Dialysis osteoarthropathy

Introduction to dialysis osteoarthrosis Dialysis-related arthropathy is one of the important complications of chronic dialysis patients. After the introduction of clinical medicine in dialysis therapy in the early 1960s, the complications of rheumatism were quickly recognized. In 1964, Caner and Decker reported acute arthritis and periarthritis, which was later found to be associated with apatite crystallization. If hyperphosphatemia is adequately treated, its onset is reduced. Around 1975, Assenat found amyloid deposits in the carpal tunnel tissue of long-term dialysis patients. By 1985, Gejyo et al. confirmed that the main component of this amyloid deposit was 2-microglobulin (2M), so it was called 2-microglobulin amyloidosis. basic knowledge The proportion of illness: 0.001% - 0.005% Susceptible people: no specific population Mode of infection: non-infectious Complications: heart failure amyloidosis

Causes of dialysis osteoarthrosis

(1) Causes of the disease

The main reasons for amyloidosis in dialysis patients are:

1. 2-microglobulin retention 2-microglobulin has a molecular weight of 11,800, which can be filtered by glomerulus and metabolized in the renal tubules. The long-term hemodialysis patients are lost due to glomerular and tubular function. Hemodialysis can only remove substances with a molecular weight below 500, so the serum 2-microglobulin content of patients increases by about 60 times that of normal people. Chronic aggregation of this molecule is the main cause of dialysis osteoarthrosis.

2. The structure of 2-microglobulin changes and the amino group of biologically acting proteins are modified by advanced glycosylation end product (AGE) by non-enzymatic glycosylation reaction to form a new one. Uremic toxin, which promotes dialysis-related amyloidosis, accelerates vascular sclerosis and tissue aging, and aggravates complications of diabetes (insulin resistance, neuropathy, retinopathy, nephropathy, etc.) and participates in the pathological processes of certain senile diseases The protein modified by the advanced glycation end product has pathophysiological activity, and it has been confirmed that the main component in the amyloid deposit of dialysis osteoarthrosis is 2-microglobulin modified by the advanced glycation end product. They stimulate the chemotaxis of human monocyte macrophages, stimulate the production of the inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor (TNF-), and delay the apoptosis of monocytes. Promote its differentiation into inflammatory macrophages; inhibit fibroblast collagen synthesis, increase collagenase secretion; stimulate bone resorption of osteoclasts and induce inflammation around the amyloid follicle , Play an important role in bone and joint destruction and bone lesions, sugar beta] 2-microglobulin of the more acidic groups, readily polymerize into amyloid.

(two) pathogenesis

Biocompatibility of dialysis membrane Biocompatibility refers to the reaction of biological materials with blood tissues and organs. In hemodialysis, due to the non-inertness of the membrane surface, and hemodialysis is an iterative process. The tiniest response of each interaction between the blood membranes ultimately leads to important clinical consequences.

These consequences include:

1. Bioincompatibility can lead to activation of the complement alternative pathway, producing C5a, C3a and C5b, thereby activating macrophages, producing and releasing inflammatory cytokines and reactive oxygen species, interleukin-1, and leukocyte-mediated Interleukin-6 and TNF increase the rate of bone turnover, causing destruction of matrix proteins to cause bone cystic changes.

2. Bioincompatibility causes the body's immune function to be low, repeated inflammatory reactions, formation of AGE-2m in situ, macrophage uptake of amyloid precursor 2-microglobulin and AGE-2-microglobulin, matrix The protein is simultaneously destroyed to cause amyloidosis. In addition, the endotoxin present in the dialysate is an inducer of cytokine production, which promotes the release of cytokines (IL-1, IL-6, TNF) and destroys matrix proteins. Accelerated amyloidosis.

Dialysis osteoarthrosis prevention

1. Increase the clearance of 2-microglobulin by high-throughput dialysis membrane (polyfluoride membrane F60, F80, AN69) hemofilrtation and hemodia filtration technology, as well as peritoneal dialysis, can reduce and Delay the development of 2-microglobulin amyloidosis.

2. Avoid the release of 2-microglobulin. Use a biocompatible membrane to ensure the purity of the dialysate and remove endotoxin from the dialysate.

Dialysis osteoarthrosis complications Complications heart failure amyloidosis

1. Chronic finger flexor tendon synovitis can cause progressive loss of the function of the extensor muscle of the diseased finger, accompanied by trigger finger symptoms, joint swelling, joint effusion and recurrent joint capsule hemorrhage, destructive spondyloarthropathy Mainly involving the cervical vertebrae and often multiple, cystic bone damage, cystic bone damage occurring at the femoral head or acetabulum is likely to lead to pathological fractures.

2. Systemic amyloidosis can cause myocardial lesions and heart failure, gastrointestinal bleeding, perforation, skin 2-microglobulin amyloid deposition, etc., risk factors for amyloidosis associated with 2-microglobulin include:

(1) Age: The older the dialysis is, the higher the incidence of dialysis osteoarthrosis.

(2) The longer the duration of chronic renal failure, the greater the incidence of dialysis osteoarthrosis.

(3) The composition and purity of dialysate (such as aluminum content, endotoxin, etc.) are considered to be important factors in reducing amyloidosis.

(4) Membrane (material and pore size): The application of synthetic membranes and high-flow treatments have a lower incidence of dialysis osteoarthrosis than low-throughput complement-activated membranes (copper-like membranes).

Symptoms of dialysis osteoarthrosis Common symptoms Joint swelling Joint pain Calcification Joint effusion Bone destruction Calcium deposit Subcutaneous deposition appears... Synovial thickening

1. Dialysis-related amyloidosis dialysis-related amyloidosis is a common systemic disabling complication of long-term dialysis patients (hemodialysis or peritoneal dialysis). The lesion mainly invades the tissues around the joints and joints, resulting in bone and joints. Residual lesions, autopsy confirmed that the amyloid deposition of the tissue is often earlier than the clinical symptoms and radiographic findings of the disease.

(1) Carpal tunnel syndrome: Most of the early clinical manifestations of dialysis-related amyloidosis, mainly caused by 2-microglobulin amyloid deposition in the carpal canal sheath, synovial membrane, flexor tendon or flexion Muscle ligament, resulting in relatively narrow carpal tunnel cavity, carpal tunnel internal pressure rise, median nerve compression, clinical manifestations of hand pain, numbness, sensation, fish muscle atrophy and dysfunction, slamming the wrist median nerve can not only cause Local pain, and can cause pain and sensation in the median nerve distribution area away from the sniper site (Tinel sign positive), allowing the patient's wrist to flex, and the opposite hand can cause the index finger, middle finger and ring finger sensation loss (Phalens sign) Positive).

(2) Osteoarthrosis: Osteoarthrosis often occurs in patients with long-term dialysis. Joint pain is a prominent clinical manifestation, mainly involving the shoulder joints, mostly bilateral, exacerbated during dialysis, and the tendon sheath and synovial membrane increase. Thickness can lead to decreased joint mobility, especially affecting the shoulder joint, wrist joint, finger joint, chronic finger flexor tendon synovitis can cause progressive loss of the function of the extensor muscle of the lesion, accompanied by trigger finger symptoms, joints can also occur Swelling, joint effusion and recurrent joint capsule hemorrhage.

(3) Destructive joint disease: Most patients with long-term dialysis, destructive spondyloarthropathy mainly involving the cervical vertebrae and often multiple, characterized by narrowing of the intervertebral space, erosion of adjacent lamina, bone destruction, no Osteophytes formation, lesions can be rapidly progressive, lesions involving the spinous process joints, resulting in severe spinal advancement and nerve compression symptoms, radiographic changes appear earlier, but often clinically asymptomatic or only mild pain Even can cause serious neurological complications.

(4) cystic bone damage and pathological fracture: cystic bone damage is multiple subchondral osteolytic changes, the number and size increase with time, occur in the vicinity of the synovial joint, more common in the hand joint, wrist joint, Shoulder joints, humerus, femur, femoral head, hip, foot and cervical vertebrae (Fig. 1), cystic bone lesions occurring at the femoral head or acetabulum are prone to pathological fractures.

(5) Systemic amyloidosis: dialysis amyloidosis is a systemic disease involving 2-microglobulin amyloid deposits involving many tissues such as heart, liver, spleen, lung, blood vessels, etc., which can cause myocardial lesions and Heart failure, gastrointestinal bleeding, perforation, 2-microglobulin amyloid deposition of the skin, etc.

2. Crystalline-associated arthritis Common gout disease in patients with renal failure who have not undergone dialysis is rare in hemodialysis patients because hemodialysis can effectively remove uric acid from plasma, crystal deposition disease of calcium pyrophosphate dihydroxy compound. It is also rare that calcium oxalate deposition may cause cartilage calcium deposition and synovial membranes, calcification around the skin and joints, cumulative flexor tendon may produce finger flexion and acute inflammation or chronic inflammation, but there are few cells in the joint effusion, in addition, In patients with chronic renal failure, oxalate deposition occurs when hemodialysis does not effectively remove oxalate, and it is more likely to occur when excessive oxalate precursors such as vitamin C are ingested.

Calcium phosphate is the main component of apatite crystallization, and it is also the main component of the deposition of calcium-containing substances around the joints of dialysis patients. The size of the sediment varies greatly. Small can be the calcification of the joints, and the large pseudotumor masses can affect. Joint movement, although most of these joint calcifications are asymptomatic, can also cause acute arthritis (Figure 2), with the full treatment of hyperphosphatemia, the incidence of joint disease is reduced.

Examination of dialysis osteoarthrosis

Blood routine examination, complement C5a, C3a and C5b, 2-microglobulin examination is necessary.

1. Histological examination (gold standard for diagnosis) The deposition of amyloid in joint tissue was positive for potassium permanganate-Congo red staining, positive for anti-2-microglobulin staining, and irregular alignment was observed under electron microscope, diameter 8 ~10 nm amyloid fibrils, bone biopsy showed cystic lesions containing 2-microglobulin amyloid.

2. Electromyography often indicates neurogenic damage, consistent with peripheral neuropathy, and the median nerve conduction velocity is slowed down.

3. Imaging examination

(1) Bone X-ray examination: common subchondral bone erosion is cystic bone damage, which is a valuable diagnostic sign of 2-microglobulin amyloidosis. Series X tablets show that the size and number of cystic lesions increase with time. Increased, mainly involving the hip, wrist and shoulder joints, scaphoid or femoral neck amyloid cysts may have spontaneous fractures, cervical joints are destructive joint lesions, often tooth-like erosion process, bone destruction is often multiple, and It is roughly symmetrical, but the X-ray is hard to find.

(2) Ultrasound examination: Ultrasound examination, synovial sac and ligament, soft tissue thickening of shoulder joint, strong echo of amyloid deposition in joint capsule, diagnostic specificity 100%, sensitivity 75%79%.

(3) CT and MRI examination: it is helpful to find lesions that are not easily displayed on common X-rays, such as bone destruction of the occipital ring joint and neck joint, cystic changes of the tibia and femur, and translucent of the posterior arch of the vertebral body. The area can be clearly seen under CT. The T1 and T2 images of MRI show that the affected intervertebral disc is low signal; it is very sensitive to the synovial ligament and soft tissue thickening, and provides a reliable quantitative method for determining the extent of cystic bone damage.

(4) Flashing photography:

1123I-SAP scintillation: SAP is a serum amyloid P component synthesized by the liver. It can be non-covalently bound to all amyloid fibers. It is characterized by the inability to distinguish the cause of amyloidosis, false positive in the spleen, and false on the hip and shoulder. Negative performance,

2131I-2-microglobulin scintigraphy: sensitivity is superior to radiological diagnosis, but not for patients with better residual renal function.

Diagnosis and differential diagnosis of dialysis osteoarthrosis

According to the clinical manifestations, combined with bone biopsy to show cystic lesions containing 2-microglobulin amyloid, it can be diagnosed.

Differential diagnosis

1. The frequency of septic arthropathy occurring in dialysis patients is much larger than that of ordinary people, often involving multiple joints, mostly caused by uncommon microorganisms, especially in patients treated with deferoxamine. The diagnosis requires aspiration of joint effusion. White blood cell count and bacteriological examination, low cell count in amyloid effusion, high white blood cell count suggests apatite-induced arthritis or septic arthritis, and infectious discitis is also needed to occur in dialysis The patient's destructive spinal joint disease is differentiated.

2. Renal osteopathy Renal osteopathy is one of the common causes of joint pain. Severe secondary hyperparathyroidism can cause bone pain, bone destruction and pain at the tendon attachment point. The latter can cause tendon rupture, aluminum Overload causes acral neuralgia and is easily confused with amyloid joint disease.

Rheumatic diseases and rheumatoid arthritis can occur in patients with hemodialysis, because hemodialysis patients and patients with rheumatoid arthritis can develop amyloidosis (20% to 60% of rheumatoid arthritis can also occur amyloid It is difficult to diagnose rheumatic diseases in hemodialysis patients by increasing the rate of non-specific ESR.

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