[Impact of the Lubrizol Rouen plant fire of September 26, 2019 on ophthalmic emergency room visits]. / Impact de l'incendie de l'usine Lubrizol à Rouen le 26 septembre 2019 sur la fréquentation des urgences ophtalmologiques.

INTRODUCTION: A fire at the Lubrizol chemical factory in Rouen on September 26, 2019 generated a huge column of smoke directed northeast toward the city. As the eye might be particularly affected by the smoke and other toxic emissions from the fire, we assessed the impact of this industrial and ecological disaster on irritative eye surface disease in the week following the accident. MATERIALS AND METHODS: We retrospectively collected the medical data of the patients who presented to the Ophthalmology Emergency Department (OED) of Rouen University Hospital (the only OED open during the days following the accident) during the week following the fire (W1). We compared these data with those of patients who presented during the week before the fire (W-1). We also collected data on patients presenting to the ED in general during W-1 and W1, including the number of visits directly related to the fire. RESULTS: 361 patients presented to the OED during W1 following the fire, compared with 384 in W-1. Of these patients, 83 (23%) had ocular surface disease in W1, versus 76 (20%) in W-1. Conjunctivitis was found in 54 patients in W1 (39 viral, 9 allergic, 6 undetermined) versus 44 in W-1 (27 viral, 12 allergic, 5 undetermined). A dry irritative syndrome was present in 29 patients in W1 versus 32 in W-1. Only 4 patients directly attributed their symptoms to the fire: 2 viral conjunctivitis, 1 allergic conjunctivitis and 1 worried patient (at D2, D5, D7 and D7 following the fire respectively). DISCUSSION: The number of emergency eye consultations did not change in the week following the Lubrizol factory fire (except for a decrease the day of the accident, related to the lock-down). There was a higher number of consultations in W1 for conjunctivitis, mostly viral in appearance and probably not directly related to the fire. The number of consultations for dry irritative syndrome was comparable between the two periods. Despite major media coverage of the event at the national level and a very high level of concern among the population, the fire does not seem to have had an effect on OED activity at Rouen University Hospital, nor on general ED visits. The stay-at-home order on the first day may have had a protective effect, avoiding direct exposure to smoke. The long-term consequences of the soot deposits on the ground as the smoke cloud passed over remain undetermined and are under surveillance. A review of the literature on the ocular consequences of industrial accidents is presented. CONCLUSION: The Ophthalmology Emergency Department did not record increased activity in the week following the Lubrizol Rouen fire, and ocular surface disease did not give rise to more consultations than the week before the fire. This suggests that there was no or minimal immediate ocular toxicity of the smoke from the fire.

Physician satisfaction with transition from CPOE to paper-based prescription.

INTRODUCTION: In January 2015, Rouen University Hospital's information system experienced serious issues. It was necessary to rapidly switch from the computerized provider order entry (CPOE) system towards a paper-based order entry (PBOE) system. This was an opportunity to evaluate prescriber opinion on the two provider order entry (POE) systems. METHODS: All residents were asked to fill an augmented version of the POE satisfaction and usage survey for both POE systems. The results were compared to identify the strengths and weaknesses of each system. RESULTS: Fifty-one respondents had used the CPOE system and the PBOE system. Overall, satisfaction was higher with PBOE than CPOE (odds ratio (OR)=3.74; p<0.001). Usability (OR=4.00; p<0.001), reliability (OR=8.54; p<0.001), time consumption (OR=0.50; p<0.05 - survey statement was formulated negatively), and communication with nurses (OR=14.27; p<0.0001) reached statistically better agreement. The more experience with CPOE the more residents were disillusioned with the reliability (OR=6.55; p<0.01), the usability (OR=5.68; p<0.01) and the patient safety (OR=0.27; p<0.05 - survey statement was formulated negatively) of CPOE. Although safety issues were reported for both systems, the causes were different; PBOE imposed frequent rewriting of the order while CPOE lack of usability might be unsafe. Another important issue with both POE systems was time consumption. CONCLUSION: Residents did not report any increase in safety issues with the rapid switch from CPOE to PBOE. They even seemed more satisfied with the rollback to paper, which remains a possible degraded mode in case of health information technology collapse.

[Assessment of vaccination coverage among travelers to areas where yellow fever is endemic (Senegal)]. / Évaluation de la couverture vaccinale des voyageurs se rendant en zone d'endémicité amarile (Sénégal).

This prospective survey, conducted at the Dakar airport from August 18, 2011, to May 8, 2012, asked a sample of travelers living in France and returning there after a stay in Senegal to complete a questionnaire. The aim of the study was to assess the determinants of vaccination coverage against yellow fever. The study included 10 298 travelers, with a median age of 48 years (interquartile range: 27-58); 52% were tourists, and 22% were traveling for business purposes. The measured level of anti-yellow fever vaccination coverage was 39.3%. Vaccination coverage was influenced by the travelers' level of knowledge and their perception of the risk.

Muscle imaging in dominant core myopathies linked or unlinked to the ryanodine receptor 1 gene.

OBJECTIVE: To characterize the muscle involvement of patients with central core disease (CCD) caused by mutations in the ryanodine receptor 1 gene (RYR1) and to compare these findings with those from patients with core myopathies unlinked to the RYR1 gene. METHODS: We performed a systematic muscular imaging assessment in 11 patients with an RYR1 gene mutation and compared these findings with those of 5 patients from two unrelated families with autosomal dominant core myopathies not linked to RYR1, ACTA1, or MYH7 gene loci. RESULTS: All patients with RYR1 CCD had a characteristic pattern with predominant involvement of the gluteus maximus, adductor magnus, sartorius, vastus intermediolateralis, soleus, and lateral gastrocnemius muscles. In contrast, muscle CT in the first family not linked to RYR1 showed predominant affection of the gluteus minimus and hamstring muscles, whereas the second family presented with predominant involvement of the gluteus minimus, vastus intermediolateralis, tibialis anterior, and medial gastrocnemius muscles. In addition to muscle imaging data, we present detailed information on the clinical and pathologic findings of these novel phenotypes of core myopathies not linked to RYR1. CONCLUSIONS: Our data suggest genetic heterogeneity in autosomal dominant core myopathies and the existence of additional unidentified genes.

[DRESS syndrome related to Hexaquine (quinine and thiamine)]. / Syndrome d'hypersensibilité médicamenteuse à l'Hexaquine (quinine et thiamine).

BACKGROUND: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS syndrome) is a severe drug eruption defined as an association of a drug reaction, mostly cutaneous, laboratory abnormalities with the presence of hypereosinophilia and/or atypical lymphocytes, and involvement of one or more organs. We report a case of DRESS syndrome associated with quinine or thiamine (which in France are combined in Hexaquine with serious hepatitis and renal failure and associated viral reactivation of Human Herpes Virus 6 (HHV6). OBSERVATION: A twenty-three year-old woman was hospitalized for asthenia, fever, erythroderma, facial edema and painful cervical lymph nodes. Laboratory results showed inflammatory syndrome, hypogammaglobulinemia and the presence of activated atypical lymphocytes. Broad screening for infectious serology showed HHV6 reactivation with marked increase in specific IgG levels within two weeks and detection of circulating DNA in blood by PCR (polymerase chain reaction). Two severe complications subsequently appeared: cytolytic hepatitis and interstitial nephritis. The outcome was favorable with oral corticosteroid therapy. Repeated history-taking did not initially identify any causal agent, but several weeks later, the patient remembered taking Hexaquine (quinine and thiamine) for essential muscular cramps daily for 27 days before the onset of symptoms. The patient had taken no other medication during the previous weeks. One year later, at the end of an enteroviral infection, a skin rash similar to the first episode was seen but in isolation on this occasion, suggesting minor reactivation of DRESS syndrome. DISCUSSION: To our knowledge, ours is the first reported case of DRESS syndrome associated with this drug. Because of the difficulty of identifying the causative drug, even though taken alone, our case once again illustrates the importance of spending adequate time on history taking. Although the physiopathology of DRESS syndrome has not yet been fully elucidated, it is nevertheless probable that it is a multi-factor phenomenon (involving medication and viruses among others).

Primary intracranial myopericytoma: report of three cases and review of the literature.

Myopericytoma is a benign tumour generally arising in the subcutaneous and superficial soft tissues of the extremities. Very few cases have been reported in other locations and intracranial examples are exceptional. We now report on three cases of primary intracranial myopericytoma and review the literature on that rare entity. The patients were women in their fifties who presented with decreased visual acuity in two cases and raised intracranial pressure in one case. The tumour involved, respectively, the anterior cranial fossa, the orbital apex and the pineal region. Gross total resection was achieved in all three cases. Histological analysis revealed oval-to-spindle shaped myoid-appearing cells with a striking tendency for concentric perivascular growth. The lesional cells showed apparent differentiation towards perivascular myoid cells as witnessed by smooth muscle actin expression. In one case, an epithelioid differentiation was also present. None of the patients received adjuvant therapy. One patient died of unrelated causes 6 months after surgery. The other two are alive and well at 9 and 12 month follow-up respectively. Myopericytoma is a recently described neoplasm, and it is likely that reappraisal of intracranial haemangiopericytoma with which it shares many histopathologic features will lead to more case reports of primary intracranial myopericytoma.

[Neutrophilic dermatosis associated with propylthiouracil-induced p-ANCA (p-antineutrophil cytoplasmic antibodies)]. / Dermatose neutrophilique associée à des anticorps anticytoplasme des polynucléaires neutrophiles (p-ANCA) induits par le propylthiouracil.

INTRODUCTION: We report on a patient who progressively developed polymorphic expressions of neutrophilic dermatosis (Sneddon-Wilkinson subcorneal pustulosis and pyoderma gangrenosum) associated with p-antineutrophil cytoplasmic antibodies (p-ANCA), while receiving propylthiouracil for hyperthyroidism. To our knowledge, such associations have never been published so far. CASE-REPORT: A 40 year-old woman was treated with propylthiouracil for Graves'disease. After 16 months of therapy, she noted flares of pustular lesions surrounded with erythematous halo mainly localized on the trunk. The lesions became chronic, and were not improved by potent topical corticosteroids. When first seen in our department in February 2003, the eruption was typical of Sneddon-Wilkinson subcorneal pustulosis. This diagnosis was confirmed by the histological examination of a skin biopsy of a pustule. One month later, she developed an inflammatory progressively ulcerative lesion on the right ankle, typical of pyoderma gangrenosum. The diagnosis was confirmed by the histological examination of a skin biopsy taken on the evolving border of the lesion and showed polynuclear neutrophilic infiltration without vasculitis. Direct immunofluorescence was negative. The presence of serum anti-myeloperoxydase p-ANCA was known for this patient since October 2002. No IgA monoclonal gammapathy was revealed on extensive biological check-up. Systemic oral corticosteroid therapy (1 mg/kg/day) dramatically improved skin lesions with complete healing within 8 weeks. DISCUSSION: Propylthiouracil is well known to induce the occurrence of ANCA in 20 to 64p. 100 of patients treated for Graves'disease. The mechanisms involved are badly recognized so far. Cutaneous vasculitis, glomerulonephritis and polychondritis may be clinically associated with those antibodies. Rare observations of neutrophilic dermatosis, mostly Sweet's syndrome, have been described in patients with propylthiouracil-induced ANCA. One case-report described a 44 year-old woman who developed pyoderma gangrenosum associated with propylthiouracil-induced p-ANCA. These manifestations usually appear within 2 years, as our patient. The data in the literature, allows us to report the polymorphic expressions of neutrophilic dermatosis in this patient with p-ANCA which could be related to propylthiouracil. Such association of Sneddon-Wilkinson subcorneal pustulosis and pyoderma gangrenosum with p-ANCA has never been described in this endocrinologic context so far. Furthermore we propose that neutrophilic dermatosis should be inscribed in the list of side effects induced by propylthiouracil therapy.

Towards the molecular elucidation of congenital myasthenic syndromes: identification of mutations in MuSK.

Congenital myasthenic syndromes (CMS) are rare genetic diseases affecting the neuromuscular junction (NMJ) and characterized by a dysfunction of the neurotransmission. They are heterogeneous at the pathophysiological level and can be classified in three categories according to their origin: presynaptic, synaptic or postsynaptic. The strategy for the diagnosis and characterization of CMS relies on the clinic, EMG, muscle biopsy, identification of mutations in genes known to be responsible for CMS and the demonstration that the gene mutations are the cause of the disease by using experimental approaches. As an example of such strategy, we report briefly here the characterization of the first case of a human neuromuscular transmission dysfunction due to mutations in the gene encoding a postsynaptic molecule, the muscle-specific receptor tyrosine kinase (MuSK). Gene analysis identified two heteroallelic mutations, a frameshift mutation (c.220insC) and a missense mutation (V790M). The muscle biopsy showed marked pre- and postsynaptic structural abnormalities of the neuromuscular junction as well as a severe decrease in acetylcholine receptor epsilon-subunit and MuSK expression. In vitro and in vivo expression experiments were performed using mutant MuSK reproducing the human mutations. The results obtained strongly suggested that the missense mutation, in the presence of a null mutation on the other allele, was responsible for the severe synaptic changes observed in the patient and, hence, is causing the disease. However the molecular origin of a large number of CMS is still unknown. There are hundreds of molecules known to be present at the NMJ and mutations in the genes coding for these synaptic molecules are likely to be responsible for a neuromuscular block.

Clinical and histopathological aspects of central core disease associated and non-associated with RYR1 locus.

We analysed the clinical, histochemical, ultrastructural and genetic data of patients affected by central core disease (CCD) studied during the last 20 years. From a total series of 86 CCD-families, we have identified 46 CCD families with RYR1 mutations (16 autosomal dominant, 8 autosomal recessive, 17 sporadic cases and 5 de novo mutations). Out of the other 40 CCD families, the RyR1 gene was entirely excluded in 7 families, by cDNA sequencing or linkage analysis, indicating a genetic heterogeneity of CCD.

Topical imiquimod treatment of lentigo maligna: clinical and histologic evaluation.

We have treated extensive lentigo maligna in two elderly patients with Imiquimod 5% (Aldara). It was applied 3 times weekly, for 3 to 5 months. Clinical and histological remission was observed over 13 months of follow-up care. Tolerance was good. We suggest that topical imiquimod could be an interesting therapeutic alternative.

[Congenital myasthenic syndromes due to mutations in the rapsyn gene]. / Syndromes myasthéniques congénitaux dus à des mutations du gène de la rapsyne.

Congenital myasthenic syndromes (CMS) are genetic diseases characterized by dysfunctional neuromuscular transmission and usually start during the neonatal period. Most are due to postsynaptic abnormalities, specifically to mutations in the acetylcholine receptor (AChR) genes. In 2002, the group of A Engel reported the first cases of CMS with mutations in the gene coding rapsyn, a postsynaptic molecule which stabilizes AChR aggregates at the neuromuscular junction. Since this first publication, more than 30 other cases, including six in France, have been reported. Study of these published cases allows us to distinguish three classes of phenotypes: 1) severe neonatal cases; 2) more benign cases, starting during infancy; 3) cases with facial malformations, involving Jewish patients originating from the Near-East. Comparison of the observations of other groups with our own has led us to the following conclusions: the N88K mutation is frequent (homozygous in 50% of cases); besides the N88K mutation, the second mutation varies considerably; heterozygous allelic cases (N88K + another mutation) are severe; there is probably a founder effect in the European population. There is phenotypic variability in the homozygous N88K cases, with benign cases and severe cases of early expression. A Engel and colleagues report that the seven cases of benign CMS with facial malformation, previously described in the Jewish population of Iraq and Iran, were caused by mutation in the promoter region of the rapsyn gene.

Zygomycosis caused by Cunninghamella bertholletiae in a kidney transplant recipient.

Infections caused by Cunninghamella bertholletiae are rare but severe. Only 32 cases have been reported as yet, but in 26 of these this species was a contributing cause of the death of the patient. This opportunistic mould in the order Mucorales infects immunocompromized patients suffering from haematological malignancies or diabetes mellitus, as well as solid organ transplant patients. The lung is the organ most often involved. Two cases of primary cutaneous infection have been previously reported subsequent to soft-tissue injuries. We report a case of primary cutaneous C. bertholletiae zygomycosis in a 54-year-old, insulin-dependent diabetic man who was treated with tacrolimus and steroids after kidney transplantation. No extracutaneous involvement was found. In this patient, the infection may have been related to insulin injections. The patient recovered after an early surgical excision of the lesion and daily administration of itraconazole for 2 months. This case emphasizes the importance of an early diagnosis of cutaneous zygomycosis, which often presents as necrotic-looking lesions. Prompt institution of antifungal therapy and rapid surgical intervention are necessary to improve the prospects of patients who have contracted these potentially severe infections.

[Lymphangioma with epithelial hyperplasia included in a Bardet-Biedl syndrome]. / Lymphangiome avec hyperplasie épithéliale associé à un syndrome de Bardet-Biedl.

INTRODUCTION: The Bardet-Biedl syndrome is a rare autosomal recessive disorder, which associates obesity, pigmentary retinopathy, hexadactyly, hypogenitalism, renal dysfunction and mental retardation. Other abnormalities can be observed in the Bardet-Biedl syndrome, but few cutaneous abnormalities have been described. CASE REPORT: A 41 year-old woman, suffering from a Bardet-Biedl syndrome diagnosed when she was 7 Years old, presented with an atypical pseudo verruca-like, dark red lesion of the interbuttock area that had developed over fifteen Years and had become a handicap. The histological examination revealed a double component: epithelial, papillomatous and acanthosic on the one hand and vascular and lymphatic on the other, suggesting a lymphangioma with epidermal hyperplasia. Magnetic resonance imaging of the sacral area revealed a median subcutaneous lesion, extending deeply to the third coccygial vertebra. DISCUSSION: Such a lymphangioma is unusual. Because it occurred during a rare polymalformative syndrome, we suggest that it may represent a new clinical sign that can be observed during the Bardet-Biedl syndrome.

[Subcutaneous mycosis due to Scopulariopsis brevicaulis in an aplasic patient]. / Mycose sous-cutanée à Scopulariopsis brevicaulis chez un malade en aplasie.

INTRODUCTION: Among the filamentous fungi of the Hyphomycete class, Annellospore group, the Scopulariopsis genera presently includes 16 species considered as opportunist pathogens. We report some unusual cutaneous manifestations due to Scopulariopsis brevicaulis in an immunodepressed patient. OBSERVATION: A 67 year-old man presented with a lymphomatous form of Waldenström's macroglobulinemia. During chemotherapy with medullar aplasia, inflammatory cutaneous nodules appeared on the forearm and leg. Microbiological and histological examinations identified Scopulariopsis brevicaulis. The patient improved with rapid remission from aplasia using hematopoietic growth factors and treatment with itraconazole. COMMENTS: In a patient in medullar aplasia, the rapid onset of an extra-ungual cutaneous localization (forearm and leg) of a Scopulariopsis brevicaulis infection, without systemic involvement, suggests that the cutaneous inoculation occurred through scratching (from the nails) or from another cutaneous origin. Prolonged neutropenia enhanced the pathogenicity of this mycosis. The mycological and histological examinations are fundamental to confirm the diagnosis.

[Papulo-erythematous eruption of neonatal lupus]. / Lupus néonatal: éruption papulo-érythémateuse diffuse.

INTRODUCTION: Neonatal lupus is rare and cutaneous lesions are usually suggestive of the diagnosis. We describe the case an infant with atypical clinical and histological aspects. CASE REPORT: A female newborn, 6 weeks of life, presented since 3 weeks a papulo-erythematous eruption involving the trunk and the 4 limbs. Cutaneous biopsy showed a dermal infiltrate of mononuclear cells, which corresponded morphologically to lymphocytes. But myelo-monocytic origin was proved by immunostaining. This result could be seen in hematodermia and macrophagic activation syndrome, but we had no clinical sign for these diagnosis. Later, she presented an erythema of the eyelids and erythematous papules of the face leading to suspicion of neonatal lupus. Questioning the mother revealed that she had Raynaud's syndrome since 1995. Antinuclear factors were positive in the patient and her mother, corresponding to antiSSA and antiSSB antibodies. She exhibited cytolytic hepatitis but no congenital heart block. Direct immunofluorescence was negative. The clinical evolution was good with complete clearing of the eruption at the age of 3 months. At 10 months, clinical and biological examinations were normal, with no arguments for haematological disease. DISCUSSION: This observation is original because of the initial papulo-erythematous eruption which is rare in neonatal lupus. Diagnosis was confirmed when specific secondary cutaneous lesions appeared. The biopsy of the first eruption showed a myelo-monocytic infiltrate which has never been described in neonatal lupus. However cutaneous biopsies are rarely performed in neonatal lupus and immunostaining is lacking in the literature.

[Muscle-localized tumorlike polyarteritis nodosa]. / Périartérite noueuse musculaire localisée pseudotumorale.

INTRODUCTION: Systemic vasculitis presenting as a tumorlike lesion are unusual and affect mainly the uro-genital system and breast. Muscle-localized tumorlike periarteritis nodosa are scarce. EXEGESIS: We report localized tumorlike polyarteritis nodosa affecting the forearm muscles in a 90-year-old woman. CONCLUSION: Other cases of polyarteritis nodosa localized to muscles are reviewed. This limited form has a benign clinical course and responds promptly to treatment with corticosteroids alone but relapses may occur.