Rheumatologic Manifestations:

Dr. Nicole Vumbaco | DVM
Apr 24, 2020
4 min read

Updated: Nov 5, 2022

Many patients with Bartonellosis experience a variety of connective tissue derangements and are often diagnosed with an 'Undifferentiated or Mixed Connective Tissue Disorder'. This results in myalgias, arthralgias, hypermobility and fairly significant generalized pain.

Reported Musculoskeletal Symptoms of Bartonellosis:

Myalgia (muscle pain)
Myositis (muscle inflammation)
Migratory Arthropathy (shifting joint pain, mainly medium/larger joints- knee, elbow, wrist, hip, etc; can include smaller joints)
Long Bone Pain (primarily in the shins)
Acquired Joint Laxity and Hypermobility, EDS III like syndrome
Generalized Body Pain
Excruciating Feet Pain
RA, Lupus, Scleroderma, Fibromyaligia, MS-like symptoms (headache, joint/muscle pain, fatigue, memory problems, numbness and tingling in extremities, weakness, myofascial pain, etc)- bartonella can mimic disease of autoimmunity
Joint Injuries/Delayed Healing/Tendinitis/Tendinosis/Bursitis
Osteomyelitis (rarest presentation but most well-known)
Muscle Fasciculations or Twitching
Arthritis
Back and Hip Pain
Neuralgia
Abnormal Temperature Changes in Hands/Feet
General Malaise +/- a Cyclic, Low Grade Fever

Initially, these symptoms may be vague but can become cyclic, migratory and progressive. As time passes, your symptom profile feels more defined but specialist's remain unable to truly classify it. About 25% of all rheumatic patients fit into this category; To which, patients with musculoskeletal presentations of bartonella generally fall.

In this situation, the diagnosis of an 'Undifferentiated, Systemic Rheumatic Disorder' (or an 'Undifferentiated Connective Tissue Disease') is made. Within this, The American College of Rheumatology recognize that these disorders are likely secondary to an underlying inflammatory tissue injury rather than true autoimmunity. Of great importance, Bartonellosis is one of many chronic infections that cause chronic low-grade inflammation and are capable of mimicking and/or inducing Autoimmunity.

Further complicating these complex cases, an 'acquired hypermobility' has been documented and in some instances, misdiagnosed as 'Ehler-Danlos Syndrome' or 'EDS III' (an inherited condition affecting the connective tissue); only to greatly improve or resolve with appropriate bartonella treatment. Overlapping syndromes of Mast Cell Activation and Postural Orthostatic Tachycardia have contributing factors and correlations to both. More research is underway to determine it's connection to autoimmunity and further evaluate "the extent to which Bartonella spp. may colonize collagen and/or bone and if persistent infection and inflammation can contribute to the pathogenesis of hypermobility (EDS) that may include progressive joint pain, tendinosis, and instability".

What We Currently Know:

Bartonella is highly abundant in connective tissue and creates adhesions in the extracellular matrix (ECM) via host proteins with collagen, laminin, fibronectin and integrins
1. Pap31, BadA (Bartonella Adhesin A), and TAAs (Trimeric Autotransporter Adhesins) are surface proteins bartonella have that allow it to bind to:
  1. Collagen Type 9, Type 10 and possibly, Collagen Type 4.
  2. Fibronectin and Vitronectin (glycoproteins needed for tissue remodeling)
  3. Heparin (a highly sulfated glycosaminoglycan with multiple biological functions that is stored within Mast Cells* [another cell bartonella infects] and released at sites of tissue injury)
  4. Hyaluronic Acid (a non-sulfated glycosaminoglycan -- essential for joint lubrication and is the ground substance of connective tissue and neural tissue) -- In the brain, hyaluronic acid is the main component of the ECM -- When degraded it causes a pro-inflammatory response by using microglial cells*
Bartonella stimulated-cytokines (like Interleukin-8 or IL-8) intentionally induce an inflammatory response which forward feeds the spread of infection. This leads to:
1. Endothelial proliferation (reproduction of cells that line the inside of blood vessels* and lymphatic vessels)
2. Inhibition of our host cells to undergo apoptosis (decreases a cell's ability to undergo programmed and controlled cell death)
3. Stimulation of endothelial migration (increases new capillary or blood source formation)
4. Increased epidermal growth factor (stimulates the growth and survival of different cell types)
5. Upregulation of MMP-2 and MMP-9 (Matrix Metallopeptidase) which breakdown and degrade parts of our ECM and collagen.
  1. Damaged collagen tissue sends out signals recruiting CD34+ Hematopoietic Progenitor Cells* to the site of damage that allows them to take advantage of the local inflammation.

Remember that Bartonella is an intracellular bacteria.

Areas with an * symbol indicate that it's a cell bartonella infects and lives within

While this is a lot to take in, there is so much more to understand -- Below is a short list of scholarly articles and case reports outlining the ways bartonella infections can cause musculoskeletal injury and pain. The 1st case report is of great significance to me!! It describes a 31 yr old female veterinarian's case and is what prompted my 2nd wave of investigation into Bartonellosis. This report read almost identical to my clinical picture (joint breakdown, degenerative arthritis, arthralgia, muscle pain, progressive joint hypermobility, joint laxity, subluxation, Mild Mast Cell Activation Syndrome, Vit D deficiency, etc). The 2nd discusses it's relation to degenerative joint disease. Both were pivotal in my search for an answer.