Effectiveness and safety of dupilumab in the treatment of atopic dermatitis in children (6-11 years): data from a French multicentre retrospective cohort in daily practice.

BACKGROUND: Dupilumab is the first biotherapy available for the treatment of moderate-to-severe childhood atopic dermatitis (AD). OBJECTIVE: The aim of this study was to evaluate the effectiveness and safety of dupilumab in daily practice. METHODS: Patients aged 6-11, who had received a first dose of dupilumab, were included in this multicentre retrospective cohort study. The primary endpoint was change in SCORAD after 3 months of treatment. Secondary endpoints were change in IGA score at 3 months, proportion of patients with SCORAD50 and SCORAD75, description of adverse events and proportion of children in our cohort who would be excluded from pivotal phase 3 clinical trial. RESULTS: Eighty patients were included. After 3 months of treatment, there was a significant decrease in SCORAD (mean: 21.8 ± 13.8 vs 53.9 ± 18.5; P < 0.0001) and IGA (1.3 ± 0.8 vs 3.5 ± 0.7; P < 0.0001). Conjunctivitis was observed in 11.3% (n = 9/80); three patients experienced dupilumab facial redness (DFR); 17.5% (n = 14/80) reported injection site reactions; 6.3% (n = 5/80) discontinued treatment. 61.2% (n = 49/80) children were ineligible in the phase 3 trial. LIMITATIONS: There is no control group. Because it was a real life study based on information from patient medical records in a French multicentre cohort, we cannot rule out the presence of reporting bias generated by the use of patient reported characteristics and missing information. CONCLUSION: These real-life data confirm the efficacy and safety of dupilumab in children with moderate to severe AD extended to dyshidrosis and atopic prurigo, but it also revealed a lower frequency of DFR and conjunctivitis. However, administration in injectable form may be a barrier in this age group.

[Sebotropic drug eruption after ingestion of bee pollen]. / Éruption induite à tropisme sébacé après consommation de pollen d'abeille.

INTRODUCTION: The medical literature contains five cases of exanthema with sebaceous tropism induced by consumption of kava-kava extract filed under the name of sebotropic drug reaction. Herein we report a new case following consumption of bee pollen. PATIENTS AND METHODS: A 37-year-old man consulted for erythemato-papular and fixed plaques of the face, upper trunk and shoulders present for 3 days. Standard blood tests were normal except for neutrophil leukocytosis at 9.8 G/l and eosinophilia at 1.4 G/l. Cutaneous biopsy of a facial plaque revealed folliculocentric lesions with necrosis of sebocytes in the sebaceous gland, associated with an eosinophil-rich infiltrate. The patient had begun consuming bee-pollen granules 3 weeks before the onset of symptoms. The rash regressed within 3 weeks of cessation of pollen consumption. Patch tests (ICDRG battery, propolis 1% Vaseline dilution and bee pollen provided by the patient, both pure and in a 30% dilution in Vaseline) were negative at 48 and 72h. DISCUSSION: The clinical-pathological correlation was consistent with a diagnosis of sebotropic drug reaction induced by the consumption of bee pollen. The diagnosis was based on papular exanthema of the seborrheic zones occurring 2 to 3 weeks after initial intake of the offending substance, with histological evidence of inflammatory necrosis of the sebaceous glands. CONCLUSION: We report what is to our knowledge the first case of sebotropic drug reaction following ingestion of bee pollen.

[Baboon syndrome due to a polysensitization with corticosteroids]. / Syndrome babouin associé à une polysensibilisation aux corticoïdes.

BACKGROUND: The Baboon syndrome is a form of systemic contact dermatitis. We report the case of a patient who presented a Baboon syndrom following oral medication with betamethasone. CASE REPORT: A 58 year-old man had consulted for eczema involving the groin, the buttocks and the axillae. It was clinically a baboon syndrome related to oral betamethasone (Celestene) treatment, ingested 48 hours earlier. The exploration with a patch-test confirmed the sensitization to betamethasone. This exploration also showed a sensitization to all four classes of corticosteroids. Prolonged withdrawal of all corticosteroids led to the clear improvement of his eczema. DISCUSSION: The baboon syndrome of this patient was the symptom of a systemic eczema due to betamethasone. The patient was sensitized by the percutaneous route. The application of many topical corticosteroids had provoked this polysensitization. It was impossible to consider a safe corticosteroid for this patient.

[Cutaneous and subcutaneous hematomas observed in dermatology: 17 cases]. / Hématomes cutanés et sous-cutanés vus en dermatologie: 17 cas.

INTRODUCTION: Cutaneous hematomas are a cause of hospitalization in departments of dermatology. Their clinical diagnosis can be difficult, particularly since they can masquerade as thrombophlebitis or abscesses. We conducted a retrospective study so as to specify their frequency, clinical aspects and circumstances of occurrence. PATIENTS AND METHODS: The search for hospitalizations was conducted, using a computer data coding and key word "hematoma", from January 1997 to March 2003. The following items were studied: age, gender, clinical aspect on admission, topography, use of anti-platelets or anticoagulants, the existence of documented overdosing, treatment before hospitalization and existence of fever. RESULTS: The 17 patients hospitalized for hematomas were 9 women and 8 men with a mean age of 71 years. Thirteen patients were treated with: antivitamin K (5 cases), low molecular weight heparin (3 cases), anti-platelets (4 cases), or a combination of antivitamin K and anti-platelets (1 case). Four patients had no antivitamin K or anti-platelet treatment; their coagulation control was normal and they were younger than the patients taking a treatment (55 versus 76 years). The hematomas always involved the lower limbs. The clinical aspect was: simple hematoma (3 cases), inflammatory or over-infected hematoma (11 cases) and post-hematoma ulceration (3 cases). Seven patients were febrile either before or during their hospitalization. A context of trauma was noted in 10 patients. In the 9 patients treated with antivitamin K or low molecular weight heparin, overdosing was documented in 5. The treatments received before hospitalization were: general antibiotherapy (7 cases), local antibiotherapy (1 case) and low molecular weight heparin (7 cases). DISCUSSION: Hematomas of the legs usually occur in elderly patients, treated with anticoagulants or anti-platelets. They present in the form of ecchymotic tumefaction, frequently inflammatory or febrile. Therapeutic overdosing is common. The ratio with the erysipelas hospitalized in our department is of 1/8; over the past 5 years we have observed a mean of 3 cases per year. Hence they are not uncommon and dermatologists must be aware of their clinical aspects and the circumstances in which they occur.

[Erythroderma and multiple cutaneous necrosis revealing a dermatomyositis]. / Erythrodermie et nécroses cutanées multiples révélant une dermatomyosite.

INTRODUCTION: We report an original case of dermatomyositis associated with neoplasia, which initial clinical expression was erythroderma and multiple cutaneous necrosis. OBSERVATION: A 64-year-old patient was admitted at hospital for erythroderma. He had a diffuse and inflammatory erythema with thrill, periorbital oedema, periungueal telangiectasia and epidermal necrosis. Physical examination also revealed symmetric proximal muscle weakness as well as hepatomegaly. There were biological signs of myolysis. Complementary investigations revealed a liver carcinoma with lung metastasis. The patient first underwent topical corticosteroid treatment, which provided partial improvement of the clinical and biological signs of disease. Thereafter he was treated with prednisone and tamoxifen. Death occurred at home 4 months after the diagnosis. DISCUSSION: Diagnosis of dermatomyositis was definitely set according to the criteria of Bohan and Peter. Epidermal necrosis, present in our observation, occur classically in dermatomyositis where they are a predictive factor of association with neoplasia. Other recognized predictive factors are the age of the patient and persistent itching. Erythroderma linked to dermatomyositis is a very unusual event: 4 cases have been reported in the literature, only one of which was associated with cancer. On the other hand, numerous cases of diffuse erythema were reported, which are close to erythroderma. It is not possible to set out that this clinical form is a factor of bad prognosis of dermatomyositis. As a matter of fact, in the published cases, one does not find more frequent deceases, pejorative signs or increased frequency of association with neoplasia.

["Sunshine at school": a network for training on sun exposure. Assessment of knowledge among 683 children]. / Le soleil à l'école: réseau d'éducation à l'exposition solaire. Evaluation des connaissances chez 683 enfants de CM1 et CM2.

INTRODUCTION: The protection of children from sun exposure appears inadequate. We assessed the knowledge of pre-teenagers, before and after they attended a training session on sun exposure. This investigation was carried out in Orléans and in 5 surrounding cities, from September 2000 to April 2002. MATERIAL AND METHODS: A didactic slide show on sun exposure and photoprotection was presented to 683 children in grade 4 and 5 by a nurse and a dermatologist during 30 informative sessions. The children filled in questionnaires at each training session and then one month later. The questionnaires contained 10 closed questions involving 32 cognitive and behavioral items. RESULTS: Forty-five percent of the children claimed that they were exposed to the sun more than one hour a day during holidays, 14 p. 100 more than 3 hours a day; 26 p. 100 declared they had never been sunburnt; 46 p. 100 said they had been less than 5 times, 15 p. 100 from 5 to 10 times and 12 p. 100 more than 10 times; 74 p. 100 of the children claimed they enjoyed getting sun-tanned; 80 p. 100 knew that sun exposure could lead to serious diseases, while 73 p. 100 realized that contracting sunburns during childhood increases the risk of subsequent skin cancers; 89 p. 100 knew of the necessity of sun-screen use prior to exposure, 94 p. 100 knew that they help to protect the skin whereas 78 p. 100 knew it must be applied on a regular basis; 77 p. 100 of the children had been informed of the importance of sun protection factor; 92 p. 100 of them were aware of the relevance of a cap and sunglasses for protection from the sun, whereas only 45 p. 100 knew of the need for a tee-shirt. DISCUSSION: Our study showed that children are generally aware of the dangers of sun exposure. This might be the result of previously initiated information and prevention campaigns on skin cancers. This study suggests the efficiency of such projects, and the lasting effects of the information received within one month. However, large numbers of children are still overexposed and subsequently suffer from traumas. The appeal of sun embellishment appears to go back to childhood, and should be taken into account from the early stages of childhood in future preventive actions. An efficient policy of education on sun exposure - including teaching tools relevant to each age--still has to be developed.

An epidemic of allergic contact dermatitis due to epilating products.

Over a period of 19 months, 33 cases of acute allergic contact dermatitis from Veet epilating waxes and/or the accompanying tissue (Reckitt Benckiser, Massy, France) were observed in France and Belgium. The lesions started on the legs and spread to other parts of the body, especially the face, and were sometimes so severe that hospitalization and/or systemic corticosteroids were required. Primary sensitization occurred as early as after the first application in several patients. Patch tests were performed in 26 of the patients and produced strong positive reactions to the tissue (25 times) and/or the wax (13 times). The allergenic culprits in the wax were modified-colophonium derivatives (colophonium in the standard series testing negatively in all except 4 patients), while methoxy PEG-22/dodecyl glycol copolymer and to a lesser degree lauryl alcohol turned out to be the main causal allergens in the tissue.

[Bone evaluation in ten adults with cutaneous mastocytosis]. / Evaluation de l'état osseux chez dix adultes atteints de mastocytose cutanée.

BACKGROUND: To systematically evaluate the bone status, searching for osteoporosis in patients with cutaneous mastocytosis. PATIENTS AND METHODS: In a prospective study from March 1997 to June 2000, we included all new patients examined for cutaneous signs of mastocytosis. Past history, physical examination, skin biopsy, laboratory tests, bone densitometry, cytology and histopathology of bone marrow and other complementary investigations were performed in all these patients. RESULTS: Ten patients were included. Two patients had osteoporosis. Five others had osteopenia. Four patients had bone marrow involvement due to mastocytosis. One of these four patients had myelodysplasia. DISCUSSION: This study suggests better investigation of bone density and bone marrow in patients who have cutaneous mastocytosis. Systematic histopathology of bone marrow and osteodensitometry help to detect patients with systemic involvement. Bone densitometry is particularly effective for early detection of patients at risk for fracture and is of practical interest since patients with osteoporosis can now be treated with Pamidronate.

[Dyshidrosis and acral purpura during polymorphic dermatitis in pregnancy: 2 cases]. / Dyshidrose et purpura acral au cours de la dermatite polymorphe gravidique: 2 cas.

BACKGROUND: We describe two severe cases of polymorphic eruption of pregnancy associated with dyshidrosis and purpuric lesions. CASE-REPORT: Two patients, primigravida at 35 and 34 weeks of amenorrhea, were admitted in our department for a severe and itchy eruption. In the first case, some papular lesions were particularly concentrated on the abdominal striae, associated with vesicles on the limbs. There were plantar dyshidrosis and purpuric macules on the toes. In the second case, there were a maculopapular eruption on the abdomen and limbs, some vesicles and bullae of palms and soles, and a purpura of heels. In both cases, the skin biopsy showed dermic inflammatory, direct immunofluorescence and Pemphigoide Gestationis Factor research were negatives. The two patients were treated with betamethasone dipropionate (Diprosone(R)), and hydroxyzine (Atarax(R)). They gave birth to healthy babies. DISCUSSION: Dyshidrosis is not exceptional in polymorphic eruption of pregnancy. Indeed, in the several series of polymorphic eruption of pregnancy we checked, a pompholyx distribution was observed in 5 p. 100 of the cases. It is not necessary a sign of pemphigoid gestationis, even if this localization is commonly observed. The purpuric lesions are unusual because, according to our knowledge, there is no description of purpura associated with palmoplantar lesions in polymorphic eruption of pregnancy. The purpuric lesions may be secondary to high capillary permeability, increased by severe dermic inflammation of the polymorphic eruption of pregnancy and, possibly, high level of circulating estrogens.

[Localized bullous eruption after intravenous injection of aciclovir: toxic or immunoallergic mechanism?]. / Eruption bulleuse localisée après injection intraveineuse d'aciclovir: mécanisme toxique ou immunoallergique?

OBJECTIVE: To report a case of bullous eruption at and far from the site of aciclovir injection. CASE REPORT: A 50-year-old man was treated with intravenous aciclovir for Herpes simplex meningoencephalitis. Ten days after treatment onset, blisters appeared on his right forearm, at and far from the site of aciclovir injection. DISCUSSION: This adverse effect has not been frequently reported. To date, bullous eruptions were considered to result from extravasation of the aciclovir solution. In this case, an immunoallergic pattern was discussed with the presence of a histological leukocytoclastic vasculitis.

[Paresthetic notalgia and multiple endocrine neoplasia type 2a (Sipple's syndrome): 3 cases]. / Notalgie paresthésique et néoplasie endocrinienne multiple de type IIA (syndrome de Sipple): 3 cas.

INTRODUCTION: Notalgia paresthetica is an isolated sensory mononeuropathy. Patients have a pruritus in the mid-upper back. Its association with multiple endocrine neoplasia type IIA has been reported in a few cases. We report three cases of this association. CASE REPORTS: Case n(o) 1: A 45 year-old woman had multiple endocrine neoplasia type IIA with a medullary thyroid carcinoma and a primary hyperparathyroidism; she had a mid-upper back pigmented lesion. Histological examination showed dermal melanosis and deposits of amyloid in the dermis. Case n(o) 2: A woman had a multiple endocrine neoplasia type IIA which was diagnosed at the age of 60; she had a surgical treatment for a pheochromocytoma, a medullary thyroid carcinoma, and a primary hyperparathyroidism; she had dermatological examination for a pruriginous lesion of the mid-upper back. Case n(o) 3: The daughter of the patient n(o) 2 had had a surgical cure for a medullary thyroid carcinoma and a pheochromocytoma at the age of 31; she had a papulous and pruriginous lesion in the left scapular area. Her daughter and her sister had a multiple endocrine neoplasia type IIA without notalgia paresthetica. DISCUSSION: Notalgia paresthetica is a benign cutaneous disorder which can be associated with multiple endocrine neoplasia type IIA. It can be considered that notalgia paresthetica is an early clinical marker of multiple endocrine neoplasia type IIA. Patients with a familial history of notalgia paresthetica or with an onset of notalgia paresthetica in childhood should be screened for multiple endocrine neoplasia type IIA. Patients with multiple endocrine neoplasia must also been screened for notalgia paresthetica because its finding is an argument for a familial form of multiple endocrine neoplasia type IIA. Dermatologists should be aware of this association.

[Palmoplantar filiform parakeratotic hyperkeratosis and digestive adenocarcinoma]. / Hyperkératose palmo-plantaire filiforme parakératosique et adénocarcinome digestif.

INTRODUCTION: There are very few observations of filiform palmo-plantar hyperkeratosis reported. Nevertheless it's worth knowing this entity for his potential association with a visceral neoplasia. CASE REPORT: We report the first case of filiform palmo-plantar hyperkeratosis associated with a digestive adenocarcinoma and a polycystic kidney disease. DISCUSSION: After a review of palmar and plantar filiform hyperkeratosis in the literature, we will discuss the possible association with neoplasia or other pathologies. This pathology requires a strict clinical and paraclinical follow-up.

[Bazex paraneoplastic acrokeratosis. Treatment with acitretin]. / Acrokératose paranéoplasique de Bazex. Traitement par acitrétine.

INTRODUCTION: Bazex paraneoplastic acrokeratosis remains a therapeutic challenge when the cancer cannot be treated. We report the third patient in which a complete clearance of the lesions was obtained with oral acitretine. CASE REPORT: A 67 year-old patient had Bazex paraneoplastic acrokeratosis. Despite a complete cancer screening, no cancer was found. A cervical lymph node metastasis was treated with surgery and radiotherapy. Because the cutaneous lesions got worse after this treatment, the patient received oral acitretine. A complete clearing of the lesions was observed within 2 months. DISCUSSION: Only 2 similar cases have been reported to our knowledge. The comparison with these 2 cases supports the efficacy of oral retinoids in this disease. The search and the treatment of the cancer remain compulsory. CONCLUSION: In some definite cases, oral retinoids can be proposed as a treatment of cutaneous lesions in Bazex paraneoplastic acrokeratosis.