Virginie Prendki

Kikuchi-Fujimoto disease: retrospective study of 91 cases and review of the literature.

AbstractKikuchi-Fujimoto disease (KFD) is a rare cause of lymphadenopathy, most often cervical. It has been mainly described in Asia. There are few data available on this disease in Europe. We conducted this retrospective, observational, multicenter study to describe KFD in France and to determine the characteristics of severe forms of the disease and forms associated with systemic lupus erythematosus (SLE). We included 91 cases of KFD, diagnosed between January 1989 and January 2011 in 13 French hospital centers (median age, 30 ± 10.4 yr; 77% female). The ethnic origins of the patients were European (33%), Afro-Caribbean (32%), North African (15.4%), and Asian (13%). Eighteen patients had a history of systemic disease, including 11 with SLE. Lymph node involvement was cervical (90%), often in the context of polyadenopathy (52%), and it was associated with hepatomegaly and splenomegaly in 14.8% of cases. Deeper sites of involvement were noted in 18% of cases. Constitutional signs consisted mainly of fever (67%), asthenia (74.4%), and weight loss (51.2%). Other manifestations included skin rash (32.9%), arthromyalgia (34.1%), 2 cases of aseptic meningitis, and 3 cases of hemophagocytic lymphohistiocytosis. Biological signs included lymphocytopenia (63.8%) and increase of acute phase reactants (56.4%). Antinuclear antibodies (ANAs) and anti-DNA antibodies were present in 45.2% and 18% of the patients sampled, respectively. Concomitant viral infection was detected in 8 patients (8.8%). Systemic corticosteroids were prescribed in 32% of cases, hydroxychloroquine in 17.6%, and intravenous immunoglobulin in 3 patients. The disease course was always favorable. Recurrence was observed in 21% of cases. In the 33 patients with ANA at diagnosis, SLE was known in 11 patients, diagnosed concomitantly in 10 cases and in the year following diagnosis in 2 cases; 6 patients did not have SLE, and 4 patients were lost to follow-up (median follow-up, 19 mo; range, 3–39 mo). The presence of weight loss, arthralgia, skin lesions, and ANA was associated with the development of SLE (p < 0.05). Male sex and lymphopenia were associated with severe forms of KFD (p < 0.05). KFD can occur in all populations, irrespective of ethnic origin. Deep forms are common. An association with SLE should be investigated. A prospective study is required to determine the risk factors for the development of SLE.

Strongyloidiasis in man 75 years after initial exposure.

To the Editor: Strongyloidiasis, caused by the roundworm Strongyloides stercoralis, affects 100–200 million persons worldwide (1) and is endemic to Southeast Asia, sub-Saharan Africa, Latin America, and the southeastern United States (2). Endogenous autoinfection enables this nematode to develop into its host, which leads to the persistence of chronic infection several decades after a person has left a disease-endemic area (3). We encountered a case of prolonged strongyloidiasis with an infection going back >75 years. An 83-year-old man who lived in Paris and had no medical history sought treatment for fatigue and weight loss. Results of a clinical examination were normal. Laboratory investigations showed mild hyperleukocytosis (12 × 109 cells/L) with hypereosinophilia (2.4 × 109 cells/L), which was observed for >3 months. Results of stool examinations were negative for parasites. Because of the patient’s poor condition, cancer or hematologic malignancy were suspected, but results of various examinations, including a computed tomography scan of the body and bone marrow aspiration, were normal. After several weeks, the patient disclosed that he had spent a few years in Vietnam >75 years ago. The only other travel abroad reported by the patient was a 10-day stay in a tourist hotel in the Canary Islands 15 years before this illness. At this point in his assessment, results of serologic testing were positive for Strongyloides spp., and a new stool examination showed Strongyloides larvae. Serologic test results were negative for human T-cell lymphotropic virus type 1. The patient received 2 doses of 12 mg of ivermectin within 15 days and fully recovered. Hypereosinophilia and Strongyloides larvae in feces disappeared. S. stercoralis roundworms are ubiquitous intestinal parasites, endemic to tropical and subtropical regions. The larvae can develop into filariform larvae, which can penetrate the human skin and migrate through circulation to the lungs before settling in the intestine. In the human host, adult parasites may be generated by parthenogenesis in the mucosa of the small intestine. The resultant larvae can also penetrate the skin or the intestinal mucosa to establish a cycle of repeated endogenous reinfection. The parasite may then cause a long-lived autoinfection in the host, leading to chronic infection that can last for several decades (3,4). Immunocompetent persons are usually asymptomatic and periodically exhibit eosinophilia. In immunocompromised patients, the endogenous autoinfection cycle may result in the overproduction and dissemination of larvae into intestinal and extraintestinal tissues, including the central nervous system, leading to the hyperinfection syndrome which can be lethal (5). Most cases (96%) occur in immigrants, but some have been described in patients with a history of travel, sometimes many years previously. S. stercoralis infections have been reported up to 65 years after initial exposure in veterans who served in Asia during World War II (4,6). Although our patient exhibited poor general condition, he likely did not experience hyperinfection syndrome because he was not immunosuppressed, and he completely recovered after receiving standard ivermectin treatment. That the patient was originally infected in the Canary Islands seems improbable, although a low level of transmission exists in rural and disadvantaged areas in continental Spain, Portugal, and Italy (7). We did not find evidence of Strongyloides spp. transmission in the Canary Islands. In particular, the patient stayed in a high-status tourist hotel for a short period, and he never walked in bare feet. He was probably infected when he lived in Vietnam. This case highlights the importance of systematically considering chronic strongyloidiasis when seeking a diagnosis for persistent hypereosinophilia, even in patients with no underlying disease, and the value of systematically obtaining any history of travel in disease-endemic areas even if it occurred many years previously. The endogenous autoinfection cycle can possibly persist for a lifetime. In addition, systematic examination of stool samples should be carried out, and ivermectin should be given when an immunosuppressive drug is required in a patient who has a history of travel to, or residence in, an area to which strongyloidiasis is endemic.

Imported Amoebic Liver Abscess in France

Background Worldwide, amoebic liver abscess (ALA) can be found in individuals in non-endemic areas, especially in foreign-born travelers. Methods We performed a retrospective analysis of ALA in patients admitted to French hospitals between 2002 and 2006. We compared imported ALA cases in European and foreign-born patients and assessed the factors associated with abscess size using a logistic regression model. Results We investigated 90 ALA cases. Patient median age was 41. The male:female ratio was 3.5∶1. We were able to determine the origin for 75 patients: 38 were European-born and 37 foreign-born. With respect to clinical characteristics, no significant difference was observed between European and foreign-born patients except a longer lag time between the return to France after traveling abroad and the onset of symptoms for foreign-born. Factors associated with an abscess size of more than 69 mm were being male (OR = 11.25, p<0.01), aged more than 41 years old (OR = 3.63, p = 0.02) and being an immigrant (OR = 11.56, p = 0.03). Percutaneous aspiration was not based on initial abscess size but was carried out significantly more often on patients who were admitted to surgical units (OR = 10, p<0.01). The median time to abscess disappearance for 24 ALA was 7.5 months. Conclusions/Significance In this study on imported ALA was one of the largest worldwide in terms of the number of cases included males, older patients and foreign-born patients presented with larger abscesses, suggesting that hormonal and immunological factors may be involved in ALA physiopathology. The long lag time before developing ALA after returning to a non-endemic area must be highlighted to clinicians so that they will consider Entamoeba histolytica as a possible pathogen of liver abscesses more often.

Outcome of patients over 80 years of age on prolonged suppressive antibiotic therapy for at least 6 months for prosthetic joint infection

OBJECTIVES To describe elderly patients treated with prolonged suppressive antibiotic therapy for a prosthetic joint infection (PJI) in cases where the infected prosthesis could not be removed. METHODS All patients aged ≥80 years with a documented PJI and treated with prolonged suppressive antibiotic therapy for more than 6 months were included retrospectively in this study. The following events were noted: failure including persisting infection, relapse, new infection, treatment discontinuation due to severe adverse events, and related death, and also unrelated death. RESULTS Thirty-eight patients with a median age of 84 years (80-95 years) were included; there were 24 hip infections, 13 knee infections, and one shoulder infection. The main causative organisms were Staphylococcus aureus (39%) and Streptococcus agalactiae (16%). The most commonly prescribed antibiotics as prolonged suppressive therapy were penicillins. The median follow-up duration was 24 months; 60% of the patients were event-free at 24 months and were still on prolonged suppressive antibiotic therapy. Fifteen events (six failures and nine unrelated deaths) were observed. Hypoalbuminaemia, the presence of a sinus tract, and a staphylococcal PJI were associated with an increased risk of an event. CONCLUSIONS Prolonged suppressive antibiotic therapy is an alternative therapy in elderly patients with PJI when surgery is contraindicated and when the bacteria are susceptible to well-tolerated oral antimicrobial therapy such as beta-lactams.

Prevalence and Clinical Significance of Kupffer Cell Hyperplasia With Hemophagocytosis in Liver Biopsies

Hemophagocytic syndrome (HS) is a rare life-threatening condition due to uncontrolled macrophagic activation. Liver involvement is constant in HS, characterized by Küpffer cell hyperplasia with hemophagocytosis. Conversely, the specificity, frequency, and clinical significance of this histologic lesion remain poorly investigated. We aimed to evaluate the prevalence of this elementary lesion in liver biopsies (LB) to attempt to identify its clinical significance and to investigate its potential association with perforin expression deficiency. Küpffer cell hyperplasia with hemophagocytosis has been systematically searched for in consecutive LBs in a 6-year period. In positive cases, clinical, biological, and outcome characteristics have been retrospectively recorded. The ratio of perforin to CD3+ lymphocytes was assessed on immunostained LB sections. This histologic lesion was detected in LB of 69 of 5194 patients (1.3%). It was not associated with hepatotropic viral infection, alcohol-related chronic liver disease, or autoimmune chronic liver disease. Although only 36% of patients with this histologic lesion had a complete HS (association of fever, splenomegaly, bicytopenia, hypertriglyceridemia, hyperferritinemia, and/or hypofibrinogenemia), almost all patients had similar underlying diseases (human immunodeficiency virus infection, malignant hemopathy, and autoimmune disease) and/or acute ongoing infections (tuberculosis, cytomegalovirus, and Epstein-Barr virus). A decrease of the perforin to CD3+ lymphocytes ratio was specifically associated with this lesion. Küpffer cell hyperplasia with hemophagocytosis in LB is a rare finding; although it does not necessarily denote a complete HS, it is associated with the same underlying disease and/or infection, with a decrease in intrahepatic perforin-positive lymphocytes.

Visualization of amyloid arthropathy in light-chain systemic amyloidosis on F-18 FDG PET/CT scan.

We report a case of 63-year-old man with symmetrical joint swelling of the interphalangeal and metacarpal joints, associated with isolated hypogammaglobulinemia. Accessory glands biopsy revealed the presence of amyloidal deposits. PET/CT showed increased F-18 FDG activity in thickened soft tissues corresponding to amyloid arthropathy. Like multiple myeloma, PET/CT could be an interesting imaging in light-chain amyloidosis.

Vincristine efficacy and safety in treating immune thrombocytopenia: a retrospective study of 35 patients.

Although vincristine (VCR) is sometimes prescribed for newly diagnosed immune thrombocytopenia (ITP), its efficacy in refractory ITP and sustained efficacy has yet to be demonstrated. We describe our clinical experience and recommend vincristines correct place in ITP management. This retrospective study analysed data from 35 patients with newly diagnosed (ND), persistent (P) or chronic (C) ITP treated with VCR. The initial response rate, defined as >30 × 109 platelets/L, reached 86% after a median of 7 [interquartile range (IQR) 6–13] days. In ND and P ITP, even when previous therapies were inefficient, initial response was 87.5%, suggesting that this treatment could be used particularly in rescue. Median survival time, without failure or relapse, was 15 months (Kaplan–Meier curve). Predictive factors (univariate analysis) of an initial and long‐term response were a small number of prior treatments received. However, at 2 yr, only seven patients had sustained response. Eight (23%) patients experienced adverse events: neuropathy for seven and bowel obstruction for one. Vincristine efficacy in ITP was confirmed, and it could be a good strategy for treating resistant ITP, especially in emergencies. In this era of new therapeutics, VCR deserves to remain on the list of ITP treatments because of its initial efficacy, safety and low cost.

Campylobacter infection after prosthetic joint surgery

Abstract Few cases of Campylobacter prosthetic joint infection (PJI) have been reported so far. We describe the demographic characteristics, underlying conditions, clinical features, treatment, and outcome of 8 patients with Campylobacter PJI in our hospital. All strains were confirmed at the French National Reference Center for Campylobacter and Helicobacter. Seven patients were infected with C. fetus and 1 with C. jejuni. Most patients were elderly and immunocompromised. Four had bacteremia, one of these with a pacemaker endocarditis. All the patients received at least 3 months of antibiotic treatment and 6 were treated surgically. The outcome was favorable at 2 years of follow-up in all except for 1 patient. Campylobacter PJI cases are rare but likely to become more frequent. C. fetus bacteremia should motivate physicians to look for a secondary localization such as a Campylobacter PJI.

Q fever and Mediterranean spotted fever associated with hemophagocytic syndrome: case study and literature review

BACKGROUND Hemophagocytosis during Q fever (QF) and Mediterranean spotted fever (MSF) is rare and only a few cases have been reported. We aimed to investigate the characteristics, outcome, and treatment of QF/MSF-associated hemophagocytosis. METHODS We retrospectively reviewed all patients with a diagnosis of QF or MSF and suspected hemophagocytic syndrome (HS), according to Henters criteria, between 2002 and 2011, and compared the latter to patients without HS or with lymphoma-associated HS. RESULTS Seventeen patients with HS (median age 42 years, range 5-68 years; five females (29%)) with QF (n=8) and MSF (n=9) were included in this study. When comparing patients with QF- and MSF-associated HS with patients without HS (n=11), HS-associated signs (splenomegaly, ferritinemia, hypertriglyceridemia, and cytopenia) were significantly more frequent in patients with histological HS (p<0.05), along with a greater number of Henters criteria. Despite the presence of HS-associated signs, treatment was similar in these two subgroups, including the time to recovery and the outcome. When compared to lymphoma-associated HS (n=10), the outcome in QF/MSF-associated HS was significantly different, with mortality in 70% of lymphoma patients versus none in QF- and MSF-associated HS (p<0.05). CONCLUSION Hemophagocytosis is a rare occurrence during the course of QF and MSF. The presence of profound cytopenia is quite unusual in QF and MSF and should bring to mind the presence of associated HS. Nevertheless, hemophagocytic syndrome is associated with a good outcome in this condition.

Chronic Malaria Revealed by a New Fluorescence Pattern on the Antinuclear Autoantibodies Test

Background Several clinical forms of malaria such as chronic carriage, gestational malaria or hyper-reactive malarial splenomegaly may follow a cryptic evolution with afebrile chronic fatigue sometimes accompanied by anemia and/or splenomegaly. Conventional parasitological tests are often negative or not performed, and severe complications may occur. Extensive explorations of these conditions often include the search for antinuclear autoantibodies (ANA). Methods We analysed fluorescence patterns in the ANA test in patients with either chronic cryptic or acute symptomatic malaria, then conducted a one-year prospective study at a single hospital on all available sera drawn for ANA detections. We then identified autoantibodies differentially expressed in malaria patients and in controls using human protein microarray. Results We uncovered and defined a new, malaria-related, nucleo-cytoplasmic ANA pattern displaying the specific association of a nuclear speckled pattern with diffuse cytoplasmic perinuclearly-enhanced fluorescence. In the one-year prospective analysis, 79% of sera displaying this new nucleo-cytoplasmic fluorescence were from patients with malaria. This specific pattern, not seen in other parasitic diseases, allowed a timely reorientation of the diagnosis toward malaria. To assess if the autoantibody immune response was due to autoreactivity or molecular mimicry we isolated 42 autoantigens, targets of malarial autoantibodies. BLAST analysis indicated that 23 of recognized autoantigens were homologous to plasmodial proteins suggesting autoimmune responses directly driven by the plasmodial infection. Conclusion In patients with malaria in whom parasitological tests have not been performed recognition of this new, malaria-related fluorescence pattern on the ANA test is highly suggestive of the diagnosis and triggers immediate, easy confirmation and adapted therapy.