Cléa Melenotte

Query rectal bleeding

Unite de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, Faculte de Medecine, Universite de la Mediterranee, Marseille, France (M Million MD, Elisabeth Botelho-Nevers MD, Prof P Brouqui MD, Prof D Raoult MD); Service de Chirurgie Vasculaire, (O Hartung MD, M Claudel MD), Service d’Imagerie Medicale, (F Craighero MD), and Service des Maladies Infectieuses et Tropicales, Hopital Nord, Marseille, France (C Melenotte MD, M Million MD, Elisabeth Botelho-Nevers MD, Prof P Brouqui MD)

Severe measles, vitamin A deficiency, and the Roma community in Europe.

To the Editor: The Roma community in Europe is a subgroup of the Romani people, whose origins are in northern India and who have been known in English-speaking countries as “gypsies.” Measles outbreaks, including severe cases, were reported in the European Roma community during 2008-2010 (1,2). We describe the potential roles of malnutrition and vitamin A deficiency as risk factors for severe measles in adults from this community. In Europe, >25,000 cases of measles, more than half of which occurred in France, were reported during a 2011 outbreak (3). The exact proportion of measles cases occurring among the Roma community in France during the outbreak are not available (2). Measles epidemiology has changed; the disease now mainly affects children <1 year old and young adults, the latter of whom are mostly unvaccinated or have unknown vaccination status (2,4). Roma people in Europe experience some of the worst health conditions in the industrialized world: they live in overcrowded conditions and have limited access to prevention programs and to healthcare services (2,5). In such populations, deficiencies of vitamins, such as A, C, and E, have been reported (6). Vitamin A deficiency has been associated with severe cases of measles in children in developing countries (7,8). To date, we did not find published data associating vitamin A deficiency with severe measles among adults. We describe 6 adults from the Roma community in Marseille, France, who had measles and low levels of vitamin A; 2 of these persons had severe measles. Case-patients 1 and 2 were men who were 21 and 25 years of age, respectively. They were admitted to North Hospital, Marseille, France, with typical signs of measles (fever, cough, and maculopapular rash). They had no medical history of serious illness, including no immunocompromising conditions, and no history of measles vaccination. For both patients, the diagnosis of measles was confirmed by the results of PCR performed on pharyngeal and urinary samples. In case-patient 1, acute meningoencephalitis developed, and he was transferred to the intensive care unit for 3 days. During his stay, the patient was found to have active viral hepatitis B. Case-patient 2 had the following signs and symptoms: abdominal pain and vomiting, severe hepatitis (serum transaminases level 10× higher than the upper reference limit; total bilirubin within reference range), and keratitis. Other causes of viral or bacterial hepatitis were ruled out by serologic testing, and the patient did not frequently drink alcohol. Case-patients 1 and 2 had vitamin A deficiency with values of 0.31 mg/L and 0.2 mg/L, respectively, (reference range 0.5–0.8 mg/L). We measured vitamin A levels in blood samples from the next 4 consecutive hospitalized patients with measles, all of whom were from the Roma community. They did not have complications of measles, but were hospitalized for infection-control reasons. All 4 patients had low levels of vitamin A (0.16–0.34 mg/L) (Table). In case-patient 4, the blood level of retinol-binding protein was 0.026 g/L (normal range 0.02–0.05 g/L), confirming vitamin A deficiency. Vitamin A supplementation was administered intramuscularly as recommended by the World Health Organization (200,000 IU followed by a second dose the next day) to each patient (8). The 6 patients progressed to recovery. Low levels of vitamin A (0.36–0.46 mg/L) were also found for 2 other patients from the Roma community who did not have measles (Table). Table Characteristics of 6 measles case-patients and 2 control patients with vitamin A deficiency, Roma community, France* Serum vitamin A concentrations do not always reflect total vitamin A stores (9). In severe protein–calorie malnutrition, and during intercurrent infection, serum retinol levels could be artificially low in relation to a decrease in retinol-binding protein level (9). However, the diagnosis of vitamin A deficiency is usually supported by low levels of serum vitamin A and levels of retinol-binding protein within the reference range as described for at least 1 of the case-patients reported here. Vitamin A deficiency affects the severity of illness and the rate of deaths associated with measles, and it is known to induce severe measles-related complications in children, delaying recovery and promoting xerophthalmia, corneal ulcer, and blindness (7,8,10). Acute measles precipitates vitamin A deficiency by depleting vitamin A stores and increasing its utilization, leading to more severe ocular injury (7,8). Vitamin A supplementation given to children with measles has been associated with better outcomes (7,8). Although it is too early to associate vitamin A deficiency with severe measles in adult patients, such an association is possible. Adults with low levels of vitamin A but not infected with measles could be at higher risk for more severe disease if they become infected with the virus. We conclude that all adults who have measles should be assessed for vitamin A and retinol-binding protein levels and should be considered for vitamin A supplementation, as are children (8). A prospective case-control study assessing vitamin A deficiency in the Roma adult community is necessary to assess its consequences on measles outcome. Aside from preventing complications among the Roma people, improving vaccine coverage in this nomadic population is crucial for reducing measles virus circulation among the general population.

Clinical features of actinomycosis: A retrospective, multicenter study of 28 cases of miscellaneous presentations.

AbstractActinomycosis is a rare heterogeneous anaerobic infection with misleading clinical presentations that delay diagnosis. A significant number of misdiagnosed cases have been reported in specific localizations, but studies including various forms of actinomycosis have rarely been published.We performed a multicenter retrospective chart review of laboratory-confirmed actinomycosis cases from January 2000 until January 2014. We described clinical characteristics, diagnostic procedures, differential diagnosis, and management of actinomycosis of clinical significance.Twenty-eight patients were included from 6 hospitals in France. Disease was diagnosed predominately in the abdomen/pelvis (n = 9), orocervicofacial (n = 5), cardiothoracic (n = 5), skeletal (n = 3), hematogenous (n = 3), soft tissue (n = 2), and intracranially (n = 1). Four patients (14%) were immunocompromised. In most cases (92 %), the diagnosis of actinomycosis was not suspected on admission, as clinical features were not specific. Diagnosis was obtained from either microbiology (50%, n = 14) or histopathology (42%, n = 12), or from both methods (7%, n = 2). Surgical biopsy was needed for definite diagnosis in 71% of cases (n = 20). Coinfection was found in 13 patients (46%), among which 3 patients were diagnosed from histologic criteria only. Two-thirds of patients were treated with amoxicillin. Median duration of antibiotics was 120 days (interquartile range 60–180), whereas the median follow-up time was 12 months (interquartile range 5.25–18). Two patients died.This study highlights the distinct and miscellaneous patterns of actinomycosis to prompt accurate diagnosis and earlier treatments, thus improving the outcome. Surgical biopsy should be performed when possible while raising histologists and microbiologists awareness of possible actinomycosis to enhance the chance of diagnosis and use specific molecular methods.

Measles encephalitis the return: mild encephalitis with reversible splenial lesion

A 20-year-old man, without a past medical history, was admitted for febrile coma (Glasgow coma scale score 9, temperature 39 8C). A maculopapular rash was observed on the face, trunk, arms, and proximal portion of the legs. A cerebral computed tomography (CT) scan was normal. Lumbar puncture showed 16 10 leukocytes/l, 20 10 erythrocytes/l, a cerebrospinal fluid (CSF) protein level of 0.7 g/l, and CSF glucose of 4 mmol/l (glycemia: 5.1 mmol/l). A measles-specific PCR was positive on salivary, urinary, and nasal samples. Specific PCR and culture of the CSF were all negative, including for measles. Diffusion-weighted magnetic resonance imaging (MRI) showed hyperintensity of the splenium of the corpus callosum (Figure 1). Complete recovery was observed after 1 week, and the control imaging by diffusion-weighted MRI was normal (Figure 2). Mild encephalitis with reversible splenial lesion (MERS) is an aspecific cerebral lesion visible on MRI. The most common causes are infectious agents, drugs, and hydroelectric disorders.

18F-FDG PET/CT as a central tool in the shift from chronic Q fever to Coxiella burnetii persistent focalized infection: A consecutive case series.

AbstractBecause Q fever is mostly diagnosed serologically, localizing a persistent focus of Coxiella burnetii infection can be challenging. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) could be an interesting tool in this context.We performed a retrospective study on patients diagnosed with C burnetii infection, who had undergone 18F-FDG PET/CT between 2009 and 2015. When positive 18F-FDG PET/CT results were obtained, we tried to determine if it changed the previous diagnosis by discovering or confirming a suspected focus of C burnetii infection.One hundred sixty-seven patients benefited from 18F-FDG PET/CT. The most frequent clinical subgroup before 18F-FDG PET/CT was patients with no identified focus of infection, despite high IgG1 serological titers (34%). For 59% (n = 99) of patients, a hypermetabolic focus was identified. For 62 patients (62.6%), the positive 18F-FDG PET/CT allowed the diagnosis to be changed. For 24 of them, (38.7%), a previously unsuspected focus of infection was discovered. Forty-two (42%) positive patients had more than 1 hypermetabolic focus. We observed 21 valvular foci, 34 vascular foci, and a high proportion of osteoarticular localizations (n = 21). We also observed lymphadenitis (n = 27), bone marrow hypermetabolism (n = 11), and 9 pulmonary localizations.We confirmed that18F-FDG PET/CT is a central tool in the diagnosis of C burnetii focalized persistent infection. We proposed new diagnostic scores for 2 main clinical entities identified using 18F-FDG PET/CT: osteoarticular persistent infections and lymphadenitis.

Atypical measles syndrome in adults: still around.

Measles, a vaccine-preventable disease, is currently responsible for worldwide outbreaks mainly due to the failure to maintain high coverage of childhood immunisation. Atypical measles syndrome was first described in the 1960s in association with the inactivated measles vaccine. We report a case of atypical measles syndrome in a 29-year-old man without previous measles immunisation. He presented with fever, shortness of breath and a purpuric rash. Radiological investigations allowed the diagnosis of severe nodular pneumonia. Positive PCR in nasal and pharyngeal samples, and positive serology for a primary infection confirmed measles diagnosis. Both clinical symptoms and pulmonary nodules regressed spontaneously, whereas mediastinal lymph nodes increased and persisted up to 3 months after the primary infection. Physicians should be aware of the atypical measles syndrome presentation in order to limit the delay of diagnosis, to avoid unnecessary investigations and to prevent the potential spread of this infectious disease.

Sitosterolemia: A new mutation in a Mediterranean patient

Sitosterolemia is a rare autosomal recessive disorder characterised by a high plasma level of sterols. A homozygous mutation or the compound heterozygous mutation in the ABCG5 gene or the ABCG8 gene leads to a complete loss of function of the ATP-binding cassette (ABC) heterodimer transporter G5-G8, which is localised to the apical membrane of enterocytes and hepatocytes. In enterocytes, this complex rejects plant sterols, whereas it promotes their excretion into the bile in the liver. The loss of function of the transporter ABCG5-G8 leads to a high concentration of plasma plant sterols and to its accumulation in tissues. We report here a new mutation of sitosterolemia in a 59-year-old woman with xanthelasma, precocious atherosclerosis, haemolytic anemia and macrothrombocytopenia. She was treated before the availability of Ezetimibe wich is now the gold standard treatment of this disease.

Rosai-Dorfman disease initially misdiagnosed as sarcoidosis.

Cherry consumption and decreased risk of recurrent gout attacks. Arthritis Rheum 2012;64:4004–11. 2. Gelber AC, Solomon DH. If life serves up a bowl of cherries, and gout attacks are “the pits”: implications for therapy [editorial]. Arthritis Rheum 2012;64:3827–30. 3. Schlesinger N, Ron Y, Chen CC. Do cherries reduce acute gouty attacks in patients with gouty arthritis? [abstract] Ann Rheum Dis 2007;67 Suppl 3:iii0742. 4. Schlesinger N. Prophylaxis with cherries should be considered in the treatment of gout [abstract]. Ann Rheum Dis 2010;69 Suppl 3:iii380. 5. Schlesinger N, Rabinowitz R, Schlesinger M. Effect of cherry juice concentrate on the secretion of interleukins by human monocytes exposed to monosodium urate crystals in vitro [abstract]. Ann Rheum Dis 2010;69 Suppl 3:iii379. 6. Schlesinger N, Rabinowitz R, Schlesinger M. Pilot studies of cherry juice concentrate for gout flare prophylaxis. J Arthritis 2012; 1:1–5. 7. Di Giovine FS, Malawista SE, Nuki G, Duff GW. Interleukin 1 (IL 1) as a mediator of crystal arthritis: stimulation of T cell and synovial fibroblast mitogenesis by urate crystal-induced IL 1. J Immunol 1987;138:3213–8.

Coxiella burnetii: A Hidden Pathogen in Interstitial Lung Disease?

We report 7 patients with interstitial lung disease seen at computed tomographic scan review. Coxiella burnetii infection was diagnosed in situ in 1 lung biopsy specimen. Q fever may be a cofactor of interstitial lung disease, especially in endemic areas.

Pro-apoptotic effect of doxycycline and hydroxychloroquine on B-cell lymphoma induced by C. burnetii

The combination of doxycycline with hydroxychloroquine is the cornerstone of treatment for persistent Coxiella burnetii infection, and we have used this combination for years in the National Reference Center for Q fever. While C. burnetii blocks apoptosis of the host cells in order to survive and proliferate, doxycycline on the other hand has a pro-apoptotic effect [1, 2]. We recently described the history of a patient with a C. burnetii vascular infection who 18 months later developed B-cell non-Hodgkin lymphoma [3]. At the date of the Q fever diagnosis, doxycycline 200 mg once per day in combination with hydroxychloroquine 200 mg three times per day was introduced. Analyzing antibiotic blood levels, we noted that plasma doxycycline levels were not detectable during the first year of the infection, while plasma hydroxychloroquine levels were within expected therapeutic values (Figure 1). Eighteen months after the diagnosis of C. burnetii vascular infection, follicular lymphoma was diagnosed on a retroperitoneal biopsy (Figure 1). Rituximab chemotherapy was instituted for two years, doxycycline was reintroduced and hydroxychloroquine was stopped. When rituximab was stopped, 4 years after the diagnosis of Q fever, the patient was in remission, and doxycycline was prolonged for a 7-month period (Figure 1). The patient was considered cured of the C. burnetii infection (phase I C. burnetii antibodies were 100, versus 800 at the time of the Q fever diagnosis), but the lymphoma recurred one year after doxycycline was stopped. Lymphoma developed while doxycycline was not effective and relapse was observed while doxycycline was stopped (Figure 1). This observation emphasizes the benefits of doxycycline as a pro-apoptotic medication. To survive within host cells, C. burnetii utilizes an anti-apoptotic strategy. It establishes a replicative niche in a lysozyme-like parasitophorous acid vacuole that is permissive for bacterial replication [1]. At the same time, C. burnetii inhibits host cell apoptosis by reducing the levels of caspase-3. C. burnetii-infected cells have been associated with a decrease in pro-apoptotic bcl-2 family proteins such as Bax and Bak and a dramatically increased synthesis of the anti-apoptotic bcl-2 family protein A1/ bfl1, which promotes mitochondrial outer membrane integrity [4]. Therefore, mitochondrial fission is inhibited, and levels of caspase-3, otherwise called “executioner” caspase, are reduced and apoptosis is thus inhibited [4]. On the other hand, doxycycline presents proapoptotic properties in addition to its antibacterial activity. In fact, doxycycline inhibits cell growth and promotes apoptosis in tumor cells by activating caspase-3 and caspase-9. Doxycycline is able to enhance the therapeutic activity of anticancer therapy, reduce its side effects, and prevent tumor formation [2, 5]. The anti-tumoral effect of doxycycline has been demonstrated in breast, ovarian, prostate, lung, pancreatic and colon cancer cells, and in melanoma, oral squamous cell carcinoma and in twothirds of MALT lymphoma associated with Chlamydia psittaci [5]. Pulvino et al. have recently reported that doxycycline inhibits the growth of B-cell lymphoma in vitro and in vivo (in mice) for diffuse large B-cell lymphoma (DLBCL) and in vitro for several other types of non-Hodgkin lymphoma (NHL)(2). Doxycycline accumulates in DLBCL cells in high concentrations and affects crucial signaling pathways for lymphomagenesis; NF-kB, STAT3, ERK and the COP-9 signalosome CSN5, which are essential for DLBCL cell survival [2, 5] . Hydroxychloroquine potentiates the bactericidal activity of doxycycline by alkalinizing the vacuolar pH [4]. This antimalarial drug is found to be effective against bacterial and viral infections, but also has activity as an anti-inflammatory drug currently used in rheumatoid Letter to the Editor