Cat scratch disease is a relatively common zoonotic bacterial disease caused primarily by Bartonella henselae. It is characterized by subacute regional lymphadenitis that is often associated with systemic symptoms such as fever and malaise.1 Approximately 10% of patients with cat scratch disease develop atypical disease, including neuroretinitis, encephalitis, Parinaud's oculoglandular syndrome, erythema nodosum, arthritis, osteomyelitis, and other manifestations.1 Although the disease has been reported in all age groups, including elderly patients and children,2,3 to the best of our knowledge, it has not been previously reported in pregnant women. Its occurrence during pregnancy is of particular concern 1) because of the prolonged, often febrile course of cat scratch disease, which may last weeks or months; 2) because of occasional reports of bacteremia in cat scratch disease; 3) because vertical transmission of Bartonella species has been reported in naturally infected bacteremic rodents4 and B henselae has been identified in an aborted equine fetus5; and 4) because B henselae DNA was found in autopsy tissue from a neonate born to a woman with confirmed B henselae infection who died 9 days after birth.6 These facts suggest that B henselae infection may be directly or indirectly harmful to the fetus and may pose a potential risk for perinatal transmission. In this series, eight women with cat scratch disease diagnosed during pregnancy are reported, including follow-up of their offspring. The objective of this study was to describe the pregnancy outcome, including long-term follow-up of the offspring, of pregnant women with cat scratch disease.
PATIENTS AND METHODS
A cat scratch disease surveillance study was started in Israel in 1991. Clinical specimens obtained from patients suspected by their primary physicians to have cat scratch disease were sent to a single laboratory. Demographic, epidemiologic, and clinical data were collected by means of a structured questionnaire sent to the referring physician, and missing information was obtained by contacting the referring physician or the patient or his or her family. For the purpose of this study, a case of cat scratch disease was defined as a patient with a history of cat exposure with regional lymphadenitis (typical cat scratch disease), one of the previously described atypical manifestations, at least one confirmatory test (or a combination): positive serology for anti-B henselae immunoglobulin (Ig) M or IgG antibodies or both by enzyme immunoassay, or polymerase chain reaction (PCR) assay detecting B henselae DNA in affected lymph node tissue or pus aspirate, all in the absence of another diagnosis. Methods for the enzyme immunoassay and PCR assay have been previously described.1
Eight pregnant women diagnosed with cat scratch disease between 2000 and 2010 were included in the current study. During that period, 1,630,709 births (1,621,097 live births) were reported in Israel (based on data from the Israeli Central Bureau of Statistics). Medical records of the pregnant women and their offspring were obtained.
Children were evaluated initially at birth. Routine follow-up of growth and development was assessed over the subsequent years by the family physician or pediatrician. Mothers and occasionally the children's pediatricians were contacted by telephone to obtain relevant information. The study was approved by the institutional review board of Tel Aviv Sourasky Medical Center.
During an 11-year period, the following eight patients were diagnosed with cat scratch disease during pregnancy:
- Case 1 was a 29-year-old woman with Gaucher disease and extensive cat and kitten exposure presenting with fever of 39°C and weakness during gestational week 8. Physical examination revealed right, tender, cervical, and preauricular lymphadenopathy. She was treated with penicillin V followed by cephalexin. Two serum specimens taken 1 and 3 weeks after disease onset demonstrated seroconversion of anti-B henselae IgM antibodies. She delivered a healthy 3,330-g boy at 40 weeks of gestation. On the last telephone follow-up, her son was a normal, healthy 5.5-year-old.
- Case 2 was a 34-year-old cat owner with right axillary and cervical lymphadenopathy of 4 weeks' duration who was evaluated during gestational week 16. She worked as a zootherapist in a psychiatric hospital where she had close contact with cats, dogs, pet rodents, chickens, rabbits, and turtles. A serum sample tested positive for anti-B henselae IgG and IgM antibodies. A serum sample taken for another reason 3 months before her conception and kept frozen at −80°C was found negative for B henselae antibodies. Amniotic fluid obtained at 17 weeks of gestation was tested negative for B henselae DNA by a PCR assay. A healthy 4,300-g boy was born by vaginal delivery at 42 weeks of gestation. Six months later, the child's health and development were normal.
- Case 3 was a 28-year-old woman who, 1 month after a cat scratch, developed left painful epitrochlear and axillary lymphadenitis. She was treated with clindamycin without improvement. Azithromycin was prescribed. Serology performed 6 weeks after disease onset was positive for anti-B henselae IgG antibodies and negative for IgM. Two weeks later she was found to be 4 weeks pregnant. Polymerase chain reaction of pus aspirated from the epitrochlear lymph node identified B henselae DNA. As a result of toxemia of pregnancy, she underwent emergency cesarean delivery at 34 weeks of gestation. A healthy 1,914-g girl was born. At last follow-up, she is a normal 7-month-old and weighs 7.2 kg.
- Case 4 was a 29-year-old woman presenting with right painful axillary lymphadenitis 1 month after having been bitten in her right arm by a kitten. Because of concerns about the possibility of malignancy as a result of an extensive history of breast cancer in the patient's family, a chest and abdominal computed tomography (CT) was done. Eight weeks after disease onset, serum anti-B henselae IgG and IgM antibodies were detected. At that time, the patient also learned that she was pregnant. As a result of exposure to CT-related high-dose radiation during early pregnancy, she elected to terminate her pregnancy. Pathologic examination of the fetus was not performed.
- Case 5 was a 25-year-old woman presenting with a large, tender, submental mass of 4 weeks' duration. At that time, she was 22 weeks pregnant. As a kindergarten teacher, she used to play with children in the sandbox, which also was frequented by stray cats. Despite several courses of oral antibiotics, the mass increased in size. Aspiration drained a large amount of thick, odorless pus. Serology revealed very high titers of anti-B henselae IgG antibodies. She delivered a healthy, well-developed, 3,000-g girl at 37 weeks of gestation. Follow-up until the age of 3.5 years was unremarkable.
- Case 6 was a 33-year-old woman who presented during gestational week 40 with blurred vision in her right eye. Ophthalmologic examination revealed right optic disc edema and stellate macular exudates (macular star), typical of cat scratch disease neuroretinitis. During gestational week 32, she had a low-grade fever with associated weakness and myalgia. She owned a 7-year-old domestic cat and often fed stray cats in her neighborhood. She tested seropositive for B henselae IgG and IgM antibodies. The patient gave birth by vaginal delivery to a healthy 3,725-g boy. Her vision as well as funduscopic findings improved subsequently. At last follow-up, her child was 1 year 10 months old with normal health and development.
- Case 7 was a 37-year-old previously healthy cat owner admitted to the hospital for evaluation of fever, generalized malaise, myalgia, arthralgia, bilateral, pretibial erythema nodosum, and enlarged, tender inguinal lymphadenitis of 2 weeks' duration. Anti-B henselae antibody assay was positive for IgG and negative for IgM. All her symptoms improved after taking oral diclofenac. At that time she was found to be 5 weeks pregnant. She gave birth to a healthy, well-developed, 3,450-g girl at 40 weeks of gestation. On a follow-up phone call at age 9.5 years, the child was reported to be healthy and well-developed.
- Case 8 was a 37-year-old previously healthy woman admitted to the hospital for evaluation of an enlarged, tender, left epitrochlear lymph node of 6 days' duration accompanied by malaise, headache, night sweats, and nausea. The patient owned a cat, fed stray cats, and was often scratched by them. An inflammatory pustule, typical of a primary inoculation lesion of cat scratch disease, was noticed 3 weeks before the onset of her symptoms. At that time, the patient learned that she was 6 weeks pregnant. An ultrasonogram revealed a live fetus. A few days later there was vaginal bleeding, and a new ultrasonogram showed a small fetus without a pulse. Evacuation of the conceptus was performed. She later developed severe myalgia, symmetrical polyarthralgia, and pretibial erythema nodosum. Serologic testing of two blood samples taken 3 weeks apart demonstrated seroconversion of anti-B henselae IgG. IgM remained negative. Polymerase chain reaction performed on pus aspirated from the epitrochlear lymph node identified B henselae DNA.
The clinical presentation, laboratory findings, and pregnancy outcome of the eight cases are shown in Table 1.
In this study, we report eight pregnant women with cat scratch disease. One patient had early spontaneous abortion; one chose to terminate pregnancy; the other six delivered apparently normal neonates. We monitored the medical history and development of these children for a median of 4.5 years (range 6 months to 9.5 years), and no pathology was identified. There was no evidence of transplacental transmission of B henselae in the one patient who first presented with cat scratch disease clinical manifestations at 12 weeks of gestation and underwent amniocentesis, which was PCR-negative for B henselae 5 weeks later. A cause-and-effect relationship between infection by B henselae at an early stage of pregnancy and the occurrence of stillbirth remains speculative in our patient with spontaneous abortion because unfortunately, histopathologic examination was not performed on the abortus or placenta.
Vertical transmission of Bartonella species was found to occur among naturally infected rodents; however, transmission occurred only among bacteremic animals.4 Other reports have also demonstrated vertical transmission of B henselae and other Bartonella species in infected equines and bacteremic mice,5,7 whereas others found that B henselae caused reproductive failure in female bacteremic cats, but transplacental transmission was not demonstrated.8 In immunocompetent humans with cat scratch disease, bacteremia is extremely rare, particularly among those with typical disease9; however, bacteremia has been reported in patients with cat scratch disease with neurologic manifestations or neuroretinitis,10,11 and B henselae DNA has been detected in the ocular fluid of a patient with neuroretinitis.12 One of our patients was diagnosed with neuroretinitis at the end of her pregnancy. Based on the known incubation period of B henselae in cat scratch disease and the natural history of cat scratch disease-associated neuroretinitis, it is reasonable to assume that she acquired cat scratch disease and possibly became bacteremic with B henselae during the third trimester. Follow-up of the child for 22 months did not reveal any organic or developmental pathology. Breitschwerdt et al found B henselae DNA in autopsy tissue from a neonate who died 9 days after birth with hypoplastic left heart syndrome. Their finding is the first and only report suggesting that vertical transmission of Bartonella species can occur in humans and be potentially teratogenic.6
In our small series, all women had a history of exposure to cats, two of whom had a history of a scratch or a bite from kittens before their clinical presentation, and seven of the eight had regional lymphadenopathy, all suggestive of cat scratch disease. Nevertheless, diagnosis was delayed for weeks in these patients. Patient 4 demonstrates what may transpire as a result of the lack of awareness of cat scratch disease. Despite the typical manifestations of large, tender lymphadenopathy appearing several weeks after a kitten bite on the ipsilateral upper extremity, malignancy rather than cat scratch disease was considered to be likely in this young patient. A chest and abdominal CT was therefore performed before an attempt to diagnose cat scratch disease or other infection. This patient later elected to terminate her pregnancy as a result of concerns regarding fetal exposure to high-dose radiation, although it is exceptionally unlikely that any single diagnostic radiologic study, including diagnostic CT, would deliver a radiation dose sufficient to justify pregnancy termination.13
Data on the efficacy of antibiotic therapy in cat scratch disease are limited, and in mild to moderate cases, antibiotics are not indicated, particularly because in immunocompetent patients, cat scratch disease, typical or atypical, usually resolves without treatment and without sequelae. Azithromycin has been shown to have a favorable effect in a small comparative study and may be considered in more severe cases of typical cat scratch disease.14 Because azithromycin is considered safe in pregnancy, we suggest adopting the same approach in pregnant women with typical cat scratch disease. Treatment of atypical cat scratch disease is more challenging and needs to be individualized in pregnancy because data regarding this topic are extremely limited or nonexistent, and doxycycline, which is included in most suggested regimens for atypical cat scratch disease, is contraindicated during pregnancy.
Although our report is seriously limited as a result of the small number of pregnant women with cat scratch disease, it is the largest description of pregnancy outcome in women with cat scratch disease. With the exception of one woman who had spontaneous abortion during the first trimester, a few weeks after the onset of cat scratch disease, we did not find evidence for immediate or long-term sequelae in the six affected mothers who delivered newborns or in their offspring.
The diagnosis of cat scratch disease should be considered by family physicians as well as by obstetrician–gynecologists whenever a pregnant woman presents with clinical manifestations consistent with cat scratch disease, especially with a history of recent cat exposure. Because the data on cat scratch disease in pregnant women and pregnancy outcome are limited, we believe that close monitoring of infected women during pregnancy is advisable. However, more data are needed to determine the optimal diagnostic and therapeutic approach as well as the role of vertical transmission of B henselae in cat scratch disease.
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