infectious disease
An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
that most often results from a scratch or bite of a
cat
The cat (''Felis catus'') is a domestic species of small carnivorous mammal. It is the only domesticated species in the family Felidae and is commonly referred to as the domestic cat or house cat to distinguish it from the wild members of ...
. Symptoms typically include a non-painful bump or blister at the site of injury and painful and swollen
lymph nodes
A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that includ ...
. People may feel tired, have a headache, or a
fever
Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...
. Symptoms typically begin within 3–14 days following infection.
Cat-scratch disease is caused by the
bacterium
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
''
Bartonella henselae
''Bartonella henselae'', formerly ''Rochalimæa henselae'', is a bacterium that is the causative agent of cat-scratch disease ( bartonellosis).
''Bartonella henselae'' is a member of the genus ''Bartonella'', one of the most common types of bacte ...
'' which is believed to be spread by the cat's saliva. Young cats pose a greater risk than older cats. Occasionally dog scratches or bites may be involved. Diagnosis is generally based on symptoms. Confirmation is possible by blood tests.
The primary treatment is supportive.
Antibiotics
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention o ...
speed healing and are recommended in those with severe disease or immune problems. Recovery typically occurs within 4 months but can require a year. About 1 in 10,000 people are affected. It is more common in children.
Signs and symptoms
Cat-scratch disease commonly presents as tender, swollen lymph nodes near the site of the inoculating bite or scratch or on the neck, and is usually limited to one side. This condition is referred to as regional
lymphadenopathy
Lymphadenopathy or adenopathy is a disease of the lymph nodes, in which they are abnormal in size or consistency. Lymphadenopathy of an inflammatory type (the most common type) is lymphadenitis, producing swollen or enlarged lymph nodes. In cli ...
and occurs 1–3 weeks after inoculation. Lymphadenopathy most commonly occurs in the
axilla
The axilla (also, armpit, underarm or oxter) is the area on the human body directly under the shoulder joint. It includes the axillary space, an anatomical space within the shoulder girdle between the arm and the thoracic cage, bounded superior ...
, arms, neck, or jaw, but may also occur near the groin or around the ear. A
vesicle
Vesicle may refer to:
; In cellular biology or chemistry
* Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane
* Synaptic vesicle
; In human embryology
* Vesicle (embryology), bulge-like features o ...
or an
erythema
Erythema (from the Greek , meaning red) is redness of the skin or mucous membranes, caused by hyperemia (increased blood flow) in superficial capillaries. It occurs with any skin injury, infection, or inflammation. Examples of erythema not assoc ...
tous
papule
A papule is a small, well-defined bump in the skin. It may have a rounded, pointed or flat top, and may have a dip. It can appear with a stalk, be thread-like or look warty. It can be soft or firm and its surface may be rough or smooth. Some h ...
may form at the site of initial infection.
Most people also develop systemic symptoms such as
malaise
As a medical term, malaise is a feeling of general discomfort, uneasiness or lack of wellbeing and often the first sign of an infection or other disease. The word has existed in French since at least the 12th century.
The term is often used ...
,
decreased appetite
Anorexia is a medical term for a loss of appetite. While the term in non-scientific publications is often used interchangeably with anorexia nervosa, many possible causes exist for a loss of appetite, some of which may be harmless, while others ...
, and aches. Other associated complaints include
headache
Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches.
Headaches can occur as a result ...
,
chills
Chills is a feeling of coldness occurring during a high fever, but sometimes is also a common symptom which occurs alone in specific people. It occurs during fever due to the release of cytokines and prostaglandins as part of the inflammatory r ...
arthritis
Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In som ...
,
backache
Back pain is pain felt in the back. It may be classified as neck pain (cervical), middle back pain (thoracic), lower back pain (lumbar) or coccydynia (tailbone or sacral pain) based on the segment affected. The lumbar area is the most common ...
, and abdominal pain. It may take 7 to 14 days, or as long as two months, for symptoms to appear. Most cases are
benign
Malignancy () is the tendency of a medical condition to become progressively worse.
Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous benign tumor, ''benign'' tumor in that a malign ...
and self-limiting, but
lymphadenopathy
Lymphadenopathy or adenopathy is a disease of the lymph nodes, in which they are abnormal in size or consistency. Lymphadenopathy of an inflammatory type (the most common type) is lymphadenitis, producing swollen or enlarged lymph nodes. In cli ...
may persist for several months after other symptoms disappear. The disease usually resolves spontaneously, with or without treatment, in one month.
In rare situations, CSD can lead to the development of serious neurologic or cardiac sequelae such as
meningoencephalitis
Meningoencephalitis (; from ; ; and the medical suffix ''-itis'', "inflammation"), also known as herpes meningoencephalitis, is a medical condition that simultaneously resembles both meningitis, which is an infection or inflammation of the menin ...
,
encephalopathy
Encephalopathy (; from grc, ἐνκέφαλος "brain" + πάθος "suffering") means any disorder or disease of the brain, especially chronic degenerative conditions. In modern usage, encephalopathy does not refer to a single disease, but r ...
,
seizure
An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...
s, or
endocarditis
Endocarditis is an inflammation of the inner layer of the heart, the endocardium. It usually involves the heart valves. Other structures that may be involved include the interventricular septum, the chordae tendineae, the mural endocardium, or the ...
. Endocarditis associated with ''Bartonella'' infection has a particularly high mortality.
Parinaud's oculoglandular syndrome
Parinaud's oculoglandular syndrome (POS) is a medical condition characterized by a specific set of symptoms affecting the eye and nearby lymph nodes. Named after the French ophthalmologist Henri Parinaud, it should not be confused with the neurolo ...
is the most common ocular manifestation of CSD, and is a granulomatous
conjunctivitis
Conjunctivitis, also known as pink eye, is inflammation of the conjunctiva, outermost layer of the white part of the eye and the inner surface of the eyelid. It makes the eye appear pink or reddish. Pain, burning, scratchiness, or itchiness may ...
with concurrent swelling of the lymph node near the ear.
Optic neuritis
Optic neuritis describes any condition that causes inflammation of the optic nerve; it may be associated with demyelinating diseases, or infectious or inflammatory processes.
It is also known as optic papillitis (when the head of the optic nerv ...
or neuroretinitis is one of the atypical presentations.
People who are
immunocompromised
Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...
are susceptible to other conditions associated with ''B. henselae'' and ''B. quintana'', such as
bacillary angiomatosis
Bacillary angiomatosis (BA) is a form of angiomatosis associated with bacteria of the genus '' Bartonella''.
Symptoms
Cutaneous BA is characterised by the presence of lesions on or under the skin. Appearing in numbers from one to hundreds, these l ...
or
bacillary peliosis
Bacillary peliosis is a form of peliosis hepatis that has been associated with bacteria in the genus ''Bartonella
''Bartonella'' is a genus of Gram-negative bacteria. It is the only genus in the family Bartonellaceae. Facultative intracellular ...
. Bacillary angiomatosis is primarily a vascular skin lesion that may extend to bone or be present in other areas of the body. In the typical scenario, the patient has
HIV
The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...
Bacillary peliosis
Bacillary peliosis is a form of peliosis hepatis that has been associated with bacteria in the genus ''Bartonella
''Bartonella'' is a genus of Gram-negative bacteria. It is the only genus in the family Bartonellaceae. Facultative intracellular ...
is caused by ''B. henselae'' that most often affects people with HIV and other conditions causing severe immune compromise. The
liver
The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
and
spleen
The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .
are primarily affected, with findings of blood-filled cystic spaces on pathology.
Cause
''Bartonella henselae'' is a
fastidious
A fastidious organism is any organism that has complex or particular nutritional requirements. In other words, a fastidious organism will only grow when specific nutrients are included in its medium. The more restrictive term fastidious microorgan ...
, intracellular,
Gram-negative bacterium
Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall ...
.
Transmission
The cat was recognized as the
natural reservoir
In infectious disease ecology and epidemiology, a natural reservoir, also known as a disease reservoir or a reservoir of infection, is the population of organisms or the specific environment in which an infectious pathogen naturally lives and rep ...
of the disease in 1950 by Robert Debré.
Kitten
A kitten is a juvenile cat. After being born, kittens display primary altriciality and are totally dependent on their mothers for survival. They normally do not open their eyes for seven to ten days. After about two weeks, kittens develop qu ...
s are more likely to carry the
bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
in their
blood
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...
, so may be more likely to transmit the disease than adult cats. However, fleas serve as a vector for transmission of ''B. henselae'' among cats, and viable ''B. henselae'' are excreted in the feces of ''
Ctenocephalides felis
The cat flea (scientific name ''Ctenocephalides felis'') is an extremely common parasitic insect whose principal host is the domestic cat, although a high proportion of the fleas found on dogs also belong to this species. This is despite the wide ...
'', the cat flea. Cats could be infected with ''B. henselae'' through intradermal inoculation using flea feces containing ''B. henselae''.
As a consequence, a likely means of transmission of ''B. henselae'' from cats to humans may be inoculation with flea feces containing ''B. henselae'' through a contaminated cat scratch wound or by cat saliva transmitted in a bite.
Tick
Ticks (order Ixodida) are parasitic arachnids that are part of the mite superorder Parasitiformes. Adult ticks are approximately 3 to 5 mm in length depending on age, sex, species, and "fullness". Ticks are external parasites, living by ...
s can also act as vectors and occasionally transmit the bacteria to humans. Combined clinical and PCR-based research has shown that other organisms can transmit Bartonella, including spiders. Cryptic ''Bartonella'' infection may be a much larger problem than previously thought, constituting an unrecognized occupational health hazard of veterinarians.
Diagnosis
The best diagnostic method available is
polymerase chain reaction
The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) t ...
, which has a sensitivity of 43-76% and a specificity (in one study) of 100%. The
Warthin–Starry stain
The Warthin–Starry stain (WS) is a silver nitrate-based staining method (a silver stain) used in histology. It was first introduced in 1920 by American pathologists Aldred Scott Warthin (1866-1931) and Allen Chronister Starry (1890-1973), for th ...
can be helpful to show the presence of ''B. henselae'', but is often difficult to interpret. ''B. henselae'' is difficult to culture and can take 2–6 weeks to incubate.
Histology
Cat-scratch disease is characterized by granulomatous inflammation on histological examination of the lymph nodes. Under the microscope, the skin lesion demonstrates a circumscribed focus of necrosis, surrounded by
histiocyte
A histiocyte is a vertebrate cell that is part of the mononuclear phagocyte system (also known as the reticuloendothelial system or lymphoreticular system). The mononuclear phagocytic system is part of the organism's immune system. The histiocyt ...
s, often accompanied by multinucleated giant cells,
lymphocyte
A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic ad ...
s, and
eosinophil
Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells (WBCs) and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. A ...
s. The regional lymph nodes demonstrate follicular
hyperplasia
Hyperplasia (from ancient Greek ὑπέρ ''huper'' 'over' + πλάσις ''plasis'' 'formation'), or hypergenesis, is an enlargement of an organ or tissue caused by an increase in the amount of organic tissue that results from cell proliferati ...
with central stellate necrosis with
neutrophil
Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying in ...
s, surrounded by palisading histiocytes (suppurative
granuloma
A granuloma is an aggregation of macrophages that forms in response to chronic inflammation. This occurs when the immune system attempts to isolate foreign substances that it is otherwise unable to eliminate. Such substances include infectious ...
s) and sinuses packed with monocytoid
B cell
B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...
s, usually without perifollicular and intrafollicular epithelioid cells. This pattern, although typical, is only present in a minority of cases.
Prevention
Cat-scratch disease can be primarily prevented by taking effective flea control measures; since cats are mostly exposed to fleas when they are outside, keeping cats inside can help prevent infestation. Strictly-indoor cats without exposure to indoor-outdoor animals are generally at negligible risk of infestation. Cats which are carrying the bacterium, ''B. henselae,'' are asymptomatic, thus thoroughly washing hands after handling a cat or cat feces is an important factor in preventing potential cat-scratch disease transmission from possibly infected cats to humans.
Treatment
Most healthy people clear the infection without treatment, but in 5 to 14% of individuals, the organisms disseminate and infect the liver, spleen, eye, or central nervous system. Although some experts recommend not treating typical CSD in immunocompetent people with mild to moderate illness, treatment of all people with antimicrobial agents (Grade 2B) is suggested due to the probability of disseminated disease. The preferred antibiotic for treatment is
azithromycin
Azithromycin, sold under the brand names Zithromax (in oral form) and Azasite (as an eye drop), is an antibiotic medication used for the treatment of a number of bacterial infections. This includes middle ear infections, strep throat, pneumon ...
, since this agent is the only one studied in a randomized controlled study.
Azithromycin is preferentially used in pregnancy to avoid the teratogenic side effects of
doxycycline
Doxycycline is a broad-spectrum tetracycline class antibiotic used in the treatment of infections caused by bacteria and certain parasites. It is used to treat bacterial pneumonia, acne, chlamydia infections, Lyme disease, cholera, typhus, an ...
. However, doxycycline is preferred to treat ''B. henselae'' infections with optic neuritis due to its ability to adequately penetrate the tissues of the eye and
central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
.
Epidemiology
Cat-scratch disease has a worldwide distribution, but it is a nonreportable disease in humans, so public health data on this disease are inadequate. Geographical location, present season, and variables associated with cats (such as exposure and degree of flea infestation) all play a factor in the prevalence of CSD within a population. In warmer climates, the CSD is more prevalent during the fall and winter, which may be attributed to the breeding season for adult cats, which allows for the birth of kittens.'' B henselae,'' the bacterium responsible for causing CSD, is more prevalent in younger cats (less than one year old) than it is in adult cats.
To determine recent incidence of CSD in the United States, the Truven Health MarketScan Commercial Claims and Encounters database was analyzed in a case control study from 2005 to 2013. The database consisted of healthcare insurance claims for employees, their spouses, and their dependents. All participants were under 65 years of age, from all 50 states. The length of the study period was 9 years and was based on 280,522,578 person-years; factors such as year, length of insurance coverage, region, age, and sex were used to calculate the person-years incidence rate to eliminate
confounding variables
In statistics, a confounder (also confounding variable, confounding factor, extraneous determinant or lurking variable) is a variable that influences both the dependent variable and independent variable, causing a spurious association. Con ...
among the entire study population.
A total of 13,273 subjects were diagnosed with CSD, and both in- and outpatient cases were analyzed. The study revealed an incidence rate of 4.5/100,000 outpatient cases of cat-scratch disease. For inpatient cases, the incidence rate was much lower at 0.19/100,000 population. Incidence of CSD was highest in 2005 among outpatient cases and then slowly declined. The Southern states had the most significant decrease of incidence over time. Mountain regions have the lowest incidence of this disease because fleas are not commonly found in these areas.
Distribution of CSD among children aged 5–9 was of the highest incidence in the analyzed database, followed by women aged 60–64. Incidence among females was higher than that among males in all age groups. According to data on social trends, women are more likely to own a cat over men; which supports higher incidence rates of this disease in women. Risk of contracting CSD increases as the number of cats residing in the home increases. The number of pet cats in the United States is estimated to be 57 million. Due to the large population of cats residing in the United States, the ability of this disease to continue to infect humans is vast. Laboratory diagnosis of CSD has improved in recent years, which may support an increase in incidence of the disease in future populations.
Outbreaks
Historically, the number of reported cases of CSD has been low, there has been a significant increase in reports in urban and suburban areas in the northeast region of United States. An example of the increased incidence can be found in Essex County, New Jersey. In 2016, there were 6 reported cases. In 2017, there were 51 reported cases. In 2018, there were 263 reported cases. Although usually treated with antibiotics and minimal long-term effects, there have been 3 reported case of tachycardia more than one year after exposure. Pathologists believe that the increased incidence of CSD is due to cat owners neglecting to vaccinate their cats.
in 1889, and the clinical syndrome was first described in 1950 by
Robert Debré
Robert Debré (7 December 1882 – 29 April 1978) was a French physician (pediatrician) at Necker-Enfants Malades Hospital in Paris.
The largest pediatric hospital in Paris, l'Hôpital Robert-Debré - located in the North-East part of Paris (19 ...
Afipia felis
''Afipia felis'' is the type species of the ''Afipia'' bacterial genus. It was formerly thought to cause cat-scratch disease. It is a Gram-negative, oxidase-positive, nonfermentative rod in the alpha-2 subgroup of the class Proteobacteria. It is ...
'' in 1991 after it was successfully cultured and isolated. The causative organism of CSD was originally believed to be ''Afipia felis'', but this was disproved by immunological studies in the 1990s demonstrating that people with cat-scratch fever developed antibodies to two other organisms, ''B. henselae'' (originally known as ''Rochalimea henselae'' before the genera ''Bartonella'' and ''Rochalimea'' were combined) and ''B. clarridgeiae'', which is a
rod-shaped
A bacillus (), also called a bacilliform bacterium or often just a rod (when the context makes the sense clear), is a rod-shaped bacterium or archaeon. Bacilli are found in many different taxonomic groups of bacteria. However, the name ''Bacillu ...
Gram-negative
Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall ...