128: Calcium & Mineral Depositon Disorders Flashcards
(145 cards)
1
Q
What are the three hormones that control calcium concentration in the serum?
A
- Parathyroid hormone (PTH)
- Calcitonin
- 1,25-dihydroxyvitamin D3 (1,25(OH2)D3)
2
Q
What is the function of Parathyroid hormone (PTH)?
A
- Increases calcium concentration in the serum
- Increases renal tubular reabsorption of calcium
- Increases renal clearance of phosphate
- Stimulates osteoclastic bone resorption by mobilizing calcium from bone
3
Q
What is the role of calcitonin in calcium regulation?
A
- Lowers serum calcium concentration
- Inhibits osteoclast activity, leading to decreased calcium release from bones
4
Q
How does 1,25-dihydroxyvitamin D3 (1,25(OH2)D3) affect calcium levels?
A
- Increases plasma calcium concentration
- Stimulates active transport of calcium across the intestine
- Mobilizes calcium from bones, requiring the presence of PTH for this effect
5
Q
What is calcification and how does it relate to cutaneous tissues?
A
- Calcification is the deposition of insoluble calcium salts.
- When it occurs in cutaneous tissues, it is known as calcinosis cutis.
- It commonly occurs secondary to local tissue alteration or preexisting calcification.
6
Q
What is ossification and how does it differ from calcification?
A
- Ossification is the formation of true bony tissue by deposition of calcium and phosphorus in a proteinaceous matrix as hydroxyapatite crystals.
- Unlike calcification, ossification involves the creation of bone tissue, which may occur without underlying tissue abnormalities.
7
Q
What are the major classifications of cutaneous calcification?
A
Classification | Description |
|—————-|————-|
| Dystrophic | Most common; occurs due to local tissue injury; calcium and phosphate metabolism and serum levels are normal.
| Metastatic | Occurs due to elevated serum calcium levels, affecting multiple tissues.
8
Q
What are the results of calcium salt deposition in tissues?
A
Calcium salts deposit in the dermis, subcutaneous tissue, or vascular endothelium when local calcium concentration exceeds its solubility in the tissue.
9
Q
What are the categories of calcium deposition disorders?
A
Dystrophic, metastatic, idiopathic, and iatrogenic.
10
Q
What is the primary function of calcium in the body?
A
Calcium is key to skeletal muscle and myocardial contraction, neurotransmission, and blood coagulation.
11
Q
What hormones control ionic calcium concentration in the serum?
A
Parathyroid hormone (PTH), calcitonin, and 1,25-dihydroxyvitamin D3 (1,25(OH2)D3).
12
Q
What is the effect of parathyroid hormone (PTH) on calcium levels?
A
PTH increases calcium concentration by mobilizing calcium from bones and increasing renal tubular reabsorption of calcium.
13
Q
What is the role of calcitonin in calcium regulation?
A
Calcitonin lowers serum calcium concentration by inhibiting osteoclast activity.
14
Q
How is vitamin D3 activated in the body?
A
Vitamin D3 is hydroxylated in the liver and then in the kidney to become biologically active.
15
Q
What is calcification and how does it occur in tissues?
A
Calcification is the deposition of insoluble calcium salts, often occurring secondary to local tissue alteration or preexisting calcification.
16
Q
What is ossification?
A
Ossification is the formation of true bony tissue by deposition of calcium and phosphorus in a proteinaceous matrix as hydroxyapatite crystals.
17
Q
What are the major classifications of cutaneous calcification?
A
Dystrophic and metastatic calcification are the major classifications, with dystrophic being the most common due to local tissue injury.
18
Q
Explain the role of parathyroid hormone (PTH) in calcium regulation.
A
PTH increases calcium concentration by enhancing renal tubular reabsorption of calcium, increasing renal clearance of phosphate, and stimulating 1α-hydroxylase activity to increase 1,25(OH)2D3 levels, which boosts intestinal calcium absorption. It also mobilizes calcium from bones by stimulating osteoblasts to release factors that activate osteoclasts.
19
Q
What is the role of vitamin D3 in calcium homeostasis?
A
Vitamin D3 increases plasma calcium concentration by stimulating active calcium transport across the intestine and mobilizing calcium from bones. It also regulates growth and differentiation of the skin through the vitamin D receptor (VDR).
20
Q
What is the difference between calcification and ossification?
A
Calcification refers to the accumulation of calcium salts in body tissue, which can occur in various conditions, while ossification is the process of bone formation, where cartilage is replaced by bone tissue. Calcification can occur in soft tissues, whereas ossification specifically pertains to bone.
21
Q
What is the most common type of calcification?
A
The most common type of calcification is dystrophic calcification, which occurs in damaged or necrotic tissues, regardless of serum calcium levels.
22
Q
What type of calcification is associated with an underlying defect in calcium and/or phosphate metabolism?
A
Metastatic calcification is associated with an underlying defect in calcium and/or phosphate metabolism, leading to abnormal deposition of calcium salts in normal tissues.
23
Q
What type of calcification is related to local tissue injury?
A
Dystrophic calcification is related to local tissue injury, occurring in areas of tissue damage or necrosis, regardless of serum calcium levels.
24
Q
What type of calcification has no identifiable tissue abnormality?
A
Idiopathic calcification occurs without identifiable tissue abnormalities, despite abnormal calcium and/or phosphate metabolism.
25
What type of calcification has normal serum and phosphate metabolism but abnormalities in collagen?
Iatrogenic calcification can occur with normal serum and phosphate metabolism but may involve abnormalities in collagen, often due to medical interventions or treatments.
26
What is dystrophic calcification?
Calcification that occurs in damaged or necrotic tissue, often associated with underlying defects in calcium and/or phosphate metabolism.
27
What are the common cutaneous lesions associated with scleroderma and CREST syndrome?
Nodules and plaques develop in skin, subcutaneous tissue, muscle, or tendons, primarily in the upper extremities.
28
What is the treatment for calcinosis cutis in scleroderma?
There is no standard treatment, but a diet low in calcium and phosphate along with aluminum hydroxide may help.
29
What is the most common type of calcification?
Dystrophic calcification.
30
What type of calcification is associated with local tissue injury?
Metastatic calcification.
31
What type of calcification occurs with an underlying defect in calcium and/or phosphate metabolism?
Idiopathic calcification.
32
What type of calcification has no identifiable tissue abnormality?
Iatrogenic calcification.
33
What is the significance of serum fetuin-A levels in pseudoxanthoma elasticum?
Patients have significantly reduced serum fetuin-A levels, which may allow increased calcification of elastic fibers.
34
Describe the pathogenesis of dystrophic calcification and its common causes.
Dystrophic calcification occurs due to local tissue injury, where calcium and phosphate metabolism and serum levels are normal. Local tissue abnormalities, such as in collagen, elastin, or subcutaneous fat, may trigger calcification. Internal organs remain unaffected.
35
What are the clinical features and treatment options for calcinosis cutis in CREST syndrome?
Calcinosis cutis in CREST syndrome presents as nodules and plaques in the skin, subcutaneous tissue, muscle, or tendons, most commonly in the upper extremities. Enlarged calcifications may ulcerate and exude chalky material. Treatment includes a low-calcium and phosphate diet, aluminum hydroxide, disodium etidronate, diltiazem, and surgical removal of calcium deposits.
36
What is the difference between calcification and ossification?
Calcification is the deposition of insoluble calcium salts, while ossification is the formation of true bony tissue by depositing calcium and phosphorus in a proteinaceous matrix as hydroxyapatite crystals.
37
What are the treatment options for calcinosis cutis in dermatomyositis?
Treatment includes aggressive early management of juvenile dermatomyositis, which reduces calcinosis occurrence. Calcinosis may improve spontaneously, but treatment is generally difficult.
38
What are the clinical features of calcinosis universalis in dermatomyositis?
Calcinosis universalis involves extensive calcium deposition along fascial planes, skin, and muscle, forming an 'exoskeleton.' It is associated with significant morbidity and mortality.
39
What are the clinical features of subcutaneous fat necrosis of the newborn?
Subcutaneous fat necrosis of the newborn presents as erythematous nodules and plaques over the cheeks, back, buttocks, and extremities. Lesions may calcify and clear spontaneously.
40
What are the clinical features of pancreatic panniculitis?
Pancreatic panniculitis occurs in patients with pancreatitis or pancreatic adenocarcinoma. It presents as erythematous nodules caused by calcium soap formation from fatty acids.
41
A patient presents with nodules and plaques in the skin, subcutaneous tissue, and tendons, along with esophageal dysfunction and telangiectasia. What condition might this indicate?
This presentation is indicative of CREST syndrome (Calcinosis cutis, Raynaud phenomenon, esophageal dysfunction, sclerodactyly, telangiectasia).
42
A young patient develops erythematous nodules over the cheeks and buttocks, which later calcify. What condition could this be?
This could be subcutaneous fat necrosis of the newborn, which occurs in the first few weeks of life and may lead to calcification.
43
A patient with juvenile dermatomyositis develops calcinosis universalis. What does this condition involve?
Calcinosis universalis involves extensive calcium deposition along fascial planes, skin, and muscle, forming an 'exoskeleton' and is associated with significant morbidity and mortality.
44
A patient with scleroderma develops nodules and plaques in the upper extremities that ulcerate and exude chalky material. What is the recommended treatment?
Treatment options include a diet low in calcium and phosphate, aluminum hydroxide, disodium etidronate, diltiazem, and surgical removal of calcium deposits.
45
A patient with CREST syndrome develops calcinosis cutis. What is the most common site of deposition?
The most common site of deposition is the upper extremities, such as fingers and wrists.
46
A patient with juvenile dermatomyositis develops calcinosis on the elbows and knees. What is the recommended approach to reduce its occurrence?
Aggressive early treatment of juvenile dermatomyositis is associated with a decrease in the occurrence of dystrophic calcification.
47
What is the relationship between chronic renal failure and metastatic calcification?
Chronic renal failure leads to decreased clearance of phosphate, resulting in hyperphosphatemia. This condition impairs the production of 1,25(OH2)D3, decreasing calcium absorption and leading to hypocalcemia. The hypocalcemia stimulates increased PTH production, causing bone resorption and mobilization of calcium and phosphate into the serum, which can result in marked hyperphosphatemia. If the solubility product of calcium and phosphate is exceeded, metastatic calcification occurs, leading to either benign nodular calcification or calciphylaxis.
48
What are the clinical features of calciphylaxis?
Calciphylaxis is characterized by:
1. **Progressive vascular calcification**
2. **Soft tissue necrosis**
3. **Ischemic necrosis of the skin**
4. **Presentation**: Firm, extremely painful, reticulated violaceous plaques associated with soft tissue necrosis and ulceration.
5. **Common sites**: Lower extremities are most frequent.
6. **Mortality rate**: Approximately 80%, usually due to gangrene and sepsis.
49
What are the key features of benign nodular calcification?
Benign nodular calcification features include:
- Occurs at **periarticular sites**
- Size and number correlate with the degree of **hyperphosphatemia**
- Usually **asymptomatic** except for mass effect
- Disappears with normalization of calcium and phosphate levels
- May require **surgical removal** if interfering with function
- Reported following subcutaneous administration of LMW heparin in renal transplant patients, resolving after cessation of nadoparin.
50
What are the common cutaneous neoplasms associated with calcification and ossification?
Common cutaneous neoplasms associated with calcification and ossification include:
| Neoplasm | Calcification (%) | Ossification (%) |
|----------|------------------|------------------|
| Pilomatricomas | 75% | 15-20% |
| Desmoplastic malignant melanoma | Rare | Rare |
| Atypical fibroxanthoma | Rare | Rare |
| Hemangioma | Rare | Rare |
| Neuilemmoma | Rare | Rare |
| Trichoepithelioma | Rare | Rare |
| Seborrheic keratosis | Rare | Rare |
| Mixed tumors (chondroid syringomas) | Rare | Rare |
51
What is metastatic calcification and what conditions can lead to it?
Metastatic calcification occurs when the solubility product of calcium and phosphate is exceeded, often due to chronic renal failure, leading to hyperphosphatemia and secondary hyperparathyroidism.
52
What are the characteristics of benign nodular calcification?
Benign nodular calcification occurs at periarticular sites, correlates with hyperphosphatemia, is usually asymptomatic, and may require surgical removal if it interferes with function.
53
What is calciphyaxis and in which patients does it occur?
Calciphyaxis is a life-threatening disorder characterized by vascular calcification and soft tissue necrosis, occurring almost exclusively in patients with chronic renal failure and prolonged secondary hyperparathyroidism.
54
What are the common cutaneous neoplasms associated with calcification?
Common cutaneous neoplasms include pilomatricomas, which show calcification and ossification, and other tumors like pilar cysts and seborrheic keratosis.
55
What role does the APC gene play in pilomatricomas?
Mutations in the APC gene or β-catenin gene are associated with pilomatricomas, which are the most common cutaneous neoplasms with calcification and ossification.
56
What are the potential infectious agents that can cause dystrophic calcification?
Infectious agents such as Onchocerca volvulus and Taenia solium can cause enough damage to lead to dystrophic calcification.
57
What is the significance of hyperphosphatemia in chronic renal failure?
Hyperphosphatemia results from decreased clearance of phosphate in chronic renal failure, leading to increased PTH production and subsequent complications like metastatic calcification.
58
What are the clinical features of pseudoxanthoma elasticum?
Pseudoxanthoma elasticum is characterized by progressive calcification of elastin fibers in the skin, Bruch's membranes of the retina, and the cardiovascular system. Patients often have reduced serum fetuin-A levels, an anti-mineralization protein.
59
What is the role of β-catenin in ossification in pilomatricomas?
β-catenin signaling is necessary for bone morphogenic protein 2-dependent ossification in pilomatricomas. High levels of β-catenin are due to mutations in the APC gene or activating mutations in the β-catenin gene.
60
What are the clinical features of porphyria cutanea tarda?
Porphyria cutanea tarda presents with sclerodermoid plaques and dystrophic calcification, often on the preauricular area, scalp, neck, and hands. Ulceration with transepidermal elimination of calcium sheets may occur.
61
What are the clinical features of Werner syndrome?
Werner syndrome is a genetic disorder associated with premature aging, including calcification and ossification abnormalities.
62
What are the clinical features of Rothmund-Thomson syndrome?
Rothmund-Thomson syndrome is a genetic disorder associated with skin abnormalities, including calcification and ossification.
63
What mutation is associated with pseudoxanthoma elasticum?
The condition is associated with an ABCC6 mutation, which affects transmembrane transport.
64
What is the underlying cause of subcutaneous nodules in Ehlers-Danlos syndrome?
The nodules are due to disorders of fibrillar collagen metabolism caused by mutations in collagen genes or enzymes regulating collagen biosynthesis.
65
Where are sclerodermoid plaques commonly located in porphyria cutanea tarda?
The plaques are commonly located on the preauricular area, scalp, neck, and dorsa of the hands.
66
What signaling pathway is involved in ossification within pilomatricomas?
The ossification is mediated by β-catenin signaling, which is necessary for bone morphogenic protein 2-dependent ossification.
67
What is the anti-mineralization protein reduced in pseudoxanthoma elasticum?
The protein is fetuin-A, which helps prevent calcification of elastic fibers.
68
What causes calcification of healing surgical incisions in Ehlers-Danlos syndrome?
The calcification is due to disorders of fibrillar collagen metabolism.
69
What is the treatment approach for porphyria cutanea tarda with ulceration?
Treatment involves managing the underlying porphyria and addressing the calcification.
70
What is the multifaceted approach to managing calcium-phosphate product abnormalities in calciphylaxis?
The management includes: 1. Low calcium dialysis 2. Use of phosphate binders that combine calcium acetate and magnesium carbonate 3. Parathyroidectomy (when medical management fails) 4. Other possible treatments: pamidronate, cinacalcet, hyperbaric oxygen, low-dose tissue plasminogen activator 5. Sodium thiosulfate, which has antioxidant effects and enhances calcium chelation, though its exact mechanism is unknown. 6. Aggressive management of wound infections and judicious use of debridement to lower the incidence of sepsis and death.
71
What are the initial signs and symptoms of hypervitaminosis D?
Initial signs and symptoms include: - Weakness - Lethargy - Headache - Nausea - Polyuria.
72
What characterizes tumoral calcinosis?
Tumoral calcinosis is characterized by: - Deposition of calcific masses around major joints (hips, shoulders, elbows, knees) - Masses can be intramuscular or subcutaneous and may enlarge, causing significant impairment of joint function.
73
What is idiopathic calcification of the scrotum?
Idiopathic calcification of the scrotum appears in otherwise healthy males and tends to increase in size and number over time. Eventually, they may break down and exude a chalky material. Histologically, it shows epidermal cysts with inflamed cysts and calcium deposits.
74
What complications can arise from IV calcium chloride and calcium gluconate therapy?
Complications include: - Calcified nodules may appear at sites of extravasation due to elevated tissue concentration of calcium and tissue damage. - A secondary inflammatory response can result in calcium deposits being either absorbed or transdermally eliminated.
75
What is the primary cause of hypervitaminosis D?
Chronic ingestion of vitamin D in supraphysiologic doses.
76
What is Milk-Alkali Syndrome associated with?
Excessive ingestion of calcium-containing foods or antacids leading to hypercalcemia.
77
What are the complications of Milk-Alkali Syndrome?
Irreversible renal failure, nephrocalcinosis, and subcutaneous calcification.
78
What are the clinical features of subepidermal calcified nodules?
Subepidermal calcified nodules appear as hard, solitary lesions on exposed areas of the head and extremities in children. They may be congenital or acquired.
79
What are the clinical features of idiopathic calcification of the scrotum?
Idiopathic calcification of the scrotum appears as nodules that increase in size and number over time, potentially breaking down to exude chalky material. Histology suggests dystrophic calcification of cysts.
80
What are the clinical features of milk-alkali syndrome?
Milk-alkali syndrome results from excessive ingestion of calcium-containing foods or antacids, leading to hypercalcemia, nephrocalcinosis, and subcutaneous calcification, predominantly in periarticular tissues.
81
What are the clinical features of tumoral calcinosis?
Tumoral calcinosis involves calcific masses around major joints, such as hips and shoulders, which may impair joint function. It can be sporadic or familial, with familial cases linked to GALNT3, KLOTHO, and FGF23 mutations.
82
What is the likely diagnosis for a patient with chronic renal failure and firm, painful plaques on the lower extremities?
The likely diagnosis is calciphylaxis, a life-threatening disorder characterized by progressive vascular calcification and ischemic necrosis of the skin.
83
What is the likely condition for a patient with deposition of calcific masses around major joints?
The likely condition is tumoral calcinosis, characterized by calcific masses around major joints.
84
What is benign nodular calcification in a patient with chronic renal failure?
This condition is benign nodular calcification, which occurs at periarticular sites and is usually asymptomatic.
85
What is the treatment approach for a patient with chronic renal failure and calciphylaxis?
Treatment includes normalizing calcium-phosphate product, low calcium dialysis, phosphate binders, parathyroidectomy, and sodium thiosulfate.
86
What is the likely cause of hypercalcemia and nephrolithiasis in a patient with hypervitaminosis D?
The likely cause is chronic ingestion of vitamin D in supraphysiologic doses (50,000-100,000 units/day).
87
What is the likely diagnosis for a patient with calcific masses around major joints and normal overlying skin?
The likely diagnosis is tumoral calcinosis, which may be sporadic or familial.
88
What is the underlying cause of metastatic calcification in chronic renal failure?
The underlying cause is hyperphosphatemia and secondary hyperparathyroidism, leading to calcium and phosphate mobilization into the serum.
89
What is the mortality rate of calciphylaxis?
The mortality rate of calciphylaxis is approximately 80%, usually due to gangrene and sepsis.
90
What are the initial symptoms of hypervitaminosis D?
Initial symptoms include weakness, lethargy, headache, nausea, and polyuria.
91
What gene mutations are associated with familial tumoral calcinosis?
Mutations in GALNT3, KLOTHO, and FGF23 are associated with familial tumoral calcinosis.
92
What are the common sites of metastatic calcification in chronic renal failure?
Common sites include blood vessels, kidneys, lungs, and gastric mucosa.
93
What are the primary characteristics of Fibrodysplasia Ossificans Progressiva (FOP)?
- Autosomal dominant disorder
- Caused by ACVR1/ALK2 mutation of the activin gene (gain-of-function)
- Leads to overactive BMP signaling, resulting in ectopic bone formation
- Progressive ossification of deep connective tissues, leading to significant morbidity and mortality
- Endochondral type of ossification, with skin involvement as a result of direct extension from underlying tissues
- Characteristic features include dysmorphic great toes, abnormal phalanges of hands, hearing loss, cognitive impairment, and cataracts.
94
What are the key features of Albright Hereditary Osteodystrophy (AHO)?
- Autosomal dominant disorder characterized by ossification of cutaneous and subcutaneous tissues in childhood
- Features include brachydactyly dimpling over the metacarpophalangeal joints (Albright sign), obesity, round or moon facies, short stature, and mental retardation
- Most patients have a deficient end-organ response to PTH or pseudohypoparathyroidism with hypocalcemia and hyperphosphatemia.
- Inheritance of an inactivating mutation in GNAS1 from the mother results in pseudohypoparathyroidism Type Ia, while paternal inheritance leads to POH.
95
What is Progressive Osseous Heteroplasia (POH) and its clinical features?
- Progressive ossification of skin and deep tissues during infancy or childhood
- Ossification begins in the dermis and progresses to involve deeper tissues, such as muscle and overlying skin
- Skin involvement described as a papular eruption resembling 'rice grains' with a gritty consistency
- Bone formation is most commonly intramembranous, with criteria including progressive heterotopic ossification and no parathyroid hormone resistance.
- Secondary orthopedic problems may arise if cutaneous ossification is severe enough to limit motion.
96
What is the significance of miliary osteoma cutis?
- Miliary osteoma cutis commonly occurs as multiple small, firm nodules on the faces of young women with a history of acne vulgaris.
- There are reports of multiple miliary osteoma cutis in older patients without acne vulgaris or other underlying skin disease, indicating its potential occurrence independent of acne.
97
What is the typical presentation of Miliary Osteoma Cutis?
Occurs as multiple small, firm nodules on the faces of young women with a history of acne vulgaris.
98
What is the significance of the 'rice grains' appearance in skin involvement?
It indicates skin involvement in Progressive Osseous Heteroplasia, resembling a papular eruption with a gritty consistency.
99
What are the common features of patients with Platelike Osteoma Cutis?
They appear to have forms of frustes of AHO or POH, indicating a connection to these syndromes.
100
What are the clinical features of fibrodysplasia ossificans progressiva (FOP)?
FOP is an autosomal dominant disorder caused by ACVR1/ALK2 mutations, leading to progressive ossification of deep connective tissues. Features include dysmorphic great toes, abnormal phalanges, hearing loss, and mild cognitive impairment.
101
What are the clinical features of Albright hereditary osteodystrophy (AHO)?
AHO is characterized by intramembranous bone formation in the skin, brachydactyly, dimpling over metacarpophalangeal joints, obesity, round facies, short stature, and mental retardation. It is associated with inactivating mutations in the GNAS1 gene.
102
What are the clinical features of progressive osseous heteroplasia (POH)?
POH involves progressive ossification of skin and deep tissues during infancy or childhood. Ossification begins in the dermis and progresses to deeper tissues, potentially causing limb-length discrepancies or joint ankylosis.
103
What are the clinical features of miliary osteoma cutis of the face?
Miliary osteoma cutis of the face presents as multiple small, firm nodules, often in young women with a history of acne vulgaris.
104
What is the condition called when a patient with Down syndrome presents with calcinosis cutis on the dorsal hands and forearms?
This condition is called milia-like idiopathic calcinosis cutis.
105
What is the likely diagnosis for a patient with a history of acne vulgaris who develops multiple small, firm nodules on the face?
The likely diagnosis is miliary osteoma cutis of the face, commonly associated with a history of acne vulgaris.
106
What is the likely diagnosis for a patient presenting with progressive ossification of deep connective tissues, abnormal phalanges of the hands, and hearing loss?
The likely diagnosis is Fibrodysplasia Ossificans Progressiva (FOP), an autosomal dominant condition caused by a mutation in the ACVR1/ALK2 gene.
107
What is the histological finding in a patient with Down syndrome who develops calcinosis cutis on the dorsal hands and forearms?
The histological finding includes calcified sweat gland hamartomas.
108
What is the treatment of choice for a patient with idiopathic calcification of the scrotum who develops nodules that exude chalky material?
The treatment of choice is excision, although new nodules may develop at other sites.
109
What is hyperuricemia and its significance in gout?
Hyperuricemia is a risk factor for gout, but acute gouty arthritis may also occur in patients with normal serum uric acid levels.
110
What is the clinical syndrome characterized by the deposition of monosodium urate crystals in joints and synovial fluid?
Gout is a clinical syndrome caused by a group of heterogeneous diseases characterized by the deposition of monosodium urate crystals in synovial fluid and joints, which can occur with or without hyperuricemia, renal disease, or nephrolithiasis.
111
What are the common risk factors associated with gout?
Common risk factors for gout include alcohol consumption, purine-rich foods (meat and seafood), obesity, and renal insufficiency.
112
What are the four stages of gout?
Gout can be divided into four stages: 1) Asymptomatic hyperuricemia, 2) Acute gouty arthritis, 3) Intercritical gout (between gouty attacks), 4) Chronic tophaceous gout.
113
What is the most common site of initial involvement in acute gouty arthritis?
The most common site of initial involvement in acute gouty arthritis is the first metatarsophalangeal joint, also known as podagra.
114
What are the clinical manifestations of acute gouty arthritis?
Clinical manifestations of acute gouty arthritis include sudden onset of joint pain, usually in the lower extremities. The affected joint is erythematous and exquisitely tender to palpation.
115
What is the goal of therapy for acute gout?
The goal of therapy for acute gout is analgesia and reduction in inflammation.
116
What are the first-line treatments for acute gout?
NSAIDs and Colchicine.
117
What is the recommended dosing regimen for colchicine to reduce GI side effects?
1.2 mg followed in 1 hour by 0.6 mg.
118
What is the role of corticosteroids in gout treatment?
Both oral and intraarticular corticosteroids are believed to be effective.
119
What dietary adjustments are recommended for patients with gout?
Dietary adjustments for patients with gout include decreasing purine intake, avoiding drugs that decrease uric acid excretion, maintaining adequate hydration, losing weight, and controlling hypertension and hyperlipidemia.
120
What is the first-line drug for lowering serum urate in gout patients?
The first-line drug for lowering serum urate in gout patients is Allopurinol.
121
What is the recommended urate level to maintain in patients with tophi or frequent gout attacks?
The recommended urate level to maintain in patients with tophi or frequent gout attacks is consistently at < 6 mg/dL.
122
What are common side effects of allopurinol?
Common side effects associated with Allopurinol include dyspepsia, headache, diarrhea, pruritic papular eruption, thrombocytopenia, and hepatic function abnormalities.
123
What is the significance of febuxostat in gout treatment?
It appears to be roughly equivalent to allopurinol but shows higher efficacy in patients with renal impairment.
124
What is rasburicase used for in gout treatment?
It is FDA approved for short-course therapy to prevent tumor lysis syndrome.
125
What are the clinical features of chronic tophaceous gout?
Chronic tophaceous gout involves urate crystal deposits in soft tissues, cartilage, and tendons, forming tophi. It may lead to bone destruction and deformity.
126
What are the clinical features of intercritical gout?
Intercritical gout refers to the interval between gout attacks, typically lasting 6 months to 2 years. Attacks become more severe and polyarticular over time.
127
What is the pathognomonic sign of gout?
The pathognomonic sign of gout is the presence of tophi, which are urate crystal deposits in soft tissues, cartilage, and tendons.
128
What is the mechanism of action of allopurinol in gout treatment?
Allopurinol decreases uric acid production by inhibiting xanthine oxidase.
129
What is the mechanism of action of febuxostat in gout treatment?
Febuxostat is a xanthine oxidase inhibitor that decreases uric acid production.
130
What is the role of uricases in gout treatment?
Uricases, such as rasburicase and pegloticase, convert uric acid to allantoin for excretion.
131
What are the potential side effects of urate-lowering drugs?
A rare side effect of urate-lowering drugs can induce fever, interstitial nephritis, acute renal failure, and Toxic Epidermal Necrolysis (TEN).
132
What is Lesinurad and its mechanism of action?
Lesinurad is a recently FDA-approved selective uric acid reabsorption inhibitor that inhibits URAT1, a urate transporter responsible for most renal reabsorption of uric acid.
133
What can certain drugs induce?
Certain drugs can induce fever, interstitial nephritis, acute renal failure, and Toxic Epidermal Necrolysis (TEN).
134
What is the significance of the FDA-approved drug for short-course therapy to prevent tumor lysis syndrome?
The FDA-approved drug for short-course therapy to prevent tumor lysis syndrome helps manage the rapid release of uric acid into the bloodstream during cancer treatment, preventing gouty attacks and renal complications.
135
What is Lesinurad and its function?
Lesinurad is an FDA-approved selective uric acid reabsorption inhibitor that inhibits URAT1 and OAT4, responsible for renal reabsorption of uric acid.
136
What is the role of URAT1 in uric acid metabolism?
URAT1 is a urate transporter responsible for most renal reabsorption of uric acid.
137
What is the significance of combining Lesinurad with a xanthine oxidase inhibitor?
Lesinurad is administered with a xanthine oxidase inhibitor in patients who have not achieved control with the xanthine oxidase inhibitor alone.
138
What are the potential side effects of Lesinurad?
Lesinurad can precipitate acute renal failure in patients with underlying renal disease.
139
What is the goal of urate-lowering drugs?
The goal of urate-lowering drugs is to maintain the serum urate level consistently at a desired level.
140
A patient with refractory chronic gout is prescribed an FDA-approved IV uricase. What is this drug?
The FDA-approved IV uricase for refractory chronic gout is pegloticase.
141
What is the advantage of pegloticase for refractory chronic gout?
Pegloticase is a pegylated uricase with decreased immunogenicity and increased serum half-life, making it effective for refractory chronic gout.
142
What is the daily dosage of febuxostat for gout?
The daily dosage of febuxostat is 40 mg once daily.
143
What is the mechanism of action of lesinurad?
Lesinurad is a selective uric acid reabsorption inhibitor that inhibits URAT1 and OAT4.
144
What is a major limitation of rasburicase for refractory chronic gout?
Rasburicase is highly immunogenic and has a plasma half-life of less than 24 hours.
145
What are the potential infusion reactions of pegloticase?
Infusion reactions include flushing, urticaria, hypotension, and anaphylaxis.
