Bartonella

Bartonella is a genus of gram-negative bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview in the family Bartonellaceae. As a facultative intracellular parasite, Bartonella can infect healthy people as well as act as an opportunistic pathogen. Bartonella species are transmitted by vectors such as ticks, fleas, sandflies, and mosquitoes. B. henselae is the most common of the 3 species known to cause human disease; it is a zoonosis that causes cat-scratch disease and bacillary angiomatosis (BA). The other 2 species are human-specific: B. bacilliformis causes trench fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever and BA, and B. quintana causes Oroya fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, verruga peruana, and Carrion’s disease.

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General Characteristics

Basic features

  • Genus: Bartonella, closely related to the genera Brucella Brucella Brucellosis (also known as undulant fever, Mediterranean fever, or Malta fever) is a zoonotic infection that spreads predominantly through ingestion of unpasteurized dairy products or direct contact with infected animal products. Clinical manifestations include fever, arthralgias, malaise, lymphadenopathy, and hepatosplenomegaly. Brucella/Brucellosis and Agrobacterium
  • Family: Bartonellaceae
  • Facultative intracellular parasitic bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview
  • Stain very poorly using Gram stain:
    • Sometimes classified as gram-negative
    • Stain black with silver-impregnated stains (e.g., Warthin-Starry stain)
  • At least 22 named species; the 3 most relevant medically are: 
    •  B. henselae
    • B. quintana (formerly known as Rickettsiae quintana)
    • B. bacilliformis
Transmission electron micrographs showing morphology of b. Bacilliformis

Transmission electron micrographs showing morphology of Bartonella bacilliformis:
Scale bars represent 100 nm in panel A and 500 nm in panel B.

Image: “Transmission electron micrographs showing morphology of B. bacilliformis” by Michael F. Minnick, Burt E. Anderson, Amorce Lima, James M. Battisti, Phillip G. Lawyer, and Richard J. Birtles. License: Public Domain

Epidemiology and Pathogenesis

Epidemiology

  • Bartonella spp. have a worldwide distribution.
  • No types of bartonellosis have a sex predilection
  • Cat-scratch disease (B. henselae):
    • Worldwide distribution
    • Affects approximately 1 in 10,000 persons
    • More common in children and adolescents than in adults (except for immunocompromised adults)
  • Carrion’s disease (B. bacilliformis)
    • Very rare infectious disease
    • Found only in Peru (endemic), Ecuador, and Colombia or associated with a history of recent travel to these regions
  • Trench fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever (B. quintana) is most common in populations prone to infestations with lice, such as the homeless

Transmission

  • Mainly transmitted by vectors like fleas, lice, sandflies, or ticks
  • Zoonotic disease (transmitted from animals to people)
  • Reservoirs: 
    • Humans
    • Domestic animals, especially cats (asymptomatic carriers)
    • Wild animals, especially rodents, coyotes, or foxes

Host risk factors

  • Immunocompromised patients: 
    • Chemotherapy
    • Organ transplant
    • HIV/AIDS → bacillary angiomatosis is an AIDS-defining condition
  • Homelessness
  • Poor hygiene
  • Alcoholism

Pathogenesis

  • After exposure from a reservoir or vector, bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview colonize the endothelial cells of the new host.
  • From the endothelial cells, the bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview are released into the bloodstream, where they infect erythrocytes Erythrocytes Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes.
  • Bacteria invade and replicate in erythrocytes Erythrocytes Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes and in endothelial cells.
    • All Bartonella spp. induce host tissues to produce hypoxia-inducible factor-1α, which drives the production of vascular endothelial growth factor, causing vascular proliferation (angiogenesis).
    • Microscopic pathology of angiogenesis: capillary proliferation with prominent epithelioid endothelial cells showing nuclear atypia and mitosis, associated with neutrophils and bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview
    • Facultative intracellular properties help in the evasion of a host immune response.
    • B. bacilliformis
      • Uses a polar flagellum for motility
      • Replicates in vacuoles
    • B. henselae and B. quintana:
      • Invade endothelial cells
      • Make a protein binder that adheres to feline RBC membranes
    • B. quintana:
      • Invades endothelial cells
      • Forms bacterial aggregates that are internally taken in by the invasome, a unique phagosomal structure
      • Invasomes proliferate and make intracellular blebs.
  • The intraerythrocytic life cycle causes hemolytic anemia Hemolytic Anemia Hemolytic anemia (HA) is the term given to a large group of anemias that are caused by the premature destruction/hemolysis of circulating red blood cells (RBCs). Hemolysis can occur within (intravascular hemolysis) or outside the blood vessels (extravascular hemolysis). Hemolytic Anemia.
  • Endothelial cell proliferation causes microvascular thrombosis and vessel occlusion, leading to tissue ischemia 
  • Erythrocytes are taken in by another vector (blood-sucking arthropod) to be transmitted to the next host.
Pathogenesis of bartonella

Pathogenesis of Bartonella:
Following transmission by an arthropod vector (a), the Bartonella bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview colonize the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin (b). The bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview are then transported to the vascular endothelium (c) and are seeded into the bloodstream to invade erythrocytes Erythrocytes Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes (d). After replication inside the RBC (e), the bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview persist in the intraerythrocytic niche (f), making them competent for transmission by another bloodsucking arthropod (g).

Image by Lecturio. License: CC BY-NC-SA 4.0

Diseases Caused by Bartonella

Bartonellosis in humans is caused by 3 main species of Bartonella bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview and produces a wide range of symptoms and diseases depending on the species and the immune state of the infected individual.

Table: Diseases caused by Bartonella species
Species Disease
B. bacilliformis Carrion’s disease, also known as:
  • Oroya fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever: initial bacteremic form
  • Verruga peruana: late-onset, eruptive form
B. quintana
  • Trench fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever (“5-day fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever”)
  • BA: if severely immunosuppressed; an AIDS-defining condition
  • Endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis (often culture-negative)
B. henselae
  • CSD
  • BA: if severely immunosuppressed; an AIDS-defining condition
  • Peliosis hepatis: BA in liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver, spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen, lymph nodes
  • Endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis: with atypical CSD; often culture-negative
  • Neuroretinitis: with atypical CSD
  • Meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis/ encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis: with atypical CSD
BA: bacillary angiomatosis
CSD: cat-scatch disease

Carrion’s disease (South American bartonellosis)

Transmission:

  • Carried by night-biting sandflies of the genus Lutzomyia (formerly Phlebotomus)

Clinical presentation:

  • Biphasic clinical course that used to be considered 2 separate diseases
  • Acute phase:
    • Also known as Oroya fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
    • Develops 3–12 weeks after initial exposure
    • Sudden-onset high fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever and chills
    • Profuse sweating
    • Severe headache
    • Weakness
    • Paleness of the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin
    • Abdominal, muscular, or joint pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
    • Meningoencephalitis and/or seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
    • Severe hemolytic anemia Hemolytic Anemia Hemolytic anemia (HA) is the term given to a large group of anemias that are caused by the premature destruction/hemolysis of circulating red blood cells (RBCs). Hemolysis can occur within (intravascular hemolysis) or outside the blood vessels (extravascular hemolysis). Hemolytic Anemia may lead to:
      • Confusion, disorientation, or coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma
      • Chest pain Chest Pain Chest pain is one of the most common and challenging complaints that may present in an inpatient and outpatient setting. The differential diagnosis of chest pain is large and includes cardiac, gastrointestinal, pulmonary, musculoskeletal, and psychiatric etiologies. Chest Pain
      • Thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia
      • Dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea
      • Organ dysfunction
  • Chronic phase:
    • Also known as verruga peruana
    • Usually develops within weeks or months in untreated individuals who may or may not have manifested the acute phase of the disease
    • Characteristic skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin lesions
      • Reddish-purple in color
      • Develop in outbreaks over several regions of the body at once or in a migratory pattern
      • Usually located on exposed skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin, such as the face, arms, and legs, but may also develop in mucous membranes and internal organs
      • Lesions are initially small and become nodular (0.2 to 4 cm in diameter)
      • Can potentially bleed, ulcerate, or become pustules

Trench fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever

Transmission:

  • Mainly carried by the human body louse vector Pediculus humanus var. corporis (along with other species of lice, ticks, and fleas)
  • Transmission via inoculation of infected louse feces into abrasions of the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin or into conjunctivae 

Clinical presentation:

  • Incubation period: 5–20 days (average, 7.7)
  • Classic trench fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever can range from mild flu-like illness to a debilitating illness 
  • Acute illness usually presents with malaise, fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, headache, dizziness, nausea and vomiting, bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, and sometimes a macular truncal rash 
  • The fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever is usually episodic, presenting every 5 days (“5-day fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever” or “quintan fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever”).

Cat-scratch disease (CSD)

Transmission:

  • Cats are the most important carriers, though there are cases of transmission from dogs.
  • Routes of transmission:
    • Scratch or bite from an infected cat
    • Bite from cat fleas
    • Contact with cat saliva through broken skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin or mucosal surfaces

Clinical presentation:

  • May not manifest until several days or weeks after the initial exposure
  • Characteristic papular lesions
    • Begin as a macule at the site of infection that can become a painless papule after 3–10 days
    • The papule may become a vesicle, crust, and heal with a scar after 1–3 weeks.
  • Gradual enlargement of regional lymph nodes
    • Usually located in the axilla Axilla The axilla is a pyramid-shaped space located between the upper thorax and the arm. The axilla has a base, an apex, and 4 walls (anterior, medial, lateral, posterior). The base of the pyramid is made up of the axillary skin. The apex is the axillary inlet, located between the 1st rib, superior border of the scapula, and clavicle. Axilla and Brachial Plexus, neck, or groin regions
    • Swollen nodes are tender and can last 2–3 months or longer
    • May appear red and warm to the touch
    • Suppuration may occur
  • General or flu-like symptoms:
    • Malaise, back and body aches
    • Fatigue
    • Headache
    • Low-grade fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
    • Loss of appetite and weight loss
    • Sore throat
  • Complications (“atypical CSD”), which usually present in immunocompromised individuals:
    • Granulomatous hepatitis and/or splenitis
    • Osteomyelitis Osteomyelitis Osteomyelitis is an infection of the bone that results from the spread of microorganisms from the blood (hematogenous), nearby infected tissue, or open wounds (non-hematogenous). Infections are most commonly caused by Staphylococcus aureus. Osteomyelitis
    • Bacillary angiomatosis
    • Meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis and/or encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis 
    • Neuroretinitis
    • Parinaud’s oculoglandular syndrome (similar to conjunctivitis Conjunctivitis Conjunctivitis is a common inflammation of the bulbar and/or palpebral conjunctiva. It can be classified into infectious (mostly viral) and noninfectious conjunctivitis, which includes allergic causes. Patients commonly present with red eyes, increased tearing, burning, foreign body sensation, and photophobia. Conjunctivitis plus lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy)
    • Parotitis
    • Endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis
Clinical presentation of a patient with bacillary angiomatosis

Clinical presentation of a patient with bacillary angiomatosis:
A: Multiple red papules on the chest and abdomen
B: 2 nodules on the back
C: Papules on the face with a subcutaneous mass lesion over the left zygomatic arch

Image: “Bacillary angiomatosis presenting with facial tumor and multiple abscesses” by Markowicz M, Käser S, Müller A, Lang G, Lang S, Mayerhöfer M, Stanek G, Rieger A. License: CC BY 4.0

Bacillary angiomatosis

  • Occurs primarily in immunocompromised individuals
    • Especially in patients with AIDS and a CD4 count < 100 cells/μL
    • Constitutes an AIDS-defining condition
  • Vascular proliferative disease that mainly affects the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin, but can develop in other organs (e.g., bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow, liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver, spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen, or lymph nodes)
  • Characteristic erythematous skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin lesions
    • Usually elevated
    • May be surrounded by a scaly ring 
    • Very friable and bleed easily

Peliosis hepatis

  • Occurs primarily in immunocompromised individuals, especially in patients with AIDS
  • Vascular proliferation of sinusoid hepatic capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries that result in blood-filled sacs within the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver parenchyma
  • Commonly associated with peliosis of the spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen and lymph nodes

Diagnosis

Most cases of bartonellosis can be diagnosed through the detection of characteristic symptoms and physical findings and a complete medical history. Specialized laboratory tests are used to confirm the diagnosis. 

  • Bartonella infection can be difficult to detect, confirm, and diagnose. 
  • Serologic testing is the most cost-effective diagnostic tool, but false negatives can occur even during active infection.
  • Detection of IgG and IgM antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins in blood serum by indirect immunofluorescence assays are used to detect B. henselae in suspected cases of cat-scratch disease. 
  • Microscopic examination of Giemsa-stained blood smears is used to detect B. bacilliformis in suspected cases of Carrion’s disease. 
  • PCR analysis of tissue and body fluid is the most specific diagnostic test to detect Bartonella spp.
  • Other Bartonella spp. are visible only with silver stains.
  • Abdominal imaging tests are used to confirm suspected cases of liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver and spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen complications.

Management

Aside from supportive care, management is dependent on the specific species of Bartonella contracted and the severity of each case.  

  • CSD:
    • In mild cases: Antibiotics may not be necessary, but azithromycin can shorten the duration of symptoms.
    • In moderate cases: azithromycin, erythromycin, or doxycycline (may add steroids for refractory lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy)
    • In severe cases: rifampin and either erythromycin or doxycycline
  • Carrion’s disease:
    • Acute phase: chloramphenicol Chloramphenicol Chloramphenicol, the only clinically relevant drug in the amphenicol class, is a potent inhibitor of bacterial protein synthesis by binding to the 50S ribosomal subunit and preventing peptide bond formation. Chloramphenicol is a broad-spectrum antibiotic with wide distribution; however, due to its toxicity, its use is limited to severe infections. Chloramphenicol or ciprofloxacin (in pediatric cases, ciprofloxacin is not used and beta-lactams are added)
    • Chronic phase: rifampin or macrolides Macrolides Macrolides and ketolides are antibiotics that inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit and blocking transpeptidation. These antibiotics have a broad spectrum of antimicrobial activity but are best known for their coverage of atypical microorganisms. Macrolides and Ketolides
  • Trench fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever: doxycycline and gentamicin
  • Bartonellosis in immunocompromised patients: prolonged course of erythromycin or doxycycline

Differential Diagnosis

  • Cervical lymphadenitis: cervical lymph nodes may become enlarged, inflamed, and tender owing to viral infections (e.g., adenovirus Adenovirus Adenovirus (member of the family Adenoviridae) is a nonenveloped, double-stranded DNA virus. Adenovirus is transmitted in a variety of ways, and it can have various presentations based on the site of entry. Presentation can include febrile pharyngitis, conjunctivitis, acute respiratory disease, atypical pneumonia, and gastroenteritis. Adenovirus) or bacterial infections (e.g., Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus aureus). Management of cervical lymphadenitis is by diagnosing the underlying cause. Biopsies are rarely needed.
  • Hodgkin lymphoma Hodgkin lymphoma Hodgkin lymphoma (HL) is a malignancy of B lymphocytes originating in the lymph nodes. The pathognomonic histologic finding of HL is a Hodgkin/Reed-Sternberg (HRS) cell (giant multinucleated B cells with eosinophilic inclusions). The disease presents most commonly with lymphadenopathy, night sweats, weight loss, fever, splenomegaly and hepatomegaly. Hodgkin Lymphoma: malignancy of B lymphocytes B lymphocytes B lymphocytes, also known as B cells, are important components of the adaptive immune system. In the bone marrow, the hematopoietic stem cells go through a series of steps to become mature naive B cells. The cells migrate to secondary lymphoid organs for activation and further maturation. B Cells within lymph nodes. The histologic finding for Hodgkin lymphoma Hodgkin lymphoma Hodgkin lymphoma (HL) is a malignancy of B lymphocytes originating in the lymph nodes. The pathognomonic histologic finding of HL is a Hodgkin/Reed-Sternberg (HRS) cell (giant multinucleated B cells with eosinophilic inclusions). The disease presents most commonly with lymphadenopathy, night sweats, weight loss, fever, splenomegaly and hepatomegaly. Hodgkin Lymphoma is a Reed-Sternberg cell (giant B cell with eosinophilic inclusions). Presentation of the disease is with lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy and constitutional “B symptoms.” Hodgkin lymphoma Hodgkin lymphoma Hodgkin lymphoma (HL) is a malignancy of B lymphocytes originating in the lymph nodes. The pathognomonic histologic finding of HL is a Hodgkin/Reed-Sternberg (HRS) cell (giant multinucleated B cells with eosinophilic inclusions). The disease presents most commonly with lymphadenopathy, night sweats, weight loss, fever, splenomegaly and hepatomegaly. Hodgkin Lymphoma is managed with chemotherapy and radiotherapy. 
  • Non-Hodgkin lymphomas (NHL): diverse group of malignancies of B-cell, T-cell, and natural killer (NK)–cell origin. Lymph nodes are involved in ⅔ of NHLs; the remainder of NHLs are extranodal. In the United States, NHLs are 10ⅹ more common than Hodgkin lymphoma Hodgkin lymphoma Hodgkin lymphoma (HL) is a malignancy of B lymphocytes originating in the lymph nodes. The pathognomonic histologic finding of HL is a Hodgkin/Reed-Sternberg (HRS) cell (giant multinucleated B cells with eosinophilic inclusions). The disease presents most commonly with lymphadenopathy, night sweats, weight loss, fever, splenomegaly and hepatomegaly. Hodgkin Lymphoma and represent a common cause of cancer-related death.
  • Cellulitis Cellulitis Cellulitis is a common infection caused by bacteria that affects the dermis and subcutaneous tissue of the skin. It is frequently caused by Staphylococcus aureus and Streptococcus pyogenes. The skin infection presents as an erythematous and edematous area with warmth and tenderness. Cellulitis: common and painful bacterial skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin infection that affects the deeper layers of the dermis and subcutaneous tissue. Cellulitis Cellulitis Cellulitis is a common infection caused by bacteria that affects the dermis and subcutaneous tissue of the skin. It is frequently caused by Staphylococcus aureus and Streptococcus pyogenes. The skin infection presents as an erythematous and edematous area with warmth and tenderness. Cellulitis presents as an erythematous, edematous area that feels warm and tender to the touch. The condition is caused most commonly by Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus aureus and Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus pyogenes. Diagnosis is usually clinical, and management is with antibiotics based on suspected organisms.
  • Kaposi’s sarcoma: aggressive, malignant vascular tumor that is an AIDS-defining condition and usually presents in patients with a CD4 count < 500 cells/μL. Kaposi’s sarcoma is caused by HHV-8 and is transmitted via saliva and sexual contact. The condition presents as a pink, red, purple, or brown papular or plaque-like lesions that are not painful or pruritic.
  • Hemangioma: benign tumor made up of blood vessels and capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries. Hemangioma usually presents as a purple or red, well-demarcated papule.
  • Pyogenic granuloma: benign, vascular lesion of unknown cause or origin. Pyogenic granuloma sometimes develops after minor trauma or injury. The granuloma appears as a red or purple papule that is friable and bleeds easily. 
  • Brucellosis Brucellosis Brucellosis (also known as undulant fever, Mediterranean fever, or Malta fever) is a zoonotic infection that spreads predominantly through ingestion of unpasteurized dairy products or direct contact with infected animal products. Clinical manifestations include fever, arthralgias, malaise, lymphadenopathy, and hepatosplenomegaly. Brucella/Brucellosis: zoonotic infection that spreads predominantly through ingestion of unpasteurized dairy products or direct contact with infected animal products. Clinical manifestations of brucellosis include fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, arthralgias, malaise, lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy, and hepatosplenomegaly. Clinical manifestations, exposure history, serology, and culture data are used in the diagnosis. Treatment involves a combination of antibiotics, including doxycycline, rifampin, and aminoglycosides Aminoglycosides Aminoglycosides are a class of antibiotics including gentamicin, tobramycin, amikacin, neomycin, plazomicin, and streptomycin. The class binds the 30S ribosomal subunit to inhibit bacterial protein synthesis. Unlike other medications with a similar mechanism of action, aminoglycosides are bactericidal. Aminoglycosides.

References

  1. Hammoud, K. (2019). Bartonellosis (Bartonella Infection). Emedicine. Retrieved February 18, 2021, from https://emedicine.medscape.com/article/213169-overview#a6.
  2. Spach, D. (2020). Clinical features, diagnosis, and treatment of Bartonella quintana. UpToDate. Retrieved February 18, 2021, from https://www.uptodate.com/contents/clinical-features-diagnosis-and-treatment-of-bartonella-quintana-infections
  3. Nelson VA, Saha S, Mead PS. (2016). Cat-scratch disease in the United States, 2005-2013. Emerg Infect Dis 22:1741–1746. https://pubmed.ncbi.nlm.nih.gov/27648778/
  4. Versalovic J, Carroll KC, Funke G, Jorgensen JH, Landry ML, Warnock DW. (2011). Manual of Clinical Microbiology, 10th ed. Washington, DC: ASM Press.
  5. Angelakis E, Raoult D. (2014). Pathogenicity and treatment of Bartonella infections. Int J Antimicrob Agents 44:16–25. https://pubmed.ncbi.nlm.nih.gov/24933445/
  6. Eicher SC, Dehio C. (2012). Bartonella entry mechanisms into mammalian host cells. Cell Microbiol 14:1166–1173. https://doi.org/https://doi.org/10.1111/j.1462-5822.2012.01806.x
  7. Corey C. (2018). Herpes simplex virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology: Overview infections. In Jameson JL, et al. (Eds.), Harrison’s Principles of Internal Medicine, 20th ed. Vol. 1, pp. 1345–1354. 
  8. Giladi M, Ephros M. (2018). Bartonella infections, including cat-scratch disease. In Jameson JL, et al. (Ed.s), Harrison’s Principles of Internal Medicine, 20th ed. Vol. 1, pp. 1209–1214. 

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