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Gout

Gout is a heterogeneous metabolic disease associated with elevated serum uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis, or “gout flare,” followed later by chronic deforming arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis. The kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy can also be affected, and urate crystals can precipitate as chalkstone-like deposits (“tophi”) in the soft tissues, synovial tissues, or in bones near the joints. Hyperuricemia is due to overproduction and/or underexcretion of uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis and is a necessary but insufficient precondition to developing urate crystal deposition disease (most hyperuricemic individuals never experience clinical gout). The most commonly involved joint is the first metatarsophalangeal joint Metatarsophalangeal Joint Foot: Anatomy. The identification Identification Defense Mechanisms of urate crystals in joint aspirate or tophi is diagnostic. Effective therapies to relieve the pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways of a gout flare include nonsteroidal anti-inflammatory drugs ( NSAIDs NSAIDS Primary vs Secondary Headaches), colchicine Colchicine A major alkaloid from colchicum autumnale l. And found also in other colchicum species. Its primary therapeutic use is in the treatment of gout. Gout Drugs, and glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids; the choice of therapy depends on the individual and if there are any contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation.

Last updated: Jul 10, 2023

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Epidemiology and Etiology

Epidemiology

  • In the United States, the general prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency is approximately 3%.
  • Risk increases with higher body mass index Body mass index An indicator of body density as determined by the relationship of body weight to body height. Bmi=weight (kg)/height squared (m2). Bmi correlates with body fat (adipose tissue). Their relationship varies with age and gender. For adults, bmi falls into these categories: below 18. 5 (underweight); 18. 5-24. 9 (normal); 25. 0-29. 9 (overweight); 30. 0 and above (obese). Obesity ( BMI BMI An indicator of body density as determined by the relationship of body weight to body height. Bmi=weight (kg)/height squared (m2). Bmi correlates with body fat (adipose tissue). Their relationship varies with age and gender. For adults, bmi falls into these categories: below 18. 5 (underweight); 18. 5-24. 9 (normal); 25. 0-29. 9 (overweight); 30. 0 and above (obese). Obesity): prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency is 1%2% in those with normal body mass index Body mass index An indicator of body density as determined by the relationship of body weight to body height. Bmi=weight (kg)/height squared (m2). Bmi correlates with body fat (adipose tissue). Their relationship varies with age and gender. For adults, bmi falls into these categories: below 18. 5 (underweight); 18. 5-24. 9 (normal); 25. 0-29. 9 (overweight); 30. 0 and above (obese). Obesity ( BMI BMI An indicator of body density as determined by the relationship of body weight to body height. Bmi=weight (kg)/height squared (m2). Bmi correlates with body fat (adipose tissue). Their relationship varies with age and gender. For adults, bmi falls into these categories: below 18. 5 (underweight); 18. 5-24. 9 (normal); 25. 0-29. 9 (overweight); 30. 0 and above (obese). Obesity), and 5%7% with class II or class III obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity
  • Middle-aged to elderly men and postmenopausal women are most often affected.
  • Rare in childhood unless there is an inherited enzyme defect or a malignancy Malignancy Hemothorax

Etiology

  • Hyperuricemia ( plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products urate > 6.8 mg/dL) is necessary but not sufficient for the development of gout.
    • Only 10% of individuals with hyperuricemia develop gout.
    • Elevated uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis (UA) can result from reduced excretion (90%), overproduction, or both.
  • Gout can occur in primary or secondary forms:
    • Primary gout (90%):
      • Unknown enzyme defects: usually due to decreased excretion of UA
      • Known enzyme defects: e.g., Lesch-Nyhan syndrome Lesch-Nyhan syndrome An inherited disorder transmitted as a sex-linked trait and caused by a deficiency of an enzyme of purine metabolism; hypoxanthine phosphoribosyltransferase. Elevation of uric acid in the serum leads to the development of renal calculi and gouty arthritis. Purine Salvage Deficiencies and variants of hypoxanthine-guanine phosphoribosyltransferase deficiency (due to increased purine production), glycogen storage diseases Glycogen Storage Diseases A group of inherited metabolic disorders involving the enzymes responsible for the synthesis and degradation of glycogen. In some patients, prominent liver involvement is presented. In others, more generalized storage of glycogen occurs, sometimes with prominent cardiac involvement. Benign Liver Tumors (due to decreased excretion of UA) 
    • Secondary gout (10%):
      • Increased nucleic acid turnover (e.g., leukemia), due to increased UA production
      • Chronic renal disease (due to decreased excretion of UA)

Risk factors that increase UA levels

  • Diets:
    • Rich in meat and seafood 
    • Beverages containing fruit sugar (fructose), alcohol
  • Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity
  • Medical conditions: untreated high blood pressure, diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus, metabolic syndrome Metabolic syndrome Metabolic syndrome is a cluster of conditions that significantly increases the risk for several secondary diseases, notably cardiovascular disease, type 2 diabetes, and nonalcoholic fatty liver. In general, it is agreed that hypertension, insulin resistance/hyperglycemia, and hyperlipidemia, along with central obesity, are components of the metabolic syndrome. Metabolic Syndrome, heart and kidney diseases
  • Certain medications
    • Thiazide Thiazide Heterocyclic compounds with sulfur and nitrogen in the ring. This term commonly refers to the benzothiadiazines that inhibit sodium-potassium-chloride symporters and are used as diuretics. Hyponatremia diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication
    • Low-dose aspirin Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Nonsteroidal Antiinflammatory Drugs (NSAIDs) 
    • Anti-rejection/ immunosuppressive drugs Immunosuppressive drugs Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-cells or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. Organ Transplantation used in organ transplantation Organ Transplantation Transplantation is a procedure that involves the removal of an organ or living tissue and placing it into a different part of the body or into a different person. Organ transplantations have become the therapeutic option of choice for many individuals with end-stage organ failure. Organ Transplantation
  • Family history Family History Adult Health Maintenance of gout
  • Age and sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria: higher prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency in middle-aged and older men, but UA levels in post-menopausal women approach those of men
  • Recent surgery or trauma
  • Dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration

Mnemonic

Drugs causing acute precipitation of gout: FACT

F: Furosemide diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication

A: Aspirin/Alcohol

C: Anti-Cancer drugs (e.g., cyclosporine Cyclosporine A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. Immunosuppressants)

T: Thiazide diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication

Pathophysiology

  • Purine compounds, whether they are synthesized in the body or come from eating high-purine foods, can raise UA levels.
  • Uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis is excreted mainly through the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy.
  • Overproduction or underexcretion (more common) of UA can lead to hyperuricemia → supersaturation → deposition of monosodium urate (MSU) crystals in the tissues
  • These MSU deposit in the soft tissue Soft Tissue Soft Tissue Abscess and synovium as MSUcrystals (“tophi”).
    • Can erode the 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. Bones: Structure and Types and damage other tissues such as tendons and cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage: Histology
    • Cause recurrent monoarticular arthritis Monoarticular Arthritis Septic Arthritis and chronic deforming arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis 
  • The precise relationship between hyperuricemia and gout is unclear:
    • The majority (90%) of people with hyperuricemia do not have gout.
    • Normal or low serum UA levels do not rule out gout.
    • However, all patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with gout will have hyperuricemia (> 6.8 mg/dL) at some point, although levels may fluctuate.

Clinical Presentation

Gout flares

  • Typically monoarticular (< 20% are polyarticular)
  • Commonly occurs in the lower extremities, most often at the base of the great toe (first metatarsophalangeal [MTP] joint, or podagra) or the knee
  • Intensely inflammatory, causing severe pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, redness Redness Inflammation, warmth, swelling Swelling Inflammation, and disability Disability Determination of the degree of a physical, mental, or emotional handicap. The diagnosis is applied to legal qualification for benefits and income under disability insurance and to eligibility for social security and workman’s compensation benefits. ABCDE Assessment
  • Peaking within 1224 hours and resolving within 310 days even without treatment
  • Onset more often at night

Intercritical gout

Upon resolution of an acute gout flare, patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship enter an intercritical (between-flares) period.

  • Most often entirely asymptomatic
  • Variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables in duration
  • Most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship left untreated will develop a recurrent flare within 2 years.
  • Monosodium urate crystals may continue to deposit as tophi in various tissues.

Tophaceous gout

  • Nodular deposit of monosodium urate crystals associated with chronic inflammation Chronic Inflammation Inflammation with a foreign-body giant cell reaction
  • Found in cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage: Histology, subcutaneous and periarticular tissues, tendons (e.g., Achilles tendon), olecranon Olecranon A prominent projection of the ulna that articulates with the humerus and forms the outer protuberance of the elbow joint. Arm: Anatomy bursae, ear helix, kidney, and elsewhere
  • Can cause destruction of 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. Bones: Structure and Types and soft tissue Soft Tissue Soft Tissue Abscess

Associated renal complications

  • Nephrolithiasis Nephrolithiasis Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis
  • Chronic urate nephropathy

Related videos

Diagnosis

  • Diagnosis is established via microscopic analysis of the joint aspirate, which shows:
    • Crystals of MSU, which are negatively birefringent (yellow when parallel to compensator filter) and needle-shaped
    • WBC > 2,000/μL with > 50% neutrophils Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. Innate Immunity: Phagocytes and Antigen Presentation (an acute inflammatory synovial fluid)
  • X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests:
    • Shows no changes early in the disease
    • As the disease progresses, punched-out erosions Erosions Corneal Abrasions, Erosion, and Ulcers with an overhanging rim of cortical 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. Bones: Structure and Types develop.
  • Blood work may show:
Monosodium urate crystals in elbow joint fluid - gout

Monosodium urate crystals, negatively birefringent (appearing as needle-like yellow crystals when parallel to the polarizing light with a red compensator, and blue when perpendicular), from a patient’s joint aspirate. This finding is diagnostic of gout.

Image: “Monosodium Urate Crystals in Elbow Joint Fluid” by Ed Uthman. License: CC BY 2.0

Management

Management differs for acute and chronic gout.

Acute gout

The goal of management is to reduce inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation.

  • Nonsteroidal anti-inflammatory drugs ( NSAIDs NSAIDS Primary vs Secondary Headaches): contraindicated in active peptic ulcer Peptic ulcer Peptic ulcer disease (PUD) refers to the full-thickness ulcerations of duodenal or gastric mucosa. The ulcerations form when exposure to acid and digestive enzymes overcomes mucosal defense mechanisms. The most common etiologies include Helicobacter pylori (H. pylori) infection and prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs). Peptic Ulcer Disease disease, impaired kidney function, heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR), and elevated international normalized ratio International normalized ratio System established by the world health organization and the international committee on thrombosis and hemostasis for monitoring and reporting blood coagulation tests. Under this system, results are standardized using the international sensitivity index for the particular test reagent/instrument combination used. Hemostasis (INR)
  • Colchicine Colchicine A major alkaloid from colchicum autumnale l. And found also in other colchicum species. Its primary therapeutic use is in the treatment of gout. Gout Drugs: contraindicated in severe renal or 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: Anatomy disease
  • Glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids: can be given via IV, IM, oral, or intra-articular routes. Make sure to rule out septic arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis before giving corticosteroids Corticosteroids Chorioretinitis.
  • Antihyperuricemic drugs ( allopurinol Allopurinol A xanthine oxidase inhibitor that decreases uric acid production. It also acts as an antimetabolite on some simpler organisms. Gout Drugs and febuxostat Febuxostat A thiazole derivative and inhibitor of xanthine oxidase that is used for the treatment of hyperuricemia in patients with chronic gout. Gout Drugs) are usually contraindicated/not recommended in an acute attack as they may cause the disease to flare up.
Management of acute gout algorithm

Algorithm for the management of acute gout

Image by Lecturio.

Chronic gout

The goal of management is to minimize urate deposition in tissues.

General measures

  • Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery to achieve BMI BMI An indicator of body density as determined by the relationship of body weight to body height. Bmi=weight (kg)/height squared (m2). Bmi correlates with body fat (adipose tissue). Their relationship varies with age and gender. For adults, bmi falls into these categories: below 18. 5 (underweight); 18. 5-24. 9 (normal); 25. 0-29. 9 (overweight); 30. 0 and above (obese). Obesity < 25
  • Avoid foods with a high purine content (e.g., seafood, meat, alcohol [varies among different beverages])
  • Avoid certain medications that cause hyperuricemia

Medical measures

  • Indications to start medical management for chronic gout are recurrent attacks (> 1/year), tophi, and urate kidney stones Kidney stones Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis.
  • Antihyperuricemic drugs ( allopurinol Allopurinol A xanthine oxidase inhibitor that decreases uric acid production. It also acts as an antimetabolite on some simpler organisms. Gout Drugs and febuxostat Febuxostat A thiazole derivative and inhibitor of xanthine oxidase that is used for the treatment of hyperuricemia in patients with chronic gout. Gout Drugs) decrease UA production by inhibiting xanthine oxidase Oxidase Neisseria (an enzyme involved in endogenous purine synthesis Synthesis Polymerase Chain Reaction (PCR)).
  • Uricosuric drugs ( probenecid Probenecid The prototypical uricosuric agent. It inhibits the renal excretion of organic anions and reduces tubular reabsorption of urate. Probenecid has also been used to treat patients with renal impairment, and, because it reduces the renal tubular excretion of other drugs, has been used as an adjunct to antibacterial therapy. Gout Drugs) are used very rarely.
  • Give prophylactic colchicine Colchicine A major alkaloid from colchicum autumnale l. And found also in other colchicum species. Its primary therapeutic use is in the treatment of gout. Gout Drugs/ NSAIDs NSAIDS Primary vs Secondary Headaches prior to starting antihyperuricemic drugs to avoid flare-ups.
  • Newer medication: pegloticase Pegloticase Gout Drugs, a recombinant pegylated (i.e., linked to methoxy polyethylene glycol Polyethylene Glycol Laxatives) uricase.
Gout management diagram

Summary of the pathophysiology and drugs used for gout

Image by Lecturio.

Differential Diagnosis

The following conditions are differential diagnoses of gout:

  • Septic arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis: an infection of a joint with extremely high WBC counts in synovial fluid (> 100,000 cells/mL) are most supportive of a diagnosis of septic arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis. Gram stain Gram stain Klebsiella and synovial fluid culture are performed for diagnosis.
  • Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes pyrophosphate crystal deposition disease (CPPD, pseudogout): positively birefringent crystals in synovial fluid. Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes pyrophosphate crystal deposition disease also has a characteristic radiographic appearance of chondrocalcinosis Chondrocalcinosis Presence of calcium pyrophosphate in the connective tissues such as the cartilaginous structures of joints. When accompanied by gout-like symptoms, it is referred to as pseudogout. Gitelman Syndrome
  • Trauma: a stress fracture Fracture A fracture is a disruption of the cortex of any bone and periosteum and is commonly due to mechanical stress after an injury or accident. Open fractures due to trauma can be a medical emergency. Fractures are frequently associated with automobile accidents, workplace injuries, and trauma. Overview of Bone Fractures or traumatic process in the 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. Bones: Structure and Types or joint can mimic a gout flare.
  • 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: a 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. Skin: Structure and Functions infection that affects the deeper layers of the dermis Dermis A layer of vascularized connective tissue underneath the epidermis. The surface of the dermis contains innervated papillae. Embedded in or beneath the dermis are sweat glands; hair follicles; and sebaceous glands. Skin: Structure and Functions and subcutaneous tissue Subcutaneous tissue Loose connective tissue lying under the dermis, which binds skin loosely to subjacent tissues. It may contain a pad of adipocytes, which vary in number according to the area of the body and vary in size according to the nutritional state. Soft Tissue Abscess. Typical signs of acute inflammation Acute Inflammation Inflammation ( rubor Rubor Inflammation, dolor Dolor Inflammation, calor Calor Inflammation, tumor Tumor Inflammation) are present but joint mobility is usually preserved.
  • Rheumatoid arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis: an autoimmune inflammatory polyarthritis Polyarthritis Rheumatoid Arthritis. Tophi may be mistaken for rheumatoid nodules Rheumatoid Nodules Rheumatoid Arthritis but the clinicoradiological presentation and the lack of crystals in the nodular lesions can differentiate the 2 conditions.
  • Dactylitis Dactylitis Ankylosing Spondylitis: severe bacterial inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the finger and toe joints that can resemble tophaceous gout with acute flare. The condition can usually be distinguished from gout based on the history and physical examination.
  • 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: an infection (usually bacterial) of the 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. Bones: Structure and Types. Diagnosis is made by noting deep bony tenderness and clinical signs of acute systemic inflammation Systemic Inflammation Surgical Site Infections; CBC and magnetic resonance imaging (MRI) are helpful if routine radiologic findings are not supportive.
  • Basic calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes (BCP) crystal disease (hydroxyapatite [ HA HA 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] crystal deposition disease): painful and probably underdiagnosed periarthritis or arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis due to the deposition of BCP crystals in the synovium. The condition can cause severe joint damage, as in the Milwaukee shoulder syndrome seen in elderly women.

References

  1. Horvai H. (2020). In Kumar, V., Abbas, A. K., Aster, J.C., (Eds.), Robbins & Cotran Pathologic Basis of Disease. (10 ed., pp. 12046). Elsevier, Inc.
  2. Juraschek SP, Miller ER 3rd, Gelber AC. Body mass index, obesity, and prevalent gout in the United States in 19881994 and 2007-2010. Arthritis Care Res (Hoboken). 2013 Jan;65(1):12732. 
  3. Gaffo AL. (2019). Clinical manifestations and diagnosis of gout. Retrieved on August 31, 2020, from https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-gout#H87540416
  4. Schumacher HR, Chen LX. (2018). In Jameson JL, et al. (Ed.), Harrison’s Principles of Internal Medicine (20th ed. Vol 2, pp. 26312633). 
  5. Le T, Bhusan V, Sochat M, et al (Eds.) (2020).  First Aid for the USMLE Step 1, 30th ed. (p. 467).

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