A tophus (Latin: "stone", plural tophi) is a deposit of monosodium urate crystals, in people with longstanding high levels of
uric acid
Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the metabolic breakdown of ...
in the blood, a condition known as
hyperuricemia
Hyperuricaemia or hyperuricemia is an abnormally high level of uric acid in the blood. In the pH conditions of body fluid, uric acid exists largely as urate, the ion form. Serum uric acid concentrations greater than 6 mg/dL for females, 7&nbs ...
. Tophi are
pathognomonic Pathognomonic (rare synonym ''pathognomic'') is a term, often used in medicine, that means "characteristic for a particular disease". A pathognomonic sign is a particular sign whose presence means that a particular disease is present beyond any doub ...
for the disease
gout
Gout ( ) is a form of inflammatory arthritis characterized by recurrent attacks of a red, tender, hot and swollen joint, caused by deposition of monosodium urate monohydrate crystals. Pain typically comes on rapidly, reaching maximal intensit ...
. Most people with tophi have had previous attacks of acute
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 ...
, eventually leading to the formation of tophi. Chronic tophaceous gout is known as
Harrison Syndrome
Gout ( ) is a form of inflammatory arthritis characterized by recurrent attacks of a red, tender, hot and swollen joint, caused by deposition of monosodium urate monohydrate crystals. Pain typically comes on rapidly, reaching maximal intensit ...
.
Tophi form in the
joints
A joint or articulation (or articular surface) is the connection made between bones, ossicles, or other hard structures in the body which link an animal's skeletal system into a functional whole.Saladin, Ken. Anatomy & Physiology. 7th ed. McGraw- ...
,
cartilage
Cartilage is a resilient and smooth type of connective tissue. In tetrapods, it covers and protects the ends of long bones at the joints as articular cartilage, and is a structural component of many body parts including the rib cage, the neck an ...
,
bone
A bone is a Stiffness, rigid Organ (biology), organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red blood cell, red and white blood cells, store minerals, provid ...
s, and other places throughout the body. Sometimes, tophi break through the
skin
Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation.
Other cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...
and appear as white or yellowish-white, chalky
nodules. Without treatment, tophi may develop on average about ten years after the onset of gout, although their first appearance can range from three to forty-two years. The development of gouty tophi can also limit joint function and cause bone destruction, leading to noticeable disabilities, especially when gout cannot successfully be treated.
When uric acid levels and gout symptoms cannot be controlled with standard gout medicines that decrease the production of
uric acid
Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the metabolic breakdown of ...
(e.g.,
allopurinol
Allopurinol is a medication used to decrease high blood uric acid levels. It is specifically used to prevent gout, prevent specific types of kidney stones and for the high uric acid levels that can occur with chemotherapy. It is taken by mouth ...
,
febuxostat
Febuxostat, sold under the brand names Uloric and Adenuric among others, is a medication used long-term to treat gout due to high uric acid levels. It is generally recommended only for people who cannot take allopurinol. When initially started, m ...
) or increase uric acid
elimination from the body through the kidneys (e.g.,
probenecid
Probenecid, also sold under the brand name Probalan, is a medication that increases uric acid excretion in the urine. It is primarily used in treating gout and hyperuricemia.
Probenecid was developed as an alternative to caronamide to competitive ...
), this can be referred to as
refractory
In materials science, a refractory material or refractory is a material that is resistant to decomposition by heat, pressure, or chemical attack, and retains strength and form at high temperatures. Refractories are polycrystalline, polyphase, ...
chronic gout (RCG). They are more apt to appear early in the course of the disease in people who are older.
Although less common, tophi can also form in the kidneys and nasal
cartilage
Cartilage is a resilient and smooth type of connective tissue. In tetrapods, it covers and protects the ends of long bones at the joints as articular cartilage, and is a structural component of many body parts including the rib cage, the neck an ...
.
Pathophysiology
It appears that monosodium urate crystals trigger a distinct physiological
NETosis pathway that coats them in DNA. These coated crystals then persist in tissues as a
foreign body granuloma
A foreign body reaction (FBR) is a typical tissue response to a foreign body within biological tissue. It usually includes the formation of a foreign body granuloma. Tissue-encapsulation of an implant is an example, as is inflammation around a sp ...
constituting gouty tophus.
Additional images
File:Gross pathology of tophus.jpg, Gross pathology
Gross pathology refers to macroscopic manifestations of disease in organs, tissues, and body cavities. The term is commonly used by anatomical pathologists to refer to diagnostically useful findings made during the gross examination portion of ...
of a large tophus
Image:Gouty_tophus_-_intermed_mag.jpg, Micrograph
A micrograph or photomicrograph is a photograph or digital image taken through a microscope or similar device to show a magnified image of an object. This is opposed to a macrograph or photomacrograph, an image which is also taken on a mic ...
of a gouty tophus
Image:Tophus in knee.jpg, A tophus inside a knee
In humans and other primates, the knee joins the thigh with the leg and consists of two joints: one between the femur and tibia (tibiofemoral joint), and one between the femur and patella (patellofemoral joint). It is the largest joint in the hu ...
joint being removed by arthroscopic surgery
Arthroscopy (also called arthroscopic or keyhole surgery) is a minimally invasive surgical procedure on a joint in which an examination and sometimes treatment of damage is performed using an arthroscope, an endoscope that is inserted into the jo ...
image:2015.7.30 Uric Acid synovial Tophus 7.tif, Tophus of uric acid crystals from toe joint fluid (100x polarized light)
See also
*
Chondrocalcinosis
Chondrocalcinosis or cartilage calcification is calcification (accumulation of calcium salts) in hyaline cartilage and/or fibrocartilage.Rothschild, Bruce M It can be seen on radiography.
Causes
Buildup of calcium phosphate in the ankle joints h ...
(pseudogout)
References
External links
Gross pathology
Rheumatology
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