[Digital necrosis revealing cold agglutinin disease: Treatment with rituximab]. / Nécroses digitales révélant une maladie des agglutinines froides : traitement par rituximab.

BACKGROUND: Digital necrosis is rarer than lower limb necrosis and constitutes a medical or surgical emergency. Etiological evaluation is required. Cold agglutinin disease is a cause of digital necrosis but diagnosis is difficult. PATIENTS AND METHODS: Herein we report the case of a 57-year-old man presenting recent paroxysmal acrosyndrome of the left hand subsequently complicated by digital necrosis following occupational exposure to cold in his work as a forklift driver. After etiological evaluation, a diagnosis of primary cold agglutinin disease was made. Intravenous rituximab and topical treatment resulted in complete healing. DISCUSSION: Cold agglutinin disease is a rare type of auto-immune hemolytic anemia. Following exposure to cold, paroxysmal cutaneous signs are frequent. The disease may be either primary or secondary with B-cell lymphoproliferative disorder, auto-immune disease or infection. A thorough workup is required. To date, the treatment combining the best positive response rate and good safety is rituximab in weekly perfusions over a 1-month period.

[Nail-fold capillaroscopy in dermatology]. / La capillaroscopie péri-unguéale en dermatologie.

Nail-fold capillaroscopy is a non-invasive tool to study the microcirculation and is increasingly being used in dermatology, angiology and rheumatology. More recently, the use of video-capillaroscopy has allowed computer storage of capillaroscopic images (video-capillaroscopy), enabling evaluation of changes in capillaroscopic abnormalities during the follow-up of patients with systemic sclerosis or mixed connective tissue disease. Qualitative and quantitative assessment of the nail-fold dermal capillaries and of their organization can readily distinguish between a normal capillaroscopic pattern in primary Raynaud phenomenon and a specific sclerodermic pattern in secondary Raynaud phenomenon carrying a very high risk of systemic sclerosis. Apart from its important role as a diagnostic tool for distinguishing between primary and secondary Raynaud phenomenon, capillaroscopy is now used to predict the risk of development of digital ulcers and of future visceral complications in patients with systemic sclerosis. Moreover, nail-fold capillaroscopy is essential for differential diagnosis between connective tissue diseases, for the etiologic diagnosis of digital necrosis and diffuse interstitial lung disease, and in sclerodermiform syndromes.

Evaluation of a rabies ELISA as an alternative method to seroneutralisation tests in the context of international trade of domestic carnivores.

For several years, international movements with pets have greatly increased. Most countries have relaxed their quarantine measures and adopted a scheme combining vaccination of pets against rabies followed by a serological test to check the efficacy of vaccination. This new scheme has been strongly supported by the OIE, WHO and the European Commission to facilitate the free movement of people and pets around the world. Currently, only two reference methods are recognised and prescribed (the FAVN test and the RFFIT) to measure rabies antibody levels in serum samples for international trade. They are reliable and valuable methods of assessing the efficacy of rabies vaccination but they are time-consuming and require well-trained people and specialised laboratory facilities. A few years ago, an ELISA (Platelia™ Rabies II kit ad usum Veterinarium) was developed for domestic carnivores and wildlife. To our knowledge, this ELISA is the only one certified and prescribed by the OIE. Following its marketing, one task of the EURL for rabies serology was to evaluate the performance of laboratories using this new kit. The results revealed that 26% of the participants, which were already approved laboratories for rabies serology, failed the inter-laboratory trial. Such unsatisfactory results have never been observed during any of the previous proficiency tests organised annually since 2000 by the EURL for rabies serology using reference methods. More investigations were undertaken through internal and collaborative studies to assess the performance of this newly marketed ELISA kit. The results of the internal study revealed that even with a specificity of 100%, the sensitivity evaluated on 593 samples of domestic carnivores came to 78.2%. An issue regarding the underestimation of serum titres was also revealed during the study. The results of a collaborative study involving 23 international laboratories reinforced the preliminary conclusions regarding lack of sensitivity. Indeed, only 5 laboratories out of the 23 obtained satisfactory results. We therefore suggest adopting a threshold of 0.3 EU/mL instead of 0.5 EU/mL to increase the sensitivity of the test.

Evaluation of an ELISA to detect rabies antibodies in orally vaccinated foxes and raccoon dogs sampled in the field.

The assessment of the efficacy of oral vaccination in wildlife is based on detection in the teeth of a biomarker (tetracycline) which is incorporated in the vaccine bait, and the quantification of rabies antibodies. A blocking ELISA was evaluated and compared with the FAVN test and a validated in-house ELISA, using sera from foxes and raccoon dogs collected following oral vaccination campaigns in France and Estonia. Specificity reached 100% in sera from naïve animals. A high concordance (95%) was observed between the BioPro ELISA and the FAVN test, which was similar in sera from red foxes and raccoon dogs. Concordance between the BioPro ELISA and the in-house ELISA reached 96.5% for sera from red foxes. The agreement with tetracycline results was excellent in the fox for both the BioPro ELISA (95.9%) and the FAVN test (91.8%). Concordance was slightly lower in the raccoon dog, with a value of 82.8% for the BioPro ELISA and 78.4% for the FAVN test. Rabies antibodies were detected with the BioPro ELISA in animals vaccinated with different types of vaccines and in highly haemolysed sera. The BioPro ELISA is a valuable test to assess the efficacy of oral vaccination in foxes and raccoon dogs.

Measurement of the cutaneous blood flow reserve in normal humans by laser-Doppler flowmetry.

AIM: To assess the normality of the cutaneous blood flow reserve (CR). METHODS: To explore the feasibility and reproducibility of laser-Doppler flowmetry for CR measurement, we prospectively measured CR in 17 healthy subjects on the dorsum of the foot and pulp of the big toe. CR was defined as the sum of the venoarteriolar reflex (VAR), i.e. postural vasoconstriction, and postischemic reactive vasodilation (H), expressed as % of the resting supine flux and assessed by using laser-Doppler flowmetry. RESULTS: For the dorsal foot, VAR%+/-SEM was 61+/-14, H%, 752.5+/-214 and CR, 813.5+/-217. On the pulp of the big toe, VAR% was 61.6+/-4.7, H%, 588.2+/-174 and CR, 649.9+/-176. CR measurement variability was assessed by calculating the inter-individual coefficient of variation of CR, which was 1.1 for both the dorsal foot and pulp of the big toe. Reproducibility was assessed by calculating the CR intraclass correlation coefficient, which was 0.49 for the dorsal foot and 0.64 for the pulp of the big toe. CONCLUSIONS: The CR is proposed as a new parameter for assessing the microvascular integrity and contractile reserve of the skin. Laser-Doppler flowmetry is suitable for this non-invasive evaluation. The method displayed large variability, and its reproducibility varied from moderate for the dorsal foot, to substantial for the toe. Further studies are necessary to demonstrate its clinical usefulness.

Cutaneous microvascular effects of mid-term hormone replacement therapy in healthy postmenopausal women: a prospective placebo controlled trial.

OBJECTIVE: To study the mid-term effects of Hormone Replacement Therapy (HRT) on cutaneous microcirculatory blood flow and reactivity in healthy postmenopausal women. DESIGN: In a double-blind placebo controlled randomized study, 16 healthy postmenopausal women received either placebo or HRT (micronized estradiol: 1 mg/day, day 1-28, promegestrone: 0.25 mg/day, day 14-28). This regimen was completed 6 times. Cutaneous microcirculatory blood flow was recorded by laser-Doppler velocimetry on the foot dorsum, in the supine and then dependent positions, and after post-ischemic hyperemia. RESULTS: At day 0, the two groups were similar and none of the following data differed significantly between treated and placebo group: (supine flux: 11.8 +/- 1.8 u vs. 13.2 +/- 3.9, venoarteriolar reflex: 5.6 +/- 1.3 vs. 6 +/- 3.3, and post-ischemic hyperemia: 35.2 +/- 3.9 vs.48.3+/-11). At the end of the study (day 26-28 of 6th cycle), the supine flux was 9.8 +/- 2.1 in the HRT group vs.12.9 +/- 6 in the placebo group (NS), the venoarteriolar reflex, 1.2 +/- 2 vs. 7+/-1.7 (p=0.04), and post ischemic hyperemia, 31.8 +/- 5.4 vs. 39.5 +/- 4.6 (NS). Intragroup values did not change significantly for any of the microcirculatory parameters measured, which remained stable throughout the 6 months of the study. Intergroup values for these parameters did not change either, except for the venoarteriolar reflex, which was lower at the end of the study in the HRT (EP period, cycle 6 day 26-28) than placebo group (p=0.04). CONCLUSIONS: HRT does not impair the resting supine cutaneous microcirculation blood flow or post-ischemic hyperemia.

Importance of cutaneous postural reflex vasoconstriction in patients with atherosclerotic occlusive disease of the lower extremities.

OBJECTIVE: The present study was designed to measure the cutaneous postural vasoconstrictive reflex (PVR) in normal controls and patients with atherosclerotic occlusive disease of the lower extremities, and to determine its diagnostic and prognostic relevance. EXPERIMENTAL DESIGN: The postural vasoconstrictive reflex was recorded in 34 patients with atherosclerotic occlusive disease of the lower limbs and 27 normal controls, using laser-Doppler flowmetry. Patients also had ankle and toe pressure measurements and transcutaneous oximetry (TcPO2). SETTING: University hospital. RESULTS: The PVR on the pulp of the big toe was 20+/-7 arbitrary perfusion units in normal controls, 9.4+/-12 in patients with claudication, and -19 +/- 5 in patients with rest pain and/or gangrene, who differed from the claudicant and control groups (p=0.001 and 0.0001 respectively). The sensitivity of negative PVR in the big toe was 89% for the diagnosis of rest pain and/or gangrene, and its specificity, 83%. The severity of foot ischaemia and PVR values exhibited a significant inverse correlation (r=-0.56, p<0.0001). All patients with a poor outcome, ie. death and/or major amputation within 100 days of follow-up, had a negative PVR, and all patients with a positive PVR had a good 100-day prognosis without even a minor amputation. CONCLUSIONS: Laser-Doppler provides useful additional information in the assessment of foot ischaemia severity by showing that postural vasoconstriction is impaired in patients with severe atherosclerotic occlusive disease of the lower limbs, resulting in increased skin microcirculatory flow during leg dependency.