. Kunkeler,
R.L.P. Lijnen,
A.P. Oranje,
M.A. De Rie,
F.B. De Waard-van der Spek,
C.W. Hol,
P.C.M. Van De Kerkhof
[show abstract]
[hide abstract]
ABSTRACT: Background Calcipotriol ointment and short-contact dithranol cream therapy are well-established topical treatments for psoriasis. Quality of life, i.e. the physical, psychological, and social functioning and well-being of the patient, has become an essential outcome measure in chronic skin disease.Objectives To compare the quality-of-life outcomes of calcipotriol ointment with that of short-contact dithranol cream in a supervised treatment regimen, and to determine the degree of improvement in quality of life these topical treatments can accomplish.Methods In a multicentre randomized controlled trial in six centres in the Netherlands, 106 patients with chronic plaque psoriasis were included, 54 receiving calcipotriol ointment twice daily and 52 dithranol cream once daily in a 12-week intensive treatment programme. Patients were treated at the day-care centre, using the care instruction principle of daily visits during the first week and twice-weekly visits subsequently for up to 12 weeks. Quality of life was assessed with the Skindex-29 and the Medical Outcomes Study 36-item Short-Form General Health Survey (SF-36).Results At the end of treatment, no statistically significant differences were found between the calcipotriol and the dithranol group in any of the quality-of-life domains or scales of the Skindex-29 and the SF-36. Over time, a significant improvement of quality of life was found on all three scales of the dermatology-specific Skindex-29, predominantly of a moderate magnitude. In the calcipotriol group, a significant change of a small magnitude was found in the Physical Component Summary of the SF-36. No significant changes were found in the Mental Component Summary (or on any of the eight scales composing the questionnaire) of the SF-36.Conclusions The hypothesis was confirmed, that no statistically significant differences in improvement of quality of life could be found between calcipotriol ointment and dithranol short-contact cream in a day-care setting. Given this result, both calcipotriol and dithranol can be welcome alternatives for the patient. Calcipotriol, being more practical and patient friendly, can be considered as a first-line approach in clinical practice. However, in patients recalcitrant to calcipotriol and/or other topical treatments, preference should be given to the dithranol regimen. Topical treatment in combination with interventions explicitly focusing on improvement of coping behaviour and psychosocial functioning may further increase the degree of improvement in the psychosocial domains of quality of life. The results of this study are likely to give further evidence to the notion that the generic SF-36 is little or not responsive to small to moderate changes in quality of life in mild to moderate psoriasis.
British Journal of Dermatology 12/2007; 158(2):375 - 381. · 3.67 Impact Factor
-
Nederlands tijdschrift voor geneeskunde 12/2006; 150(45):2514-5; author reply 2515.
-
[show abstract]
[hide abstract]
ABSTRACT: During a two-year study, 505 teledermatology consultations were carried out on 503 patients of 29 participating general practitioners (GPs) in the province of Friesland. One overview and two detail digital photographs of the skin problems were taken on a digital camera and attached to an email message containing standard clinical information. These email messages were sent to a dermatologist, who replied by email after evaluation. After a median follow-up time of 548 days, the GPs were interviewed about the dermatological referrals. The reduction in referrals was 51% (0.95 confidence interval = 47-58%) when the GP had the intention to refer. When the GPs had no intention to refer, there turned out to be a secondary traditional consultation in 17% of cases. The reduction of 51% of referrals after store-and-forward teledermatology consultation was similar to that seen in other studies of videoconferencing. Consultation using digital store-and-forward teledermatology by the GP can halve the number of referrals to a dermatologist for selected patients.
Journal of Telemedicine and Telecare 02/2006; 12(2):75-8. · 1.21 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Teledermatological consultation can be effected in two ways. One is 'store-and-forward' which involves storing photographic digital images and sending them to a consultant dermatologist who then replies by e-mail, and the other is by videoconferencing using a real time interactive audiovisual link. In daily general practice the first method is the easiest to implement. In 76-90% of cases, a diagnosis or differential diagnosis made in this way corresponds with the diagnosis made at the more usual face-to-face examination. The advantage of teledermatological consultation is that diagnosis and therapy take place faster than after regular referral and it is better than no referral at all. The referring physician should deliver data on the patient's history and physical examination in a standardized format. The same is true for the encoded personal data, the working diagnosis, and referral request. One overview and 2 detailed photos from two angles are normally taken. The overview shows the extent and localization of the skin abnormality. The patient has to consent to a teledermatological consultation. The responsibility for the treatment lies with the doctor who sees the patient face-to-face. The data that is transmitted must be encrypted or coded in such a way that it cannot be traced back to one particular person.
Nederlands tijdschrift voor geneeskunde 03/2004; 148(7):314-8.
-
[show abstract]
[hide abstract]
ABSTRACT: Lymphedema is a symptom of tissue fluid accumulation which arises as a consequence of impaired lymphatic drainage. This reduced drainage can be either congenital or acquired, for example after breast cancer treatment. Early diagnosis of a swollen limb and adequate treatment are important in order to prevent irreversible tissue changes. The medical history and characteristic clinical presentation form the cornerstone of the diagnostic process. Lymphoscintigraphy can be used to obtain additional information about the functioning of the lymphatic system. Information and recommendations on precautions, preventive measurements and self-management instructions are important to all patients with (risk of) lymphedema. Treatment for lymphedema has to be adjusted to the patient and may consist of several therapeutic options, including manual lymphatic drainage. After volume reduction has been accomplished, a well-fitted compressive garment is essential in the maintenance phase. Surgical procedures for lymphedema are strictly indicated and should be performed by protocol in a multidisciplinary setting with long-term follow-up. Lymphedema is seen in many medical disciplines. A treatment plan is drawn up on the basis of a thorough knowledge of the diagnostics and treatment, with targeted referral to paramedical personnel. As it is a chronic condition, lymphedema requires life-long treatment and follow-up. In view of the complex nature of lymphedema it is recommended that local lymphedema protocols be developed.
Nederlands tijdschrift voor geneeskunde 05/2003; 147(14):648-52.
-
P C van de Kerkhof,
F Cambazard,
P E Hutchinson,
E Haneke,
E Wong,
P Souteyrand, R J Damstra,
P Combemale,
M H Neumann,
R J Chalmers,
L Olsen,
J Revuz
[show abstract]
[hide abstract]
ABSTRACT: Our purpose was to find out whether the addition of calcipotriol ointment (50 micrograms/g) to systemic treatment with acitretin produces additional therapeutic effects and thereby an acitretin-sparing effect, and further to investigate the safety and tolerability of this combination. A multicentre, randomized, double-blind placebo-controlled study was designed. Patients were randomized to receive calcipotriol or placebo. All patients were treated with a starting dose of 20 mg acitretin per day and doses were adjusted at 2-weekly intervals with increments of 10 mg per day up to a maximum of 70 mg per day. The dose requirement for acitretin, clinical signs and adverse events were recorded. Seventy-six patients were randomized to treatment with calcipotriol 50 micrograms/g ointment twice daily and 59 patients to treatment with the vehicle only twice daily. Clearance or marked improvement was achieved by 67% of the patients in the calcipotriol group and by 41% of the patients in the placebo group (P = 0.006). Calcipotriol treatment proved to have a statistically significant additional effect to acitretin on the Psoriasis Area and Severity Index, redness, thickness and scaliness as compared with placebo. Clearance or marked improvement was achieved with a statistically significantly lower cumulative dose of acitretin by the patients in the calcipotriol group as compared with the placebo group. The number of patients reporting adverse events was pronounced and largely related to acitretin. No significant differences were observed between the two treatment groups with respect to adverse events. Laboratory assessments were essentially normal. The addition of calcipotriol ointment to acitretin treatment contributes to the efficacy, reduces the cumulative dose of acitretin to reach marked improvement or clearance, and is well-tolerated and safe.
British Journal of Dermatology 01/1998; 138(1):84-9. · 3.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Occupational contact allergy to 1,2-benzisothiazolin-3-one (1,2-BIT, Proxel) is analysed. This compound is widely used in industry as a preservative in water-based solutions such as pastes, paints and cutting oils. The optimal concentration for patch testing proved to be 0.4 g/l (0.04%) in water. In 4 out of 17 patients (23%) at occupational risk (painters, paper-hangers), contact allergy to 1,2-BIT was found. Of 556 consecutive dermatological patients without clear occupational risk, 10 (1.8%) showed positive patch tests to 1,2-BIT; in 3 patients 1,2-BIT contact allergy was related to domestic paper-hanging. Although the chemical structure of 1,2-BIT shows some analogy with the preservative Kathon CG, true cross-sensitivity was found to be unlikely.
Contact Dermatitis 09/1992; 27(2):105-9. · 3.51 Impact Factor
-
British Journal of Dermatology 10/1991; 125(3):280-1. · 3.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Two patients with psoriasis vulgaris who travelled to endemic malaria areas developed erythroderma and generalized psoriasis guttata 3-4 weeks after starting prophylactic antimalarial medication with chloroquine/proguanil. The lesions resolved after 3 months of intensive treatment and discontinuation of the antimalarial drugs. The literature on these less known adverse effects of antimalarials in psoriatic patients is reviewed. Because of the severity of a malaria infection we advise psoriasis patients to have adequate malaria prophylaxis.
Nederlands tijdschrift voor geneeskunde 05/1991; 135(15):671-3.
-
[show abstract]
[hide abstract]
ABSTRACT: A clinical controlled study is presented for the treatment of condylomata acuminata with cryotherapy in 64 patients. Condylomata resolved in 83% within 4 weeks and 96% after 6 weeks by using cryotherapy. The results were significantly better compared with the control group of 70 patients (13% and 45% after 4 weeks and 6 weeks, respectively). Other therapeutic modalities are reviewed. Cryotherapy is an elegant and effective method for the treatment of condylomata acuminata without discomfort to the patient.
The Journal of dermatologic surgery and oncology 04/1991; 17(3):273-6.
-
[show abstract]
[hide abstract]
ABSTRACT: Teledermatological consultation can be effected in two ways. One is 'store-and-forward' which involves storing photographic digital images and sending them to a consultant dermatologist who then replies by e-mail, and the other is by videoconferencing using a real time interactive audiovisual link. In daily general practice the first method is the easiest to implement. In 76-90% of cases, a diagnosis or differential diagnosis made in this way corresponds with the diagnosis made at the more usual face-to-face examination. The advantage of teledermatological consultation is that diagnosis and therapy take place faster than after regular referral and it is better than no referral at all. The referring physician should deliver data on the patient's history and physical examination in a standardized format. The same is true for the encoded personal data, the working diagnosis, and referral request. One overview and 2 detailed photos from two angles are normally taken. The overview shows the extent and localization of the skin abnormality. The patient has to consent to a teledermatological consultation. The responsibility for the treatment lies with the doctor who sees the patient face-to-face. The data that is transmitted must be encrypted or coded in such a way that it cannot be traced back to one particular person
