Frequency and prognosis of associated malignancies in 504 patients with lymphomatoid papulosis.

BACKGROUND: Lymphomatoid papulosis (LyP) can be associated with other haematological malignancies (HM), but reported percentages vary from 20% to over 50%. OBJECTIVE: To evaluate the frequency and prognostic significance of associated HM and non-HM in LyP patients. METHODS: In this multicentre cohort study, the complete Dutch LyP population was included from the Dutch Cutaneous Lymphoma Registry between 1985 and 2018. Clinical and histopathological information was retrieved from every individual patient. RESULTS: After a median follow-up of 120 months (range, 6-585), an associated HM was observed in 78/504 (15.5%) patients. Most common associated HM were mycosis fungoides (MF; n = 31) and anaplastic large-cell lymphoma (ALCL; n = 29), while 19 patients had another HM of B-cell (n = 14) or myeloid origin (n = 5). Even after a 25-year follow-up period, percentages of associated HM did not exceed 20%. Thirty-nine of 465 patients (8.4%) without a prior or concurrent associated HM developed an associated HM during follow-up, after a median of 68 months (range of 3-286 months). Nine of 78 patients died of associated HM, including 6/22 patients developing extracutaneous ALCL, while all patients with associated MF or skin-limited ALCL had an excellent prognosis. Compared with the general population, LyP patients showed an increased risk (relative risk, 2.8; 95% confidence intervals, 2.4-3.3) for non-HM, in particular cutaneous squamous cell carcinoma, melanoma and intestinal/lung/bladder cancer. CONCLUSIONS: An associated HM was reported in 15.5% of the LyP patients, particularly MF and ALCL. Although the frequency of associated HM is lower than suggested and the prognosis of most patients with associated HM is excellent, a small subgroup will develop aggressive disease, in particular extracutaneous ALCL. Furthermore, LyP patients have a higher risk of developing other malignancies. Clinicians should be aware of these risks, and LyP patients require close monitoring.

Evaluation of treatment results in multifocal primary cutaneous anaplastic large cell lymphoma: report of the Dutch Cutaneous Lymphoma Group.

BACKGROUND: There is no consensus on the treatment of multifocal primary cutaneous anaplastic large cell lymphoma (C-ALCL). Radiotherapy (RT) and methotrexate (MTX) are the current treatment options, but their efficacy is unknown. Recently, targeted therapies showed promising results in C-ALCL, and may therefore be an attractive first choice of treatment. OBJECTIVES: To assess the efficacy of conventional treatment strategies for patients with multifocal C-ALCL, and to define which patients may require novel targeted therapies. METHODS: In this multicentre study, treatment was evaluated in patients initially presenting (n = 24) or relapsing with multifocal C-ALCL (n = 17; 23 relapses). Distinction was made between patients with five or less lesions (n = 36) and more than five lesions (n = 11). RESULTS: Treatments most commonly used were RT (n = 21), systemic chemotherapy (n = 9) and low-dose MTX (n = 7) with complete response rates of 100%, 78% and 43%, respectively, and an overall response rate of 100%, 100% and 57%, respectively. Four patients showed complete spontaneous regression. In total, 16 of 24 patients (67%) first presenting with multifocal C-ALCL relapsed, including all five patients initially treated with CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone). Compared with patients presenting with two to five skin lesions, patients presenting with more than five lesions had a higher chance of developing extracutaneous relapse (56% vs. 20%) and more often died of lymphoma (44% vs. 7%). CONCLUSIONS: Patients with five or less lesions should be treated with low-dose RT (2 × 4 Gy). Maintenance low-dose MTX (20 mg weekly) is a suitable option in patients with more than five lesions. Targeted therapies may be considered in rare patients who are refractory to MTX or patients developing extracutaneous disease.

Recommendations for treatment in folliculotropic mycosis fungoides: report of the Dutch Cutaneous Lymphoma Group.

BACKGROUND: Folliculotropic mycosis fungoides (FMF) is an aggressive variant of mycosis fungoides (MF) and generally less responsive to standard skin-directed therapies (SDTs). Recent studies distinguished indolent (early-stage FMF) and more aggressive (advanced-stage FMF) subgroups. The optimal treatment for both subgroups remains to be defined. OBJECTIVES: To evaluate initial treatment results in patients with early- and advanced-stage FMF. METHODS: A study was undertaken of 203 patients (84 early-stage, 102 advanced-stage, 17 extracutaneous FMF) included in the Dutch Cutaneous Lymphoma Registry between 1985 and 2014. Type and results of initial treatment were retrieved from the Dutch Registry. Main outcomes were complete remission (CR); sustained complete remission; partial remission (PR), > 50% improvement; and overall response (OR; CR + PR). RESULTS: Patients with early-stage FMF were treated with nonaggressive SDTs in 67 of 84 cases resulting, respectively, in CR and OR of 28% and 83% for monotherapy topical steroids, 0% and 83% for ultraviolet B (UVB), and 30% and 88% for psoralen plus ultraviolet A (PUVA). In patients with advanced-stage FMF these SDTs were less effective (combined CR and OR 10% and 52%, respectively). In patients with advanced-stage FMF local radiotherapy (CR 63%; OR 100%), total skin electron beam irradiation (CR 59%; OR 100%) and PUVA combined with local radiotherapy (CR 5%, OR 75%) were most effective. CONCLUSIONS: The results of the present study demonstrate that not all patients with FMF should be treated aggressively. Patients with early-stage FMF may benefit very well from standard SDTs also used in early-stage classic MF and have an excellent prognosis.

Erysipelas as a sign of subclinical primary lymphoedema: a prospective quantitative scintigraphic study of 40 patients with unilateral erysipelas of the leg.

BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.

[A verrucous plaque on the lower leg]. / Een wratachtige afwijking op het onderbeen.

A 10-year-old boy presented with an asymptomatic, congenital, dark brown coloured, well circumscribed, verrucous, hyperkeratotic plaque on his left leg. This was diagnosed as verrucous haemangioma.

[Chronic venous insufficiency]. / Chronische veneuze insufficiëntie.

Chronic venous insufficiency (CVI) is a complex of symptoms occurring on the lower leg, which includes varicose veins, oedema, pigmentation and venous leg ulceration. Most patients have severe complaints, which result in a high medical consumption, mainly due to venous leg ulceration. CVI is caused by a decompensation of the venous system together with reflux in the superficial, deep and/or perforating veins of the lower leg in supine position. The exact pathogenesis of the skin symptoms is still largely unclear. An increased walking venous pressure induces macrocirculatory and microcirculatory changes such as dermal pericapillary fibrin cuffs, leukocyte accumulation and the activation of cytokines. CVI can be treated in several ways: compression therapy, if needs be combined with sclerotherapy or surgery, or with supportive medication.

[Favorable results with duplex-guided compression sclerotherapy for varices of the small saphenous vein; a retrospective study]. / Gunstige resultaten van duplexgeleide sclerocompressietherapie bij varices van de V. saphena parva; een retrospectief onderzoek.

OBJECTIVE: Assessment of the efficacy of duplex-guided compression sclerotherapy in patients with varices of the small saphenous vein (SSV). DESIGN: Retrospective. METHOD: Data were collected from 109 patients (14% male and 86% female; average age 51.4 years (SD: 10.6)) with 121 SSV varices which were sclerosed under duplex guidance with polidocanol 3% during the period 1 December 1998-31 May 2001 in the Dermatology department at Maastricht University Hospital, the Netherlands. After-care consisted of a compression bandage for 1 week and a therapeutic elastic stocking for 6 weeks. Check-ups took place after 3-6 months and after 12 months. Sclerosis was repeated if the procedure had failed. Success was defined as occlusion or by the absence of reflux and a reduction in the complaints. RESULTS: After 3-6 months the treatment was successful in 88/113 varices (78%) for which data were available, and after 12 months treatment was successful in 46/57 (81%). CONCLUSION: Sclerosis of the SSV under duplex guidance, with repeat treatment if required, gave favourable results.

Lymphedema, cardiac septal defects, and characteristic facies: possible new case of Irons-Bianchi syndrome.

We describe a Dutch girl with fetal hydrops, congenital lymphedema of the lower legs, complex congenital cardiac malformation, and a typical face with epicanthal folds. This particular combination of symptoms has been previously described by Irons and Bianchi in 1996. Our report confirms their observation and suggests that this particular constellation of symptoms may constitute a new syndrome. Molecular analysis confirms this statement by demonstrating absence of mutations in several genes known to be involved in syndromes with lymphedema.

Recurrent leg ulcers in a young man with hyperhomocysteinemia, factor V Leiden and impaired fibrinolysis.

We present a young male patient referred to our hospital with leg ulcers on both legs that were more than 3 years refractory to standard treatment with compression therapy. By thrombophilia screening factor V Leiden mutation, hyperhomocysteinemia and evidence for impaired fibrinolysis were found. Treatment with folic acid in combination with long-term oral anticoagulant therapy was added to non-elastic compression therapy. The leg ulcers showed slow improvement and complete healing within 3 years. During a 6-year follow-up period neither new thrombo-embolic events occurred nor recurrence of ulcerations. This case suggests a potential synergistic pathogenic role of factor V Leiden, hyperhomocysteinemia and impaired fibrinolysis in the development of postthrombotic syndrome and his sequelae. We postulate that increased formation of thrombi in the microcirculation of the skin in combination with ambulatory venous hypertension due to recurrent deep venous thrombosis might explain our observation.