Most chilblains observed during the COVID-19 outbreak occur in patients who are negative for COVID-19 on polymerase chain reaction and serology testing.

BACKGROUND: Acral lesions, mainly chilblains, are the most frequently reported cutaneous lesions associated with COVID-19. In more than 80% of patients tested, nasopharyngeal swabs were negative on reverse transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2 when performed, and serology was generally not performed. METHODS: A national survey was launched on 30 March 2020 by the French Society of Dermatology asking physicians to report cases of skin manifestations in patients with suspected or confirmed COVID-19 by using a standardized questionnaire. We report the results for acral manifestations. RESULTS: We collected 311 cases of acral manifestations [58.5% women, median age 25.7 years (range 18-39)]. The most frequent clinical presentation (65%) was typical chilblains. In total, 93 cases (30%) showed clinical suspicion of COVID-19, 67 (22%) had only less specific infectious symptoms and 151 (49%) had no clinical signs preceding or during the course of acral lesions. Histology of skin biopsies was consistent with chilblains. Overall, 12 patients showed significant immunological abnormalities. Of the 150 (48%) patients who were tested, 10 patients were positive. Seven of 121 (6%) RT-PCR-tested patients were positive for SARS-CoV-2, and five of 75 (7%) serology-tested patients had IgG anti-SARS-CoV-2. Tested/untested patients or those with/without confirmed COVID-19 did not differ in age, sex, history or acral lesion clinical characteristics. CONCLUSIONS: The results of this survey do not rule out that SARS-CoV-2 could be directly responsible for some cases of chilblains, but we found no evidence of SARS-CoV-2 infection in the large majority of patients with acral lesions during the COVID-19 lockdown period in France. What is already known about this topic? About 1000 cases of acral lesions, mainly chilblains, were reported during the COVID-19 outbreak. Chilblains were reported to occur in young people within 2 weeks of infectious signs, which were mild when present. Most cases did not have COVID-19 confirmed by reverse transcription polymerase chain reaction (RT-PCR), and few serology results were available. What does this study add? Among 311 patients with acral lesions, mainly chilblains, during the COVID-19 lockdown period in France, the majority of patients tested had no evidence of SARS-CoV-2 infection. Overall, 70 of 75 patients were seronegative for SARS-Cov-2 serology and 114 of 121 patients were negative for SARS-CoV-2 RT-PCR.

Tattoo complications in treated and non-treated psoriatic patients.

BACKGROUND: Tattooing is a widespread phenomenon, with an estimated prevalence of 10-30% in Western populations. For psoriasis patients, current recommendations are to avoid having a tattoo if the disease is active and they are receiving immunosuppressive treatments. Although scientific data supporting these recommendations are lacking, dermatologists are often reluctant to advocate tattooing in psoriasis patients. OBJECTIVE: We aimed to evaluate the frequency of tattoo complications in patients with psoriasis and determine whether the occurrence of complications was associated with psoriasis status and treatments received at the time of tattooing. METHODS: We performed a multicentre cross-sectional study. Adults with psoriasis were consecutively included and classified as tattooed or non-tattooed. Prevalence of complications associated with tattoos was then evaluated according to psoriasis onset and treatments. The study was divided into three parts, in which data were collected through a series of questionnaires filled in by the dermatologist. Complications included pruritus, oedema, allergic reaction/eczema, infection/superinfection, granuloma, lichenification, photosensitivity, Koebner phenomenon and psoriasis flare after tattooing. Diagnosis of complications was made retrospectively. RESULTS: We included 2053 psoriatic patients, 20.2% had 894 tattoos. Amongst non-tattooed patients, 15.4% had wished to be tattooed, with psoriasis being stated as a reason for not having a tattoo by 44.0% and 5.7% indicating that they planned to have a tattoo in the future. Local complications, such as oedema, pruritus, allergy and Koebner phenomenon, were reported in tattoos in 6.6%, most frequently in patients with psoriasis requiring treatment at the time of tattooing (P < 0.0001). No severe complications were reported. CONCLUSIONS: The rate of tattoo complications in psoriasis patients was low. Although the risk of complications was highest amongst patients with psoriasis requiring treatment at the time of tattooing, all the complications observed were benign. These results can be helpful for practitioners to give objective information to patients.

[Cryosurgery and photodynamic therapy for the treatment of Paget's disease of the vulva: two cases]. / Traitement de la maladie de Paget vulvaire par cryochirurgie et photothérapie dynamique topique.

BACKGROUND: Surgery is the standard treatment for vulvar Paget's disease, despite its mutilating consequences and the high associated recurrence rate. Alternative treatments such as CO2 laser, application of imiquimod and topical photodynamic therapy (PDT) have recently been proposed. We report on two patients with vulvar Paget's disease treated with combined cryosurgery and PDT. PATIENTS AND METHODS: Case 1: a 40-year-old pregnant woman presented large vulvar lesions suggestive of Paget's disease. After imiquimod treatment failed, three sessions of cryosurgery were performed on all lesions at 5-month intervals, followed by PDT sessions for the residual erythema. Because of recurrent focal lesions, further sessions of localized cryosurgery were performed for 18 months. Case 2: a 61-year-old patient with extensive vulvar Paget's disease relapsed after imiquimod treatment and was treated by cryosurgery and multiple PDT sessions. She was in complete remission 12 months after this treatment. DISCUSSION: Combined cryosurgery and PDT may offer a therapeutic alternative to conventional surgery for the treatment of large or recurrent multifocal vulvar Paget's disease, or in elderly people. Indeed, although palliative, these two non-invasive techniques can be used to treat many lesions in a single session. Recurrences can be treated again using either technique, or both, without any aesthetic or functional consequences.

Loss of heterozygosity on 10q and mutational status of PTEN and BMPR1A in colorectal primary tumours and metastases.

We investigated the possible role of chromosome 10q losses in colorectal cancer metastasis by carrying out an allelic imbalance study on a series of microsatellite instability-negative (MSI-) primary tumours (n=32) and metastases (n=36) from 49 patients. Our results demonstrate that 10q allelic losses are associated with a significant proportion (25%) of MSI- colorectal tumours, but are not involved in the metastatic process. PTEN and BMPR1A, two genes located in the common deleted region, were screened for mutations in samples with loss of heterozygosity. The absence or low frequency of mutations indicates that the inactivation of these genes by deletion of one allele and mutation of the other one plays only a minor role in MSI- tumours.

Local hepatic immune response in rats during primary infection with Fasciola hepatica.

The distribution of lymphocyte subpopulations (TCD4+, TCD8+, TCD43+ and Ig+ cells), macrophages and eosinophils were analysed in the inflammatory infiltrates associated with hepatic lesions and in hepatic lymph nodes (HLN) from rats experimentally infected with F. hepatica and necropsied 1, 2, 3, 4, 6 and 8 week post infection (WPI). We also investigated the fixation of immunoglobulin isotypes on migrating flukes in the liver. As early as 1WPI, portal tract areas surrounding migratory tunnels were infiltrated with immune and inflammatory cells. The dominant cells were eosinophils and to lesser extent, macrophages and lymphocytes (TCD4+, TCD8+ and B). Most of the inflammatory and immune cells reached the posterior part of flukes, whereas in front of the parasites these cells were fewer in number. Except for eosinophils, no immune cells penetrated through granuloma consisting of hepatic necrotic cells. As early as 1WPI, IgM could be detected in the liver, and to a lesser extent IgA, IgG2a and IgG2b. At 2WPI, IgE and IgG1 began being detected. IgG2c was detectable at 3WPI. In HLN, we observed numerous microscopic follicles in the cortical zone with proliferation of germinal centres and medullary cords. The protective role of infiltrating cell populations and immunoglobulin isotypes and possible mechanisms of immune evasion by the parasite are discussed.

[Localized bullous pemphigoid following radiotherapy]. / Pemphigoïde localisée après radiothérapie.

BACKGROUND: Bullous pemphigoid is the most frequent autoimmune blistering dermatologic disease. Induction of pemphigoid has been observed after administration of certain drugs but also after various irradiation procedures. We report a case of pemphigoid strictly confined to the irradiated area. CASE REPORT: A 66-year-old woman had been irradiated 16 years before because of a breast carcinoma. She presented with a blistering rash strictly confined to the irradiated area. The diagnosis of pemphigoid was confirmed with pathologic examination, direct immunofluorescence, direct immunofluorescence of sodium chloride-separated skin, electron microscopy and immunoelectron microscopy. Indirect immunofluorescence and serum immunoblot were also positive. The patient was successfully treated with topical steroids. DISCUSSION: The location on the area of radiotherapy and the limited character of lesions were unusual. A few cases of pemphigoid strictly localized to the area of radiotherapy have been published. However, in our case, only direct immunofluorescence and immunoelectron microscopy reliably confirmed the diagnosis. The unusual location of this pemphigoid is not due to the regional variation in the expression of the antigen. Other hypotheses concerning the pathogenesis of localized pemphigoid should be examined.

Local immune response to experimental Fasciola hepatica infection in sheep.

Macrophages, eosinophils, neutrophils and lymphocyte subpopulations (OvCD5+, OvCD4+, OvCD8+, OvWC1+ and lg+) were identified in sections of hepatic tissue and hepatic lymph nodes from sheep experimentally infected with F. hepatica and necropsied 14, 28, 42 or 56 days post infection. The migratory tunnels produced by juvenile flukes appeared as local areas of necrosis surrounded by infiltrating inflammatory cells, particularly numerous macrophages, eosinophils and OvCD4+ lymphocytes n addition, B lymphocyte proliferation was observed in hepatic lymph nodes and in hepatic portal tracts. Only three juvenile flukes were identified in the sections. They where partially in contact with healthy tissue and partially with neutrophils, macrophages and eosinophils; they were covered by IgM Host-parasite interactions resulting from immune response regulation by helper T lymphocytes and from immune evasion by the parasite are discussed.

Effect of hypodermin A, an enzyme secreted by Hypoderma lineatum (Insect Oestridae), on the bovine immune system.

The absence of any inflammatory reaction around the first instar larvae (L1) of Hypoderma sp. in previously uninfested cattle suggested that these larvae may escape the non-specific defence system of the host. Immunosuppression had been noted during an experimental infestation. The aim of this work was to determine more precisely the potential role of hypodermin A (HA), an enzyme secreted by the larvae, in this immunosuppression. HA was found to have no effect on unstimulated lymphocytes from naive cattle but could influence the response of these cells to mitogens. In calves, injection of HA was accompanied by a decrease in the lymphocyte proliferative response to mitogens. This immunodepression lasted only for the duration of enzyme injections. In cattle, when HA is added, the antigen-dependent proliferative response increased significantly after 1 week of injection and disappeared 2 weeks after the end of the injection period. Finally, the rate of production of anti-HA antibodies increased at the same rate for calves and cows, and achieved a similar level. These results suggest that HA significantly modified the lymphoproliferative response for naive cattle and, to a lesser extent, immune cattle during the time of administration only.

Degradation of bovine C3 by serine proteases from parasites Hypoderma lineatum (Diptera, Oestridae).

Purified enzymes of Hypoderma lineatum (Insecta, Oestridae), were assayed for their proteolytic activity on bovine C3 in normal cattle sera. The products of cleavage by these serine proteases (hypodermins A, B, and C), were analysed by electrophoresis in SDS polyacrylamide gels followed by immunoblotting. The enzymatic attack was initially directed at the alpha polypeptide chain by hypodermin A at a concentration of 1 micrograms/ml of serum and by hypodermin B at 5 micrograms/ml. The generated peptides differed in their molecular size from those produced during natural degradation of C3 in a control serum by physiologically relevant enzymes. Hypodermin A, at a concentration of 1 microgram/ml, also caused a cleavage of the beta chain. At 5 micrograms/ml, hypodermin A induced total degradation of the C3 molecule. Hypodermin B (5 micrograms/ml) starts splitting C3 near cleavage sites of factor I. Bovine C3 appears to be highly sensitive to hypodermins A and B in normal sera. Apparent molecular sizes and alignment of the bovine C3 cleavage products are presented schematically. Hypodermin C, a collagenolytic enzyme, had no effect on C3 in normal sera. The biological consequences for the immunopathological reactions associated with hypodermosis are discussed.

[Cimetidine treatment of primary hyperparathyroidism]. / Traitement par la cimétidine de l'hyperparathyroidie primitive.

Since Sherwood's report in 1979, contradictory findings have been published with regarding the treatment of primary hyperparathyroidism with Cimetidine. We studied 16 patients with primary hyperparathyroidism treated with 1,200 mg of Cimetidine and followed-up clinically and biochemically. A decrease in serum calcium and urinary CAMP was observed after the fourth week of Cimetidine therapy with no significant change in parathormone levels. In none of the cases did Cimetidine seem to provide a treatment of hyperparathyroidism, a condition which remains curable with surgery.

[Cimetidine treatment of primary hyperparathyroidism]. / Traitement par la cimétidine de l'hyperparathyroïdie primitive.

Since Sherwood's report in 1979, contradictory findings have been published with regards to the treatment of primary hyperparathyroidism with cimetidine. We studied 16 patients with primary hyperparathyroidism treated with 1,200 mg of Cimetidine and followed-up clinically and biochemically. A decrease in serum calcium and urinary CAMP was observed after the fourth week of cimetidine therapy with no significant change in parathormone levels. In none of the cases did Cimetidine seem to provide a treatment of hyperparathyroidism, a condition which remains curable with surgery.

[Suppurative thyroiditis and epithelioma of the piriform sinus]. / Thyroïdite suppurée et épithélioma du sinus piriforme.

The authors report a case of suppurative thyroiditis revealing cancer of the piriform sinus. The course ran two distinct phases. Initially, symptoms resolved under methylprednisolone and ampicillin given with a diagnosis of acute thyroiditis. After corticosteroids were discontinued, a tumefaction in the thyroid area recurred, with clinical features indicating centesis that removed 30 cc of pus ORL examination connected this suppurative thyroiditis to an epithelioma of a piriform sinus.

[Plasma concentrations and urinary excretion of gonadotropins in azoo and oligospermia. Relationship with spermatogenesis and plasma concentration of androgens (author's transl)]. / Concentrations plasmatiques et élimination urinaire des gonadotrophines chez les sujets azoo et oligospermiques. Relations avec la spermatogénèse et la concentration plasmatique des androgènes.

Plasma concentrations and urinary excretions rate of gonadotropins, testosterone, delta 4-androstenedione, dehydroepiandrosterone and 17 and 17 alpha-hydroxyprogesterone plasma concentrations have been studied in 69 patients with oligo or azoospermia and compared with results obtained in 30 normal control subjects. A sperm count and a caryotype have been done in all patients and a testicular biopsy in 35. Analysis of the histo-hormonal correlations does not show a particular stage of spermatogenesis associated with a modification in FSH production. There is a quantitative relationship between spermatogenesis and FSH production. Plasma testosterone is low and LH production normal in excretory azoospermia. In the other patients plasma testosterone is also low but associated with an increased production of LH. Finally there is a direct relationship between urinary excretion of LH and FSH in both normal subjects and patients, suggesting a modulation by specific factors of a common regulation of the secretion of both gonadotropins.

[Hereditary Sipple syndrome (author's transl)]. / Syndrome de Sipple héréditaire.

This entity, isolated by Gorlin, is characterized by the presence of cutaneous and mucous neuromas, facial disfiguration resembling acromegalia as well as morphological changes to the extremities similar to those produced by Marfan's disease. These factors are also associated with multiple endocrinological neoplasms type II of Sipple's syndrome. In other words, malignant tumors developing from thyroid "C" cells as well as from bilateral benign pheochromocytoma (neoplasias which derive from the A.P.U.D. system). It is considered to be hereditary in nature and transmitted as a dominant trait. Its evolution is triphasic, and the prognosis is extremely dismal. There may exist incomplete or benign forms, in the course of which the endocrinological neoplasms may appear very late or not at all. Generally, the diagnosis is easy. This entity can be calssified with other diseases stemming from the neural ridge, in other words "neurocristopathies" but in spite of these similarities with disease of the same embryological origin, it would seem that this particular entity is genetically autonomous. The only effective treatment is surgical, for thyroid neoplasms, as well as neoplasms occurring in the medullo-adrenal glands. It should be noted that this line of treatment must be undertaken with the utmost precaution.

[Plasma concentrations of LH and of sex steroids during the normal menstrual cycle and during contraceptive treatment]. / Concentrations plasmatiques de LH et des stéroïdes sexuels pendant le cycle menstruel normal et sous thérapeutique contraceptive

The authors have studied the long-term effects of combined oestrogen-progestogen on the secretion of gonadotrophins and on ovarian function. Estimation of the radio-immune levels of the plasma concentrations of the pituitary luteinizing hormone (LH), of oestradiol (E2), of progesterone (P) and of 20 alpha hydroxyprogesterone (20 alpha OHP) and of testosterone (T) served as a base for this study. A test cycle and 8 cycles in which a combination of 50 micrograms of ethinyl-oestradiol and 0.5 mg of norgestrel were administered were studied in 4 normal volunteer women. A pituitary stimulation test using 50 micrograms of gonadotrophin "releasing factor" (LH-RH) was given during the 7th cycle. Ovarian stimulation using human menopausal gonadotrophins (HMG) was given during the 8th cycle of treatment in 3 of the women and in 3 other subjects. Pituitary secretion of LH and ovarian secretion of E2 and P are partially inhibited. Pituitary response to the injection of LH-RH stays normal but 5 out 6 patients had no response to stimulation by gonadotrophins. These results allow us to conclude that the lowering of production of gonadotrophins during treatment with combination oestrogen and progestagens is responsible for inhibition of ovarian activity, and that there is a delay before the latter respond to stimulation by either endogenous or exogenous gonadotrophins.

PIP: Plasma luteinizing hormone (LH), estradiol, progesterone, 20alpha-hydroxyprogesterone, and testosterone were radioimmunoassayed daily throughout a normal menstrual cycle, the 3rd, 6th, and 9th cycles during oral contraception with Stediril, and during stimulation with LH-releasing factor (LH-RF), human menopausal gonadotropin (HMG), and human chorionic gonadotropin (HCG). 6 women aged 23-30 took Stediril (50 mcg ethinyl estradiol and .5 mg norgestrel, combined) for 1 year. I n the control menstrual cycle, LH rose to a plateau in the follicular and luteal phases, and a high midcycle peak; estradiol rose progressively until its midcycle peak, then fell and rose again; testosterone varied with higher peaks at midcycle; progesterone began to rise on the day of the LH peak to a maximum 5-9 days after ovulation; 20alpha-hydroxyprogesterone resembled progesterone but at a lower magnit ude. During pill cycles, the subjects took 1 mg dectancyl every 6 hours starting the day before blood sampling to inhibit adrenal corticosteroids. LH, estradiol, and progesterone were very low and invariant from Days 9 to 18. 50 mcg LH-RH elicited a significant LH peak (90-370 ng/ml) within 15-30 minutes. 75 IU FSH did not stimulate formation of a corpus luteum in 3 subjects taking 4 mg dexamethasone per day, although 150 IU FSH caused a corpus luteum to develop in 1 of 3 not taking the corticosteroid. Thus LH, estradiol, and progesterone secretions were incompletely inhibited by Stediril.