Marguerite B. Vigliani

Recurrent Burkholderia gladioli Suppurative Lymphadenitis associated with Neutralizing Anti-IL-12p70 Autoantibodies

IntroductionBurkholderia gladioli is a rare human pathogen, and pul-monary infections occur almost exclusively in cystic fibro-sis, chronic granulomatous disease and lung transplant pa-tients [1–3]. A single case of disseminated disease wasdescribed in a woman with anti-interferon gamma (IFNγ)autoantibodies [4]. Other opportunistic infections are com-mon with defects in the IFNγ/Interleukin-12 (IL-12) path-way [5]. While high-titer neutralizing anti-IL-12 autoanti-bodies can occur with thymoma, their association with in-fections has not been clearly established [6–8]. We report acase of severe B. gladioli infection associated with autoan-tibodies to IL-12p70 in a Southeast Asian woman withrecurring B. gladioli suppurative lymphadenitis.Case ReportA 45-year-old Cambodian woman presented with 2 monthsof progressive left-sided cervical lymphadenitis and tonsil-litis. Approximately 2 years earlier she had similar findingson the right side of her neck when excisional lymph nodebiopsy revealed B. gladioli. She received 3 weeks of oralantibiotics followed by 6 weeks of meropenem for pre-sumed melioidosis. Although she reported continued painand restricted neck motion, her acute infection appeared tohave resolved.As an adolescent in Cambodia, she had worked in ricepaddies before immigrating to the United States over30 years earlier. She had not been in Cambodia since thattime. She had intractable bloody diarrhea during her preg-nancy 13 years prior with large rectal granulomata.Postpartum, she developed perirectal and pelvic abscesseswith fistulae which required multiple surgeries and6monthsof oral antibiotics before resolution. The etiologic agent wasnever identified. Her daughter is healthy without recurrentinfections.She was a thin, chronically-ill appearing woman withbilateral tender, fluctuant cervical and submandibularlymphadenopathy and tonsillar swelling. Notable labs in-cluded a normocytic anemia, leukocytosis without elevatedband forms, and negative HIV serologies. There was noevidence of a monoclonal gammopathy on serum proteinelectrophoresis with immunofixation. Her cervical lymphnodes were massively enlarged and suppurative upon exci-sion, and histopathology revealed granulocytes and histio-cytes with intracellular gram-negative bacilli (Fig. 1) anddid not suggest any lymphoproliferative disease. B. gladioliwas isolated from all excised tissues and confirmed bycomparative 16S ribosomal RNA analysis by the Centersfor Disease Control and Prevention (CDC). Complement,superoxide production, immunoglobulin levels, and T cellquantitation were normal. An intradermal tuberculin test was

First Trimester Typhoid Fever with Vertical Transmission of Salmonella Typhi, an Intracellular Organism

We report a case in which placental abruption occurred at 16 weeks following first trimester diagnosis and treatment for typhoid fever. Unexpectedly Salmonella enterica serovar Typhi (S. Typhi) was found in fetal tissues at autopsy. Using information from the murine model of typhoid fever in pregnancy, we draw parallels between S. Typhi and L. monocytogenes to develop a plausible hypothesis to explain how this organism was able to cross the placenta in the first trimester to cause abruption, inflammation, and expulsion of the fetus and placenta. We hope that this model for understanding placental infections by the hematogenous route helps to raise awareness that organisms not typically associated with TORCH infection can nevertheless cause placental infection and pregnancy loss.

INTRACELLULAR ORGANISMS AS PLACENTAL INVADERS

In this article we present a novel model for how the human placenta might get infected via the hematogenous route. We present a list of diverse placental pathogens, like Listeria monocytogenes or Cytomegalovirus, which are familiar to most obstetricians, but others, like Salmonella typhi, have only been reported in case studies or small case series. Remarkably, all of these organisms on this list are either obligate or facultative intracellular organisms. These pathogens are able to enter and survive inside host immune cells for at least a portion of their life cycle. We suggest that many blood-borne pathogens might arrive at the placenta via transportation inside of maternal leukocytes that enter the decidua in early pregnancy. We discuss mechanisms by which extravillous trophoblasts could get infected in the decidua and spread infection to other layers in the placenta. We hope to raise awareness among OB/GYN clinicians that organisms not typically associated with the TORCH list might cause placental infections and pregnancy complications.

Chorioamnionitis and Intrauterine Fetal Death after Second-Trimester Amniocentesis

We report an intrauterine fetal death that occurred less than 24 h after transabdominal amniocentesis. Chorioamnionitis was confirmed by amniotic fluid culture which showed multiple enteric organisms and postmortem examination of the fetus that showed Clostridium perfringens. The patient was treated with intravenous broad-spectrum antibiotics and uterine evacuation and her condition rapidly improved. Intra-amniotic infection after amniocentesis requires a high index of suspicion and prompt aggressive treatment with broad spectrum antibiotics and uterine evacuation to prevent maternal sepsis-related morbidity and mortality.

Luckenschadel skull: a forgotten entity.

BACKGROUND: Luckenschadel skull is an ossification disorder in which the fetal skull appears fenestrated. It is almost always associated with Chiari II malformation and meningomyelocele. CASE: We report a case of fatal subgaleal hemorrhage occurring in a full-term infant with undiagnosed Chiari II malformation, meningomyelocele, and luckenschadel skull. A cesarean delivery was performed after attempted vacuum and forceps delivery for fetal distress. CONCLUSION: Obstetricians should be aware that fetuses with antenatal diagnosis of neural tube defects could have luckenschadel skull. Questions are raised concerning the possible clinical significance of this anomaly, especially in the context of a vacuum delivery.

Multiple recurrent abscesses in a patient with undiagnosed IL-12 deficiency and infection by Burkholderia gladioli

We report the occurrence of two severe illnesses experienced by one patient over a 19 year period of time. Both illnesses were characterized by severe inflammation and tissue destruction. Signs and symptoms of the first illness were characteristic of lymphogranuloma venereum (LGV). The second illness mimicked scrofula. During the second illness the patient was discovered to have a rare immunodeficiency due to auto-antibodies to Interleukin (IL)-12 and infection by Burkholderia gladioli, a plant pathogen usually harmless in humans. We were able to retrieve biopsies from the first illness to establish that B. gladioli was already present during the original presentation. That first illness lasted 5 year s, but she survived without the correct pathogen ever being identified, and without a diagnosis of immunodeficiency. After a remission of 10 year s, she experienced her second illness. The responses to treatment before and after the correct diagnoses were established provide us with an excellent opportunity to consider and discuss how disease expression reflects complex relationships between host defenses and microbial characteristics.

A Report of Two Cases of Age-Related Changes in Cervical Morphology in Postmenopausal Women with Vaginal Adenosis

This paper presents two cases of women who had extensive vaginal adenosis from prenatal DES exposure, extending almost halfway down the vaginal canal. Both women were followed for decades with annual exams and Pap smears until after menopause. Clinical examination in both cases initially showed an absent pars vaginalis of the cervix, vaginal adenosis, and shallowness of the fornices. Several decades of annual exams showed these stigmata of DES exposure gradually disappear as the upper vagina progressively contracted. After menopause the upper vagina in both cases transformed into what appeared to be a normal cervix with all adenosis involuted into a normal endocervical canal. A timeline was created to show the morphological changes that were observed over time. This timeline illustrates how severe vaginal stenosis above the level of the squamocolumnar junction developed in middle age and was followed in the postmenopause by fusion of the upper vaginal walls in the midline resulting in the appearance of a normal, but prolapsed, cervix.

Vertical Transmission of Salmonella typhi, an Intracellular Organism.

INTRODUCTION: A recent case of typhoid fever in the first trimester of pregnancy stimulated our curiosity about organisms that can cross the placenta. Despite early diagnosis and prompt treatment with appropriate antibiotic therapy, fetal loss occurred at 16 weeks of gestation as a result of abruption, and Salmonella enterica serovar typhi (S. typhi) were found in the fetus at autopsy. METHODS: We reviewed all reported cases of typhoid fever in pregnancy and found that infection early in pregnancy carried a worse prognosis for the fetus. We studied the life cycle of S. typhi and found that it had a partially intracellular lifecycle, like other placental invaders. We found a murine model of typhoid fever in pregnancy, which bears many resemblances to our case, as a result of widespread placental necrosis and inflammation. RESULTS: Using information from the murine model and parallels between S. typhi and Listeria monocytogenes, we developed a plausible hypothesis to explain how S. typhi was able to cross the placenta. We hypothesize that bacteremia in the first trimester gave the organism the opportunity to infect maternal decidua, enabling it to enter juxtaposed extravillous trophoblasts, which have maternal immune modifications that might be permissive to intracellular organisms. CONCLUSION: The unexpected finding of S. typhi organisms in a fetus after first-trimester typhoid fever supports the concept that any organism with even a partially intracellular life cycle may potentially infect the placenta through the hematogenous route. Given sufficient invasive and evasive strategies, some intracellular organisms like S. typhi may cause significant damage.

Finding the difficult-to-visualize ventral cervix with the bruno speculum.

T ability to visualize the cervix remains a prerequisite for obtaining a satisfactory Pap smear or for investigating complaints of vaginal discharge, postcoital bleeding, postmenopausal bleeding, and irregular bleeding and sometimes for obtaining evidence after a sexual assault. Experienced clinicians, however, certainly know the feeling of frustration when they cannot visualize the cervix despite all efforts. There are a number of clinical and anatomical conditions that can make pelvic examination very challenging, leading to clinician frustration as noted by Rabbitstew [1]. This article describes some of these challenges and introduces a speculum that can help visualize the cervix in a number of difficult cases. Not uncommon is the patient with a retroverted, retroflexed uterus, wedged in the hollow of the pelvis as a result of uterine enlargement, fibroids, adhesions, endometriosis, or other abnormality that limits uterine mobility. Visualizing the cervix in this situation may be restricted because the cervix may be abutting firmly against or positioned well behind the pubic symphysis. Another difficult-to-visualize cervix is the ventrally located cervix located on the anterior vaginal wall, which gets hidden behind the anterior blade of a conventional speculum. The conventional speculum has an anterior blade that is too long for finding the cervix in these situations. Most examiners have developed their own technique of withdrawing the speculum blades partially or completely, then reinserting them to try to find the cervix. Other helpful techniques include elevating the end of the table, putting the patient in McRobert’s or Sim’s position, using a headlamp, or having the examiner kneel on the floor. There are many times when all these maneuvers and others still fail to bring the cervix into view. Louis C. Bruno, MD, who was a practicing obstetrician and gynecologist in Providence, RI, died in August 2010. Dr Bruno was a very talented surgeon, a revered teacher, an author of medical articles, and the inventor of a speculum that he left to the larger medical community. The speculum is named the ‘‘Bruno speculum’’ after its inventor. Because of its novel design, it helps overcome the problem of the ventrally located cervix. Reprint requests to: Marguerite B. Vigliani, MD, Warren Alpert School of Medicine at Brown University, 450 Veterans Memorial Pkwy, Suite 101, East Providence, RI 02914. E-mail: mbvmd@fullchannel.net The author has declared that there are no conflicts of interest.

Nonclassic 21-hydroxylase deficiency presenting as endometrial hyperplasia with uterine bleeding in a 67-year-old woman.

OBJECTIVE To report for the first time a case of postmenopausal endometrial hyperplasia caused by nonclassic 21-hydroxylase deficiency (NC21OHD). The specific combination of mutations associated with this case has never before been reported. DESIGN Case report. SETTING Private academic practice. PATIENT(S) A 67-year-old woman with uterine bleeding due to endometrial hyperplasia was found to have premenopausal gonadotropins with elevated estrogens. Endocrine workup revealed increased 17-hydroxyprogesterone (17-OHP), which led to molecular testing to establish a diagnosis of NC21OHD. INTERVENTION(S) Trial of suppression with low-dose oral dexamethasone. MAIN OUTCOME MEASURE(S) Resolution of postmenopausal bleeding. RESULT(S) Total estrogens normalized with treatment, and the endometrial stripe became normal. CONCLUSION(S) This is an unusual case of NC21OHD in which the sole presentation was persistent endometrial hyperplasia, with bleeding past the normal age for menopause. In women with unusual endometrial hyperplasias of this type, we suggest endocrine testing before proceeding to hysterectomy.